Generalizability assessment of head and neck cancer NTCP models based on the TRIPOD criteria

This review aimed to provide an overview of the level of maturity of normal tissue complication probability (NTCP) models for head and neck cancer (HNC) patients. A systematic literature review was performed to retrieve NTCP models for HNC toxicities. Patient population characteristics, NTCP model and the predictors, treatment technique and endpoint definition were extracted per article. Models were then scored based on the TRIPOD (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) consensus guidelines to evaluate their generalizability. 335 articles on photon and proton therapy of HNC were identified and 52 relevant articles were further analyzed. Eighteen articles on xerostomia and sticky saliva (TRIPOD types 1a-2b: 15; TRIPOD type 3: 1; TRIPOD types 4a: 1 & 4b:1), thirteen articles on dysphagia and tube feeding dependence (TRIPOD types 1a-2b: 7; TRIPOD type 3: 2; TRIPOD types 4a:2 & 4b:2), five articles on oral mucositis (TRIPOD types 1a-2b: 4; TRIPOD type 4b: 1), seven articles on hypothyroidism (TRIPOD types 1a-2b: 4; TRIPOD type 3: 1; TRIPOD types 4a: 1 & 4b:1), four articles on hearing loss and tinnitus (TRIPOD type 1a: 4) and ten articles on esophagitis (TRIPOD types 1a-2b: 9; TRIPOD type 4a: 1) were included. External validation studies of HNC NTCP models are scarce. Moreover, the majority of them were validating a model developed by the same researchers. Only 2 independent external validation studies were found. There is a strong need to publish external validation studies to get more mature NTCP models applicable in clinical practice.