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

PURPOSE: 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.

METHODS

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).

RESULTS

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.

CONCLUSION

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.