Title: CANONIC ANKI / ABOPM · Biomarker Interpretation
Tags: GOLD biomarker_interp SILVER guideline_drift

Q: mCODE FHIR rollout across 51 hospitals next quarter — looking for operational lessons from centers that have done this
A: Alexa Park · Fellow · Heme/Onc · breast focus
@devon_khan MD Anderson enforced mCODE at BOTH the registry AND tumor-board-documentation level — we learned fast that registry-only enforcement creates a shadow dataset that the clinical team doesn't trust. On the free-text-to-mCODE gap: we built a 'rescue' templated prompt in our EHR that fires on tumor-board note save and asks the clinician to map the free-text problem list to the mCODE disease primary code. Adoption was 40% at launch, 82% at month 6, stable at 91% after the first accreditation review. The reason: clinicians stopped trusting the registry numbers and started trusting the mCODE-structured ones. About 15% of our cancer types needed custom extensions — we pushed them upstream to the mCODE working group and landed 3 in STU4.
Thread: @devon_khan · Contributors: @alexa_park · Origin: https://onconex.ai/onconex/community/seed-onco-eng-02

Q: NTRK fusion in tumor-agnostic context — larotrectinib indication
A: AI note — cites the primary sources.
NCCN Guidelines Occult Primary v1.2024; Drilon A et al NEJM 2018 (larotrectinib); Solomon JP Mod Pathol 2020. ABOPM exam note: the fusion gene-first approach (NTRK, ALK, RET, ROS1) requires biomarker literacy across all solid tumor histologies; precision oncology is no longer organ-specific.
Marcus Freeman · Attending · Genomic pathology · PharmGKB CPIC contributor
Key testing caveat: NTRK IHC has reasonable sensitivity but poor specificity for NTRK3; confirmation with FISH or RNA-seq is needed for fusion detection. DNA-based NGS misses intronic breakpoints — always pair with RNA-seq for fusion detection. Reference: Solomon JP et al Mod Pathol 2020 (NTRK testing recommendations).
Thread: @alexa_park · Contributors: @canonic, @marcus_freeman · Origin: https://onconex.ai/onconex/community/onco-bio-01

Q: MSI-H vs TMB-H — when they disagree, which drives therapy?
A: AI note — cites the primary sources.
NCCN Endometrial v3.2024; Marabelle A Lancet Oncol 2020; ESMO Precision Medicine WG 2020. Pearl: dMMR (IHC MSH2/MSH6/MLH1/PMS2 loss) is the pathology-first surrogate for MSI-H — in endometrial it is now standard universal screening per NCCN.
Marcus Freeman · Attending · Genomic pathology · PharmGKB CPIC contributor
Agree — MSI-H is the stronger driver. TMB-H pembrolizumab approval (KEYNOTE-158) was controversial because of cross-histology variability; some cancer types (melanoma, NSCLC) respond better than others at same TMB. ESMO 2020 precision medicine recommendations downweight TMB-H outside MSI-H + checkpoint-native histologies. Reference: Marabelle A et al Lancet Oncol 2020 (KEYNOTE-158).
Thread: @alexa_park · Contributors: @canonic, @marcus_freeman · Origin: https://onconex.ai/onconex/community/onco-bio-03

Q: HRD score interpretation — BRCA vs genomic scar signatures
A: AI note — cites the primary sources.
NCCN Ovarian Cancer v2.2024; González-Martín NEJM 2019; Myriad myChoice CDx package insert. Note: the HRD cutoff 42 is assay-specific — FoundationOne CDx HRD+ uses a different threshold. Cross-platform comparison is not validated.
Marcus Freeman · Attending · Genomic pathology · PharmGKB CPIC contributor
HRD status is validated for first-line maintenance decisions in ovarian HGSC but not for subsequent lines. SOLO-1 (BRCA+) + PAOLA-1 (HRD+/BRCA-) + PRIMA (HRD+) are the three pivotal trials. HRD+/BRCA- benefits less than BRCA+ but benefits more than HR-proficient. Reference: González-Martín A et al NEJM 2019 (PRIMA); Ray-Coquard I et al NEJM 2019 (PAOLA-1).
Thread: @alexa_park · Contributors: @canonic, @marcus_freeman · Origin: https://onconex.ai/onconex/community/onco-bio-02