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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
GIST is a sarcoma of the gut wall driven almost always by a KIT or PDGFRA mutation. It was the proof that a pill can control a solid tumour: imatinib turned a median survival of about a year into one of eight years or more, and the mutation now dictates which drug to use.
GIST arises from interstitial cells of Cajal and carries activating KIT mutations (~75%, mostly exon 11, some exon 9) or PDGFRA mutations (~10%, including the imatinib-resistant D842V); the remainder are SDH-deficient (young patients, Carney-Stratakis), NF1-associated, or BRAF/NTRK-driven. Risk after resection is estimated from size, mitotic rate and site (Miettinen/AFIP, modified NIH).
Surgery is the only cure; adjuvant imatinib for three years improves survival in high-risk disease (SSGXVIII), with five years or longer under study. Advanced disease is treated with imatinib (400 mg; 800 mg for exon 9), then sunitinib (2006), regorafenib (2013) and ripretinib (INVICTUS, 2020) in sequence; avapritinib is the drug for PDGFRA D842V (2020). Resistance comes from secondary KIT mutations in the ATP-binding pocket (exon 13/14) or activation loop (exon 17/18) and is heterogeneous across lesions, which is why single next-generation inhibitors have struggled (INTRIGUE: ripretinib not superior to sunitinib overall, but better in ctDNA-defined exon 11 + 17/18 disease, now tested in INSIGHT) and why combinations (bezuclastinib + sunitinib, Peak) and ctDNA-guided selection are the current strategy. SDH-deficient GIST is TKI-insensitive and slow-growing; temozolomide has activity.
| Setting | Approach | Guideline |
|---|---|---|
| Localised, resectable | Complete resection without lymphadenectomy; adjuvant imatinib 3 years for high-risk (SSGXVIII); neoadjuvant imatinib to downsize when organ-sparing matters. | NCCN Category 1 (adjuvant imatinib, high risk), ESMO-MCBS A |
| Advanced, first line | Imatinib 400 mg (800 mg for KIT exon 9); avapritinib for PDGFRA D842V; continue until progression. | NCCN Category 1 |
| Advanced, second line | Sunitinib (or ripretinib for KIT exon 11 + 17/18 secondary mutations per ctDNA, INSIGHT). | NCCN Category 1 (sunitinib) |
| Advanced, third/fourth line | Regorafenib, then ripretinib (INVICTUS); rechallenge or continue TKI beyond progression; clinical trials (bezuclastinib-sunitinib). | NCCN Category 1 (regorafenib, ripretinib) |