Identifying threshold of CT-defined muscle loss after radiotherapy for survival in oral cavity cancer using machine learning

Objectives: Muscle loss after radiotherapy is associated with poorer survival in patients with oral cavity squamous cell carcinoma (OCSCC). However, the threshold of muscle loss remains unclear. This study aimed to utilize explainable artificial intelligence to identify the threshold of muscle loss associated with survival in OCSCC.

Materials and methods: We enrolled 1087 patients with OCSCC treated with surgery and adjuvant radiotherapy at two tertiary centers (660 in the derivation cohort and 427 in the external validation cohort). Skeletal muscle index (SMI) was measured using pre- and post-radiotherapy computed tomography (CT) at the C3 vertebral level. Random forest (RF), eXtreme Gradient Boosting (XGBoost), and Categorical Boosting (CatBoost) models were developed to predict all-cause mortality, and their performances were evaluated using the area under the curve (AUC). Muscle loss threshold was identified using the SHapley Additive exPlanations (SHAP) method and validated using Cox regression analysis.

Results: In the external validation cohort, the RF, XGBoost, and CatBoost models achieved favorable performance in predicting all-cause mortality (AUC: 0.898, 0.859, and 0.842). The SHAP method demonstrated that SMI change after radiotherapy was the most important feature for predicting all-cause mortality and consistently identified SMI loss ≥ 4.2% as the threshold in all three models. In multivariable analysis, SMI loss ≥ 4.2% was independently associated with increased all-cause mortality risk in both cohorts (derivation cohort: hazard ratio: 6.66, p < 0.001; external validation cohort: hazard ratio: 8.46, p < 0.001).

Conclusion: This study can assist clinicians in identifying patients with considerable muscle loss after treatment and guide interventions to improve muscle mass.

Key points: Question Muscle loss after radiotherapy is associated with poorer survival in patients with oral cavity cancer; however, the threshold of muscle loss remains unclear. Findings Explainable artificial intelligence identified muscle loss ≥ 4.2% as the threshold of increased all-cause mortality risk in both derivation and external validation cohorts. Clinical Relevance Muscle loss ≥ 4.2% may be the optimal threshold for survival in patients who receive adjuvant radiotherapy for oral cavity cancer. This threshold can guide clinicians in improving muscle mass after radiotherapy.