KEY POINTS
- This international multicenter retrospective series included 12 consecutive patients with progressive unresectable hepatic metastases from SDH-deficient GIST treated at three referral centers in Europe and the USA. Median age was only 27 years, and eight patients were female.
- Germline alterations involved SDHA in 6 patients, SDHB in 3 and SDHC in 3. Nine patients (75%) had previously undergone gastrectomy or additional cytoreductive surgery, and seven (58%) had received prior systemic treatment, predominantly tyrosine kinase inhibitors.
- Disease was usually extensive: 9/12 patients received bilobar Y-90 treatment. Five were treated with glass microspheres, six with resin and one with both across separate procedures; activity was calculated using MIRD, partition or modified body-surface-area methods rather than a standardized tumor absorbed-dose target.
- Best mRECIST response included 1 complete response (8.3%), 7 partial responses (58.3%) and 4 stable diseases (33.3%), producing an objective response rate of 66.7% and disease-control rate of 100%. Median maximum depth of response was 52.5%.
- At median follow-up of 32 months (range 3–77), only 2 patients had progressed, at 10 and 40 months after SIRT. Median progression-free and overall survival were not reached; only one patient died, from progressive peritoneal metastases while hepatic disease remained controlled.
- Treatment was generally well tolerated. Only one grade ≥3 event was reported: cholecystitis after right-lobar radioembolization requiring cholecystectomy. No clinically recognized delayed radioembolization-induced chronic hepatotoxicity was documented.
- The apparent durability is compelling but difficult to interpret because SDH-deficient GIST can have an indolent and highly variable natural history. Patient selection, heterogeneous Y-90 devices and dosimetry, prior systemic treatment and lack of a comparator make the results unsuitable for estimating treatment benefit causally.
CLINICAL TAKEAWAY
For selected patients with liver-dominant progressive SDH-deficient GIST, Y-90 radioembolization appears to offer potentially durable hepatic control despite the limited activity of conventional systemic therapy. The response signal is striking enough to justify prospective registry-level evaluation, but n=12 is far too small to establish a new treatment standard.