Adverse genotype or anatomic risk in GIST: PDGFRA D842V (imatinib-resistant — avapritinib...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`RF-GIST-HIGH-RISK-BIOLOGY`
Type	Red flag
Status	reviewed 2026-04-26 \| pending_clinical_signoff
Diseases	`DIS-GIST`
Sources	`SRC-NCCN-MELANOMA-2025` `SRC-ONCOKB`

Red Flag Origin

Definition	Adverse genotype or anatomic risk in GIST: PDGFRA D842V (imatinib-resistant — avapritinib indicated), KIT exon 9 mutation (requires imatinib 800 mg), SDH-deficient / KIT-PDGFRA wild-type (TKI-refractory), tumor rupture, mitotic rate >10/50 HPF, or size >10 cm — each shifts adjuvant duration or 1L drug choice.
Clinical direction	intensify
Category	high-risk-biology

Trigger Logic

{
  "any_of": [
    {
      "finding": "BIO-PDGFRA",
      "value": "D842V"
    },
    {
      "finding": "BIO-KIT",
      "value": "exon-9"
    },
    {
      "finding": "sdh_deficient",
      "value": true
    },
    {
      "finding": "kit_pdgfra_wildtype",
      "value": true
    },
    {
      "finding": "tumor_rupture",
      "value": true
    },
    {
      "comparator": ">",
      "finding": "mitotic_rate_per_50hpf",
      "threshold": 10
    },
    {
      "comparator": ">",
      "finding": "primary_tumor_size_cm",
      "threshold": 10
    }
  ],
  "type": "biomarker"
}

Notes

Genotype is the dominant decision axis in GIST. PDGFRA D842V is imatinib-RESISTANT — avapritinib 1L (NAVIGATOR / VOYAGER, ORR ~88%). KIT exon 9 (typically small bowel) requires imatinib 800 mg/day from start (B2222 / EORTC-62005 dose effect; PFS ~19 vs 6 mo on 400 mg). SDH-deficient (Carney triad / Carney-Stratakis, gastric, young) responds poorly to TKI — clinical trial preferred. Tumor rupture upgrades to highest-risk per Joensuu / NIH consensus → 6 yr extended adjuvant (SSG-XXII). Mitoses >10/50 HPF + size >10 cm + non-gastric primary all push to extended adjuvant duration.

Used By

Indications

IND-GIST-4L-RIPRETINIB - IND-GIST-4L-RIPRETINIB