abstract = {<i>Objective.</i> This study investigates key factors influencing deep learning-based dose prediction models for head and neck cancer radiation therapy (RT). The goal is to evaluate model accuracy, robustness, and computational efficiency, and to identify key components necessary for optimal performance.<br><i>Approach.</i> We systematically analyze the impact of input and dose grid resolution, input type, loss function, model architecture, and noise on model performance. Two datasets are used: a public dataset (OpenKBP) and an in-house clinical dataset (LUMC). Model performance is primarily evaluated using two metrics: dose score and dose-volume histogram (DVH) score.<br><i>Main results.</i> High-resolution inputs improve prediction accuracy (dose score and DVH score) by 8.6-13.5\% compared to low resolution. Using a combination of CT, planning target volumes (PTVs), and organs-at-risk (OARs) as input significantly enhances accuracy, with improvements of 57.4-86.8\% over using CT alone. Integrating mean absolute error (MAE) loss with value-based and criteria-based DVH loss functions further boosts DVH score by 7.2-7.5\% compared to MAE loss alone. In the robustness analysis, most models show minimal degradation under Poisson noise (0-0.3 Gy) but are more susceptible to adversarial noise (0.2-7.8 Gy). Notably, certain models, such as SwinUNETR, demonstrate superior robustness against adversarial perturbations.<br><i>Significance.</i> These findings highlight the importance of optimizing deep learning models and provide valuable guidance for achieving more accurate and reliable radiotherapy dose prediction.},
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