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GIST Resistance — SCE Medical Oncology MCQ

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HardGI CancersGIST ResistanceSCE Medical Oncology

A 45-year-old man with metastatic GIST (KIT exon 11 mutation) has been on imatinib 400 mg daily for 3 years with stable disease. CT now shows enlargement of one hepatic lesion while all others remain stable — a 'nodule within a nodule' appearance. What does this represent?

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Correct answer: D — Focal resistance — a resistant clone emerging within a responding lesion

The 'nodule within a nodule' sign on CT is pathognomonic of focal/clonal resistance in GIST on imatinib. A new enhancing focus develops within a previously responding (hypoattenuating) metastasis, indicating emergence of a secondary KIT/PDGFRA resistance mutation. Management options include dose escalation of imatinib (800 mg for KIT exon 9), switching to sunitinib (standard second-line) or, for truly localised resistance, surgical resection or ablation of the resistant nodule while continuing imatinib.

Reference: ESMO 2024 GIST Guidelines; Demetri et al Lancet 2006; Choi criteria for GIST response