How important is it to get a tissue sample to test mutations and proteins at this point

Why Tissue Testing Matters NOW (For You Specifically)

You're at a critical decision point: your current combination (gemcitabine/abraxane + avutometinib/defactinib) is showing progression in your lungs and liver, despite your tumor markers (CEA and CA 19-9) staying normal. This is exactly when additional biomarker testing can be most valuable.

Here's the clinical reasoning:

What We Already Know About Your Tumor:

• You have pMMR (proficient mismatch repair), which means you're NOT a candidate for immunotherapy alone
• Your markers are normal, which is unusual for progression—suggesting your tumor may have different biology than typical pancreatic cancer

What We DON'T Know Yet:

• Whether you have BRCA1/BRCA2 mutations (opens platinum-based therapy options)
• Your KRAS mutation status and specific type (some KRAS variants respond to newer targeted drugs)
• Microsatellite instability (MSI) status (different from MMR, but important)
• PD-L1 expression (could inform immunotherapy combinations)
• Other actionable mutations (PALB2, TP53, SMAD4 patterns)

The Practical Reality: Tissue vs. Liquid Biopsy

Tissue Biopsy (Endoscopic Ultrasound or CT-guided):

• Pros: Most comprehensive, can test multiple pathways, best for pancreatic cancer
• Cons: Invasive procedure, small risk of pancreatitis, takes time
• Timing: Given your liver involvement and current symptoms, your oncologist needs to assess if you're stable enough for the procedure

Liquid Biopsy (Blood test):

• Pros: Non-invasive, faster results, can detect circulating tumor DNA
• Cons: Less comprehensive than tissue, may miss some mutations
• Reality: For pancreatic cancer, liquid biopsy is improving but tissue is still preferred when feasible

What NCCN Guidelines Say

According to NCCN Pancreatic Cancer Guidelines, when patients show progression on initial therapy:

• Repeat biomarker testing (including BRCA, KRAS, MSI) is recommended to identify alternative treatment pathways
• The specific testing approach depends on your performance status and whether tissue is safely accessible

Your current situation—progression with normal markers—actually makes this testing MORE important, not less.

Your Specific Consideration: Hepatic Abscesses

This is important context: you had hepatic abscesses (liver infections) that required antibiotics. Your current AST is elevated at 57 U/L (normal is ~30-40). This means:

• Your liver is stressed from both the cancer spread AND the infection history
• Your oncologist needs to assess whether you're well enough for an invasive biopsy
• A liquid biopsy might be the safer first step given your liver status

Questions to Ask Your Oncologist THIS WEEK

1. "Given my progression, should we do additional biomarker testing? Would tissue biopsy or liquid biopsy be safer given my liver history?"

2. "What specific mutations or biomarkers would change my treatment options? (BRCA, KRAS variants, MSI, PD-L1?)"

3. "If we find a BRCA mutation, what treatment options open up? If we find MSI-high, what changes?"

4. "How soon could we get results, and would that affect our treatment timeline?"

5. "Given my elevated liver enzymes and abscess history, what's the safest way to get this testing done?"

The Bottom Line on Timing

Yes, tissue/biomarker testing is important right now. Here's why:

• You've already tried FOLFIRINOX → RMC-6236 → current combination
• Your progression suggests your tumor may have specific vulnerabilities your team hasn't identified yet
• Testing could reveal options like BRCA-directed therapy (platinum + PARP inhibitors) or other targeted approaches
• The sooner you know, the sooner you can pivot to something that might work better

However, the method of testing (tissue vs. liquid) and timing depend on your current health status—especially given your liver involvement and recent infection.

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This information is for educational purposes only. Always consult your healthcare team for personalized medical advice and decisions. Your oncologist will determine whether you're stable enough for tissue biopsy and which biomarkers are most relevant to test based on your complete clinical picture.