Normal tissue complication probability modeling of acute hematologic toxicity in cervical cancer patients treated with chemoradiotherapy

Abstract

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 (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 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 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 (white blood cell) vs. V10 and V20 were as follows: -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) than 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.

Figure 1

Univariate plot of white blood cell count log(WBC Nadir) vs. bone marrow volume receiving 20 Gy or more (V₂₀) in the combined cohort. Regression coefficient (β) = −0.021 k/μL/%, p=0.002. *Log transformed.

Figure 2

Plot of observed white blood cell count (WBC) nadir (k/μL) vs. predicted WBC nadir in the combined cohort.

Figure 3

Receiver Operating Characteristic curves for grade ≥ 3 toxicity as a function of V₁₀ (a) and V₂₀ (b). The sensitivity and specificity corresponding to the optimal choice of cutoff is indicated by the intersection of the left-most diagonal line and the ROC curve.

Figure 3

Receiver Operating Characteristic curves for grade ≥ 3 toxicity as a function of V₁₀ (a) and V₂₀ (b). The sensitivity and specificity corresponding to the optimal choice of cutoff is indicated by the intersection of the left-most diagonal line and the ROC curve.