Selective Internal Radiation Therapy (SIRT) for SDH-Deficient GIST Demonstrates Encouraging Durable Response Rates:...

Background/Objectives: Succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumors (GISTs) are a rare subgroup of GISTs and respond poorly to conventional systemic therapies. This study describes long-term outcomes after yttrium-90 (Y-90) selective internal radiation therapy (SIRT) for progression of unresectable SDH-deficient GIST hepatic metastases. Methods: We performed a retrospective review of consecutive patients treated with SIRT at three tertiary referral centers in Europe and the United States. Data collection included demographics, tumor profiling, prior therapies, Y-90 dosimetry approach, imaging response, adverse events, and long-term outcomes. Results: Twelve patients (66.7% female) with a median age of 27 years (range, 17-57 years) were included. One patient had a complete response (8.3%) and seven had partial responses (58.3%) by modified Response Evaluation Criteria in Solid Tumors. Four patients (33.3%) had tumor shrinkage that did not meet partial response criteria. The objective response rate was 66.7%, with a disease control rate of 100%. One grade 3 or higher adverse event was observed (cholecystitis requiring cholecystectomy). At a median follow-up of 32 months (range, 3-77 months), two patients experienced disease progression. Median overall survival was not reached, with one death during follow-up. Conclusions: SIRT appears safe and effective for patients with progressive, unresectable SDH-deficient GIST hepatic metastases, with durable responses and limited serious toxicity. These findings suggest that SDH-deficient GIST may be more sensitive to radiation than previously appreciated and that SIRT may be a useful liver-directed approach for patients with limited systemic options.