Dosimetric and Clinical Impact of Bone Marrow-sparing Radiation Therapy for Anal Cancer: A Systematic Review.

Purpose: This systematic review investigated the technical considerations, dosimetric feasibility, and clinical impact on hematologic toxicity (HT) associated with bone marrow (BM)-sparing radiation therapy in anal cancer. Methods and Materials: Original studies reporting associations between BM dosimetry and HT were identified from 6 databases and independently screened by 2 reviewers and reported according to the preferred reporting items for systematic reviews and meta-analyses 2020 standards. Study quality and risk of bias were appraised using Joanna Briggs Institute tools and the Grading of Recommendations, Assessment, Development, and Evaluation approach. Dosimetry analysis included active BM (ABM) structural definition, optimization strategies, and achievable dose reduction. Clinical efficacy was assessed using response measurement tools, toxicity predictors, and reported acute and late HT. Results: Thirty-five studies met the inclusion criteria. The outer pelvic bone marrow (PBM) was the most common BM surrogate, followed by the ilium, lumbar-sacrum, and lower pelvis. Contouring variations of the lumbar-sacrum were noted in 15 studies, primarily in the L3 to L5 vertebrae and inferior sacrum/coccyx. ABM was defined in 14 studies using various imaging modalities, including fluorodeoxyglucose-positron emission tomography, computed tomography, fluorothymidine positron emission tomography, or magnetic resonance imaging scans. Dosimetric findings suggested that selective sparing of PBM or its subunits reduced PBM V10 to V20 by 0% to 47%, and ABM V3 to V45 by 2% to 14%. Clinically derived predictors highlighted the importance of limiting low-to-intermediate dose exposure to the whole pelvis and lumbar-sacrum. Dose-response modeling accounted for variation in assessment tools and study endpoints. A wide range of acute HT rates was reported, with comparable outcomes among patients treated with and without BM-sparing intensity-modulated radiation therapy. Conclusions: Multimodality imaging facilitates the structure delineation of PBM and its substructures. Dose reduction to these structures can be achieved by using various planning strategies and treatment techniques. Predictive model development requires a comprehensive analysis of response measures and clinical confounders. Given the multifactorial and heterogeneous nature of HT, further investigation is required to determine whether BM dose sparing translates into clinically meaningful HT reduction.