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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.
Most GISTs are driven by a mutation in exon 11 of the KIT gene, which keeps the KIT growth receptor switched on. Imatinib blocks it: given for three years after surgery in higher-risk tumours it prevents relapse and extends life, and in metastatic disease it controls the tumour for years before resistance develops.
Gastrointestinal stromal tumours arise from the interstitial cells of Cajal in the gut wall, and in 1998 Hirota showed that most carry activating mutations of KIT. Exon 11 mutations, which affect the juxtamembrane domain that normally holds the receptor inactive, account for around two thirds of all GISTs, occur at every site, and are the most sensitive to imatinib at 400 mg daily. Deletions involving codons 557 and 558 carry a worse prognosis than substitutions. Mutation testing is required before treatment because exon 9, PDGFRA D842V and wild-type tumours behave differently, and risk of relapse after surgery is estimated from size, mitotic count and site using the Miettinen or modified NIH criteria.
Surgery removes localised tumours with clear margins and without lymph node dissection, since GIST rarely spreads to nodes. Adjuvant imatinib for one year improved recurrence-free survival in ACOSOG Z9001 (2009), and the Scandinavian SSG XVIII trial (JAMA 2012) showed that three years beat one in high-risk tumours, with five-year overall survival of 92 percent against 82 percent; three years is standard for high-risk disease, and trials of five years are ongoing. Neoadjuvant imatinib shrinks large or awkwardly placed tumours, at the rectum or gastro-oesophageal junction, to allow organ-sparing surgery.
| Setting | Approach | Guideline |
|---|---|---|
| Localised, resectable | Complete surgical resection without lymphadenectomy; laparoscopic for smaller gastric tumours; neoadjuvant imatinib for large or poorly placed tumours. | not mapped |
| After resection, high risk | Three years of adjuvant imatinib 400 mg (SSG XVIII); trials of longer courses. | not mapped |
| Metastatic, first line | Imatinib 400 mg continued until progression, with CT response assessment by Choi criteria. | not mapped |
| Progression on imatinib | Dose escalation to 800 mg, then sunitinib, regorafenib and ripretinib, ideally guided by the secondary mutation on circulating tumour DNA. | not mapped |