4$π$ Planning for the Reduction of Predicted Hematologic Toxicity Risk in Cervical Cancer Radiotherapy

Abstract

Purpose: In conventional coplanar radiotherapy for cervical cancer, nearby pelvic bones receive high radiation doses, increasing the risk of acute hematologic toxicity (HT). This study aims to estimate the HT risk reduction achievable with non-coplanar (4$π$) radiotherapy. Methods: We retrospectively analyzed 114 cervical cancer patients treated with coplanar volumetric modulated arc therapy (VMAT) between 2021 and 2023. Radiomic features from planning CTs were extracted and combined with clinical and dosimetric data to train predictive machine learning models. Patients were then replanned using integrated non-coplanar beam orientation and fluence map optimization (4$π$ planning). The top performing model was applied to these new plans to evaluate potential HT reduction. Results: Models combined radiomics, clinical, and dosimetric features achieved the highest predictive performance (AUC = 0.79). Feature importance analysis highlighted CT radiomic and dosimetric variables as the strongest predictors. Compared to VMAT, 4$π$ non-coplanar planning significantly reduced doses to the bone marrow (V10Gy, V20Gy, V30Gy, and V40Gy by 28%, 52%, 47%, and 33%, respectively) while significantly reducing dose to other pelvic organs at risk (OAR). When evaluated by the model, this improved dosimetry translated into a 23% reduction in predicted HT risk (risk ratio: 0.77; 95% CI: 0.75-0.79 and odds ratio: 0.68; 95% CI:0.65-0.71). Conclusions: Non-coplanar 4$π$ radiotherapy significantly lowers radiation doses to major pelvic bones during cervical cancer treatment without compromising target coverage or sparing of other OARs. Based on our predictive model, this superior dosimetry should translate to a marked reduction in acute hematologic toxicity.