Steven E. Schild

Yuzhen Ding, Hongying Feng, Yunze Yang et al.

Purpose: In some proton therapy facilities, patient alignment relies on two 2D orthogonal kV images, taken at fixed, oblique angles, as no 3D on-the-bed imaging is available. The visibility of the tumor in kV images is limited since the patient's 3D anatomy is projected onto a 2D plane, especially when the tumor is behind high-density structures such as bones. This can lead to large patient setup errors. A solution is to reconstruct the 3D CT image from the kV images obtained at the treatment isocenter in the treatment position. Methods: An asymmetric autoencoder-like network built with vision-transformer blocks was developed. The data was collected from 1 head and neck patient: 2 orthogonal kV images (1024x1024 voxels), 1 3D CT with padding (512x512x512) acquired from the in-room CT-on-rails before kVs were taken and 2 digitally-reconstructed-radiograph (DRR) images (512x512) based on the CT. We resampled kV images every 8 voxels and DRR and CT every 4 voxels, thus formed a dataset consisting of 262,144 samples, in which the images have a dimension of 128 for each direction. In training, both kV and DRR images were utilized, and the encoder was encouraged to learn the jointed feature map from both kV and DRR images. In testing, only independent kV images were used. The full-size synthetic CT (sCT) was achieved by concatenating the sCTs generated by the model according to their spatial information. The image quality of the synthetic CT (sCT) was evaluated using mean absolute error (MAE) and per-voxel-absolute-CT-number-difference volume histogram (CDVH). Results: The model achieved a speed of 2.1s and a MAE of <40HU. The CDVH showed that <5% of the voxels had a per-voxel-absolute-CT-number-difference larger than 185 HU. Conclusion: A patient-specific vision-transformer-based network was developed and shown to be accurate and efficient to reconstruct 3D CT images from kV images.

Caiwen Jiang, Yuzhen Ding, Mi Jia et al.

Proton therapy offers superior organ-at-risk sparing but is highly sensitive to anatomical changes, making accurate deformable image registration (DIR) across longitudinal CT scans essential. Conventional DIR methods are often too slow for emerging online adaptive workflows, while existing deep learning-based approaches are primarily designed for generic benchmarks and underutilize clinically relevant information beyond images. To address this gap, we propose a clinically scalable coarse-to-fine deformable registration framework that integrates multimodal information from the proton radiotherapy workflow to accommodate diverse clinical scenarios. The model employs dual CNN-based encoders for hierarchical feature extraction and a transformer-based decoder to progressively refine deformation fields. Beyond CT intensities, clinically critical priors, including target and organ-at-risk contours, dose distributions, and treatment planning text, are incorporated through anatomy- and risk-guided attention, text-conditioned feature modulation, and foreground-aware optimization, enabling anatomically focused and clinically informed deformation estimation. We evaluate the proposed framework on a large-scale proton therapy DIR dataset comprising 1,222 paired planning and repeat CT scans across multiple anatomical regions and disease types. Extensive experiments demonstrate consistent improvements over state-of-the-art methods, enabling fast and robust clinically meaningful registration.

Junjie Cui, Peilong Wang, Jason Holmes et al.

Purpose: To develop a retrieval-augmented generation (RAG) system powered by LLaMA-4 109B for automated, protocol-aware, and interpretable evaluation of radiotherapy treatment plans. Methods and Materials: We curated a multi-protocol dataset of 614 radiotherapy plans across four disease sites and constructed a knowledge base containing normalized dose metrics and protocol-defined constraints. The RAG system integrates three core modules: a retrieval engine optimized across five SentenceTransformer backbones, a percentile prediction component based on cohort similarity, and a clinical constraint checker. These tools are directed by a large language model (LLM) using a multi-step prompt-driven reasoning pipeline to produce concise, grounded evaluations. Results: Retrieval hyperparameters were optimized using Gaussian Process on a scalarized loss function combining root mean squared error (RMSE), mean absolute error (MAE), and clinically motivated accuracy thresholds. The best configuration, based on all-MiniLM-L6-v2, achieved perfect nearest-neighbor accuracy within a 5-percentile-point margin and a sub-2pt MAE. When tested end-to-end, the RAG system achieved 100% agreement with the computed values by standalone retrieval and constraint-checking modules on both percentile estimates and constraint identification, confirming reliable execution of all retrieval, prediction and checking steps. Conclusion: Our findings highlight the feasibility of combining structured population-based scoring with modular tool-augmented reasoning for transparent, scalable plan evaluation in radiation therapy. The system offers traceable outputs, minimizes hallucination, and demonstrates robustness across protocols. Future directions include clinician-led validation, and improved domain-adapted retrieval models to enhance real-world integration.

Yuzhen Ding, Jason Holmes, Hongying Feng et al.

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.