<![CDATA[Accurate prediction of treatment response after yttrium-90 (Y-90) radioembolization is essential for optimizing the management of hepatocellular carcinoma (HCC), particularly as immunotherapy increasingly influences treatment strategies. This systematic review aimed to synthesize evidence on imaging and dosimetric predictors of radiologic response and assess their relevance in the immunotherapy era. PubMed, Embase, Cochrane CENTRAL, Scopus, and Web of Science were searched from inception through August 10, 2026. Eligible studies evaluated imaging or dosimetric predictors in adults undergoing Y-90 radioembolization. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool, supplemented by relevant Prediction Model Risk of Bias Assessment Tool (PROBAST) domains for prediction-model studies, while certainty of evidence was evaluated using a GRADE-informed approach. Fourteen studies were included in the narrative synthesis because methodological heterogeneity precluded meta-analysis. Higher tumor-absorbed doses consistently predicted objective and complete responses. In a randomized trial, personalized dosimetry increased the objective response rate of targeted lesions from 36% to 71%. However, dose thresholds varied according to microsphere type and dosimetric methodology. Radiomics demonstrated promising discriminatory performance, with areas under the receiver operating characteristic curve (AUCs) reaching 0.89, although small sample sizes and limited external validation reduced the certainty of the evidence. Models combining imaging and dosimetric parameters showed potential complementary predictive value. No included study specifically evaluated concurrent immunotherapy. Personalized dosimetry currently provides the strongest evidence for optimizing treatment response, whereas radiomics requires further prospective and external validation. Standardized, multicenter studies are needed to establish reproducible dose thresholds and evaluate Y-90 radioembolization in combination with immunotherapy.]]>
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