ESMO SUMMIT MIDDLE EAST 2018Clinical Case Presentation

Shailesh V. Shrikhande, MS, MD, FRCS (Hon)

Chief, GI and HPB Surgery

Professor & HOD Surgical Oncology

Tata Memorial Centre, Mumbai, India

6-7 April 2018, Dubai, UAE

CONFLICT OF INTEREST DISCLOSURE

Honorarium received by Tata Memorial Hospital

Covidien, IRCAD Meeting 2016, Taiwan

Johnson & Johnson, Gastric Advisory Council 2015, Seoul, Korea

Merck Serono, Asia Pacific mCRC Meeting 2015, Singapore

EXPERT PANEL

Josep Tabernero, Medical Oncologist

Marwan Ghosn, Medical Oncologist

Syed M. Hasnain, Radiation Oncologist

Mohsen Mokhtar, Medical Oncologist

Eric Van Cutsem, Medical Oncologist

Fortunato Ciardiello, Medical Oncologist

CASE 1: HISTORY (OCTOBER 2016)

50 year old gentleman

Diabetic on Rx – 5 yrs

Presented with abdominal pain – 1 month

H/o 10 kg LOW – over 3 months

Clinical examination

Vitals stable, no icterus

ECOG 1

PA - large palpable mass 8x6 cm in Right hypochondrium

PR - no growth

EVALUATION

USG abdomen and pelvis:

Large GB mass infiltrating liver

Hb: 16 gm%

Liver Functions:

Bilirubin 0.5 mg%

Albumin 4.3 mg%

Liver Enzymes - WNL

ROLE OF TUMOR MARKERS?

S. CA 19.9 : 44960.0 units

S. CEA: 169.71 units

TUMOR MARKERS

CEA: Specificity 90%; Sensitivity only 50% when used for screening

CA 19-9: Sensitivity and specificity 75%

Minimal clinical value compared with clinical awareness but useful for follow up

NEXT MODE OF EVALUATION?

A. Contrast enhanced CT scan

B. MRI

C. PET

INVESTIGATIONS

CECT abdomen (October 2016)

Large enhancing lesion involving GB & extending into liver seg IVa, IVb & V

Loss of fat plane with hepatic flexure of colon

Multiple portal & portocaval nodes largest 1.7 X 1.5cm

Solitary pulmonary millimetric nodule in right upper lobe ant seg - indeterminate

ROLE OF PET SCAN?

LOF plane with duodenum and

colon

Enhancing mass lesion in

relation to GB fossa

Peripherally Enhancing lesion Central necrosis

PET CT (25.11.2016)

Peripherally enhancing centrally necrotic bulky soft tissue mass measuring 6.9 x

6.1 x 7.3 cm is noted in the right lobe of liver

Loss of fat planes with hepatic flexure and duodenum with perilesional nodules

GB cannot be differentiated separately from the mass

Low grade FDG avid peripancreatic and portocaval nodes are noted measuring 9

mm with a max SUV of 6.52

ROLE OF STAGING LAPAROSCOPY?

A. YES

B. NO

STAGING LAPAROSCOPY

Most CA GB patients do not require palliative operations, and incidence of

occult metastatic disease is high and hence staging laparoscopy makes

sense

Yield is as high as 48% (Weber et al, 2002)

Even in patients who had prior simple cholecystectomy, yield is as high as

20% and is indicated

STAGING LAPAROSCOPY (16.11.2016)

No evidence of peritoneal / omental liver metastases

Hepatic flexure of colon and duodenum adherent to GB; no frank infiltration

MANAGEMENT PLAN ?

A. Radical Curative Surgery

B. Neoadjuvant chemotherapy and reassess for Surgery

C. Neoadjuvant chemoradiotherapy and reassess for Surgery

D. Palliative treatment options

DO WE NEED A BIOPSY?

USG guided GB mass (03.11.2016)

Moderately differentiated adenocarcinoma

ROLE OF CHEMOTHERAPY AND RADIOTHERAPY IN

GB CANCERS

Is there any strong evidence or recommendation ?

Should we routinely use neoadjuvant treatment in Ca GB ?

What are the indications for neoadjuvant treatment?

ON-GOING TRIAL AT TATA MEMORIAL

In POLCA-GB trial - CTRT arm (NCT02867865)

Received EBRT to GB tumor mass to a dose of 52Gy/25#/35 days - SIB technique

Remaining PTV 45gy/25# using 6MV photons with Intensity Modulated Arc technique from

6/12/16 to 9/1/17

Along with 5 cycles of concurrent Gemcitabine on 06-12-2016, 13-12-2016, 20-12-2016, 27-

12-2016 and 03-01-2017.

Received 2# Gem - Cis (LD 21.2.2017)

CT Abdomen (14.03.2017)

Residual lesion in GB fossa with liver infiltration- SD

Episode of hematemesis on 9th March at home

UGI Endoscopy (11.03.2017)

Acute ulcer in the bulb of duodenum

UGIE (07/04/17)

Diffuse erythema in antro-pyloric region

Small superficial ulcer 0.5 x 0.5 with clean base in pre-pyloric region

Duodenum: D1 and D1-D2 junction showed infiltrated mucosa and erythema.

D2-Normal. No active bleeding.

Response assessment PET (12/04/2017)

Significant decrease in the size and metabolic activity of the GB fossa mass and LN with

residual viable disease; Metabolic activity of Right SCF node

Right SCF FNAC

Necrotizing granulomatous inflammation, suggestive of tuberculosis.

Malignant cells not seen

FURTHER PLAN?

A. Continue chemotherapy

B. Assess for Surgery

Started on ATT (April 2017)

After 1 month of ATT posted for Surgery

Plan:

Radical Cholecystectomy with Distal Gastrectomy

Underwent Radical Cholecystectomy with Distal Gastrectomy, D1 resection with

ante-colic Gastro-jejunostomy on 12.05.17

Intraoperative findings

➢GB mass fistulized in D1

➢No colonic involvement

➢Peri-portal and porto-caval nodes

➢Inter-aortocaval nodes negative on FS

Recovered uneventfully except for serous discharge with prolonged drain for 2 weeks

HISTOPATHOLOGY

No residual viable tumor

Cystic duct margin: free of tumor

Gastric and duodenal margin: free of tumor

Lymph nodes: 6 negative nodes

ADJUVANT TREATMENT

3# Gemcitabin + Cisplatin

ABC 02 TRIAL

ADJUVANT CAPECITABINE FOR BILIARY TRACT CANCER:

THE BILCAP RANDOMIZED STUDY.

Conclusion:

Cape improves OS in BTC when used as adjuvant and should become standard of care.

FOLLOW UP

Asymptomatic at last follow up

Normal tumor markers

USG A+P: No e/o disease

Future Oncology 2015

HPB 2018 (ARTICLE IN PRESS)

CHAUDHARI V, SHRIKHANDE SV, GOEL M ET AL.

OUTCOME OF NEOADJUVANT CHEMOTHERAPY IN “LOCALLY ADVANCED/BORDERLINE

RESECTABLE” GALLBLADDER CANCER: THE NEED TO DEFINE INDICATIONS.

Proposes clinico-radiologic criteria to define borderline resectable / locally advanced GBC

160 consecutive patients (2010 to 2016)

Chemotherapy with neoadjuvant intent in locally advanced/borderline resectable GBC showed

good response rates (clinical benefit rate 70%)

Curative surgical resection or disease stabilisation in significant number of patients (66/160)

Definitive surgery after favourable response to NACT results in good survival.

TATA MEMORIAL HOSPITAL CRITERIA FOR BR / LA GBC • TUMOUR

• (T3-T4 tumours)

• Contiguous Liver involvement > 2cm

• Involvement of bile duct causing obstructive jaundice

• (Type I/II block on MRCP/ERCP/PTBD)

• Radiological / Endoscopic involvement of antropyloric region of stomach, duodenum, hepatic flexure of colon or small intestine

• NODE

• (N1 station)

• Radiological suspicion of lymph node involvement N1 - Hepatic artery (Station 8), Hepatoduodenal ligament (Station12), Retro

pancreatic / retroduodenal (Station 13)

• Size > 1cm in short axis, round in shape, and heterogenous enhancement on CT/PET scan.

• VASCULAR

• (T4 tumours)

• Impingement/ involvement (<180-degree angle) of one or more of the following blood vessels:

• Common Hepatic Artery and Right & Left Hepatic artery

• Main Portal vein and Right & Left Portal vein

• FOR INCIDENTAL GBC

• Residual/Recurrent mass in GB fossa /liver bed

• N1 nodes as per nodal criteria.

• Involvement of bile duct causing OJ (Type I/II Block)

CASE 2: HISTORY

62 year / Male / ECOG 1

Recently diagnosed diabetic

Presented with abdominal pain 2 months

O/E

GC: Good

No Pallor / Icterus / SCLN

PA: Soft, no mass

INVESTIGATIONS

Liver Function Tests

Bilirubin 0.8 mg%

Albumin 4.4 mg%

AST/ALT 14 / 15

Hb: 14.6 gm%

USG abdomen: Pancreatic mass

ROLE OF TUMOR MARKERS IN PANCREATIC CANCER

CEA: 7.5 units

CA 19-9: 911 units

NEXT MODE OF EVALUATION

A. Contrast enhanced CT scan (CECT)

B. MRI

C. PET

D. EUS

MDCT PANCREATIC PROTOCOL, NCCN (2016)

Hypodense mass at

pancreatic neck

Collaterals at

SMV-SV junction

SMV-SV

confluence

involved

Hypodense

mass at neck

of pancreas

Distal SMV stump

available for

reconstruction

MDCT (08.08.2016)

Hypodense mass 2.6 x 2.6 cm at pancreatic neck

Encasing distal most part of SMV and proximal 9 mm of PV near the confluence,

with significant luminal narrowing

Portal vein mildly dilated (15 mm at Porta), few dilated portosystemic collaterals,

Splenic vein not encased

The lesion abuts the common hepatic artery and SMA

No significant LN, no distant metastases

ROLE OF STAGING LAPAROSCOPY?

A. Yes

B. No

Indications

CA 19-9 > 1000

Pancreatic body mass > 4 cm

ROLE OF BIOPSY

EUS guided biopsy?

USG guided FNAC

Adenocarcinoma

WITH THIS INFORMATION….

Is it,

A. Resectable?

B. BRPC?

C. LAPC?

With regard to the porto-venous axis, any degree of

involvement falls into the category of borderline resectable

disease as long as the vein can be technically resected and

reconstructed

BRPC: MANAGEMENT PLAN?

A. Upfront Surgery

B. NACT and reassess for Surgery

C. NACT/RT and reassess for Surgery

BORDERLINE RESECTABLE:

NACT VS NACT/RT, RESULT OF 3 META-ANALYSIS

Neoadjuvant Therapy in BRPC: Systematic Review and Meta-Analysis

63% pts resected

87% R0

Median OS 25.9 months (resected)

FOLFIRINOX

(n=64)

Gem-based

Resection

rate

72% 67%

R0 60% 58%

G3 /4 Toxicity 53% 30%

Tang K. Pancreatology 2016;16: 28-37

Toxicity

Grade 3 & 4 toxicity 37.3%

Tang K. Pancreatology 2016;16: 28-37

Plan:

NACT and reassess

Received 4# FOLFIRINOX

POST NACT: REASSESSMENT

CECT Scan

• Partial Response

• SMV appears encased up to 2.3 cm near portal

confluence

• Splenic vein encased near confluence up to

length of 1.6 cm

• Main PV appears partially encased for 2 cm

Disease at neck

with SMV SV

junction involved

S. CA 19.9 611 units

S. CEA 6.75 units

PLAN : Pylorus preserving / Classical pancreaticosplenectomy with portal

vein confluence resection with SOS PTFE Graft reconstruction (28.12.16)

INTRAOPERATIVE FINDINGS

Tumor involving the head, neck and body of pancreas

Encasement of the PV, SMV and the SMV - PV junction

The SMA adventitia was involved and was resected from the SMA

No omental, peritoneal or liver deposits.

PANCREATIC HEAD, NECK AND BODY WAS INVOLVED

SMV looped

RADICAL TOTAL PANCREATECTOMY SPECIMEN

ISGPS, TYPE III PORTAL VEIN RESECTION

POSTOPERATIVE TUMOR BED

HPR: CAN YOU ELABORATE ON IMPORTANCE OF EACH AS

PROGNOSTICATION ?

WHAT IS ADEQUATE LYMPHADENECTOMY IN CA PANCREAS ?

ROLE OF EXTENDED RESECTIONS IN CA PANCREAS ?

IS THERE ANY ROLE OF ARTERIAL RESECTIONS ?

MDAC; ypT3N0

LVI +

PNI+

Retroperitoneal/SMA surface involved

0/24 Nodes

Post op period:

Uneventful recovery

Received 6# single agent Gemcitabine

FOLLOW UP

Developed B/L multiple liver metastases recently

• In the intention-to-treat analysis, the 1-YSR and 2-YSR in the neoadjuvant treatment group

(74% and 41%) were nearly twice as high as in the upfront surgery group (48% and 26%)

• In the PP1 and PP2 analysis, there was no difference in the 2-YSR between the groups

Jang J, et al. Ann Surg 2018

In 44% of pCR patients, no recurrence or death was observed.

Median OS 27 months; in pCR group median OS

was not yet met at 60 months; patients without a

pCR 26 months

pCR , a negative lymph node status

and neodjuvant FOLFIRINOX

independent predictors of OS

He J, et al. Ann Surg 2018