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Selective Internal Radiation Therapy (SIRT) for SDH-Deficient GIST Demonstrates Encouraging Durable Response Rates: An International Multicenter Case Series
by
, ,
Zachary T. Berman
1,2,*
,
Peter Hohenberger
3
,
Ramesh Bulusu
4,
Steven C. Rose
1,
Paul T. Fanta
2,5,
Jonathan Evans
6,
Steffen Diehl
7,
Franka Menge
3,
Nasim Ali
8 and
Jason K. Sicklick
1,2,9 1
Department of Radiology, Division of Interventional Radiology, University of California San Diego, San Diego, CA 92103, USA
2
Moores Cancer Center, University of California San Diego, La Jolla, CA 92037, USA
3
Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, 68135 Mannheim, Germany
4
Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0QQ, UK
5
Department of Medicine, Division of Medical Oncology, University of California San Diego, San Diego, CA 92093 , USA
6
Department of Radiology, Royal Liverpool University Hospital, Prescot St., Liverpool L7 8XP, UK
7
Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Heidelberg University, 68167 Mannheim, Germany
8
The Clatterbridge Cancer Centre NHS Foundation Trust, Wirral CH63 4JY , UK
9
Department of Surgery, Division of Surgical Oncology, University of California San Diego, San Diego, CA 92093, USA
*
Author to whom correspondence should be addressed.
Cancers 2026, 18(16), 2704; https://doi.org/10.3390/cancers18162704
Submission received: 9 July 2026
/
Revised: 12 August 2026
/
Accepted: 18 August 2026
/
Published: 20 August 2026
(This article belongs to the Section Methods and Technologies Development)
Simple Summary
Succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST) is a rare disease that often affects younger patients and has limited response to standard systemic therapies. Liver metastases are usually unresectable as they tend to be multifocal or bilobar. This international multicenter case series describes 12 patients treated with yttrium-90 selective internal radiation therapy for SDH-deficient GIST liver metastases. Treatment achieved disease control in all patients, an objective response in two-thirds, and durable intrahepatic control with limited toxicity. These findings support liver-directed radioembolization as a useful option for carefully selected patients and justify a multicenter registry-based study.
Abstract
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.
