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 (CRT), and to develop a normal tissue complication probability (NTCP) model for HT. METHODS AND MATERIALS We tested associations between hematologic nadirs during CRT and the volume of BM receiving ≥ 10 and 20 Gy (V10 and V20) 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 37 identically treated patients from a prior study, forming a cohort of 81 patients for NTCP 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 (WBC) nadir and V10 (regression coefficient (β)=−0.060, p=0.009) and V20 (β=−0.044, p=0.010). In the combined cohort, the (adjusted) β estimates for log(WBC) vs. V10 and V20 were: −0.022 (p=0.025) and −0.021 (p=0.002), respectively. Patients with V10 ≥ 95% were more likely to experience grade ≥ 3 leukopenia (68.8% vs. 24.6%, p<0.001) as were patients with V20 > 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 V10 < 95% and V20 < 76% may reduce HT.

PURPOSE Death from noncancer causes (competing mortality) is an important event in head and neck cancer, but studies identifying predictors of this event are lacking. We sought to identify predictors of competing mortality and develop a risk stratification model for competing events. PATIENTS AND METHODS Cohort study of 479 patients with stage III to IV carcinoma of the head and neck diagnosed between August 1993 and November 2004. Patients were treated on consecutive prospective clinical trials involving organ-preserving chemoradiotherapy and surgery. We used multivariable competing risks regression models to analyze factors associated with the cumulative incidence of competing mortality, locoregional and distant failure, and second malignancies as first events. Results Median follow-up was 52 months median for survivors. The 5-year cumulative incidence of competing mortality was 19.6% (95% CI, 15.8 to 23.4). On multivariable analysis, competing mortality was associated with female sex (hazard ratio [HR], 1.72; 95% CI, 1.13 to 2.63), increasing age (HR, 1.30; 95% CI, 1.04 to 1.62), increasing Charlson Comorbidity Index (HR, 1.24; 95% CI, 1.05 to 1.47), decreasing body mass index (HR, 0.33; 95% CI, 0.13 to 0.84), and decreasing distance traveled to the treating center (HR, 0.65; 95% CI, 0.44 to 0.98). Patients with zero, one, two, and > or = three risk factors had 5-year competing mortality of 8.9% (95% CI, 3.0% to 14.8%), 12.4% (95% CI, 7.0% to 17.8%), 22.1% (95% CI, 14.5% to 29.7%), and 39.3% (95% CI, 28.6% to 50.1%), respectively. CONCLUSION Competing mortality in advanced head and neck cancer is associated with several demographic and health status characteristics. Analyses of risk factors for competing mortality may be useful in outcomes reporting and designing clinical trials.