About this document "Allen morris insights for hackathon": summarize this thread

Summary of Allen Morris's Hackathon Thread

This is a detailed pathology and treatment strategy discussion about Mo's rare sarcoma case from a community pathologist's perspective.

Key Points from Dr. [removed] Morris:

The Clinical Picture

• Mo has a low-grade sarcoma that transformed to high-grade (exact subtype unclear)
• Described as a potential "unicorn case" - possibly present at birth, then dedifferentiated into an undifferentiated EGFR-driven sarcoma
• Known molecular alterations: EGFR-KDD and PDGFRB (likely linked)
• Untested targets mentioned: B7-H3, GD2, PRAME, HER2, PD-L1, TMB, HLA-A24

Dr. [removed] Main Recommendations:

1. Pathology First (Before Treatment Discussion):

• Share all pathology reports and genomic data with Hackathon participants
• Get blinded reviews from 2+ academic sarcoma pathology groups (Stanford, UCSF, Mayo)
• Pin down the most accurate diagnosis possible - not just "Sarcoma, NOS, EGFR+"
• This is critical because sarcoma now has 70+ molecularly-defined entities with overlapping features

2. Treatment Strategy Considerations:

• Draw from EGFR+ non-small cell lung cancer (NSCLC) evidence, especially sarcomatoid variants
• Consider EGFR-targeted TKIs: afatinib, osimertinib
• If fresh tissue available: prioritize functional drug testing (SageMedic) for EGFR-directed therapies
• Explore novel approaches like integrin-targeted antibody therapy (Dr. [removed] work at Tufts)

3. Information Gaps to Address:

• What was discussed at the tumor board?
• Why were specific untested targets (B7-H3, PD-L1, TMB, HLA-A24) highlighted?
• Are these for vaccine candidates or immune checkpoint inhibitor (ICI) prediction?

Dr. [removed] Apfel's Response (SageMedic CEO):

Praised the LLM analysis but noted limitations:

• LLMs default to NCCN guidelines → clinical trials, missing "out of the box" reasoning
• Thin on diagnostic side - should consider more functional profiling options

His Treatment Priority Ranking (if money no object):

1. CeGAT's anti-cancer peptide vaccines - 20% durable response in GBM, virtually side-effect free
2. SAGE Oncotest (functional profiling) - more accessible
3. CAR-T therapy (HER2 > B7-H3) - 20% response rate but severe side effects possible

If budget-constrained: Try to get into HER2 CAR-T clinical trial at Baylor (NCT04995003) - explicitly accepts "undifferentiated sarcoma"

Bottom Line:

This thread emphasizes getting the diagnosis right first through multiple expert pathology reviews, then pursuing functional testing to guide therapy selection, rather than jumping straight to standard protocols that may not fit this rare case.

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This information is for educational purposes only. Always consult your healthcare team for personalized medical advice and decisions.