Optimization of Automated Radiotherapy Planning for Head and Neck Cancers and Brain Tumors Using Knowledge-Based...

Objectives: Our objective was to develop and evaluate a locally trained knowledge-based planning (KBP) model for head and neck (H&N), brain, and central nervous system malignancies using RapidPlan, and to determine whether standard statistical metrics such as the coefficient of determination (R²) and outlier frequency are definitive predictors of clinical utility. Methods: An institutional dataset of 594 plans was retrospectively curated into a 497-plan training set. Performance was evaluated in 370 paired plan comparisons generated with identical beam geometry. Training-validation overlap was explicitly quantified at both plan and patient levels, and a plan-level held-out sensitivity analysis was performed. Additional analyses included monitor units (MUs), subgroup assessment, clinically relevant OAR threshold achievement, and 95% confidence intervals for paired differences. Results: The validation set included 370 plans from 289 patients. At the plan level, 303 validation plans overlapped with the training model, and 67 were held-out cases; at the patient level, no fully patient-independent validation cohort was available. RapidPlan maintained target coverage while reducing OAR doses, including oral cavity Dmean (-7.62%Rx; 95% CI: -8.91 to -6.32; p < 0.001) and larynx Dmean (-7.57%Rx; 95% CI: -9.14 to -6.00; p < 0.001). The same direction of benefit was observed in the plan-level held-out subset. MU did not increase with RapidPlan and decreased from 764.2 ± 275.5 to 695.8 ± 210.3 MU (Delta = -68.4 MU; 95% CI: -89.4 to -47.4; p < 0.001). Conclusions: A high R² was not required for clinically useful optimization objectives in this heterogeneous cohort. However, the retrospective design and patient-level overlap limit claims of full generalizability. The model should therefore be interpreted as a clinically useful standardization and decision-support tool requiring expert review rather than as a replacement for the judgment of physicists and radiation oncologists.