Slide deck from Caris Life Sciences' Virtual Molecular Tumor Board (VMTB) on December 23rd hosted by Dr. John Marshall at COE network member MedStar Georgetown University Hospital

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Virtual Molecular Tumor Board
December 23, 2015
Host: MedStar Georgetown University Hospital
Leader: Dr. John Marshall
Cases:
• Lung cancer with BRCA2 mutation
• Colon adenocarcinoma with BRCA2 mutation

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Patient 1

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History
• Male, mid-60’s, non-smoker
• Diagnosed with Lung cancer, adenocarcinoma
– Poorly differentiated
– T1N0M1, bony metastases in left ileum
• Bronchoscopy confirmed adenocarcinoma of the lung
• MRI confirms lesions in the left ileum
• Tissue sent for Caris Molecular Intelligence tumor profiling

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Pathology
H&E 20x

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BRCA sequencing results

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Germline Testing

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Discussion
• Stage 4 lung adenocarcinoma EGFR/ALK/ROS1 negative
• Confirmed germline BRCA2 mutation
– Additional genetic counseling implications
– Lack of typical family history for HBOC
• Treatment:
– Carboplatin/ Alimta/ Avastin
– Radiation to bony metastases
– Denosumab q 6 weeks for bony mets

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Raymond et al, JNCI 2016

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Recommendations from authors
1. Discuss the possibility of germline findings
when consenting patients for tumor testing
2. Ascertain patient’s wish for disclosure of
germline findings
3. Involve genetic counselors and other
specialists when necessary for interpretation
of somatic sequencing results
Raymond et al, JNCI 2016

11. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
Patient 2

12. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
History
• Early 60’s presents with colon mass
– biopsy positive for adenocarcinoma
– Unusual path and presentation and eventual testing showed a
bile duct cancer with spread to the colon
• Initial treatment on c-met gem/cisplatin trial,
immediate SBO requiring surgery.
• SBO/TPN currently treated with gem/cis off study
– some improvement.
• Tissue sent for Caris Molecular Intelligence Profiling

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Family history
• No significant history of cancer
• Jewish ancestry

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BRCA2 pathogenic mutation

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CNV analysis

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Molecular Tumor Summary
• BRCA2 R2336H, exon 13, pathogenic mutation
• EGFR exon 21 VUS
• KRAS, NRAS, HRAS wildtype
• No gene amplifications
• IHC:
– Predicted response: 5-FU, Taxanes, Cetuximab
– Non-response: Irinotecan

17. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
Discussion
• BRCA2 pathogenic mutation
– Genetic counseling?
– Somatic versus germline?
– BRCA1 but not BRCA2 previously reported to have
some elevated colon cancer risk (Phelan et al 2014, BJC).
– More data emerging from expanded germline panel
studies – broader syndrome phenotypes are being
observed

18. The information contained in these slides is provided for educational purposes only and has been permanently de-identified.
Next Molecular Tumor Board:
January 26, 2016
5pm ET (4pm CT)
Host: Fox Chase Cancer Center
Leader: Dr. Namrata Vijayvergia