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Updated: Jul 15, 2026

Y-90 Radioembolization and PD-1 Inhibitor as Neoadjuvant Treatment in Hepatocellular Carcinoma
Published on: May 24, 2024
Effects of dose heterogeneity on response and toxicity after 90Y-SIRT for HCC
Huan Xi1, Xinlin Zheng2, Andor W J M Glaudemans2
1Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands. h.xi@umcg.nl.
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.
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