Tumor response prediction in ⁹⁰Y radioembolization with PET-based radiomics features and absorbed dose metrics

Purpose: To evaluate whether lesion radiomics features and absorbed dose metrics extracted from post-therapy ⁹⁰Y PET can be integrated to better predict outcomes in microsphere radioembolization of liver malignancies Methods: Given the noisy nature of ⁹⁰Y PET, first, a liver phantom study with repeated acquisitions and varying reconstruction parameters was used to identify a subset of robust radiomics features for the patient analysis. In 36 radioembolization procedures, ⁹⁰Y PET/CT was performed within a couple of hours to extract 46 radiomics features and estimate absorbed dose in 105 primary and metastatic liver lesions. Robust radiomics modeling was based on bootstrapped multivariate logistic regression with shrinkage regularization (LASSO) and Cox regression with LASSO. Nested cross-validation and bootstrap resampling were used for optimal parameter/feature selection and for guarding against overfitting risks. Spearman rank correlation was used to analyze feature associations. Area under the receiver-operating characteristics curve (AUC) was used for lesion response (at first follow-up) analysis while Kaplan-Meier plots and c-index were used to assess progression model performance. Models with absorbed dose only, radiomics only, and combined models were developed to predict lesion outcome. Results: The phantom study identified 15/46 reproducible and robust radiomics features that were subsequently used in the patient models. A lesion response model with zone percentage (ZP) and mean absorbed dose achieved an AUC of 0.729 (95% CI 0.702–0.758), and a progression model with zone size nonuniformity (ZSN) and absorbed dose achieved a c-index of 0.803 (95% CI 0.790–0.815) on nested cross-validation (CV). Although the combined models outperformed the radiomics only and absorbed dose only models, statistical significance was not achieved with the current limited data set to establish expected superiority. Conclusion: We have developed new lesion-level response and progression models using textural radiomics features, derived from ⁹⁰Y PET combined with mean absorbed dose for predicting outcome in radioembolization. These encouraging, but limited results, will need further validation in independent and larger datasets prior to any clinical adoption.