Development of a nomogram for predicting grade 2 or higher acute hematologic toxicity of cervical cancer after the pelvic bone marrow sparing radiotherapy

Abstract

Background: Acute hematologic toxicity (HT) is a common complication during radiotherapy of cervical cancer which may lead to treatment delay or interruption. Despite the use of intensity-modulated radiation therapy (IMRT) with the pelvic bone marrow (PBM) sparing, some patients still suffer from acute HT. We aimed to identify predictors associated with HT and develop a nomogram for predicting grade 2 or higher (G2+) acute HT in cervical cancer following the PBM sparing strategy.

Methods: This study retrospectively analyzed 125 patients with cervical cancer who underwent IMRT with the PBM sparing strategy at our institution. Univariate and multivariate logistic regression, best subset regression, and least absolute shrinkage and selection operator (LASSO) regression, respectively, were used for predictor screening, and Akaike information criterion (AIC) was used to determine the best model for developing the nomogram. Finally, we quantified the risk of G2+ acute HT based on this model to establish a risk stratification.

Results: The independent predictors used to develop the nomogram were histological grade, pre-radiotherapy chemotherapy, pre-radiotherapy HT, and radiotherapy [IMRT alone vs. concurrent chemoradiotherapy (CCRT)] which were determined by the univariate and multivariate logistic regression with the minimum AIC of 125.49. Meanwhile, the heat map showed that there is no multicollinearity among the predictors. The nomogram was well-calibrated to reality, with a Brier score of 0.15. The AUC value was 0.82, and the median Brier score and AUC in 1000 five-fold cross-validation were 0.16 and 0.80, respectively. The web version developed together was very easy to use. The risk stratification indicated that high-risk patients (risk point > 195.67) were more likely to develop G2+ acute HT [odds ratio (OR) = 2.17, 95% confidence interval (CI): 1.30-3.05].

Conclusion: This nomogram well-predicted the risk of G2+ acute HT during IMRT in cervical cancer after the PBM sparing strategy, and the constructed risk stratification could assist physicians in screening high-risk patients and provide a useful reference for future prevention and treatment strategies for acute HT.

Keywords: cervical cancer; hematologic toxicity; intensity-modulated radiation therapy; nomogram; risk stratification.