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Caris Centers of Excellence Virtual Molecular Tumor Board Fox Chase - Jan 26, 2016 (No Audio)

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Slide deck from Caris Life Sciences' Virtual Molecular Tumor Board hosted by the COE Member Fox Chase Cancer Center (Temple Health).

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Caris Centers of Excellence Virtual Molecular Tumor Board Fox Chase - Jan 26, 2016 (No Audio)

  1. 1. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Virtual Molecular Tumor Board Fox Chase Cancer Center January 26, 2016 Presented by: Namrata Vijayvergia, M.D. Patient 1: Gastro-esophageal adenocarcinoma with EGFR amplification Patient 2: Peritoneal carcinomatosis from upper GI primary with BRAF mutation Patient 3: Pancreatic adenocarcinoma with BRCA2 mutation
  2. 2. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Patient 1
  3. 3. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. History • Male, late 60’s, presented with abdominal pain, weight gain • Diagnostic Workup: – CT: celiac nodes, liver masses and retroperitoneal nodes, and mass suggesting Gastroesophageal junction adenocarcinoma – Liver biopsy: upper GI adenocarcinoma with moderate differentiation – EGD with biopsy confirmed GE junction cancer • Initial specimen HER2 2.0 by FISH and 2+ IHC • Dx: Stage 4 GE junction cancer, metastatic to liver and nodes
  4. 4. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Pathology H & E 20x
  5. 5. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.The information contained in these slides is provided for educational purposes only and has been permanently de-identified. FOLFOX+T (11 months) Docetaxel (2 months) FOLFIRI (3 months) Case #1. Male, late 60’s, with metastatic esophageal adenocarcinoma. HER2 testing: IHC 2+ (equivocal); Ratio 2.0 by ISH (positive) @ Integrated Oncology Second biopsy: HER2 IHC 1+ (20%); Ratio 1.36 (negative) EGFR IHC 2+ (60%); Ratio 12.67 (amplified) + 2 months
  6. 6. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Repeat Biopsy
  7. 7. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
  8. 8. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
  9. 9. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Nature, 2014 TCGA data on gastric cancer
  10. 10. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Mutation Count vs CNA 0.0 0.2 0.4 0.6 0.8 1 10 100 1000 10000 #ofmutations Four molecular subclasses of GC Genome unstable (MSI) Chromosome instability (CIN) Genome stable (diffuse) Epstein-Barr virus+
  11. 11. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
  12. 12. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.The information contained in these slides is provided for educational purposes only and has been permanently de-identified. EG AC mutations (TCGA, 2014) RTK MAPK DDR Epi
  13. 13. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Epidermal growth factor receptor copy number gain (EGFR CNG) and response to gefitinib in oesophageal cancer (OC): Results of a biomarker analysis of a phase III trial of gefitinib versus placebo (TRANS-COG) Dutton S.J. Lancet Oncol. 2014 Jul;15(8):894-904 • Gefitinib single agent therapy in 450 pts with Mts EC. • EGFR FISH results for 295 patients • EGFR amplifications in 48/295 (16.3%) • In EGFR-amp. OS improved (HR=0.52, CI=0.28-0.96, p=0.033) • Survival for G. vs. P. 9 months- 27 vs.5%, 12 months-13 vs.0% • No difference in EGFR normal CN. • EGFR amplification (6%) pts gained greatest benefit from G. (OS, HR=0.19, 95% CI=0.05-0.65, p=0.007). Abstract, R. Petty et al.
  14. 14. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Discussion • Erlotinib in setting of EGFR amplification • Clinical outcomes with EGFR amplification vs. mutation – Erlotinib is recognized on Lung NCCN compendium for EGFR amplification – Report of about of at least 29% GE junction tumors with EGFR expression (Sgroi, ASCO 2008) • Future treatment options – TOP2A / anthracyclines? – MGMT / temozolomide? – Available studies
  15. 15. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Patient 2
  16. 16. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. History • Female, late 70’s • PMH: stage one rectal carcinoma, COPD, psoriarsis, GERD, bronchiectasis • FH: MGM with colon cancer, sister with Gyn cancer • ECOG 1 performance status • Now with peritoneal carcinomatosis and liver metastasis of upper GI/pancreaticobiliary origin • Initial CEA: 13.5, CA-19-9: 141
  17. 17. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Treatment History • Started on FOLFOX – Required dose reduction of oxaliplatin (cytopenia) – Also some infusion reaction • After 5 months – Some clinical improvement – Markers reduced: • CEA: 4.0 • CA-19-9: 62
  18. 18. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Pathology H & E 20x TS 20x
  19. 19. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Molecular Tumor Summary
  20. 20. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.The information contained in these slides is provided for educational purposes only and has been permanently de-identified. BRAF Inhibitors Dabrafenib
  21. 21. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Discussion • Role of BRAF inhibitors in upper GI cancers? – Mutations reported in about 13% of pancreatic cancers especially with acinar differentiation (Jiao et al, J Pathol, 2014) – Rare in biliary (<1%) (Goeppert et al, Mod Pathol, 2014) – Unknown outcomes with BRAF inhibitors • Low Thymidylate Synthase (TS): – Suggests ongoing role for 5-FU-based therapy – Clinically responding to FOLFOX – TOPO1 predicts lower chance of irinotecan response
  22. 22. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Patient 3
  23. 23. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. History • Female, late 40’s, with abdominal pain and bloating • PMH: Hodgkins stage 2A during twenties • FH: unremarkable • Workup: – CT revealed pancreatic mass and liver lesions – EUS/biopsies revealed carcinoma of duodenal wall and pancreas, gastric wall negative for malignancy • Dx: Pancreatic/duodenal adenocarcinoma – Poorly differentiated, With Squamous feature – Stage 4
  24. 24. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Pathology H & E 40x PD-L1 40x
  25. 25. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
  26. 26. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
  27. 27. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Molecular Tumor Summary NGS • BRCA2 S1982fs exon 11 pathogenic mutation • PIK3CA G1007R exon 21 pathogenic mutation • KRAS G12V exon 2 pathogenic mutation PD-L1 positive by IHC
  28. 28. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Discussion • Management of BRCA2 mutation – Genetic counseling implications – Germline confirmation? – Role for PARPi? – 21% response rate to olaparib monotherapy in pancreatic patients with BRCA2 germline mutations (Kaufman JCO 2015) – Mitomycin-C (9-12 week response) (Vyas, Anti-Cancer Drugs 2015) • PDL1 positive: Role for immunotherapy? • KRAS exon 2 mutation • PIK3CA mutation
  29. 29. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. The next Virtual Molecular Tumor Board Hosted by Dr. Lee Schwartzberg West Cancer Center Date: Tuesday February 23, 2016 Please direct questions regarding the VMTB to cariscentersofexcellence@carisls.com 29

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