Guidelines
ESMO/EURACAN/GENTURIS Guidelines for Treatment of Gastrointestinal Stromal Tumors
In September 2021, a clinical practice guideline for gastrointestinal stromal tumors (GISTs) was published by the European Society for Medical Oncology (ESMO), the European Reference Network for Rare Adult Solid Cancers (EURACAN), and the European Reference Network for Genetic Tumour Risk Syndromes (GENTURIS). [16] Treatment recommendations included the following.
Treatment recommendations for localized disease include the following:
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Standard treatment is complete surgical excision of the lesion, with no dissection of clinically negative lymph nodes. R0 excision is the goal. If laparoscopic excision is planned, it must follow the principles of oncologic surgery. For low-risk GISTs located in unfavorable locations, R1 margins may be acceptable in some cases.
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Adjuvant imatinib therapy (400 mg/day for 3 years) is the standard treatment for patients with a significant risk of relapse. In the case of KIT exon 9 mutation, adjuvant imatinib at a higher dosage (800 mg/day for 3 years) may be considered.
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Adjuvant therapy should not be employed for PDGFRA exon 18 D842V–mutated GISTs and should be avoided in NF1-related and SDH expression–negative GISTs.
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Patients with a very high risk of relapse due to tumor rupture at the time of surgery should be considered for adjuvant imatinib.
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If R0 surgery is not feasible or implies major sequelae and the tumor has a sensitive mutation, preoperative imatinib treatment is standard. For PDGFRA-D842V mutation, neoadjuvant avapritinib may be considered.
Treatment recommendations for advanced/metastatic disease include the following:
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Imatinib (400 mg/day) is the standard first-line treatment for patients with locally advanced, inoperable, and metastatic disease, except for GIST without KIT/PDGFRA mutations or with a PDGFRA-D842V mutation. Imatinib is also the standard treatment for metastatic disease when all lesions have been surgically removed and the tumor has a sensitive genotype, though surgery is not recommended as a primary approach in the metastatic setting.
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Standard first-line treatment for patients with KIT exon 9 mutation is imatinib 800 mg/day.
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Standard first-line treatment for patients with PDGFRA-D842V mutations is avapritinib 300 mg/day.
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For metastatic disease, treatment should be continued indefinitely unless the patient cannot tolerate it or specifically requests to stop it.
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Surgery of residual metastatic disease should be individualized.
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For an individual patient with limited progression of disease, surgical excision while imatinib is continued. If the tumor is progressing on imatinib 400 mg/day, the dosage can be increased to 800 mg/day (with the exception of insensitive mutations).
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For confirmed progression or (rare) intolerance on imatinib, standard second-line treatment is sunitinib either (a) 50 mg/day, 4 weeks on and 2 weeks off, or (b) 37.5 mg q24hr. For patients progressing on or failing to respond to imatinib and sunitinib, regorafenib 160 mg day for 3 out of every 4 weeks is the standard third-line therapy. For patients progressing on or intolerant of imatinib, sunitinib, and regorafenib, ripretinib 150 mg/day is the standard fourth-line treatment.
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SDH-deficient GISTs are insensitive to imatinib and can have some sensitivity to sunitinib and regorafenib; NTRK-rearranged GISTs are sensitive to treatment with NTRK inhibitors (eg, larotrectinib and entrectinib); and BRAF-mutated GISTs benefit from BRAF inhibitors (including BRAF–MEK inhibitor combinations).
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Rechallenge with imatinib (to which the patient has already been exposed with evidence of response) or continuation of treatment beyond progression is an option.
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Radiation therapy may be considered as a palliative resource for selected patients.
Media Gallery
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Benign gastric tumors. CT scan of the abdomen showing a large GIST in the wall of the lesser curvature of the stomach.
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Classification of benign gastric tumors.
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Upper endoscopy showing multiple gastric polyps.
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