NORMAL TISSUE COMPLICATION PROBABILITY MODELING OF ACUTE HEMATOLOGIC TOXICITY IN CERVICAL CANCER PATIENTS TREATED WITH CHEMORADIOTHERAPY

Purpose: To test the hypothesis that increased pelvic bone marrow (BM) irradiation is associated with increased hematologic toxicity (HT) in cervical cancer patients undergoing chemoradiotherapy and to develop a normal tissue complication probability (NTCP) model for HT. Methods and Materials: We tested associations between hematologic nadirs during chemoradiotherapy and the volume of BM receiving >= 10 and 20 Gy (V-10 and V-20) using a previously developed linear regression model. The validation cohort consisted of 44 cervical cancer patients treated with concurrent cisplatin and pelvic radiotherapy. Subsequently, these data were pooled with data from 37 identically treated patients from a previous study, forming a cohort of 81 patients for normal tissue complication probability analysis. Generalized linear modeling was used to test associations between hematologic nadirs and dosimetric parameters, adjusting for body mass index. Receiver operating characteristic curves were used to derive optimal dosimetric planning constraints. Results: In the validation cohort, significant negative correlations were observed between white blood cell count nadir and V-10 (regression coefficient (beta) = -0.060, p = 0.009) and V-20 (beta = -0.044, p = 0.010). In the combined cohort, the (adjusted) beta estimates for log (white blood cell) vs. V-10 and V-20 were as follows: -0.022 (p = 0.025) and -0.021 (p = 0.002), respectively. Patients with V-10 >= 95% were more likely to experience Grade >= 3 leukopenia (68.8% vs. 24.6%, p <0.001) than were patients with V-20> 76% (57.7% vs. 21.8%,p = 0.001). Conclusions: These findings support the hypothesis that HT increases with increasing pelvic BM volume irradiated. Efforts to maintain V-10 < 95% and V-20 < 76% may reduce HT. (C) 2011 Elsevier Inc.