Yes he had oxaliplatin in Capox so he has had that twice with no results

I want to acknowledge what you're sharing - your husband has metastatic duodenal cancer with significant progression despite two rounds of CAPOX (oxaliplatin + capecitabine), and his genomic testing has revealed some important findings. This is a challenging situation, and I'm glad you're actively seeking information about next steps.

Understanding His Current Situation

What the imaging shows: His PET scan demonstrates widespread FDG-avid (metabolically active) lesions with progression - meaning the cancer is growing and spreading despite the chemotherapy he's already received. This tells his oncology team that the current approach isn't working and a treatment change is needed.

What his genomic test reveals - This is important:

His tumor has several significant findings:

1. HRD signature positive - This is potentially meaningful. HRD (Homologous Recombination Deficiency) suggests the cancer cells have difficulty repairing DNA damage. This finding, combined with his BRCA1 mutation (Q1756fs*74), opens specific treatment pathways.

2. Microsatellite stable (MSS) - This means immunotherapy alone (like checkpoint inhibitors) is less likely to be effective, which is important context.

3. MTAP loss - This is an emerging biomarker that some newer therapies target.

4. Other mutations (CDKN2A/2B loss, NF1, SMARCA4, CREBBP) - These provide additional information about the tumor's biology.

Clinical Reasoning for His Case

For metastatic duodenal adenocarcinoma that has progressed on standard chemotherapy, oncologists typically consider:

• PARP inhibitors - Given his HRD signature and BRCA1 mutation, PARP inhibitors (like olaparib or rucaparib) are specifically designed to exploit this vulnerability. According to NCCN Guidelines for gastric cancer (duodenal cancer follows similar principles), PARP inhibitors are increasingly considered for HRD-positive tumors.

• Targeted therapies - Depending on other factors, targeted approaches may be considered.

• Clinical trials - Given his specific mutation profile, he may be eligible for trials targeting MTAP loss or other pathways.

• Combination approaches - Sometimes PARP inhibitors are combined with other agents.

Critical Questions for His Oncology Team

Given his genomic results and progression on CAPOX, I'd strongly recommend asking:

1. "Given my HRD signature and BRCA1 mutation, have you considered PARP inhibitor therapy? If not, why not?" - This is a specific, evidence-based question based on his biomarkers.

2. "What clinical trials might I be eligible for given my specific mutation profile (MTAP loss, BRCA1 mutation, HRD signature)?" - Clinical trials may offer access to newer combinations.

3. "What is your recommended next treatment, and what is the rationale based on my genomic results?" - This ensures his doctor is using the genomic data to guide decisions.

4. "Are there any other genomic findings that should influence treatment selection?" - Make sure all findings are being considered.

5. "If this next treatment doesn't work, what would be the plan after that?" - Understanding the treatment sequence helps with planning.

Regarding Your Second Opinion Question

For BC Canada specifically:

• BC Cancer (provincial cancer agency) can facilitate second opinions through their tumor boards
• You can request a referral through his primary oncologist
• Many academic centers (like BC Cancer's Vancouver center) have expertise in rare cancers like duodenal adenocarcinoma
• His genomic report is portable - any oncologist can review it

The genomic data he has (FoundationOne CDx) is comprehensive and will be valuable for any second opinion consultation.

Important Context

The fact that his tumor is microsatellite stable (not MSI-high) and MMR intact (as you mentioned in your earlier question) means certain immunotherapy approaches are less likely to work as monotherapy, which is why the HRD signature and BRCA1 mutation become even more important - they point toward PARP inhibitor strategies.

This information is for educational purposes only. Always consult your healthcare team for personalized medical advice and decisions. Your husband's oncologist will determine the most appropriate next treatment based on his complete clinical picture, performance status, and other factors.

I'm here to help you understand his reports and formulate questions. Do you want me to explain any of the other genetic findings in more detail?