Improving Clinical Target Volume Segmentation Accuracy using Anatomical Priors and Active Learning for the AGITG TOPGEAR Clinical Trial

Training deep learning-based medical image segmentation models is challenging with limited curated datasets. For AGITG TOPGEAR, a gastric cancer trial, the Clinical Target Volume (CTV) is complex and defined by multiple anatomical landmarks, making upfront training data preparation difficult for an automated contour QA segmentation model. We investigate anatomical priors, derived from surrounding organ segmentations, to provide spatial context and improve TOPGEAR CTV segmentation accuracy. We also evaluate active learning, iteratively expanding the training dataset by selecting cases expected to improve performance. One hundred TOPGEAR CT scans were retrospectively analyzed. An initial set of 10 expert-contoured cases was used to train an nnU-Net model. TotalSegmentator generated a voxel-wise anatomical prior map from surrounding structures as an additional input channel. Active learning was simulated over four iterations, selecting cases by model uncertainty and segmentation performance. All models used five-fold cross-validation for an ensemble uncertainty measure. Evaluation used a hold-out testing set of 50 cases. The anatomical prior improved CTV segmentation accuracy, increasing mean Dice Similarity Coefficient (DSC) from 0.84 to 0.86. Active learning similarly improved performance to 0.86, with greatest benefit in the final round. Combining the anatomical prior with active learning achieved the highest accuracy, with a DSC of 0.87. Model uncertainty correlated with DSC, supporting its use in identifying suboptimal predictions and guiding active learning. Anatomical priors and active learning each improved CTV segmentation accuracy and generalizability, with their combination achieving the best performance, supporting integration into segmentation model development for automated contour QA in radiotherapy clinical trials.

Dose-PlanNet: Physics Based Radiotherapy Dose Prediction with Deep Learning

Automating prostate radiotherapy treatment planning is dosimetrically complex, particularly for extreme hypofractionated regimens. In this study, we introduce Dose-PlanNet, a physics-guided 3D deep learning architecture designed to predict dose distributions. This model's performance was evaluated on a cohort of patients treated in a prospective trial where two different dose fractionation regimens were employed. Dose-PlanNet achieved comparable target coverage ($D_{95}$), though statistical analysis revealed a marginal reduction in target homogeneity ($p<0.001$) offset. However the model achieved statistically significant improvements in high-dose organ-at-risk sparing ($p<0.001$). When evaluated against strict Prospective Randomized protocol volumetric constraints, automated plans met prespecified clinical acceptance criteria in $11$ out of $14$ Moderate Hypofraction Arm plans and $9$ out of $12$ Stereotactic Body Radiation Therapy Arm plans. This pipeline demonstrates that physics-informed deep learning can accelerate radiotherapy workflows while safely maintaining the stringent dosimetric quality required for high-precision clinical deployment.

Image-Conditioned Diffusion Models for Quality Assurance of Organ-at-Risk Segmentations in Radiotherapy

Accurate organ-at-risk segmentation is essential for radiotherapy planning, but reviewing segmentations is time-consuming and subjective. We investigate normative modelling for segmentation error detection in head-and-neck CT, comparing a VAE framework with an image-conditioned segmentation diffusion model. Models were evaluated on RADCURE brainstem and spinal cord segmentations using simulated boundary and width perturbations. Error detection was assessed using the Dice similarity coefficient and the Distance to Agreement (DTA) between the input and reconstructed segmentations. While both models detected some simulated errors, regional DTA showed that the diffusion model localised subtle boundary errors more consistently. These results support image-conditioned diffusion reconstruction as a promising framework for localised, anatomy-aware segmentation QA.

DoseBridge: Denoising Diffusion Bridge Model for Dose Prediction in Lung Intensity-Modulated 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.

Toward CT-Equivalent Image Quality in Low-Dose Radiotherapy Planning: Conditional Diffusion-Based CBCT-to-CT Synthesis and the Impact of CBCT Input Representation

During standard radiotherapy planning, repeated CT acquisitions are often required for patient registration, verification, and adaptive planning, resulting in increased cumulative X-ray dose. To mitigate this, low-dose cone-beam CT (CBCT) is routinely acquired during treatment delivery. However, CBCT image quality remains insufficient for accurate dose calculation and adaptive radiotherapy planning due to increased scatter, noise, beam hardening, and reconstruction related artifacts. This study develops a supervised deep learning based CBCT to CT synthesis framework using a conditional denoising diffusion probabilistic model (DDPM), where the generation of a CT-based planning for accurate positioning and dose calculation is obtained using generative models with low dose CBCT imaging. Beyond demonstrating CBCT to CT synthesis, the primary objective is to investigate how the representation of CBCT input data, either standard clinical DICOM CBCT images or filtered back-projection (FDK) reconstructions from raw projection data, affects the performance of diffusion based CT synthesis. The overarching aim is to assess whether physics aware CBCT representations better support CT-equivalent image quality while maintaining reduced imaging dose in radiotherapy workflows.

Text-Guided Refinement of Multi-sequence Glioma Subregion Segmentation with a Vision-Language Foundation Model

Background: Accurate glioma subregion delineation is important for radiotherapy planning and longitudinal monitoring, but manual contour correction is time-consuming. Models such as nnU-Net may generalize imperfectly and lack clinician-directed text correction. Purpose: We investigated adapting a three-dimensional (3D) vision-language foundation model for text-guided brain tumor segmentation refinement. Methods: We developed a lightweight VoxTell-based framework. Pretrained VoxTell generated initial masks. Oracle prompts derived from segmentation errors encoded target, action, location, imaging evidence, edit size, and preservation constraints. Frozen Qwen/VoxTell prompt embeddings were injected through trainable projections into its multiscale decoder conditioning; other weights remained frozen. Training, validation, and testing used 901, 100, and 250 BraTS-GLI cases. Cross-dataset transfer was evaluated on 100 meningioma, metastasis, pediatric tumor, and UPENN-GBM cases. Results: On the internal test set using post-contrast T1-weighted input, correct instructions improved subregion Dice similarity coefficient (DSC; enhancing tumor, edema, and necrotic/non-enhancing core) from $0.774\pm0.158$ to $0.796\pm0.137$. They outperformed blank prompts ($0.762\pm0.155$; Holm-adjusted $p<0.001$, $d_z=0.71$) and contradictory prompts ($0.770\pm0.163$; $p<0.001$, $d_z=0.48$). In cross-dataset testing, correct instructions improved DSC from $0.527\pm0.287$ to $0.550\pm0.278$ and outperformed contradictory instructions ($0.504\pm0.275$; $p<0.001$, $d_z=0.43$). Conclusion: A 3D vision-language foundation model can perform instruction-guided refinement of glioma subregion segmentations. Sensitivity to correct, blank, and contradictory prompts suggests text-dependent contour editing rather than nonspecific post-processing, supporting further evaluation as a clinician-in-the-loop tool.

BAT-RM: A Boundary-Aware Transformer with Region-Aware Multi-Directional Mamba for Clinically Deployed Cervical Cancer Radiotherapy Auto-Contouring

We present a clinically deployed end-to-end auto-contouring system for cervical cancer radiotherapy planning, anchored by the Boundary-Aware Transformer with Region-Aware Mamba (BAT-RM), a hybrid architecture that integrates Sobel-gated boundary attention, a linear-time, multi-directional Mamba module for long-range context, and a boundary-skeleton-guided fusion gate. This design achieves linear-time complexity for long-range context modeling, avoiding the quadratic cost of full spatial self-attention. The full pipeline spans multi-institutional data collection, rigorous inter-rater quality assurance, external validation in an independent cohort, and a web-based clinical interface natively compatible with Varian, RayStation, and Monaco. Against four baselines, BAT-RM achieves superior performance across seven anatomical classes, with statistically significant improvements in target volumes, including GTV and CTV, and in organs at risk such as the rectum and bladder. A prospective multi-center reader study involving 13 radiation oncologists demonstrated that AI assistance elevates junior oncologists' IoU from 0.899 to 0.965, approaching senior-level accuracy, while reducing contouring time by more than 80%. The system also reduced expert consultation rates and improved inter-reader consistency, reflecting gains in both efficiency and quality assurance. Following clinical deployment at a partner hospital, the system reduced patient wait times from days to hours without additional staffing, enabling same-day or next-day initiation of treatment for routine cases. BAT-RM demonstrates that a rigorous research pipeline, from data curation to clinical deployment, can translate directly into measurable patient benefit in resource-constrained settings where the demand for radiotherapy far exceeds specialist capacity.

WING: A Window-Prior-Based Generative Network with Gated Inception for Cross-Modality CT Synthesis

Generating CT volumes from MRI and CBCT can improve treatment planning in adaptive radiotherapy while avoiding additional radiation exposure. However, direct regression of CT intensities is challenged by the inherently high dynamic range and long-tailed distributions, thereby averaging out sparse yet clinically important structures. To alleviate this issue, we reformulate the regression target into multiple windowed representations, leveraging the inductive prior that CT intensities are structure-deterministic and window-separable. These windowed views exhibit smoother distributions and admit structured fusion back to the full-range CT. Building on this reformulation, we introduce WING, a WINdow-prior-based Generative network comprising: 1) a new Gated Inception Generator to produce multi-window predictions, enabling multi-shape kernel interactions to capture cross-modality correspondence; 2) a Fuse-and-Refine Transformer to aggregate the windowed outputs and learn residuals for detail refinement; and 3) a joint adversarial training objective to enhance window-conditioned realism. Extensive experiments demonstrate that our compact WING achieves state-of-the-art performance on the MRI-to-CT and CBCT-to-CT benchmarks, while supporting multi-anatomy synthesis with a single model.

A practical probabilistic framework for deformable image registration uncertainty in radiotherapy dose propagation

Deformable image registration (DIR) is widely used in radiotherapy for dose propagation and accumulation, but uncertainty in the underlying deformation can substantially affect clinically relevant dose estimates. We present a practical probabilistic framework for propagating DIR uncertainty to voxel-wise dose statistics and dose-volume histograms (DVHs). The method models the mapped correspondence at each voxel as a random variable governed by a transparent local certainty map that can be defined by simple safety margins, structure-boundary mismatch, or structure-wise conservative uncertainty values. This yields interpretable quantities such as dose probabilities, expected dose, confidence bounds, and induced DVH envelopes. The framework is designed to remain lightweight and interpretable: it avoids complex biomechanical or ensemble-based uncertainty models and instead emphasizes simple parameterization, computational feasibility, and transparent dose metrics. We further introduce a structure-guided in/out strategy as an optional refinement that restricts mapping probabilities to anatomically plausible target regions. The approach is demonstrated on a prostate radiotherapy case study and used to compare different certainty-map strategies and probability kernels. The experiments show that the certainty-map design has a stronger effect on resulting dose and DVH uncertainty bounds than the specific kernel choice, while the additional benefit of the in/out strategy is case-dependent and modest in the present example. Overall, the proposed framework provides a transparent way to incorporate DIR uncertainty into radiotherapy dose assessment and to study how modelling choices affect propagated dose metrics.