Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA...

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PET/CT in Breast Cancer Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical Engineering President, Society of Nuclear Medicine and Molecular Imaging

Transcript of Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA...

Page 1: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

PET/CT in Breast Cancer Hossein Jadvar, MD, PhD, MPH, MBA

Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical Engineering

President, Society of Nuclear Medicine and Molecular Imaging

Page 2: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Outline • Breast Cancer Demographics • Conventional Diagnosis • Brief overview of PET/CT and FDG • Clinical Applications of FDG PET/CT in BrCa • Clinical Impact on Management • Summary

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Page 3: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer Demographics 2015

• Prevalence (2012): 2,975,314 • Incidence: 231,840 (14.0% of all new cancer cases) • Estimated Deaths: 40,290 (6.8% of all cancer deaths) • Lifetime Cancer Risk: 12.3% (1 of 8); Median age: 61 y • %Cases by Stage: 61%local; 32% regional; 6% distant • 5-year Survival: 89.4%

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5-y survival by stage

Page 4: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer Histopathologic types and Metastases

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Weigelt B et al. Nat Rev Cancer 2005

Page 5: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer: Diagnosis • Physical examination (self breast exam) • Mammography

– overall sensitivity: 54-81%, specificity:25-40%, PPV: 10-35% – difficult to biopsy small lesions – non-palpable lesion – equivocal findings (ultrasonography) – dense breasts, augmentation mammoplasty, treated breast

• MRI – sensitivity: 88-100%, specificity: < 85%

• 99mTc-MIBI (Breast-Specific Gamma Cameras) – lesions >1.5 cm – palpable: sensitivity 91-95%; non-palpable: sensitivity 65-72% – specificity: ~75-90%

Page 6: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer: Subtypes

• Luminal A – ER+ and/or PR+, HER2-, Ki-67 low (<14%)

• Luminal B (HER2-) – ER+ and/or PR+, HER2-, Ki-67 high (>14%)

• Luminal B (HER2+) – ER+ and/or PR+, any Ki-67 index

• HER2+, ER-, PR- • Triple Negative: ER-, PR-, HER2-

• Inflammatory BrCA (IBC): no establsihed molecular criteria for differentiating from non-inflammatory ca; poor prognosis 12th Intl. Breast Conf. Goldhirsch A, Ann Oncol 2011.

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Breast Cancer: Staging

Lee JH et al. J Nucl Med 2009.

Locally advanced breast cancer T3 = Primary > 5 cm T4 = Any size with skin or chest wall invasion N2 = Fixed axillary LN

Page 8: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer: Axillary Nodal Staging • 20-30% nodal metastasis at early BrCa • Predictor of recurrence and survival • Five-year DFS

– 75% - no nodal involvement – 45% - involvement of 1-3 nodes – 20% - involvement of ≥ 4 nodes

• Surgical staging (ALND vs. ALND if SLN+) is SOC – 70-80% of patients with negative nodes – chronic lymphedema (8-25%), wound complications

(8%), shoulder dysfunction (2%) • Sentinel LN localization and biopsy

Page 9: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Hallmarks of Cancer Hanahan D, et al. Cell 2000; Cell 2011; Cancer Cell 2012.

• self-sufficiency in growth signals • insensitivity to anti-growth

signals • evasion of apoptosis • limitless replicative potential • sustained angiogenesis • tissue invasion and metastasis • evasion of tumors from the

immune system • increased glucose metabolism

(Warburg effect)

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Tumor FDG Uptake http://www.genenames.org/cgi-bin/hgnc_search.pl

Page 11: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer Biologic Correlates of FDG Uptake in Tumor

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• Cell type (Ductal > Lobular) and tumor volume (necrosis) • Histologic grade • Glut-1, Hexokinase • Microvessel density; Mitotic activity index • P53 mutation; uPA/PAI1 protein • ER, PR, HER2-neu status (higher uptake with ER- and triple

negative tumors) • High uptake high risk of mets, poor prognosis • Decline in uptake after Rx predictive of favorable response uPA=urokinase-type plasminogen activator PAI1=plasminogen activator inhibitor 1 HER2/neu=ERBB2=epidermal growth factor receptor 2 (15-20% tumors; trastuzumab) Grover-Mckay, 1998; Brown, NMB 2002; Bos, JCO 2002; Weigelt, Nat Rev Cancer 2005; Osborne, JNM 2010; Jadvar, JNM 2009; Wang, AJR 2011; Morris, Cancer 2012

Page 12: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer FDG Uptake Variants

• FP – Fibroadenoma, dysplasia; ductal ectasia, infection,

inflammation (mastitis); silicon leak; fact necrosis

• FN – Small lesions (< 1 cm); carcinoma-in-situ; lobular ca;

tubular ca, mucinous ca

• Variable – Menstrual cycle; lactation; dense breasts

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Page 13: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Normal Breast and FDG Uptake

Vranjesevic et al. JNM 2003

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Dense

Mixed

Fatty

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Lactating Breast

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Courtesy of Dr. Dominique Delbeke (Vanderbilt)

Page 15: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer: FDG PET/CT Clinical applications

• Incidental FDG uptake • Detection of Primary Tumor

• Staging

• Restaging after Therapy

• Monitoring Therapy Response

• Prognostication Jadvar

Page 16: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

J Nucl Med 2009

Page 17: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer FDG PET/CT

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Page 18: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer: Subtypes and SUV

Groheux D et al. EJNMMI 2011.

Page 19: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer: Subtypes and SUV

Kitajima K et al. EJNMMI 2015.

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Jadvar

Primary Infiltrating Ductal

Breast Adenocarcinoma

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Breast Cancer FDG PET/CT: Multifocal Tumors

Couretesy of Dr. Dominique Delbeke (Vanderbilt)

Page 22: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer: FDG PET/CT Luminal A invasive ductal CA, ER 100%, PR 50%, HER2 0, nuclear grade 1, 2 cm left breast SUVmax = 2.72

Kitajima K et al. EJNMMI 2015

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Page 23: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer: FDG PET/CT HER2+ invasive ductal CA, ER 0%, PR 0%, HER2 3+, nuclear grade 2, Ki-67 50%, 3.2 cm right breast SUVmax = 10.57

Kitajima K et al. EJNMMI 2015

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Page 24: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer: FDG PET/CT 27 yo F with BRCA1 after bilateral mastectomy Courtesy of P. Colletti

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Page 25: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer: FDG PET/CT

• Staging

• PET may be useful for >T2 (> 2 cm) lesions

• may modify stage and change management

(Bernsdorf, Ann Oncol 2012; Groheux, JNCI 2012)

• Detect previously unsuspected distant disease

(Alberini, Cancer 2009; Carkaci, JNM 2009)

Page 26: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer: FDG PET/CT

• Staging – PET- axilla does not exclude involvement (SLN

mapping) – Meta Analysis: pooled sensitivity 69%, pooled specificity 88% (Quan A, JCO 2005)

– Size: Sens. (<5mm:20%; 6-10mm:80%; >10mm:90%)

– PET+ often stages the axilla (needs verification)

– extra-axillary basin (e.g. IM) Wahl R. JNM 2003

Eubank, JCO 2001; Vernonesi, Ann Oncol 2007;Pritchard, JCO 2012

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Page 27: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer: FDG PET/CT Postop scan of a pt with preop clinical stage determined by CI as stage I; underwent R breast-conserving surgery and SLNB (neg). Postop pathology revealed TN invasive ductal carcinoma; restaged as IV and systemic Rx started – Gunalp, Exp Ther Med 2012

Page 28: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer FDG PET for Axillary Nodal Staging

Study N Sensitivity Specificity Comments

Wahl, 2004 308 61% 80% Multi-center, mostly T1

Keleman, 2003 15 20% 94% vs SLNB

Barranger, 2003 32 20% 100% vs SLNB

Fehr, 2004 30 20% 93% vs SLNB

Kumar, 2006 80 44% 95% Mostly SLNB

FDG PET has low sensitivity compared to SLNB

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Ann Nucl Med 2007

Page 30: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

75 yo F with breast cancer: pre-operative breast MRI identifies L breast lesion; FDG PET/CT shows liver and pleural metastases – Iagaru A et al. Ann Nucl Med 2007

Page 31: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

43 yo F with breast cancer; post-operative FDG PET-CT shows cervical and lumbar spine metastases; breast MRI was neagtive – Iagaru A et al. Ann Nucl Med 2007

Page 32: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

46 yo F with R breast DCIS: post-operative MRI showed non-specific changes and FDG PET/CT demonstrated residual disease (confirmed on histopathology) – Courtesy of A. Iagaru (Stanford)

Page 33: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer: FDG PET and MRI

• 40 patients with 42 lesions (23 benign, 19 CA) • PET and MRI complementary • poss. reduce bx 55% 17%

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Breast Cancer

Sensitivity Specificity

MRI 89% 74%

PET 63% 91%

Walter, Eur Radiol 2003; Courtesy D. Delbeke

Page 34: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer: Integrated PET/MRI (Siemens Biograph mMR) 52 yo F with 3 invasive ductal carcinomas – Kong, Hell JNM 2014

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Page 35: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

NCCN Guidelines: FDG PET/CT for Breast Cancer (v.3.2014)

• Early stage ( I, IIA): PET or PET/CT scanning NOT recommended

• Stage some IIB (locally advanced) IIIA (T3, N1, M0) or IIIB and Stage IV: CT C/A/P, bone scan, abdominal MRI or FDG PET may be considered

• unsuspected regional nodal disease and/or distant metastasis in locally advanced breast

• equivocal standard imaging results

Page 36: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer: Monitoring Therapy Response

• Chemotherapy – Most studies with heterogeneous tumor phenotypes,

assessment time after start of chemotherapy, response criteria, verification standard

– overall results similar to other cancers – Prediction of CR after 1st chemo cycle: Sens 90%,

Spec 74% (Schelling M. J Clin Oncol 2000)

– significant decline in tumor uptake is associated with favorable response and improved patient outcome

Tateishi, Radiology 2012; Martoni, Cancer 2010 Jadvar

Page 37: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer: Monitoring Therapy Response

• Hormonal Therapy – Women with ER+ disease – Metabolic flare ~1-2 week(s) after tamoxifen – Metabolic flare favorable response – Metabolic response may be correlated with outcome

Mortazavi-Jehanno, EJNM 2012; Mortimer, JCO 2001

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Page 38: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer: Therapy Response Assessment

Lee JH et al. J Nucl Med 2009;50:738-748. Lee JH et al. J Nucl Med 2009.

Page 39: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

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Pre-Rx Post-Rx 53 y F w/ poorly differentiated ductal R BrCA treated w/ R mastectomy + chemo

Pre-Rx PET: extensive metastases

Post-Rx PET: no evident disease

Page 40: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer: Monitoring Therapy Response

51 yo F w/ R IBC (HER2+, Ki-67 68%), ALN+, & pulmonary infection A) Pre-chemotherpay B) Post-chemotherapy

(CR) Champion L et al, JNM 2015

Page 41: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer: Monitoring Therapy Response

35 yo F w/ R IBC (Ki-67 30%) , ALN+ A) Pre-chemotherpay B) Post-chemotherapy

(PR) Champion L et al, JNM 2015

Page 42: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer: Therapy Response Assessment

0123456

FDG

SUV

Day 0Day 63

Responders Non-Responders

P < .001 P = NS

Wahl RW et al. J Clin Oncol 1993.

Page 43: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Responder

Non-Responder

Baseline 1st Course 2nd Course

Breast Cancer: Therapy Response Assessment

Schelling et al. J Clin Oncol 2000.

Page 44: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer: Metabolic “Flare” after Estradiol Predicts Hormonal Rx Response and Survival

Dehdashti F et al. Br Ca Res Treat. 2008

Page 45: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer FDG PET/CT

• Restaging after Therapy – Similar to most other cancers, PET more useful than

CI for differentiation post-Rx change from recurrence

– Highly sensitive (>90%) and specific (>85%) – May change clinical anagement – Not recommended routinely for clinically

asymptomatic surveillance (unless high suspicion) Radan, Cancer 2006; Manohar, Nucl Med Commun 2012; Dirisamer, EJR 2010; Khatcheressian, JCO 2012; Yap, JNM 2001; Kamel, J Cancer Res Clin Oncol 2003

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Page 46: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer FDG PET/CT: Unsuspected Nodal Metastasis Eubank et al JCO 2001; Courtesy of D. Delbeke

Page 47: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer: FDG PET/CT • Osseous Metastatic Disease

– 89 patients with FDG PET and planar/SPECT MDP – Overall FDG and MDP complementary but may start

with FDG PET/CT first; useful for f/u therapy monitoring (Nakai, EJNM 2005; Bombardieri E. QJNM 2001)

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Bone lesion (radiographic)

FDG 99mTc-MDP

Osteoblastic 56% 100% Osteolytic 100% 70%

Mixed 95% 84% none 88% 25%

Page 48: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer: Meta-analysis for Bone Metastses

FDG PET vs. Bone Scintigraphy

Shie P et al. Clin Nucl Med 2008.

Page 49: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Cook JRC, 2006; Habibian MR, et al. 2008

Breast Cancer: Bone Metastases

Blastic

Lytic

Marrow

18F-NaF 18F-FDG

18F-FDG

18F-FDG

Page 50: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer: Prognosis Son SH et al. AJR 2015

Page 51: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

0 10 20 30 40 50 60

0.0

0.2

0.4

0.6

0.8

1.0 c) Percentage SUV Change

diff≤ −41diff> −41

% mg/ml% mg/ml

= 0.0054p

> 41%

< 41%

% Decline in FDG SUV

0 10 20 30 40 50 60

0.0

0.2

0.4

0.6

0.8

1.0 a) Initial Standardized Uptake Value (SUV)

SUV1 ≤5SUV1 >5

mg/mlmg/ml

= 0.028p

prop

ortio

n wi

thou

t SR

E

Initial SUV

< 5.1

> 5.1

Breast Cancer: FDG Uptake Predicts Outcome of Bone-Dominant Breast Cancer

Time to Skeletal-Related Event Time to Progression

Specht et al. Br Ca Res Treat 2007 Courtesy of David Mankoff Courtesy of D. Delbeke

Page 52: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

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PET in Oncology: Breast Cancer Impact

• 254 patients with clinical stages II and III BrCa • unsuspected N3 disease (infra-, supra-clavicular, IM

nodes) in 16% • Change in clinical stage 30.3% (95%CI: 25-36%) • unsuspected mets

– overall 21% – 2.3% stage IIA, 10.7% stage IIB – 17.5% stage IIIA, 36.5% stage IIIB, 47.1% stage IIIC Groheux, JNM 2011; J Natl Cancer Inst 2012

Page 53: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Jadvar

PET in Oncology: Breast Cancer Impact

• 125 women with recurrent or metastatic disease • Retrospective chart review and PET comparison to CI • Sensitivity 94%, Specificity 91% • Extent of disease:

– increase by 43%; decrease by 24%

• Therapy plan change in 27% • PET contributes significantly to defining the extent

of disease and clinical management of patients with advanced breast cancer Eubank, AJR 2004

Page 54: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

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PET in Oncology: Breast Cancer Diagnostic and Therapeutic Impact (Survey)

• Standard questionnaires mailed to referring physicians

• 31% response rate

• Change in clinical stage 36% (28% upstage, 8% downstage)

• Change in intermodality management 28%

• Change in intramodality management 30%

• Major impact on staging and management (~30% of patients)

Yap C et al. J Nucl Med 2001.

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x−ray x-ray

Compression paddles

γ-ray camera

γ−ray γ-ray

camera

γ-ray

compression paddles

Positron Emission Mammography (PEM) mean spatial resolution at center of FOV

2.01 mm radial, 2.04 mm tangential, 1.84 mm axial

Levine EA et al. Ann Surg Oncol 2003;10:86-91. Courtesy of Lee Adler, M.D. Tafra L et al. Am J Surg 2005;190 (4):628-632. *Berg WA et al. The Breast J. 2006;12 (4):309-323. Glass & Shah. Proc (Bayl Univ Med Cent) 2013; Raylman R, Phys Med Biol 2008

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Jadvar

J Nucl Med 2012

Page 57: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Positron Emission Mammography (PEM)

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TP

TP

FP

TN

Page 58: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

PEM-MRI Directed Breast Biopsy (PEM Flex Solo II by Naviscan PET Systems, Inc)

MacDonald L et al. J Nucl Med 2009.

PEM spatial resolution FHWM: 2.4 mm

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Breast Cancer: FDG PET -- Meta Analysis • Incidental Uptake

– 13 articles, prevalence 0.82% (95%CI: 0.51-1.2%) – 60% IDC (95% CI: 53-66%) – Bertagna, Jpn J Radiol 2014; Shin, J

Breast Cancer 2015; Dunne, Br J Radiol 2013; Kim, Acta Radiol 2012; Kang, AJR 2011

• Cancer Screening Program (Japan) – 62,054 asymptomatic women – 473 possible cases (0.8% prevalence) – 161 breast cancer (34% cancer incidence) – Sensitivity 84%, PPV 42% – USA: ACR AUC for br. ca. screening – insufficient evidence Mainiero, JACR 2013; Minamimoto, Clin Breast Cancer 2015

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Page 60: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer: FDG PET -- Meta Analysis • Primary Tumor

– 144 patients, Detection rate: 68% (pT1) vs. 92% (pT2), FN rate: 24% (ductal CA) vs. 65% (lobular CA) - Avril, JCO 2000

– 85 articles (23,255 cancers), higher FDG uptake with HER2 overexpression -- Elias, Cancer Epidemio,l Biomarkers Prev 2014

• PEM – 8 articles (873 patients) – Caldarella, Clin Breast Cancer 2014

– pooled sensitivity 85% (95% CI: 83-88%) – pooled specificity 79% (95% CI: 74-83%)

• PEM vs. WB PET/CT – Kalinyak, EJNMMI 2014

– 178 pre-surgical patients; size: 1.6+0.8 cm (0.5-4.0 cm) – tumor detection: 95% PEM, 87% PET/CT Jadvar

Page 61: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer: FDG PET -- Meta Analysis • Axillary Node Status

– 26 studies (2591 patients) – pooled sensitivity 63% (95% CI: 52-74%) – pooled specificity 94% (95%CI: 91-96%) – mean sensitivity 11% (<2mm), 57% (>2mm) Cooper, Eur J Surg Oncol 2011

• Detection of Distant Metastases – Hong, Surg Oncol 2013

– 8 articles (748 patients) – pooled sensitivity 96% (95%CI: 90-98%) – pooled specificity 95% (95% CI: 92-97%)

Jadvar

Page 62: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer: FDG PET -- Meta Analysis • BS vs. PET/CT – Rong, Surg Oncol 2013

– 7 studies (668 patients) – BS pooled sens/spec 81%, 96% – PET/CT pooled sens/spec 93%, 99%

• BS vs. MRI vs. PET/CT – Liu, Skeletal Radiol 2011 – 13 articles; per patient basis – BS pooled sens/spec 87%, 88% – PET/CT pooled sens/spec 83%, 95% – MRI pooled sens/spec 97%, 97% – MRI better on per patient-basis; PET/CT higher specificity

(at cost of lower sensivity) on per-lesion-basis. Jadvar

Page 63: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Breast Cancer: FDG PET -- Meta Analysis Neoadjuvant Chemotherapy Response

• Cheng, Acta Radiol 2012 – 17 studies (781 patients) – Pooled sensitivity 84% – pooled specificity 71%

• Mohanga, Clin Breast Cancer 2013 – 15 articles (745 patients) – pooled sensitivity 81% – pooled specificity 79%

Jadvar

Page 64: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Jadvar

FDG PET/CT in Breast Cancer Summary

• Limited utility: detection of small primary tumors; in staging the axilla (micromets); blastic bone mets [PROBLEM-SOLVING TOOL]

• SUV: ductal CA > lobular CA > dense breast • higher tumor SUV associated with poorer prognosis • no need for SLN bx in PET + axilla • Good diagnostic performance for recurrent/Met disease • Impact on clinical management • Useful in therapy monitoring; metabolic flare with hormonal Rx is

predictive of response • Tumor extent and uptake level are predictive of outcome • Positron emission mammography-guided biopsy

Page 65: Hossein Jadvar, MD, PhD, MPH, MBA - Human Health Campus · Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Vice Chair of Research Associate Professor of Biomedical

Acknowledgement Patrick Colletti MD (USC) Dominique Delbeke, MD, PhD (Vanderbilt) Andrei Iagaru, MD (Stanford) David Schuster, MD (Emory) USA National Institutes of Health R01-CA111613 R21-CA142426 R21-EB017568 P30-CA014089


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