AbstractBackground and purposeOsteoradionecrosis (ORN) of the mandible represents a severe, debilitating complication of radiation therapy (RT) for head and neck cancer (HNC). At present, no Normal Tissue Complication Probability (NTCP) models for risk of ORN exist. The aim of this study was to develop a multivariable clinical/dose-based NTCP model for the prediction of ORN any grade (ORNI-IV) and Grade IV (ORNIV) following radiotherapy (± chemotherapy) in HNC patients.MethodsIncluded HNC patients were treated with (chemo-)radiotherapy between 2005 and 2015. Mandible bone radiation dose-volume parameters, and clinical variables (i.e. age, sex, tumor site, pre-RT dental extractions, chemotherapy history, post-operative RT and smoking status), were considered as potential predictors. The patient cohort was randomly divided into a training (70%) and independent test (30%) cohort. Bootstrapped forward variable selection was performed in the training cohort to select the predictors for the NTCP models. Final NTCP model(s) were validated on the holdback test subset.ResultsOf 1259 included HNC patients, 13.7% (n=173 patients) developed any grade ORN (ORNII-IV primary endpoint) and 5% (n=65) ORNIV (secondary endpoint). All dose and volume parameters of the mandible bone were significantly associated with the development of ORN in univariable models. Multivariable analyses identified D30% and pre-RT dental extraction as independent predictors for both ORNI-IV and ORNIV best-performing NTCP models with an AUC of 0.78 (AUCvalidation=0.75) and 0.81 (AUCvalidation=0.82), respectively.ConclusionThis study presented NTCP models – based on mandible bone D30% and pre-RT dental extraction – that predict ORNI-IV and ORNIV (i.e. needing invasive surgical intervention) following HNC radiotherapy. Our results suggest that less than 30% of the mandible should receive a dose of 35Gy or more for an ORNI-IV risk lower than 5%. These NTCP models can improve ORN prevention and management by identifying patients at risk of ORN.
Development of a multivariable normal tissue complication probability (NTCP) model for tube feeding dependence after curative radiotherapy/chemo-radiotherapy in head and neck cancer