The efficacy and safety of radiotherapy combined with tyrosine kinase inhibitors in the treatment of advanced GIST.

Abstract

e23519 Background: Phase II multicenter study (identifier NCT00515931) have found that gastrointestinal stromal tumor (GIST) is moderately sensitive to radiotherapy, and we have applied this treatment for patients with advanced GIST. Methods: Patients with GIST progressing or metastasis were received radiotherapy. The tumors were treated with external beam radiotherapy and conventional fractionation. Radiotherapy was administered as simultaneous integrated boost (SIB), if the tumor with a fixed position or a diameter exceeding 10 cm. The tumor edge radiotherapy dose was 45–50.4 Gy. Based on the tumor contour, the dose is escalated by 10% for each uniform inward margin reduction of 1–2 cm. Systemic therapy was maintained unaltered during the study. The primary observation was target lesion response to radiotherapy. Results: Thirteen patients received radiation therapy in our center until July 1, 2024 (Table). The median largest target tumor diameter was 9.9 cm (range, from 4.2 to 21.1 cm). Genetic detection of primary tumors was completed in 11 patients, including 8 with KIT exon 11 mutation (73%), 1 with KIT exon 9 mutation (9%), and 2 with wild type for KIT/PDGFRA mutation (18%). All the patients receive tyrosine kinase inhibitors during radiotherapy, 5 (39%) receive imatinib, 2 (15%) sunitinib, 2 (15%) regorafenib, 3 (23%) repaitinib and 1 (8%) had a combination of imatinib and sunitinib. The time from GIST diagnosis to start of radiotherapy was 72 months (range, from 10 to 166 months). The median tumor edge dose was 47.5 Gy (range, from 45 to 50.4 Gy). Radiographic efficacy was evaluated 3-6 months after the end of radiotherapy. According to the Recist1.1 standard, all the target lesions was stabilized disease (n=13,100%). Efficacy was evaluated in 11 patients according to Choi's criteria, 8 patients had partial response and 3 patients were stabilized disease. There was no difference in radiotherapy efficacy among different genotypes. The median follow-up time was 6 months (range, from 3 to 23 months), none of the radiotherapy-treated lesions progressed during the follow-up. Radiotherapy was generally well tolerated. Adverse events were usually mild to moderate (grade 1 or 2), none of the patients had grade 3-4 adverse reactions. Conclusions: The most patients had durable stabilization of the target lesions to radiotherapy. Advanced GIST patients benefit frequently from radiotherapy. The model of radiotherapy combined with TKI in the treatment of advanced GIST patients deserves further exploration. Characteristics of the patients and the tumors. Characteristic Median (range) Number (%) Age (years) 58（29-79） Gender Male 9 (69%) Female 4 (31%) Radiotherapy sites Liver 1 (8%) Intra-abdominal 11 (84%) Soft tissue 1 (8%) No. of systemic therapies prior to radiotherapy 1 6 (46%) 2 4 (31%) 3–5 3 (23%)