Radiotherapy

Designing effective chemotherapy regimens is hindered by tumor heterogeneity and drug resistance, which complicate the deployment of patient-specific model-based optimal control across diverse populations. We develop and compare closed-loop deep reinforcement learning (DRL) dosing policies with continuous (TD3) and discrete (DQN) action spaces trained on a high-dimensional heterogeneous tumor model. The DRL policies are benchmarked against a Pontryagin's Maximum Principle (PMP)-derived open-loop benchmark. We assess generalization under parametric heterogeneity using a 100-patient virtual cohort with plus or minus 10 percent uniform perturbations in growth and drug-sensitivity parameters. Across this cohort, TD3 achieves higher average tumor reduction, while DQN yields tighter inter-patient dosing consistency, revealing a clear efficacy-consistency trade-off in this study. Our simulations assume full observation of all tumor subpopulations; translation to sparse and noisy clinical measurements will require partial-observability formulations and/or state estimation. Overall, the results show that simulation-trained DRL can learn state-dependent feedback dosing policies that complement open-loop optimal control benchmarks.

Delineating lung tumours on computed tomography (CT) takes a considerable share of the time spent on radiotherapy planning, and a contour proposed by a model can be refined interactively by the clinician. Promptable foundation models such as SAM 3 support this workflow by writing each correction into a session memory that conditions the remaining slices, while the model weights stay fixed. On 690 test cases from five public CT cohorts, fine-tuning SAM 3 on lung tumours raises the Dice obtained from a single point prompt from 0.298 to 0.757, and seven rounds of corrections raise it further to 0.765, but under memory conditioning alone the accuracy on slices the annotator has not touched stops improving after six rounds. We therefore treat each correction as a training signal and propose LeCor, which performs test-time training on a small set of case adapters that are reset for every case and meta-learned such that a single gradient step driven by a click improves the slices that were not clicked. On the 133 test cases that span at least eight slices, LeCor raises the Dice reached after seven correction rounds from 0.787 with the fine-tuned model to 0.827, reduces the number of cases that never reach a Dice of 0.80 from 47 to 27, and reaches in three correction rounds the accuracy that the fine-tuned model attains in seven.

In proton therapy, plans are typically optimized on a single planning CT, making robustness evaluation essential under anatomical changes. However, current scenarios often rely on simplified perturbations that poorly capture complex, patient-specific variability. We propose SynthRCT, a scalable conditional generative framework for 3D anatomical deformation synthesis. Based on a conditional variational autoencoder, SynthRCT learns a latent deformation space and decodes sampled latent codes into local stationary velocity fields conditioned on an input anatomy. Local fields are assembled into coherent full-volume transformations, enabling memory-scalable generation for large field-of-view CT data. We validate the approach on respiratory 4DCT data with multiple breathing-phase anatomies per subject. SynthRCT enables patient-specific sampling of plausible anatomical transformations beyond predefined robustness scenarios. Code available at: https://github.com/TomasGuija/SynthRCT.

Uncertainty arising from inter-observer variability in medical image segmentation plays an important role in developing treatment plans. Research in this area is inhibited by the lack of multiple annotations for large-scale medical datasets, especially for volumetric data, which suffers from additional scaling and computational complexity challenges. Flow matching has emerged as a powerful framework for generative modelling and has also been demonstrated to maintain strong performance when working with latent representations of images. In this work, we introduce a latent-to-latent flow technique for stochastic segmentation of medical volumes via encoded representations of both the image and label space. We evaluate our method on two challenging applications covering delineation uncertainty for radiotherapy planning and multiple organ structure segmentation, improving efficiency up to 14x compared with full resolution models while maintaining clinically relevant performance.

Architecture category. Hybrid method: a physics-based analytical pencil-beam (PB) dose engine followed by a 3-D convolutional residual-correction network (RepVGG-U-Net). We addressed the DoseRAD2026 proton dose-prediction task with PyDoseRT Proton, a GPU-accelerated engine implemented in PyTorch and augmented by a learned residual toward Monte Carlo (MC) accuracy. A double-Gaussian PB kernel was calibrated to GATE/Geant4 integrated depth doses in water in two stages: a classical per-energy curve fit, then a gradient-based fit of the full 3-D dose through the PyTorch physics engine as it retains a differentiable execution path for gradient-based optimization of dose-dependent objectives. The engine computes each beamlet on a beam's-eye-view (BEV) lattice with variance-preserving Gaussian splitting, an analytic nuclear halo, and a Fermi-Eyges heterogeneity term, then rotates the result into the patient frame. Additionally, a compact residual U-Net predicts an additive correction in BEV space. It is conditioned on voxelwise material-label embeddings, a discrete energy embedding and spot size. The same model was used for all anatomical sites (thoracic and abdominal). It was trained with a patient-space L1 objective emphasizing the scored high-dose region and multi-scale BEV deep supervision. The submitted CT configuration obtained preliminary-test beamlet MAE 0.0066, image-z IDD distance 0.0025, plan MAE 0.0049, 98.30% gamma pass rate (1%/1 mm), and DVH error 0.460.

Background: Accurate segmentation of the Left Anterior Descending (LAD) artery in 3D free-breathing, non-contrast CT is critical for cardiac dose sparing in thoracic radiotherapy. The LAD is extremely small, has poor soft-tissue contrast, and varies substantially across patients; even manual contours show limited inter-observer agreement, underscoring the ambiguity of the vessel boundaries. Purpose: To develop a transformer-based framework that improves LAD delineation in low-contrast, imbalanced CT through local-global context modeling and uncertainty-guided optimization. Methods: We propose NA-UNETR, a 3D transformer-based segmentation model whose Neighborhood Attention (NA) and Dilated NA (DiNA) blocks jointly capture fine structural detail and long-range context. Given the scarcity of annotated LAD data, the model is pretrained on 1,000 CTA volumes of general coronary anatomy and fine-tuned with LoRA-based parameter-efficient adaptation on 20 free-breathing institutional CT scans. A composite Dice-Focal and Hausdorff loss, dynamically balanced via homoscedastic uncertainty, improves overlap and boundary accuracy. Results: NA-UNETR reached 45.64% Dice, 38.16 mm HD95, and 10.01 mm ASD, improving Dice by 3.10 percentage points over nnU-Net and reducing HD95 by 2.96 mm relative to Swin UNETR, with the strongest boundary accuracy among all models and improved centerline stability. On ImageCAS it achieved 79.49% Dice, 8.89 mm HD95, and 1.02 mm ASD. Ablations confirmed that residual blocks, variable kernels, and uncertainty-weighted loss each contributed. Conclusions: NA-UNETR balances local precision and global context for thin, low-contrast LAD structures, offering a computationally efficient framework for substructure-level cardiac segmentation in radiotherapy planning.

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.

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.

The convergence of the Metaverse and Large Language Model (LLM)-based AI agent is catalyzing a shift toward autonomous, immersive, and personalized pedagogical frameworks in medical education. This paper presents a novel agentic AI-driven immersive simulation specifically designed for High Dose Rate (HDR) vaginal cylinder (VC) brachytherapy in cancer care. By integrating Virtual Reality (VR) and mobile computing, the system establishes a high-fidelity, risk-free environment that allows trainees to master complex procedural skills without the facility or safety constraints posed by physical anatomy or live radioactive sources. A core contribution of this work is the seamless integration of a knowledge-aware assistant leveraging Retrieval-Augmented Generation (RAG) to ground agent interactions in authoritative clinical guidelines. This architecture also enables an interactive agent to provide natural language interfaces and hands-free, real-time guidance during intricate medical maneuvers. We validate the proposed system through a prototype deployment comprising a Meta Quest 3 interface linked to a local GPU-accelerated AI backend, demonstrating a feasible architecture for HDR brachytherapy simulation. Experimental results indicate that the system maintains suitable end-to-end latency and high context precision, answer completeness, and relevance in the RAG-enhanced pedagogical support.

Four-dimensional cone beam CT (4D CBCT) is important for image-guided radiation therapy of thoracic cancers, but its use is limited by long scan times, causing high patient dose and motion/sparse-sampling artifacts. We propose a deep learning method for motion-resolved 4D CBCT reconstruction from conventional free-breathing scans, without a respiratory signal or explicit projection binning. Our CNN takes free-breathing 3D CBCT projections as input and predicts a static volume at maximum inhalation plus ten displacement vector fields (DVFs) spanning a breathing cycle. The network extends U-Net: the encoder acts on filtered projection stacks, the decoder acts in the volume domain, and skip connections are replaced with non-trainable back-projection functions at multiple resolutions to transfer features between domains. The model is trained on simulated CBCT scans and evaluated on 11 unseen simulated patients and 13 clinical free-breathing scans. Two additional models (60 s and 6 s scans) were evaluated by clinical experts on three and two scans, comparing single phases of our 4D reconstruction to reference 3D SART-TV images for tumor and esophagus visibility. Experts preferred our method for tumor visibility (59% vs. 36% no preference, 5% reference) and esophagus visibility (47% vs. 42%, 11%). On simulated data, image quality matched SART-TV (mean RMSE: -1.19 HU, PSNR: +0.09 dB, SSIM: -0.009) while enabling 4D reconstruction. On clinical scans, our method showed sharper dynamic structures (e.g., diaphragm) and fewer motion streak artifacts than traditional reconstruction. This non-patient-specific CNN predicts static volumes and full 4D respiratory motion models from a single free-breathing scan, without a respiratory surrogate or projection binning, reducing motion artifacts while adding motion-modeling capability.

Microwave ablation (MWA) is a promising minimally invasive treatment for liver tumors, but its therapeutic outcome strongly depends on patient-specific planning of antenna insertion trajectory, power, and treatment duration. Accurate numerical simulation can provide physically reliable ablation predictions; however, its high computational cost limits its use in optimization-based planning, where repeated forward evaluations are required. To address this issue, we propose a digital twin-based automatic planning framework that combines a neural ablation prediction model with a genetic algorithm. The model was trained on multiphysics simulation data generated from patient-specific tumor and vessel structures, antenna configurations, and treatment conditions, and was used as a fast forward model during planning. The prediction model achieved a Dice score of 95.1%, enabling accurate deep learning-based optimization. In 13 unseen planning cases, the proposed method improved ablation efficiency by 54.3% and reduced organ damage by 55.0% compared with clinician-defined planning, while slightly shortening the insertion path length by 3.3%. Most generated plans were also judged clinically applicable by MWA specialists. Furthermore, the framework enabled approximately 420-fold faster planning than numerical-simulation-based planning, demonstrating its potential as a fast digital twin for quantitative and personalized MWA treatment planning. The code is available at: https://github.com/SeonAengCho/MWA-Planning.git

Head-and-neck (HN) proton therapy is highly sensitive to anatomical change over a 4-to-6-week course, as tumor shrinkage, weight loss, and setup variation can misposition the Bragg peak near critical organs such as the parotids, oral cavity, brainstem, and spinal cord, leading to target underdosing or organ-at-risk overdosing. Online adaptive proton therapy replans on the anatomy of the day, yet standard workflows rely on offline replanning that requires repeated CT acquisition and roughly a week of preparation, adding burden, cost, and delay. We investigate whether a patient's treatment-day anatomy can be predicted before image acquisition by transferring longitudinal change from a population database. We propose a digital-twin framework built on a pretrained foundation-model deformable registration network used without patient-specific training. A first registration aligns a prior patient's planning CT to the target and carries the prior's during-treatment quality assurance CT (QACT) into the target frame; a second registration estimates the prior's planning-to-QACT change, which is then applied to the target's own planning CT to synthesize predicted CTs (pdCTs) with propagated contours. Using 88 HN patients, each with a planning CT and three QACTs, we show that pdCTs better match treatment-day anatomy than the static planning CT. Compared with the planning CT alone, normalized cross-correlation improves by 22.8%, Dice for organs-at-risk by 20.2%, and CT-number error decreases by 23.4%. Gains are largest for patients with major anatomical change and negligible when anatomy is stable. This cross-patient motion transfer leverages the digital-twin concept to anticipate treatment-day anatomy, enabling personalized online adaptive proton therapy without repeated imaging.

We present HERMES (Hybrid Ensemble for Radiotherapy-target segmentation, Malignancy staging, and Event-free Survival), a single containerized algorithm for the three HECKTOR 2026 subtasks: segmentation of the primary tumor (GTVp) and pathological lymph nodes (GTVn), radiological T/N staging, and recurrence-free survival (RFS), computed from a paired FDG-PET/CT scan and an electronic health record. A 10-fold ensemble of STU-Net Small networks produces the segmentation; the predicted mask then drives two downstream tasks. Rather than pass a generic radiomics vector to the staging models, we derive from the predicted masks a compact set of geometry features aligned with the size and number axes of AJCC/UICC 7th-edition radiological N/T staging. On internal cross-validation these features raise N-stage balanced accuracy from 0.691 to 0.720 (+0.030), our largest single design gain, at lower feature dimensionality. For prognosis we combine complementary deep and clinical risk experts in an equal-weight ensemble, and train one deep expert with a concordance-tracking survival loss of our own, whose value approximates the concordance index during training. Every component was selected on honest out-of-fold predictions under a regularization-oriented protocol, with no tuning on the public validation set, and deployed as two decorrelated submissions. On the HECKTOR 2026 validation leaderboard, HERMES achieved a weighted score of 0.6454 (Mean Dice 0.641, T balanced accuracy 0.580, N balanced accuracy 0.642, RFS C-index 0.679) and qualified for the testing phase. Team: AMC_HNC.

In proton therapy planning, respiratory-gated non-contrast CT (NCCT) is commonly used for lesion segmentation; however, accurate delineation remains challenging due to low lesion-to-background contrast. Although learning-based methods have shown strong performance, they often struggle with non-contrast image segmentation. Inspired by clinical practice, where contrast-enhanced MRI is referenced to delineate lesions on NCCT, we propose ViPSAM, a visual prompting framework that leverages complementary cross-modality information. Built upon the Segment Anything Model (SAM), ViPSAM introduces a visual prompt encoder to extract guidance features from contrast-enhanced images and a visual-guided cross-attention module to integrate non-contrast and contrast-enhanced features, thereby enhancing lesion-relevant representations in low-contrast regions. The mask decoder is further adapted in a parameter-efficient manner to utilize visual prompts effectively. We evaluate the proposed method on liver lesion segmentation using NCCT acquired for proton therapy. Experimental results demonstrate that ViPSAM outperforms representative U-Net- and SAM-based methods, indicating that cross-modality visual prompting enables more robust and accurate segmentation in non-contrast images.

Brain tumor progression exhibits spatially heterogeneous growth, patient-specific treatment response, and complex interactions with surrounding anatomy, making accurate long-term prediction challenging. We propose an AI-augmented adaptive digital twin (DT) framework for brain tumor evolution prediction and treatment scheduling. The framework integrates an interpretable reaction--diffusion (RD) model, a 3D residual learning module for model-form correction, patient-specific DT updating during recursive rollout, and model predictive control (MPC) for constrained chemotherapy and radiotherapy scheduling. Experiments on 387 synthetic tumor trajectories with 120-step evolution show that the baseline RD model captures tumor location and overall temporal behavior but underestimates heterogeneous tumor burden during long-horizon prediction. Hybrid RD--residual modeling reduces masked voxel-wise mean squared error by 84.3% and increases Dice overlap by 43.5% relative to the RD baseline under dense simulated observations. Online DT updating further reduces mean squared error by 45.9% and improves Dice overlap by 9.6% compared with the non-updated hybrid model. In MPC-based scheduling simulations, the updated DT controller reduces final tumor burden by 22.4% relative to a fixed treatment schedule under the terminal-burden objective. Together, these results demonstrate a unified framework for patient-specific initialization, mechanistic modeling, adaptive learning, and constrained treatment optimization. Although validated using patient-data-informed synthetic trajectories rather than clinical longitudinal data, the proposed framework establishes a foundation for future translation to real-world adaptive treatment planning.

Positive margins in head and neck oncologic surgery require mapping specimen-side pathology findings to the patient resection bed. This is challenging because pathologists identify the positive margin on slices of the resected, deformed specimen, while surgeons must relocate the corresponding site on the resection bed using only verbal descriptions and no visual guidance. We present a marker-free augmented reality (AR) workflow for mapping a margin label from a three-dimensional specimen scan to the resection bed. The method combines contour-constrained deformation, residual alignment to a depth scan, surface-based fusion to a head-mounted display, and target projection onto the reconstructed bed. Bead-suture correspondences estimate specimen deformation, whereas patient-to-display fusion does not require external fiducial markers. Following formative experiments, five residents and surgeons performed cadaveric cheek and scalp re-resection tasks under verbal guidance, verbal guidance with specimen examination, and AR guidance. Deformation target errors were $7.63 \pm 3.74$ mm for the cheek and $3.72 \pm 1.02$ mm for the scalp; residual specimen-to-bed distances were $2.43 \pm 2.15$ mm and $2.19 \pm 1.06$ mm, respectively. Fusion error did not differ significantly between marker-free and marker-based methods on either cadaver; overall marker-free fusion error was $2.15 \pm 0.87$ mm. End-to-end margin localization error decreased from $21.40 \pm 3.84$ mm with verbal guidance and $16.09 \pm 4.30$ mm with specimen examination to $6.19 \pm 1.79$ mm with AR guidance ($p < 0.001$). Online fusion required $5.23 \pm 0.34$ s. These results demonstrate effective marker-free AR guidance for positive-margin localization and support more precise tumor resection.

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.

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.

Modern software systems increasingly depend on data for analysis, prediction, testing, and decision-making. Yet many important domains, including medicine, safety-critical systems, and regulated industries, lack abundant, shareable, or representative data. Synthetic data generation is often proposed as a remedy, but our experience engineering software for intraoperative radiotherapy (IORT) in breast cancer treatment suggests that synthetic data shifts rather than solves the central engineering problem. The key challenge becomes deciding which properties synthetic data must preserve, how these properties should be elicited from stakeholders, how they can be validated under privacy constraints, and how they evolve. We call this problem property-driven synthetic data engineering. Drawing on a collaboration with oncologists and preliminary experiments with a sensitive IORT dataset, we identify challenges in requirements, validation, privacy, and pipeline evolution. We argue that automated software engineering research should develop methods and tools for eliciting, formalizing, checking, and evolving validity properties for synthetic data in data-scarce software systems.

Image-guided therapies, including radiotherapy, biopsy and deep brain stimulation, rely on real-time targeting of anatomical structures. However, in the presence of motion, imaging latencies create a temporal misalignment between observed and true anatomy, compromising treatment accuracy. Artificial intelligence-based frameworks have increasingly been presented to close this latency gap, but leading personalised models can fail due to a lack of stable anatomical grounding. Foundation models can provide grounded behaviour, but they do not adapt to real-time, individual patient dynamics. Here we introduce a closed-loop coupling framework that synergises patient-specific temporal prediction with continuous segmentation-based anatomical interpretation from a foundation model. A personalised model predicts future anatomy to compensate for system latency, while a streaming foundation model provides anatomical supervision used to continuously update the temporal predictor in real time during treatment. We validate the framework using a digital phantom and intrafraction magnetic resonance imaging (MRI) from patients undergoing MRI-guided radiotherapy. For a prediction horizon of 400 ms, the proposed method improves anatomical prediction and reduces dosimetric error compared with existing approaches, within clinically relevant latency constraints. These results establish closed-loop coupling as a general strategy for real-time image-guided intervention.

Four-dimensional computed tomography (4DCT) captures the full respiratory cycle of thoracic anatomy, yet current Internal Target Volume contouring workflows process each phase in isolation, discarding temporal coherence and leaving contours vulnerable to phase-specific artifacts. We present a lightweight framework that applies parameter-efficient fine-tuning to the Segment Anything Model 3 (SAM 3) via low-rank adaptation (LoRA) to align its text-prompted segmentation with the medical domain using only seven annotated 3D CT volumes. Furthermore, the framework incorporates a hard negative mining strategy to improve boundary discrimination in low-contrast thoracic regions. At inference, phase-wise predictions are refined through phase-coherent temporal filtering and spatial connectivity analysis. Since respiratory motion is continuous and periodic, genuine anatomy appears in contiguous blocks of phases, whereas transient artifacts appear sporadically and are thus effectively suppressed. Experiments on pulmonary and cardiac structures yield median Dice scores of 0.968 and 0.910 with 95th-percentile Hausdorff distances of 0.998 mm and 2.931 mm, respectively. The proposed framework effectively eliminates the severe false-positive predictions inherent in the zero-shot inference of the unadapted SAM 3. With only seven annotated volumes, the framework retains over 95% of full-data accuracy, and the entire pipeline is trainable on a single consumer-grade GPU, demonstrating a scalable, data-efficient solution for adaptive radiotherapy.

Estimating the probability that a treatment outperforms a control for an individual patient, called the Individual Probability of Treatment Benefit (IPTB), offers a clinically intuitive alternative to population-average metrics. However, existing methods for IPTB estimation are largely confined to binary treatment settings, despite the prevalence of dose-varying interventions in clinical practice. We propose a general framework for IPTB estimation with ordinal outcomes under discrete dose assignments, called Dose-AIPTB (Dose Attention-based IPTB). Our approach recasts the problem as binary classification over the unobserved sign of the individual treatment effect, constructing pseudo-labels from covariate-similar pairwise comparisons and aggregating them via attention mechanisms or Nadaraya-Watson kernel regression. This formulation naturally accommodates multiple discrete dose levels, extending beyond the binary treatment paradigm. Through numerical experiments on real-world and synthetic data under covariate shift, varying sample sizes, and heterogeneous outcomes, we demonstrate that attention-based aggregation consistently outperforms kernel alternatives. The framework provides a foundation for personalized dose selection grounded in individual-level benefit probabilities. Codes implementing the model are publicly available at https://github.com/NTAILab/AIPTBDose.

Background and purpose: oART enables daily plan adaptation to interfraction anatomical variations, but cumulative dose estimation remains limited by DIR, segmentation, and anatomical uncertainties. We introduce IMPACT-DoseAcc, an uncertainty-aware dose accumulation framework, within IMPACT for semantic feature-driven image analysis. The framework is modality- and disease-agnostic and is applied to CBCT-guided oART for cervical cancer (LACC). Material and Methods: Nine LACC patients were retrospectively analyzed using daily CBCT-derived virtual CTs for dose recalculation. IMPACT-DoseAcc focuses on uncertainty from DIR, without modeling vCT-generation uncertainty. Two DIR uncertainty strategies were tested within IMPACT-Reg: a Bayesian segmentation-guided approach using one probabilistic model to quantify anatomical uncertainty, and an ensemble of segmentation models targeting structures to capture epistemic variability. Voxel-wise uncertainty maps were propagated through dose warping and accumulation to generate probabilistic dose-volume histograms. Ensemble uncertainty was quantified from voxel-wise standard deviation across deformation fields, and geometric error was assessed using surface distance between warped and validated contours. Anatomical-variability weighting refined aggregation. Results: Ensemble DIR uncertainty correlated with geometric error, with Pearson coefficients of 0.63 for CTVt and 0.66 for bladder. For CTVt, pDVHs achieved 96.3 +/- 3.9% coverage, showing calibration of propagated uncertainty. Weighting stabilized estimates across fractions and organs. Conclusions: IMPACT-DoseAcc propagates registration-driven uncertainty to cumulative dose metrics, improving interpretation of accumulated dose under anatomical variations. Its 3DSlicer integration supports reproducible, uncertainty-informed ART workflows.

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.

Prospective reconstruction is crucial in many clinical applications such as MRI-guided radiotherapy, which demands accurate image reconstruction and fast motion estimation from currently acquired measurements. However, prospective reconstruction remains challenging due to ultra-sparse sampling and stringent latency requirements. In this work, we propose PDMR, a Prospective Dynamic 3D MRI Reconstruction framework with latent-space motion tracking. Our core idea is to learn an efficient and generalizable latent manifold of motion fields offline, enabling rapid online adaptation for prospective reconstruction. Specifically, we parameterize the deformation vector fields (DVFs) on a low-dimensional manifold, effectively reducing the search space for fast online adaptation, and employ a tri-plane representation to achieve geometry-aware and memory-efficient encoding of 3D motion. Experiments on both XCAT digital phantoms and in-house abdominal MRI datasets demonstrate that PDMR achieves high-fidelity and temporally consistent reconstruction across multiple prospective scenarios (Immediate and After-2min), outperforming state-of-the-art retrospective and online methods. Our results suggest a promising pathway toward ultra-fast, motion-aware prospective MRI reconstruction in clinical practice.

In this work, we propose a prototype machine-to-machine (M2M) knowledge-guided Large Language Model (LLM) framework for automated radiotherapy treatment planning. In the proposed paradigm, Treatment Planning Parameter (TPP) distribution knowledge discovered by a Deep Reinforcement Learning (DRL) agent is transferred to an LLM agent through in-context learning, enabling autonomous iterative planning without human intervention. While standard LLM-based planning often lacks physical intuition and struggles with convergence, the integration of DRL-derived guidance constrains the agent to a physically valid parameter space. Experimental evaluations are performed across three diverse planning scenarios: basic prostate cases, complex prostate configurations with increased organ-at-risk (OAR) constraints, and liver cases. The evaluation results demonstrate that the guided LLM agent consistently achieves optimal planning scores while significantly reducing the number of iterations compared to unguided planning. Analysis of the final TPP configurations reveals that the agent successfully learns a hierarchical priority of objectives, effectively restoring a logical "cause-and-effect" relationship between parameter tuning and dosimetric outcomes. Crucially, this prototype framework exhibits robust generalizability, maintaining high planning quality regardless of specific patient anatomy, treatment site, or initial plan quality. By bridging the specialized optimization of DRL with the adaptive reasoning of LLMs, this M2M framework establishes a scalable foundation towards generalizable autonomous treatment planning, ultimately benefiting clinical practice in realistic environments.

Objective: To describe the design and early clinical evaluation of The Daily Dose (TDD), an LLM-driven, automated clinical summarization and clinical-trial identification system integrated into routine radiation oncology practice. Design: Mixed-methods evaluation using a cross-sectional, anonymous clinician survey administered after 1 month of system deployment. Exposure: Daily automated delivery of physician-specific email summaries generated using RadOnc-GPT, including patient schedules, concise EHR-derived clinical-status summaries, and automated identification of potentially relevant clinical trials for new or consult visits. Main Outcomes and Measures: Primary outcomes included self-reported usability, satisfaction, perceived usefulness, perceived impact on workflow, time savings, and intention for continued use. Internal consistency reliability was assessed using Cronbach's $α$. Results: Among 55 respondents, 52 (94.5%) worked in radiation oncology, and 38 (69.1%) were attending physicians. Most participants (83.6%) reported using TDD daily or several times per week. Mean (SD) scores were 3.89 (1.04) for usability and satisfaction, 3.43 (1.24) for perceived usefulness, and 3.80 (1.17) for impact and future use (5-point Likert scale). Overall satisfaction was positively associated with perceived time savings ($p < .001$). Participants reported variable time savings, with 27% estimating $\geq 10$ minutes saved per day. The questionnaire demonstrated excellent internal consistency (overall Cronbach's $α$ = 0.97).

Artificial intelligence is increasingly integrated into radiotherapy workflows, yet such pipelines remain vulnerable to out-of-distribution image data that may introduce unexpected behavior in clinical tasks. Deep learning-based anomaly detection for pelvic magnetic resonance imaging (MRI) remains largely unexplored, and transparent evaluation of its feasibility for full automation is limited. We developed and evaluated a fully automated, unsupervised anomaly-detection framework for pelvic and brain MRI. A two-stage framework was trained on reference images from public datasets: LUND-PROBE for pelvic MRI, and IXI, fastMRI, and fastMRI+ for brain MRI. In the first stage, MRI slices were compressed into discrete tokens; in the second, the distribution of normal tokens was modeled. Anomaly evidence was estimated by combining perceptual image differences with token-surprisal scores based on negative log-likelihood. Automated detection was evaluated on pelvic MRI with synthetic global and real clinical anomalies, and on brain MRI with clinically annotated fastMRI+ abnormalities. Sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and false-positive behavior in held-out normal cases were assessed. The framework achieved robust detection across hidden evaluation cohorts, with AUCs of 0.97 (95% CI, 0.95-0.98) and 0.81 (95% CI, 0.74-0.87) for pelvic and brain MRI, respectively. Heatmap analysis showed strong spatial agreement between detected anomalies and ground-truth locations, supporting localization accuracy and interpretability. These results support the potential of unsupervised anomaly detection as an automated MRI quality-control layer for radiotherapy workflows, with transparent visualization of image regions likely to compromise downstream AI-based tasks.

Cone-beam CT (CBCT) is routinely acquired during radiotherapy for patient setup, but its quantitative reliability is degraded by scatter, noise, and reconstruction artifacts, limiting Hounsfield Unit (HU) accuracy. We propose EPC-3D-Diff, a novel conditional 3D latent diffusion framework for volumetric CBCT to CT synthesis that introduces a projection domain equivariance loss derived from acquisition physics. Unlike common image domain equivariance, we exploit the fact that an in plane rotation of the volume corresponds to an angular shift in its projections. During training, we enforce this relationship by forward projecting rotated synthesized CT volumes and matching them to appropriately angle shifted projections of the paired target CT, yielding a physics consistent equivariance constraint integrated into the diffusion objective. To capture full 3D context efficiently, conditional diffusion is performed in a compact latent space learnt by a lightweight 3D autoencoder, preserving axial depth while downsampling in plane resolution for stable training. We validate on a paired head CBCT/CT phantom dataset, including repeat scans, and paired clinical data using patient wise splits, and perform single and mixed domain training, ablations, and comparisons with diffusion and CycleGAN. EPC-3D-Diff generalizes well and achieved substantial improvements, +7.4 dB (phantom) and +1.8 dB (clinical data) in PSNR compared to state of the art methods, alongside improved SSIM and HU accuracy, within tissue boundaries. Overall, EPC-3D-Diff improves robustness and physics consistency, supporting HU aware synthesis for downstream radiotherapy workflows. The open source code for EPC-3D-Diff is available at https://github.com/ALZAHRAALTALIB/EPC-3D-Diff.

Volumetric Modulated Arc Therapy (VMAT) is a cornerstone of modern radiation therapy, enabling highly conformal tumor irradiation and healthy-tissue sparing. Yet, its planning solves inverse and nested optimization for multi-leaf collimators, monitor units and dose parameters, while enforcing their consistency to ensure mechanical deliverability. Nevertheless, this process often requires repeated re-optimization when treatment configurations change, resulting in substantial planning time per patient. To address these problems, we present a diffusion-driven Learning-to-Optimize (L2O) method for end-to-end VMAT planning. A distribution-matching distilled diffusion model learns a clinically feasible manifold of fluence maps, enabling their one-shot generation. On top of this, an LSTM-based L2O module learns gradient update dynamics to swiftly refine fluence maps toward prescribed dose objectives during inference. Experimental results on clinical and public prostate cancer cohorts demonstrate improved planning efficiency, flexibility, and machine deliverability over currently available end-to-end VMAT planners.

Radiation therapy (RT) requires precise dose delivery over multiple fractions, with CT fundamental for treatment planning due to its electron density information. Repeated CT acquisitions impose radiation exposure and logistical burdens, MRI lacks electron density, and cone-beam CT (CBCT) requires correction for dose calculation. Synthetic CT (sCT) generation addresses these by converting MRI or CBCT into CT-equivalent images with accurate Hounsfield Unit (HU) values, enabling MRI-only RT and CBCT-based adaptive workflows. Building on SynthRAD2023, SynthRAD2025 benchmarked sCT methods on 2,362 patients from five European centers across head and neck, thorax, and abdomen. Two tasks: MRI-to-CT (890 cases) and CBCT-to-CT (1,472 cases), evaluated via image similarity (MAE, PSNR, MS-SSIM), segmentation (Dice, HD95), and dosimetric metrics from photon and proton plans. With 803 participants and 12/13 valid submissions, Task 1 top performance reached MAE $64.8\pm21.3$ HU, PSNR $\sim$30 dB, MS-SSIM $\sim$0.936, Dice 0.79, photon $γ_{2\%/2\text{mm}}>98\%$, proton $γ\approx85\%$. Task 2 improved: MAE $48.3\pm13.4$ HU, PSNR 32.6 dB, MS-SSIM 0.968, Dice 0.86, photon $γ>99\%$, proton $γ\approx89\%$. Strong image--segmentation correlations ($ρ=0.78$--$0.79$) but moderate dose correlations confirmed image quality is insufficient as a dosimetric surrogate. Head-and-neck cases were most consistent; thoracic and abdominal cases showed greater variability. Residual errors at tissue interfaces propagate along beam paths, affecting proton dose more than photon. SynthRAD2025 demonstrates that deep learning yields clinically relevant sCTs, especially for CBCT-to-CT, while identifying persistent MRI-to-CT challenges and underscoring dose-based evaluation as essential for clinical validation.

Anatomical structure masks are widely adopted in radiotherapy dose prediction, as they provide explicit geometric constraints that facilitate structure-dose coupling. However, conventional manual delineation of these masks requires precise annotation of structure boundaries relevant to radiotherapy, which is time-consuming and labor-intensive. To address these limitations, we propose a scribble-guided dose prediction framework that relies solely on anatomical structures annotated with sparse scribbles. Specifically, we design a Scribble Completion Module (SCM) to generate dense anatomical masks by propagating sparse scribble labels to semantically similar voxels. During the propagation process, a supervoxel-based regularization is introduced to preserve geometric boundary consistency to ensure anatomical plausibility. Furthermore, we propose a Structure-Guided Dose Generation Module (SGDGM) to strengthen the correspondence between sparse structural cues and dose distribution. Herein, the completed dense masks derived from scribbles serve as structural guidance to condition the dose prediction network. This scribble-mask-dose consistency encourages high-dose concentration within target volumes while effectively sparing surrounding organs-at-risk. Extensive experiments on the open-source GDP-HMM dataset demonstrate that the proposed method maintains superior dose prediction performance while substantially reducing annotation cost, providing a practical paradigm for dose prediction under sparse structural annotation. The code and reannotated scribbles are made publicly available at https://github.com/iCherishxixixi/ScribbleDose.

Medical image segmentation models can perform unevenly across subgroups. Most existing fairness methods focus on improving average subgroup performance, implicitly treating each subgroup as internally homogeneous. However, this can hide difficult cases within a subgroup, where high-loss samples are obscured by the subgroup mean. We call this problem \textbf{intra-group hidden failure}. To solve this, we propose \textbf{DuetFair} mechanism, a dual-axis fairness framework that jointly considers inter-subgroup adaptation and intra-subgroup robustness. Based on DuetFair, we introduce \textbf{FairDRO}, which combines distribution-aware mixture-of-experts (dMoE) with subgroup-conditioned distributionally robust optimization (DRO) loss aggregation. This design allows the model to adapt across subgroups while also reducing hidden failures within each subgroup. We evaluate FairDRO on three medical image segmentation benchmarks with varying degrees of within-group heterogeneity. FairDRO achieves the best equity-scaled performance on Harvard-FairSeg and improves worst-case subgroup performance on HAM10000 under both age- and race-based grouping schemes. On the 3D radiotherapy target cohort, FairDRO further improves worst-group Dice by 3.5 points ($\uparrow 6.0\%$) under the tumor-stage grouping and by 4.1 points ($\uparrow 7.4\%$) under the institution grouping over the strongest baseline.

Voxel-wise dose prediction is a critical yet challenging task in practical radiotherapy (RT) planning, as bespoke models trained from scratch often struggle to generalize across diverse clinical settings. Meanwhile, generative models trained on billion-scale datasets from vision domains have achieved impressive performance. Herein, we propose DiffKT3D, a unified Any2Any 3D diffusion framework that leverages prior knowledge from pretrained video diffusion models for efficient and clinically meaningful dose prediction. To enable flexible conditioning across multiple clinical modalities (CT, anatomical structures, body, beam settings, etc.), we introduce an Any2Any conditional paradigm utilizing modality-specific embeddings without cross-attention overhead. Further, we design a novel reinforcement learning (RL) post-training mechanism guided by a clinically-informed Scorecard explicitly tailored to institutional treatment preferences. Compared with winner of GDP-HMM challenge, DiffKT3D sets a new state-of-the-art in dose prediction by reducing voxel-level MAE from 2.07 to 1.93. In addition, DiffKT3D achieves superior image quality and preference match. These results demonstrate that transferring diffusion priors via modality-aware conditioning and clinically aligned RL post-training can provide a robust and generalizable solution for RT planning across various clinical scenarios.

Accurately communicating the side effects of cancer treatments to cancer survivors is critical, particularly in settings such as informed consent, where clinicians must clearly and comprehensively convey potential treatment toxicities. However, this task remains challenging due to clinical knowledge deficits about adverse treatment effects and fragmentation across electronic health record (EHR) systems. Large language models (LLMs) have the potential to assist in this task, though their reliability in oncology survivorship contexts remains poorly understood. We present a deployment-oriented stress-testing framework for evaluating LLM-generated radiation side effect lists in breast cancer treatment and survivorship care. Using 21 breast cancer patient profiles, we construct paired patient clinical scenarios that differ only in radiotherapy regimens to evaluate seven instruction-tuned LLMs under multiple prompting regimes. We then compare LLM outputs to a clinician-curated reference derived from informed consent documents at two major academic medical centers and developed by a team including more than seven breast radiation oncologists. The reference maps radiation dose-fractionation, fields, and locations to associated toxicities, broken down by frequency and temporal onset. Across models, we reveal sensitivity to minor documentation changes, trade-offs between precision and recall, and systematic under-recall of rare and long-term side effects. When used alone, constraints on the number of side effects generated reduce precision, and grounding outputs in clinician-curated side effect lists substantially improves reliability and robustness. These findings highlight important limitations of LLM use in oncology and suggest practical design choices for safer and more informative survivorship-focused applications.

Deep learning-based organs/structures-at-risk(OARs) auto-contouring models can improve radiotherapy workflows, but models trained on adult data often underperform in pediatric patients. Developing robust pediatric-specific models is hindered by data scarcity and fragmentation across centers. Federated learning (FL) enables privacy-preserving collaborative training without the need for data sharing. We evaluated the feasibility and performance of FL for developing pediatric-specific OAR segmentation models across two European medical centers. Computed tomography (CT) images from pediatric patients from Utrecht and Heidelberg with a renal tumor or abdominal neuroblastoma were retrospectively collected and locally processed. An nnU-Net-based framework segmented 19 OARs using local and FL schemes. FL was implemented with secure weight exchange on a cloud storage across institutional firewalls. Performance was assessed using the Dice similarity coefficient (DSC), 95th percentile Hausdorff distance, and mean surface distance. Robustness to patient orientation, false-positive segmentation of surgically removed kidneys, and failure cases were identified. A total of 310 postoperative CTs from 272 patients (105 renal tumors, 167 neuroblastomas) were included. Local models performed well on their respective center data but showed significantly reduced cross-center performance for four to seven of the nine evaluated OARs (DSC). In contrast, the FL model matched local performance for at least seven of nine OARs and achieved the best cross-center results across three metrics, with DSC gains of 0.003-0.007 over local models. FL also maintained stable performance across patient orientations and reduced false-positive kidney segmentations. Real-world FL improves cross-center robustness of CT-based OAR segmentation models in pediatric upper abdominal tumors.

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.

Skull-base meningiomas are often characterized by favorable long-term prognosis, yet their anatomical complexity and proximity to critical neurovascular structures make treatment selection challenging. Stereotactic radiosurgery with CyberKnife represents an effective therapeutic option when surgical resection is not feasible; however, not all patients benefit equally from this treatment. Early identification of patients likely to respond to radiosurgery remains an open clinical problem. In this study, we propose a radiomics- and clinical feature-driven framework for predicting volumetric response in skull-base meningiomas treated with CyberKnife. Unlike most existing approaches that focus on progression-free survival or recurrence, our method targets volumetric response as an indicator of treatment efficacy. Pre-treatment MRI images from 104 patients were processed to extract radiomic features, which were combined with clinical variables and analyzed using six models. To ensure methodological rigor, the entire modeling process was implemented within a nested cross-validation scheme. Among the evaluated models, TabPFN achieved the best overall performance, with an AUC of 0.81 and consistently favorable classification metrics. These results suggest that advanced machine learning architectures, when combined with robust validation strategies, can effectively capture patterns associated with treatment response even in small-sample, high-dimensional settings.

Time-resolved volumetric MR imaging that reconstructs a 3D MRI within sub-seconds to resolve deformable motion is essential for motion-adaptive radiotherapy. Representing patient anatomy and associated motion fields as 3D Gaussians, we developed a spatiotemporal Gaussian representation-based framework (DREME-GSMR), which enables time-resolved dynamic MRI reconstruction from a pre-treatment 3D MR scan without any prior anatomical/motion model. DREME-GSMR represents a reference MRI volume and a corresponding low-rank motion model (as motion-basis components) using 3D Gaussians, and incorporates a dual-path MLP/CNN motion encoder to estimate temporal motion coefficients of the motion model from raw k-space-derived signals. Furthermore, using the solved motion model, DREME-GSMR can infer motion coefficients directly from new online k-space data, allowing subsequent intra-treatment volumetric MR imaging and motion tracking (real-time imaging). A motion-augmentation strategy is further introduced to improve robustness to unseen motion patterns during real-time imaging. DREME-GSMR was evaluated on the XCAT digital phantom, a physical motion phantom, and MR-LINAC datasets acquired from 6 healthy volunteers and 20 patients (with independent sequential scans for cross-evaluation). DREME-GSMR reconstructs MRIs of a ~400ms temporal resolution, with an inference time of ~10ms/volume. In XCAT experiments, DREME-GSMR achieved mean(s.d.) SSIM, tumor center-of-mass-error(COME), and DSC of 0.92(0.01)/0.91(0.02), 0.50(0.15)/0.65(0.19) mm, and 0.92(0.02)/0.92(0.03) for dynamic reconstruction/real-time imaging. For the physical phantom, the mean target COME was 1.19(0.94)/1.40(1.15) mm for dynamic/real-time imaging, while for volunteers and patients, the mean liver COME for real-time imaging was 1.31(0.82) and 0.96(0.64) mm, respectively.

Radiotherapy workflows for oncological patients increasingly rely on multi-modal medical imaging, commonly involving both Magnetic Resonance Imaging (MRI) and Computed Tomography (CT). MRI-only treatment planning has emerged as an attractive alternative, as it reduces patient exposure to ionizing radiation and avoids errors introduced by inter-modality registration. While nnU-Net-based frameworks are predominantly used for MRI-to-CT synthesis, we explore Mamba-based architectures for this task to investigate the applicability of state-space modeling for cross-modality medical image translation and assess its performance relative to established convolutional architectures. Specifically, we adapt the SegMamba architecture, originally proposed for segmentation, to perform image-to-image generation. Our 3D Mamba architecture effectively captures complex volumetric features and long-range dependencies, thus allowing accurate CT synthesis while maintaining a relatively low parameter count. Experiments were conducted on a subset of SynthRAD2025 dataset, comprising registered single-channel MRI-CT volume pairs across three anatomical regions. Quantitative evaluation is performed via a combination of image similarity metrics computed in Hounsfield Units (HU) and segmentation-based metrics obtained from TotalSegmentator to ensure geometric consistency is preserved. The findings pave the way for the integration of state-space models into radiotherapy workflows.

Delineating the clinical target volume (CTV) in radiotherapy involves complex margins constrained by tumor location and anatomical barriers. While deep learning models automate this process, their rigid reliance on expert-annotated data requires costly retraining whenever clinical guidelines update. To overcome this limitation, we introduce OncoAgent, a novel guideline-aware AI agent framework that seamlessly converts textual clinical guidelines into three-dimensional target contours in a training-free manner. Evaluated on esophageal cancer cases, the agent achieves a zero-shot Dice similarity coefficient of 0.842 for the CTV and 0.880 for the planning target volume, demonstrating performance highly comparable to a fully supervised nnU-Net baseline. Notably, in a blinded clinical evaluation, physicians strongly preferred OncoAgent over the supervised baseline, rating it higher in guideline compliance, modification effort, and clinical acceptability. Furthermore, the framework generalizes zero-shot to alternative esophageal guidelines and other anatomical sites (e.g., prostate) without any retraining. Beyond mere volumetric overlap, our agent-based paradigm offers near-instantaneous adaptability to alternative guidelines, providing a scalable and transparent pathway toward interpretability in radiotherapy treatment planning.

The integration of complementary medicine into oncology represents a paradigm shift that has seen to increasing adoption of Traditional Chinese Medicine (TCM) as an adjuvant to radiotherapy. About twenty-five years since the formal institutionalization of integrated oncology, it is opportune to synthesize the trajectory of evidence for TCM as an adjuvant to radiotherapy. Here we conduct a large-scale analysis of 69,745 publications (2000 - 2025), emerging a cyclical evolution defined by coordinated expansion and contraction in publication output, international collaboration, and funding commitments that mirrors a define-ideate-test pattern. Using a theme modeling workflow designed to determine a stable thematic structure of the field, we identify five dominant thematic axes - cancer types, supportive care, clinical endpoints, mechanisms, and methodology - that signal a focus on patient well-being, scientific rigor and mechanistic exploration. Cross-theme integration of TCM is patient-centered and systems-oriented. Together with the emergent cycles of evolution, the thematic structure demonstrates progressive specialization and potential defragmentation of the field or saturation of existing research agenda. The analysis points to a field that has matured its current research agenda and is likely at the cusp of something new. Additionally, the field exhibits positive reporting of findings that is homogeneous across publication types, thematic areas, and the cycles of evolution suggesting a system-wide positive reporting bias agnostic to structural drivers.

High-stakes decision-making involves navigating multiple competing objectives with expensive evaluations. For instance, in brachytherapy, clinicians must balance maximizing tumor coverage (e.g., an aspirational target or soft bound of >95% coverage) against strict organ dose limits (e.g., a non-negotiable hard bound of <601cGy to the bladder). Selecting Pareto-optimal solutions that match implicit preferences is challenging, as exhaustive Pareto frontier exploration is computationally and cognitively prohibitive, necessitating interactive frameworks to guide users. While decision-makers (DMs) often possess domain knowledge to narrow the search via such soft-hard bounds, current methods often lack systematic approaches to iteratively refine these multi-faceted preference structures. Furthermore, DMs often require confidence that they have not overlooked superior alternatives, a paramount necessity in high-stakes scenarios. We present Active-MoSH, an interactive local-global framework designed for this process. Its local component integrates probabilistic preference learning with an active sampling strategy to adaptively refine Pareto subsets while minimizing cognitive burden. To bolster decision confidence, Active-MoSH's global component, C-MoSH, leverages multi-objective sensitivity analysis to identify potentially overlooked, high-value points beyond immediate feedback. We demonstrate Active-MoSH's performance benefits through diverse synthetic and real-world applications. A high-stakes case study with real cervical cancer brachytherapy treatment plans and an image selection user study further validate our hypotheses regarding the framework's ability to improve convergence, enhance DM confidence, and provide expressive preference articulation.

Radiotherapy (RT) planning is complex, subjective, and time-intensive. Advances with artificial intelligence (AI) promise to improve its precision and efficiency, but progress is often limited by the scarcity of large, standardized datasets. To address this, we introduce the Automated Iterative RT Planning (AIRTP) system, a scalable solution for generating high-quality treatment plans. This scalable solution is designed to generate substantial volumes of consistently high-quality treatment plans, overcoming a key obstacle in the advancement of AI-driven RT planning. Our AIRTP pipeline adheres to clinical guidelines and automates essential steps, including organ-at-risk (OAR) contouring, helper structure creation, beam setup, optimization, and plan quality improvement, using AI integrated with RT planning software like Varian Eclipse. Furthermore, a novel approach for determining optimization parameters to reproduce 3D dose distributions, i.e. a method to convert dose predictions to deliverable treatment plans constrained by machine limitations is proposed. A comparative analysis of plan quality reveals that our automated pipeline produces treatment plans of quality comparable to those generated manually, which traditionally require several hours of labor per plan. Committed to public research, the first data release of our AIRTP pipeline includes nine cohorts covering head-and-neck and lung cancer sites to support an AAPM 2025 challenge. To our best knowledge, this dataset features more than 10 times number of plans compared to the largest existing well-curated public dataset. Repo: https://github.com/RiqiangGao/GDP-HMM_AAPMChallenge.