Multivariate normal tissue complication probability modeling of vaginal late toxicity after brachytherapy for cervical cancer

Abstract Purpose To explore the best variables combination for a predictive model of vaginal toxicity in cervical cancer patients undergoing brachytherapy (BT). Methods and Materials Clinical and 3-dimensional dosimetric parameters were retrospectively extracted from an institutional database of consecutive patients undergoing intracavitary BT after external beam radiation therapy from 2006 to 2013 for a cervical cancer. A least absolute shrinkage and selection operator selection procedure in Cox's proportional hazards regression model was performed to select a set of relevant predictors for a multivariate normal tissue complication probability model of Grade ≥2 vaginal late toxicity. Outcomes reliability was internally assessed by bootstrap resampling method. Results One hundred sixty-nine women were included in the present study with a median followup time of 3.8 years (interquartile range [IQR], 1.9–5.6 years). The 2 years and 5 years cumulative incidence rates of Grade ≥2 late vaginal toxicity were 19.9% and 27.5%, respectively. Among 31 metrics and six clinical factors extracted, the optimal model included two dosimetric variables: V70 Gy and D5 % (the percentage volume that received a dose greater or equal to 70 Gy and the minimum dose given to the hottest 5% volume, respectively). Area under the ROC curve at 2 and 5 years of followup were 0.85 and 0.91, respectively. Regarding internal validation, median area under the ROC curve of bootstrap predictions was 0.83 (IQR, 0.78–0.88) and 0.89 (IQR, 0.85–0.93) at 2 and 5 years of followup, respectively. Conclusions A multivariate normal tissue complication probability model for severe vaginal toxicity based on two dosimetric variables (V70 Gy and D5 % ) provides reliable discrimination capability in a cohort of cervical cancer treated with external beam radiation therapy and BT.