A multi-center, multi-organ, multi-omic prediction model for treatment-induced severe oral mucositis in nasopharyngeal carcinoma

Purpose: Oral mucositis (OM) is one of the most prevalent and crippling treatment-related toxicities experienced by nasopharyngeal carcinoma (NPC) patients receiving radiotherapy (RT), posing a tremendous adverse impact on quality of life. This multi-center study aimed to develop and externally validate a multi-omic prediction model for severe OM. Methods: Four hundred and sixty-four histologically confirmed NPC patients were retrospectively recruited from two public hospitals in Hong Kong. Model development was conducted on one institution (n = 363), and the other was reserved for external validation (n = 101). Severe OM was defined as the occurrence of CTCAE grade 3 or higher OM during RT. Two predictive models were constructed: 1) conventional clinical and DVH features and 2) a multi-omic approach including clinical, radiomic and dosiomic features. Results: The multi-omic model, consisting of chemotherapy status and radiomic and dosiomic features, outperformed the conventional model in internal and external validation, achieving AUC scores of 0.67 [95% CI: (0.61, 0.73)] and 0.65 [95% CI: (0.53, 0.77)], respectively, compared to the conventional model with 0.63 [95% CI: (0.56, 0.69)] and 0.56 [95% CI: (0.44, 0.67)], respectively. In multivariate analysis, only the multi-omic model signature was significantly correlated with severe OM in external validation (p = 0.017), demonstrating the independent predictive value of the multi-omic approach. Conclusion: A multi-omic model with combined clinical, radiomic and dosiomic features achieved superior pre-treatment prediction of severe OM. Further exploration is warranted to facilitate improved clinical decision-making and enable more effective and personalized care for the prevention and management of OM in NPC patients.