Four longitudinal phenotypes of radiation-associated dysphagia following oropharyngeal radiotherapy: a latent class trajectory analysis

Background and purpose. Patients with oropharyngeal cancer (OPC) treated with radiotherapy (RT) exhibit heterogeneous courses of radiation-associated dysphagia (RAD) during recovery, yet most survivorship models typically treat RAD uniformly. This study aimed to identify distinct, data-driven RAD longitudinal Phenotypes based on imaging-graded swallow function from pre-treatment to 30 months post-RT and to characterize their baseline predictors. Materials and methods. Heterogeneous linear mixed-effects latent class trajectory modeling was applied to longitudinal DIGEST scores from the Stiefel MDA-OPC prospective registry. Eligible patients had [≥]3 Modified Barium Swallow (MBS) assessments between baseline and 30 months post-RT. Models were evaluated across functional forms and 1-5 latent classes; final selection used the Bayesian Information Criterion. Baseline predictors of class membership were identified via binary logistic regression. Results. The cohort comprised 650 OPC patients (2,116 MBS assessments; mean age 61 years, 89% male, 93% HPV-positive). Four RAD Phenotypes were identified: No/Minimal RAD (n=385/650, 59%), Mild/Moderate RAD (n=104/650, 16%), Moderate/Severe Transient RAD (n=94/650, 15%), and Moderate/Severe Progressing RAD (n=67/650, 10%). Classification quality was acceptable (mean posterior probabilities 0.78-0.89; entropy 0.69). Baseline DIGEST impairment, base-of-tongue primary, advanced T stage, and age [≥]60 independently predicted membership in higher-burden Phenotypes (AUC=0.845; 10-fold CV-AUC=0.835). Conclusion. RAD following RT for OPC comprises four biologically and clinically distinct longitudinal Phenotypes, predictable from pre-treatment characteristics. These findings support trajectory phenotyping as outcome framework for RAD research and risk-adaptive survivorship care.