Diffusion Transformer-based Universal Dose Denoising for Pencil Beam Scanning Proton Therapy

Purpose: Intensity-modulated proton therapy (IMPT) offers precise tumor coverage while sparing organs at risk (OARs) in head and neck (H&N) cancer. However, its sensitivity to anatomical changes requires frequent adaptation through online adaptive radiation therapy (oART), which depends on fast, accurate dose calculation via Monte Carlo (MC) simulations. Reducing particle count accelerates MC but degrades accuracy. To address this, denoising low-statistics MC dose maps is proposed to enable fast, high-quality dose generation. Methods: We developed a diffusion transformer-based denoising framework. IMPT plans and 3D CT images from 80 H&N patients were used to generate noisy and high-statistics dose maps using MCsquare (1 min and 10 min per plan, respectively). Data were standardized into uniform chunks with zero-padding, normalized, and transformed into quasi-Gaussian distributions. Testing was done on 10 H&N, 10 lung, 10 breast, and 10 prostate cancer cases, preprocessed identically. The model was trained with noisy dose maps and CT images as input and high-statistics dose maps as ground truth, using a combined loss of mean square error (MSE), residual loss, and regional MAE (focusing on top/bottom 10% dose voxels). Performance was assessed via MAE, 3D Gamma passing rate, and DVH indices. Results: The model achieved MAEs of 0.195 (H&N), 0.120 (lung), 0.172 (breast), and 0.376 Gy[RBE] (prostate). 3D Gamma passing rates exceeded 92% (3%/2mm) across all sites. DVH indices for clinical target volumes (CTVs) and OARs closely matched the ground truth. Conclusion: A diffusion transformer-based denoising framework was developed and, though trained only on H&N data, generalizes well across multiple disease sites.