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Caris Centers of Excellence Virtual Molecular Tumor Board - Sep 28, 2015 - West Cancer Center

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Slide deck from Caris Life Sciences' Virtual Molecular Tumor Board hosted by COE Network Member, West Cancer Center

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Caris Centers of Excellence Virtual Molecular Tumor Board - Sep 28, 2015 - West Cancer Center

  1. 1. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Virtual Molecular Tumor Board Hosted By: Dr. Lee Schwartzberg West Cancer Center September 28, 2015 Cases: • Unknown primary • NSCLC with c-KIT mutation • Breast cancer with BRCA2 mutation • Renal cell carcinoma with VHL and PTEN mutations • Concurrent advanced malignancies with VHL and 2 PTEN mutations
  2. 2. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
  3. 3. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Patient 1
  4. 4. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. History • 31 year old woman • Fall: abdominal bloating following SNVD in Spring • 6 months later: R pleural effusion, large volume ascites, R ovarian mass. – Ca 125: 111; Ca19-9: 41,149; CEA 2. – EGD reported negative. – No panc mass on CT • 3 weeks later: TAH/BSO – Metastatic signet ring cell adenocarcinoma on ovary and in ascites. – IHCs: HER2 -, CK7+, GATA3-. Most c/2 upper GI or pancreatic/biliary origin. MMR proficient • 3 months later: Started FOLFOX
  5. 5. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. History continued • Cancer Type ID: 90% likely ovarian • Genetics: 25 gene panel negative for germline mutation except for VUS in PMS2 • 3 months later: Hospitalized and re-evaluation – EGD showed poorly differentiated signet ring cell involving stomach and duodenum – Switched to taxotere/5FU
  6. 6. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Pathology H&E 10x H&E 20x
  7. 7. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Molecular Tumor Summary • NGS findings: – KRAS exon 3 A59E pathogenic mutation – GNAS exon 8 R201H pathogenic mutation • IHC predicted benefit: – ERCC1 (platinum), TS (5-FU), TUBB3/PGP (taxanes) – Non-beneficial: topotecan, anthracyclines, BRAF, temozolomide
  8. 8. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Discussion • Unknown primary – Treating as GI primary (colon vs. gastric) – Avoid cetuximab with exon 3 KRAS mutation – Has received the predicted beneficial drugs for colon cancer – Consider clinical trial
  9. 9. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Patient 2
  10. 10. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. History • 60 year old male • Presented with LUL mass, mediastinal and hilar adenopathy, contralateral lung lesion and adrenal metastases. – MRI head: multiple brain mets. Heavy smoker and hx of colon cancer 2007 – NSCLC, adenocarcinoma T4N2M1. Molecular testing referred to in note but not documented • Received whole brain radiotherapy, and treated with Carbo / Alimta + Alimta maintenance with systemic and brain response • One year later: Brain mixed response, progressive disease in lungs and LNs. – Rebiopsied: met adenocarcinoma. – Tissue sent for Caris Molecular Intelligence tumor profiling. – Started second line chemo with docetaxel and palliative care
  11. 11. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Pathology H&E 10x H&E 20x
  12. 12. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Molecular Tumor Summary NGS findings: – CKIT exon 11 W557R pathogenic mutation – TP53 exon 10 E339X pathogenic mutation – BRCA1 exon 23, E1829K (VUS) IHC findings: – PD-1 positive, PD-L1 negative – EGFR H-score positive – TOPO1 (irinotecan benefit)
  13. 13. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Discussion • c-KIT pathogenic mutation – Consider imatinib, sunitinib, etc? – Alone or sequenced with platinum doublet – References: – 11 of 34 patients with CKIT+ NSCLC responded to imatinib. (Donnenberg et al. 2012, PLOS One)
  14. 14. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Patient 3
  15. 15. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. History • 43 year old woman • Presented to hospital with unrelenting hip pain – Pathologic fracture, underwent acetabular repair. Path: mod diff adenocarcinoma, c/w breast – CT: liver and bone mets – Ca15.3 235, CEA 2.6 – Mammogram R breast mass – Began AC + denosumab
  16. 16. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Pathology H&E 10x H&E 20x
  17. 17. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. NGS findings: IHC findings: •AR+, ER+, PR+ Other predicted benefit: •RRM1 (gemcitabine), TS (5-FU), TLE3 (taxanes) Molecular Tumor Summary BRCA2 Mutated, Pathogenic | Exon 9 | K242X PIK3CA Mutated, Pathogenic | Exon 10 | E545K TP53 Mutated, Presumed Pathogenic | Exon 4 | T125K
  18. 18. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Discussion • Likelihood of representing a germline mutation • Genetic counseling for BRCA2 mutation • Use of platinum or PARP inhibitor with BRCA2m – Olaparib monotherapy in BRCA-mutant breast cancer: • 8 of 62 (12.9%) patients responded • (Kaufman et al, JCO. V33: 244-250 , 2015.)
  19. 19. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Patient 4
  20. 20. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. History • 46 year old man • Presented with painless hematuria. – W/u: L renal mass, multiple pulmonary nodules. • Nephrectomy – Clear cell Ca, Furhman grade III, 4 cm. Lung bx: met renal cancer. – Started sutent-achieved CR systemically by Spring 2013. • 1 year later: Solitary hemmorhagic cerebellar. – Treated with gamma knife x 3 over next 15 months. • 6 month later: Recurrent disease in L sacrum and adjacent soft tissue. – Rebiopsy: Metastatic renal clear cell carcinoma – Tumor sent for Caris Molecular Intelligence Tumor Profiling. – Began everolimus.
  21. 21. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Pathology H&E 10x H&E 20x
  22. 22. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Molecular Tumor Summary • VHL exon 3 L169P pathogenic mutation • PTEN exon 1 K13X pathogenic mutation • PTEN absent by IHC • PIK3CA wildtype • IHC findings: – Predicted benefit for taxanes, capecitabine, temozolomide, topotecan – Predicted lack of benefit for platinums (ERCC1)
  23. 23. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Role of PTEN
  24. 24. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Discussion • Any likelihood of PTEN of VHL representing germline mutations • Availability of PTEN directed therapies: – mTOR or AKT inhibitors
  25. 25. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Patient 5
  26. 26. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. History • 52 year old woman • Squamous cell carcinoma of lung, stage 3B – Treated with cis/gem, followed by nivolumab • PET avid lesion noted on right renal hilum – With retroperitoneal lymph node involvement – Biopsy of retroperitoneal node suggested urothelial origin. – Tissue sent for Caris Molecular Intelligence Tumor Profiling.
  27. 27. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Pathology H&E 10x H&E 20x
  28. 28. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Pathology PTEN IHC 20x
  29. 29. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Molecular Tumor Summary • NGS findings: – KRAS exon 3 E36K pathogenic mutation – VHL exon 3 R200W pathogenic mutation – PTEN two pathogenic mutations: • Exon 6 Q171X • Exon 7 S229X • IHC findings: – PD-L1 negative – PTEN IHC positive – Predicted benefit: TUBB3(taxanes), TOP2A (doxo)
  30. 30. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Role of VHL
  31. 31. The information contained in these slides is provided for educational purposes only and has been permanently de-identified. Discussion • Significance of mutations: – KRAS – VHL – Two PTEN point mutations • With retention of IHC positivity • Second primary vs distant metastasis?

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