Predictors of acute toxicities during definitive chemoradiation using intensity-modulated radiotherapy for anal squamous cell carcinoma

Purpose. To identify clinical and dosimetric factors associated with acute hematologic and gastrointestinal (GI) toxicities during definitive therapy using intensity-modulated radiotherapy (IMRT) for anal squamous cell carcinoma (ASCC). Materials and methods. We retrospectively analyzed 108 ASCC patients treated with IMRT. Clinical information included age, gender, stage, concurrent chemotherapy, mitomycin (MMC) chemotherapy and weekly hematologic and GI toxicity during IMRT. From contours of the bony pelvis and bowel, dose-volume parameters were extracted. Logistic regression models were used to test associations between toxicities and clinical or dosimetric predictors. Results. The median age was 59 years, 81 patients were women and 84 patients received concurrent MMC and 5-fluorouracil (5FU). On multivariate analysis (MVA), the model most predictive of Grade 2 + anemia included the maximum bony pelvis dose (Dmax), female gender, and T stage [p = 0.035, cross validation area under the curve (cvAUC) = 0.66]. The strongest model of Grade 2 + leukopenia included V10 (percentage of pelvic bone volume receiving 10 Gy) and number of MMC cycles (p = 0.276, cvAUC = 0.57). The model including MMC cycle number and T stage correlated best with Grade 2 + neutropenia (p = 0.306, cvAUC = 0.57). The model predictive of combined Grade 2 + hematologic toxicity (HT) included V10 and T stage (p = 0.016, cvAUC = 0.66). A model including VA45 (absolute bowel volume receiving 45 Gy) and MOH5 (mean dose to hottest 5% of bowel volume) best predicted diarrhea (p = 0.517, cvAUC = 0.56). Conclusion. Dosimetric constraints to the pelvic bones should be integrated into IMRT planning to reduce toxicity, potentially reducing treatment interruptions and improving disease outcomes in ASCC. Specifically, our results indicate that Dmax should be confined to 57 Gy to minimize anemia and that V10 should be restricted to 87% to reduce incidence of all HT.