An artificial intelligence-based endoscopic ultrasonography risk assessment and stratification for gastric stromal tumors.

Localized GIST: small (<2 cm) oesophagogastric or duodenal submucosal nodules should be assessed by endoscopic ultrasound and kept under annual surveillance, with excision reserved for lesions that grow or become symptomatic; if a biopsy diagnosis of GIST is obtained, resection is advised unless major morbidity is expected. For all other localized disease, standard treatment is complete surgical excision with microscopically negative (R0) margins, wide margins are not required and routine lymph node dissection is unnecessary because nodal involvement is rare, using function-preserving technique and taking care not to rupture the tumour (rupture worsens prognosis and is treated as metastatic risk). After an R1 (microscopically positive) resection, re-excision may be considered if the original site can be identified and major functional consequences are not expected. Mutational analysis of KIT and PDGFRA is standard practice in all GISTs (it may be omitted only for non-rectal GISTs <2 cm) and guides both prognosis and therapy. Adjuvant imatinib 400 mg/day for 3 years is recommended for completely resected tumours at significant (high) risk of relapse, where risk is estimated from mitotic index, tumour size and tumour site (plus rupture); adjuvant treatment is only appropriate when the mutation is imatinib-sensitive and is not indicated for imatinib-insensitive genotypes such as PDGFRA D842V (and is unlikely to benefit SDH-deficient or NF1-associated GIST). Metastatic or unresectable GIST: first-line imatinib 400 mg/day, except for tumours with a KIT exon 9 mutation where the starting dose is 800 mg/day; treatment is continued indefinitely and should not be interrupted, since interruption is generally followed by progression (surgery of residual/responding metastatic disease may be considered on a case-by-case basis). On progression or intolerance, sequential therapy is second-line sunitinib 50 mg/day (4 weeks on / 2 weeks off, or 37.5 mg/day continuously), third-line regorafenib 160 mg/day (3 weeks on / 1 week off), and fourth-line ripretinib 150 mg/day. PDGFRA D842V-mutant GIST is resistant to imatinib and is treated first-line with avapritinib 300 mg/day (these patients do not receive imatinib).