Generalizable dose denoising using diffusion transformer framework for pencil beam scanning proton therapy

Most radiotherapy dose-prediction models use only CT images and anatomical structures, although intensity-modulated proton therapy (IMPT) dose also depends strongly on beam geometry and available clinical datasets are often small. We present DoseBridge, a denoising diffusion bridge model that uses the patient CT as a structured bridge endpoint and encodes plan-specific beam geometry in a spatially aligned beam mask. Multiscale fusion combines CT, target, organ-at-risk, and beam-mask representations with 1.95% additional parameters. DoseBridge was retrospectively evaluated on single-institution CT images and treatment plans from 52 patients with advanced-stage lung cancer treated with 60 Gy in 30 fractions; 42 cases were used for training and 10 for testing. Performance was assessed using image-similarity, dose-volume, and Lyman-Kutcher-Burman normal-tissue complication probability (NTCP) metrics and compared with two deep-learning models. On the test cohort, DoseBridge achieved a mean absolute error of 4.170 Gy, peak signal-to-noise ratio of 23.06 dB, and structural similarity index of 0.798, outperforming both comparison models on these metrics. Clinical target volume D95 differed from the reference dose by 0.62 +/- 1.6 Gy; signed organ-at-risk mean-dose differences ranged from -0.32 to 0.24 Gy, and NTCP differences were -0.40 +/- 2.2 and 0.52 +/- 3.4 percentage points for acute esophagitis and radiation pneumonitis, respectively. Changing only the beam mask redirected predicted low-dose entrance regions while preserving the high-dose target region. To our knowledge, DoseBridge is the first denoising diffusion bridge model for radiotherapy dose prediction. These results support its feasibility as a beam-aware planning prior for lung IMPT, pending evaluation in larger external cohorts.

We introduce a novel learning framework for accelerated Monte Carlo (MC) dose calculation termed Energy-Shifting. This approach leverages deep learning to synthesize highly complex polyenergetic dose distributions directly from simple monoenergetic inputs under identical beam configurations. Unlike conventional denoising techniques, which rely on noisy low-count dose maps that compromise beam profile integrity, our method achieves superior cross-domain generalization on unseen datasets by integrating high-fidelity anatomical textures and source-specific beam similarity into the model's input space. Furthermore, we propose a novel 3D architecture termed TransUNetSE3D, featuring Transformer blocks for global context and Residual Squeeze-and-Excitation (SE) modules for adaptive channel-wise feature recalibration. Hierarchical representations of these blocks are fused into the network's latent space alongside the primary dose-map parameters, allowing physics-aware reconstruction. This hybrid design outperforms existing UNet and Transformer-based benchmarks in both spatial precision and structural preservation, while maintaining the execution speed necessary for real-time use. Our proposed pipeline achieves a Gamma Passing Rate exceeding 98% (3%/3mm) compared to the MC reference, evaluated within the framework of a treatment planning system (TPS) using 6MV TrueBeam Lineac Accelerator (LINAC) for prostate radiotherapy. These results offer a robust solution for fast volumetric dosimetry in adaptive radiotherapy.

Learning-based fluence map prediction offers a fast alternative to iterative inverse planning in intensity-modulated radiation therapy (IMRT), but its robustness under realistic distribution shifts remains unclear. We study a two-stage transformer pipeline that maps anatomy (CT and contours) to dose and then to beamlet fluence maps. We compare fluence-stage transformer backbones with hierarchical, global, and hybrid attention, trained with a physics-informed loss enforcing energy consistency. Robustness is evaluated under geometric perturbations, radiometric noise, reduced training data, and domain shifts using a prostate IMRT dataset, with additional evaluation of the dose stage on public datasets. Results show smooth degradation under moderate perturbations but sharp failures under severe rotations and noise. Hierarchical transformers (e.g., SwinUNETR) exhibit slower growth in upper-quartile energy error, indicating improved robustness. We further show that SSIM alone fails to capture clinically relevant errors, highlighting the need for physics-informed evaluation.