2019 Latin America Conference on Lung Ca ncer · IASLC 2019 Latin America Conference on Lung Cancer...

ABSTRACTBOOK

2019 Latin America Conference onLung Cancer

October 17-19 , 2019 | MEXICO CITY, MEXICO

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Conquering Thoracic Cancers Worldwide

IASLC 2019 Latin America Conference on Lung Cancer (LALCA 2019) | Abstract BookLALCA2019.IASLC.ORG

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Announcing the launch of

A new open access journal from the IASLC

JTO Clinical and Research Reports is the official open access journal of the International Association for the Study of Lung Cancer. It aims to complement the Journal of Thoracic Oncology by offering authors a gold open access publication option and publishing the following article types in particular:

• Phase I trials

• Well performed single-armphase II trials

• Subset analyses of published trials

• Impactful retrospective studies

• Database analysis

• Large institutional series

• High-quality case reports

• Region-specific clinical trials

• Subspecialty thoracic oncology studies

• Selected high-quality meeting reports

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IASLC 2019 Latin America Conference on Lung Cancer (LALCA 2019) | Abstract Book

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Table of Contents

Presidential Symposium 4-6

Invited Speakers 7-20

Poster Discussion #1 21-23

Poster Discussion #2 23-26

Poster Session 1 27-39

Poster Session 2 39-51

Author Index 52-55

Conference Secretariat

International Conference Services Ltd. (ICS)Suite 300 - 1201 West Pender StreetVancouver, BC, Canada V6E 2V2Phone +1 604 681 2153Fax +1 604 681 1049www.icsevents.com


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Presidential Symposium

Saturday, October 19, 09:15 - 09:50O.01

Topic: Biology and Pathogenesis

Challenges of Interpreting NGS Liquid Biopsy (LB) Results in Advanced NSCLC: Are ESCAT and OncoKB Scales Reliable?

A. Russo, M. Mccusker, J. Chen, K.A. Scilla, R. Mehra, A. Gittens, C.D. RolfoUniversity of Maryland Greenebaum Comprehensive Cancer Center, Baltimore/United States of America

Background: Plasma genotyping through next generation sequencing (NGS) is entering clinical practice in NSCLC. Several commercially available platforms can identify a wide variety of somatic aberrations. The correct interpretation of these results can be challenging and vendors include therapeutic suggestions to guide oncologists. Novel levels of evidence tools have been developed to rank genomic alterations in tissue, but not still used in LB.

Method: Advanced NSCLC patients underwent commercial 73-gene cfDNA NGS analysis. ESMO Scale for Clinical Actionability (ESCAT) and OncoKB were used to grade levels of evidence for categorize aberrations and compared with variant allele frequency (VAF), treatment decisions, and vendor suggestions.

Results:

77 samples from 73 advanced NSCLC patients at the time of diagnosis (49%) or during disease course (51%) were analyzed. Median turnaround time was 8 days (range 5-17), with no genotyping failures. cfDNA NGS analysis revealed 323 unique somatic alternations. According to ESCAT (IA-IV) and OncoKB (1-4), 87 and 88 genetic alterations were potentially actionable, respectively, and 26% received a matched targeted drug. Discrepancies between these two tools and vendor suggestions were reported in 4 cases (Fig. 1). We performed a subset analysis of 64 samples: Median VAF was 4.37 % (range 0.16-43.05) and a VAF < 1% was reported in 16 samples; 45% of alterations (excluding amplifications) were clonal events (cfDNA% divided by VAF > 0.5). Among EGFR and ALK positive samples median VAF was 7.98% (range 0.29-41.2); 3/17 samples presented a VAF below 1%, with no detrimental effect on treatment response.

Conclusion: The application of ESCAT and OncoKB is feasible in LB. Discrepancies between vendor therapeutic suggestions and evidence-based grading systems requests caution in the use of information outside the molecular tumor board. Driver mutations with low VAF are amenable to receive treatment. VAF could be included as complementary tool to grading systems to better understand the significance of aberrations.

Keywords: Liquid biopsy, NGS, precision medicine, NSCLC

O.02

Topic: Immunotherapy

Long-term Survival Outcomes with Nivolumab (NIVO) in Pts with Previously Treated Advanced Non-small Cell Lung Cancer (NSCLC): Impact of Early Disease Control and Response

J. Brahmer1, L. Horn2, B. Hossein3, S. Ramalingam4, A. Pluzanski5, M.A. Burgio6, M.C. Garassino7, L.Q.M. Chow8, S. Gettinger9, L. Crino6, D. Planchard10, C. Butts11, A. Drilon12, J. Wojcik-Tomaszewska13, G. Otterson14, S. Agrawal15, A. Li16, J.R. Penrod16, S.J. Antonia17, Y. Bautista18

1Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore/United States of America, 2Department Of Medicine, Division Of Hematology And Oncology, Vanderbilt University Medical Center, Nashville/United States of America, 3Fox Chase Cancer Center, Philadelphia/United States of America, 4Winship Cancer Institute of Emory University, Atlanta/United States of America, 5Klinika Nowotworow Pluca i Klatki Piersiowej, Centrum Onkologii - Instytut Im, Warsaw/Poland, 6Medical Oncology Unit, Istituto Scientifico Romagnolo Per lo Studio e la Cura dei Tumori (IRST) IRCSS, Meldola/Italy, 71Fondazione IRCCS Istituto Nazionale dei Tumori, Milan/Italy, 8Division of Medical Oncology, Department of Medicine, University of Washington, Seattle/United States of America, 9Yale Cancer Center, New Heaven/United States of America, 10Institut Gustave Roussy, Department of Medical Oncology, Thoracic Group, Villejuif/France, 11Department of Oncology, Division of Medical Oncology, Cross Cancer Institute, Edmonton/Canada, 12Memorial Sloan Kettering Cancer Center, New York/United States of America, 13Wojewodzkie Centrum Onkologii, Gdansk/Poland, 14The Ohio State University, Columbus/United States of America, 15Bristol-Myers Squibb, Princeton, New Jersey/United States of America, 16Bristol Myers Squibb, New Jersey/United States of America, 17H. Lee Moffitt Cancer Center & Research Institute, Tampa/United States of America, 18Centro Medico Nacional Siglo XXI, IMSS, Mexico/Mexico

Background: Historically, 5-y overall survival (OS) with chemotherapy for pts with metastatic lung cancer was ~5%; with the advent of immunotherapy, this has increased to ~15%. CheckMate (CM) 017, 057, 063, and 003 are NIVO studies with extensive follow-up in pts with previously treated advanced NSCLC. Using pooled data from these studies, we evaluated the long-term benefit (up to 4 y) of NIVO and impact of early response or disease control on subsequent long-term OS.

Method: Progression-free survival (PFS) and OS were estimated for pts with NSCLC across histologies treated with NIVO in pooled analyses of CM 017, 057, 063, and 003 (n=664), and for pts randomized to NIVO (n=427) or docetaxel (DOC; n=427) in pooled analyses of CM 017/057. Other analyses for CM 017/057 included estimation of OS in pts alive at 6 mo by response status at 6 mo, and OS in all responders (complete or partial response [CR/PR]) from time of response.

Results: In pooled analyses of the 4 studies, 4-y OS rates for NIVO in all pts and those with PD-L1 ≥1% and <1% were 14%, 19%, and 11%, respectively. In CM 017/057, the 4-y OS rate in all pts was higher with NIVO vs DOC (14% vs 5%). Pts with either CR/PR or stable disease (SD) at 6 mo had longer subsequent OS with NIVO vs DOC; for pts with PD at 6 mo, 1-y OS rates were higher with NIVO vs DOC, while 2-4 y OS rates were similar (Table). For responders (CR/PR) in CM 017/057, 4-y OS rate from time of response with NIVO vs DOC was 54% vs 12%; median duration of response was 24 mo vs 6 mo, respectively. Overall, the NIVO discontinuation rate due to treatment-related adverse events (AEs) was 8.7%; most common treatment-related select AEs were skin reactions (incidence rate, 38.6 per 100 person-y).

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Conclusion: These large pooled analyses show pts with CR/PR or SD with NIVO at 6 mo derived marked OS benefit; this long-term benefit was improved vs pts with DOC with the same response status at 6 mo. The NIVO safety profile was consistent with prior reports.

Keyword: non-small cell lung cancer, immunotherapy, nivolumab

O.03

Topic: Advanced NSCLC

KEYNOTE-189: OS Update and Progression After the Next Line of Therapy (PFS2) with Pembrolizumab + Chemotherapy for Metastatic Nonsquamous NSCLC

S. Gadgeel1, M.C. Garassino2, E. Esteban3, G. Speranza4, E. Felip5, M.J. Hochmair6, S. Powell7, S.Y.-S. Cheng8, H.G. Bischoff9, N. Peled10, R. Hui11, M. Reck12, T. Kurata13, E.B. Garon14, M. Boyer15, J. Yang16, M.C. Pietanza16, D. Rodríguez-Abreu17

1Karmanos Cancer Institute, Detroit (currently at University of Michigan, Ann Arbor)/United States of America, 2Fondazione IRCCS Istituto Nazionale dei Tumori, Milan/Italy, 3Hospital Universitario Central de Asturias, Oviedo/Spain, 4Centre integré de cancérologie de la Montérégie, Université de Sherbrooke, Greenfield Park/Canada, 5Vall d’Hebron University, Vall d’Hebron Institute of Oncology (VHIO), Barcelona/Spain, 6Department of Respiratory and Critical Care Medicine and Ludwig Boltzmann Institute for COPD and Respiratory Epidemiology, Vienna/Austria, 7Sanford Health, Sioux Falls/United States of America, 8Sunnybrook Health Sciences Centre, Toronto/Canada, 9Thoraxklinik, Heidelberg/Germany, 10Davidoff Cancer Center, Tel Aviv University, Petah Tikva (currently at Soroka Medical Center, Ben-Gurion University, Beer-Sheeva)/Israel, 11Westmead Hospital and University of Sydney, Sydney/Australia, 12LungenClinic, Airway Research Center North, German Center for Lung Research, Grosshansdorf/Germany, 13Kansai Medical University Hospital, Osaka/Japan, 14David Geffen School of Medicine at UCLA, Los Angeles/United States of America, 15Chris O’Brien Lifehouse, Camperdown/Australia, 16Merck & Co., Inc., Kenilworth/United States of America, 17Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria/Spain

Background: Pembrolizumab plus chemotherapy (pemetrexed-platinum) significantly improved OS and PFS over chemotherapy alone as 1L therapy for metastatic nonsquamous NSCLC with manageable safety in the KEYNOTE-189 study (NCT02578680). Benefit was observed regardless of PD-L1 TPS. We present updated OS based on longer follow-up and PFS2.

Method: Eligible patients were randomized 2:1 to pembrolizumab (n=410) or placebo (n=206) plus pemetrexed and carboplatin or cisplatin for 4 cycles followed by pembrolizumab or placebo for up to 35 cycles plus maintenance pemetrexed. Patients receiving placebo plus chemotherapy could crossover to receive pembrolizumab upon PD. Poststudy anticancer therapy and outcomes were collected. PFS2 was defined as time from randomization to PD per investigator after start of 2L therapy or death, whichever occurred first. There was no multiplicity adjustment, and all P values are nominal. Data cutoff was September 21, 2018.

Results: With 18.7-month median follow-up, pembrolizumab plus chemotherapy continued to provide longer OS (HR 0.56 [95% CI 0.45–0.70], P<0.00001; median 22.0 vs 10.7 months) and PFS (HR 0.48 [95% CI 0.40–0.58], P<0.00001). Benefit was seen in all PD-L1 TPS groups (Table). 2L+ therapy was received by 45% in the pembrolizumab plus chemotherapy arm and 59% (54% 2L+ immunotherapy) in the chemotherapy alone arm. PFS2 was longer for patients who received 1L pembrolizumab plus chemotherapy (HR 0.49 [95% CI 0.40–0.59], P<0.00001; median 17.0 vs 9.0 months), with no difference by TPS (Table).

Conclusion: 1L pembrolizumab plus chemotherapy continued to show substantial OS benefit in metastatic nonsquamous NSCLC, regardless of PD-L1 TPS and despite 54% of patients in the chemotherapy alone arm receiving subsequent immunotherapy. Median OS, PFS and PFS2 were approximately doubled with pembrolizumab plus chemotherapy. These data confirm that pembrolizumab should be given as part of 1L therapy to maximize outcomes in both PD-L1–expressing and PD-L1–non-expressing NSCLC.

Keywords: PD-L1, pembrolizumab, chemotherapy, NSCLC

O.04


Results from the IASLC Global Survey on Molecular Testing in Lung Cancer

M.V. Garcia1, M. Smeltzer2, M. Wynes3, S. Lantuejoul4, R.A. Soo5, L. Dalurzo6, E. Felip7, K. Howell2, K. Kerr8, E. Kim9, C. Mathias10, P. Postmus11, C. Powell12, S. Ramalingam13, K. Richeimer3, M. Taylor2, M. Tsuboi14, I. Wistuba15, K. Wood3, G. Scagliotti16, F. Hirsch17

1University of Colorado Anschutz Medical Campus, Aurora, Colorado/United States of America, 2School Of Public Health, University of Memphis, Memphis/United States of America, 3International Association for the Study of Lung Cancer, Aurora/United States of America, 4Centre Hospitalier Universitaire de Grenoble, Grenoble/France, 5Department of Haematology-Oncology, National University Hospital, 119074, Singapore/Singapore, 6Hospital Italiano de Buenos Aires, Buenos Aires/Argentina, 7Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona/Spain, 8University of Aberdeen, School of Medicine and Dentistry, Aberdeen/United Kingdom, 9Levine Cancer Institute, Charlotte/United States of America, 10NOB and Hospital Português, Salvador/Brazil, 11University of Liverpool, Liverpool/United Kingdom, 12Mount Sinai-National Jewish Health Respiratory Institute, New York/United States of America, 13Winship Cancer Institute of Emory University, Atlanta/United States of America, 14National Cancer Center Hospital East, Tokyo/Japan, 15UT MD Anderson Cancer, Houston, Texas/United States of America, 16University of Torino, Orbassano/Italy, 17Mount Sinai Cancer Center, New York/United States of America

Background: The IASLC conducted an international survey to evaluate current practice and barriers to molecular testing (MT) in lung cancer. Here we compared results from Latin America (LA) to other regions of the world.

Method: Surveys were available in 7 languages and translated into English for analysis. The survey included: a 7-question introduction, followed by three specific tracks: 32 questions on tests/treating patients, 45 questions on performing/interpreting assays, and 24 questions on tissue acquisition. Respondents also identified barriers to implementing/offering MT. IASLC criteria were used to group responses into the following geographic regions: LA, US/Canada, Asia, Europe, and the rest of the world (Other). Regional comparisons used the Chi-squared test, free-text was analyzed with Nvivo.

Results: There were 2,537 responses from 102 countries. 11% of responses were from LA, 11% US/Canada, 52% Asia, 19% Europe,

PD-L1 TPS ≥50%n=202

PD-L1 TPS 1-49%n=186

PD-L1 TPS <1%n=190

OS, HR (95% CI)

0.59 (0.39–0.88)

0.62 (0.42–0.92)

0.52 (0.36–0.74)

PFS, HR (95% CI)

0.36 (0.26–0.51)

0.51 (0.36–0.73)

0.64 (0.47–0.89)

PFS2, HR (95% CI)

0.47 (0.33–0.69)

0.59 (0.41–0.86)

0.46 (0.33–0.66)


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and 7% Other. Respondents varied by specialty, including 45% Medical Oncologists, 12% Pulmonologists, 12% Thoracic Surgeons, 9% Pathologists, and 22% scientists or other. The frequency of MT was low overall and varied by region. Respondents from LA reported a higher frequency of patients who did not receive testing compared to other regions (74% vs 61% in requesting/treating track, p<0.0001; 88% vs 67% in tissue specimen acquisition, p=0.0017). The most frequent barrier to MT in every region was cost. The second largest barrier in LA was access, similar to Europe/Other. 52% of respondents reported patients/physicians were unsure/not satisfied with the state of MT in their countries, with the highest dissatisfaction in LA (80%, p=0.0066). 82% of respondents who perform/interpret assays typically received results within 10 days, which occurred most frequently in LA (89%) (p<0.0001). 23% reported >10% of cases were rejected due to inadequate samples, with 26% reporting this in LA (p=0.5590). However, across all regions, 47% stated there was no policy or strategy to improve the quality of the tissue samples in their countries. Among respondents who request/treat, 37% had difficulty in understanding MT reports, most of whom cited a need for more technical and scientific knowledge. However, LA and Europe respondents reported the least difficulty in understanding (p<0.0001). Overall, only 67% of respondents were aware of CAP/IASLC/AMP guidelines, 70% for LA (p=0.0041).

Conclusion: Adoption of MT in clinical practice for lung cancer is low in LA as well as across the globe, with cost and access being main barriers. Global and regional initiatives should be developed to address the barriers preventing MT in these regions.

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IASLC Foundation RELAUNCH!The IASLC Foundation has taken on a new name and a new look!

The International Lung Cancer Foundation (ILCF) has adopted a striking new look to inspire confidence in our mission. Please join us on our journey and

thank you to all who have continued to support us. Together we will fight to conquer thoracic malignancies!

For more information please visit: IASLC.org/ILCF

I N S P I R I N G H O P E T H R O U G H R E S E A R C H

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Invited Speakers

I.1-1Thursday, October 17, 2019, 10:40 - 11:00

IASLC Pre-Conference School of Thoracic Oncology

Oligometastatic Disease in Non-small Cell Lung Cancer. Single Center Experience Oncology Hospital XXI Century

Y. Bautista1, G. Cabada1, G. Nuñez1, M. Perez1

1IMSS, Mexico/Mexico

Objectives: Radical treatment in oligometastatic disease in NSCLC has Improved outcome in overall survival. We defined oligometastic disease in patients with less than five synchronous metastases and 3 organs and mediastinal lymph node involvement is not counted as a metastatic site. We describe a single center experience of an academic hospital of oncology assessed by computed tomography for diagnosis, and radiotherapy as a radical treatment.

Materials and Methods: In this retrospective study we evaluate progression free survival using radiotherapy (stereotactic body radiotherapy and three-dimensional conformal radiotherapy) in patients with oligometastatic NSCLC with pathologically confirmed stage IV NSCLC with ≤5 synchronous metastases, and there were assessed by CT. All patients received four to six initial cycles of systemic treatment. We reviewed files from 2017 to 2019. During treatment of radiotherapy patients received pemetrexed as maintenance.

Results: Sixteen patients were included in the analysis. The mean age was 62.5 years (range: 48-78 years). At diagnosis, 31% of patients presented with CNS metastases. Following radiotherapy, 16 (68.75%) patients achieved a stable disease, while 4 (25%) had a partial response and 1(6.25%) with complete response. The median PFS was 5.7 months (95% CI: 6.3-5.07).

Conclusion: Patients with oligometastatic NSCLC who undergo radiotherapy have a favorable response and progression free survival.

Keywords: Oligometastatic, Lung, Metastatic, Radiotherapy

I.1-2

Efficacy of Pemetrexed maintenance in Patients of Metastatic Non-squamous Non-small-cell Lung Cancer. Single Center Experience. Academic Hospital IMSS XXI Century

Y. Bautista1, G. Nuñez1, G. Cabada1, M. Perez1

1IMSS, Mexico/Mexico

Purpose: Pemetrexed has been approved for maintenance therapy of advanced nonsquamous non-small-cell lung cancer (NSCLC). The purpose of this study was to describe real-world maintenance use of pemetrexed in Mexico City Oncology Hospital IMSS.

Patients and Methods: It was a retrospective study and where included files of patients with advanced nonsquamous NSCLC metastatic received carboplatin (area under the curve, 5), gemcitabine (1250 mg/m2) o pemetrexed (500 mg/m2) and carboplatin (area under the curve 5) for four cycles to six cycles. Patients without progression after four cycles to six cycles received pemetrexed (500 mg/m2) until progression. The primary point was response, SLP. 16 patients have radiotherapy in oligometastatic disease concomitant with radiotherapy.

Results: We evaluated 35 files of patients with demographic/clinical factors: median age 60 years (45-78 years), gender (35% female and 62% male), about smoking status there were 65% positive, brain metastases (8.5%), median of cycles were 11.4

(51cycles -2 cycles) and follow-up of 24 months and median progression free survival of 8.2 months (95% CI: 8.8-7.5).

Conclusion: Pemetrexed is efficacious as maintenance therapy for advanced nonsquamous NSCLC and we had better progression free survival. However, it should be evaluated in a prospective study.

Keywords: Maintenance, Lung, Pemetrexed, Advanced

I.1-3Thursday, October 17, 2019, 08:50 - 9:10

IASLC Pre-Conference School of Pathology

Update of Staging, Challenges for Pathologists

L. Dalurzo1

1Pathology, Hospital Italiano de Buenos Aires, Buenos Aires/Argentina

Clinical and pathological staging play a crucial role in predicting survivor and influencing treatment option in lung cancer patients. The last revision of AJCC and UICC, 8th edition of lung cancer staging, was released in 2017 and has being effective internationally from 2018.

One of the most important changes in the 8th Staging Edition for pTNM are related with the size of the tumor (pT) and the application of 2015 WHO Lung Cancer Classification of adenocarcinoma. (1)

Several published studies demonstrated that the size of the tumor from 1 to 5 cm is very important in lung cancer, each centimeter increase in tumor diameter is associated with worsening survival. According to these studies, for (T) descriptors of 8th edition of TNM the new tumor-size groups were created: T1a, ≤1 cm; T1b, >1 to 2 cm; T1c, >2 to 3 cm; T2a, >3 to 4 cm; T2b, >4 to 5 cm; T3, >5 to 7 cm; and T4, >7 cm.

In 2011, new entities of adenocarcinoma as adenocarcinoma in situ, minimally invasive adenocarcinoma, and lepidic predominant adenocarcinoma were defined and subsequently incorporated into the 2015 World Health Organization classification of lung cancer. To fit these entities into the T classification of the staging system, Tis and T1mi were introduced for adenocarcinoma in situ and minimally invasive adenocarcinoma, respectively.In non-mucinous lung adenocarcinomas with a lepidic component, total gross tumor size should be recorded but only the invasive component is used as a descriptor of the T-categories. The lepidic component of the tumor as the amount of this growth, may potentially be difficult or could be underestimated grossly. To help to find and evaluate grossly these lesions we can carefully inflate the specimen with a mixture of optimal cutting temperature medium (OCT) before sectioning or we can make serial section followed by washing of the specimen before formalin fixation. To complete the evaluation of tumor size in non-mucinous lung adenocarcinomas with lepidic growth it is also important the microscopic reexamination of the specimen with a careful correlation with radiographic findings.

In microscopic evaluation, each adenocarcinoma subtype component of the tumor could be difficult to determine and the interpretation could be potentially different for different pathologists. There are interesting studies about intra observer and inter observer lung pathologists reproducibility of the classification of adenocarcinoma.(2) They represent the challenge that sometimes pathologists face with the application of 2015 adenocarcinoma classification, especially important when the subtype of the tumor evaluated impacts over the size of the invasive tumor and in consequence the pT for staging.

If the invasive and lepidic components are mixed in different areas and the size of the invasive component cannot be

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measured in a single discrete focus, the pT can be estimated by multiplying the total size by the percentage of the invasive components: invasive size = % of invasive component x tumor diameter.

For separate tumor nodules (intrapulmonary metastasis), the classification recommended in the 7th edition has not changed: T3 for ipsilateral separate cancer nodules in the same lobe, T4 for ipsilateral separate cancer nodules in a different lobe, and M1a for a separate cancer nodule(s) in a contralateral lobe(s). The reported incidence of lung carcinoma patients presenting with multiple nodules ranges from 0.2% to 20%. Classification of multiple lung nodules as either multiple primary tumors or intrapulmonary metastases can be challenging. The 8th edition of the AJCC staging manual categorized multifocal lung cancer into four disease patterns. (I) two or more distinct and histologically different masses (considered unrelated and staged as individual cancers); (II) multiple ground-glass or part-solid nodules, histologically with lepidic growth pattern (considered separate tumors, T staged based on highest T stage lesion); (III) patchy areas of ground-glass and consolidations, histologically often invasive mucinous adenocarcinomas (considered single tumor with diffuse “pneumonic-type” involvement); and (IV) separate nodules with the same histologic features based on comprehensive histologic subtyping (considered intrapulmonary metastases). These patterns are based on clinical presentation (including radiologic impression and distribution of disease), histological assessment, and outcomes. Histologic and molecular features, in conjunction with clinical and radiological information, can all be tools to assist with staging of multiple nodules. Histologic features of adenocarcinomas are best characterized using histologic subtyping (percentage of lepidic, acinar, solid, papillary and micropapillary pattern) and comprehensive histologic assessment. Genomic alterations are commonly assessed using fluorescence in-situ hybridization and next generation sequencing (NGS). The AJCC considers exactly matching breakpoints by comparative genomic hybridization (CGH) as the only evidence for intrapulmonary metastases, and clearly different histologic types or subtypes as the only evidence for separate primary tumors. (3)

Involvement of the Pleura: When the visceral pleura is infiltrated by cancer, a pT1 cancer by size (3 cm or less) continues to be upstaged to pT2a. Elastic stains are of value in identifying pleural invasion in this setting. Beside there is no difference in staging between PL1 and PL2, this should be documented, tumor with neoplastic cells on the visceral pleural surface (PL2) have higher recurrence and worse prognosis.

The nodal stages have been able to consistently separate the patients into different prognostic group and remain unchanged from the earlier edition. The explorative analysis of pathologically-classified cases suggested that prognosis can be more accurately defined if combined with the number of stations in N1 and N2 location. Subdividing the N1 and N2 descriptors into involvement of single or multiple lymph node may help future studies on prognostication.

For metastatic disease (M descriptor) the new M1b category comprises patients with only one metastasis in one distant organ, whereas M1c implies multiple distant metastases in one or several organs.

1- Nicholson AG, et al. Eight Edition Staging of Thoracic Malignancies: Implications for the Reporting Pahtologist. Arch Pathol Lab Med. 2018 May;142 (5):645-661.

2- Shih AR, et al. Problems in the reproducibility of Classification of small lung adenocarcinoma: An International Interobserver Study. Histopathology. 2019 May 20. doi: 10.1111/his.13922.

3- Schenider F, Dacic S. Histopathologic and Molecular Approach to staging of multiple lung nodules. Transl Lung Cancer Res. 2017 Oct: 6(5): 540-549.

Keywords: Staging, Pathology

I.2Thursday, October 17, 2019, 10:30 - 10:45

IASLC Pre-Conference School of Nursing

Respiratory Rehab of the Postoperative Patient

M.A. Hernández1

1Instituto Nacional de Cancerologia, Mexico/Mexico

Lung cancer is the most common cancer and is the leading cause of cancer death worldwide. The most common type of primary lung cancer is non-small cell lung cancer (NSCLC). 67% of patients with lung cancer have 2 or more chronic conditions, the most common one being Chronic Obstructive Pulmonary Disease. Pulmonary rehabilitation programs can be given in three stages: before surgery (prehabilitation), after surgery and in advanced disease (1). The main objective of pulmonary rehabilitation after surgery is to improve or restore impairments associated with the disease and treatment, focused on exercise capacity and muscle strength. Other benefits are to promote a healthy lifestyle, reducing symptoms, and improving quality of life. Patients with lung cancer can have several physical and psychological impairments. These include reduced exercise capacity, peripheral muscle weakness, poor respiratory function, reduced shoulder range of motion (post-surgery), low physical activity levels, poor nutrition, anxiety, depression, distress, and reduced health-related quality of life. All of these impairments are responsive to pulmonary rehabilitation (2). Lung cancer treatment options are surgery, chemotherapy, radiotherapy, or targeted therapy. These treatments have multiple side-effects, which can cause inactivity to the patient. An exercise training program in non-lung cancer patients has demonstrated a significant impact in controlling symptoms and improving quality of life. In lung cancer patients, there is not enough scientific evidence supporting a standard pulmonary physiotherapy program, assessment of the patient’s impairments, and individualized exercise prescription. We should take precautions to look for contraindications before prescribing pulmonary rehabilitation to a patient. Some of the contraindications are extreme fatigue, nausea, fever, anemia, thrombocytopenia, neutropenia, lymphedema, cachexia, muscle atrophy, high risk for bone fracture, and cardiorespiratory limitation (3). In patients who are candidates for surgery, lung resection results in an immediate reduction in VO2 peak by 12% following a lobectomy, and 18% following pneumonectomy. Exercise capacity usually recovers to baseline by six months post-lobectomy, but in the case of pneumonectomy, exercise capacity loss is still evident six months after surgery. These impairments can also be targeted with post-operative pulmonary rehabilitation (2). The duration of a rehabilitation program varies between 3 to 20 weeks, as well as the time before surgery (4). There is no evidence for the optimal duration and timing for initiation. Although there is an improvement in the patient´s functional status, and reducing perioperative pulmonary complications and length of stay, ambiguous results have been obtained regarding lung function improvement. Pulmonary physiotherapy for lung resection candidates focuses on chest expansion, bronchial clearance, postural correction, and inspiratory muscle training which is practiced not only in the preoperative course but also postoperatively as a recovery and maintenance approach. The programs tested in the studies to date predominately involve aerobic and resistance exercises and are delivered as a supervised outpatient training program.

Most research has been focused on operable NSCLC (pre or post-surgery). Growing evidence supports that exercise during chemotherapy, radiotherapy, and advanced/palliative care can be beneficial for patients. Despite the evidence supporting physical activity and exercise training for people with cancer, evidence has not translated effectively into practice, and

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there has not been a routine integration of exercise/cancer rehabilitation programs for patients in most parts of the world. References1. Kendall F, Abreu P, Pinho P, Oliveira J, Bastos P. The role of physiotherapy in patients undergoing pulmonary surgery for lung cancer. A literature review. Rev Port Pneumol (2006). 2017;23(6):343-51.2. Sebio Garcia R, Yanez Brage MI, Gimenez Moolhuyzen E, Granger CL, Denehy L. Functional and postoperative outcomes after preoperative exercise training in patients with lung cancer: a systematic review and meta-analysis. Interact Cardiovasc Thorac Surg. 2016;23(3):486-97.3. Clini E. Textbook of pulmonary rehabilitation. New York, NY: Springer Berlin Heidelberg; 2017. pages cm p.4. Pouwels S, Fiddelaers J, Teijink JA, Woorst JF, Siebenga J, Smeenk FW. Preoperative exercise therapy in lung surgery patients: A systematic review. Respir Med. 2015;109(12):1495-504.

Keywords: Lung cancer rehab, Rehab



Symptom Management in Early Stage Lung Cancer

A. M. Acevedo1

1St. Joseph Hospital, Mission Viejo, United States

The most common symptom leading to the diagnosis of lung cancer is cough, sometimes associated with wheezing or hemoptysis, from irritation due to a tumor located in or near the bronchus. Other early symptoms can include chest wall pain if the tumor is located peripherally, particularly if it is invading the pleura. Dyspnea is often a late symptom but can occur if the tumor is occluding the airway or causing volume loss. Anorexia with weight loss can occur in association with energy expenditure and fatigue from the effort of breathing, as well as the caloric demands of the tumor itself (usually late stage disease). Local effects of lung neoplasms include Horner syndrome (unilateral constricted pupil, drooping of the eyelid, and dry skin) if the tumor invades the sympathetic chain in the upper part of the chest, and superior vena cava syndrome if the tumor impedes venous return from the head, neck, and upper extremity. Pleural and pericardial effusions may cause dyspnea and chest pain syndromes. Metastatic disease may cause bone pain, and neurologic symptoms from brain involvement. Small cell lung cancer may produce hormones that are released independently from endocrine organs to cause what are classified as paraneoplastic syndromes, which can lead to Cushing’s syndrome (high corticosteroid levels), SIADH (fluid retention and low sodium levels), and hypercalcemia.

Most early stage lung cancer produces few if any specific symptoms, and most of those, such as cough and/or dyspnea, are commonly associated with other diseases, so clinicians must be vigilant in inquiring about appropriate aspects of one’s medical history (tobacco use, secondhand smoke, radon or asbestos exposure, etc.) and should have a degree of suspicion when a patient presents with vague symptoms. CT lung screening of appropriate asymptomatic individuals (>30 pack-years of tobacco use, age >55, less than 15 years since quitting) will identify an otherwise undiagnosed neoplasm in one out of 320 patients screened. This compares extremely favorably with other cancer screening. For example, almost 2000 asymptomatic women need to be screened with mammography to detect one patient with breast cancer.



Advances in Radiotherapy and Radiotherapy Innovations

M. Blake1

1Centro Médico Abc, Mexico City/Mexico

Radiotherapy treatments have evolved in the last two decades in an impressive way, from the 2D planning to the IMRT and SABR treatments, several intermediate modalities have been evolving and this has permitted that the oncologic treatments become saver and more efficient. In our Country also this technology has become more available and more people have access to this type of treatment and benefit from it. This is the reason why this is so important to describe each radiotherapy technique and its therapeutic implications and clinical uses. In this talk we also are going to present the result of a phase II study of SABR in oligometastatic lung cancer patients.

This talk is about the evolution of radiotherapy, the innovations and the characteristics of patients that are receiving this type of treatment. Also, the importance of speaking about these new approaches with the oncologic team in order to select the best option for every patient. We are going to present the results of a phase II study of SABR in oligometastatic lung cancer patients. Patients with stage IV non-small cell lung cancer, treated initially with systemic therapy and those with partial response, with thoracic residual disease, received treatment with SABR. The aim of the study is to report local control (LC), progression free survival (PFS) and overall survival (OS) after the SABR treatment.

Describe the results of the study, how local control to oligometastatic disease can benefit the patient in terms of progression free survival and overall survival and also the feasibility of this new technic of radiation therapy treatment and its high tolerability among patients. In Mexico this type of technology is becoming more available.

The evolution of radiation treatment has been impressive in the last two decades and now we can see that treatments are becoming more efficient and less toxic due to the high doses delivered to tumor cells in contrast to low doses to organs at risk.

Keywords: Radiation therapy innovations, SABR, SBRT



Nutritional Support of the Lung Cancer Patient

J. Turcott1

1Instituto Nacional de Cancerología of Mexico, Mexico City/Mexico

Lung cancer (LC) has the most lethal mortality rate between all the cancer types. In newly diagnosed LC patients the 5-year survival is estimated in 5-16%. Malnutrition is considered as a pivotal to decrease quality of life, prognosis and survival in LC. At the time of diagnosis, malnutrition can be observed in at least 45% of the patients and this proportion increase as the disease progression. LC patients present a considerable symptom burden and are at a high risk of involuntary weight loss. Anorexia, dysgeusia and cachexia are among the main factors that affect nutritional status. Over one half of the patients diagnosed with advanced LC experience anorexia (loss of appetite) and 35% of treatment naïve Non-small Cell Lung Cancer (NSCLC) patients reported disgeusia (taste alteration), proportion increased until 56% in patients treated with chemotherapy and 66% in patients treated with radiotherapy. Anorexia and dyspepsia are directly related with lower energy and nutrimental consumption and contribute to

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the development of cachexia. Cachexia is mainly characterized by the loss of muscle mass induced by cancer associated inflammatory response. Early assessment of nutritional status, including the determination of anorexia, dysgeusia and risk of cachexia in LC patients is imperative in order to timely treat them to improve prognosis. Nutritional support should be focused individualizing the nutritional risks confronting each patient, including mainly the energy balance of the diet, achieve energy needs, assess the need of nutritional supplements consumption or alternative ways of feeding.

There are recently available tools for an easy and fast assessment of nutritional risk in LC patients. The nutritional risk evaluation of LC patients should include the anorexia cachexia scale (ACS) section from the Functional Assessment of Anorexia–Cachexia Therapy (FAACT). ACS has been validated in LC patients identifying a cutoff value of ≤32 (sensitivity: 80.3% and specificity: 85%) for the determination of anorexia with the propose of consider a stimulant of appetite to achieve the energy requirements. Dysgeusia can be defined as a taste alteration and can be perceived as a distortion of taste (dysgeusia), absence of taste (ageusia), decreased detection sensitivity (hypogeusia), or increased sensitivity to any or all tastes (hypergeusia). But disgeusia is closely related with quality of life because obstruct the pleasure of eat. So the identification of the magnitude of dysgeusia is the annoyance that represent for the LC patient. One of the most widely used tests is the taste and smell survey (TSS), which is a 16-item questionnaire that can help guide the taste alteration complain and give advice to improve the sense of taste making the eating process a more pleasant experience. Moreover, a cachexia grading system which takes into consideration body mass index (BMI) and weight loss to stratify patients into 5 risk categories (0 [pre-cachexia] - 4 [refractory cachexia]) was performed from a data set population of 8,160 heterogeneous cancer patients, with significant impact on survival according to the risk grade category.

After 8-weeks of treatment, patients who received Nabilone increased their caloric-intake (342-kcal) compared to patients receiving placebo (p = 0.040). However, it was discontinued in Mexico. Another option considered to improve appetite is mirtazapina, available in Mexico and with preliminary reported improvement of appetite. Moreover, there is a current randomized clinical trial running in Instituto Nacional de Cancerología of Mexico comparing mirtazapine versus placebo in NSCLC-patients for the evaluation of improvement of appetite, energy-intake and quality-of-life. On the other hand, since dysgeusia is presented before treatment, nutritional advice should start at LC diagnosis to prevent or improve the taste disturbances. Preparing food with-reduced or absence altogether of condiments, choosing foods with a milder flavor, with a cold or warm temperature which could be more enjoyable to the patients. Additionally, LC patients classified with cachexia-grading system showed those with low-risk had a significantly longer survival compared with intermediate or high risk (Figure-1).

The highlights after the opportune nutritional risk evaluation of LC patients are concentrated in reach an optimums proportion of proteins, carbohydrate and lipids in the caloric intake including if is necessary oral nutritional supplements (ONS). Cancer patients consuming two ONS per day during 8 weeks after their first cycle of chemotherapy showed increment in body weight, fat-free mass, skeletal muscle mass, body cell mass, and fat mass compared to those without ONS. Once the cachexia is evident, a multitargeted approach seems essential for its treatment, including combination of nutritional support, appetite stimulants drugs and a suitable program of pulmonary rehabilitation and/or physical exercises. The food plan should be centralized in the complete symptoms burden and be promoting the enjoyment of eating. It is important to start as early as possible for avoid progression of cachexia stage even before weight loss can be presented. The continuous follow up of patients should be approximately every 3 weeks. The future of the multidisciplinary approach to the management of LC patients must therefore not overlook the important role of nutrition in the quality of life and clinical outcomes.

Keywords: Anorexia, Dysgeusia, Cachexia, Lung cancer



Stigma Around Palliative Care: Why It Exists and How to Manage It

C. Zimmermann1

1Princess Margaret Cancer Centre, Toronto/Canada

It has been shown that early involvement of palliative care improves outcomes for patients with advanced cancer as well as for their caregivers. Several trials, systematic reviews and meta-analyses have demonstrated benefits in quality of life, symptom control, mood, and satisfaction with care. However, palliative care services tend to be involved only in the last weeks of life. One possible reason for this reluctance to engage with palliative care is the stigma that is often associated with it, and the misunderstanding among healthcare workers and the public that palliative care is equivalent to end-of-life care. We conducted several studies investigating the opinions of oncologists, palliative care physicians, patients, caregivers and the public about palliative care in general and early palliative care in particular. Our overall aim was to investigate possible reasons for the lack of referral or late referral to palliative care in order to inform policy and practice in this regard.

We conducted a large qualitative study, in which we interviewed 71 patients with advanced cancer and their caregivers who had been randomized (or not) to receive early palliative care in a previous cluster randomized trial. A total of 48 patients (26 intervention, 22 control) and 23 caregivers (14 intervention, 9 control) completed interviews; we assessed their attitudes and perceptions about palliative care using a grounded theory methodology. We also conducted several surveys. The first was a national survey of oncologists (n=603, response rate 72%) regarding their referral practices to palliative care. We then conducted another survey, this time of palliative care physicians (n=531, response rate 71%) to assess their attitudes toward early palliative care and their readiness to provide this care. Both surveys were administered both online (by email) and by regular mail. Most recently, we conducted a large online survey of the Canadian public (n=1518) regarding their knowledge and attitudes related to palliative care. This last survey was distributed by MD Analytics, a healthcare research firm.

In the grounded theory study, participants in both trials arms associated palliative care with death, hopelessness, dependency and end-of-life comfort care. Participants stated that they feared and avoided palliative care, and that their perceptions often originated from interactions with health care professionals or from the media. During the trial, the impression of palliative care for intervention group participants changed to one of “ongoing care” that improved their “quality of living” but they still felt that the term palliative care carried a stigma. Intervention group participants emphasized the need for education by health care professionals on the meaning of palliative care; a vocal subgroup called for the renaming of palliative care, though they had no suggestion for a name.

In the survey of oncologists, 84% stated that they referred patients usually/always, but most referred late in the disease course. Forty-four percent agreed that patients had negative perceptions of palliative care. One third would refer earlier to palliative care if it was renamed supportive care. Predictors of earlier referral included satisfaction with palliative care service availability, acceptance of the palliative care service of patients on chemotherapy and completing a rotation in palliative care.

In the survey of palliative care physicians, more than 90% supported early palliative care referral, but only half had resources to deliver it, and only 20% received early referrals. Those with adequate resources were more likely to be family physicians (p=0.02) and to work on teams (p=0.03). Those receiving early referrals were less likely to agree that patients should stop chemotherapy before referral (p = 0.009). Although

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60% agreed that patients perceive the term “palliative care” negatively, only 21% of palliative care specialists supported renaming the specialty.

In the survey of the Canadian public, 59% stated they did not know, prior to reading the World Health Organization (WHO) definition, that palliative care could be involved early in the course of illness, and 45% did not know palliative care could be provided together with other treatments aimed at prolonging life. Eighty-nine percent felt the WHO palliative care definition helped them to better understand what palliative care is, and 91% believed that Canadians should be made aware that palliative care can be included early in the course of a patient’s illness. Only 15% of participants thought that a change in name of palliative care would increase their willingness to engage with palliative care if they were diagnosed with a serious illness.

The stigma around palliative care is mainly due to the association of palliative care with end-of-life care and is perpetuated by late referral practices. Reasons for this late referral pattern may include factors at the level of the patient and family (e.g. lack of understanding of palliative care), the oncologist (e.g. lack of education in palliative care), and the palliative care team (e.g. lack of availability or prohibitive referral criteria). In order to reduce stigmatization of palliative care and to promote early access to palliative care for patients with cancer, several changes are suggested. Oncologists would benefit from palliative care training during their residency programs, which could promote integration with palliative care specialists and improve understanding of the relevance of palliative care early in the disease. Palliative care physicians would benefit from reviewing their referral criteria, and from collaboration with primary care teams to enable more timely provision of palliative care. Lastly, a coordinated effort needs to be made to educate the public about palliative care and its relevance early in the disease course. Although renaming of palliative care services could be considered on an individual basis, only a minority of oncologists, palliative care physicians and members of the public thought that renaming palliative care would be helpful.

Keywords: Palliative, Stigma, Referral, Cancer, Survey


IASLC Pre-Conference Advocacy Group Meeting

Role of Patients in the Health System

I. Zervino1

1Fundacion Pacientes de Cancer de Pulmon, Beccar/Argentina

Health systems are designed for acute diseases and most pathologies are chronic. There are access barriers that do not depend only on financing.

Judiacialization as a symptom of an unworkable system. Trends indicate that the situation will worsen if there are no structural changes.

Analysis of the experience of accompanying patients to navigate the health system.

It is necessary to explore the possible alternatives to involve patients in the public policy discussions in health.

The patient can play a significant role in the transformations necessary for the system.

Keywords: Patient, Health system, Public policies


IASLC Pre-Conference Advocacy Group Meeting

Re-thinking Access to Care

M. Perez Vela1

1Fundación Rebecca de Alba, A.C (FRA), Mexico City/Mexico

Lung cancer represents a burden to patients, families and governments around the world. In low income countries, it is a public health issue that needs public health policies to acknowledge and create quality access. In México, due to the complexity of the health system care access is linked to employment condition. Seguro Popular, a public health policy created in 2000 to give health coverage to informally employed patients includes in its Catastrophic Expense Catalogue only 7 types of cancer in adults excluding lung cancer. Other public health policies have limited access to quality and innovative treatments for many illnesses including lung cancer, besides, lung cancer patients are stigmatized and usually blamed for having brought the illness on themselves. Lung cancer in Mexico and other Latin American countries correlates to poverty, low educational and cultural level and the lack of public policies to create successful prevention and early detection programs. The importance of patient organizations is crucial in the construction of such policies.

FRA adapted a navigation model to meet the needs of cancer patients in Mexico based on the acknowledgement that every patient diagnosed with cancer has to deal with the same variables: loosing health, losing their job, migration, to receive treatment, restructuration of the family system. Through a navigation model that systematically accompanies the patient and caregiver directly in the oncology medical center to process their clinical file, Schedule their treatment visits, understand the treatment scheme, supply them with information on how to navigate the health system and to get to know the support organizations available, empowers the patient and caregiver to comprehend the importance to complete treatment. Networking with other cancer organizations broadens the range of support to patients. Educational and information support groups are held periodically, monthly or every two weeks in different hospitals in order for patients and families to share their experiences dealing with cancer.

Patient navigation benefits cancer patients and their caregivers and families, it empowers and educates patients to better cope with the disease. Patient navigation accompanies the patient in their journey to complete treatment and in other cases to a better quality of life during the illness. Medical centers in Mexico do not consider patient navigation as an organic need to improve the service they offer to patients it is mostly done by organizations. Through patient navigation the organization gets to know and share the patient´s journey, the obstacles and barriers in the way to completing treatment, it is also a source of data that can help build better health care and access plans for the medical center but also for public policies.

Patient advocacy is core for any public policy Patient Navigation could be an important source of information to build it. Patient navigation should be organic to the health system in every country, foremost in low income countries. Lung cancer patients in Mexico are a particularly vulnerable group, patient navigation should be part of a public policy tending to improve their quality of life. Access is much more than been treated, it means been diagnosed at an early stage, been able to understand this diagnosis, been accompanied by someone who knows the system, been able to take informed decisions over the best treatment available and having a patient centered health system.

Keywords: Patient navigation, Access, Lung cancer

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Cancer Control Program and Tobacco Forum

Importance of Smoking Cessation in the Treatment of Lung Cancer Patients

C. Dresler1

1Action on Smoking or Health, USA, Montrose/United States

Tobacco use remains the leading cause of preventable death worldwide and is a significant risk factor for oncologic, cardiorespiratory, and pulmonary diseases. Evidence to date predicts that persistent tobacco use during therapy reduces the efficacy of disease treatment. (2014 US Surgeon General Report; Dresler, Lung Cancer 2003) To maximally improve outcomes from cancer therapeutic intervention, tobacco cessation in the persistent user should be uniformly provided as part of routine clinical care.

The 2014 US Surgeon General’s Report reported on a causal relationship between smoking and most cancers; continued tobacco use in cancer patients/survivors have higher all-cause and cancer-specific mortality; and people who continue to smoke have a higher risk of cancer recurrence, poorer response to treatment, and increased treatment toxicity. In addition, persistent smoking impacts weight, appetite, wound healing, pain control and second primaries.

Unfortunately, tobacco use is uncommonly captured in clinical oncology trials. If tobacco use is assessed, it is usually at the initiation of the study, and not assessed throughout the intervention. There has been the development of a validated survey (C-TUQ) for assessment of tobacco use in clinical trials.(Land S, 2016 Clinical Cancer Res) Also, in the paper by Gritz, et al., there is a survey that can be incorporated in the clinical assessment - outside of a clinical trials. (Gritz ER, 2005 Cancer Epidemiol Biomarkers Prev)

There is rarely an assessment of the impact of persistent tobacco use on the outcomes of the study. Although oncologists acknowledge the importance of tobacco use in cancer patients, they uncommonly intervene with their patients to assist in their tobacco cessation. (Warren GW, 2013 JOP; Warren GW, 2013 JTO) It is even difficult to identify the prevalence of smoking or other tobacco use in cancer patients or survivors.

Tobacco use rates are dropping in a few upper income countries, but even in patients with a diagnosis of lung cancer, there is still a substantial prevalence of smoking. In lower and middle income countries, where there is still a substantial prevalence of smoking, that prevalence in cancer patients is likely to be even higher. Although tobacco prevention and control are the best methods to prevent lung cancer - even with a diagnosis of cancer, it is important to assist patients to quit to maximize the treatment outcome.

Keywords: Smoking cessation in lung cancer

I.9-1Thursday, October 17, 17:00 – 18:00

Release of Special Issue Session

Lung Cancer Epidemiology, Diagnosis and Treatment: Release of the Special Issue by “Salud Pública de México”

O. Arrieta1

1Thoracic Oncology Unit, Instituto Nacional de Cancerología, México City/Mexico

The greatest disease burden worldwide is chronic diseases. For the Mexican context, the highest incidence and mortality are represented by cardiovascular disease, diabetes mellitus, and

cancer. Despite the overwhelming evidence supporting this fact, until know, Mexican population-based cancer registries have just been proposed towards population prevention. In this context, lung cancer (LC)represents an important challenge for global health as it is recognized as the leading cause of cancer death in Mexico and the world. Additionally, most cases are considered preventable deaths, considering the largest attributable fraction is due to tobacco smoke exposure. Therefore there is a tremendous need to address this problem from an integral vision that includes preventive axes, which should be emphasized. As well as the improvement of medical approach strategies in patients who already harbor LC. This constitutes the importance of the special number of lung cancer in the Mexican Public Health magazine. According to data from the Global Cancer Observatory (Globocan), approximately 190,667 incident cases of cancer occur each year in Mexico, from which 7,811 correspond to LC cases. Despite not being the neoplasm with the highest incidence in the country, it still represents a major cause of death.

In this special issue, four perspectives are presented with a multidisciplinary vision that gives them great originality and transcendence. Among them is a section on the epidemiology of LC in terms of incidence and mortality. It also includes a group of contributions on the progress in terms of prevention and control of smoking and other associated exposures, which is already part of a tradition of the RSPM. Further, the publication of proposals for evidence of population-based health policies, a section on LC epigenetics and perspectives for improving diagnosis and treatment is included as well. All of this with the purpose of finally address the need for clinical trials to improve health coverage and quality of life and appropriate and context-based clinical guidelines.

To address this need the special issue also includes the National Clinical Practice Guideline for the management of non-small cell lung cancer in early, locally advanced and metastatic stages. This work has been the result of the collaboration of about 60 specialists in thoracic oncology, medical oncology, surgical oncology, radiology, among many other areas, to prepare a document in which the standard of care for patients with this disease is detailed according to the most recent medical literature. The following describes some of the main contributions derived from research and consensus groups that need to be emphasized. Likewise, the disease burden for the national context with different perspectives is described, one of them considering the effect of age, period and cohort, as well as the trends of mortality stratified by urban-rural area and the economic burden that it represents in the Mexican Social Security Institute System. Through this type of approach, we can identify the geographic areas that require additional interventions.

An article on trends in mortality is included during this period that highlights the progress that has been made and the challenges we still face in specific populations. The work Lung cancer in Mexico: Findings from the Global Burden of Disease Study, 1990-2016 complements the national vision with the findings of this great study internationally.

On the other hand, in the biological question the issue of the mutational profile is addressed by means of next-generation sequencing (NGS) in Mexican population and, from two reviews, addressing LC etiology and treatment, which included the potential association of Mycobacterium tuberculosis infection with risk of developing this neoplasm, and relevance of epigenetics in non-small cell carcinomas and their genomic evolution on small cell cancer. Finally, in this inter-institutional, national and international effort, the elements that are provided are aimed to generate an organized social response not only to guarantee access to early diagnosis and treatment but also to recognize the need to reinforce and consolidate population policies for LC prevention and high-quality control.

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I.10Friday, October 18, 2019, 08:30 - 09:30

Diagnostic Imaging Innovation

Initial Experience with EBUS TBNA for the Management of Lung Cancer in an Andean Latin American Country: Peru

P. García-Mantilla1,2, S. Castro-Bernardini21Guillermo Almenara Hospital - Peruvian Social Health Insurance, Lima/Peru, 2SANNA San Borja Private Clinic, Lima/Peru

Endobronchial Ultrasound guided Transbronchial Needle Aspiration (EBUS-TBNA) is an established way for sampling mediastinal lymph nodes and parenchymal lesions located adjacent to the central airways to aid in diagnosis and staging of lung cancer. Real-time endobronchial ultrasound (EBUS) guidance is a particular method of fine needle aspiration biopsy, a minimally invasive diagnostic test used to obtain adequate samples of tissue with a high diagnostic yield.

In the developed world, EBUS has become the standard of care and has rapidly reached a pivotal role in the diagnosis and staging of lung cancer even with a potential high yield for molecular analysis. This safe technique is also a valuable and practical tool for re-staging of Non-Small Cell Lung Cancer.

Therefore, in the era of precision medicine for lung cancer treatment, developing countries in Latin America should already have access to this minimally invasive procedure that avoids unnecessary invasive methods and surgeries.

A total of 14 lesions were punctured, 13 were hilar and mediastinal lymphadenopathies and 01 was a right basal lung nodule. No complications were experienced. Six lesions were targeted in region 7, three in region 4R, three in region 4L, and one in region 11Rs. The size of the lesions ranged from 7 mm to 20 mm. EBUS-TBNA identified malignant cells in 11 lesions (10 adenophaties and 01 lung nodule) and benign cells in three adenophaties.

Keywords: Bronchoscopy, EBUS-TBNA, Lung cancer, Staging

I.11Friday, October 18, 2019, 08:30 - 08:45

Diagnostic Imaging Innovation

Diagnosis in LATAM Region: Differences in Access to Technology

M. A. Hernández1

1Instituto Nacional de Cancerologia, Mexico City/Mexico

Inequality in service coverage and access to required assistance persist and is strongly determined by socioeconomic characteristics and geographical barriers. In Latin America (LATAM) and the Caribbean, over 30% of the population do not have access to health care for economic reasons, and 21% do not seek care because of geographical barriers. The latest available consensus shows that in 2010 there were about 42 million indigenous people in LATAM, making up nearly 8 percent of the total population. Indigenous people face significant barriers to adequate healthcare due to linguistic differences between patients and healthcare professionals (1). Likewise, indigenous families who must travel long or costly distances to get medical attention experience apathy to search for health services. Furthermore, in urban areas, the population show high levels of dissatisfaction with their health care system, which may explain why a broad population of Latin Americans with sufficient income chose private services over universal public services. In 2018, over 60% of newly diagnosed patients with lung cancer were located in low and medium-income countries as the ones in LATAM. Therefore two-thirds of the deaths attributed to lung cancer worldwide occur in these countries. In 2009 half of the economic resources destined for cancer were addressed only

for pharmacotherapy. Compared to high-income countries, only 0.125% of the per capita income is intended for treatment acquisition (2, 3).

The challenges that face LATAM to make a diagnosis and give treatment are not always related with economic factors. There are other barriers such as a) lack in investment in research, b) limitations with the current established health care services where lung cancer is not considered a priority even though is the leading cause of cancer-related death worldwide, and c) limitations in drug supplies, and its affordability. Also, the low number of cancer specialists per head of population contributes to work overload and restricts them from participating in clinical cancer research (4). This situation is deleterious to the development of clinical trials, and national health authorities should ensure sufficient cancer specialists for the population volume. In this regard, we urge governments to design and implement better public policy and infrastructure for lung cancer prevention, screening, and treatment availability. In the last decade, lung screening programs have been established in high-income countries. However, only two extensive studies have shown benefit in lung cancer timely detection within the high-risk population. These encourage the incorporation of early lung cancer detection campaigns (5). The experience in low-income LATAM countries is limited to a Brazilian study in which they screened 800 patients with a high prevalence of granulomatous disease as in the rest of LATAM region. This research exposes LATAM ethnic differences and environmental exposures (wood-smoke exposure) that differs from high-income countries. Screening requires medical equipment and health care personal to obtain good results when detecting a vulnerable population. A Cost-effective lung screening program is subject to demographic characteristics and how the program is designed. Inequalities in access to health services among and within LATAM countries prevails, which means that we need to ensure equity in both access and quality of services. We need new policies that allow better coverage of human and technological resources for lung cancer patients. Until now, there is insufficient evidence for screening and treatment programs for lung cancer done in LATAM despite being the most common cancer worldwide.

References1. OECD/CAF/ECLAC. Latin American Economic Outlook 2018: Rethinking Institutions for Development,. Paris; 2018.2. Raez LE, Cardona AF, Santos ES, Catoe H, Rolfo C, Lopes G, et al. The burden of lung cancer in Latin-America and challenges in the access to genomic profiling, immunotherapy and targeted treatments. Lung Cancer. 2018;119:7-13.3. Raez LE, Santos ES, Rolfo C, Lopes G, Barrios C, Cardona A, et al. Challenges in Facing the Lung Cancer Epidemic and Treating Advanced Disease in Latin America. Clin Lung Cancer. 2017;18(1):e71-e9.4. Rolfo C, Caglevic C, Bretel D, Hong D, Raez LE, Cardona AF, et al. Cancer clinical research in Latin America: current situation and opportunities. Expert opinion from the first ESMO workshop on clinical trials, Lima, 2015. ESMO Open. 2016;1(4): e000055.5. Kielstra P. Lung cancer in Latin America: Time to stop looking away. Economist Intelligence Unit. 2018;1(1):1-65.

Keywords: Lung cancer diagnosis, LATAM cancer

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I.12Friday, October 18, 2019, 09:00 - 09:15 Diagnostic Imaging Innovation

Interventional Radiology and RFA

J. Guerrero Ixtlahuac1

1Instituto Nacional de Cancerologia, Tlalpan/Mexico

Lung cancer is the leading cause of cancer death in the world; only 17% of stage I patients are inoperable at diagnosis; without treatment lost a 5-year survival of 6% and a half of 9 months. The locoregional therapies are an alternative with a curative intention for inoperable patients in stages I achieving focal cell death avoiding damage to healthy tissues.

There are multiple options which are the following: Thermal: Cryoablation, microwave ablation, radiofrequency ablation, FOCUSED; Non-thermal: irreversible alcohol and electroporation and finally SBRT.

Radiofrequency ablation: It is based on forming an alternating current circuit between the patient and the ablation machine: the electric current transmitted to the 14-17G needle travels through the tissue resistance by agitating the ions generating heat (60-100 ° C necrosis coagulative and carbonization> 110 ° C), the residual energy is absorbed by a gel patch placed on the patient. Disadvantage: Heat dissipation effect by cooling in vessels> 3mm and bronchi of more than 2cm in diameter conditioning absence of ablation around the blood vessel.

Microwave ablation: Heat generation is based on the generation of electromagnetic fields that mobilize water ions generating heat, its advantage is that the heat generated is homogeneous with temperatures around 150 ° C without being affected by electrical conduction or dissipation of Heat however has a low availability, high cost and both microwave and radiofrequency ablation merit general anesthesia due to the pain generated by thermal ablation, especially the latter.

Cryoablation: Its effect is due to the expansion of the Argon at high pressure (Joule-Thompson effect) generating local cold, from -20 ° C there is a direct cellular damage due to rupture of the membrane by crystals following a period of defrosting of 10 minutes in which the endothelial damage allows the direct flow of vascular space to the extracellular space and through osmosis the interstitial water penetrates the permeable membrane destroying the cell, its advantage is the proper visualization of the ice ball, it does not need general anesthesia and generates immune response; Disadvantage is the low availability and the risk of bleeding.

Alcohol ablation: It is less and less used for its low effectiveness, its effect is due to the fact that it conditions coagulative necrosis and protein denaturation; Advantages: simplicity, low cost, safety- ablation of tumors difficult to treat with ARF due to proximity to vessels or bronchi, Disadvantages: high recurrence rate 49% in lesions> 2 cm, multiple sessions (painful) and occasionally ethanol toxicity.

Irreversible electroporation: Its mechanism of action is due to electrical pulses of high voltage and low energy that creates defects in the membrane conditioning apoptosis and elimination of cell debris by phagocytosis; The process takes 8-10 weeks, so it is important not to assess PET-CT or CT before 3 months.

The indications are patients are inoperable NSCLC stage I and II, salvage therapy in advanced stages and limited metastatic disease of low volume, Inoperable patients: Major criteria: FEV1 ≤ 50%, DLCO ≤ 50%, and minors criteria: ≥ 75 years, Pulmonary hypertension, Left ventricular function ≤ 40%, pO2 <55 mmHg arterial at rest-exercise and pCO2> 45 mmHg. Lesions smaller than 3.5cm, away from 3mm diameter vessels and bronchi> 2cm, are preferred.

Radiofrequency ablation in stage I patients achieves a global survival of 94% 1 years, 86% 2 years and 61% 5 years with a 45 month progression-free period in tumors <3cm; Pastorino et

al reports a 5-year global metastasectomy survival of 36% and Baere et al reports 5-year overall survival in patients treated with RFA of 51%.

The worst candidates for ablation: KRAS mutation and micropapillary histological subtype. Surveillance is by contrast CT and mRECIST criteria, evaluating areas of residual enhancement with contrast medium or by PET-CT using PERCIST criteria.

Complications are minor in expert hands compared to that reported in most of the world literature: pneumothorax: 17-54%, 93% of the pneumothorax resolve with Heimlich valve, 4% pulmonary hemorrhage, 4% self-limited hemoptysis 0.061% air embolism and seeding tumor 0.01-0.06%.

The immune-stimulating effect of ablative therapies is currently being studied; which is explained by the exposure of phagocytic tumor antigens by macrophages promoting the expression of (IL-1), IL-6, NF-κβ and tumor necrosis factor-α (TNF-α).

Keywords: RFA, Interventional radiology, Lung cancer

I.12-1Friday, October 18, 2019, 10:45 - 11:00

2019 American Society of Clinical Oncology (ASCO) / IASLC Symposia: Lung Cancer Pathology in the Era of Targeted Therapy

New Next Generation Sequencing Platforms (NGS) Versus Tailored Panels

I. Wistuba1

1Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Texas/USA

Large scale application of this technology in tumor molecular characterization of lung cancer led to the generation of databases that catalog the next generation of sequencing (NGS) tumor genome. Several NGS platforms and assays have been developed and applied in the clinical setting to genotyping of tumor for targeted therapy, including lung non-small cell carcinoma (NSCLC). These NGS platforms have all the features required to carry out simultaneous analysis of a large number of genes (hot-spots and exomes) with actionable alterations (mutations, copy number changes and translocation) in tumor tissue, and thus providing a more precise molecular characterization of the tumor. Such targeted NGS panels for somatic aberrations detection, include actionable lung cancer genes (100-400 genes) aiming to increase the percentage of patients with detectable actionable somatic gene alterations that can be used to guide treatment decision in standard of care and clinical trial settings. Importantly, these NGS panels can be applied to clinically relevant tumor biopsies (formalin-fixed and paraffin-embedded tissues and cytology specimens), and cell freed DNA samples (liquid biopsy). In summary, NGS panels have the following benefits in lung cancer: a) Provide information in multiple targetable gene abnormalities; b) data on actionable mutation, copy number variations, indels and translocations; c) can be performed in routine small FFPE tissue samples and liquid biopsy (cfDNA); d) turn-around time acceptable for clinical management and costs being significantly reduced; e) clinically, it offers to patients more options to get off-label treatment and enter in genomic-based clinical trials; and, f) may provide information on tumor mutational burden (TMB) and other potential genomic-based immune-suppressive genotypes (e.g., LKB1 mutations). Although NGS panels are preferred, there are other more cost effective genotyping platforms that can provide information on the minimal set of genes abnormalities (EGFR, ALK, MET, ROS1, BRAF, NTRK) required for the proper management of NSCLC patients testing panels of gene hot-spot abnormalities using quantitative (q)PCR and digital droplet (dd)PCR methodologies. The integration right genotyping testing multi-gene panels in lung cancer management of patients is of great clinical importance, as well as the selection of the right platform for each clinical setting.

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I.13Friday, October 18, 2019, 11:00 - 11:15

2019 American Society of Clinical Oncology (ASCO) / IASLC Symposia: Lung Cancer Pathology in the Era of Targeted Therapy

Molecular Testing for Lung Cancer Available in Latin America

M. Varella-Garcia1

1University of Colorado Anschutz Medical Campus, Aurora/United States

Access to lung cancer (LC) diagnostic and treatment methods varies extensively around the globe. Latin America (LA, including Caribbean) is a large area comprising 30+ countries and 650+ million people. Incidence of lung cancer ranked third among the new cancer cases but first in death rate. In order to capture information regarding current practices and barriers to molecular testing (MT) in lung cancer, the IASLC conducted a survey among three tracks of health professionals. T1 included professionals performing, interpreting and reporting the molecular assays, T2 included professionals requesting the tests and treating LC patients, and T3 included professionals responsible for tissue/specimen procurement for LC MT. There is an IASLC committee working on the data analyses and on their behalf, I am preliminary presenting here some results from 254 participants from 17 LA countries, including 33 from T1 (13%), 169 from T2 (67%) and 52 from T3 (20%). These respondents represented respectively 8, 16 and 13 countries.

Based on the T1 data, the genes most commonly tested were EGFR, BRAF and KRAS for mutations, ALK and ROS1 for rearrangements and PDL1 for protein expression. Other genes less frequently tested were ERBB2 (HER2), RET and MET. In most labs (59%), single assays still prevailed, whereas 41% of labs multiplexed their assays. In most of the T1 respondents’ labs (74%) the fraction of cases rejected due to sample inadequacy was low, although in some labs these cases ranged between 10% and 30% of the workload. Two major factors influencing the failure to generate a result were insufficient amount of tumor cells in the specimen and poor tissue quality usually consequence of inadequate fixation. Enrichment for tumor cells through micro and macrodissection was often performed (85%). Twelve labs acknowledged offering MT on liquid biopsies. The average turnaround time (TAT) for providing results was listed as under 10 business days by most T1 respondents (89%). In most cases, the labs had costs reimbursed by pharmaceutical companies but patient direct payment, private health insurance system and government funds were also relevant financial resources. Most labs acknowledged conducting validation tests before implementation of new assays and regularly participating in proficiency testing efforts. Few T1 respondents (N=4) considered that LC patients/physicians in their countries were satisfied with the MT conditions, although N=10 respondents indicated that they were satisfied.

Based on the T2 data, we learned that 81% of respondents requested MT for all LC patients, while 17% requested only in special conditions, such as cases with adenocarcinoma histology or component, never-smoker, female, and young age. 30% of T2 respondents were not aware of the CAP/IASLC/AMP guidelines. Approximately 30% used labs in the same institution/city, 40% referred to a central lab in their country and 40% outsourced to a lab in another country. Tests more commonly ordered were EGFR and BRAF mutations, ALK and ROS1 rearrangements, and PDL1 expression. Less common, KRAS and HER2 mutations, MET amplification and exon 14 skipping, and RET rearrangement. Rebiopsy at disease progression was common when LC patient was on an EGFR TKI (85%), less common when other TKI was in use (52%). Overall, request for MT on liquid biopsy was common (74%). The MT was reported to fail to generate a conclusive result in <10%, 10 to 30%, or >30% of cases, respectively, by 58%, 31% and 11% of T2 respondents. The perception of TAT by T2 respondents was longer than the TAT declared by T1 respondents, 47% agreed to have received reports within 10 business days while 53% extended to >10 business days. About

23% of T2 respondents were not aware of test technical details but the knowledgeable ones have agreed with the T1 respondents in that single assays prevailed over multiplex assays. Most T2 respondents admitted to understand the MT report well (87%) but 13% recognized lack of scientific or technical knowledge or complained about poor quality of the report.

Among T3 respondents, only 38 worked actively in procurement of LC specimens for MT and only 76% of them conceded to know the ideal conditions for preservation of LC specimens for MT and have them available in their practice. 38% of T3 respondents had only a fair/poor degree of knowledge about how LC MT is performed but 72% have close pathologist assistance to evaluate tissue sufficiency and oversee tissue processing and handling after the procedure through detailed protocols, phone call or discussion in multidisciplinary meetings. Unfortunately, 29% of T3 respondents are not informed when a specimen they have procured fails to generate a result in the molecular lab.

Multidisciplinary meetings to discuss clinical cases at least once a month were common in the respondents’ institutions. These meetings are attended by physicians of different specialties such as pathologists, medical oncologists, thoracic surgeons, intervention radiologists, pulmonologists, hematologists, and by other health care professionals closely related to lung cancer care such as nurses, cancer scientists, biologists, biochemists, biotechnologists, biostatisticians, and bioinformaticians,

The perception of the T2 and T3 respondents regarding the fraction of LC patients who were molecularly tested differed when they compared the settings of their own clinic and of their country. Considering the 4 categories of LC patients tested as <25%, 25%-49%, 50%-74%, and 75%-100%, the T2 respondents estimated the frequencies of patients in their own clinic as 18%, 7%, 29% and 46%, and in their country as 39%, 35%, 22% and 4%, respectively. The T3 respondents estimated the frequencies of patients in their own clinic as 34%, 22%, 29% and 15%, and in their country as 66%, 22%, 10% and 2%, respectively. These differences strongly suggest that T2 and T3 respondents are not an unbiased representation of their peers in their countries.

Despite the limitation of the small sampling size, this study represents a significant effort in surveying the conditions of MT in LC in the LA region. These analyses identified strengths and weaknesses, and the detailed assessment will support regional initiatives to improve specific conditions and provide best therapeutic options to LC patients.

Special acknowledgments to Murry W. Wynes, Matthew P. Smeltzer, and Meghan B. Taylor for providing preliminary data.

Keywords: Biomarkers, Molecular diagnostic

I.13-1Friday, October 18, 2019, 10:45 – 11:00

Novel Diagnostic and Prognostic Markers

New Technologies for Liquid Biopsies and Looking for Cost Effective Options for LATAM (RT-PCR, cfRNA, Exosomes, ECVs and CTCs)

L. Raez1

1Memorial Cancer Institute/Memorial Health Care System, Pembroke Pines/United States of America

Liquid Biopsies have been going to the front lines in the diagnosis of cancer. They are more accepted and the health care providers are getting used to use them as alternative or complement of tissue biopsies. Our 2018 IASCL guidelines in liquid biopsies written by Rolfo et al in the Journal of Thoracic Oncology suggest the use of liquid biopises in cases that there is not enough tissue or a new biopsy is not feasible. But now that we have been discovering resistant mutations in the EGFR gene (T790m, c797, etc), ALK fusions and others it is becoming necessary to repeat the NGS analysis to find the best therapy

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for the patient, then to repeat or do multiple tissue biopsies to accomplish this goal and that becomes very cumbersome and difficult. In the specific case of lung cancer, biopsies are not easy because they can cause pneumothorax and lung cancer patients are not totally healthy most of them are smokers and they have already emphysema and/or COPD that increases the chances of complications if the biopsies don’t go well. However, there are still concerns about liquid biopsies how reliable are? and if they can totally replace tissue biopsies one day? Our own experience already published in more than 80 patients showed that tissue biopsies are not enough or don’t have any extra tissue in around 21% of the patients and all of these patients benefited of the liquid biopsy approach (NGS in cfDNA) however, there were cases that the liquid biopsy was unable to find the molecular aberration and the tissue did, then it’s for now safe to say that they are complementary. Another problem of the liquid biopsies is the cost specially for Latin America (LATAM), the NGS platforms are very expensive despite the fact that the prices have been decreasing in the last years but are still not affordable for the majority of the LATAM population; hence the options to do in LATAM hotspot testing, RT-PCR, FISH, exosomes and other technologies. However, there are challenges, we know for example that hotspot testing that is commonly use in LATAM due to its lower cost, it’s not very comprehensive and miss frequently mutations or genetic aberrations. RT-PCR is very sensitive and reliable but probably is a better test to find a specific genetic aberration than to do a panel analysis of several genetic aberrations at the same time unless we have the probes for all genes; and a similar problem we have with FISH: now we can use FISH to diagnose ALK, ROS1, NTRK1-3 and RET however that means that we will need to do at least 6 different FISH tests! Only to cover these genetic aberrations and we still have to test the patient for EGFR and other genes something that makes them more expensive than running NGS one time. Probably IHC is a good alternative for LATAM for now, we have good validation of IHC for ALK diagnosis and soon we hope to have one for ROS-1; there are also several attempts to make NTRK 1-3 IHC better but probably with so many variants is a very hard task and still will not cover other genetic aberrations like BRAF, KRAS and others. These are exiting times for LATAM and other countries giving the patients there the opportunity to access molecular targets but we are far from adequate coverage of most of the patients.

I.14Friday, October 18, 2019, 12:15 - 12:30

Case Presentations and Review of New Developments in Surgery

Sublobar Resection for Lung Cancer

M. Block1

1Memorial Healthcare System · Department of Thoracic Surgery, Hollywood/United States

Small, less than 2 cm diameter lung cancers, present a challenge. Resection of just the nodule with a generous margin of normal lung is technically possible, but the only randomized trial to compare it to lobectomy demonstrated inferior survival. That trial is now 25 years old, and two important developments have led to renewed interest in the oncologic value of sublobar resection. First, increasing use of chest CT for early detection has led to the discovery of small lung cancers, many with biologically indolent behavior, for which a lobectomy seems extreme and possibly unnecessary. And second, developments in minimal invasive surgical techniques have led to increasing feasibility and decreasing morbidity of Sublobar resection, especially in patients with limited lung function. An important distinction to be made with Sublobar resection is the difference between a “wedge” resection and a segmentectomy. A wedge is a simple excision by division of lung parenchyma around the tumor, without regard to anatomy. In contrast, a segmentectomy is an anatomic resection that mirrors a lobectomy in its attention to lymphatic and venous drainage, and parenchymal anatomic boundaries. Segmentectomy necessarily includes a hilar dissection with harvest of N1 nodes. Thus segmentectomy should have better

pathologic staging and improved oncologic outcomes, on par with lobectomy for small cancers. The renewed interest in Sublobar resection has led to a proliferation of retrospective and meta-analyses that suggest oncologic equivalence to lobectomy for small lung cancers. A prospective randomized trial is underway, but the results are not yet available. Current practice remains lobectomy when feasible, but segmentectomy should be a consideration for small cancers completely confined to an anatomic segment, especially for tumors with signs of indolent biology and in patients with limited lung function.

Keywords: Lung cancer, Lobectomy, Segmentectomy

I.15Friday, October 18, 2019, 14:15 - 14:30

Radiotherapy Innovations

Lung Cancer Oligometastatic: Radiosurgery

B. Amendola1

1Innovative Cancer Institute, South Miami/United States

Lung cancer represents the second most common malignancy in both men and women. It is estimated in 2019 that there will be 228,150 new cases in the U.S.A. with an estimated death of 174,510.

More than 40% of patients with lung cancer present with stage IV disease. However, there appears to be an oligometastatic disease state in select patients with lung cancer: controlled primary tumors, limited nodal burden, good performance status, and metachronous presentation. These patient and tumor attributes have consistently been demonstrated to predict for improved survival in patients with oligometastatic NSCLC.

This theory for cancer progression was described by Hellman and Weichselbaum in 1995, when they put forward the oligometastatic hypothesis. Their theory was based on a multistep progression of certain types of cancer, such as prostate, colorectal, and melanoma, suggesting different subcategories of metastatic disease. Early in the metastatic process, there could be limited progression when oligometastases may be treated aggressively and can be cured.

In this presentation, we will discuss the value of Radiosurgery in early and advanced lung cancer, and particularly the role in oligometastatic disease.

Review of the oligometastatic NSCLC literature, including 49 publications and 2,176 individual patients with NSCLC with five or fewer metastases in patients receiving locally ablative treatment to all sites of oligometastases showed significant control of disease. These locally ablative treatments consisted of surgical metastasectomy, percutaneous ablation, and stereotactic ablative body radiotherapy. Outcomes were variable with overall survival (OS) ranging from 6.2 to 52 months (median 19 months).

Significant predictors for OS included control of the primary tumor, N-stage, and disease-free interval ranging from 6 to 12 months. Since most of the patients were younger with good performance status and a controlled primary tumor, patient selection is of utmost importance.

Other factors for best overall survival were metachronous vs synchronous metastases, lower N-stage, and histology (adenocarcinoma vs squamous cell). Given the high 5-year OS and relatively low risk, the literature supports the aggressive management of oligometastatic lung cancer.

Keywords: Radiosurgery, Lung cancer, Oligometastases

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I.16Friday, October 18, 2019, 14:45 - 15:00

Radiotherapy Innovations

Optimal Radiotherapy for LA-NSCLC

P. Iyengar1

1UT Southwestern Medical Center, Dallas/United States

Treatment paradigms for locally advanced non-small cell lung cancer (NSCLC) have not changed dramatically till recently. RTOG 0617 demonstrated that escalation of radiation dose was not associated with improved survival. It has shown, however, that with more modern radiation techniques, median survival at five years can reach 30%. As is the case with stage IV NSCLC, the use of immunotherapy has completely changed our strategies for treating stage III NSCLC patients. The PACIFIC study has now established the standard of care for locally advanced NSCLC patients, chemoradiation followed by adjuvant immunotherapy. This change in treatment paradigm may just be the tip of the iceberg. This presentation will provide an understanding of the foundations that have led us to a current standard of care for treatment of stage III NSCLC and will also provide a view of the many studies incorporating immunotherapy that have been initiated for this patient population. Finally, the presentation will offer speculation on the future directions of treatment strategies that may be employed to treat locally advanced NSCLC.

Keywords: Locally advanced NSCLC, Immunotherapy, Radiation

I.17Saturday, October 19, 2019, 14:10 - 14:20

Targeted Therapy

ALK Genomic Aberrations in NSCLC and Clinical Implications

F. R. Hirsch1

1Mount Sinai, United States

Anaplastic Lymphoma Kinase (ALK) genomic aberrations in NSCLC was one of the first genomic aberrations, which was successfully targeted with specific drug, e.g. crizotinib, and led to rapid development of personalized therapy in NSCLC.

Crizotinib as single agent showed remarkable response (70-80%) in patients with advanced NSCLC, who had the EML-4/ALK- translocation, which occurs in 2-5% of the patients. The genomic abnormality was originally diagnosed by FISH using a defined criterion (split- apart FISH pattern in at least 15% of the cells). However, later the US FDA also approved ALK-IHC for diagnosis using the Ventana ALK-specific antibody, D5F3). Today, this genomic abnormality is mostly detected by NGS. Not only was crizotinib associated to high response rate, but also to long-term outcomes (Solomon BJ et al). However, most of the ALK-positive patients progressed, particularly in the brain. During the studies with crizotinib resistance mutations were seen

Second generation ALK- targeted therapies were developed, e. g. alectinib, ceritinib and brigatinib, primarily studied after progression of crizotinib. The new generation ALK-inhibitors showed significant better effect compared to standard chemotherapy and had particularly a good penetration and effect in the CNS. Alectinib was clinically compared to crizotinib as first line therapy in two large randomized studies (J-ALEX and ALEX), and both demonstrated significantly better outcome with alectinib (updated results from ALEX-study showed HR(DFS)= 0.43 with a median disease-free survival of 27.8 months versus 22.8 months for crizotinib), which was approved based on these studies for first line therapy in ALK-positive NSCLC ( Hida T et al, Shaw A et al).

Brigatinib was also developed as a second-generation agent and was compared to crizotinib in the ALTA-1 study as first line therapy (HR for PFS=0.49) (Camidge DR et al), but has never been

compared to alectinib. Brigatinib was demonstrated to be clearly superior to crizotinib, both with regard to outcome as well as for CNS effect. A question is, however, whether brigatinib is equal or better than alectinib as first line therapy in ALK-positive patients.

The third generation ALK-inhibitors have been developed represented by lorlatinib. Ongoing randomized studies have to demonstrate the relative role of lorlatinib compared to other generation ALK-inhibitors.

The most important question on this stage is how to sequence the different generations ALK-inhibitors. At most places alectinib is adapted as first line therapy, but there is no clear consensus on what comes after alectinib when the patient is progressing. In the future guidance based on resistant mutation pattern might direct subsequent therapy, but mutation guided therapy for ALK-positive patients has still to be fully developed. The sequencing of different ALK-inhibitors are currently studied in the US national Cancer Institute launched ALK Masterprotocol.

References:1.Solomon BJ et al: N Engl J Med 2014; 371: 2167-2177 (Crizotinib)2. Hida T et al: Lancet 2017 (Alectinib) 3. Peters S et al: N Engl J Med 2017: 377(9): 829-838 (Alectinib)4. Camidge DR et al. J Thorac Oncol 2019: (7): 1233-1243 (Alectinib) 4. Soria JC et al: Lancet 2017; 389: 917-929 (Ceritinib) 5. Camidge DR et al. N Engl J Med 2018; (21): 2027-2039 (Brigatinib)5. Shaw A et al: J Clin Oncol 2019: 37(16): 1370-1379 (Lorlatinib)

Keywords: Crizotinib, Ceritinib, Alectinib, Brigatinib, Lorlatinib


Targeted Therapy

MET, RET, BRAF Tyrosine Kinase Inhibitors and PARP Inhibitors for Lung Cancer Therapy

P. A. Bunn Jr.11University of Colorado Cancer Center, Aurora/United States

The number of molecular drivers for which tyrosine kinase inhibitors (TKI) have been approved for lung cancer therapy is increasing and now is five which includes EGFR, and BRAF mutations as well as ALK, ROS1 and TRK fusions. These molecular drivers are most frequent in lung adenocarcinomas and/or in never or light smokers. For EGFR mutations and each of the fusions, a single agent TKI is the approved therapy. For BRAF the approval is for doublet therapy and only for the v600E mutations which is somewhat more than 50% of BRAF mutations in lung cancer. The BRAF approval is for the combination of the BRAF inhibitor dabrafinib with the MEK inhibitor trametinib. The combination was approved after it showed a higher response rate (65%) and longer PFS (median 10.3 mo.) compared to dabrafinib alone. In addition, single agent dabrafinib frequently led to feedback activation of MEK which induces squamous cell carcinomas in the skin. Thus, the combination was more effective and less toxic. Interestingly, checkpoint inhibitors have more activity in patients with BRAF and KRAS mutations compared to other driver alterations.

MET exon 14 splicing mutations activate the MET receptor by a different and unique mechanism by which the mutation prevents degradation of the receptor that usually occurs through ubiquination that is defective in mutant cells. Sarcomatoid carcinomas, while rare, frequently harbor MET mutations. About 2% of lung adenocarcinomas harbor MET mutation. MET can also be activated by amplification, especially in lung cancer cells with other mutations that become resistant to other TKIs. Several MET TKIs including crizotinib, capmatinib, savolitinib, tepotinib, glesatinib, and merestinib have been demonstrated to have high response rates in both patients with de novo MET mutations and with MET amplification at TKI resistance but none

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are yet approved. Retrospective studies showed that patients with MET mutations treated with MET TKIs had higher response rates and longer survival compared to those who received chemotherapy alone. Ongoing trials may lead to approval in the near future. A bispecific EGFR/MET monoclonal antibody (JNJ372) is also in clinical trial.

RET fusions occur in about 2% of lung adenocarcinomas and like several other molecular drivers are more frequent in never smokers and younger patients. There are several fusion partners. Brain metastases seem to be more frequent in patients with any driver including RET fusions. Early trials with multi-targeted TKIs show activity but response rates were less than 50% and there was considerable toxicity. Newer agents including BLU-667 and LOXO 292 have been reported to have response rates of 55%-77%, have less toxicity and to produce responses in CNS metastases. It is likely that one or more of these might be approved in the nest year. These advances highlight the need for NGS testing that includes these molecular changes in all adenocarcinoma and never and light smokers.

PARP inhibitors inhibit DNA repair caused by certain chemotherapies, radiation therapy and are more effective in patients with other underlying DNA repair deficits. Early phase trials of several PARP inhibitors including olaparib, veliparib, talazoparib, rucaparib, and iniparib have shown activity in both SCLC and NSCLC and in both stage III in combination with chemo- and radiation therapy and in stage IV in combination with chemotherapy. These agents may be more effective in patients harboring SNFL-11 overexpression. Trials of PARP inhibitors combined with checkpoint immunotherapy are also in progress. There are ongoing phase III trials in both SCLC and NSCLC in both stage III and stage IV.

In conclusion, the growing number of molecular drivers for which there are approved therapies is growing emphasizing the need for next generation sequencing studies in all lung cancer patients who have adenocarcinoma or who are never or light smokers. While many of these abnormalities occur in only 2% of patients the benefits of TKI therapy and the low cost of adding these to NGS tests make testing imperative. PARP inhibitors have the potential to improve outcomes with chemotherapy, radiotherapy and immunotherapy.

Keywords: MET, RET, BRAF, PARP

I.18-1Saturday, October 19, 14:40 – 14:50

Targeted Therapy

NTRK Fusion Proteins

L. Raez1

1Memorial Cancer Institute/Memorial Health Care System, Pembroke Pines/United States of America

We have a new approach to cancer therapy “the Agnostic Tumor” approach. Molecular mechanisms (DNA mutations, translocations, deletions, fusions, etc.) are now the ones responsible of the origin and behavior of most of the tumors, instead of the location of the tumor as we used to think. We are in the beginning of changing the focus of cancer therapy from a single organ to a molecular marker envision. One of the best examples are the NTRK fusion proteins, NTRK genes encode for the Trk-family proteins: TrkA, TrkB, and TrkC (encoded by NTRK1, NTTRK2, and NTRK3). Normally, the NTRK family plays a role in the development of the nervous system, however, NTRK fusions are also present in solid tumors as fusion proteins responsible for growth of cancer cells, and the presence of these oncogenes is associate with poor survival in lung cancers and other tumor types. It is not surprising that these oncogenes are present in several different tumors (They are actionable in at least 17 tumor types) including adults and children. These genomic alterations are becoming a great example why the tumor agnostic approach might be the new paradigm in fighting cancer. However, there are still many challenges ahead; first for

example, the diagnostic of these genetic aberrations: we can do fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), reverse-transcriptase polymerase chain reaction (RT-PCR) and next generation sequencing (NGS) of DNA or RNA (or cfDNA in blood: liquid biopsies). Each of these approaches has strengths and weaknesses, but we also have to play this in the context of workups for other genetic abnormalities and keeping into consideration that tumor tissue specimen is very limited in many instances. Nowadays, for example, we do FISH for ALK and ROS-1 translocations, if we add three more FISH tests for each of the NTRK alterations (and maybe one more for RET fusions) will markedly increase the costs of workup in a lung cancer patient, and the gene fusion partner, that might become relevant, still might not be identified if we don’t have the right probe. RT-PCR is a great technique, but we will need a lot of primers (there are more than 60 NTRK fusions documented) to cover all the NTRK genetic abnormalities. Probably the solution is to develop better IHC? as we are doing for ALK translocations and hopefully get one day as IHC for ROS-1 and the other NTRK oncogenes so we can have a more cost-effective work up. A more practical approach might be to establish NGS in tissue or blood as the standard of care that can detect all these genetic alterations at once at the time of the diagnosis of the patient? Later we can do a more limited work up if we are looking for ALK and now NTRK resistant variants in patients that have failed treatment clinically. Nonetheless, for those who are not fans of NGS and don’t advocate this approach we can say that several NTRK 1-3 introns are not well covered by NGS. Then, we need to do whole genome gene sequencing to find them increasing the costs of the workup. These are some of the questions that remain open while we make all these diagnostic techniques more accurate and more cost effective. Some of these reasons are responsible to consider the treatment for NTRK challenging: how we can treat a patient if we can’t discover the genetic aberration? We are fortunate to have two agents: entrectenib and larotrectenib that have already been FDA approved for NTRK fusions with acceptable toxicities regardless of tumor type, patient age, and fusion type, and more data coming from other agents in development CEP-701, ARRRY-470 DS-6051b, TPX-0005. Probably LOXO 195 is the one that has been more studied for now and it’s able to rescue patients that develop resistance mutations during the treatment with larotrectenib or entrectinib.


Targeted Therapy

New Insights of EGFR Inhibition: How to Overcome Resistance & New Agents

R. Rosell11Institute Germans Trias i Pujol, Badalona/Spain

The main mechanism of resistance to first-generation EGFR TKIs is a single-nucleotide transition mutation in EGFR, cytosine to thymine (C>T) at position 2369 (ACG/ATG) causing threonine to methionine amino acid change at codon 790 (T790M). The T790M mutation occurs in cis with the original driver mutation and leads to steric hindrance and increased binding affinity for ATP. Activation-induced cytosine deaminase (AICDA) is expressed in germinal center B-lymphocytes upon antigen exposure. AICDA translocates to the nucleus, deaminates cytosine in single stranded DNA and converts it to uracil. Gefitinib, afatinib or osimertinib increase AICDA expression. A significant increase in the AICDA expression occurs in the PC9 and other EGFR-mutant cell lines upon treatment with different EGFR TKIs. AICDA is induced through the non-canonical nuclear factor-ĸB (NFĸB) (Figure). NFĸB was noted to be a mechanism of resistance to erlotinib and further studies of the Bivona group have further demonstrated that NFĸB is activated in EGFR-mutant LADCs. AICDA knockdown decreases the frequency of T790M and targeting AICDA activity directly or indirectly with NFĸB inhibitors, as well as DNA damage response inhibitors, could delay or prevent the appearance of T790M.

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The function of AICDA supports the rationale for an NFĸB-driven generation of T790M. It was demonstrated that, regardless of the use of gefitinib or osimertinib, NFĸB, STAT3 and YAP1 were activated in EGFR-mutant cell lines, including the H1975 (that harbors T790M). The downstream effectors were inhibited when the EGFR TKI was combined with blockers of the STAT3 and Src pathway. Osimertinib showed a PFS of 10.1 months versus 4.4 with platinum-pemetrexed chemotherapy in EGFR-mutant patients with T790M.

Screening for EGFR mutations is of great usefulness in customizing therapy in LADCs. However, combinatory therapies with EGFR TKIs is warranted to avoid the mechanisms of drug resistance that occur following single EGFR TKIs. The activation of STAT3 occurred a few hours after treatment with EGFR TKIs. AKT pathway is commonly activated following treatment with first- or third-generation EGFR TKIs (Figure). In addition, co-expression of other receptor tyrosine kinases is commonly present with EGFR mutations. We demonstrated that AXL expression can be driven by the Src- yes-associated protein 1 (YAP1) activation, providing a glimpse for adequate combinatory approaches. Recent articles identify AXL as a mechanism of intrinsic and acquired resistance to osimertinib. YAP1 directly regulates the expression of PD-L1 in EGFR TKI-resistant LADCs. Another downstream central effector is the protein tyrosine phosphatase SHP2 (PTPN11). The urea cycle enzyme carbamoyl phosphate synthetase-1 (CPS1) correlates with poor prognosis in EGFR-mutant LADCs (Figure).

The suppression of CPS1 potentiates the effects of EGFR inhibition and, therefore, opens an additional angle for optimizing therapy in EGFR-mutant LADCs that could most likely be extrapolated to other, oncogene driven LADCs. Among the transcriptional targets of YAP1 and its effector Forkhead box protein M1 (FOXM1), are the aurora kinases A and B (AURKA and AURKB) (Figure). Both AURKA and AURKB have been associated with resistance to EGFR TKIs. EGFR-mutant LADCs do not respond to immune checkpoint inhibitors.

Keywords: NFĸB, T790M, STAT3, CPS1, LADCs


Targeted Therapy

EGFR/ALK TKIS with Central Nervous System Penetration

I. Gil-Bazo1

1Department of Oncology. Clinica Universidad de Navarra, Pamplona/Spain

Different studies have shown that the incidence of central nervous system (CNS) involvement among patients with non-small cell lung cancer at the time of diagnosis may vary from 20% to about 30% depending on the histological subtype and the molecular features of the tumor.

Moreover, up to 50% of the patients may eventually develop brain metastasis during the disease course. In some patients indeed, and especially in those with oncogene addicted tumors, CNS infiltration may be the only site of disease progression during systemic treatment. In addition, CNS involvement has been traditionally considered to confer a dismal prognosis to NCSLC patients at any time point of the disease.

Patients with untreated brain metastasis (BM) have traditionally been excluded from clinical trials due to concerns that the particular pharmacokinetics in the CNS could preclude the correct interpretation of the results. The exclusion of patients with active BM was supported by the fact that initial attempts to use systemic drugs against CNS involvement were discouraging.

However, in recent years, the development of new-generation highly penetrant tyrosine-kinase inhibitors (TKIs) targeting EGFR and ALK oncogenes, have shown that appropriately designed drugs are extremely active in the CNS. The results

from the latest clinical trials using third generation EGFR TKIs or second generation ALK TKIs are challenging traditional dogmas that stablished first generation TKIs are not meaningfully active to prevent or even treat disease spread to CNS.

These findings have significantly changed clinical management of patients with NSCLC BM and warrant a review of the literature. In this presentation, we provide an overview of the recent results using EGFR or ALK TKIs to treat patients with CNS involvement, and how these results are challenging previous paradigms and current clinical practice including the role of brain irradiation in this new clinical setting.

Keywords: NSCLC, EGFR, ALK, TKI, CNS


Immunotherapy

Checkpoint Inhibitor Combinations Among Themselves and with Chemotherapy

C. Mathias1, H. Wakelee2

1NOB/ Grupo Oncoclínicas, Salvador/Brazil; 2Stanford University, Stanford/USA

Single-agent anti-PD-1/PD-L1 agents have had tremendous success in the treatment of Non-Small Cell Lung Cancer (NSCLC), significantly improving overall survival (OS) in patients with advanced disease. With the success of single-agent checkpoint inhibitors (CI), interest has developed in combining CI with other therapeutics in order to improve outcomes. Biological rationales suggest potential additive or synergistic benefit for combining CI with other established therapies, including enhanced tumor antigen uptake and presentation for T-cell priming, reducing the activity of immunosuppressive cells, and potentially increasing PD-L1 expression on NSCLC tumor cells. Early clinical trial data on CI combinations showed promising activity, and rapidly emerging phase III data have led to the approval of some CI combinations for the first-line treatment of metastatic non-squamous (2) and squamous (3) NSCLC. The purpose of this review is to evaluate emerging phase III data on the efficacy and safety of CI combinations for first-line advanced NSCLC.

Phase III trials with published or presented evaluating CI combinations were evaluated.

Multiple trials have combined CI with chemotherapy as first line therapy. Regimens of Pembrolizumab-chemotherapy, atezolizumab-chemotherapy, and atezolizumab-bevacizumab-chemotherapy have shown significantly improved OS compared to chemotherapy alone.

1. Pembrolizumab: KEYNOTE-189 randomized PD-L1-unselected patients NSCLC 2:1 to pembrolizumab/pemetrexed/platinum-pembrolizumab/pemetrexed maintenance (Pembro-pem, n=410) or placebo/pemetrexed/platinum-pemetrexed maintenance (Pb-pem, n=206). See Table 1(2).

2. Atezolizumab: IMpower-132 trial randomized PD-L1-unselected patients with stage IV non-squamous EGFR−/ALK− NSCLC to atezolizumab/pemetrexed/platinum-atezolizumab/pemetrexed maintenance (Atez-pem, n=292) or pemetrexed/platinum-pemetrexed maintenance (pem, n=286). See Table 1 (4).

3. Atezolizumab-Bevacizumab: IMpower-150 trial randomized PD-L1 unselected patients with stage IV non-squamous NSCLC to receive atezolizumab/carboplatin/paclitaxel-atezolizumab maintenance (Atez-CP, n=402), atezolizumab/bevacizumab/carboplatin/paclitaxel-atezolizumab/bevacizumab maintenance (Atez-Bev-CP, n = 400), or bevacizumab/carboplatin/paclitaxel-bevacizumab maintenance (Bev-CP, n=400). EGFR+/ ALK+ patients were eligible if they progressed on or were intolerant to one or more approved targeted therapies. At a median follow-

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up of approximately 20 months, OS in the ITT EGFR−/ALK− population was significantly improved (median, 19.2 vs. 14.7 months; HR, 0.78; 95% CI, 0.64–0.96; p=.02). Although not yet mature, median OS was not significantly improved for Atez-CP versus Bev-CP (19.4 vs. 14.7 months; HR, 0.88; 95% CI, 0.72–1.08; p =.20) (5). Two trials reported outcomes for squamous/NSCLC, with CI-chemotherapy showing improved OS compared with chemotherapy.

1. Pembrolizumab: KEYNOTE-407 study randomized PD-L1-unselected patients with stage IV squamous NSCLC to receive pembrolizumab/carboplatin/paclitaxel or nab-paclitaxel-pembrolizumab maintenance [Pembro-C(n)P, n=278] or placebo/carboplatin/paclitaxel or nab-paclitaxel-placebo maintenance [Pb-C(n)P, n= 281]. See Table 2 (6).

2. Atezolizumab: IMpower-131 randomized PD-L1-unselected patients with stage IV squamous NSCLC to receive atezolizumab/carboplatin/paclitaxel-atezolizumab maintenance (Atez-CP, n =338), atezolizumab/carboplatin and carboplatin/nab-paclitaxel-atezolizumab maintenance (Atez-CnP, n=343), or carboplatin/nab-paclitaxel-best supportive care (CnP, n=340). See Table 2 (7).

The other combination regimens which have shown some success are the combination PD-(L)1 plus CTLA4 inhibition. The MYSTIC trial looked at Durvalumb plus tremelimumab versus durvalumab or chemotherapy alone, but was not an overall positive study. The CheckMate227 trial included nivolumab + ipilimumab as a first line option compared to chemotherapy and in patients with PD-L1 expression of at least 1%, the combination led to superior OS compared to chemotherapy alone or single agent CI. Interestingly though, the combination of nivolumab plus chemotherapy was not superior to chemotherapy alone in patients without PD-L1 expression. Many other combination CI regimens are under investigation.

Results from phase III trials comparing CI combinations with previous standards of care have now been reported. First-line CI added to standard therapies improve overall survival for nonsquamous EGFR−/ ALK− and squamous advanced NSCLC.

New schedules and combinations involving CI are being studied in order to improve care and quality of care.

References:1. Postow MA, Callahan MK, Wolchok JD. Immune checkpoint blockade in cancer therapy. J Clin Oncol 2015;33:1974–19822. Gandhi L, Rodríguez-Abreu D, Gadgeel S et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. New Engl J Med 2018;378:2078–20923. Paez Ares L, Luft A, Vicente D et al. Pembrolizumab plus chemotherapy for Squamous non-small-cell lung cancer. New Engl J Med 2018; 379:2040-2054. Papadimitrakopoulou VA, Cobo M, Bordoni R et al. IMpower132: PFS and safety results with 1L atezolizumab + carboplatin/cisplatin + pemetrexed in stage IV non-squamous NSCLC. Abstract presented at: World Conference on Lung Cancer 2018; September 23–26, 2018; Toronto, Canada; OA05.07

Keywords: Checkpoint inhibitor combinations


Immunotherapy

Small Cell Lung Cancer Immunotherapy

W. William1

1Hospital BP - a Beneficencia Portuguesa de Sao Paulo, Sao Paulo/Brazil

Management of extensive small cell lung cancer has remained largely unchanged for the last two decades. Advances to the field have included consolidation radiation therapy to the chest and prophylactic cranial irradiation to patients responding to chemotherapy, albeit with minor / questionable impacts on outcomes.

Recently, immunotherapy has been approved by several regulatory agencies worldwide to be used in treatment-naive or previously treated patients with extensive small cell lung cancer, on the basis of phase 2 and phase 3 clinical studies. Immunotherapy options for this disease may include nivolumab, pembrolizumab, nivolumab/ipilimumab combination, platinum/etoposide/atezolizumab combination, and platinum/etoposide/durvalumab combination.

In the presentation, we will summarize results of the clinical trials that support use of the aforementioned immunotherapy-based strategies for extensive small cell lung cancers, including both efficacy and toxicity outcomes.

Keywords: Immunotherapy, Small-cell lung cancer

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Poster Discussion #1

Friday, October 18, 2019 16:15 - 17:15PD1.01

Topic: Prevention, Early Detection, Epidemiology and Tobacco Control

Associations of Variability in Metabolic Parameters with Lung Cancer in the General Population

I.Y. Cho1, D.W. Shin2, K. Han2

1Department Of Family Medicine, Samsung Medical Center, Seoul/Korea, Republic of, 2Department Of Family Medicine, Samsung Comprehensive Cancer Center, Samsung Medical Center, Seoul/Korea, Republic of

Background: Variability of metabolic parameters, such as blood cholesterol, fasting blood glucose, blood pressure and body weight can affect outcomes in health. Previous studies have shown that components of metabolic syndrome can lead to increased risks for several types of cancers such as breast and colon cancer, but not many studies have shown such effects on lung cancer. This study aimed to investigate whether variability in metabolic parameters can lead to increased risk of lung cancer in the general population.

Method: Nationally representative data from the Korean National Health Insurance System was used, and a total of 8,011,209 who were not diagnosed with lung cancer and underwent over three health examinations from 2005 to 2012 were followed until the end of 2015. Variability was measured in fasting blood glucose, total cholesterol, systolic blood pressure and body weight by using the coefficient of variation, standard deviation, variability independent of the mean and average real variability, and variability was assessed by quartiles. Subjects were also classified according to number of high-variability components (for example, a score of 4 would indicate high variability in the 4 mentioned metabolic parameters). Cox proportional hazards models were used adjusting for age, sex, smoking, regular exercise, alcohol and income.

Results: There were 44,982 events of lung cancer occurrences. High variability in each metabolic parameter was associated with higher risks for lung cancer. For blood glucose, hazard ratios and 95% confidence intervals in the highest quartile was 1.07 (1.04-1.10); for systolic blood pressure, 1.08 (1.05-1.10); for body weight, 1.04 (1.01-1.07), and for total cholesterol, 1.11 (1.08-1.14). Furthermore, the risk of lung cancer increased significantly with number of high-variability metabolic components. When comparing scores of 3 and 4 versus 0 in multivariable-adjusted model, hazard ratio for lung cancer occurrence was 1.18 (95% CI 1.14-1.22).

Conclusion: High variability in metabolic parameters, especially in total cholesterol levels, was shown to be an independent predictor of increased risk for lung cancer. Furthermore, increasing number of high-variability parameters was found to increase risk of lung cancer in a stepwise manner.

Keywords: Lung cancer, Metabolic parameters, Total cholesterol, Fasting blood glucose

PD1.02


Non-Small Cell Lung Cancer in the US Hispanic Population: A National Cancer Database Analysis

R. Kumar, S. Bhandari, G. KloeckerUniversity of Louisville, Louisville/United States of America

Background: There were 234,030 new cases of lung cancer in the US in 2018. Due to their lower smoking rate the incidence of non-small cell lung cancer (NSCLC) is 50 % lower for Hispanics (H) than Non-Hispanic Whites (NHW). Since Hs are the largest minority in the US (18% of the population), a significant number of NSCLC is diagnosed in this population. The objectives of this study were to examine the demographic patterns of non-small lung cancer (NSCLC) and cancer health disparities in the H population.

Method: We used the National Cancer Database to identify patients who were diagnosed with NSCLC between 2010-2014. Pearson’s chi-square test and Wilcoxon rank sum test were used to compare patient and cancer characteristics between Hs and NHWs. Survival was analyzed by the Kaplan-Meier method and associated log-rank test. A two-sided P-value of less than 0.05 was used to determine statistical significance.

Results: A total of 410,158 patients were included in the analysis (3% H and 97% NHW). The H group was younger (68 vs 69 years) and had less females (44% vs 48%) compared to NHW group. The H group had lower annual household income (28% vs 16% had <$38,000) and educational level (48% vs 14% lived in areas with low high school graduation rate). Other characteristics mentioned in the Table. In the treated group, the 5-year OS was better in Hs 32% vs 28.3%. The p-value was <0.001 for all comparisons.

Conclusion: Despite lower prevalence of NSCLC in the H compared to NHW population, there is a higher percentage of advanced stage at presentation and untreated NSCLC in the H population. This can be partly explained by limited healthcare access, low socioeconomic, educational and insurance status. If treated, Hs have a better survival outcome than NHWs.

Keywords: Non small cell lung cancer, Epidemiology, Hispanics

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Table. Patient and cancer characteristics

Hispanic (H) n=11,917

Non-Hispanic White (NHW) n=398,241

p-value

Uninsured (%) 8 3 <0.001

Charlson/Deyo Score (%)

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<3 96 97

>=3 4 3

Untreated (%) 19 13 <0.001

Stage (%) <0.001

I 24 29

II 9 10

III 20 20

IV 47 41

Median OS in treated group (months)

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PD1.03


A Primer on Genetic Counseling on the Thoracic Oncology Unit. Family History of Lung Cancer in Two Independent Populations Tested for BRCA1 & amp;2 and EGFR.

G. Pacheco-Cuellar, K. Campos-Gomez, J.J. Valdéz-Andrade, S. Campos-GomezThoracic Oncology Unit, Centro Oncologico Estatal ISSEMYM, Toluca de Lerdo/Mexico

Background: Germline mutations explain a small percent of lung cancer (LC), previous reports have described mutations in genes involved in Homologous Recombination Repair pathway in LC patients (pts), notably BRCA2. Also, mutations in EGRF, like T790M at diagnosis, could be inherited. Genetic counseling (CG) is a process including education, genetic cancer risk evaluation, and guidance about Genetic Testing (GT). We started a GC pilot to identify candidates for GT.

Method: This is a retrospective work to identify family history (FH) of LC in: a) Hereditary Breast/Ovarian Cancer (HBOC) pts carrying BRCA pathogenic variants, and b) LC pts carrying T790M at diagnosis. Additionally, we searched for patterns of hereditary cancer syndromes in LC pts without T790M.We included: 42 HBOC pts tested from Nov2014-mars2019, and 88 LC pts tested for EGFR from mars2018-mars2019. 20 LC pts completed a GC session and 68 LC pts had a medical record available. We collected clinical, demographic and familial variables. Three generation pedigree was gathered through GC. Descriptive and non-parametric tests were used.

Results: Mean age of LC pts was 61.55y (SD 13.8). 49 (55.7%) were females and 38 (43.2%) were non-smokers. 3 (3.4%) pts had T790M (2 females/1 male), they were older than 60y; 1 pt had 1 relative with LC, the other 2 pts had more than 2 affected relatives but none with LC. 43 pts (50%) of LC pts without T790M, had no FH of any cancer, 12 pts (14.11%) reported more than 3 relatives with Cancer; notably, 3 pts had 6 affected relatives, and 1 pt reported 10 relatives. 8 pts reported 1 relative with LC, 2 pts reported 2 LC cases and 1 pt 3 LC cases. 13.6% met criteria for GT according to FH; we found overlapping of breast, pancreatic, prostate and ovarian cancer. No statistically differences were found between these groups. Among the BRCA population, 16 pts (38.1%) had a mutation in BRCA2. None of BRCA1 pedigrees showed LC. Among the BRCA2 pts, 2 non-related cases of LC were reported; the c.2808-2811del variation was present in both families.

Conclusion: We observed LC in BRCA2 families and in 1 pt with T790M. Our sample is small but we identified at least 15 LC pts who met criteria for GT. GC improves FH taking and can guide GT. Those pts could have benefits such as identify the genetic etiology, adjust surveillance, direct therapy, calculate transmission risk and even struggle with stigma.

Keyword: Genetic counseling, BRCA2, EGFR

PD1.04

Topic: Early Stage NSCLC (Stage I - III)

Mid-term Outcomes of Uniportal Vats(U-VATS) for Early Lung Cancer

K. Hirai1, J. Usuda2

1Department Of Thoracic Surgery, Nippon Medical School Chiba Hokusoh Hospital, Inzai/Japan, 2Department Of Thoracic Surgery, Nippon Medical School, Tokyo/Japan

Background: Minimally invasive surgery, U-VATS has rapidly spread in a part of countries. It has been reported that U-VATS contributed to shorten the hospital stay and decrease the

postoperative wound pain in several journals. Based on my clinical experience for approximately six years, I hereby present the mid-term outcomes of U-VATS.

Method: U-VATS which is carried out via from 3.5 to 4.0-cm incision without using a rib spreader routinely has been applied to almost thoracic diseases in our hospital. We have experienced 162 patients with clinical stage I lung cancer undergoing U-VATS from 2012 Sept. to 2019 Jun. We hereby report mid-term clinical outcomes of U-VATS after surgery.

Results: The average of operation duration, blood loss, drainage duration and hospital stay after surgery were 162±42 min, 85.5±4 ml, 1.8± 0.3 days and 6.4±1.5 days, respectively. The average of numeric rating scale on postoperative day 7 was 2.5±0.4. The average of tumor size and the number of dissected lymph nodes were 2.8±0.7cm and 17.2 ±5.1. There was no severe complication after surgery. The conversion rate of two-port and thoracotomy was 4.9% and 2.5%. Postoperatively, pathological stage of all patients was divided into I:149/II:6/IIIA:7. Local recurrence related to lymph node (1.2%:2/162) was recognized in stage IIB and IIIA. There was no mortality rate within 30days after surgery. 5 year-disease-free survival rate and 5 year-overall survival rate was 84.1% and 80.5%, respectively.

Conclusion: U-VATS was feasible and promising operative procedure. Further detailed study and muticenter study are necessary, however U-VATS is thought to be oncologically acceptable surgical treatment.

PD1.05


Relevance of Antibiotic Use on Clinical Activity of Immune Checkpoint Inhibitors in Hispanic Patients with Advanced Non-small-cell Lung Cancer (CLICAP-ABs)

F. Barrón1, A.F. Cardona2, A. Ruiz-Patiño3, L. Zatarain Barron4, L. Corrales-Rodriguez5, C. Martín6, C. Sotelo3, J. Rodríguez3, J. Ávila3, D. Mayorga3, P. Archila3, L. Mas7, H. Freitas8, V.C. Cordeiro De Lima8, J. Otero3, H. Carranza3, C. Vargas3, R. Rosell91Instituto Nacional de Cancerologia, México City/Mexico, 2Clinical And Translational Oncology Group,, Clinica del Country, Bogotá/Colombia, 3Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá/Colombia, 4Unidad Funcional de Oncología Torácica Instituto Nacional de Cancerología, Mexico City/Mexico, 5CIMCA - CCSS, San José/Costa Rica, 6Medical Oncology Department, Instituto Fleming, Buenos Aires/Argentina, 7National Cancer Institute (INEN), Lima/Peru, 8Camargo Cancer Center, Sao Paolo/Brazil, 9Cancer Biology And Precision Medicine Program,, Catalan Institute of Oncology, Barcelona/Spain

Background: The composition of gut microbiota affects antitumor immune responses, as well as preclinical and clinical outcomes following immune checkpoint inhibitors (ICI) in cancer. Antibiotics (ATB) alter gut microbiota diversity and composition leading to dysbiosis, which may influence the effectiveness of ICI.

Method: We examined patients with advanced non-small-cell lung cancer (NSCLC) treated with anti-programmed cell death ligand-1 mAb monotherapy alone or in combination in three different countries of Latin America. Those receiving ATB within 30 days of beginning ICI were compared with those who did not. Objective response, progression free survival (PFS) and overall survival (OS) were assessed.

Results: 18 of 140 (13%) NSCLC patients received ATB. The most commonly used ATB were b-lactam or quinolones for pneumonia or urinary tract infections. In NSCLC patients, ATB was associated with 4 cases of primary PD (28.6% versus 31.5%, P=0.818), non-significant decreased PFS (median 2.66 versus 1.94 months, HR 1.63, [95% CI 0.71-3.72], P=0.247) and significantly deleterious OS (median 12.42 versus 2.04 months,

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HR 2.3, [95% CI 1.08-4.95], P=0.03). In multivariate analyses, the impact of ATB remained significant for OS.

Conclusion: ATB were associated with reduced clinical benefit from ICI in Hispanic patients with NSCLC. Modulation of ATB-related dysbiosis and gut microbiota composition may be a strategy to improve clinical outcomes with ICI.

Keywords: Antibiotics, Response rate, Immune checkpoint inhibitors

PD1.06


Improving Survival of Oligometastatic NSCLC with Stereotactic Body Radiation Therapy

L. Raez, M. Castillo, A. Botero, I. Castellon, B. Hunis, A. FalchookMemorial Cancer Institute/Memorial Health Care System, Pembroke Pines/United States of America

Background: Stereotactic body radiation therapy (SBRT) can allow non-small cell lung cancer (NSCLC) patients (pts) to stay longer with the same therapy by eliminating oligometastatic progression (OMP) improving progression free survival (PFS) and overall survival (OS).

Method: One hundred pts with metastatic NSCLC undergoing chemotherapy (CHEMO), immunotherapy (IMMUNO) or target therapy (TARGET) that had OMP defined as less than four sites of metastasis and underwent SBRT were evaluated for PFS and OS. PFS1: Time between initiation of systemic therapy and development of OMP. PFS2: Time between OMP treated with SBRT and development of further PD requiring a change in systemic therapy. Pts received IMMUNO for second line and beyond. Robotic SBRT was delivered in 1-5 fractions on consecutive days or every other day. SBRT doses were determined based on the disease site and dose tolerance of the adjacent organs.

Results: Brain metastasis (BM) were seen in 45 pts and 55 pts had extracranial metastasis (EM). 34 pts were receiving CHEMO, 34 Target and 32 IMMUNO at the time of OMP. Main endpoints (m) are shown (Table). Pts with BM that received SBRT were able to continue the same therapy for a period of 6.5-9 extra months due to the control of BM. Pts with EM that have developed PD were able to continue the same therapy an 17-21 extra months due to the ablation of OMP by SBRT. Overall PFS was: 16.5m for BM and 34m for EM and the OS were: 31m and 53m respectively.

Conclusion: Significant prolongation in PFS/OS was observed compared with historical controls thanks to the use of SBRT in pts that develop OMP while on systemic therapy. SBRT allowed patients to continue with the same systemic treatment. Our CHEMO cohort is composed of long term survivors under therapy and may not represent the average PFS/OS of pts on CHEMO. Survival data from prospective trials is needed to verify these results.

Keywords: Immunotherapy, SBRT, Targeted therapy

Poster Discussion #2

Friday, October 18, 2019 16:15 - 17:15PD2.01


PD-L1 and Other Potential Predictive Biomarkers Measured in Plasma by RT-PCR in cfRNA and cfDNA to Monitor Clinical Responses in Metastatic Lung Cancer Patients

L. Raez1, J. Usher2, D. Sumarriva1, K. Danenberg2, B. Hunis1, Y. Jaimes2, G. Domingo1, P. Danenberg3

1Memorial Cancer Institute/Memorial Health Care System, Pembroke Pines/United States of America, 2Liquid Genomics, culver city/United States of America, 3University of Southern California, Los Angeles/United States of America

Background: We have shown before that cell-free circulating tumor RNA (cfRNA) extracted from plasma of cancer patients (pts) can measure dynamic changes in gene expression that can help to evaluated disease status and predict outcome to anti-tumoral therapy in solid tumors [T. Ishiba et al. Biochem Biophys Res Commun. 2018 Jun 7; 500 (3):621-625]. We want to show here that PD-L1 and other biomarkers assessed by RNA RT-PCR can be use as predictive markers that can be used to follow Immunotherapy and chemotherapy responses in non-small cell lung cancer (NSCLC).

Method: We enrolled 54 pts with advanced NSCLC undergoing systemic therapy (STX) and we follow them for 1-year. cfRNA was extracted from resulting plasma and generated random-primed cDNA. Total cfRNA was quantitated by qPCR of β-actin, and correlated with pt clinical response (CR/PR/SD/PD) determined by CT scans. All gene expressions were measured relative to β-actin. Changes in PD-L1 expression were used to monitor response to immunotherapy in lung cancer pts. Ten milliliters of blood were collected in each of two tubes and transferred to Liquid Genomics, Inc. Blood was drawn every 6-8 weeks with an average of 5 collections were done per pt.

Results: Of the 54 enrolled pts, 30 completed 1-3 lines of STX with outcomes. The overall mutation frequency was 33% (10/30), with 27% in KRAS and 6% in EGFR. Increases or emergence of mutant allele fractions were predictive of PD status (later determined by imaging), while decreases or disappearance of mutations were predictive of SD and PR status after treatment. PD-L1 expression was detected in 87% (26/30) of pts in at least one blood draw. Immunotherapy: (Nivolumab, pembrolizumab, atezolizumab), 11/30 pts underwent immunotherapy (IO) txt. Changes in PD-L1 during IO were associated with STX outcomes. Increases in PD-L1 were associated with PD, while decreases or no changes in PD-L1 were associated with SD and PR. Of the 23 blood draws from these 11 pts, the overall concordance between changes in PD-L1 and IO outcome was 91% (21/23). Chemotherapy: 19/30 pts were given carboplatin/pemetrexed as first line therapy. Increases or decreases in PD-L1 across 28 blood draws during therapy were likewise associated with resistance or sensitivity to STX outcome (increases infer resistance; decreases infer sensitivity) in 24/28 (86%).

Conclusion: We demonstrated a strong concordance between clinical responses and changes in plasma PD-L1 done by RT-PCR RNA levels in NSCLC pts treated with IO or chemotherapy. Monitoring cfRNA expression levels of PD-L1 is a reliable method for predicting response and resistance to IO as well as chemotherapy irrespective of KRAS and EGFR.

Keywords: Immunotherapy, PD-L1, Liquid biopsies

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Location of oligometa-static progression

Median PFS1

Median PFS2

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Brain (N=45) 9 7.5 16.5 31

Chemo 5.5 6.5 12 25.5

Immuno 7 8 15 27

Target 11 9 20 47

Extracranial (N=55) 13 21 34 53

chemo 7 17 24 47

Immuno 13.5 20.5 34 49

Target 12 21 33 53


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PD2.02


Pembrolizumab plus Pemetrexed-Platinum for Patients with Metastatic Nonsquamous NSCLC and Liver or Brain Metastases: Results from KEYNOTE-189

M.C. Garassino1, S. Gadgeel2, E. Esteban3, E. Felip4, G. Speranza5, F. De Angelis6, M. Domine7, P. Clingan8, M.J. Hochmair9, S.F. Powell10, S.Y.-S. Cheng11, H.G. Bischoff12, N. Peled13, F. Grossi14, R.R. Jennens15, M. Reck16, R. Hui17, E.B. Garon18, M. Boyer19, B. Rubio-Viqueira20, S. Novello21, T. Kurata22, J.E. Gray23, A. Cardellino24, J. Yang25, M.C. Pietanza25, D. Rodríguez-Abreu26

1Fondazione IRCCS Istituto Nazionale dei Tumori, Milan/Italy, 2Karmanos Cancer Institute, Detroit (currently at University of Michigan, Ann Arbor)/United States of America, 3Hospital Universitario Central de Asturias, Oviedo/Spain, 4Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona/Spain, 5Centre integré de cancérologie de la Montérégie, Hôpital Charles-Le Moyne, Greenfield Park/Canada, 6Integrated Health and Social Services Centres, Montérégie Centre, Greenfield Park/Canada, 7Fundación Jiménez Díaz, Madrid/Spain, 8Southern Medical Day Care Centre, Wollongong/Australia, 9Department of Respiratory & Critical Care Medicine, Ludwig Boltzmann Institute of COPD & Respiratory Epidemiology, Otto Wagner Hospital, Vienna/Austria, 10Sanford Health, Sioux Falls/United States of America, 11Sunnybrook Health Sciences Centre, Toronto/Canada, 12Thoraxklinik, Heidelberg/Germany, 13Davidoff Cancer Center, Tel Aviv University, Petah Tikva (currently at Soroka Medical Center, Ben-Gurion University, Beer-Sheeva)/Israel, 14Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan/Italy, 15Epworth Healthcare, Richmond/Australia, 16LungenClinic, Airway Research Center North, German Center for Lung Research, Grosshansdorf/Germany, 17Westmead Hospital and University of Sydney, Sydney/Australia, 18David Geffen School of Medicine at UCLA, Los Angeles/United States of America, 19Chris O’Brien Lifehouse, Camperdown/Australia, 20Hospital Universitario Quirón Madrid, Madrid/Spain, 21Department of Oncology, University of Turin, Azienda Ospedaliero-Universitaria San Luigi, Orbassano/Italy, 22Kansai Medical University Hospital, Osaka/Japan, 23Moffitt Cancer Center, Tampa/United States of America, 24ExecuPharm Inc., King of Prussia/United States of America, 25Merck & Co., Inc., Kenilworth/United States of America, 26Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria/Spain

Background: KEYNOTE-189 is a randomized, placebo-controlled, phase 3 study of pembrolizumab plus pemetrexed-platinum versus placebo plus pemetrexed-platinum among patients with metastatic nonsquamous NSCLC. At median follow-up of 10.5 months, patients in the pembrolizumab-combination arm had improved OS (HR, 0.49; 95% CI, 0.38–0.64; P<0.001) and PFS (HR, 0.52; 95% CI, 0.43–0.64; P<0.001) compared with patients in the placebo-combination arm. We present a retrospective, exploratory evaluation of outcomes among patients with liver or brain metastases at baseline from an updated analysis.

Method: Patients with untreated metastatic nonsquamous NSCLC, ECOG PS 0/1, and without EGFR/ALK alteration were randomized 2:1 to receive up to 35 Q3W cycles of pembrolizumab 200 mg or placebo plus 4 cycles of pemetrexed 500 mg/m2 and carboplatin AUC 5 mg/mL/min or cisplatin 75 mg/m2 followed by maintenance pemetrexed. Randomization was stratified by PD-L1 TPS (<1% vs ≥1%), platinum (carboplatin vs cisplatin), and smoking status (current/former vs never). Response was assessed by RECIST v1.1 per blinded, independent central review. OS and PFS were primary endpoints.

Results: 616 patients were randomized (pembrolizumab-combination, n=410; placebo-combination, n=206). At data cutoff, median follow-up was 18.7 months. At baseline, 19% of patients had liver metastases and 18% had brain metastases. HRs for OS and PFS favored the pembrolizumab-combination vs placebo-combination across all groups and were similar for patients with/without liver or brain metastases.

Conclusion: Pembrolizumab plus pemetrexed-platinum provided superior outcomes vs chemotherapy alone irrespective of liver or brain metastases in patients with untreated metastatic nonsquamous NSCLC. Benefit was observed in patients with brain or liver metastases, for whom prognosis is historically poor.

Keyword: PD-L1, Pembrolizumab, Chemotherapy, NSCLC

PD2.03


Exploration of Factors Relating to Immune Response in Patients Treated with Immune Checkpoint Inhibitors for Non-small Cell Lung Cancer (NSCLC) A.F. Cardona1, O. Arrieta2, A. Ruiz-Patiño3, L. Zatarain Barron4, L. Corrales-Rodriguez5, C. Martín6, F. Barrón7, C. Sotelo3, J. Rodríguez3, L. Ricaurte3, H. Freitas8, V.C. Cordeiro De Lima8, L. Mas9, J. Ávila3, D. Mayorga3, P. Archila3, J. Otero3, H. Carranza3, C. Vargas3, R. Rosell101Clinical And Translational Oncology Group,, Clinica del Country, Bogotá/Colombia, 2Thoracic Oncology Unit, Instituto Nacional de Cancerología, México City/Mexico, 3Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá/Colombia, 4Unidad Funcional de Oncología Torácica Instituto Nacional de Cancerología, Mexico City/Mexico, 5CIMCA - CCSS, San José/Costa Rica, 6Medical Oncology Department, Instituto Fleming, Buenos Aires/Argentina, 7Instituto Nacional de Cancerologia, México City/Mexico, 8Camargo Cancer Center, Sao Paolo/Brazil, 9National Cancer Institute (INEN), Lima/Peru, 10Cancer Biology And Precision Medicine Program,, Catalan Institute of Oncology, Barcelona/Spain

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PFS OS

N* Me-dian, mo (95% CI)

HR(95% CI)

Me-dian, mo (95% CI)

HR(95% CI)

Patients With Liver Metasta-ses

Pembro-lizumab-combina-tion

66 6.1(4.7–8.5)

0.52(0.34–0.81)

12.6(8.1–19.1)

0.62(0.39–0.98)

Placebo-combina-tion

49 3.4(2.8–4.7)

6.6(4.6–7.6)

Patients Without Liver Me-tastases

Pembro-lizumab -combina-tion

344 9.2(8.8–11.0)

0.48(0.39–0.59)

23.7(20.1–25.9)

0.58(0.45–0.74)


157 5.4(4.9–6.7)

13.2(10.0–16.4)

Patients With Brain Metasta-ses


73 66.9(5.4–11.0)

0.42(0.27–0.67)

19.2(15.0–25.9)

0.41(0.24–0.67)


35 4.7(2.2–5.5)

7.5(4.6–10.0)

Patients Without Brain Me-tastases


337 9.2 (8.3–10.9)

0.48(0.39–0.59)

22.4(19.7–25.4)

0.59 (0.46–0.75)


171 4.9 (4.7–5.9)

12.1(9.1–15.0)

*25 patients had both brain and liver metastases.

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Background: Although the introduction of immune checkpoint inhibitors (ICIs) has yielded substantial benefits in terms of survival in the treatment of Non-Small Cell Lung Cancer (NSCLC), the possibility of activation of dormant autoimmune diseases or onset of immune mediated toxicities is a reality. The objective of this study was to explore intrinsic immunological factors associated with poor outcomes.

Method: In a retrospective cohort study of 48 patients, without any prior medical history of autoimmunity, treated for advanced/metastatic NSCLC with ICI´s were assessed. Determination of HLA-A*02011 as well as acute phase reactants and antiphospholipid antibodies was performed. Additionally, evaluation of survival in a time to event manner was conducted using the Kaplan Meier method and Cox regressions.

Results: Median follow-up was 27.3 months, of the included patients 26 were male (54%) with a median age of 62 years old and there were no individuals with and ECOG performance score >1. Median overall survival (OS) was reached at 22.47 months. When analyzing the presence of the HLA-A*02011 serotype, 6 patients tested positive (12.5%). Additionally, all presented with borderline or abnormal B2glycoprotein IgM and IgG, 2Bmicroglubulin and elevated C reactive protein. Four patients (66%) experienced reactive lymphadenopathy during treatment and all suffered some form of venous thromboembolism. When analyzing OS, this group of patients had a significantly worse outcome (6.53 vs 22.47 months, HR= 4.47, [95%CI 1.47 – 13.61], p<0.001) compared with their counterparts. Overall response rate for the whole was superior for the HLA-A*02011 positive patients achieving 41.4% and 33%, p<0.001, respectively.

Conclusion: The presence of the HLA-A*02011 could potentially predispose to a paradoxical and pathological activation of the immune system without offering any benefit in terms of tumor control. Larger studies validating these findings are warranted.

Keywords: B2glycoprotein, Autoimmune diseases, Antiphospholipid antibodies

PD2.04


Long Term Efficacy and Safety of Ensartinib in Pre-treated Anaplastic Lymphoma Kinase (ALK) Positive Non-small Cell Lung Cancer (NSCLC) Patients (eXalt2)

T. Leal1, H. Wakelee2, K.L. Reckamp3, A. Chiappori4, G.R. Oxnard5, S.N. Waqar6, S.P. Patel7, G.R. Blumenschein8, J.W. Neal2, K. Harrow9, A. Holzhausen9, G. Selvaggi9, J. Zhou9, L. Horn10

1University of Wisconsin School of Medicine and Public Health, Madison/United States of America, 2Stanford University and Cancer Institute, Stanford/United States of America, 3City of Hope Comprehensive Cancer Center, Duarte/United States of America, 4H. Lee Moffitt Cancer Center & Research Institute, Tampa/United States of America, 5Dana-Farber Cancer Institute, Boston/United States of America, 6Washington University School of Medicine, St. Louis/United States of America, 7UC San Diego Moores Cancer Center, La Jolla/United States of America, 8MD Anderson Cancer Center, Houston/United States of America, 9Xcovery Holdings, Inc., Palm Beach Gardens/United States of America, 10Department Of Medicine, Division Of Hematology And Oncology, Vanderbilt University Medical Center, Nashville/United States of America

Background: Ensartinib has shown efficacy in ALK+ NSCLC patients previously treated with crizotinib and/or next generation ALK inhibitors (ALKi). This clinical benefit is associated with high intracranial (IC) activity in patients with brain metastases and a favorable safety profile. We report updated data in pre-treated NSCLC cohorts from the eXalt2 study.

Method: eXalt2 is an ongoing multicenter Phase I/II study. We report data on patients treated with ensartinib >200mg PO, once daily on a continuous 28-day schedule (NCT01625234). Patients

received ensartinib until disease progression, unacceptable toxicity or investigator discretion. Patients with asymptomatic brain metastases were allowed to enroll. All patients were assessed for adverse events (AEs) using CTCAE version 4.03, and response to treatment was assessed locally every 8 weeks using RECIST 1.1.

Results: As of 20 May 2019, 73 pre-treated ALK+ NSCLC response evaluable patients were assessed (Table). The median progression free survival (PFS) was 9.1 months (m) (IQR, 5.8-11.7) and 2.8 m (IQR, 1.7-5.7) respectively in post-crizotinib (n=41) and post second generation ALKi (n=32) cohorts, with 12/32 (38%) having received >3 lines of ALK inhibitors. Overall response rate (ORR) was 59% (uORR 66%) in the post-crizotinib cohort resulting in a disease control rate (DCR) of 95%, and ORR in the post second generation ALKi cohort was 9% (uORR 16%) resulting in a DCR of 56%. IC responses were observed in both cohorts, with an IC ORR of 50% (8/16, including 2 complete responses) and IC DCR of 100%. Safety profile of these 73 patients is similar to previously reported safety data, with rash being the most common drug-related AE (56%, mostly grades 1-2).

Conclusion: Ensartinib is well tolerated and active in pre-treated ALK+ NSCLC patients with high DCR, remarkable intracranial efficacy and a favorable safety profile. Updated survival outcomes will be presented at the conference.

Keywords: ALK, NSCLC, Ensartinib, CNS

PD2.05


Overall Survival in Pts with EGFRm+ NSCLC Receiving Sequential Afatinib and Osimertinib: Updated Analysis of the GioTag Study

M.J. Hochmair1, A. Morabito2, D. Hao3, C.-T. Yang4, R.A. Soo5, J.C.-H. Yang6, R. Gucalp7, B. Halmos7, L. Wang8, A. Märten9, T. Cufer10

1Department of Respiratory and Critical Care Medicine, and Ludwig Boltzmann Institute of COPD and Respiratory Epidemiology, Otto Wagner Hospital, Sanatoriumstrasse 2, 1140, Vienna/Austria, 2Thoracic Medical Oncology, Istituto Nazionale Tumori, “Fondazione G.Pascale”-IRCCS, 80131, Naples/Italy, 3Tom Baker Cancer Center, Cummings School of Medicine, University of Calgary, T2N 4N2, Calgary/Canada, 4Department of Thoracic Medicine, Chang Gung Memorial Hospital, 33305, Taoyuan/Taiwan, 5Department of Haematology-Oncology, National University Hospital, 119074, Singapore/Singapore, 6Department of Oncology, National Taiwan University Hospital and National Taiwan University Cancer Center, 100, Taipei/

Table. Baseline Patient Demographics

N (%) Post-Crizotinib (n=41)

Post 2nd Gen-eration ALK TKI (n=32)

Median Age (Range) 54 (20-83) 54 (32-77)

Gender: Male / Female 22 (54) / 19 (46) 15 (47) / 17 (53)

Race: Caucasian Asian Black/African American Unknown / Other

31 (76) 4 (10) 0 6 (15)

21 (66) 10 (31) 1 (3) 0

ECOG: 0 / 1 13 (32) / 28 (68) 10 (31) / 21 (66)*

Prior ALK TKI Treatment: Crizotinib only Alectinib only Crizotinib and ceri-tinib Crizotinib and alec-tinib Ceritinib and alectinib Crizotinib, ceritinib and alectinib Crizotinib, ceri-tinib and brigatinib

41 (100) 0 0 0 0 0 0

0 1 (3) 9 (28) 13 (41) 1 (3) 7 (22) 1 (3)

* ECOG for 1 patient not done at baseline

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Taiwan, 7Department of Oncology, Montefiore/Albert Einstein Cancer Center, 10461, Bronx/United States of America, 8Boehringer Ingelheim Taiwan Limited, 104, Taipei City/Taiwan, 9Boehringer Ingelheim International GmbH, 55216, Ingelheim am Rhein/Germany, 10University Clinic Golnik, University of Ljubljana, Ljubljana/Slovenia

Background: While the superiority of second- and third-generation EGFR tyrosine kinase inhibitors (TKIs) over first-generation agents has been clearly demonstrated, the optimal sequence of EGFR TKIs is less clear, especially as there is no established targeted therapy after osimertinib failure. In the observational GioTag study (NCT03370770), patients with EGFRm+ NSCLC were treated with sequential afatinib and osimertinib in a ‘real-world’ clinical setting, including patients with poor prognosis (ECOG PS ≥2: 15%; stable brain metastases: 10%).1 Encouraging time to treatment failure (TTF) was seen in the primary analysis (overall: 27.6 months; Del19-positive patients: 30.3 months; Asian patients: 46.7 months). In this analysis, we report OS and updated TTF.

Method: Data were retrospectively collected between Dec 2017 and June 2018 for 204 patients with EGFRm+ (Del19, L858R) NSCLC who were T790M-positive after first-line afatinib and received subsequent osimertinib. TTF was the primary outcome; OS analysis was exploratory. Data were collected from electronic health records (EHRs; n=126) or medical charts (n=77). For logistical reasons, this interim analysis includes updated data (as at April 2019) from patients with available EHRs (all USA; n=94).

Results: After a median follow-up of 30.3 months, median OS was 41.3 months (90% CI: 36.8–46.3) in the overall dataset (n=203) and 45.7 months (90% CI: 45.3–51.5) in Del19-positive patients (n=149). At 2 years, OS was 80%; OS in Asian patients was immature. Updated median TTF was 28.1 months (90% CI: 26.8–30.3) in the overall dataset, and 30.6 months (90% CI: 27.6–32.0) in Del19-positive patients. Outcomes were not affected by afatinib starting dose. Median TTF with osimertinib was 15.6 months (90% CI: 13.8–17.1) in the overall dataset, and 16.4 months (90% CI: 14.9–17.9) in Del19-positive patients.

Conclusion: Encouraging OS and TTF were seen with sequential afatinib and osimertinib in patients with EGFR T790M-positive NSCLC, especially in Del19-positive patients, supporting the use of this regimen. Prior treatment with afatinib did not preclude prolonged TTF with second-line osimertinib (15.6 months overall; 16.4 months in Del19-positive patients). The final analysis, incorporating updated data from manual chart reviews and anticipated in early 2020, will provide further insights into the long-term OS of patients treated with sequential afatinib–osimertinib. 1. Hochmair MJ, et al. Future Oncol. 2018;14:2861–74.

Keywords: Osimertinib, Sequential, NSCLC, Afatinib

PD2.06


EGFR Inhibitors + Bevacizumab Demonstrated Superior Efficacy Compared with EGFR Inhibitors Alone as First-line Treatment in Advanced NSCLC Patients with EGFR Mutations and BIM Deletion Polymorphisms

A.F. Cardona1, O. Arrieta2, A. Ruiz-Patiño3, L. Zatarain Barron4, L. Corrales-Rodriguez5, C. Martín6, F. Barrón7, C. Sotelo3, J. Rodríguez3, L. Ricaurte3, J. Ávila3, D. Mayorga3, P. Archila3, J. Otero3, H. Freitas8, V.C. Cordeiro De Lima8, L. Mas9, H. Carranza3, C. Vargas3, R. Rosell101Clinical And Translational Oncology Group, Clinica del Country, Bogotá/Colombia, 2Thoracic Oncology Unit, Instituto Nacional de Cancerología, México City/Mexico, 3Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá/Colombia, 4Unidad Funcional de Oncología Torácica Instituto Nacional de Cancerología, Mexico City/Mexico, 5CIMCA - CCSS, San José/Costa Rica, 6Medical Oncology Department, Instituto Fleming, Buenos Aires/Argentina, 7Instituto Nacional de Cancerologia, México City/Mexico, 8Camargo Cancer Center, Sao Paolo/Brazil,

9National Cancer Institute (INEN), Lima/Peru, 10Cancer Biology And Precision Medicine Program,, Catalan Institute of Oncology, Barcelona/Spain

Background: BIM activation is essential for EGFR-TKIs triggered apoptosis in EGFR-mutant Non-small-cell lung cancer (NSCLC). A 2903-bp germline deletion in intron 2 of the BIM gene results in generation of alternatively spliced isoforms that lack the crucial BH3 domain, impairing the apoptotic response to TKIs and conferring NSCLC cells intrinsic resistance to these medications. Patients with both alterations have poor clinical evolution. The current study aimed to investigate the clinical efficacy and tolerability of EGFR-TKIs plus bevacizumab (Bev) versus EGFR-TKIs alone as first-line treatment in advanced NSCLC patients with EGFR mutations and BIM deletions (BIMdel).

Method: A retrospective analysis was conducted. BIMdel was detected using polymerase chain reaction (PCR) analysis and direct sequencing of DNA from tumor and peripheral blood cells (PBCs). We also assessed BIM protein expression by immunohistochemistry and BIM mRNA levels by RT-PCR. Clinical characteristics, overall survival (OS), progression-free-survival (PFS), objective response rate (ORR) and treatment-related adverse events were compared in the EGFR-TKIs versus EGFR-TKIs plus Bev groups.

Results: 32 patients were included; 16 of them received EGFR-TKIs and 18 received EGFR-TKIs plus Bev. The addition of Bev resulted in a significantly higher ORR compared with TKIs alone (94% vs. 44%, p=0.0014). Median PFS was longer with the use of the combination compared with TKIs alone (11.1 vs. 7.77 months; p < 0.001). Median OS tended to be longer in the EGFR-TKIs plus Bev group than in TKIs alone (30.9 vs. 25.4 months; p = 0.06). EGFR-TKIs plus Bev was associated with more grade >3 hematological and thrombotic adverse events. The expression of BIM by immunohistochemistry did not influence PFS and OS, however when stratifying BIM mRNA levels by the median (≥2.2 vs. <2.1) allowed to find a prognostic trend in favor of those with higher BIM mRNA levels (32.2 vs. 25.2 months respectively; p = 0.058).

Conclusion: EGFR-TKIs plus Bev conferred a significantly higher ORR and PFS in advanced NSCLC patients with EGFR mutation and BIMdel. Further prospective studies are needed to validate these findings

Keywords: Bevacizumab, EGFR, BIM

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EGFR Mutations in Lung Cancer in Northern Mexican Population

K.E. López Reséndiz, O. Barboza Quintana, R. Garza Guajardo, N. Vilches Cisneros, J.P. Flores GutiérrezHospital Universitario Dr. Jose Eleuterio Gonzalez, Monterrey, Nuevo Leon/Mexico

Background: Lung cancer is the most common cause of death from cancer worldwide, responsible for 1.59 million deaths. Multiple studies support the predictive value in treatment selection, EGFR mutations are also prognostic for survival benefit. EGFR gene exon 19 deletion and the exon 21 L858R substitution account for approximately 90% of all EGFR mutations. The aim of this study is evaluate the frequency of EGFR mutations in lung cancer in Northern Mexican population.

Method: DNA extraction is performed using a commercial extraction kit, the process is performed by real-time PCR on an automated platform in a closed circuit with a commercial panel. The DNA quantification quality control process is analyzed, validating with positive and negative controls, then analysis of the 29 known mutations of EGFR gene exons 18, 19, 20, 21. All the concepts were evaluated with descriptive statistics. IBM SPSS Statistics version 4 software was used, using Chi-squared test.

Results: This study includes 450 patients. The median age of the patients is 64 years (range 30-90). Activating mutations were found in the EGFR gene in 141 patients (31.33%). Of the patients with mutations found, 79 (56.02%) patients had exon 19 deletion (DelEx19) and 43 (30.49%) patients have L858R mutation (Ex21), which represent 86.52% of the total mutations found. EGFR mutations were more frequent in older patients (82.97% >51 years), than in the younger ones (14.18% <50 years). The age range with the highest number of EGFR mutations was 61-70 years (28.36%).

Conclusion: 31.33% of mutations were found in our cases. EGFR exon 19 deletions and the exon 21 L858R substitutions were more frequent compared to the other mutations. The frequency of mutations in EGFR coincides with the literature that mutations are more prevalent in women. A study published in 2011 evaluated the frequency of mutations in EGFR and KRAS in NSCLC in different ethnic groups and found that in Mexico the frequency of EGFR mutations was 31.2%.

Keywords: Non-small cell lung cancer, Mutation, EGFR, Mexico

P1.02


ALK Gene Rearrangement in Patients with Lung Cancer in Northern Mexican Population


Background: EGFR mutation and re-arrangement of the ALK gene are two of the molecular targets evaluated in all cases of patients with primary lung adenocarcinoma. ALK rearrangements are mutually exclusive with mutations in EGFR or KRAS. These mutations are helpful in choosing targeted therapy for the patient. The aim of this study is to evaluate the frequency of ALK gene rearrangement in patients with Lung cancer in Northern Mexico population and histological patterns.

Method: 450 patients with NSLC were evaluated from 2006 to 2017. In all cases we perform immunohistochemistry with clone D3F5 in an automated platform. FISH rearrangement for ALK break apart were done a commercial kit. We follow the recommended criteria of IASLC for the evaluation of the FISH probes. Immunohistochemistry and FISH test were reviewed by 2 pathologists with experience and training in the evaluation of both test.

Results: This study includes 450 patients. The median age of the patients with ALK gene rearrangement was 53 years (range 37-82) and male to female ratio of 1:8. 65 (14.44%) were positive by inmmunohistochemistry in any intensity and percentage of neoplastic cells, and only 17 (3.77%) were positive or ALK rearrangement by FISH. All the cases which was negative for immunohistochemistry was negative by FISH.

Conclusion: We found ALK rearrangements in 17 cases (3.77%), this figure is similar in Hispanic resident in USA and Latin-American population, however reports in Mexican population are between 4 and 10.5 %. This difference it will be due to different cohorts of patients, methodology types of FISH probes used for the detection of ALK rearrangements and ethnic differences.

Keywords: Mexico, Non-small cell lung cancer, ALK, Mutation

P1.03


Case Series of Double Mutations in Patients with Lung Adenocarcinoma


Background: The introduction of targeted therapies has increased the survival time in a subset of patients with NSCLC. The National Comprehensive Cancer Network (NCCN) clinical practice guidelines in oncology recommend measuring the local EGFR gene mutations of NSCLC patients before treatment.

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84 (59.57%) 137 (44.33%)

57 (40.42%) 172 (55.66%)

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Specific muta-tion of EGFR Exon 19 deletion Exon 21 L858R G719X L861Q Insertion S768I T790M

46 (58.22%) 27 (62.79%) 4 (80%) 3 (42.85%) 2 (50%) 1 (100%) 1 (50%)

33 (41.77%) 16 (37.20%) 1 (20%) 4 (57.14%) 2 (50%) 0 (0%) 1 (50%)

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Sensitivity to EGFR TKIs in patients with double or multiple mutations is not well described. In the literature there are few reported cases of double mutations. We present a series of six cases of Lung Adenocarcinoma with double mutations found between 2006 and 2017 in a hospital in Northern Mexico.

Method: 450 patients with Lung cancer were evaluated from 2006 to 2017. DNA extraction is performed using a commercial extraction kit, the process is performed by real-time PCR on an automated platform in a closed circuit with a commercial panel. The DNA quantification quality control process is analyzed, validating with positive and negative controls, then analysis of the 29 known mutations of EGFR gene exons 18, 19, 20, 21.

Results: This study includes 450 patients, 141 (31.33%) patients had EGFR mutations, of which six (4.25%) had double exons EGFR mutations. Of the six cases with double mutations, male to female ratio was 1:1. The histological patterns reported in the double mutations were: 3 (50%) cases with acinar pattern, 2 (33.33%) with micropapillary pattern, and 1 (16.66%) solid pattern. The median age of the six patients is 54 years (range 38-78).

Conclusion: EGFR co-mutation had a significantly lower mean progression-free survival than those with a single mutation (5.7 months vs. 12.3 months). The response rate to TKI was significantly worse in those with co-mutation compared to those without co-mutation (38% vs 89%). There are few studies evaluating all the characteristics of cases with double mutations, such as histological pattern and the mutations of EGFR gene exons. Further research on double mutations is suggested because of the impact on treatment and prognosis of the patient.

P1.04


Prevalence, Pattern and Factors Associated with Dual Tobacco Use in a Rural Community in South Eastern Nigeria

U. Ofonakara1, O.E. Ekesi21Community Medicine, Federal Teaching Hospital Abakaliki/National Primary Health Care Development Agency, Abakaliki/Nigeria, 2Health Economics, Madonna University, Okija/Nigeria

Background: National prevalence studies have consistently shown higher rates of dual tobacco use in South Eastern Nigeria but little is known about the pattern and factors associated with dual tobacco use in these parts of the country. Dual tobacco use is a greater health problem than mono use and needs to be researched. The aim of this study was to determine the pattern and factors associated with dual tobacco use among residents of a rural community in South Eastern Nigeria.

Method: A cross-sectional descriptive study was carried out among 490 residents of Ukpo community selected using a two-stage sampling method. Data was collected using a pre-tested interviewer-

administered questionnaire adapted from the Global Adult Tobacco Survey. Odd ratios and 95% confidence intervals were computed and P values of < 0.05 were considered statistically significant.

Results: The results showed that respondents were mostly male 300(61.2%) and aged between 20 and 70 years with a mean of 42.2 ± 15.4 years. Almost a quarter of the respondents, 101 (20.6%) were ever- dual tobacco users. Also, 210(42.9%) use only smokeless tobacco while only 110 (22.4%) use only smoked tobacco Dry snuff (73.8% of smokeless tobacco forms) cigarettes 82.2% (of smoked tobacco forms) were the most common forms of tobacco used. The primary reasons for tobacco use were: to relieve stress (61.2%); to increase levels of alertness (56.4%); for personal pleasure (55.9%) and social acceptance (52.1%). Age (p<0.0001), male gender (p<0.0001) and lower educational attainment (p<0.0001) were associated with dual tobacco use. About half of the respondents (51%) were aware that dual tobacco is more dangerous to human health than mono use and only about (27.1%) were aware that tobacco use is associated with lung cancer and COPD. Many of the respondents agreed that tobacco is a way of promoting friendship (65%) and should be used within their community (73%).

Conclusion: Efforts targeted at raising community awareness of the health effects of dual tobacco use are needed in rural communities where dual tobacco use is disproportionately high. Programs should be directed to males with lower educational attainment.

Keyword: Tobacco, Lung cancer

P1.05


Lung Cancer Patients – Major Causes of Hospitalization and Mortality

C. Custódio, V. Sacramento, M. Felizardo, S. FurtadoHospital Beatriz Angelo, Loures/Portugal

Background: Lung cancer (LC) is the leading cause of cancer-related mortality and a major source of morbidity and health care costs with high hospitalization rates. The aim of this study was to identify the major causes of hospitalization and of mortality in patients with LC at a district hospital.

Method: A retrospective analysis of patient’s clinical records admitted in the Pneumology ward of our hospital from May 2014 to May 2019 with LC diagnosis was performed. We characterized patients according to demographic characteristic, comorbidities, histology, clinical stage, causes of hospitalization and outcome.

Results: 246 patients (392 admissions) were analyzed. 72.4% were male. Mean age was 66.5 ± 10.2 years. 78.5% had active or past smoking habits. The most prevalent comorbidities were cardiovascular disease (48.8%) and chronic obstructive pulmonary disease (34.6%). Adenocarcinoma was the most frequent histology found (57.3%). 65.7% of patients had advanced stage disease at admission and 68.3% were under active therapeutics. The median length of hospitalization was 10 days (IQR 6-18). The major causes of hospitalization were respiratory infection (26.5%) and disease progression (18.4%). We found that empirical antibiotic therapy was used in 44.6% of admissions, only 11.2% of patients had positive bacteriological tests (most common bacteria identified were Klebsiella pneumoniae and Escherichia coli). 74 patients (30.1%) died. We found a strong statistically significant association between mortality and advance stage disease (p value: 0,006) and disease progression as cause of hospitalization (p value: 0,001). Hospitalization ≥ 10 days was strongly associated with infectious intercurrence (p value: 0,0001) and with mortality (p value: 0,016).

Conclusion: Respiratory infection represents a major cause of admissions of LC patients in our ward. These patients have

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multiple causes for immunosuppression, therefore high suspicion and early intervention are needed to minimize the impact on patient’s quality of life, length of hospitalization and associated mortality. Disease progression was the second cause, so in order to optimize end of life strategies and avoid potentially unnecessary admissions we reinforce the need of a palliative care with a multidisciplinary approach.

Keyword: Lung cancer, Hospitalization, Mortality, Palliative care

P1.06


Determination of Exposure to Tobacco Smoke and the Percentage of Global DNA Methylation in Smokers and Patients with Lung Cancer

A.G. Alcázar-Ramos1, M.A. Meraz-Ríos2, M.D.P. Figueroa-Corona2, D.G. García-Gutiérrez1, A.D. Bertadillo-Jilote1, I.F. Pérez-Ramírez1, K.L. García-Mejía1, B. Ugalde-Villanueva1, K.I. Lira-De León1

1Maestría En Química Clínica Diagnóstica, Universidad Autónoma de Querétaro, Santigo de Queretaro/Mexico, 2Biomedicina Molecular, Centro de Investigaciones y de Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de Mexico/Mexico

Background: Smoking is a disease caused by nicotine addiction and is the first cause of preventable death worldwide. In Mexico, according to the ENCODAT National Survey of Drug, Alcohol and Tobacco Consumption (2016-2017), the prevalence of consumption was 20.1% in the population aged 18 to 65 years. Smoking also is associated with cancer, the INCAN (National Institute of Cancerlogy) report that the 87% of cases of lung cancer and 82% of deaths due to lung disease are due to tobacco use.

Method: Therefore, the objective of this project was to quantify the degree of exposure to tobacco smoke (cotinine) and the percentage of global DNA methylation in non-smokers, smokers and patients with lung cancer, as possible factors associated with the development of lung cancer. We recruited 30 participants to evaluate these parameters in the groups of study, both methods were analyzed by ELISA.

Results: The results showed that cotinine values were in average averages of 1.24 ng / mL in non-smokers, 3.7 ng / mL in smokers and 0.45 ng / mL in lung cancer. Whereas the averages in the percentage of global DNA methylation were: 3.31%, 1.95% and 1.58%, respectively. Although there was no significant statistical difference between the groups, we observed similarity in the percentage of global DNA methylation with a value <1% in the 50% of patients with lung cancer and 22.2% of smokers.

Conclusion: The above suggests that these low of percent methylation values could be used as a possible predisposing factor for lung cancer.

Keywords: Cotinine, DNA methylation, Lung cancer

P1.07


Habits in Tobacco Consumption of a Population of Queretaro

K.L. García-Mejía1, A.L. Vega-Rodríguez1, A.G. Alcázar-Ramos1, R. Salas-Coronado2, N.F. Santos-Sánchez2, B. Hernández-Carlos2, M.D.P. Figueroa-Corona3, M.A. Meraz-Ríos3, K.I. Lira-De León1

1Maestría En Química Clínica Diagnóstica, Universidad Autónoma de Querétaro, Santigo de Queretaro/Mexico, 2Instituto De Agroindustrias, Universidad Tecnológica de la Mixteca, Huajuapan de León, Oaxaca/Mexico, 3Biomedicina Molecular, Centro de Investigaciones y de Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de Mexico/Mexico

Background: According to ENCODAT in Mexico, 43,000 people die due to diseases attributed to smoking, an amount that represents 8.4% of the total deaths in the country. In addition, it represents a high economic cost for the Mexican health system. The tobacco epidemic has remained unchanged since 2009. The state of Queretaro has a population of 1.5 million people aged 12 to 65 years, of which 281 thousand are smokers of which 127 thousand smokes daily and 155 thousand smoke occasionally.

Method: Therefore, the objective of this project was describing the smoking habits of a group of active, passive and non-smoking smokers in the city of Queretaro. With the information of a form made to each participant, after the signing of their informed consent, the obtained data were analyzed to expose the results with the use of descriptive statistic.

Results: 165 people participated in the applied survey, with an age of 18 to 74 years. The prevalence of active smokers is higher in men than in women with 26.2% compared to 11.47% respectively, women have a higher prevalence in secondhand smoke and 34.32% of the population studied is free from the habit of smoking and second-hand smoke, the number of cigarettes per day on average was 5.3, the number of years on average of smoking was 13.1 years. 43.47% of active smokers do not perform any physical activity. In addition, no relationship was found between having a bad habit of smoking and poor diet. The main cancer observed in the family history was breast, then prostate and skin cancer.

Conclusion: It is important that in the city of Queretaro smoke-free places increase, that people have the education to ask if they are upset that they smoke in front of people who do not, and also that passive people can freely express that they do not like that habit, this would have the benefit of reducing secondhand smoke when it is not a decision of its own and increasing the percentage of the population not exposed. Lung cancer was not found among the main ones due to its frequency in the relatives of the study group, but it is known that of all the types it is the most deadly cancer and the main risk factor is the smoking that causes 85% of the cases.

Keywords: Querétaro, Prevalence, Tobacco consumption

P1.08


A Retrospective Study of 230 Cases of Lung Disease - Talk about the Relationship Between Heavy Physical Labor and Lung Cancer

Y. ZhangThoracic Surgery Department, The First Hospital of Lanzhou University, lanzhou/China

Background: In developing countries, there are still many patients with tuberculosis, chronic pneumonia, chronic bronchitis and silicosis and lung cancer. In China’s backward regions and rural areas, there are millions of patients who require long-term treatment and professional care for lung cancer. Most of the affected population are those who have been engaged in heavy physical labor for a long time. The age is between 38 and 55 years old, and it costs billions of dollars each year. How to find out the cause of the problem, how to solve this problem is urgently needed by us.

Method: This study conducted a retrospective study of 230 heavy-duty laborers hospitalized in the First Hospital of Lanzhou University from 2000 to 2018, including youth (18-30), middle-aged (31-50), and old (by age). >51) Three groups, divided into Non-small cell lung cancer, small cell lung cancer, special occupational lung cancer (painter and Asphalt road workers) by disease. Divided into three levels according to labor time and labor intensity: level 1 (labor time <8 hours, energy consumption <2000 calories / 24 hours), level 2 (labor time 8-12 hours, energy

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consumption 2000-4000 calories / 24 hours), level 3 ( Labor time > 12 hours, energy consumption > 4000 calories / 24 hours). To discuss the relationship between the patient’s illness time and labor time, the relationship between labor intensity and onset time, the relationship between sleep time and labor time distribution and disease, the relationship between disease type and hospitalization time and labor intensity and labor time were reviewed.

Results: The study found that age, labor time and labor intensity, as well as rest time are directly related to lung cancer. The older patients were east to get the higher the incidence of lung cancer; the longer the physical labor time, the higher the incidence of lung cancer; the higher the physical labor intensity, the higher the incidence of lung disease; the shorter the rest time, the higher the incidence of lung disease; labor The longer the patient and the more labor intensive, the longer the hospital stay, and the slower the recovery and remission.

Conclusion: The correlation between heavy physical labor and lung disease may be related to the higher demand for cardiopulmonary function. A large amount of energy consumption will result in a decline in the function of the immune system, loss of nutrients, and decreased cell viability. Insufficient sleep can also lead to immune system disorders and decreased organ function. The working environment, diet, and lifestyle habits of heavy physical labor can also affect the occurrence of lung diseases. How to pay attention to the health of heavy physical workers is the direction we need to work hard.

P1.08-A


Sherlock Lung Tracing Lung Cancer Mutational Processes in Never-smokers

L. Mendoza1, T. Zhang1, M. Garcia-Closas1, M. Abubakar1, O. Arrieta2, P. Hofman3, D. Christiani4, N. Lopez-Bigas5, B. Rothberg6, T. Peikert7, D. Gordenin8, L. Alexandrov9, G. Getz10, D. Wedge11, M.T. Landi1.1National Cancer Institute, NIH, Bethesda, Maryland/USA, 2National Institute of Cancer INCan, Mexico City/Mexico, 3University of Nice, Nice/France, 4Harvard University, Boston/ USA, 5Institute for Research in Biomedicine IRB, Barcelona/Spain, 6Yale University, New Haven, Connecticut/USA, 7Mayo Clinic, Rochester, Minnesota/USA, 8National Institute of Environmental Health Sciences NIEHS, Durham, North Carolina/USA, 9University of California San Diego, La Jolla, California/USA, 10Broad Institute, Cambridge, Massachusetts/ USA, 11Oxford University, Oxford/UK

Background: Lung cancer in never-smokers represents 10-25% of lung cancers worldwide; ranks among the most common causes of cancer mortality; and has a distinct natural history, predominant histological subtype (adenocarcinoma), different profile of oncogenic mutations, and response to targeted therapy compared to lung cancer in smokers. There are few known environmental and genetic risk factors for lung cancer in never-smokers; however, a large fraction of cases cannot be explained. One promising approach to identify etiological factors involved in lung tumorigenesis in never-smokers is the study of “mutational signatures” that exogeneous and endogenous processes leave on the tumor and surrounding tissue. This approach has identified 50+ mutational signatures in other cancer types, corresponding to several oncogenic processes.

Method: We are conducting an integrative genomic analysis of mutational signatures in tumors and surrounding non-tumor lung tissue from 2,000 never-smokers. Study subjects include a subset of “special exposure cases” exposed to high levels of known risk factors (n=~500) and “general population cases” without known risk factors (n=~1,500). Subjects are drawn from studies with lung tissue samples and high-quality epidemiological and clinical data. We are striving to

include subjects from many geographical areas and ethnic groups to study the contribution of different germline and environmental factors. The tumor/normal genomics analysis are ongoing and include whole genome sequencing (WGS), RNA sequencing, and genome-wide methylation arrays. The integrated molecular landscape will be ordered along the evolutionary trajectory of the tumors to infer the cascade of events leading to tumor formation and progression. Data on the molecular and evolutionary landscape will be combined with data from histological examination of H&E slides from multiple tissue blocks per tumor and related to CT imaging to provide a more refined classification of lung cancers among never-smokers. Additional studies will include lineage phylogenetic analysis to infer the clonal evolution of lung tumors using multi-region tumor sampling; deep target sequencing of cancer driver genes and ultra-low pass WGS of cell-free circulating tumor DNA; tumor microenvironment analyses based on immunohistochemistry or fluorescence-based imaging and RNA sequencing; and analyses of large-scale electronic medical records.

Result: Preliminary results will be shown, highlighting the large differences in the molecular landscape of lung cancer in never-smokers from that of smokers.

Conclusion: This comprehensive study will improve our understanding of the etiology and progression of lung cancer in never-smokers and provide clues into prognosis and treatment.

Keywords: Lung cancer, Never-smokers, Mutational signatures, Whole genome sequencing

P1.09

Topic: SCLC, Mesothelioma, Thymoma

Heterogeneous versus Homogeneous Radiation Dose Calculations of Twice Daily Fractionation in Small Cell Lung Carcinoma

R. Thibodeau1, H. Li1, A. Gajra2, S. Tanny1, J. Bogart1

1Radiation Oncology, SUNY Upstate Cancer Center, Syracuse/United States of America, 2Medical Oncology, SUNY Upstate Cancer Center, Syracuse/United States of America

Background: The standard radiotherapy treatment regimen for small-cell lung cancer was determined using homogeneous dose calculations, while modern trials use heterogeneity corrected treatment plans. We assessed differences in dose delivered using heterogeneous and homogeneous dose calculations in a cohort of patients treated for limited-stage small cell lung cancer (LS-SCLC).

Method: Retrospective analysis of 35 patients (3D-CRT, n=22; IMRT, n=13) with stage IIA-IIIB (American Joint Committee on Cancer 2010) treated with chemoradiotherapy from 2011-2017. Treatment plans were analyzed using superposition/convolution algorithms and dosimetric data was collected. Two plans were generated for each patient with one using the same unit density, and another plan with the same monitor units and applying density corrections. The prescription was 45 Gy in 30 fractions of 1.5 Gy. Patients treated with multiple plans were evaluated using a corrected/uncorrected plan sum. Variations in tumor dose >5% are considered clinically significant. A two-sided paired student t-tests was used to evaluate the dosimetric differences.

Results: Compared with homogeneous radiation dose calculations, heterogeneous plans resulted in a median dose difference in the PTV D95 of -3.0% (range -15.1% to 9.6%) with median dose differences of -0.1% (range -4.8% to 12.5%, p = 0.62) using 3D-CRT and -10.0% (range -15.9% to -5.3%, p < 0.01) using IMRT. The overall median dose differences found in the Lung V20 was -5.6% (range -17.3% to 5.4%); with median dose differences found of -4.2% (range -9.4 to 5.4, p < 0.01) using 3D-CRT and -8.9% (range -17.3 to -3.5, p < 0.01) using IMRT.

Conclusion: The incorporation of heterogeneity tissue correction results in an overall reduced dose delivered to the target

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compared with traditional planning. These differences are modest for 3D treatment plans but may be clinically relevant for the IMRT cohort (>5% deviation). Assessment of larger datasets may be warranted and consideration of twice-daily treatment regimens using higher dose per fraction may be worthy of future study.

Keywords: Small cell lung cancer, Radiation dosimetry, Radiation oncology, Heterogeneity corrections

P1.10


Survival of Thymoma Is Extensive in Latin-American Patients: Results from over 10 Years of Experience (CLICaP-LATimus)

L. Mas1, A.K. Patane2, O. Arrieta3, T. Soria4, A.F. Cardona5, C. Martín6, A. Ruiz-Patiño7, R. Ruiz1, P. Rioja1, S. Lozano1, L. Zatarain Barron8, F. Barrón9, M. Corassa10, H. Freitas11, V.C. Cordeiro De Lima11, L. Corrales-Rodriguez12, C. Sotelo7, J. Rodríguez7, L. Ricaurte7, J. Ávila7, D. Mayorga7, M. Bravo7, P. Archila7, J. Otero7, H. Carranza7, C. Vargas7, R. Rosell13, J. Remon14

1National Cancer Institute (INEN), Lima/Peru, 2Hospital de Rehabilitación María Ferrer, Buenos Aires/Argentina, 3Thoracic Oncology Unit, Instituto Nacional de Cancerología, México City/Mexico, 4Hospital Oncológico SOLCA, Quito/Ecuador, 5Clinical And Translational Oncology Group, Clinica del Country, Bogotá/Colombia, 6Medical Oncology Department, Instituto Fleming, Buenos Aires/Argentina, 7Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá/Colombia, 8Unidad Funcional de Oncología Torácica Instituto Nacional de Cancerología, Mexico City/Mexico, 9Instituto Nacional de Cancerologia, México City/Mexico, 10Hospital AC Camargo, Sao Paolo/Brazil, 11Camargo Cancer Center, Sao Paolo/Brazil, 12CIMCA - CCSS, San José/Costa Rica, 13Cancer Biology And Precision Medicine Program,, Catalan Institute of Oncology, Barcelona/Spain, 14Hospital Vall d´Hebron, Barcelona/Spain

Background: Thymomas are a group of rare neoplasm of the anterior mediastinum. Due to their low incidence, large cooperative studies are required to evaluate outcomes. The objective of this study is to present the results and experience in treatment of this pathology in Latin-America.

Method: A retrospective multicenter cohort study was conducted by The Latin-American Consortium for the Investigation of Lung Cancer (CLICaP). Patients with histologically proven thymomas between 1997 and 2018 were included in the analysis. Variables including clinical, pathological and therapeutic outcomes were registered in a centralized manner.

Results: A total of 105 patients were included. Median age at diagnosis was 54 years old (20-84), and with 60% (n = 38) of the included patients were female. Only 11% (n=7) of the patients had an ECOG performance score >1. Twenty-four patients (22.9%, 95%CI 14.8-30.9) presented with pulmonary or distant metastatic involvement with a median of 2 metastatic sites. Furthermore, 21.9 % of patients (n=23, 95%CI 13.9-29.8%) concurrently presented myasthenia gravis. Surgery was performed in 55 patients (52.3%, 95%CI 42.8 – 61.9%), comprising of 15 tumorectomies, 37 thymectomies and 5 biopsies achieving an R0 resection rate of 78% (95%CI 67.3-89.1%). Adjuvant treatment in the form of either chemotherapy, radiotherapy or both was offered to 3(5%), 7(12.7%) and 5(9%) patients, respectively. Disease progression was documented in 10 cases (9%, 95%CI3.9-15.1%) of which 6 (60%) were locoregional, 1 (10%) distant progression and 3 (30%) both locoregional and distant. Median overall survival (OS) was estimated at around 139.5 months (95%CI 86.1-NA). Cox regression indicated that OS was significantly improved by resection (139.5 vs 25.7 months, HR 4.17 [95%CI 12.6-17.8 months]).

Conclusion: Survival in patients with thymomas continues to be very favorable, especially in patients who receive adequate local control. The benefit of adjuvant treatment in this setting remains unclear.

Keywords: Local control, Adjuvant therapy, Survival

P1.11


Multicenter Study of Histological Types Incidence and Pathological Features of Malignant Pleural Mesothelioma (MPM) in Argentina

C. Poleri1, G. Acosta Haab2, N. Falcoff3, G. Guman4, L. Dalurzo5, A. Iotti6, M.E. Martín7, G. Olmedo8, M. Rayá4, A. Reginatto4, A. Werbach3, G. Demellis9, M.J. Labanca5, L. Leguina2, M.F. Mora9

1Consultorio de Patología Torácica, Ciudad de Buenos Aires/Argentina, 2Hospital Oncología “María Curie”, San Isidro Patología, Ciudad de Buenos Aires/Argentina, 3Pathology, Hospital Prof. Dr. B. Houssay/ Hospital del Tórax A. Cetrángolo, Vicente López/Argentina, 4Pathology, Hospital de Rehabilitación Respiratoria María Ferrer, Ciudad de Buenos Aires/Argentina, 5Hospital Italiano de Buenos Aires, Buenos Aires/Argentina, 6Pathology, Hospital Británico, Buenos Aires/Argentina, 7Pathology, Hospital Gral. de Agudos Enrique Tornú, Ciudad de Buenos Aires/Argentina, 8Laboratorio Privado de Patología, Ciudad de Buenos Aires/Argentina, 9San Isidro Patología, San Isidro/Argentina

Background: The pathological diagnosis of MPM allows to identify different biological aggressiveness contributing to therapeutic decisions. OBJECTIVES: Analyze the morphological and immunohistochemical profile of a series of MPM and describe incidence of their histological types. Recognize the transitional pattern proposed as an aggressive clinical-pathological entity.

Method: A retrospective and multicenter study was carried out by 8 Argentinian pathology laboratories. We review slides with MPM diagnosis (2009-2018) according the 2015 WHO criteria and iMig 2018 recommendations. We described: types, necrosis, nuclear atypia and mitosis/10HPF. The transitional pattern was considered extensive or focal.

Results: Cases: 398. Men: 59%, female 41 %, median age: 66 (24-91). Samples: 78% surgical biopsies, 16.5% small biopsies; 2.5% from pleurectomies and 3% from pleuroneumonectomies. Histological types: 77% epithelioid (E-MPM), 12% biphasic, 10% sarcomatoid and 1% transitional. Patients ≥ 66 years had no E-MPM more than <66 (X2: p<0.028).

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Predominant patterns of E-MPM were: 36.5% tubular/acinar, 33% solid, 12% trabecular, 11% papillary, 3% pleomorphic, 2% micropapillary, 2% adenomatoid and one case was deciduoid. We highlight that 59% of the E-MPM presented a second pattern: papillary (16%), solid (15%), tubular (11%), trabecular (7.5%) and micropapillary (5%). Immunohistochemistry: There were no differences in Calretinin expression between E-MPM and no E-MPM. The E-MPM had cytokeratin 5 expression in 91% of the cases and WT-1 in 90%; no E-MPM in 68% and 70% (p<0.001). Transitional morphological features were found in 12 surgical samples: 4 cases extensive and 8 cases focally (4 biphasic, 3 sarcomatoid and 1 epithelioid solid predominant). 3/4 extensive cases were ≥ 66 years old, 4/4 had necrosis and nuclear score II and III.

Conclusion: The findings show the intra-tumoral heterogeneity of MPM and that the variability of composite grading can be analyzed in routine cases. Standardizing immunohistochemical panels for MPM diagnosis is mandatory. Detailed histopathological diagnosis can help to select the appropriate treatment for each patient.

Keywords: Mesothelioma, Pathology

P1.12


Real World Characterization and Treatment Patterns of Patients with Thymic Carcinoma: Lessons from a Latin American Collaborative Study (CLICaP-LATimus)

L. Mas1, A.K. Patane2, O. Arrieta3, T. Soria4, A.F. Cardona5, C. Martín6, A. Ruiz-Patiño7, R. Ruiz1, P. Rioja1, S. Lozano1, L. Zatarain Barron8, F. Barrón9, M. Corassa10, H. Freitas11, V.C. Cordeiro De Lima11, L. Corrales-Rodriguez12, C. Sotelo7, J. Rodríguez7, L. Ricaurte7, J. Ávila7, D. Mayorga7, M. Bravo7, P. Archila7, J. Otero7, H. Carranza7, C. Vargas7, R. Rosell13, J. Remon14

1National Cancer Institute (INEN), Lima/Peru, 2Hospital de Rehabilitación María Ferrer, Buenos Aires/Argentina, 3Thoracic Oncology Unit, Instituto Nacional de Cancerología, México City/Mexico, 4Hospital Oncológico SOLCA, Quito/Ecuador, 5Clinical And Translational Oncology Group, Clinica del Country, Bogotá/Colombia, 6Medical Oncology Department, Instituto Fleming, Buenos Aires/Argentina, 7Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá/Colombia, 8Unidad Funcional de Oncología Torácica Instituto Nacional de Cancerología, Mexico City/Mexico, 9Instituto Nacional de Cancerologia, México City/Mexico, 10Hospital AC Camargo, Sao Paolo/Brazil, 11Camargo Cancer Center, Sao Paolo/Brazil, 12CIMCA - CCSS, San José/Costa Rica, 13Cancer Biology And Precision Medicine Program,, Catalan Institute of Oncology, Barcelona/Spain, 14Hospital Vall d´Hebron, Barcelona/Spain

Background: Thymic carcinoma is a rare tumor that represents a clinical challenge, especially in resource limited settings. The objective of the present study was to characterize patients who presented this disease in Latin-America.

Method: From 2014 until 2018, a multinational Latin-American cooperative retrospective cohort study was performed. Patients with histologically confirmed thymic carcinoma were included. Clinical, pathological and treatment variables were collected across 7 participating nations.

Results: A total of 31 patients were included. Median age at diagnosis was 58 years old (34-69), 48% (n=15) of individuals were women with all but 2 patients (6.5%) achieving an ECOG performance score <2. All patients debuted with Stage IV disease; 24 patients (66%, [95%CI 62-92%]) as stage IVa and 7 as stage IVb (33%, [95%CI 7-37%]) with a median LDH level of 396.5 U/L (153-1529 U/L) and a median of 2 metastatic sites. 13 (41.9%, [95%CI 25-59%]) patients received preoperatory treatment consisting of chemotherapy (n=8, 42%) and chemoradiotherapy (n=5, 16%). Among these patients only 4 (12.9%) were subjected to surgery, two of which underwent a

tumorectomy and 2 a thymectomy. 28 (90%, [95%CI 79.9-100%]) received palliative chemotherapy either with sunitinib (n=7, 25%) or cytotoxic agents. Median overall survival (OS) was reached at 20.2 months (95%CI 19-NA months). Patients who received preoperative treatment had a significantly prolonged OS (17.6 vs 26 months, HR 2.93 [95%CI 1.04-8.27 months], p = 0.03).

Conclusion: Thymic carcinoma constitutes an aggressive disease that is often diagnosed in advanced stages. These results suggest that multimodal treatment can be beneficial even in locally advanced cases. Larger clinical trial validating these conclusions are warranted.

Keywords: Thymic carcinoma, LDH, Survival

P1.13


Advanced Small Cells Lung Cancer: 5 Year Experience at the National Oncology Institute of Panama, 2014-2018

T. Sowley, A. Crismatt, O. CastilloMedical Oncology, Instituto Oncologico Nacional de Panamá, Panama/Panama

Background: Small Cell Lung Cancer (SCLC) is a very aggressive disease and it represents approximately 10%-15% of patients with Lung Cancer. Until recently with the promising activity of immunotherapy, there was no advance in treatment since the discovery of the role of platin-based/etoposide doublet chemotherapy in the 1980s but with frequent and rapid development of acquired resistance. In Panama, is not a very common disease, but when it is found, the outlook for these patients with SCLC remains dismal as reported worldwide.

Method: We retrospectively reviewed the electronic medical records of patients diagnosed with SCLC between January 2014 and December 2018. The objectives were to describe the incidence, clinical characteristics, treatment and to the determine the overall survival of our patients.

Results: There 36 patients diagnosed with SCLC during this period for an incidence of 8,0%. The mean age of diagnosis is 68 years (41 - 85) and 72,2% were males. ECOG 0-1 was found in 50% of the patients. 87,9% of the patients were smokers with 66,7% being heavy smokers. The majority of cases were diagnosed with advanced disease with 83,3% in extensive stage disease. Brain metastasis was present in 35% of the cases and all received WBRT. 61,7% could receive first line chemotherapy: 51,7% with CDDP/Etoposide and 42,9% with Carboplatin/Etoposide, and 8,8% could receive second line chemotherapy with Irinotecan. The median overall survival was 6,7 months (95% CI 4,1 - 9,2).

Conclusion: Our findings shows a lower incidence but with similar clinical characteristics, treatment and overall survival as reported worldwide. This supports the aggressive nature of the disease and the need of new treatment strategies.

P1.14


Morbidity, Mortality and Oncologic Outcomes in Bronchoplastic Procedures Performed in a Mexican Public Reference Hospital

B. Zavala Retes, E.M. Garcia BazanHospital De OncologÍa, Departamento De TÓrax, INSTITUTO MEXICANO DEL SEGURO SOCIAL, CIUDAD DE MÉXICO/Mexico

Background: Pulmonary cancer still represents the first cause of non-skin cancer related death worldwide, not being Mexico excluded from this epidemiological behavior; neuroendocrine tumors represent approximately 14% of all lung cancers, only one third of patients are diagnosed in a thorax confined

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stage; as a part of the multidisciplinary management of such pathology, surgery is, in early resectable disease (T1-T2, N0, M0), an adequate and standardized treatment option. Despite the benefit of oncological resection in these patients, a limiting factor result of the healthy lung tissue forfeited in classic oncological resections (lobectomy and pneumonectomy), thus, bronchoplastic procedures play an important role in selected patients by either sparing normal lung tissue and allowing resections in patients who otherwise would not tolerate a mayor resection without jeopardize oncologic results.

Method: We present a case series of 25 patients who underwent broncoplastic procedures for neuroendocrine malignancy in a retrospective fashion over a 10-year period. We analyze the morbidity and mortality directly associated to the procedure as well as the oncologic results by disease free survival and overall survival.

Results: Morbidity presented in 20% of the patients; 30-day mortality in 0%; bronchopleural fistula in 16%, pneumonia in 12%, empyema in 8%, cardiac arrhythmias in 1%; 3-year survival was 47% and disease-free survival had a median of 23 months.

Conclusion: The oncological benefit of a bronchoplastic procedure is proved in selected patients with bronchial neuroendocrine tumors that fit anatomical requirements, the results may be equal to that of the mayor oncological resections and our surgical oncology department morbidity, mortality and oncologic outcomes match those mentioned in literature.

P1.16


Awake Thoracoscopic Lung Cancer Biopsy

E. Peña Gomez Portugal1, A. Leticia Solano Nieto2, F. Bolaños Morales3

1Experimental Surgery, National Institute of Medical Science and Nutrition Salvador Zubiran, MEXICO CITY/Mexico, 2Anesthesiology, IMSS, mexico/Mexico, 3Thoracic Surgery, INER, MEXICO/Mexico

Background: An adequate tissue biopsy in lung cancer permits the pathology to perform increasingly complex and quantitative biomarkers in the samples, that will allow the oncologist to see responses therapy over time according to the mutations that is the standard of care to lung cancer patients. The minimally invasive approach allows the patients to incorporate to his work with a lower hospital stay less pain and less damage to other tissues; and the awake protocol minimize the accompanying risk of traqueal intubation, the potential effects of general anesthesics, the risk of needed a longer intubation.

Method: All patients from high risk thoracic surgery consult with a limit spirometry, hipoxemia and hypercapnia, oxygen dependent secondary to chronic respiratory disease not related to recent neoplasic. It includes 34 (100%) pleural biopsies of which 8 (23.5%) female, 26 (76.5%) male; lung biopsies were 6 (100%) of which 5 (83.3%) female male 1 (16.7%). Surgical approach include dexmedetomidine bolous 20 minutes prior to surgery, and continuous infusion oxygen delivery throw facial mask, transoperative psycotherapy and full cardiopulmonary monitoring, accompanying of hypnotic and ansyolitics in short bolus, intercostal block in 3 spaces and spinale erector patient partial lateral position, the unique porth was decided according to the target localization and the topographic relation at the CT. Looking for diminished damage to the oncologic tissues and preserved health surround structures and lung function. All patients tolerate the procedure, all with pleural dreinage, sufficient tissue to pathology and microbiology laboratory was achieved.

Results: All patients had a satisfactory histopathologic result including a relationship woman man for pleural pathologic disease 3:1, for lung disease 0.2. The pathologic diagnosis in pleural biopsies, 34 (100%), pleural fibrosis 6 (19.4%), paquipleuritis 17 ( 50%), mesothelial hyperplasia 2

(5.9%), mucinous adenocarcinoma 2 (5.9%), differentiated adenocarcinoma (20.6%) the pathologic diagnosis in lung biopsies 6 (100%), organized pneumonia 1 (16.7%), epidermoid cancer 2 (33.3%), lung abscess 1 (16.7%), adenocarcinoma 2 (33.3%) papilar 1 and mucinous 1. All of them had a short hospital stay average 2 days, no one needed mechanical ventilation, no transfusion, the average operating room time was 47 minutes, the average heart rate 84 beats per minute, oxygen saturation 87% and CO2 31.

Conclusion: The single porth approach with a localized target and the awake thoracic surgical procedure need a major surgical skills and expertise in thoracic anatomy, this approach is feasible and reproducible using specialized instruments, permit optimized surgical time room, avoid almost all the risk and adverse reaction of anesthesic in cancer patients, let the patient to start respiratory rehabilitation early, less damage, decrease the risk of needed an ICU entry, decrease damage to health tissue, permit a faster recovery, a faster inclusion in oncologic treatment and helps the patient to recover confidence to next steps in the oncologic process. A strict protocol in previously sick respiratory patients and a complete monitoring during surgery with psycologic support during the surgery and ansyolitic bolus permit a safe surgery with complete assessment.

Keyword: Awake surgery, Single porth, Thoracoscopic surgery, Lung cancer

P1.16-A


Surgical Therapy for Malignant Pleural Mesothelioma in Mexican Population

M.E. Marmolejo Torres1, R. Báez Saldaña1, J.A. Berrios Mejia2

1National Institute of Respiratory Disease, Mexico City/Mexico, 2Thoracic Surgery, ISSEMYM Medical Center Toluca, Metepec/Mexico

Background: Malignant pleural mesothelioma (MPM) remains an aggressive thoracic malignancy associated with poor prognosis. There is no standard treatment regimen, and particularly, the impact of radical surgery remains controversial. The main goal of our retrospective single-centre study was to evaluate the surgical treatment at our division regarding their effect on the patient’s survival.

Method: We retrospectively reviewed data from 23 consecutive patients with histologically proven MPM, treated from 2012 to 2015 in National Institute of Respiratory Disease. Mexico City. The program was used: SPSS 20 SPSS Inc, Chicago, IL. Statistical tests were considered significant for P values <0.05

Results: There were 9 women (39%) and 14 men (61%) with a mean age of 57.6 years. Epitheloid subtype was found in 23 patients (100%). Extended pleurectomy/decortication was performed in 9 (39%) and extrapleural pneumonectomy in 10 (43.4), in 4 (17.3) cases the procedure could not be completed. Clinical staging was: IIB in 6(26.1%) and III in 12 (52.2%). Frecuency of complications was 12 (52.2%). 30-day mortality rate was 4.34%. Mean survival time for the collective was 25.4 months. Median survival of patients undergoing surgical resection with complete trimodal therapy was significantly longer tan that of patients undergoing surgery only (36.1 versus 18.5 months; ; p < 0.05).

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Conclusion: Our data suggest that patients undergoing surgical resection with adjuvant therapy was longer survival. A large multicenter, randomized trial, testing P/D after induction chemotherapy versus chemotherapy alone in MPM patients with good prognostic factors, is needed.

Keywords: Malignant pleural mesothelioma, Extrapleural pneumonectomy, Extended pleurectomy/decortication, Thoracic surgery

P1.17


How to Visualize Exosomes in NSCLC: “The New Guest Star in the Liquid Biopsy Movie”

S. Taverna1, P. Reclusa2, P. Verstraelen3, D. De Miguel-Pérez4, M. Pucci5, I. Pintelon1, N. Claes6, M. Gunasekaran7, R. Alessandro1, S. Bals6, S. Kaushal7, C.D. Rolfo8

1Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council, Palermo/Italy, 2Center for Oncological Research (CORE), Antwerp University, Antwerp/Belgium, 3Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, Antwerp/Belgium, 4Marlene and Stewart Greenebaum Comprehensive Cancer Center, Experimental Therapeutics Research Program, University of Maryland School of Medicine, Baltimore/United States of America, 5Department of Biomedicine, Neuroscience and Advanced Diagnostics- Section of Biology and Genetics, University of Palermo, Palermo/Italy, 6Electron Microscopy for Materials Science (EMAT), University of Antwerp, Antwerp/Belgium, 7Division of Cardiac Surgery, University of Maryland School of Medicine, Baltimore/United States of America, 8University of Maryland School of Medicine, Baltimore, Mayland/United States of America

Background: Exosomes are nano-vesicles secreted to the body fluids that act as cell-to-cell communicators, transferring genetic information. Studies on exosomes as liquid biopsy biomarkers in several tumours, including lung cancer, have become a hot topic in recent years. The discoveries regarding their composition and functionality have made them a major field of interest in cancer research. EVs, through the integrins expressed in the parental cells, are able to be internalized in a tissue-specific manner, being partially responsible of the progression of the tumour and the pre-metastatic niche formation among others. However, this specificity might lead also to new opportunities in the treatment of the tumour by using extracellular vesicles as devices for drug delivery. In order to further explore this topic, protocols

and methods for exosome tracking are required. Our aim was to develop a reliable and standardized protocol for exosome isolation and visualization during internalization in non-small cell lung cancer (NSCLC) living cells.

Method: NSCLC cell cultured exosomes were isolated by three different methods, first consisting in single ultracentrifugation, second consisting in double ultracentrifugation, including exosome washing and the third using ExoEasy Maxi Kit based on membrane affinity spin columns. Exosomes were characterized with nanoparticle tracking analysis and scanning electron microscopy (SEM). Then, exosomes were stained with PKH67 and PKH26 dyes and observed in vivo by confocal microscopy.

Results: We observed that our double ultracentrifugation method resulted in the clear identification of exosomes in comparison with the single ultracentrifugation, that contained crystal precipitates that hinder exosome visualization. In contrast, exosomes isolated by ExoEasy could be clearly observed despite containing salt impurities. According to exosome staining, PKH67, compared to PKH26, provided a better visualization of lung cancer exosomes under confocal microscopy. In the in vivo experiment, we could observe how cells capture free exosomes by cytoskeleton filopodia elongation.

Conclusion: We showed, for the first time, the in vivo internalization of exosomes in NSCLC with our developed tracking protocol without ultracentrifugation, that can be very helpful for further studies to elucidate the mechanism of exosomes internalization by target cells in drug delivery studies.

Keywords: Exosomes, Liquid biopsy, NSCLC, Visualization

P1.18


Update of the Analysis of the Status of Lymphocyte Infiltration in Patients with NSCLC

E. Richardet, M. Paradelo, P. Hernandez, L. Acosta, M. Molina, G. Ferreira, M. RichardetOncology, INSTITUTO ONCOLOGICO DE CORDOBA, Cordoba/Argentina

Background: Current evidence highlights the potential role of tumor-infiltrating lymphocytes (TILS) as a prognostic factor in many types of tumors. The TILs (CD4 and CD8) are being studied with different methods such as immunohistochemistry and optical microscopy. The main objective of our work is to identify TILS in patients with NSCLC, classified as present or absent, and its relation to progression free survival (PFS).

Method: Retrospective and analytical study of Instituto Oncológico de Córdoba, from 2004 to 2019. 187 patients with stage IIIB and IV NSCLC were analyzed. TILS are descriptively classified as present or absent. Survival curve was calculated using the Kaplan-Meier method.

Results: 63% of patients had adenocarcinoma and 37% squamous cell carcinoma. 72% were men. 82% were smokers. 65% of patients with squamous histology and % 58 with adenocarcinoma, showed TILS. Patients with adenocarcinoma with TILS present had higher PFS 13.3 months, compared to patients with absent, 8.8 months. These differences were statistically significant (PFS: p=0.004). The patients with squamous cell carcinoma with TILS had 10.8 months PFS. Those who had infiltrated absent had a PFS of 5.6 months. These differences were also statistically significant (PFS: p = 0.001).

Conclusion: Our study shows that patients whose pathological samples presented inflammatory infiltrate had higher PFS. The presence of TILS could be used as an important prognostic factor in this patient population.

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P1.19


Molecular Characterization of Lung Cancer in Young Patients. A Single-center Study from Argentina

L. Dalurzo1, J.N. Minatta2, L.N. Ortega3, C.A. Franco Cortes1, H. Diaz De Arce3, F. Jauk3

1Pathology, Hospital Italiano de Buenos Aires, Buenos Aires/Argentina, 2Oncology, Hospital Italiano de Buenos Aires, Buenos Aires/Argentina, 3Sequencing Laboratory, Hospital Italiano de Buenos Aires, Buenos Aires/Argentina

Background: Lung cancer is infrequent in patients younger than 50 years. Several molecular alterations with clinical value have been described among these patients. Next-generation sequencing (NGS) is a robust diagnostic tool to assess this kind of genomic alterations, evaluating multiple mutations and fusions in the same assay, and reducing turnaround time compared to sequential single-gene testing. There is little data available about NGS molecular testing in lung cancer young patients in Latin America.

Method: A retrospective cohort study was conducted. Cases of patients younger than 50 years, with diagnosis of lung carcinoma in Hospital Italiano of Buenos Aires between 2014 and 2019 were included. Clinical data was collected from electronic clinical records.

DNA and RNA were extracted from formalin-fixed paraffin-embedded tissue. Mutations and fusions were assessed using Oncomine Focus Assay (Thermo Fisher) DNA and RNA panel in Ion PGM (Ion Torrent) sequencer.

Confidence Interval was calculated according to Wilson score interval method.

Results: A total of 13 patients were analyzed. 7 patients were female, 11 were non-smoker, and 8 were diagnosed at stage IV. Median age was 44 (range 26-49). According to WHO 2015 histological and immunohistochemical criteria,12 cases were adenocarcinomas, whereas only 1 case was diagnosed as large-cell carcinoma. Regarding gene mutations or fusions, 2 cases were negative for those detected by the NGS panel. 7 cases showed 1, 3 cases showed 2, and 1 cases showed 4 genomic alterations. The most prevalent mutated gene was EGFR (3 cases), followed by: PIK3CA and KRAS (2 cases each), JAK3, MTOR, AKT1, MET, ERBB2 (1 case each). Among fusions, 4 cases showed ALK and 1 case showed ROS1 fusions. 8 patients (61,54% ; CI 95%: 35,52-82,29%) had targetable genomic alterations (according to drugs approved in Argentina), 4 of them (30,7% ; IC 95% 12,68-57,63%) corresponded to ALK fusions.

Conclusion: In this patient cohort, we found that Oncomine Focus Assay NGS panel is a powerful tool, useful to detect clinically relevant genomic alterations, such as DNA mutations and gene fusions, taking less time than consecutive single-gene testing. Even though ours is not a large cohort study, the prevalence of targetable mutations is higher than the one present in cohorts including older lung cancer patients. Interestingly, the prevalence of ALK fusions is notably high. We conclude that performing NGS testing for clinically relevant genomic alterations in this age group is rewarding, as patients could benefit from targeted therapy.

Keywords: Mutations, Fusions, Young, NSCLC

P1.20


S-allyl Cysteine Induces Cytotoxic Effects on Human NSCLC Cell Lines

M. Orozco-Morales1, N. Hernandez-Pedro1, P. Barrios-Bernal1, O. Arrieta2, L.M. Ruiz-Godoy3, A. Santamaría4, A.L. Colín-González3

1Personalized Medicine Laboratory, Instituto Nacional de Cancerología, Mexico city/Mexico, 2Thoracic Oncology Unit, Instituto Nacional de Cancerología, Mexico City/Mexico, 3Biobank, Instituto Nacional de Cancerología, Mexico City/Mexico, 4Laboratory Of Excitatory Amino Acid, Instituto Nacional de Neurología y Neurocirugía, Mexico City/Mexico

Background: Garlic and its sulfured compounds have been shown to modify the tumor microenvironment. Specifically, S-allyl cystein (SAC), a hydrosoluble garlic-derived compound, suppresses tumor proliferation while induces apoptosis in a wide number of cancer types. However, its antiproliferative properties and potential mechanisms of action have been poorly explored in lung cancer.

Method: In this study we investigated the possible cytotoxic role elicited by the garlic-derived compound and well-known antioxidant molecule S-allyl cysteine, on different endpoints of toxicity in three different human cancer cell lines, A-549, HCC827, H1975, in order to provide enlightening and supporting information about the antitumor properties on this molecule. For this purpose, cell lines were cultured for 24, 48 and 72 hours in the presence of increasing concentrations of SAC.

Results: The incubation with SAC resulted in a dose- and time-dependent decrease in cell viability and augmented morphological changes in all cell lines. In addition, SAC increased the frequency of apoptotic/necrotic events and enhanced the oxidative damage to lipids.

Conclusion: These results demonstrate the cytotoxic properties inherent to SAC to reduce malignant growing and proliferation of lung tumor cells.

Keywords: Lung cancer cell lines, Cytotoxicity, Garlic-derived compound, S-allyl cysteine

P1.21

Topic: Bronchoscopy

Cryotherapy in the Treatment of Endobronchial Carcinoid, Is It a Valid Alternative Treatment to Surgery?

N. Asadi1, P. Perikleous2, J. Finch2, E. Beddow2, V. Anikin2

1Thoracic Surgery, Harefield Hospital, London/United Kingdom, 2Thoracic Surgery, Harefield Hospital, Uxbridge/United Kingdom

Background: Each year in the UK around 2,900 patients are diagnosed with carcinoid, a rare, slow-growing tumour that originates in neuroendocrine cells, most commonly present in the gastrointestinal (60%) and respiratory (25-33%) tracts. Histopathologic diagnosis and classification require tissue biopsy whilst management depends on tumour’s anatomic site and size, extent, secretory profile, and general status of patient. Surgical resection remains the primary approach for most localized carcinoids; cryoextraction/cryoablation may be considered when surgery is not feasible or in preparation for surgery. We present a single centre experience in use of cryotherapy for management of carcinoid tumours.

Method: For this retrospective analysis, data were collected from prospectively populated patient databases, operative logbooks, and patients’ medical records. Between 2011-2019, a total of 26 patients diagnosed with carcinoid underwent a series of cryotherapy procedures, either alone or in combination with surgery, in our institution. Before deciding on their management strategy, patients had been appropriately discussed in our lung

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MDT meeting; they were considered for first line cryotherapy when surgical resection was deemed not possible or when they had rejected offered surgery.

Results: Cryotherapy alone resulted to compete tumour removal in 12 (46.15%) patients, as evidenced by follow-up bronchoscopies and/or histopathologic confirmation. Of those, 6 (23.07%) were unfit for surgery, 2 (7.69%) declined surgery, 2 (7.69%) did not require surgery and 2 (7.69%) underwent surgery with no residual tumour found. Successful size reduction allowed 6 (23.07%) patients to avoid pneumonectomy and 5 (19.23%) to avoid bilobectomy. 1 (3.84%) patient was diagnosed with distal disease recurrence on follow-up and was treated with radiofrequency ablation.

Conclusion: Cryotherapy can result to definitive management in unfit patients or be part of a cytoreductive strategy in preparation for surgery, aiming to reduce the size of tumour or help identify its limits, in order to avoid extensive resection and unnecessary loss in lung function.

Keywords: Carcinoid, Neuroendocrine tumours, Endobronchial tumours, Cryotherapy

P1.22

Topic: Bronchoscopy

Endobronchial Ultrasound and Transbronchial Needle Aspiration EBUS-TBNA: In a University Hospital in Latin America

L. Fernandez-Trujillo1, E.I. Morales2, A. Castro3, L. Sua4

1Department Of Internal Medicine, Pulmonology Service, Interventional Pulmonology, Fundacion Valle del Lili, Cali/Colombia, 2Department Of Internal Medicine, Pulmonology Service, Fundacion Valle del Lili, Cali/Colombia, 3Clinical Research Center, Fundacion Valle del Lili, Cali/Colombia, 4Department Of Pathology And Laboratory Medicine, Fundacion Valle del Lili, Cali/Colombia

Background: Endobronchial Ultrasound and Transbronchial Needle Aspiration (EBUS-TBNA) nowadays it has a primordial role in the workup of malignant and nonmalignant pulmonary disease. It’s the most important advancement in pulmonary medicine in the last 20 years.EBUS-TBNA is a minimally invasive technique, well tolerated, cost efficient, for real time visualization of the airways with ultrasound and for sampling the mediastinum and hilum. Its indications: diagnosis, staging, restaging of lung cancer, evaluation of metastatic lesions and non-malignant diseases. It requires multidisciplinary evaluation with image analysis, general condition of the patient, risks and benefits, also close work with pathology, performing a Rapid On-Site Evaluation (ROSE) to improve the diagnostic performance. We describe the EBUS-TBNA in Fundación Valle del Lili a University Hospital of Reference in Latin America.

Method: Prospective, descriptive study, period June/2015-June/2018. The indications were staging and restaging of lung tumors, diagnosis of lung or mediastinal masses, abnormal ganglia in CT or PET/CT equal or greater than 1cm. 108 patients were evaluated under general IV anesthesia, with a standardized protocol in the endoscopy room. The equipment used was Olympus® bronchoscope + US probe + 22G FNA.

Results: Average age of 63,5 +/- 12,9, women 53(49%), men 55(50,9%)

The quality of the sample was adequate in 105 (97,22%), positive of malignity 63(60%) negative 42(40%), inadequate samples 2(1,8%) and in one case a complete evaluation of the mediastinum was made without evidence of lesions, so no samples were taken. The ganglionary stations most frequently evaluated were 7 40(37%), 11R 22(20,3%), 11L 14(12,9%) and mediastinal mases 11(10,1%). The malignant lesions were non-small cell pulmonary carcinoma (NSCLC) 26(41,2%), metastasis head and neck tumors 10(15,8%), small cell pulmonary carcinoma 9(14,28%). 97,22% of

the smears with Diff-Quick staining presented lesion, 5 dips were performed in each station, and immunohistochemistry was made in cellblocks as well as DNA extraction for EGFR mutation studies and EML4/ALK gene rearrangements in 50% of cases of NSCLC and PDL1 in 19,2% of these cases. 10(9,26%) of the series was taken to mediastinoscopy with a 100% correlation with the results of EBUS-TBNA.

Conclusion: EBUS-TBNA is the recommended technique for lung cancer mediastinal staging. Our results adjust to international results; it is safe, minimally invasive, in many cases an outpatient procedure and a good performance when accompanied with ROSE.

Keywords: Endobronchial ultrasound and transbronchial needle aspiration (EBUS-TBNA) , Rapid on-site evaluation (ROSE)

P1.23

Topic: Bronchoscopy

EBUS and Needle Aspiration in Diagnosis and Molecular Classification of Breast Cancer Progression Metastatic to Mediastinum

L. Fernandez-Trujillo1, Y. Cañas2, E. Legarda2, L. Sua3

1Department Of Internal Medicine, Pulmonology Service, Interventional Pulmonology, Fundacion Valle del Lili, Cali/Colombia, 2Faculty Of Health Sciences, Universidad Icesi, Cali/Colombia, 3Department Of Pathology And Laboratory Medicine, Fundacion Valle del Lili Hospital Universitario, Cali/Colombia

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) plays an important role in the evaluation of extrathoracic malignancy that compromises the mediastinum, modifies the prognosis and the sequence of treatments according to the results. In breast cancer there is metastasis to mediastinal lymph nodes during the progression of the disease, 30% of patients with limited disease receiving treatment recur with bone, lung, liver and lymphatic metastases. Breast cancer experiences alterations in the expression of estrogen hormone receptors (ER), progesterone receptors (PR) and in the amplification of human epidermal growth factor receptor 2 (HER2) during progression, by different adjuvant therapies, significantly affecting survival. Therefore, molecular re-characterization of tissue in relapses is vital for better therapeutic decisions and impact on survival. EBUS-TBNA is the procedure of choice in staging, re-staging and diagnosis of lung cancer; we present its usefulness in the diagnosis and molecular classification of breast cancer progression.

Method: Between January 2015 and June 2019, EBUS-TBNA was performed with rapid on-site evaluation (ROSE) in 12 patients with breast cancer and suspected progression. Procedures were ambulatory, under general anesthesia through laryngeal mask. 21G needle puncture was performed, cytology was elaborated in liquid base, material was obtained for cellblock, immunohistochemistry, digital analysis and fluorescent in situ hybridization (FISH) were performed.

Results: Average age 56.75 (SD: 10.6). Mediastinal stations studied: 7 subcarinal (8), E11L (2) E11R (2), malignancy was confirmed in the first pass in all cases with ROSE with Diff-Quik staining, material was collected for the rest of the studies. We performed: Papanicolau (PAP), cellblock with Hematoxylin & Eosin (H & E), immunohistochemistry with GATA-3 (L50-823), TTF-1 (SP-141), CK-19 (A53-B / A2.26 ) to confirm mammary origin and ER (SP-1), PR (1E2), HER2 (4B5), Ki-67 (30-9) biomarkers with software approved by FDA (Virtuoso), which characterizes the molecular subtype of breast cancer. One case required FISH to evaluate HER2 oncogene. No patient required additional procedures such as mediastinoscopy to confirm the progression of their disease.

Conclusion: EBUS-TBNA is a minimally invasive, ambulatory, efficient and very useful procedure in the study of mediastinal, paratracheal or peribronchial lesions with suspicion of breast

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cancer progression. To be successful, must be well planned, with standardized and sequential analysis of the mediastinum. The feedback in the room with ROSE helps to optimize time, number of passes and stations studied avoiding second procedures.

Keywords: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), Breast cancer, Rapid on-site evaluation (ROSE)

P1.24

Topic: Bronchoscopy

Endobronchial Ultrasound plus Fine Needle Aspiration (EBUS-TBNA) in Lesions Simulating Pulmonary Neoplasm: Pulmonary Myospherulosis

L. Fernandez-Trujillo1, S. Sanchez1, E.I. Morales2, L. Sua3, M. Velasquez4

1Faculty Of Health Sciences, Universidad Icesi, Cali/Colombia, 2Department Of Internal Medicine, Pulmonology Service, Fundacion Valle del Lili, Cali/Colombia, 3Department Of Pathology And Laboratory Medicine, Fundacion Valle del Lili, Cali/Colombia, 4Department Of Surgery, Thoracic Surgery Service, Fundacion Valle del Lili, Cali/Colombia

Background: Myospherulosis, described in 1969 in African patients who, after receiving muscular injections of penicillin, developed inflammation at site with formation of cysts with intense infiltration of lymphocytes, histiocytes, plasma cells, giant cells, as foreign body reaction. Exogenous lipids react with patient’s erythrocytes; these are injured and perceived as foreign body by defense mechanisms, triggering severe inflammatory response. Degenerated erythrocytes are surrounded by a thin membrane, called “bag of marbles”, often confused with fungal infections or neoplastic lesions. This type of injury has not been described in lung. We present a case of pulmonary myospherulosis appearing after several thoracic surgical interventions and diagnosed with EBUS-TBNA.

Method: Case report. Review of the clinical history.

Results: Male, 63 years old, with dyslipidemia, consulted for 15 days of oppressive, severe thoracic pain with physical activity, irradiated to neck and upper limbs, which relieved at rest. Stress testing (+) with pain of maximum intensity. Referred to the emergency department, severe coronary disease was documented, arterial trunk and three vessels, percutaneous right coronary angioplasty was performed with good evolution and myocardial revascularization was planned. Pre-surgical evaluation revealed lung mass in lower left lobe (LLL), myocardial revascularization was first performed, the same day resection of LLL and lymph node dissection, histopathological diagnosis: pulmonary adenocarcinoma T2AN2M0 / EIIIA. Received adjuvant chemotherapy / radiotherapy with good response. PET-SCAN / follow-up: Metabolically active posterior / basal left lesion, postsurgical/postradiotherapy expected changes. Lesion and lymph nodes studied with EBUS-TBNA, negative histopathological result for malignancy and expression profile compatible with myospherulosis.

Conclusion: Spherulosis is a rare entity, described around soft tissue, muscle, gynecological or otorhinolaryngological tumors, but not described in lung. In addition, the use of EBUS-TBNA is not described in the diagnostic approach, situation for which we describe this case.

Keyword: Endobronchial ultrasound plus fine needle aspiration (EBUS-TBNA)

P1.25

Topic: Bronchoscopy

Rare Intimal Aortic Angiosarcoma Diagnosed via Endobronchial Ultrasound guided Transbronchial Fine Needle Aspiration (EBUS-TBNA): A Case Report

L. Fernandez-Trujillo1, D.C. Buenaventura2, E.I. Morales3, J.E. Garcia1, L. Sua1

1Faculty Of Health Sciences, Universidad Icesi, Cali/Colombia, 2Department Of Internal Medicine, Fundacion Valle del Lili Hospital Universitario, Cali/Colombia, 3Department Of Internal Medicine, Pulmonology Service, Fundacion Valle del Lili, Cali/Colombia

Background: Intimal sarcomas are very uncommon malignant tumors that develop in the main blood vessel, particularly in the pulmonary arteries and the aorta. In general, they denote a poor prognosis for the patient. The diagnosis is always challenging because of the anatomical difficulties to obtain a sample and because of the multiple possible differential diagnostics that can confuse and delay its identification. We present the case of a patient with an intimal angiosarcoma of the thoracic aorta diagnosed by an endobronchial ultrasound guided needle aspiration (EBUS-TBNA), a method that has not been reported in scientific literature before.

Method: Review of clinical history

Results: A 73-year-old man, with a previous history of smoking and chronic obstructive pulmonary disease, presented with abdominal discomfort, weight loss and dysphagia.

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He had a normal abdominal ultrasound, colonoscopy and upper gastrointestinal endoscopy. An abdominal CT-scan was performed, reporting a mass intimately related to the esophagus with irregular extrinsic compression of this structure, heterogeneous enhancement and aortic infiltration. Chest CT showed a mass in the posterior mediastinum, with homogeneous density, expanding from T5 to T8, 78x53x76 mm in size, con extrinsic compression of the left main bronchus, anterior displacement of the esophagus without cleavage plane, surrounding and infiltrating the aorta, with an intra-luminal thrombus occupying 50% of the aortic lumen. PET-CT revealed a hypermetabolic aortic and mediastinal lesion with metastasis to the suprarenal glands. An EBUS-TBNA was performed, real time samples were collected and submitted to ROSE (Rapid on Site Examination). Five samples were sent for liquid-based cytology and cell-block examination. The definitive diagnosis of the cell block reported a malignant neoplasm composed of pleomorphic large cells, abundant eosinophilic cytoplasm, anisokaryosis, dense chromatin, evident nucleolus and atypical mitosis (22 mitosis per high-power-field). The neoplasm was organized in a cohesive manner, with interposed mononuclear inflammatory cells and vast areas of tumor necrosis. Immunohistochemical analysis evidenced positive BCL-2, SMA and calponin. With Diff-Quick stain malignancy was confirmed in real time. It was classified as a high-grade mesenchymal sarcoma of the intima. Due to the extension of the lesion surgical management was not indicated. Chemotherapy with doxorubicin, ifosfamide and mesna was initiated with poor response and a bad tolerance to the treatment.

Conclusion: This is the first reported case of an intimal aortic sarcoma diagnosed with an EBUS-TBNA. It was the only suitable option to approach and obtain samples of the lesion, in this case with excellent diagnostic performance.

Keywords: Endobronchial ultrasound guided transbronchial fine needle aspiration, Angiosarcoma, Rapid on-site examination (ROSE)

P1.26

Topic: Nursing & Allied Health

Pharmaceutical Follow-up Program for Patients with Oral Drug Treatment in Non-small Cell Lung Cancer in a Heterogeneous Health Care System

G. Moreira, C.G. Ferreira, T. Montella, J. Vasconcellos, I. GoncalvesGrupo Oncoclinicas, Rio de Janeiro/Brazil

Background: Lung cancer has faced important changes in its history. With the improvement of main genetic mutations, the target-therapy have revolutionized that kind of tumour, made possible oral drugs administration procedures at anti-lung cancer treatment. In 2014, the National agency of health assistance in Brazil approved the compulsory coverage of oral drug. However, the delivered of these drugs are heterogeneus: at patient’s residence or by the patient’s health establishment. The purpose of this paper is to describe the follow-up lung cancer patient service model while making use of oral drugs in the household environment in a fragmented and heterogeneous health system.

Method: This article presents a multidisciplinary team’s expertise acting in an oral chemotherapy program, managed by pharmacists between April of 2016 and May of 2019. All patients had driver mutations at non-small lung cancer cells, were being treated at a private medical clinic and received oral drug through the health assistance.

Results: We developed a service program named the Oral Drug Project (Figure 1) in order to contribute to the better management of interdisciplinary team while handling the above mentioned patients. A total number of 79 persons where identified. 16% received the oral drug through the pharmacist at a health care facility (Group A) and 84% at home (Group B). Drug-food interactions: (Group A) 46% (Group B) 52%; Drud-drug interaction: (Group A) 67% (Group B) 61%; Suspend treatment due to non-manageable toxicity: (Group A) 1% (Group

B) 1%; Presented 1st or 2nd degree of toxicity and prematurely managed: (Group A) 51% (Group B) 58%. No hospitalizations due to drug poisoning were registered. All toxicities were identified and there were no patient abandonment during treatment.

Conclusion: The Oral Drug Program is a key factor of our patients’ follow-up, and it is possible to equalize the management of care in a fragmented and heterogeneous health system. Despite the greater percentage of patients receiving oral chemotherapy by correspondence at home, the elaboration of individual strategies of care plan allowed that all in oral drug use were followed. The involvement of the multidisciplinary team with the patient and caregiver are fundamental for better therapeutic control, better patient adherence and caregiving management, early problem identification related to the drug use, reduction of hospitalization costs and collateral effects.

Keywords: Oral drug, Target therapy, Clinical pharmacist

P1.27

Topic: Nursing & Allied Health

Longitudinal Changes on Patient Reported Outcomes and Distress among Cancer Survivors Living in Regional and Rural Australia

M. LashbrookClinical Trials Unit, Riverina Cancer Care Centre, Wagga Wagga/Australia

Background: This study investigates longitudinal patterns of physical functioning and psychological morbidity in cancer survivors residing in regional and rural communities in New South Wales, Australia.

Method: 119 patients who completed primary treatment for breast, colorectal, lung or prostate cancers self-completed the Distress Thermometer and the PROMIS-29 questionnaires at the end of treatment (T0), at three (T1) and six months (T2). Outcomes were modelled using generalized estimating equations. Associations between risk factors and physical functioning or psychological morbidity at T2 were assessed using multivariable logistic regression.

Results: Distress varied over time (p<0.001). Physical function (92%), sleep disturbance (70%), pain interference (60%) and satisfaction with role (54%) were the most commonly reported issues at T2. Approximately two fifths of survivors reported higher symptom severity for anxiety (41%), fatigue (44%) and depression (45%). At T2, depression was found to be associated with disadvantaged socio-economic index and living in regional/remote areas. Anxiety was associated with cancer type (colorectal) and advanced stage of cancer. Fatigue was associated with gender (male) and cancer type (colorectal and breast). While sleep disturbance was associated with treatment type (surgery).

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Conclusion: Persistent physical problems, in particular pain and sleep disturbance were important on-going issues to survivors. Continued monitoring of cancer survivors after cancer treatment is viewed as an essential aspect of strategic care planning. Health professionals may initiate earlier referrals and incorporate increased symptom management into clinical care to improve the wellbeing of survivors.

Keyword: Cancer, Survivorship, Breast, Colorectal, Lung, Morbidity

Poster Session 2

Saturday, October 19, 2019P2.01

Topic: Early Stage NSCLC (Stage I - III)

Prognosis of Patients with Stage I Non-Small Cell Lung Cancer

C.J. Flores1, L. Chirinos1, D. Enriquez1, L.J. Schwarz1, L. Mas2, V. Rojas3, A. Aguilar1

1Scientific & Academic Direction, Oncosalud - AUNA, Lima/Peru, 2Department Of Medical Oncology, Oncosalud - AUNA, Lima/Peru, 3Department Of Oncological Surgery, Oncosalud - AUNA, Lima/Peru

Background: The prognosis of non-small cell lung cancer (NSCLC) largely depends on tumor stage, however despite early-stage presentation and is described as a constant relapsing risk after definitive R0 resection, when only about 60% of cases can be cured with surgery alone. Prognostic factors are still needed to stratify patients by relapsing risk to design more effective strategies including adjuvant chemotherapy. Our aim was to evaluate potential prognostic factors for patients with I clinical stage I in a private cancer center. (Oncosalud – AUNA).

Method: We analyzed data of 28 cases with stage I NSCLC, treated at Oncosalud - AUNA from 2008 to 2014 (Lima – Peru). The clinical-pathological data were collected from digital medical records. Disease-free survival (DFS) and overall survival (OS) was determinate using Kaplan-Meier method and survival curves comparison were performed using log-rank or Breslow test. Cox model was used for multivariate analysis.

Results: The median age was 67 years (range 34-79), 75% were older than 60 and 57% of patients were women. Of all patients, 54% had an ECOG 0 scale and more than 70% were asymptomatic and were diagnosed incidentally. Extension of disease was T2 in 40% and the rest was T1. The most common histological type was adenocarcinoma (75%) and mainly moderately and well differentiated (78%). CYFRA 21.1 and CEA were elevated in 17% and 10% of cases, respectively. All patients had surgery with free surgical margins, negative lymph nodes, lymphovascular and perineural infiltration in 28 and 8%, respectively, and 25% had locally involved visceral pleura and 40% received adjuvant treatment with platinum-based chemotherapy. During the study period, 36% relapsed and 18% died, all relapses received platin-based chemotherapy. The median follow-up was 5 years (95%CI: 4.3-5.5), median survival was not reached, and 3-years and 5-years OS rates were 93 and 58%, respectively. The DFS rate at 3 and 5 years were 40% and 30%, respectively. From all clinical and pathological characteristics evaluated only the number of nodal resection (<6 or ≥6 nodes) was significantly associated with poor DFS with HR 7.5 (p=0.027). Other characteristics, as T stage, visceral pleura, vascular and perineural infiltration shown a slight trend to poor DFS but not statistically significant.

Conclusion: In our study, the main factor related to poor DFS was the resection of fewer than 6 nodes. Larger prospective studies are needed to evaluate the role of the number of nodes resected in stage I NSCLC as well as other pathological features.

P2.02


Second-line Afatinib vs Erlotinib for Advanced Lung Squamous Cell Carcinoma: Final Analysis of the Phase 3 LUX-Lung 8 Trial

G.D. Goss1, M. Cobo2, S. Lu3, K. Syrigos4, K.H. Lee5, E. Göker6, V. Georgoulias7, W. Li8, D. Isla9, A. Morabito10, Y.J. Min11, A. Ardizzoni12, H. Jian3, Y. Yu3, S. Bender13, A. Cseh14, E. Felip15

1University of Ottawa, Ottawa/Canada, 2Hospital Carlos Haya, Malaga/Spain, 3Shanghai Chest Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai/China, 4Athens School of Medicine, Athens/Greece, 5Chungbuk National University College of Medicine, Cheongju/Korea, Republic of, 6Ege University Faculty of Medicine, Izmir/Turkey, 7University Hospital of Heraklion, Heraklion/Greece, 8First Hospital of Jilin University, Changchun/China, 9Hospital Lozano Blesa, Zaragoza/Spain, 10Istituto Nazionale Tumori – IRCCS “Fondazione G. Pascale”, Naples/Italy, 11Ulsan University Hospital, Ulsan/Korea, Republic of, 12Policlinico S. Orsola, Bologna/Italy, 13Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield/United States of America, 14Boehringer Ingelheim RCV GmbG & Co. KG, Vienna/Austria, 15Vall d’Hebron University Hospital, Barcelona/Spain

Background: Afatinib is approved for treatment of pts with metastatic squamous NSCLC progressing after platinum-based chemotherapy, having demonstrated significantly improved progression-free survival (PFS) and overall survival (OS) vs erlotinib in the LUX-Lung 8 (LL8) trial (median PFS: 2.6 vs 1.9 months, HR [95% CI]: 0.81 [0.69–0.96]; OS: 7.9 vs 6.8 months, 0.81 [0.69–0.95]). In afatinib-treated pts, PFS and OS were longer in pts with ErbB mutation-positive vs wild-type tumors. Here we report the final analysis of OS, safety, and long-term benefit data from LL8.

Method: Pts with stage IIIB/IV lung SCC who had progressed on ≥4 cycles of platinum-based chemotherapy were randomized 1:1 to afatinib (40 mg/day) or erlotinib (150 mg/day) until disease progression. The primary endpoint was PFS and OS was a key secondary endpoint (other endpoints included ORR, DCR and safety). Mutational status was assessed in pts with long-term benefit (≥12 months on treatment).

Results: At data cut-off (Mar 2018), 795 pts were included (afatinib: 398; erlotinib: 397); baseline characteristics were similar between treatment arms. In treated pts (n=392; n=395), OS was significantly longer with afatinib vs erlotinib (7.8 vs 6.8 months; HR 0.84, 95% CI 0.73–0.97; p=0.02). Overall AE profiles were similar for afatinib and erlotinib (G≥3 AEs; n [%]: n=224 [57] and n=227 [57]; serious AEs: n=173 [44] and n=174 [44]; AEs leading to treatment discontinuation: n=79 [20] and n=67 [17], respectively). Drug-related (DR) G≥3 diarrhea and stomatitis (GT; grouped term) were more common with afatinib vs erlotinib (n=41 [10] vs n=10 [3], and n=16 [4] vs n=0 [0]). DR G≥3 rash/acne (GT) was more common with erlotinib vs afatinib (n=41 [10] vs n=23 [6]). Long-term benefit was observed in 21 afatinib-treated pts (median [range] OS: 27.5 [16.2–53.6] months), and 13 erlotinib-treated pts (median [range] OS: 20.1 [15.2–34.1] months). In the afatinib arm, ErbB family mutations were more common in pts with long-term benefit than in the overall population (5 of 10 [50%] vs 25 of 132 [19%]).

Conclusion: Consistent with previous analyses of LL8, OS was significantly improved with second-line afatinib vs erlotinib and AEs were similar across treatment arms. A higher proportion of pts had long-term benefit with afatinib vs erlotinib; in the afatinib arm, ErbB mutations were more common among long-term benefiters than in the overall population. These data position afatinib as a second-line treatment option for lung SCC, particularly in ErbB-mutated disease.

Keyword: Lung SCC, Afatinib, Erlotinib, Second-line

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P2.03


Normalization of Carcinoembryonic Antigen Levels Are Associated with a Survival Improvement in Advanced Non-small Cell Lung Cancer Patients

R. Sánchez Reyes1, F. Barrón1, L. Cabrera1, M.P. Peralta Álvarez1, L. Zatarain Barron1, A. Pereira-García1, E. Varela Santoyo2, L. Corrales-Rodriguez1, C. Martín3, A.F. Cardona4, O. Arrieta1

1Thoracic Oncology Unit, National Institute of Cancer, México City/Mexico, 2Clinic Foundation, Medica Sur, Mexico City/Mexico, 3Medical Oncology Department, Insituto Alexander Fleming, CABA/Argentina, 4Clinical And Translational Oncology Group,, Clinica del Country, Bogotá/Colombia

Background: Serum carcinoembryonic antigen (CEA) levels are elevated in approximately 65% of the Non-small cell lung cancer (NSCLC) patients with adenocarcinoma histology. Although the relation between CEA serum levels and overall survival (OS) in early and advanced NSCLC stages is not completely understood. Previous reports from our group suggest that the decrease or increase in CEA serum levels is strongly associated with treatment response to platinum-based chemotherapy. However, determination of serum CEA is not included in standard guidelines, such as the National Comprehensive Cancer Network (NCNN). The aim of this study was to analyze the progression-free survival (PFS) and overall survival (OS) in NSCLC patients with elevated CEA levels at diagnosis and to determine its possible association with systemic treatment response.

Method: We performed a retrospective analysis of patients with advanced NSCLC with an elevated serum level baseline of CEA (>20 pg/ml) that received treatment according to international guidelines. The serum CEA levels were measured every two cycles of platinum-based chemotherapy or a tyrosine kinase inhibitor (TKI) treatment. The change in serum CEA levels in response to treatment, OS and PFS were evaluated.

Results: Between March 2004 and February 2018, 748 patients with a diagnosis of advanced NSCLC and CEA levels >20 ng/mL were included in the analysis. The median age was 60.2 years old, 631 patients (84.4%) had adenocarcinoma histology. From 338 patients evaluated for EGFR mutations, 139 (31.3%) harboured an EGFR mutation. The median OS was 23.3 months (95% CI 19.4-26.9) in patients who completely normalized CEA vs 10.0 months (95% CI 8.9-11.2) in patients who did not achieve CEA normalization, with an HR 0.48 95% CI (0.35 -0.67) p <0.0001. The median OS was 15.5 months (95% CI 13.4-17.6) in patients who showed a decrease in CEA levels vs 8.8 months (95% CI 7.5-10.1) in those who did not. Reduction in CEA levels was associated with better OS, either in patients treated with TKI or platinum-based chemotherapy.

Conclusion: Although previous studies have suggested a possible relation between CEA levels and clinical outcome, its utility in the clinic has been controversial. In this study, we demonstrate normalization of serum CEA levels is related to longer OS rates and could be useful as an indirect biomarker for treatment response evaluation. Hence, we suggest its determination for the standard follow-up of advanced NSCLC patients under TKI or platinum-based chemotherapy treatment.

P2.04


NGS-Molecular Characterization of Lung Adenocarcinomas from Hispanic Patients: Level of Evidence for Therapeutic Actionability

O. Arrieta1, R. Gerson2, C. Blanco2, J. Alexander Meza3, A. Silva4, S. Rivera Rivera4, C. Zuloaga5, M. Lazaro6, E. Kazakova7, A. Villa8

1Thoracic Oncology Unit, Instituto Nacional de Cancerología, México City/Mexico, 2ABC Medical Center, Mexico City/Mexico,

3Unidad de Cancerología, Guadalajara/Mexico, 4Instituto Mexicano del Seguro Social (IMSS), Mexico City/Mexico, 5ANKER Oncología Global, Mexico City/Mexico, 6Hospital General de México “Dr. Eduardo Liceaga”, Mexico City/Mexico, 7Medical Manager, Roche, Mexico City/Mexico, 8Universidad Nacional Autónoma de México, Mexico City/Mexico

Background: Several studies have shown that NSCLC genomic background among Hispanics differs from other populations, therefore genotyping tumors in order to assess their molecular profile is adamantly needed in the current era of targeted therapy. Panel-detected oncodriver mutations can drive therapeutic approaches, and can help classify the information in order to propose strong evidence-based interventions in treatment guidelines. In this study we sought to understand the landscape of genomic drivers in a cohort of patients with lung adenocarcinoma of Hispanic ancestry.

Method: Tumor samples were collected from 48 patients with lung adenocarcinoma from march 2017 until march 2019. Samples were submitted for testing to Foundation Medicine and hybrid capture NGS was performed.

Results: A total of 282 samples were sent for evaluation, among which 48 (17%) with lung adenocarcinoma were tested by FoundationOne (FO) in tumor tissue. Among the patients included, 54.2% were men and 79.2% were >50 years of age. Most patients had a previous negative report for EGFR and ALK (in tumor tissue). Results for tumor mutation burden (TMB) were obtained from 48 (100%) samples. Median TMB was 4 mutations/Megabase (m/Mb). High TMB (>10 m/Mb) was identified in 9 (18.8%) samples. The most frequently detected alterations were in P53, KRAS and EGFR genes (Figure1). In terms of the level of evidence for therapeutic actionability, level-1 was 33.5 %, level-2 was 12.5%, level-3 14.6% and level-4 37.5%. (Figure 2).

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Conclusion: Despite an initial assessment of actionable alterations (EGFR and ALK), through a NGS-approach we were able to detect a high amount of genomic alterations linked to a high-level of evidence for therapeutic actionability (33.5%), possibly due to higher sensitivity and a higher number of genes tested in the panel, increasing therapeutic options in this molecular-driven era. This research work was conducted with the support of Roche Foundation Medicine.

Keywords: Foundation one, Adenocarcinoma, NGS

P2.05


Real World Data on Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Use in Advanced Non-small Cell Lung Cancer from a Latin American Cohort

M. Galvez-Nino, R. Ruiz, K. Roque, J. Moreno, N. Valdivieso, M. Olivera, Y. Miranda, G. Maquera, O. Cabero, M. Guillen, V. Rojas, E. Amorin, L. MasInstituto Nacional de Enfermedades Neoplasicas, Lima/Peru

Background: Targeted therapy achieves remarkable responses and prolonged survival in patients with non-small cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitors are the standard of care for EGFR mutated NSCLC, however, the difference between patients of daily clinical practice and clinical trials, and the lack of access in low and middle-income countries has limited our knowledge on the real benefit of these therapies. This study aimed to examine effectiveness and outcomes of patients with EGFR mutated NSCLC treated in a real-world Latin American setting.

Method: Retrospective analysis of EGFR mutated advanced NSCLC cases diagnosed at Instituto Nacional de Enfermedades Neoplasicas (INEN), Lima-Peru and treated with Erlotinib from 2015 to 2018. Epidemiologic and clinic-pathological data were collected from clinical files. Survival analysis was calculated with Kaplan-Meier method.

Results: During the study period, we analyzed the EGFR mutational status of 223 cases using tissue PCR or liquid biopsy in cases of insufficient material. An EGFR mutation was found in 38.6% patients (n=86). Among these, the distribution of mutations was as follows: 63%, exon 19 deletion; 25%, L858R mutation; 10%, EGFR uncommon mutations and 2% de-novo T790M. Median age at diagnosis was 60 years (range 36-84y), most patient were females (66.3%) and adenocarcinoma was the most common histological type (95.3%). A smoking history was present in 15.1% of patients. 55% of patients were treated with Erlotinib; most of them, as second line of treatment (39.6%). The objective response rate (ORR) was 65.9%. Median progression-free survival (PFS) was 18 months. No differences in PFS were found according to line of treatment (first vs second vs third or later, p=0.85) or type of mutation (exon 19 deletion vs L858R mutation, p=0.80). Out of the 18 patients who had progressed, half of them exhibited an oligometastatic pattern of progression and T790M mutation was detected as a mechanism of resistance in 27.7%.

Conclusion: Results from this cohort provide real-world evidence for the outcomes and prognosis of EGFR-mutant NSCLC Peruvian patients. The proportion of EGFR mutated NSCLC in the present series is high. Our patients exhibit a better PFS than the one reported in randomized trials of patients with advanced EGFR mutated NSCLC, and it is independent of the line of treatment or type of mutation. Further research is needed to identify the reasons behind this difference.

Keywords: Progression-free survival, Lung cancer, EGFR, Clinic-pathological

P2.06


Lung Cancer Driver Mutations and PD-L1 Expression in US Latino Patients with Advanced Lung Cancer

D. Saravia, F. Basher, A. Arora, D. Soong, D. Fanfan, J. Cotta, G. LopesSylvester Comprehensive Cancer Center, MIami/United States of America

Background: Lung cancer incidence rates in US Hispanics/Latinos (H/L) tend to be higher than those reported for most Latin American countries while mortality rates tend to be lower for H/L compared to non-Hispanic whites (NHW). Incidence and outcome disparities are probably multifactorial, however an underlying genetic basis is likely. Our aim was to report frequencies of driver mutations and PD-L1 expression in H/L in Miami in an attempt to improve therapeutic strategies that may benefit this population.

Method: Retrospective analysis on H/L pts with advanced NSCLC who received chemotherapy, immunotherapy (IO), chemotherapy combined with immunotherapy (chemoIO), and/or targeted treatment (TT) at Sylvester Comprehensive Cancer Center (SCCC) in Miami-FL. EMR was reviewed to obtain pertinent clinical information. Genomic results were obtained from Guardant 360 and Foundation One testing in blood and in tissue, respectively.

Results: 131 H/L charts were reviewed. 44% were males and 81% were adenocarcinomas. 29% were never smokers, 57% were current or former smokers (38% with ≥ 30 pack year history), and 14% had unknown smoking status. 120 pts were tested for PD-L1; 91% were positive (with 71% having TPS ≥ 50%) and 8% were negative (TPS 0%). 28% received IO, 5% as first line. 14% received chemoIO, 10% as first line. 24% received TT, 13% as first line. Frequencies of the main driver mutations are presented on the table below. Other mutations were MET (12.5%), BRAF (9.56%), PI3KCA (8.09%), STK11 (5.15%), PTEN (1.47%), and ROS1 (0.74%).

Conclusion: US H/L present a higher frequency of driver mutations than NHW as well as a high rate of PD-L1 overexpression, yet only a minority receives TT or IO as upfront therapy. Identifying persisting challenges in providing US H/L with the most appropriate treatment at the most beneficial time remains a crucial step towards achieving the goal of precision medicine in thoracic oncology.

Keywords: Mutations, Hispanics, Precision medicine

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Other popu-lations (as reported in the literature)

EGFR 25.74% 32.5% NHW=10%, East Asian=30%

KRAS 14.71% 16.6% NHW=15-25%

ALK 4.41% 4.2-10.5% NHW= 1-3%, Asian=2.3-6.7%


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P2.07


Prevalence of Hypovitaminosis D in Patients with Advanced Adenocarcinoma of Smokers and Non-smokers

I.B. Gonçalves1, A. Ferreira1, G. Fraga2, J. Vasconcellos2, T. Montella2, W. Peres1, C.G. Ferreira2

1Universidade Federal do Rio de Janeiro, Rio de Janeiro/Brazil, 2Grupo Oncoclínicas, Rio de Janeiro/Brazil

Background: In lung cancer (LC) most patients are diagnosed in advanced stages of the disease, symptomatic and eligible for systemic treatment. And adequate levels of vitamin D (VD) in this population can contribute to symptom control such as pain, decreased cytotoxic effects of chemotherapy and improve immunity and muscle function. The objective of this research was to verify the nutritional status of the VD in patients in homogenous samples with advanced adenocarcinoma of smokers and non - smokers and to relate to the habits of previous solar exposition to the disease.

Method: This was a prospective observational study, approved by an Ethics Committee, carried out with data from ambulatory patients with lung adenocarcinoma with clinical stage IV, in a specialized center for chest tumors in Rio de Janeiro, of both sexes, of the same age or greater than 20 years and Performance Status (PS) <2 seconds ECOG. The data were collected at the time of diagnosis from September 2017 to March 2019. The VD assessment was quantified by 25 (OH) D by high performance liquid chromatography (HPLC) and the cut points adopted for groups was <30ng / mL. A validated solar exposure questionnaire to complement VD status assessment was included. The sample was divided into smokers and non-smokers according to criteria adopted by the World Health Organization (WHO). The Mann Whitney test was used to compare the numerical variables between the smoking and non-smoking categories.

Results: Of the 73 patients included in the study, 54.8% were non-smokers, 50.7% were female, and 79.5% were elderly. The median VD concentration was 25.3ng / dL (17.65-32.1) and 27.2ng / dL (19-32.2) for non-smokers and 23ng / dL (16.2-32.9 ) for smokers. 65.8% of the sample had a VD deficiency according to criteria for risk groups, although we did not find differences between smokers and non-smokers (p=0.18). The median time of sun exposure was 15.7min / day and 13.83min / day for non-smokers and smokers respectively and there were no differences among them (p = 0.85).

Conclusion: We observed a higher proportion of individuals with VD deficiency in advanced stage lung adenocarcinoma in a sample predominantly of elderly individuals, with a history of low solar exposure prior to diagnosis in a country that presents adequate latitude for sun exposure throughout the year.

Keyword: Lung adenocarcinoma, Nutritional status, 25 hydroxyvitamin D, Smoking

P2.08


Osimertinib for Metastatic, EGFR Mutated Non-small Cell Lung Cancer. Real World Evidence at National Oncology Institute, Panama

F. Castillero1, O. Castillo2, T. Sowley2, A. Crismatt2

1Medical Oncology, Instituto Oncologico Nacional, Panamá/Panama, 2Medical Oncology, Instituto Oncologico Nacional de Panamá, Panama/Panama

Background: In the Flaura Trial, Osimertinib resulted in a superior median PFS (18.2 vs 10.2 months) compared with first generation EGFR-TKIs (gefitinib or erlotinib), as first line treatment for EGFR – mutated metastatic NSCLC. Because of this finding, Osimertinib

was approved in the National Oncology Institute of Panama from June 2018 for EGFR – mutated, metastatic NSCLC as first line therapy and to the patients that progressed to another EGFR Inhibitor (Gefitinib or erlotinib) and have the T790M mutation.

Method: We did a retrospective, descriptive review of EGFR mutated metastatic NSCLC patients treated with Osimertinib, in our institution from July 2018 to June 2019. We did a preliminary descriptive analysis of the patients using SPSS – 24 for the analysis.

Results: A total of 45 patients received Osimertinib in the evaluated period, 32 (71%) as first line therapy and 13 (28.9%) as second line therapy. The mean age was 65.2 (51.3-79.1) years, 34 patients (75.6%) were female, 77.8% non – smokers and 91.1% had a good performance (ECOG 0-2). The most common mutation detected was in the exon 19 (60%) and, with a median follow up of 7.5 months, just 4 (12.5%) patients treated in a first line setting, and 3 (23%) of the second line setting, has progressed. the response rate was 50%, with a disease control rate of 80.4%. This finding was independent of therapeutic line, and smoking status. Of the 10 patients with SNC disease, 6 had partial response. The main toxicities reported were three: diarrhea, rash and paronychia, but most of it (81%) were of first grade.

Conclusion: The use of osimertinib as first line therapy is feasible in developing countries, with similar outcomes with the reported in the pivotal trials and good tolerability.

P2.09


Access and Outcomes of TKI EGFR in Lung Cancer Treatment from Uruguayan Population

M.C. Rodriguez Palleiro1, A. Perez1, K. Mareco1, N. Piñeiro2, L. Delgado1, M. Cuello1

1Oncologia Clínica, Hospital de Clinicas, Montevideo/Uruguay, 2Fondo Nacional de Recursos, Montevideo/Uruguay

Background: Lung cancer represents a serious global health problem. Our country is not alien to this reality, being the most common cause of cancer deaths and representing 1400 newly diagnoses/year. The role of Tyrosine Kinase Inhibitors (TKI) of the epidermal growth factor receptor (EGFR) for the treatment of advanced non small lung cancer (NSCLC) is well known. In Uruguay EGFR mutations have an overall prevalence of 18%. The access to TKI-EGFR, erlotinib or gefitinib, is covered by the Fondo Nacional de Recursos (FNR). The FNR, is a non-state public person which provides financial coverage for highly specialized medicine procedures and high-priced medicines for the Uruguayan population. The requirements for the coverage are based on clinical trials inclusion/exclusion criterial.

Method: We use the FNR registry that collects observational data from patients receiving treatment under its coverage. Adults patients with advanced EGFRMut+ NSCLC, who had received TKI EGFR treatment between November 2011 and December 2017 were included. Demographic, clinical characteristics were analyzed, overall survival (OS) and progression free survival (PFS) were the outcomes evaluated. The study was approved by a local ethical committee.

Results: 130 treatment requests were made. The median age at diagnosis was 63 years, being 61.5% of female patients and 38.5% male. 87% were non-smokers. The most frequent mutation reported was the exon 19 delection (63.8%), followed by the exon 21 mutation (30%), others represented 4.3%. PFS for the global population was 12.9 months (95% CI: 10.4-15.3) and the OS was 19.7 months (95% CI: 16.8-22.5). No statistically differences were found in OS and PFS analyzed according to gender, mutation, or treatment received (erlotinib vs gefitinib).

Conclusion: Our results support that the use of the evidence-based approach constitutes an important element for the formulation of sustainable public policies, this cohort reported similar OS and PFS as shown in clinical trials in real-world population. The main

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finding was the low number of treatments requested for coverage, with only 130 treatments in 6 years when it was expected 130 EGFRMut+ NSCLC new diagnoses per year. Meantime other countries struggle against access, in Uruguay having that resolved, we have to improve EGFR mutation testing in NSCLC in daily oncology practice to offer the best treatment to our patients.

Keywords: Lung cancer, Uruguay, ITK, Real word outcomes

P2.10


Mutational EGFR Profile in Mexican Patients with Pulmonary Adenocarcinoma Measured by New Generation Sequencing (NGS)

C.P. Sánchez Ríos1, J. Alatorre Alexander2, M.D.R. Flores Soto3

1Oncología Torácica, National Institute of Respiratory Diseases, Mexico City/Mexico, 2Oncología Torácica, National Institute of Respiratory Diseases, MEXICO/Mexico, 3Neumologia, Instituto Nacional de Enfermedades Respiratorias, MEXICO/Mexico

Background: Lung cancer is the leading cause of cancer death. The consideration of genetic tests and targeted therapy based on genomic alteration is now the standard of care in patients with advanced pulmonary adenocarcinoma. The new generation sequencing (NGS) allows to identify the presence or absence of mutations, it is approved as a diagnostic method to identify such alterations. In our study we describe the frequency and type of EGFR mutations by NGS.

Method: Descriptive, prospective and cross-sectional study. We studied 68 samples of tumor tissue with a diagnosis of pulmonary adenocarcinoma in the period July-October 2018, analyzed by NGS for the determination of mutations in molecular drivers.

Results: Altered EGFR was found in 29.4% of the samples, of which 65% were in women and 35% in men. The most frequently identified mutation descending; Leu858Arg in exon 21 (60%), exon 20 (20%), exon 19 (15%) and exon 18 (5%). Mutation of resistance to tyrosine kinase inhibitor (T790M) was identified in 0.5%. We also analyzed whether patients who presented mutations in EGFR had a smoking risk factor found only in 5% of cases. 60% of patients with EGFR mutation had a history of exposure to biomass smoke.

Conclusion: The NGS is an alternative to identify genetic alterations in EGFR in NSCLC.

Keyword: Lung cancer, Prognosis, Mutation

P2.11


Three Years of Experience with ALK-positive Patients

J.B. Correia1, A. Figueiredo2, F. Barata2

1Pneumology, Centro Hospitalar Tondela-Viseu, EPE., Viseu/Portugal, 2Pneumology, Centro Hospitalar Universitário de Coimbra, Viseu/Portugal

Background: The new tyrosine kinase inhibitors approved for the therapy of non-small cell lung cancer (NSCLC) caused by ALK rearrangement, have been showing an improvement on overall survival, disease progression and toxicity.

Method: We performed a retrospective analysis of all the patients with NSCLC and ALK rearrangement that received crizotinib, ceritinib and alectinib as first-line or second-line therapy in our health care unit, by investigating its toxicity and the disease progression.

Results: Out of the 113 patients diagnosed with stage IV or stage IIIB lung adenocarcinoma, 17 were ALK positive (from those who had clinical indication and enough histologic material to perform

the test). In this population, the mean age was 60,76 years-old and 76,47% (n=13) were females. Sixteen patients (94,12%) were non-smokers and one (5,88%) was a smoker. By the time of the diagnosis, 94,12% (n=16) presented with stage IV disease (one of them had brain metastasis and was treated with holocranial radiotherapy) and 5,88% (n=1) presents with stage IIIB disease. 41,18% (n=7) had a Performance Status of 0 and 58,82% (n=10) of 1.Crizotinib was started as first-line therapy in 35,29% (n=6) of patients and as second-line therapy in 64,71% (n=11) (these started first with chemotherapy fulfilling either 2, 4 or 6 cycles of treatment). 10 patients showed crizotinib-induced toxicity (1 presented skin rash, 1 presented onicolisis, 6 had liver toxicity and nausea and/or diarrhea, 1 had renal toxicity and 1 presented cardiac toxicity and died). As such, crizotinib dose reduction was needed in 6 patients (4 due to liver toxicity, 1 due to renal toxicity and 1 due to skin rash) and 1 patient had his treatment shifted to ceritinib (because of liver toxicity). Considering follow-up until July 2017, complete and partial response with crizotinib was first seen in 10 and 3 patients, respectively, 3 patients presented disease progression and 1 patient doesn’t have follow-up data available yet. After a period of time, 6 patients kept their response to crizotinib and 10 patients showed disease progression (4 patients evolving with cerebral, 2 with bone metastasis, and the remaining with lesions in different locations), and 2 of them eventually died. The average time under crizotinib was 14 month (minimum month and maximum 28 month). 7 of the latter had their treatment shifted to alectinib (n= 5) or ceritinib (n=2). Regarding the data available so far, from the patients that started alectinib 2 showed partial response and 1 showed complete response, and from those under ceritinib 1 showed partial response and 1 showed stability of the disease. From those patients with progression with brain metastasis, 1 is currently under ceritinib (presenting disease stability) and 3 are under alectinib (1 presents complete response, 1 presents partial response, the third doesn’t have available follow-up data yet). Three of these patients were treated with holocranial radiotherapy.

Conclusion: The experience in our health care unit is similar to the data from other studies, showing high response rates, high overall survival and low toxicity associated to these drugs.

P2.12


Clinical and Tomographic Description of Mexican Patients with Lung Cancer with ALK Positive

C.P. Sánchez Ríos1, M.A. Ramirez Candelas2

1Oncología Torácica, National Institute of Respiratory Diseases, Mexico City/Mexico, 2Neumologia, Instituto Nacional de Enfermedades Respiratorias, MEXICO/Mexico

Background: The treatment of lung cancer is currently based in the selection of patients according to the presence of oncogenic abnormalities. The gene (ALK) is present in 3 to 7% ofpatients with non-small cell lung cancer (NSCLC) and confers sensitivity to ALK inhibitors. This study was conducted at the National Institute of Respiratory Diseases with the aim of describing the clinical and tomographic characteristics of patients with ALK rearrangement taking into account the biological behavior of this type of lung cancer is different.

Method: Retrospective observational study of patients with lung cancer from January 2013 to June 2018. Review of clinical and radiological records, with registration of sociodemographic variables, clinical, molecular profile and immunohistochemical staining (IHC) for ALK. Results expressed through measures of central tendency.

Results: A cohort was analyzed from 2013 to 2018 with a total of 751 patients diagnosed with lung cancer. The CPCNP was the most frequent with 93.74% (n = 704). The adenocarcinoma was found in 86% (n = 606). ALK rearrangement was reported in 3.3% (n = 20). The majority were 65% female, the average age was 58 + 2.4 years, smoking 40% (n = 8). Of the patients who never smoked, 92% (n = 11) reported exposure to biomass. In 25% (n = 5) functional diagnosis

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of COPD was documented. The most frequent tomographic patterns were: mass in 70% (n = 14), pleural thickening with pleural effusion in 20% (n = 4) and micronodular pattern in 10% (n = 2).

Conclusion: A clinical phenotype and behavior different to the rest of patients with NSCLC is demonstrated in ALK positive patients.

P2.13


Frequency of Uncommon EGFR Mutations in Costa Rica

R. Porras Gutiérrez1, L. Corrales-Rodriguez2, J. Abbas1, A. Mendez3

1ccss, san jose/Costa Rica, 2CIMCA - CCSS, San José/Costa Rica, 3CCSS, San Jose/Costa Rica

Background: Lung cancer is one of the neoplasms with the highest mortality around the world, being adenocarcinoma the most common subtype. EGFR is a common mutation present in adenocarcinoma, mainly in young women and nonsmokers. In Asians has a significantly higher frequency of about 40% of the mutations and around 20% in the Caucasians. EGFR mutations are diverse. Approximately 85%-90% of EGFR mutations occurred in exon 19 deletion mutations and exon 21 point mutations L858R. Among Latinos, EGFR mutations were found in 23.3%. The highest frequency was observed in Latinos from Peru (37%) followed by the United States (23%) and Mexico (18%). EGFR exon 19 deletions were the most frequent type of mutation among Latinos (47.6%) followed by EGFR L858R (38%) and exon 20 insertions (9.5%). Uncommon mutations, such as point mutations in exon 20 (S7681), substitution in the exon 18 (G719X, E790K/E790A) and complex mutations (example S768I + G719X), are present in less than 10% of all EGFR mutations. The aim of these paper is to determine the frequency of the uncommon mutations of the EGFR gen in a Latinamerican country, Costa Rica.

Method: Specimens from 269 advanced (IIIB/IV) patients were diagnosed with lung adenocarcinoma and underwent EGFR gene detection at Hospital Rafael Ángel Calderón Guardia in Costa Rica.

Results: EGFR mutation was documented in 85 cases, of which 3,5% (3 patients) presented exon 18 mutation and 17.6% (15 patients) in exon 20. The most frequent mutation observed was in 19 exon (44%) followed by 21 exon (31.7%). Mutations in 18 and 20 exons occurred with a slightly more frequency in men, unlike the mutations in exons 19 and 21.

Conclusion: The behavior of EGFR mutations in Costa Rica is similar to that already studied in the rest of the Latin American population.

Keyword: EGFR, Uncommon mutations, Adenocarcinoma

P2.14


Response Profile of Non-small Cells Lung Cancer with ALK Positive Treated with Alectinib

C.P. Sánchez Ríos1, J.F. Martinez Herrera2, J. Alatorre Alexander2

1Oncología Torácica, National Institute of Respiratory Diseases, Mexico City/Mexico, 2Oncología Torácica, National Institute of Respiratory Diseases, MEXICO/Mexico

Background: The diagnosis and treatment of lung cancer is currently governed by the selection of patients based on oncogenic alterations that allow specific therapies to be offered. The gene (ALK) is present in 3 to 7% of patients with non-small cell lung cancer (NSCLC) and confers sensitivity to ALK inhibitors with better response rates and PFS than with chemotherapy.

Method: We performed a descriptive review of the response profile in patients with NSCLC with positive ALK mutation and who received treatment with alectinib. Tomography patterns were

described, as well as the response achieved with the treatment.Results: We found 5 cases of patients with a diagnosis of NSCLC with ALK positive mutation who received treatment with Alectinib. It was found that all patients reached, until the time of the last evaluation, a partial response based on RECIST 1.1 criteria. The adverse effects presented were explained by the use of TKI.

Conclusion: A clinical phenotype and behavior different from the rest of patients with NSCLC in patients with positive ALK rearrangement is demonstrated. Alectinib is associated with disease control with minimal well tolerated adverse effects.

Keyword: Lung cancer, Prognosis, ALK, Alectinib

P2.15


Progression under Osimertinib, What Now?

M. Felizardo1, V. Sacramento1, C. Custódio2, P. Calvinho3, R. Madureira4, J. Calha5, S. Furtado1

1Pneumologia, Hospital Beatriz Ângelo, Loures/Portugal, 2Hospital Beatriz Angelo, Loures/Portugal, 3Cardiothoracic Surgery, Hospital Santa Marta, Centro Hospital Lisboa Central, Lisboa/Portugal, 4Pathology, Hospital Beatriz Ângelo, Loures/Portugal, 5Radiology, Hospital Beatriz Ângelo, Loures/Portugal

Background: Patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) generally respond well to treatment with EGFR-targeted tyrosine kinase inhibitors (TKIs) but acquired resistance to therapy is inevitable, reflecting tumor evolution. Positive clinical activity and favorable toxicity profile has led to the use of

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CLINICAL CASES

CASE NUMBER, AGE, GENDER, DIAGNO-SIS DATE

STAGE AND TOMO-GRAPHIC CARAC-TERISTIC

PRECIOUS TREAT-MENT

RESPONSE WITH ALECTINIB

AD-VERSE EVENT

1 80 FEMALE 2016 NON SMOKER

EC IIIA T3N2M0 PROGRES-SION DIS-EASE WITH MULTI-NODULAR DISEASE LUNG

VINOREL-BINE CAR-BOPLATIN RADIOTER-APY 54 Gy - PRO-GRESSION DISEASE - STAGE IV MARCH 2018 TKI

PARTIAL RESPONSE JUNE 2019

NONE

2 34 MALE 2018 NON SMOKER

LUNG TU-MOR LEFT T4N0M1B

NONE APRIL 2018 TKI FIRST LINE

PARTIAL RESPONSE MAY 2019

G1


LUNG TUMOR RIGHT AND PLEURAL EFFUSION T4N3M1B

NONE JULY 2018 TKI FIRST LINE


NONE

4 53 MALE 2018 NON SMOKER

LUNG TU-MOR LEFT T4N0M1A

NONE SEPT 2018 TKI FIRST LINE

PARTIAL RESPONSE JUNE 2019

NONE


LUNG TUMOR RIGHT T2N3M1B

NONE SEPT 2018 TKI FIRST LINE


NONE

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osimertinib mesylate to treat EGFR-mutant NSCLC with TKI resistance mediated by the EGFR T790M mutation.

Method: Section not applicable

Results: The authors present the case of a 54 year old female, former smoker (10 packs/year) patient with no relevant personal or family medical history that was initially diagnosed in February 2014 with a T2aN0M0 adenocarcinoma of the upper right lobe of the lung. A right upper lobectomy was performed followed by adjuvant chemotherapy (June to September 2014) and she remained clinically stable under follow up until February 2016. At that time she began complaints of intense pain localized to the right sacroiliac joint with functional impotence (she was unable to walk) secondary to a sacral and sacroiliac lesion (59cm) with high metabolic activity (maxSUV 8.98) in the PET scan which also revealed multiple bilateral lung nodules (no metabolic expression). The biopsy of the bone lesion identified it as a metastasis of lung adenocarcinoma harboring an exon 21 EGFR mutation c.2573T>G p. (Leu858Arg) and gefitinib was iniciated (as well as radiotherapy for the bone). The patient remained asymptomatic between May 2016 and May 2017 when anorexia and weight loss began. The chest CT-scan showed increased number and size of the known pulmonary micronodules. A surgical biopsy of one nodule confirmed the presence of EGFR T790M mutation so she started osimertinib in july 2017 with symptom control and no toxicity. Despite the clinical response, there was a slow but constant increase in the dimension of the lesions in the follow up chest CTs. A transthoracic biopsy was performed in April 2019 revealing lung adenocarcinoma with loss of the T7901M mutation and presence of exon 21 EGFR mutation c.2573T>G p. (Leu858Arg).

Conclusion: Tumor resistance to therapy is expected and should be taken into account when deciding therapeutic strategies. In EGFR mutated NSCLC, resistance mediated by the EGFR T790M mutation has been successfully overcome with osimertinib. However, resistance mechanisms that cause loss of response to osimertinib still need to be clearly identified (MET amplification, small cell transformation, resensitization to first-line EGFR TKIs?) in order to be effectively overriden and allow more effective therapeutic strategies to be devised (adequate sequencing, repeated treatment with previous TKIs?).

P2.15-A


Panorama Retro: Real World Evaluation of Molecular Testing and Treatment Patterns for EGFR Mutations in Patients with Advanced or Metastatic NSCLC (D133FR00143)

M. Cuello1, C. Martín2, S. Sena3, J. Cundom4, E. Korbenfeld5, V. Garcia Cocco6, S. Berutti7, G. Recondo8, H. Perroud9, O. Barajas10, F. Orlandi11, E. Orellana12, M. Zapata13, S. Arauchan14, A. Gómez15, C. Bonilla16, H. Marcelo17, F. Reinhold17, S. Goncalves17

1Oncologia Clínica, Hospital de Clinicas, Montevideo/Uruguay, 2Medical Oncology Department, Instituto Fleming, Buenos Aires/Argentina, 3Hospital Alemán, Buenos Aires/Argentina, 4Hospital Lanari, Buenos Aires/Argentina, 5Hospital Británico, Buenos Aires/Argentina, 6Hospital Italiano, Cordoba/Argentina, 7Hospital Italiano de La Plata, La Plata/Argentina, 8CEMIC, Buenos Aires/Argentina, 9Sanatorio de la Mujer, Rosario/Argentina, 10Fundación Arturo Lopez Perez, Región Metropolitana/Chile, 11Sociedad Porsalud Montes y Orlandi, Santiago/Chile, 12Clinica Santa Maria, Región Metropolitana/Chile, 13Fundación Hospitalaria San Vicente de Paul, Santiago/Chile, 14Oncomédica, Montería/Colombia, 15Hemato-oncologos SA, Valle del Cauca/Colombia, 16Instituto Nacional de Cancerologia ESE, Bogotá/Colombia, 17AstraZeneca, Buenos Aires/Argentina

Background: Stage IV NSCLC is a challenging disease because treatment is driven by molecular and biomarker testing. Management of these patients is well established, but real word data might not always reflect the guidelines especially in emerging countries where the lack of accurate information is a constant.

Method: This is a retrospective, multicenter study of 465 patients form Argentina, Uruguay, Chile and Colombia diagnosed during 2017. Of these, 432 were newly diagnosed, treatment naïve advanced or metastatic NSCLC (Cohort 1) and 31 were EGFRm+ patients who had progressed after a first- or second-generation EGFR-TKI (Cohort 2).

Results: For newly diagnosed patients, 77.9% of the private sector underwent molecular diagnosis but only 53.9% of the public sector had access to the testing. EGFR mutation was found in 15.05% of the population (60/432), however, almost 18% of these patients received target therapy only after a first line of chemotherapy. 20.4% of the patients had CNS metastasis at diagnosis and almost 75% received any CNS related treatment (85% radiotherapy; 15% surgery). For cohort 2, the main site of progression was seen within the thorax (59.3%) while the second site of progression was CNS (21.8%) followed by the bone (18.7%). Of the 32 patients, only 24 (75%) underwent biopsy after progression. Reasons for not performing a biopsy included poor PS and physician decision. Third generation TKI´s were given in 31% of the patients in second line and 15.6% in third or more lines.

Conclusion: In real word, for Latin American patients, access to molecular testing is still challenging, especially in public health systems. Turnaround times and test availability may interfere with the choice of first line treatment for the patients. Progression within the thorax and in CNS were the two more frequent sites of relapse. After progression to a first line target therapy, only 75% had access to a rebiopsy and of these 46.6% received a third generation TKI. These data should encourage physicians to give most effective therapy in 1st line for patients with EGFR mt+ tumors.

P2.15-B


Update of Mutation Status and PDL1 Expression in Lung Cancer. A Multicenter Local Study

N. Pilnik1, V. Bengio2, M. Canigiani3, C. Maldini21Cordoba University, Cordoba/Argentina, 2Cordoba Hospital, Cordoba/Argentina, 3University Oncology Institute, Cordoba/Argentina

Background: Advances have been made in the understanding of the biology of NSCLC in relation to the characterization of molecular features such as activations of oncogenes by mutations, translocations and amplifications, and check point expressions which are being used as predictive biomarkers.

Method: We determined the molecular alterations in EGFR, gene fusion ALK, and PDL-1 in our Caucasian and Hispanic populations. 171 small samples and resection specimens of patients with NSCLC in different institutions of Cordoba were studied during a period (2014 - 2019). In addition to Histopathology Type, we analyzed immunohistochemistry (IHC) characteristics, molecular profiles, and several clinical variables were studied.

Different tests were used to detect alterations of EGFR and fusion gene EML4-ALK expression, with the aim to identify our own profile. EGFR mutation was studied by therascreen kit, PCR, in order to detect genetic alterations in exons 18, 19, 20 and 21. ALK translocations were analyzed by FISH (Vysis- Break Apart, Abbott) and IHC (clon D5F3, ventana, Roche). With used to determinate checkpoint expression by Platoform DakoAutosteiner Link 48, Kit PD-L1 IHC 22C3 pharm Dx. We correlated the molecular profile and PDL-1 expression with different clinical variables (age, gender, and tobacco habits). Qualitative variables were compared using chi-squared test or Fisher’s test and quantitative variables were compared using the T-test.

Results: 171 samples were tested for EGFR expression and ALK alterations 63.2% of subjects were men and 88.9% were smokers.

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Note: Qualitative variables were compared using chi-squared test or Fisher’s test (*) and quantitative variables were compared using the T-test.

Conclusion: Our results showed a comparable frequency in EGFR mutations and gene fusion ALK in relation to the data published in western population. Molecular analysis of NSCLC, adenocarcinoma (AC) EGFR, ALK, and tumor proportion score in PDL-1 expression is the standard of diagnosis. These results allowed providing the most adequate therapy for patients.

P2.15-C


Phase 1 Trial Evaluating Safety, Efficacy, and PK of AMG 510, a Novel KRASG12C Inhibitor, in Non-small Cell Lung Cancer

R. Govindan1, M.G. Fakih2, T.J. Price3, G.S. Falchook4, J. Desai5, J.C. Kuo6, J.H. Strickler7, J.C. Krauss8, B.T. Li9, C.S. Denlinger10, G. Durm11, J. Ngang12, H. Henary12, G. Ngarmchamnanrith12, E. Rasmussen12, P.K. Morrow12, D.S. Hong13

1Alvin J Siteman Cancer Center at Washington University School of Medicine, St. Louis/United States of America, 2City of Hope, Duarte/United States of America, 3The Queen Elizabeth Hospital, Woodville South/Australia, 4Sarah Cannon Research Institute at HealthONE, Denver/United States of America, 5Peter MacCallum Cancer Centre, Melbourne/Australia, 6Scientia Clinical Research, Randwick/Australia, 7Duke University Medical Center, Durham/United States of America, 8University of Michigan, Ann Arbor/United States of America, 9Memorial Sloan Kettering Cancer Center, New York/United States of America, 10Fox Chase Cancer Center, Philadelphia/United States of America, 11Indiana University , Simon Cancer Center, Indianapolis/United States of America, 12Amgen Inc, Thousand Oaks/United States of America, 13MD Anderson Cancer Center, Houston/United States of America

Background: Currently, no approved therapy targets KRASG12C mutation, which occurs in approximately 13-14% of non-small cell lung cancer (NSCLC). AMG 510, a novel small molecule, specifically and irreversibly inhibits KRASG12C by locking it in an inactive GDP-bound state.

Method: This is a phase 1, first-in-human, open-label, multicenter study of AMG 510 in patients with locally advanced or metastatic KRASG12C mutant solid tumors, including NSCLC. The primary endpoint is safety; key secondary endpoints include objective response rate, assessed every 6 weeks, duration of response, progression-free survival, and PK. Key inclusion criteria: KRASG12C mutation identified through DNA sequencing; measurable or evaluable disease; progression on standard therapy; and ECOG PS ≤ 2. Patients with active (untreated) brain metastases and myocardial infarction within 6 months of study initiation were excluded. Once maximum tolerated dose is identified during dose escalation, additional patients will be enrolled in the dose expansion part. AMG 510 is given orally once daily until disease progression, intolerance, or consent withdrawal.

Results: As of 4 April 2019, 13 patients (8 females; median age: 63 years [range: 53–77]) with NSCLC were enrolled into 4 dose escalation cohorts. Median number of prior lines of therapy was 3 (range: 1–5). Median duration of treatment was 59 days (range: 9–192). No dose-limiting toxicities were identified. The most frequently reported adverse events (AEs) were decreased appetite and diarrhea, observed in 4 and 3 patients, respectively. Six patients reported 10 treatment-related adverse events (TRAEs) (6 grade 1; 2 grade 2; 2 grade 3). Two grade 3 TRAEs were anemia in a patient with baseline grade 2 anemia and diarrhea that lasted 2 days in another patient. 10 patients were evaluable for tumor response: 5 patients had a partial response (2 of which were confirmed), 4 had stable disease, and 1 had progressive disease (PD). Of all 13 patients enrolled, 11 remained on study, and 2 discontinued due to PD.

Conclusion: AMG 510 is well tolerated at all 4 dose levels and showed antitumor activity in patients with advanced KRASG12C mutant NSCLC. Enrollment is ongoing (ClinicalTrials.gov identifier: NCT03600883).

P2.16

Topic: Pathology

PD-L1 Expression in a Population with Non-Small Cell Lung Cancer in a Reference Healthcare Center in Latin-America

L. Fernandez-Trujillo1, J. Lores2, M. Aguirre2, L. Sua3

1Department Of Internal Medicine, Pulmonology Service, Interventional Pulmonology, Fundacion Valle del Lili, Cali/Colombia, 2Clinical Research Center, Fundacion Valle del Lili, Cali/Colombia, 3Department Of Pathology And Laboratory Medicine, Fundacion Valle del Lili, Cali/Colombia

Background: Non-small cell lung cancer (NSCLC) is the most common type among malignancies of the lung, and among its histological subtypes, different mutations and protein expressions have been object of study for the past years. Epidermal growth factor receptor (EGFR) mutations and EML4-ALK fusion as driver mutations have been reported to upregulate programmed death-ligand 1 (PD-L1) expression. Despite therapeutic significance of these associations has not been yet completely elucidated, studying the prevalence and correlation of these features becomes more important with time.

Method: Clinical and mutational features were described in 114 patients diagnosed with NSCLC between 2013 and 2016 at a reference health care center in Colombia. Among the patients in whom PD-L1 expression was tested, we reported its prevalence and distribution in patients positive for EGFR and ALK.

Results: The mean age was 65±12 years. 72.8%(n=83) were classified as stage IV. Adenocarcinoma was the most frequent (80.7%; n=92). The prevalence for EGFR mutations was 27% (n=30) and for EML4-ALK fusion gene was 15.8% (n=9). PD-L1 expression was tested in 57 patients from which 35% (n=20) came positive, 5 were also positive for EGFR and 4 for ALK. From all PD-L1 positives, 60% (n=12) with high expression. No association was found between gender and PD-L1 expression,

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Table 1. Characteristics of the 171 cases of lung adenocarci-noma according gender.

Variable Malen=108

Femalen=63

p

Age (mean, ±SD), years 64.7 (8.9) 61.8 (8.2) 0.032

Smoking 101 (93.5) 51 (81.0) 0.012

EGFR expression 12 (11.1) 19 (30.0) 0.002

ALK alterations 1 (0.9) 2 (3.2) 0.555*

Table 3. Characteristics of the 39 cases of lung adenocarci-noma which PDL-1 was tested.

PDL-1 totaln=39

PDL-1+n= 16 (41%)

PDL-1 –n=23 (59%)

p

Male sex, n (%)

23 (59.0) 11 (68.8) 12 (52.2)

0.3006

Age (year), mean (±SD)

65.72 (7.27) 62.12 (7.35)

65.43 (8.71)

0.7747

Smoking, n (%)

39 (100) 16 (100) 23 (100)

1

EGFR expres-sion, n (%)

3 (7.7) 1 (6.2) 2 (8.7) 1*

ALK altera-tions, n (%)

0 0 0

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and being a non-smoker was associated with a lower expression of the protein.

Conclusion: The prevalence of EGFR mutations was similar to that reported worldwide, and fusions in the EML4-ALK gene were higher than expected, as well as PD-L1 expression. Smoking has already been reported to be associated with a higher expression of PD-L1, as found in this study. More studies must be done regarding expression of the protein in patients with driver mutations to stablish reliable associations and elucidate the clinical significance of blocking PD-1/PD-L1 in EGFR and ALK-mutant NSCLC treated with TKIs.

Keywords: Non-small cell lung cancer, PD-L1

P2.17

Topic: Pathology

Intersegmental Plane Identification with Single Lung Ventilation in PSN Resection

E. Peña Gomez Portugal1, A. Leticia Solano Nieto2, O. Pichardo Meneses3, M.J. Midence Arguello1, E. Sanchez Garcia Ramos1, J. Carrillo Vidales1, R. Najera Ramirez1

1Experimental Surgery, National Institute of Medical Science and Nutrition Salvador Zubiran, MEXICO CITY/Mexico, 2Anesthesiology, IMSS, mexico/Mexico, 3Anesthesiology, ISSSTE, mexico/Mexico

Background: Taking in account that primary lung cancer is the leading cancer mortality worldwide with approximately 428900 deaths per year, and its several distinct histologic types it makes these disease a challenge in diagnostic and treatment. Also with the imaging tool that plays an important role in diagnosis and stadification in a chest X ray only when the nodule size is 40mm the diagnosis will be in a 100%. The follow up will be with the solid subsolid aspect at CT and its change or if presents a grow in diameter o volume because it migth be missing in up to 47%, this put the balance between curabillity and unnecessary surgery in approximately 34%.

Method: We present all patients that arrive to the Oncologic Thoracic Surgery consult in a period of 2 years with risk factors and PSN and predominant subsolid component irregular surface and GGO on CT, with complete protocol for surgical approach. 208 patients were include, 83 female (40%) 125 male (60%) age average 62 years old accept and sign informed consent for surgery an all related to medical concern. All patients were intubated with a common orotracheal tube and direct to the right or left lung depending of the localization of the nodule with out use of bronchoscope only the manuevers previously known to direct the tube, and confirm with elevation of the chest and auscultation. Performing the procedure in full lateral position we use CO2 throw the thoracoporth at 10mmHg initially to help colapsing the lung and then to 8mmHg to maintain, all the procedure the patient maintain a Sao2 at an average of 94%, CO2 of 32%, HR 90 per second. all patients were monitoring with a gasometry during the procedure and in base of the result the lung volume and the respiratory frequency was increase or decrease to maintain principally the CO2 level, a complete lung isolation was achieved and a correct identification of vascular and lung structure were done, the segmentectomy was done with stapler ans stapñler line was reinforced to prevent airleaks and bleeding at the line all patients were extubated and a chest tube were put in.

Results: A segmental plane was identified and a correct identification of the nodule can be done with these type of anesthesic procedure, all samples were send to pathology and all patients with adenocarcinoma were studies to mutation. 83 patients with diagnostic of adenocarcinoma, 14 patients with mutation study in blood or liquid biopsy test were negative and 2 patients PDL1 (+) and 4 EGFR (+)

Conclusion: The correct identification of the segmental plane for a surgery and localization of the PSN will help to avoid unnecesary resection and maintain the lung function ; the labeling and the mapping with indiocyanine green or blue metilen sometimes in developing countries is not possible and the correct lung isolation in some patients is a challenge for the anestesiology, these factors are related to the economy and the infraestructure of each hospital.

P2.18

Topic: Pathology

Sternal Cavernous Hemangioma and Anterior Thoracic Wall Reconstruction: Case Report

L. Fernandez-Trujillo1, M.B. Iriarte2, E.I. Morales3, M. Velasquez4, L. Sua5, B. Perez5

1Department Of Internal Medicine, Pulmonology Service, Interventional Pulmonology, Fundacion Valle del Lili, Cali/Colombia, 2Faculty Of Health Sciences, Universidad Icesi, Cali/Colombia, 3Department Of Internal Medicine, Pulmonology Service, Fundacion Valle del Lili, Cali/Colombia, 4Department Of Surgery, Thoracic Surgery Service, Fundacion Valle del Lili, Cali/Colombia, 5Department Of Pathology And Laboratory Medicine, Fundacion Valle del Lili, Cali/Colombia

Background: The sternum is considered an unusual site of tumors, with an overall incidence of 15% of all thoracic wall tumors. Primary sternal tumors are even rarer and are more malignant. Benign lesions are of varied nature, among these hemangiomas, which usually occur in soft tissues and when they appear in bone, they usually present in the skull and vertebrae. We present the case of a young male who debuted with a painful sternal mass that was evaluated and resected, confirming a cavernous hemangioma.

Method: Case description. Review of the clinical history.

Results: Male, 39 years old, with no relevant personal history, with sternal pain, not irradiated, of 2 years of evolution that had worsened in the last months and emergence of a palpable mass at that level. Physical examination: bulging of the sternum in its upper portion without inflammatory changes, without collateral circulation, no murmurs and no lymph node enlargement. Thoracic CT: expansive lytic lesion of the sternum involving the manubrium and extending to the third costo-sternal joint, without intrathoracic involvement with a cleavage plane with mediastinal vascular structures. Resection of the sternum and reconstruction with prosthetic material, pectoral and fasciocutaneous muscle flaps was performed. Intraoperative findings: Large tumor of the sternal manubrium without involvement of the clavicles or the first ribs. He presented satisfactory clinical evolution during the postoperative period. Histopathological study: Neoplasm composed of irregular vascular dilatations containing abundant erythrocytes, without cytological atypia or mitosis.

Conclusion: Hemangiomas of the sternum can cause defects in the bone cortex with an expansive growth. It is very difficult to differentiate its benign nature from malignant lesions. They are considered malignant until proven otherwise; treatment is proposed with radical surgery to achieve healing, with reconstruction to improve the quality of life, as in our case.

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Keywords: Sternal Cavernous Hemangioma, Thoracic surgery, Thoracic Wall Reconstruction

P2.19

Topic: Pathology

Pulmonary Metastasis in a Patient with Multiple Primary Adenocarcinomas: A Case Report

L. Fernandez-Trujillo1, C.A. Calderon2, E.I. Morales3, L. Sua4

1Faculty Of Health Sciences, Universidad Icesi, Cali/Colombia, 2School Of Medicine, Universidad CES, Cali/Colombia, 3Department Of Internal Medicine, Pulmonology Service, Fundacion Valle del Lili, Cali/Colombia, 4Department Of Pathology And Laboratory Medicine, Fundacion Valle del Lili, Cali/Colombia

Background: Cancer diagnosis increases with age, which is also a risk factor for the development of multiple malignant neoplasms. Patients with a primary tumor are at an 8,5% risk of developing secondary tumors. The incidence of primary neoplasms varies between 2,4% and 8%; 26% of the secondary presentations are synchronous and 74% are metachronous. We describe the case of a patient with multiple primary adenocarcinomas who develops pulmonary nodules, requiring further evaluation.

Method: Review of clinical history

Results: A 76 year old female with previous history of diabetes mellitus II and hypothyroidism presents with multiple primary adenocarcinomas including a well-differentiated ductal adenocarcinoma of the head of the pancreas with extensive vascular and perineural compromise, stage T2N0M0, managed with a distal pancreaticoduodenectomy, splenectomy and radical lymphadenectomy; an apocrine ductal carcinoma in situ of the breast, stage T3N0M0 with negative hormone receptors, managed with a mastectomy and neoadjuvant chemotherapy; a multifocal papillary thyroid carcinoma,

stage T1AN0M0, compromising the left vocal cord, managed with total thyroidectomy, radioactive iodine therapy and lymphadenectomy; and a gastrointestinal stromal spindle cell lesion, without necrosis but positive CD117, CD34, actin and desmin. A multi-gene panel test is performed for hereditary cancer syndromes (MyRISK) with complete sequencing and MLPA for BRCA1, BRCA2 with a negative result; and later MLPA and sequencing for APC, ATM, BARD1, BMPR1A, BRIP1, BRIP1, CDH1, CDK4, CDKN2A, CHECK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PATEN, RAD51C, RAD51D, SMAD4, STK11 and TP53 showing variants of uncertainsignificance and MLH1 polymorphism. Due to the positivity of serum cancer antigen 19-9, a PET-CT scan is performed identifying hypermetabolic nodules in the lingula and the left lower lobe. The patient is taken to lobectomy and wedge resection; pathology report is notable for a metastatic adenocarcinoma originated in the pancreas. NAB-Paclitaxel is initiated with complete remission.

Conclusion: In this case the patient had breast, pancreatic, thyroid and gastrointestinal adenocarcinomas, with metastatic lesions in the lung of pancreatic origin. In the literature similar reports have not been described; however hormone associated carcinomas such as simultaneous ovarian, breast, uterine and thyroid malignancies have been reported before. Cases of primary lung adenocarcinoma associated with colorectal(22%), breast(18,4%), and gastric(14,4%) neoplasms have also been illustrated. Hereditary cancer syndromes such as Lynch syndrome,Von Hippel-Lindau syndrome, Li-Fraumeni syndrome and multiple endocrine neoplasiamust be studied in this patient. Here, the available genetic tests were inconclusive and the case requires further evaluation.

Keywords: Pulmonary metastasis, Multiple primary adenocarcinomas

P2.21


Clinical Responses and Survival in Hispanic Patients vs Non-Hispanic White Patients with Non-Small Cell Lung Cancer Treated with Immunotherapy

D. Saravia1, L. Raez2, D. Sumarriva2, R. Ruiz3, T. Munoz Antonia4, B. Hunis2, D. Cress4, L. Mas3, P. Izquierdo2, D. Kaen5, S. Antonia4, G. Lopes1

1Sylvester Comprehensive Cancer Center, MIami/United States of America, 2Memorial Cancer Institute/Memorial Health Care System, Pembroke Pines/United States of America, 3National Cancer Institute (INEN), Lima/Peru, 4H. Lee Moffitt Cancer Center, Tampa/United States of America, 5Centro Oncológico Riojano Integral/Universidad Nacional de La Rioja, La Rioja/Argentina

Background: Hispanics in the US have a lower age-adjusted mortality in NSCLC and may have a different gene expression profile than NHWs. Additional data is thus needed to validate outcomes in Hispanic patients with NSCLC treated with ICIs. Our aim was to compare clinical outcomes between Hispanic and NHW patients with advanced NSCLC treated with ICIs at 5 large institutions in the US and Latin America.

Method: Retrospective clinical review on 436 Hispanic pts with advanced NSCLC that had failed at least one prior line of chemotherapy or were treated with single-agent immunotherapy as first line. Pts with actionable genetic aberrations (EGFR, ALK, and ROS-1) were excluded. Primary endpoints assessed were OS, PFS, and ORR (CR+PR) while secondary endpoint was DCR (ORR+SD).

Results: Patient characteristics are summarized in table 1. Primary endpoint results are summarized in table 2. There were no statistical significant differences seen in the secondary endpoint (DCR) among Hispanics and NHW pts.

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Table 2

Hispanics (n=256) NHW (n=180) p value

ORR

First Line 35% 30% 0.6590

Second Line 18% 19% 0.3236

Adeno 22% 24% 0.6714

SQCC 24% 23% 1.0000

PDL1 (+) 29% 32% 0.4839

PDL1 (-) 5% 17% 0.3040

Median PFS 4m 4m 0.7509

Median OS 22m 22m 0.2004

Table 1

Hispanics (n=256)

NHW (n=180)

Median age (years) 65 69

Males (%) 52 45

Line of treatment First line Second line+ Not reported

57 198 1 45 133 2

Histology Adenocarcinoma Squamous cell carcinoma Other

191 46 19 121 48 11

Conclusion: No significant differences were found in the clinical outcomes between Hispanic and NHW patients despite expected genomic differences. As expected, higher response rates were seen in first line therapy and patients with PD-L1 (+) status. These findings validate efforts in making immunotherapy more available to Hispanic patients worldwide.

Keywords: Immunotherapy, Hispanics

P2.22


Immunotherapy-related Thrombosis: Considerations and Associated Factors in Non-small Cell Lung Cancer (NSCLC) Patients

A.F. Cardona1, O. Arrieta2, A. Ruiz-Patiño3, L. Zatarain Barron4, L. Corrales-Rodriguez5, C. Martín6, F. Barrón7, C. Sotelo3, J. Rodríguez3, L. Ricaurte3, J. Ávila3, D. Mayorga3, P. Archila3, H. Freitas8, V.C. Cordeiro De Lima8, L. Mas9, J. Otero3, H. Carranza3, C. Vargas3, R. Rosell101Clinical And Translational Oncology Group,, Clinica del Country, Bogotá/Colombia, 2Thoracic Oncology Unit, Instituto Nacional de Cancerología, México City/Mexico, 3Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá/Colombia, 4Unidad Funcional de Oncología Torácica Instituto Nacional de Cancerología, Mexico City/Mexico, 5CIMCA - CCSS, San José/Costa Rica, 6Medical Oncology Department, Instituto Fleming, Buenos Aires/Argentina, 7Instituto Nacional de Cancerologia, México City/Mexico, 8Camargo Cancer Center, Sao Paolo/Brazil, 9National Cancer Institute (INEN), Lima/Peru, 10Cancer Biology And Precision Medicine Program,, Catalan Institute of Oncology, Barcelona/Spain

Background: Widespread use of immune checkpoint inhibitors (ICIs) for the treatment of lung cancer has exposed a large number of patients to these medications, increasing the incidence of rare adverse reactions such as thromboses. The present study elaborates on factors related to the occurrence of these events.

Method: In a retrospective cohort study, a total of 48 patients, 24 who experienced thrombosis and 24 matched controls who underwent evaluation after initiation of ICIs therapy for advanced/metastatic NSCLC, were included. Clinical and pathological as well as serum inflammatory and coagulation markers were evaluated.

Results: Among the 48 patients, 46% (n=26) were female, median age was 62 years old and all patients had an ECOG performance score of < 2. The median overall survival reached by the cohort was 22.47 months. Among patients who developed thrombosis there were 8 cases of deep venous thrombosis (DVT) (33%), 13 pulmonary embolisms in addition to DVT (62.5%) and 1 case of brain venous sinus thrombosis (4.2%). Apart from expected thrombosis markers such as D dimer, differences in inflammatory and immune related markers between patients who experienced thrombosis and those who did not, were observed. Abnormal values were found in the thrombosis group for B2glycoprotein 1 (33% vs 0%, OR= 4.08, [95%CI 1.65 - 12.1], p= 0.005), B2glycoprotein 1 IgG (29.2% vs 0%, OR= 4.64, [95%CI 1.73 – 16.9], p= 0.007), C Reactive protein (83.3% vs 12.5%, OR= 35, [95%CI 7.9 - 213], p< 0.001), B2microglobulin (62.5% vs 8.3%, OR= 14, [95%CI 3.11-103.7], p = 0.002), Prothrombin time (41.7% vs 4.2%, OR= 2.4, [95%CI 1.64 -3.69], p =0.01) and C Coagulation protein (50% vs 16.6%, OR =1.79, [95%CI 1.53 – 2.91], p <0.001).

Conclusion: Abnormalities in antiphospholipid antibodies, C reactive protein, B2microglobulin and coagulation in patients who suffered thrombosis during ICI treatment suggest that this phenomenon could be the result of immune and auto-inflammatory induced intravascular dysfunction.

Keywords: Immunotherapy, Thrombosis

P2.23Topic: Immunotherapy

Characterization of Hispanic Patients Who Experienced Hyperprogression During Treatment for Advanced NSCLC with Immunotherapy

O. Arrieta1, A. Ruiz-Patiño2, A.F. Cardona3, C. Martín4, L. Raez5, L. Zatarain Barron6, F. Barrón7, L. Ricaurte2, M.A. Bravo-Garzón8, L. Mas9, L. Corrales-Rodriguez10, L. Rojas3, L. Lupinacci11, F. Perazzo12, C. Bas13, O. Carranza14, C. Pupareli15, M. Rizzo16, R. Ruiz Mendoza8, C.D. Rolfo17, P. Archila2, J. Rodríguez2, C. Sotelo2, C. Vargas2, H. Carranza2, J. Otero2, L.E. Pino18, C. Ortíz3, P. Laguado3, R. Rosell191Thoracic Oncology Unit, Instituto Nacional de Cancerología, México City/Mexico, 2Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá/Colombia, 3Clinical And Translational Oncology Group,, Clinica del Country, Bogotá/Colombia, 4Medical Oncology Department, Instituto Fleming, Buenos Aires/Argentina, 5Memorial Cancer Institute/Memorial Health Care System, Pembroke Pines/United States of America, 6Unidad Funcional de Oncología Torácica Instituto Nacional de Cancerología, Mexico City/Mexico, 7Instituto Nacional de Cancerologia, México City/Mexico, 8Hospital Militar Central, Bogotá/Colombia, 9National Cancer Institute (INEN), Lima/Peru, 10CIMCA - CCSS, San José/Costa Rica, 11Hospital Italiano de Buenos Aires, Buenos Aires/Argentina, 12CEMIC, Buenos Aires/Argentina, 13Hospital Alemán, Buenos Aires/Argentina, 14Hospital Privado de la Comunidad de Mar del Plata, Mar de Plata/Argentina, 15Medical Oncology Department, Alexander Fleming, CABA/Argentina, 16Oncology, Hospital Universitario Austral, Buenos Aires/Argentina, 17University of Maryland School of Medicine, Baltimore, Mayland/United States of America, 18Fundación Santa Fe de Bogotá, Bogotá/Colombia, 19Cancer Biology And Precision Medicine Program,, Catalan Institute of Oncology, Barcelona/Spain

Background: To characterize and identify factors associated with the presentation of hyperporgression after initiation of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC).

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Method: A multicenter international retrospective study on 110 patients was conducted. Clinical variables as well as routine blood studies were recorded before initiation of treatment. Regression analysis was used to find associations. A random forest tree analysis (RFTA) based on continuous and discrete variables was used to subcategorize patients based on occurrence of hyperprogression.

Results: Median age was 64 years (Range 34-90) and 59.8 % were male patients. ECOG performance status was >1 on 8.8% of patients. Median overall survival was 12.7 months (95% CI 9.67-14 months) and progression-free survival of 4.27 months (95% CI 3.97-5.0). 44 hyperprogressors were documented (19.8%, [95%CI 14.5-25.1%]). Median time to progression was approximately 5 weeks after initiation of treatment. Factors associated included albumin and hemoglobin levels (p = 0.046 and 0.037 respectively), presence of CNS (p= 0.0009) and bone metastasis (p = 0.004) and weight loss (p= 0.004). RFTA revealed that a leucocyte count over 5.300 cells/dl was present in all hyperprogressors.

Conclusion: Hyperprogression is a phenomenon after initiation of immunotherapy which is associated with clinical and paraclinical variables. These associations could be used to withhold certain agents and prevent its occurrence in NSCLC treatment.

Keywords: Albumin, Leucocyte count, Hyperprogression

P2.24


Lung Immune Prognostic Index in Patients with Non-small Cell Lung Cancer Treated with Either Chemo or Immunotherapy

F. Barrón, B. Mota, L.A. Ramírez Tirado, L. Zatarain Barron, D. Lopez, M.P. Peralta Álvarez, O. ArrietaThoracic Oncology Unit, National Institute of Cancer, México City/Mexico

Background: The Lung Immune Prognostic Index (LIPI) is calculated prior to the initiation of treatment in patients with advanced Non-Small-Cell Lung Cancer (NSCLC). It is currently useful to stratify patients into groups that can receive a significant beneficial outcome following immune checkpoint inhibitor (ICI) therapy. The LIPI score combines the pretreatment-derived neutrophil-to-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) levels. LIPI index divides groups into a “good candidate group”, with dNLR < 3 and normal LDH; an “intermediate candidate group”, with dNLR > 3 or LDH > upper limit of normal (ULN); and a “poor candidate group”, with dNLR > 3 and LDH > ULN.

Method: In this prospective study, we decided to evaluate the prognostic value of LIPI score in pre-treated patients with advanced NSCLC treated with ICI. We included patients treated with either Pembrolizumab or Pembrolizumab plus Docetaxel, between June 2016 to May 2019 in the National Institute of Cancer, in Mexico City. LIPI index was calculated for all subjects before treatment.

Results: We included 66 patients for analysis. Median age at diagnosis was 59 years (32-83). Predominant histology was adenocarcinoma (90%), 19 (28.8%) had EGFR mutations, 27 (40.9%) were male, 36 (54.5%) were current or former smokers and 76 (97%) had a performance status of 1 or less. Among 33 patients (50%) with PD-L1 data, 15 (45.4%) had PD-L1 of at least 1% and 18 patients (54.5%) had negative results. All patients were treated with pembrolizumab, 40 patients (60.6%) as second line and 26 patients (39.4%) as the third line. The median number of cycles was 7 (1-39). Median PFS and OS were 5.1 (95% CI, 4.1-6.9) and 14.9 (95% CI, 9,6-NR) months, respectively. After calculating LIPI score, 48.4% were LIPI 0 (good prognosis), 31.8% LIPI 1 (intermediate prognosis), and 19.8% LIPI 2 (poor prognosis). Median OS for good, intermediate, and poor LIPI

was NR (95% CI, 14.9- NR), 9.6 months (95% CI, 7.5-NR) and 5.9 months (95% CI, 2.6-16.9), respectively (p=0,001).

Conclusion: Our data are consistent with prior reports in patients with NSCLC treated with PD-1 inhibitors in second or later lines of treatment and strongly suggest LIPI index can be a useful tool to identify patients which are likely to benefit from treatment with ICI.

Keywords: LIPI, Immunotherapy, Non-small-cell lung cancer, Benefit

P2.25


Immunotherapy at Any Line of Treatment Improves Survival in Hispanic Patients with Advanced Metastatic Non-small Cell Lung Cancer (NSCLC) Compared with Chemotherapy (Quijote-CLICaP) A.F. Cardona1, A. Ruiz-Patiño2, O. Arrieta3, C. Martín4, L. Raez5, L. Zatarain Barron6, F. Barrón7, L. Ricaurte2, M.A. Bravo-Garzón8, L. Mas9, L. Corrales-Rodriguez10, L. Rojas1, L. Lupinacci11, F. Perazzo12, C. Bas13, O. Carranza14, C. Pupareli15, M. Rizzo16, R. Ruiz Mendoza8, C.D. Rolfo17, P. Archila2, J. Rodríguez2, C. Sotelo2, C. Vargas2, H. Carranza2, J. Otero2, L.E. Pino18, C. Ortíz1, P. Laguado1, R. Rosell191Clinical And Translational Oncology Group,, Clinica del Country, Bogotá/Colombia, 2Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá/Colombia, 3Thoracic Oncology Unit, Instituto Nacional de Cancerología, México City/Mexico, 4Medical Oncology Department, Instituto Fleming, Buenos Aires/Argentina, 5Memorial Cancer Institute/Memorial Health Care System, Pembroke Pines/United States of America, 6Unidad Funcional de Oncología Torácica Instituto Nacional de Cancerología, Mexico City/Mexico, 7Instituto Nacional de Cancerologia, México City/Mexico, 8Hospital Militar Central, Bogotá/Colombia, 9National Cancer Institute (INEN), Lima/Peru, 10CIMCA - CCSS, San José/Costa Rica, 11Hospital Italiano de Buenos Aires, Buenos Aires/Argentina, 12CEMIC, Buenos Aires/Argentina, 13Hospital Alemán, Buenos Aires/Argentina, 14Hospital Privado de la Comunidad de Mar del Plata, Mar de Plata/Argentina, 15Medical Oncology Department, Alexander Fleming, CABA/Argentina, 16Oncology, Hospital Universitario Austral, Buenos Aires/Argentina, 17University of Maryland School of Medicine, Baltimore, Mayland/United States of America, 18Fundación Santa Fe de Bogotá, Bogotá/Colombia, 19Cancer Biology And Precision Medicine Program,, Catalan Institute of Oncology, Barcelona/Spain

Background: A significant proportion of NSCLC patients present without targetable alterations, in such case immune checkpoint inhibitors (ICIs) have become the choice of therapy. Nonetheless, the hispanic population is commonly underrepresented in the studies pertaining to these drugs. In this study we sought to compare survival outcomes of patients with advanced or metastatic NSCLC who received immunotherapy at first, second or beyond versus matched patients receiving standard chemotherapy.

Method: A retrospective multicenter international cohort study of 296 patients with unresectable/ metastatic NSCLC treated with immunotherapy either as first, second, third or fourth line was conducted. A matched comparison with a historical cohort of first line chemotherapy was conducted.

Results: Median age was 64 years (Range 34-90) and 40.2% were female patients. 91.2% of patients had an ECOG performance score ≤ 1. Immunotherapy as first line was given to 39 patients (13.7%), second line to 140 (48.8%), and as third line and beyond to 108 (37.6%). Median overall survival was 19.9 months (95% CI 14.5-22.7 months) and progression-free survival was 3.73 months (95% CI 2.8-4.2). Factors associated with increased survival included treatment as first-line (p < 0.001), type of response (p < 0.001) and PD-L1 status (p = 0.0039). Compared with the historical cohort, immunotherapy proved to be superior in terms of OS (p= 0.05) but not PFS (p= 0.2).

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Conclusion: Patients who receive immune checkpoint inhibitors as part of their treatment for NSCLC have better OS compared with matched patients treated with standard chemotherapy, regardless of treatment line.

Keywords: Immunotherapy, Survival, PD-L1

P2.26


Budget Impact Analysis of Immunotherapy as Second-line Treatment of NSCLC at Mexico’s National Institute of Cancer

L.A. Ramírez Tirado1, F. Barrón1, L. Zatarain Barron1, M.P. Peralta Álvarez1, A.A. Meneses-García1, L.M. Ruíz-Godoy1, J. De La Garza Salazar1, D.I. Palafox Torres2, M.F. Chávez Millan2, J.Á. Paladio Hernández2, A.F. Cardona3, O. Arrieta4

1Thoracic Oncology Unit, National Institute of Cancer, Mexico City/Mexico, 2Unidad De Evaluación Económica, Instituto Mexicano de Seguro Social, Mexico City/Mexico, 3Clinical And Translational Oncology Group,, Clinica del Country, Bogotá/Colombia, 4Thoracic Oncology Unit, National Institute of Cancer, México City/Mexico

Background: The highest mortality due to cancer worldwide corresponds to lung cancer (LC). Nowadays, novel therapeutic strategies such as Immune Checkpoint Inhibitors (ICI), have dramatically improved overall survival (OS), progression-free survival (PFS), and quality of life as the first or second line of treatment in patients with NSCLC. The objective of this study is to estimate the budget impact of immunotherapy as a second-line treatment for advanced NSCLC.

Method: A retrospective, descriptive analysis on resource use and a direct medical cost analysis was performed to assess the budget impact of 60 patients treated with immunotherapy as second-line treatment of NSCLC conducted at the National Institute of Cancerology (INCAN) in Mexico during 2016-2018. Resource utilisation data were collected by means of medical records. The costs associated with the total costs of treatment were estimated as a mean value with confidence intervals of 95% confidence by costing the elements of the treatment of the disease and adverse events, as well the frequency of consultations, hospital stays, and monitoring obtained in the records. Costs are presented in US dollars.

Results: The total mean monthly treatment cost was $1,649 (95% confidence interval [CI] = $1,484–$1,814), of which 93.8% represented immunotherapy costs, 5.4% drug application and monitoring, 0.8% adverse events treatment. We identified 30 potential patients per year candidates to receive immunotherapy as the second line. From which the expected costs of treatment will be $49,476 [CI] = $44,528–$57,392), of which $41,766 are immunotherapy costs, application and monitoring represent $2,400 and the rest for adverse events.

Conclusion: The therapeutic approach for the second-line treatment of patients with advanced NSCLC without actionable mutations has been revolutionized by the approval of new more efficacious drugs like pembrolizumab. Healthcare costs during immunotherapy treatment with pembrolizumab were largely attributed to anti-cancer therapy and less for adverse events. Pembrolizumab as second-line treatment of patients with advanced non-small-cell lung cancer, prolong overall survival, leading to fewer adverse events than chemotherapy.

Keywords: Pharmacoeconomy, Immunotherapy, Costs, Pembrolizumab

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Author Index

AAbbas Jad ...................................................................................................P2.13Abubakar Mustapha .......................................................................... P1.08-AAcevedo, Angela Maria .............................................................................. I.3Acosta Haab Gabriela ...............................................................................P1.11Acosta Luciana ...........................................................................................P1.18Agrawal Shruti ...........................................................................................O.02Aguilar Alfredo .........................................................................................P2.01Aguirre Marisol ......................................................................................... P2.16Alatorre Alexander Jorge ........................................................P2.10, P2.14Alcázar-Ramos Alejandra Guadalupe ................................P1.06, P1.07Alessandro Riccardo ................................................................................P1.17Alexander Meza José ............................................................................P2.04Alexandrov Ludmil ............................................................................. P1.08-AAmendola, Beatriz ......................................................................................I.15Amorin Edgar ..........................................................................................P2.05Anikin Vladimir .......................................................................................... P1.21Antonia Scoot J ........................................................................................O.02Antonia Scott ............................................................................................ P2.21Arauchan Sandra .................................................................................P2.15-AArchila Pilar .......................................................PD1.05, P1.10, P1.12, P2.22, ........................................................................ P2.23, P2.25, PD2.03, PD2.06Ardizzoni Andrea ................................................................................... P2.02Arora Arshia .............................................................................................P2.06Arrieta Oscar .............I.9-1, P1.08-A, P1.10, P1.12, P1.20, P2.03, P2.04,................................P2.22, P2.23, P2.24, P2.25, P2.26, PD2.03, PD2.06Asadi Nizar ................................................................................................. P1.21Ávila Jenny .......................PD1.05, P1.10, P1.12, P2.22, PD2.03, PD2.06

BBáez Saldaña Renata ..........................................................................P1.16-ABals Sara .......................................................................................................P1.17Barajas Olga ..........................................................................................P2.15-ABarata Fernando ........................................................................................P2.11Barboza Quintana Oralia ..............................................P1.01, P1.02, P1.03Barrios-Bernal Pedro .............................................................................P1.20Barrón Feliciano................................PD1.05, P1.10, P1.12, P2.03, P2.22, .............................................P2.23, P2.24, P2.25, P2.26, PD2.03, PD2.06Bas Carlos ....................................................................................P2.23, P2.25Basher Fahmin ........................................................................................P2.06Bautista Yolanda ...................................................................I.1-1, I.1-2, O.02Beddow Emma .......................................................................................... P1.21Bender Shaun .......................................................................................... P2.02Bengio V .................................................................................................P2.15-BBerrios Mejia Juan Alberto ...............................................................P1.16-ABertadillo-Jilote Alma Delia ................................................................P1.06Berutti Susana ......................................................................................P2.15-ABhandari Shruti .....................................................................................PD1.02Bischoff Helge G. .....................................................................O.03, PD2.02Blake, Monika ................................................................................................. I.4Blanco Carolina .......................................................................................P2.04Block, Mark ....................................................................................................I.14Blumenschein George R. ..................................................................PD2.04Bogart Jeffrey ......................................................................................... P1.09Bolaños Morales Francina ..................................................................... P1.16Bonilla Carlos ........................................................................................P2.15-ABotero Ana .............................................................................................PD1.06Boyer Michael ...........................................................................O.03, PD2.02Brahmer Julie .............................................................................................O.02Bravo-Garzón Maria A. ............................................................P2.23, P2.25Bravo Melissa .................................................................................. P1.10, P1.12Buenaventura Daisy C. .......................................................................... P1.25Bunn Jr., Paul A. ...........................................................................................I.18Burgio Marco A .........................................................................................O.02Butts Charles .............................................................................................O.02

CCabada, German ................................................................................ I1.-1, I.1-2Cabero Octavio .......................................................................................P2.05Cabrera Luis .............................................................................................P2.03

Calderon Camilo A.................................................................................. P2.19Calha Jaime ................................................................................................P2.15Calvinho Paulo ..........................................................................................P2.15Campos-Gomez Karen .......................................................................PD1.03Campos-Gomez Saul ..........................................................................PD1.03Cañas Yuliana............................................................................................ P1.23Canigiani M ............................................................................................P2.15-BCardellino Anna ...................................................................................PD2.02Cardona Andrés F. ............................ PD1.05, P1.10, P1.12, P2.03, P2.22, ..........................................................P2.23, P2.25, P2.26, PD2.03, PD2.06Carranza Hernán .................................PD1.05, P1.10, P1.12, P2.22, P2.23, ..................................................................................... P2.25, PD2.03, PD2.06Carranza Omar ...........................................................................P2.23, P2.25Carrillo Vidales Javier .............................................................................P2.17Castellon Ignacio ..................................................................................PD1.06Castillero Franklin ..................................................................................P2.08Castillo Miguel .......................................................................................PD1.06Castillo Omar ................................................................................P1.13, P2.08Castro Andres ........................................................................................... P1.22Castro-Bernardini, Socorro ...................................................................... I.10Chávez Millan Marisa Florentina ....................................................... P2.26Cheng Susanna Yee-Shan ....................................................O.03, PD2.02Chen Jingjing ..............................................................................................O.01Chiappori Alberto ...............................................................................PD2.04Chirinos Luis ..............................................................................................P2.01Cho In Young .........................................................................................PD1.01Chow Laura Q M .......................................................................................O.02Christiani David ................................................................................... P1.08-AClaes Nathalie .............................................................................................P1.17Clingan Philip ........................................................................................PD2.02Cobo Manuel ............................................................................................ P2.02Colín-González Ana Laura ...................................................................P1.20Corassa Marcelo............................................................................. P1.10, P1.12Cordeiro De Lima Vladmir Cláudio ....................... PD1.05, P1.10, P1.12,......................................................................................P2.22, PD2.03, PD2.06Corrales-Rodriguez Luis .................. PD1.05, P1.10, P1.12, P2.03, P2.13,.......................................................... P2.22, P2.23, P2.25, PD2.03, PD2.06Correia Joana Batista .............................................................................P2.11Cotta Jared ...............................................................................................P2.06Cress Doug ................................................................................................ P2.21Crino Lucio .................................................................................................O.02Crismatt Alejandro .....................................................................P1.13, P2.08Cseh Agnieszka .......................................................................................P2.02Cuello Mauricio ......................................................................P2.09, P2.15-ACufer Tanja .............................................................................................PD2.05Cundom Juan .......................................................................................P2.15-ACustódio Catarina ......................................................................P1.05, P2.15

DDalurzo Liliana ..........................................................O.04, I.1-3, P1.11, P1.19Danenberg Kathleen ...........................................................................PD2.01Danenberg Peter ..................................................................................PD2.01De Angelis Flávia .................................................................................PD2.02De La Garza Salazar Jaime ................................................................. P2.26Delgado Lucia .........................................................................................P2.09Demellis Gabriela .......................................................................................P1.11De Miguel-Pérez Diego ...........................................................................P1.17Denlinger Crystal S .............................................................................P2.15-CDesai Jayesh .........................................................................................P2.15-CDiaz De Arce Heidy ................................................................................. P1.19Domine Manuel ....................................................................................PD2.02Domingo Gelenis ..................................................................................PD2.01Dresler Carolyn ............................................................................................. I.9Drilon Alexander .......................................................................................O.02Durm Greg .............................................................................................P2.15-C

EEkesi Onyinye Emmanuella .................................................................P1.04Enriquez Daniel ........................................................................................P2.01Esteban Emilio..........................................................................O.03, PD2.02

FFakih Marwan G ...................................................................................P2.15-CFalchook Aaron .....................................................................................PD1.06

PRESENTATIONS HIGHLIGHTED IN BOLD = PRESENTING AUTHOR FOR THIS ABSTRACT

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Falchook Gerald S ...............................................................................P2.15-CFalcoff Nora ..................................................................................................P1.11Fanfan Dino ..............................................................................................P2.06Felip Enriqueta ............................................... O.03, O.04, P2.02, PD2.02Felizardo Margarida ...................................................................P1.05, P2.15Fernandez-Trujillo Liliana .............................P1.22, P1.23, P1.24, P1.25, .............................................................................................. P2.16, P2.18, P2.19Ferreira Amanda ..................................................................................... P2.07Ferreira Carlos Gil ......................................................................P1.26, P2.07Ferreira Gimena .........................................................................................P1.18Figueiredo Ana ..........................................................................................P2.11Figueroa-Corona María Del Pilar .......................................... P1.06, P1.07Finch Jonathan ......................................................................................... P1.21Flores Claudio J. ......................................................................................P2.01Flores Gutiérrez Juan Pablo ......................................P1.01, P1.02, P1.03Flores Soto Maria Del Rosario ............................................................ P2.10Fraga Gisele ............................................................................................. P2.07Franco Cortes Claudia Alejandra ....................................................... P1.19Freitas Helano .................PD1.05, P1.10, P1.12, P2.22, PD2.03, PD2.06Furtado Sofia ................................................................................P1.05, P2.15

GGadgeel Shirish ........................................................................O.03, PD2.02Gajra Ajeet .................................................................................................P1.09Galvez-Nino Marco ................................................................................P2.05Garassino Marina C. .................................................... O.02, O.03, PD2.02Garcia Bazan Eric Marco ....................................................................... P1.14Garcia-Closas Montse ....................................................................... P1.08-AGarcia Cocco Virginia ........................................................................P2.15-AGarcía-Gutiérrez David Gustavo ........................................................P1.06Garcia Juan E. ........................................................................................... P1.25García-Mantilla Pedro ................................................................................I.10Garcia Marileila Varella .......................................................................... O.04García-Mejía Karla Liliana ........................................................P1.06, P1.07Garon Edward B. .....................................................................O.03, PD2.02Garza Guajardo Raquel .................................................P1.01, P1.02, P1.03Georgoulias Vassilis ............................................................................... P2.02Gerson Raquel .........................................................................................P2.04Gettinger Scott .........................................................................................O.02Getz Gaddy .......................................................................................... P1.08-AGil-Bazo Ignacio ........................................................................................ I.20Gittens Allison ............................................................................................O.01Göker Erdem ............................................................................................ P2.02Gómez Alvaro .......................................................................................P2.15-AGonçalves Imanuely Borchardt ............................................ P1.26, P2.07Goncalves Susana ...............................................................................P2.15-AGordenin Dmitry ................................................................................. P1.08-AGoss Glenwood D. .................................................................................. P2.02Govindan Ramaswamy .....................................................................P2.15-CGray Jhanelle E. ...................................................................................PD2.02Grossi Francesco .................................................................................PD2.02Gucalp Rasim ........................................................................................PD2.05Guerrero Ixtlahuac Jorge .........................................................................I.12Guillen Maria ............................................................................................P2.05Guman Gabriela ..........................................................................................P1.11Gunasekaran Muthukumar .....................................................................P1.17

HHalmos Balazs ......................................................................................PD2.05Han Kyungdo ..........................................................................................PD1.01Hao Desiree ...........................................................................................PD2.05Harrow Kim ............................................................................................PD2.04Henary Haby ........................................................................................ P2.15-CHernández Marisol Arroyo ................................................................ I.2, I.11Hernandez Patricia ...................................................................................P1.18Hernández-Carlos Beatriz .................................................................... P1.07Hernandez-Pedro Norma .....................................................................P1.20Hirai Kyoji ...............................................................................................PD1.04Hirsch Fred ........................................................................................I.17, O.04Hochmair Maximilian J. ........................................O.03, PD2.02, PD2.05Hofman Paul ......................................................................................... P1.08-AHolzhausen Allison .............................................................................PD2.04Hong David S ........................................................................................P2.15-CHorn Leora .................................................................................O.02, PD2.04Hossein Borghaei .....................................................................................O.02

Howell Kristin .............................................................................................O.04Hui Rina .......................................................................................O.03, PD2.02Hunis Brian..................................................................P2.21, PD1.06, PD2.01

IIotti Alejandro ..............................................................................................P1.11Iriarte Maria B. ...........................................................................................P2.18Isla Dolores ............................................................................................... P2.02Iyengar Puneeth ..........................................................................................I.16Izquierdo Paola ........................................................................................ P2.21

JJaimes Yolanda .....................................................................................PD2.01Jauk Federico ............................................................................................ P1.19Jennens Ross R. ...................................................................................PD2.02Jian Hong .................................................................................................. P2.02

KKaen Diego ................................................................................................ P2.21Kaushal Sunjay ...........................................................................................P1.17Kazakova Ekaterina ...............................................................................P2.04Kerr Keith ....................................................................................................O.04Kim Edward ................................................................................................O.04Kloecker Goetz .................................................................................... PD1.02Korbenfeld Erneston ..........................................................................P2.15-AKrauss John C .......................................................................................P2.15-CKumar Rohit ...........................................................................................PD1.02Kuo James C .........................................................................................P2.15-CKurata Takayasu .......................................................................O.03, PD2.02

LLabanca María José ...................................................................................P1.11Laguado Paola ...........................................................................P2.23, P2.25Landi Maria Teresa ............................................................................. P1.08-ALantuejoul Sylvie ......................................................................................O.04Lashbrook Mari ........................................................................................P1.27Lazaro Miguel ..........................................................................................P2.04Leal Ticiana ........................................................................................... PD2.04Lee Ki Hyeong ......................................................................................... P2.02Legarda Emily........................................................................................... P1.23Leguina Laura ..............................................................................................P1.11Leticia Solano Nieto Alma ........................................................ P1.16, P2.17Li Ang ...........................................................................................................O.02Li Bob T ...................................................................................................P2.15-CLi Hsin ..........................................................................................................P1.09Lira-De León Karla Isabel ........................................................ P1.06, P1.07Li Wei .......................................................................................................... P2.02Lopes Gilberto .............................................................................P2.06, P2.21Lopez Diego ............................................................................................. P2.24Lopez-Bigas Nuria ............................................................................. P1.08-ALópez Reséndiz Karina Elyane ...................................P1.01, P1.02, P1.03Lores Juliana ............................................................................................. P2.16Lozano Sophia ................................................................................ P1.10, P1.12Lupinacci Lorena .......................................................................P2.23, P2.25Lu Shun ...................................................................................................... P2.02

MMadureira Rosa .........................................................................................P2.15Maldini C .................................................................................................P2.15-BMaquera Grisnery ...................................................................................P2.05Marcelo Horacio ...................................................................................P2.15-AMareco Karen ...........................................................................................P2.09Marmolejo Torres Maria Esther ......................................................P1.16-AMärten Angela ......................................................................................PD2.05Martín Claudio .......................PD1.05, P1.10, P1.12, P2.03, P2.22, P2.23, ....................................................................P2.25, P2.15-A, PD2.03, PD2.06Martinez Herrera Jose Fabian ............................................................ P2.14Martín María Eugenia ................................................................................P1.11Mas Luis ...................... PD1.05, P1.10, P1.12, P2.01, P2.05, P2.21, P2.22,....................................................................... P2.23, P2.25, PD2.03, PD2.06Mathias Clarissa ............................................................................... I.21, O.04Mayorga Diana ................PD1.05, P1.10, P1.12, P2.22, PD2.03, PD2.06Mccusker Michael ......................................................................................O.01


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Mehra Ranee ...............................................................................................O.01Mendez Alejandra ...................................................................................P2.13Mendoza Laura ....................................................................................P1.08-A Meneses-García Antelmo Abelardo ................................................ P2.26Meraz-Ríos Marco Antonio ..................................................... P1.06, P1.07Midence Arguello Maria Jose ..............................................................P2.17Minatta Jose Nicolás ............................................................................... P1.19Min Young J. ............................................................................................. P2.02Miranda Yesenia ......................................................................................P2.05Molina Matias ..............................................................................................P1.18Montella Tatiane ..........................................................................P1.26, P2.07Morabito Alessandro ............................................................ P2.02, PD2.05Morales Eliana I. ......................................P1.22, P1.24, P1.25, P2.18, P2.19Mora María Florencia ................................................................................P1.11Moreira Gisele ...........................................................................................P1.26Moreno Joan ............................................................................................P2.05Morrow Phuong Khanh .....................................................................P2.15-CMota Beatriz ............................................................................................. P2.24Munoz Antonia Teresita ........................................................................ P2.21

NNajera Ramirez Rubisela........................................................................P2.17Neal Joel W............................................................................................PD2.04Ngang Jude ...........................................................................................P2.15-CNgarmchamnanrith Gataree ...........................................................P2.15-CNovello Silvia.........................................................................................PD2.02Nuñez German ................................................................................... I.1-1, I.1-2

OOfonakara Uzochukwu ......................................................................... P1.04Olivera Mivael ..........................................................................................P2.05Olmedo Gloria .............................................................................................P1.11Orellana Eric ..........................................................................................P2.15-AOrlandi Francisco ................................................................................P2.15-AOrozco-Morales Mario .......................................................................... P1.20Ortega Leandro Nahuel ......................................................................... P1.19Ortíz Carlos .................................................................................P2.23, P2.25Otero Jorge ..........................................PD1.05, P1.10, P1.12, P2.22, P2.23, ..................................................................................... P2.25, PD2.03, PD2.06Otterson Gregory .....................................................................................O.02Oxnard Geoffrey R. .............................................................................PD2.04

PPacheco-Cuellar Guillermo .............................................................. PD1.03Paladio Hernández José Ángel ......................................................... P2.26Palafox Torres David Isai ..................................................................... P2.26Paradelo Martin ..........................................................................................P1.18Patane Ana Karina ........................................................................ P1.10, P1.12Patel Sandip P. ......................................................................................PD2.04Peikert Tobias ...................................................................................... P1.08-APeled Nir .....................................................................................O.03, PD2.02Peña Gomez Portugal Emmanuel .........................................P1.16, P2.17Penrod Jonh R ...........................................................................................O.02Peralta Álvarez Marco Polo ..................................... P2.03, P2.24, P2.26Perazzo Florencia......................................................................P2.23, P2.25Pereira-García Ariana ...........................................................................P2.03Peres Wilza ............................................................................................... P2.07Perez Alejandro ......................................................................................P2.09Perez Bladimir ...........................................................................................P2.18Perez Mario .......................................................................................... I.1-1, I.1-2Pérez-Ramírez Iza Fernanda ...............................................................P1.06Perikleous Periklis ....................................................................................P1.21Perroud Hernan ....................................................................................P2.15-APichardo Meneses Ofelia .......................................................................P2.17Pietanza M. Catherine ............................................................O.03, PD2.02Piñeiro Natalia .........................................................................................P2.09Pilnik Norma ......................................................................................... P2.15-BPino Luis Eduardo .....................................................................P2.23, P2.25Pintelon Isabel ............................................................................................P1.17Planchard David........................................................................................O.02Pluzanski Adam ........................................................................................O.02Poleri Claudia ..............................................................................................P1.11Porras Gutiérrez Rebeca .......................................................................P2.13Postmus Pieter ..........................................................................................O.04Powell Charles ...........................................................................................O.04

Powell Steven ............................................................................................O.03Powell Steven F. ...................................................................................PD2.02Price Timothy J ....................................................................................P2.15-CPucci Marzia ................................................................................................P1.17Pupareli Carmen ........................................................................P2.23, P2.25

RRaez Luis E. ............I.13-1, I.18-1, P2.21, P2.23, P2.25, PD1.06, PD2.01Ramalingam Suresh.....................................................................O.02, O.04Ramirez Candelas Miguel Angel .........................................................P2.12Ramírez Tirado Laura Alejandra ......................................... P2.24, P2.26Rasmussen Erik ....................................................................................P2.15-CRayá Mercedes ............................................................................................P1.11Reckamp Karen L. ...............................................................................PD2.04Reck Martin................................................................................O.03, PD2.02Reclusa Pablo .............................................................................................P1.17Recondo Gonzalo................................................................................P2.15-AReginatto Atilio ...........................................................................................P1.11Reinhold Florencia ..............................................................................P2.15-ARemon Jordi .................................................................................... P1.10, P1.12Ricaurte Luisa ....... P1.10, P1.12, P2.22, P2.23, P2.25, PD2.03, PD2.06Richardet Eduardo ...................................................................................P1.18Richardet Martin ........................................................................................P1.18Richeimer Kristin ......................................................................................O.04Rioja Patricia ................................................................................... P1.10, P1.12Rivera Rivera Samuel ............................................................................P2.04Rizzo Manglio .............................................................................P2.23, P2.25Rodríguez-Abreu Delvys ..................................................... O.03, PD2.02Rodríguez July ....................................PD1.05, P1.10, P1.12, P2.22, P2.23, ..................................................................................... P2.25, PD2.03, PD2.06Rodriguez Palleiro Maria Clara ..........................................................P2.09Rojas Leonardo ..........................................................................P2.23, P2.25Rojas Victor ................................................................................. P2.01, P2.05Rolfo Christian Diego........................................O.01, P1.17, P2.23, P2.25Roque Katia ..............................................................................................P2.05Rosell Rafael ................................I.19, PD1.05, P1.10, P1.12, P2.22, P2.23, ..................................................................................... P2.25, PD2.03, PD2.06Rothberg Bonnie ................................................................................ P1.08-ARubio-Viqueira Belén .........................................................................PD2.02Ruiz-Godoy Luz María ..............................................................P1.20, P2.26Ruiz Mendoza Rossana ...........................................................P2.23, P2.25Ruiz-Patiño Alejandro ...................................PD1.05, P1.10, P1.12, P2.22, ........................................................................ P2.23, P2.25, PD2.03, PD2.06Ruiz Rossana .........................................................P1.10, P1.12, P2.05, P2.21Russo Alessandro ......................................................................................O.01

SSacramento Vânia .......................................................................P1.05, P2.15Salas-Coronado Raúl ............................................................................. P1.07Sanchez Garcia Ramos Emilio .............................................................P2.17Sánchez Reyes Roberto .......................................................................P2.03Sánchez Ríos Carla Paola ...........................................P2.10, P2.12, P2.14Sanchez Santiago ................................................................................... P1.24Santamaría Abel ......................................................................................P1.20Santos-Sánchez Norma Francenia ................................................... P1.07Saravia Diana ..............................................................................P2.06, P2.21Scagliotti Giorgio .....................................................................................O.04Schwarz Luis J. .........................................................................................P2.01Scilla Katherine A. .....................................................................................O.01Selvaggi Giovanni................................................................................PD2.04Sena Susana ..........................................................................................P2.15-AShin Dong Wook ...................................................................................PD1.01Silva Alejandro ........................................................................................P2.04Smeltzer Matthew ....................................................................................O.04Soong Deborah .......................................................................................P2.06Soo Ross A. ...............................................................................O.04, PD2.05Soria Tannia ..................................................................................... P1.10, P1.12Sotelo Carolina ....................................PD1.05, P1.10, P1.12, P2.22, P2.23, ..................................................................................... P2.25, PD2.03, PD2.06Sowley Taysser ............................................................................P1.13, P2.08Speranza Giovanna .................................................................O.03, PD2.02Strickler John H ...................................................................................P2.15-CSua Luz.............................. P1.22, P1.23, P1.24, P1.25, P2.16, P2.18, P2.19Sumarriva Daniel ......................................................................P2.21, PD2.01Syrigos Konstantinos ............................................................................ P2.02


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TTanny Sean.................................................................................................P1.09Taverna Simona ..........................................................................................P1.17Taylor Meghan ...........................................................................................O.04Thibodeau Ryan .......................................................................................P1.09Tsuboi Masahiro ........................................................................................O.04Turcott Jenny ................................................................................................. I.5

UUgalde-Villanueva Brenda ...................................................................P1.06Usher Joshua .........................................................................................PD2.01Usuda Jitsuo ..........................................................................................PD1.04

VValdéz-Andrade Juan Jesús .............................................................PD1.03Valdivieso Natalia ...................................................................................P2.05Varela Santoyo Edgar ...........................................................................P2.03Vargas Carlos .......................................PD1.05, P1.10, P1.12, P2.22, P2.23, ..................................................................................... P2.25, PD2.03, PD2.06Varella-Garcia, Marileila ............................................................................I.13Vasconcellos Juliana .................................................................P1.26, P2.07Vega-Rodríguez Ana Laura ................................................................. P1.07Vela Nieto Miryana Perez .......................................................................... I.8Velasquez Mauricio .....................................................................P1.24, P2.18Verstraelen Peter .......................................................................................P1.17Vilches Cisneros Natalia ...............................................P1.01, P1.02, P1.03Villa Antonio .............................................................................................P2.04

WWakelee Heather ........................................................................I.21, PD2.04Wang Lara ..............................................................................................PD2.05Waqar Saiama N. .................................................................................PD2.04Wedge David ....................................................................................... P1.08-AWerbach Andrea ........................................................................................P1.11William William ...........................................................................................I.22Wistuba Ignacio ............................................................................I.12-1, O.04Wojcik-Tomaszewska Joanna ..............................................................O.02Wood Kelsey ..............................................................................................O.04Wynes Murry ..............................................................................................O.04

YYang Cheng-Ta .....................................................................................PD2.05Yang James C-H ..................................................................................PD2.05Yang Jing ....................................................................................O.03, PD2.02Yu Yongfeng ............................................................................................. P2.02

ZZapata Marcos ......................................................................................P2.15-AZatarain Barron Lucia ....................................PD1.05, P1.10, P1.12, P2.03, ................................P2.22, P2.23, P2.24, P2.25, P2.26, PD2.03, PD2.06Zavala Retes Benjamin ...........................................................................P1.14Zervino Ignacio ..............................................................................................I.7Zhang Tongwu .................................................................................... P1.08-AZhang Yu ................................................................................................... P1.08Zhou Joey ..............................................................................................PD2.04Zimmermann, Camilla ................................................................................ I.6Zuloaga Carlos ........................................................................................P2.04


LUNG CANCER NEWSThe IASLC Lung Cancer News, the IASLC’s bi-monthly newspaper, features the latest information on lung cancer research, patient care, tobacco control, expert commentary from lung cancer thought leaders around the world and more.

Look for the IASLC Lung Cancer News in your delegate bag or pick up a copy at the IASLC Booth in the Exhibit Hall.

LungCancerNews.org

INTERNATIONALASSOCIATION FOR THE STUDY OF LUNG CANCER Conquering Thoracic Cancers Worldwide

THIS IS A MEMBER BENEFIT!

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MEMBERSHIP OFFER We’re more than 7,500 strong! Won’t you join us? Take advantage of this great value now!

Here are just some of the benefits you’ll receive when you become an IASLC member:

• Member access to the Journal of Thoracic Oncology

• Discounts to the IASLC World Conference on Lung Cancer and other scientific meetings

• Opportunity to make an impact by participating on IASLC member committees

• Access to the IASLC member directory

To learn more about levels of membership and benefits, visit: www.iaslc.org/membership.

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JTO Impact Factor

increases to

12.460!Ranked 10th among 229

oncology journals.

Ranked 3rd among 63 respiratory medicine

journals

JTO is the #1 journal focused on disseminating research and therapy of thoracic malignancies,

according to Editor-in-Chief, Alex A. Adjei, MD, PhD

Two things to note about reported IFs: 1) the IF is reported for the previous year (2018 IF is reported

in 2019) and 2) the IF is always reported to the third decimal point, even if it is a zero


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IASLC 2020Meetings Schedule

Sixth AACR-IASLC International Joint Conference: Lung Cancer

January 11-14, 2020 | San Diego, CA | #Lung20

IASLC 2020 Targeted Therapies of Lung Cancer

February 19-22, 2020 | Santa Monica, CA #TTLC20

European Lung Cancer Congress 2020

April 15-18, 2020 | Geneva, Switzerland #ELCC20

Lung Cancer Hot Topic: Liquid Biopsy

May 2020

IASLC 2020 World Conference on Lung Cancer

August 9-12, 2020 | Singapore | #WCLC20

IASLC 2020 North America Conference on Lung CancerOctober 15-17, 2020 | Chicago, IL

#NACLC20

Lung Cancer Hot Topic: Immunotherapy

November 2020

HOPELIVES

Help us fight stigma and spread HOPE! Whether you are a patient, caregiver, advocate or

physician, YOU can take action to contribute to Lung Cancer Awareness Month.

Additional support by independent educational grants from Takeda and AstraZeneca The IASLC is a proud partner of the LCAM Coalition

How to spread HOPEShare or download resources: LCAM.org/resources | LCAM.org/share-your-story

Connect on social media:

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MORE RESEARCH. MORE SURVIVORS.

The LCAM Coalition is supported by over 40 partner organizations from around the world. Key focus topics:

• Clinical Trials• Precision Medicine

• Screening & Early Detection• Advocacy

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2019 Latin America Conference on Lung Ca ncer · IASLC 2019 Latin America Conference on Lung Cancer...

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