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We evaluated whether voxel-based dose heterogeneity is associated with tumour response and treatment-related toxicity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This retrospective study included 45 HCC patients with 68 lesions treated with\n                      <jats:sup>90<\/jats:sup>\n                      Y resin SIRT. Dose distributions were derived from post-therapy\n                      <jats:sup>90<\/jats:sup>\n                      Y 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\u2009\u2265\u20093 toxicity was classified as acute or latent. Lesions were stratified by median absorbed dose (D50\u2009&lt;\u2009128\u00a0Gy vs.\u2009\u2265\u2009128\u00a0Gy).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Spatial dose distribution influences outcomes beyond mean absorbed dose. Tumour response was related to a dose level dependent pattern, with hot-spot\u2013driven 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00259-026-08064-1","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T05:03:44Z","timestamp":1784005424000},"page":"7071-7081","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of dose heterogeneity on response and toxicity after 90Y-SIRT for HCC"],"prefix":"10.1007","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7623-8451","authenticated-orcid":false,"given":"Huan","family":"Xi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlin","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andor W.J.M.","family":"Glaudemans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"van Sluis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simeon J.S.","family":"Ruiter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robbert J.","family":"de Haas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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All procedures performed in this study were in accordance with the ethical standards of the institutional research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.","order":1,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable. The manuscript does not contain identifiable individual-level data, images, or videos.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The requirement for written informed consent was waived for this retrospective non-WMO study.","order":3,"name":"Ethics","label":"Consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have no relevant financial or non-financial interests to disclose.","order":4,"name":"Ethics","label":"Conflicts of interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}