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The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Patient 1
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Clinical History
• male, early 50's, metastatic CRC
• 2 years ago, presented with near obstructing sigmoid cancer, large
volume liver mets, increased LFTs
• KRAS/extended RAS WT from SC node biopsy
• Treated with XELOX + Bev- strong PR
• Cardiac event- changed to bolus 5FU/bev maintenance
• PD 12 months ago- changed to IRI + Panitumumab– PR, rash
• CEA increased- increased bowel symptoms-
• CT showed only PD in colon primary- partial obstruction
• Surgical resection of primary
• KRAS mutation on CARIS profile
• PD while off chemo during surgery, retreated with IRI + Panitumumab,
responding again
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Caris Molecular Intelligence Profile
Test One: at diagnosis
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Caris Molecular Intelligence Profile
Test One: at diagnosis
pan-RAS testing: QNS, thus no cetuximab treatment association
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Relevant Stains
• specimen 1 (2014) specimen 2 (2015)
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Caris Molecular Intelligence Profile
Test Two: 2 months later
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Caris Molecular Intelligence Profile
Test Two: 2 months later
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Caris Molecular Intelligence Profile
Test Two: 2 months later
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Molecular Tumor Summary
• KRAS
• previous LN KRAS WT
• First Caris specimen QNS
• Repeat Caris test: K-RAS exon2 G12V mutation
• BRCA1 and BRCA2 VUS
• Not clinically actionable
• Predicted beneficial cytotoxics:
• 5-FU / Capecitabine
• Irinotecan
• Taxanes
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Discussion Points
•KRAS mutated primary, mets WT
•What next?
•BRCA mutations?
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Patient 2
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Treatment Summary
• male, early 50's, met CRC
– Refractory to Oxali, irinotecan
• KRAS mut
• Enrolled on regorafanib trial
– Biopsy at baseline and on treatment for
biomarker discovery
– Currently responding
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Caris report
• QNS
– Discuss tissue sample needs for analysis and trials
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Caris Molecular Intelligence Profile
Initial testing at diagnosis
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Caris Molecular Intelligence Profile
Repeat testing
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Relevant Stains
• first specimen
(2014) second specimen (2015)
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Relevant Stains
• 2014: TOPO1
2+/15%, patchy 2015: TOPO1 2+/100% limited
sample size and bias
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Molecular Tumor Summary
• Initial testing:
• KRAS mutation G12D, exon 2
• PD-1 positive IHC, PD-L1 negative
• APC mutation S1362fs
• CMET mutation T1010I
• Subsequent testing (IHC only):
• TOPO1 positive / irinotecan beneficial
• TS positive / 5-FU & Cape non-beneficial
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Patient 3
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Clinical History
• female, early 40's, previously healthy
• Developed fatigue and iron deficiency
• Back pain
• CT abdomen revealed:
– Acending colon lesion 3.6 cm
– Liver radiodensities up to 3.2 x 2.6cm
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Pathology
• Metastatic colorectal adenocarcinoma
• KRAS codon 12 mutation in exon 2 detected
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Clinical Course
• Started on XELOX + Bevacizumab
• Required dose reduction in Xeloda and Oxaliplatin due
to severe fatigue
• Achieved stable disease
• Followed by maintenance Xeloda + Bevacizumab
• Developed abdominal pain 5 months after initial diagnosis
• CT revealed free air, suspicious for perforation
• CEA elevation to 369
• Resumed XELOX
• Developed oxaliplatin allergy
• Changed to Xeloda single agent
• Non-obstructive hyperbilirubinemia (direct bili. 6.5)
• No irinotecan
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Caris Molecular Intelligence Profile
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Caris IHC Findings
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Relevant Stains
• H & E MSH2
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Relevant Stains
• TOPO1 TS
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Relevant Stains
• PD-1 PD-L1
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Caris Molecular Intelligence Profile
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Tumor Profile Summary
• KRAS exon 2 mutation G13D (no anti-EGFR)
• cMET mutation T1010I (clinical trial options)
• PD-1 expression (clinical trial options)
• Low TS expression (capecitabine benefit)
• TOPO1 overexpression (irinotecan benefit)
• MSI-normal, normal MLH1/MSH2
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Patient 4
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Clinical History
• Demographics: male, mid-30's
Relevant medical history:
• Non-corrected undescended testes
• Initial diagnosis – RP mass – Mixed germ cell tumor
• Recurrent disease- at 6 months, one year, four years, seven
years, and nine years
• Most recent recurrence- HTN, decreased renal function due
to renal artery compression by tumor. Renal artery stent with
improvement in kidney function
• Symptoms / physical findings:
– abdominal pain, weight loss, HTN
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Prior Treatment
Initial diagnosis: PEB X 4 followed by incomplete
resection of retroperitoneal disease
At 6 months: TIP X 2 followed by triple tandem PSCT
At 1 year: Resection of residual mass-teratoma
At 4 years: Recurrent abdominal disease
resected/ nephrectomy- teratoma
At 7 years: Mass in pancreas
resected, splenectomy- GCT
At 9 years: Recurrent intra abdominal disease- GCT
EP X 4 followed by resection followed by EP X2
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Radiology
• Most recent recurrence:
• CT scan abdomen
– increased nodularity in the mesentery,
• PET scan
– 2 areas of increased uptake retroperitoneum
• Renal artery compression by tumor
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Pathology
• Initial diagnosis: RP mass- embryonal,
choriocarcinoma, yolk sac, mature teratoma
• At one year: Teratoma
• At four years: Teratoma
• At 7 years: Embryonal, yolk sac, teratoma
• At 9 years: Metastatic carcinoma c/w GCT
showing features of embryonal carcinoma
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Caris Molecular Intelligence Profile
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Caris Molecular Intelligence Profile
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Relevant Stains
• H&E: Yolk sac
component EGFR (L718R 97%): 1+/70% total
EGFR expression (IHC)
The information contained in these slides is provided for educational purposes only and has been permanently de-identified
Molecular Tumor Summary
• Standard first-line BEP treatment has no established
biomarker specific for germ cell tumor lineage
• Second-line therapies with biomarkers include taxanes
and gemcitabine
• Molecular profiling favors taxanes over gemcitabine
• Off-label considerations of potential benefit include
anthracyclines and temozolomide

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Caris Centers of Excellence Virtual Molecular Tumor Board - June 29, 2015

  • 1. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Patient 1
  • 2. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Clinical History • male, early 50's, metastatic CRC • 2 years ago, presented with near obstructing sigmoid cancer, large volume liver mets, increased LFTs • KRAS/extended RAS WT from SC node biopsy • Treated with XELOX + Bev- strong PR • Cardiac event- changed to bolus 5FU/bev maintenance • PD 12 months ago- changed to IRI + Panitumumab– PR, rash • CEA increased- increased bowel symptoms- • CT showed only PD in colon primary- partial obstruction • Surgical resection of primary • KRAS mutation on CARIS profile • PD while off chemo during surgery, retreated with IRI + Panitumumab, responding again
  • 3. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Caris Molecular Intelligence Profile Test One: at diagnosis
  • 4. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Caris Molecular Intelligence Profile Test One: at diagnosis pan-RAS testing: QNS, thus no cetuximab treatment association
  • 5. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Relevant Stains • specimen 1 (2014) specimen 2 (2015)
  • 6. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Caris Molecular Intelligence Profile Test Two: 2 months later
  • 7. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Caris Molecular Intelligence Profile Test Two: 2 months later
  • 8. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Caris Molecular Intelligence Profile Test Two: 2 months later
  • 9. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Molecular Tumor Summary • KRAS • previous LN KRAS WT • First Caris specimen QNS • Repeat Caris test: K-RAS exon2 G12V mutation • BRCA1 and BRCA2 VUS • Not clinically actionable • Predicted beneficial cytotoxics: • 5-FU / Capecitabine • Irinotecan • Taxanes
  • 10. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Discussion Points •KRAS mutated primary, mets WT •What next? •BRCA mutations?
  • 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 Treatment Summary • male, early 50's, met CRC – Refractory to Oxali, irinotecan • KRAS mut • Enrolled on regorafanib trial – Biopsy at baseline and on treatment for biomarker discovery – Currently responding
  • 13. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Caris report • QNS – Discuss tissue sample needs for analysis and trials
  • 14. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Caris Molecular Intelligence Profile Initial testing at diagnosis
  • 15. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Caris Molecular Intelligence Profile Repeat testing
  • 16. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Relevant Stains • first specimen (2014) second specimen (2015)
  • 17. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Relevant Stains • 2014: TOPO1 2+/15%, patchy 2015: TOPO1 2+/100% limited sample size and bias
  • 18. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Molecular Tumor Summary • Initial testing: • KRAS mutation G12D, exon 2 • PD-1 positive IHC, PD-L1 negative • APC mutation S1362fs • CMET mutation T1010I • Subsequent testing (IHC only): • TOPO1 positive / irinotecan beneficial • TS positive / 5-FU & Cape non-beneficial
  • 19. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Patient 3
  • 20. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Clinical History • female, early 40's, previously healthy • Developed fatigue and iron deficiency • Back pain • CT abdomen revealed: – Acending colon lesion 3.6 cm – Liver radiodensities up to 3.2 x 2.6cm
  • 21. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Pathology • Metastatic colorectal adenocarcinoma • KRAS codon 12 mutation in exon 2 detected
  • 22. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Clinical Course • Started on XELOX + Bevacizumab • Required dose reduction in Xeloda and Oxaliplatin due to severe fatigue • Achieved stable disease • Followed by maintenance Xeloda + Bevacizumab • Developed abdominal pain 5 months after initial diagnosis • CT revealed free air, suspicious for perforation • CEA elevation to 369 • Resumed XELOX • Developed oxaliplatin allergy • Changed to Xeloda single agent • Non-obstructive hyperbilirubinemia (direct bili. 6.5) • No irinotecan
  • 23. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Caris Molecular Intelligence Profile
  • 24. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Caris IHC Findings
  • 25. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Relevant Stains • H & E MSH2
  • 26. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Relevant Stains • TOPO1 TS
  • 27. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Relevant Stains • PD-1 PD-L1
  • 28. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Caris Molecular Intelligence Profile
  • 29. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Tumor Profile Summary • KRAS exon 2 mutation G13D (no anti-EGFR) • cMET mutation T1010I (clinical trial options) • PD-1 expression (clinical trial options) • Low TS expression (capecitabine benefit) • TOPO1 overexpression (irinotecan benefit) • MSI-normal, normal MLH1/MSH2
  • 30. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Patient 4
  • 31. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Clinical History • Demographics: male, mid-30's Relevant medical history: • Non-corrected undescended testes • Initial diagnosis – RP mass – Mixed germ cell tumor • Recurrent disease- at 6 months, one year, four years, seven years, and nine years • Most recent recurrence- HTN, decreased renal function due to renal artery compression by tumor. Renal artery stent with improvement in kidney function • Symptoms / physical findings: – abdominal pain, weight loss, HTN
  • 32. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Prior Treatment Initial diagnosis: PEB X 4 followed by incomplete resection of retroperitoneal disease At 6 months: TIP X 2 followed by triple tandem PSCT At 1 year: Resection of residual mass-teratoma At 4 years: Recurrent abdominal disease resected/ nephrectomy- teratoma At 7 years: Mass in pancreas resected, splenectomy- GCT At 9 years: Recurrent intra abdominal disease- GCT EP X 4 followed by resection followed by EP X2
  • 33. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Radiology • Most recent recurrence: • CT scan abdomen – increased nodularity in the mesentery, • PET scan – 2 areas of increased uptake retroperitoneum • Renal artery compression by tumor
  • 34. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Pathology • Initial diagnosis: RP mass- embryonal, choriocarcinoma, yolk sac, mature teratoma • At one year: Teratoma • At four years: Teratoma • At 7 years: Embryonal, yolk sac, teratoma • At 9 years: Metastatic carcinoma c/w GCT showing features of embryonal carcinoma
  • 35. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Caris Molecular Intelligence Profile
  • 36. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Caris Molecular Intelligence Profile
  • 37. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Relevant Stains • H&E: Yolk sac component EGFR (L718R 97%): 1+/70% total EGFR expression (IHC)
  • 38. The information contained in these slides is provided for educational purposes only and has been permanently de-identified Molecular Tumor Summary • Standard first-line BEP treatment has no established biomarker specific for germ cell tumor lineage • Second-line therapies with biomarkers include taxanes and gemcitabine • Molecular profiling favors taxanes over gemcitabine • Off-label considerations of potential benefit include anthracyclines and temozolomide