Effects of dose heterogeneity on response and toxicity after ⁹⁰Y-SIRT for HCC.

Abstract

Yttrium-90 (⁹⁰Y) selective internal radiation therapy (SIRT) is an established treatment for hepatocellular carcinoma (HCC), yet dose-response relationships remain incompletely understood. We evaluated whether voxel-based dose heterogeneity is associated with tumour response and treatment-related toxicity. This retrospective study included 45 HCC patients with 68 lesions treated with ⁹⁰Y resin SIRT. Dose distributions were derived from post-therapy ⁹⁰Y PET/CT. DVH-based metrics included hot-spot (D2, D10, Dmax), cold-spot (D90, D98, Dmin), and coverage parameters (V100, V150, V200). Tumour response was assessed using mRECIST. Grade ≥ 3 toxicity was classified as acute or latent. Lesions were stratified by median absorbed dose (D50 < 128 Gy vs. ≥ 128 Gy). Of 68 lesions, 44% achieved complete response. D50 did not differ significantly across mRECIST response categories. In low-D50 lesions, higher heterogeneity was associated with improved response. Hot-spot metrics (D2, D10, Dmax) showed similar trends. In high-D50 lesions, cold-spot metrics (D90, D98) were significantly associated with better response. Mean non-tumoral liver dose was associated with acute toxicity, while dose heterogeneity was associated with latent toxicity. Spatial dose distribution influences outcomes beyond mean absorbed dose. Tumour response was related to a dose level dependent pattern, with hot-spot-driven heterogeneity associated with response at lower dose levels and cold-spot metrics more relevant at higher dose levels. In addition, a temporal dissociation in toxicity was identified, with mean non-tumoral liver dose associated with acute injury and spatial dose heterogeneity associated with latent severe toxicity, supporting further evaluation of spatial dosimetry for individualized SIRT planning.