Ultra-selective radiation segmentectomy for early-stage hepatocellular carcinoma

Background and Aims Radiation-segmentectomy (RS) is an emerging curative-intent therapy for early-stage hepatocellular carcinoma (HCC) when resection or ablation is not feasible. This study evaluates the safety, efficacy, and dosimetric correlates of ultra-selective RS (uRS), defined as glass 90 Y-radioembolization delivered to vessels at least one order beyond parent segmental arteries, targeting <1 Couinaud segment. Methods This retrospective study included 38 patients with 42 early-stage (BCLC 0–A) HCCs treated with uRS from December 2022 to July 2024. All treatments used glass 90 Y-microspheres with perfused treatment volumes assessed by cone-beam computed-tomography (CT). Post-treatment voxel-based dosimetry was conducted using 90 Y-single-photon-emission-tomography (SPECT/CT). Tumor response and progression-free survival (PFS) were assessed by modified Response Evaluation Criteria in Solid Tumors (mRECIST). Explant pathology evaluated treatment effect in transplant recipients, and ALBI scores were tracked longitudinally. Results Median tumor size was 2.4 cm with a median perfused treatment volume of 66.3 cc (4.5% total liver). The median administered activity was 1.36 GBq (median dose 837 Gy). Complete response (CR) was achieved in 87% (n=33), with only one local progression. Median local-PFS was not reached. Among 16 tumors with explant data, 69% showed complete necrosis and 25% extensive necrosis (median 88%). Tumor D 95 >300 Gy predicted CR (97% CR vs. 0% CR with D 95 <300 Gy; p<0.001), with logistic regression yielding 0.98 AUC. Models incorporating tumor alignment within high-activity 90 Y-SPECT regions improved predictive accuracy. Over 82% of patients retained or improved ALBI grade over follow-up, with only 2 of 15 with baseline ALBI 2b declining to grade 3. Conclusions Ultra-selective radiation-segmentectomy (uRS) is a feasible and liver-sparing therapy for early-stage HCC. Voxel-based dosimetry confirms dose-response relationships and underscores the importance of tumor coverage. Impact and Implications This study demonstrates that ultra-selective radiation segmentectomy (uRS) with glass 90 Y microspheres can achieve high rates of complete imaging and pathologic response in early-stage HCC while treating very small liver volumes. These results replicate and extend prior radiation segmentectomy studies, underscoring the ablative potential of 90 Y can be maintained with even greater liver parenchymal preservation. These findings are important for patients who are not candidates for surgery or ablation, especially given low rates of liver function decline after uRS. In practice, uRS may serves as a definitive or bridging therapy to liver transplantation, while voxel-based dosimetry provides a framework for ensuring adequate tumor coverage and identifying incomplete responders.