Dosimetric predictors of acute hematologic toxicity during concurrent intensity-modulated radiotherapy and chemotherapy for anal cancer

Purpose: This study aimed at investigating whether the irradiated volume of pelvic bone marrow (PBM) and specific subsites may predict the occurrence of acute hematologic toxicity (HT) in anal cancer patients undergoing concurrent chemo-radiation. Methods: 50 patients, submitted to IMRT and concurrent chemotherapy, were analyzed. Several bony structures were defined on planning-CT: PBM and lumbar-sacral (LSBM), lower pelvis (LPBM) and iliac (IBM) bone marrow. On dose-volume histograms, dosimetric parameters were taken. Endpoints included white blood-cell-count (WBC), absolute-neutrophil-count (ANC), hemoglobin (Hb) and platelet nadirs and acute hematologic toxicity (HT) according to RTOG scoring scale. Generalized linear modeling was used to find correlations between dosimetric variables and blood cell nadirs, while logistic regression analysis was used to test correlation with ≥G3 HT. Receiver Operating Characteristic (ROC) curve analysis was used to evaluate the optimal cut-off points for predictive dosimetric variables with the Youden method. Results: Maximum detected acute HT comprised 38 % of ≥G3 leukopenia and 32 % of ≥G3 neutropenia. Grade 2 anemia was observed in 4 % of patients and ≥G3 thrombocytopenia in 10 %. On multivariate analysis a higher PBM-V₂₀ was associated with lower WBC nadir. Increased LSBM-V₄₀ was correlated with a higher likelihood to develop ≥G3 HT. A cut-off point at 41 % for LSBM-V₄₀ was found. Patients with LSBM-V₄₀ ≥41 % were more likely to develop ≥G3 HT (55.3 vs. 32.4 %; p < 0.01). Conclusions: Increased low-dose to pelvic bony structures significantly predicted for WBC decrease. Medium–high dose to specific osseous subsites was associated with a higher probability of HT. LSBM-V₄₀ was a strong predictor of ≥G3 HT. A threshold at 41 % for LSBM-V₄₀ could be used to limit HT.