Radiographic progression on imatinib (RECIST progression or new lesion), focal nodule-wit...

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

ID	`RF-GIST-TRANSFORMATION-PROGRESSION`
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	Radiographic progression on imatinib (RECIST progression or new lesion), focal nodule-within-mass pattern on CT, rising SUV on PET, or imatinib trough <1100 ng/mL — requires re-biopsy for secondary KIT mutation, consideration of imatinib dose escalation to 800 mg, or switch to sunitinib / regorafenib / ripretinib.
Clinical direction	intensify
Category	transformation-progression

Trigger Logic

{
  "any_of": [
    {
      "finding": "imatinib_progression_recist",
      "value": true
    },
    {
      "finding": "nodule_within_mass_pattern",
      "value": true
    },
    {
      "finding": "rising_suv_on_imatinib",
      "value": true
    },
    {
      "comparator": "<",
      "finding": "imatinib_trough_ng_ml",
      "threshold": 1100
    }
  ],
  "type": "composite_clinical"
}

Notes

Focal progression on imatinib classically arises from secondary KIT exon 13 / 14 (ATP-binding) or 17 / 18 (activation-loop) mutations emerging clonally. Sequence: dose-escalate to 800 mg if exon 11 with focal progression and trough low; switch to sunitinib (B2222 follow-on; ATP-binding mutations preferentially sensitive) at clear RECIST progression; regorafenib (GRID) at 3L; ripretinib (INVICTUS, switch-control inhibitor with broad coverage of secondary mutations) 4L. Imatinib trough monitoring (target ≥1100 ng/mL) flags pharmacokinetic non-response distinct from biological resistance. Nodule-within-mass is a sensitive early imaging sign of resistance (Choi response criteria literature).

Used By

No reverse references found in the YAML corpus.