Accurate fluence map prediction is essential in intensity-modulated radiation therapy (IMRT) to maximize tumor coverage while minimizing dose to healthy tissues. Conventional optimization is time-consuming and dependent on planner expertise. This study presents a deep learning framework that accelerates fluence map generation while maintaining clinical quality. An end-to-end 3D Swin-UNETR network was trained to predict nine-beam fluence maps directly from volumetric CT images and anatomical contours using 99 prostate IMRT cases (79 for training and 20 for testing). The transformer-based model employs hierarchical self-attention to capture both local anatomical structures and long-range spatial dependencies. Predicted fluence maps were imported into the Eclipse Treatment Planning System for dose recalculation, and model performance was evaluated using beam-wise fluence correlation, spatial gamma analysis, and dose-volume histogram (DVH) metrics. The proposed model achieved an average R^2 of 0.95 +/- 0.02, MAE of 0.035 +/- 0.008, and gamma passing rate of 85 +/- 10 percent (3 percent / 3 mm) on the test set, with no significant differences observed in DVH parameters between predicted and clinical plans. The Swin-UNETR framework enables fully automated, inverse-free fluence map prediction directly from anatomical inputs, enhancing spatial coherence, accuracy, and efficiency while offering a scalable and consistent solution for automated IMRT plan generation.

Proton pencil beam scanning (PBS) treatment planning for head & neck (H&N) cancers involves numerous conflicting objectives, requiring iterative objective parameter adjustments to balance multiple clinical goals. We propose a learning-driven inverse optimizer and integrate it into a proximal policy optimization (PPO)-based planning framework to automatically generate high-quality plans for patients with diverse treatment requirements. The inverse optimizer is a learning-to-optimize (L2O) method that predicts update steps by learning from task-specific data distributions. For the first time, long-context processing techniques developed for large language models (LLMs) are utilized to address the scalability limitations of existing L2O methods, enabling simultaneous optimization over a substantially large set of variables. The PPO framework functions as an outer-loop virtual planner, autonomously adjusting objective parameters through a policy network, and the inner-loop L2O inverse optimizer computes machine-deliverable spot monitor unit (MU) values based on the PPO-refined objectives. Moreover, a Swin UnetR dose predictor is trained with prescription- and beam-specific information to estimate the initial objective parameters. In our experiments, total 97 patients with bilateral or ipsilateral H&N cancers are collected for training and testing. Compared with the second-order gradient-based methods, our L2O optimizer improves the effectiveness and efficiency of the time-consuming inverse optimization by 22.97% and 36.41%, respectively, and in conjunction with the PPO-based virtual planner, plans are generated within clinically acceptable times, i.e. 2.55 hours in average, and shows improved or comparable organs-at-risk sparing with superior target coverage compared with human-generated plans.

Radiotherapy (RT) is a critical cancer treatment, with volumetric modulated arc therapy (VMAT) being a commonly used technique that enhances dose conformity by dynamically adjusting multileaf collimator (MLC) positions and monitor units (MU) throughout gantry rotation. Adaptive radiotherapy requires frequent modifications to treatment plans to account for anatomical variations, necessitating time-efficient solutions. Deep learning offers a promising solution to automate this process. To this end, we propose a two-stage, physics-guided deep learning pipeline for radiotherapy planning. In the first stage, our network is trained with direct supervision on treatment plan parameters, consisting of MLC and MU values. In the second stage, we incorporate an additional supervision signal derived from the predicted 3D dose distribution, integrating physics-based guidance into the training process. We train and evaluate our approach on 133 prostate cancer patients treated with a uniform 2-arc VMAT protocol delivering a dose of 62 Gy to the planning target volume (PTV). Our results demonstrate that the proposed approach, implemented using both 3D U-Net and UNETR architectures, consistently produces treatment plans that closely match clinical ground truths. Our method achieves a mean difference of D95% = 0.42 +/- 1.83 Gy and V95% = -0.22 +/- 1.87% at the PTV while generating dose distributions that reduce radiation exposure to organs at risk. These findings highlight the potential of physics-guided deep learning in RT planning.

High-dose-rate (HDR) brachytherapy plays a critical role in the treatment of locally advanced cervical cancer but remains highly dependent on manual treatment planning expertise. The objective of this study is to develop a fully automated HDR brachytherapy planning framework that integrates reinforcement learning (RL) and dose-based optimization to generate clinically acceptable treatment plans with improved consistency and efficiency. We propose a hierarchical two-stage autoplanning framework. In the first stage, a deep Q-network (DQN)-based RL agent iteratively selects treatment planning parameters (TPPs), which control the trade-offs between target coverage and organ-at-risk (OAR) sparing. The agent's state representation includes both dose-volume histogram (DVH) metrics and current TPP values, while its reward function incorporates clinical dose objectives and safety constraints, including D90, V150, V200 for targets, and D2cc for all relevant OARs (bladder, rectum, sigmoid, small bowel, and large bowel). In the second stage, a customized Adam-based optimizer computes the corresponding dwell time distribution for the selected TPPs using a clinically informed loss function. The framework was evaluated on a cohort of patients with complex applicator geometries. The proposed framework successfully learned clinically meaningful TPP adjustments across diverse patient anatomies. For the unseen test patients, the RL-based automated planning method achieved an average score of 93.89%, outperforming the clinical plans which averaged 91.86%. These findings are notable given that score improvements were achieved while maintaining full target coverage and reducing CTV hot spots in most cases.

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.

Effective education in radiotherapy plan quality review requires a robust, regularly updated set of examples and the flexibility to demonstrate multiple possible planning approaches and their consequences. However, the current clinic-based paradigm does not support these needs. To address this, we have developed "Virtual Dosimetrist" models that can both generate training examples of suboptimal treatment plans and then allow trainees to improve the plan quality through simple natural language prompts, as if communicating with a dosimetrist. The dose generation and modification process is accurate, rapid, and requires only modest resources. This work is the first to combine dose distribution prediction with natural language processing; providing a robust pipeline for both generating suboptimal training plans and allowing trainees to practice their critical plan review and improvement skills that addresses the challenges of the current clinic-based paradigm.

Radiotherapy is a crucial cancer treatment that demands precise planning to balance tumor eradication and preservation of healthy tissue. Traditional treatment planning (TP) is iterative, time-consuming, and reliant on human expertise, which can potentially introduce variability and inefficiency. We propose a novel framework to transform a large multimodal foundation model (MLM) into an action model for TP using a few-shot reinforcement learning (RL) approach. Our method leverages the MLM's extensive pre-existing knowledge of physics, radiation, and anatomy, enhancing it through a few-shot learning process. This allows the model to iteratively improve treatment plans using a Monte Carlo simulator. Our results demonstrate that this method outperforms conventional RL-based approaches in both quality and efficiency, achieving higher reward scores and more optimal dose distributions in simulations on prostate cancer data. This proof-of-concept suggests a promising direction for integrating advanced AI models into clinical workflows, potentially enhancing the speed, quality, and standardization of radiotherapy treatment planning.

Background and Objective: Radiation pneumonitis (RP) is a side effect of thoracic radiation therapy. Recently, Machine learning (ML) models enhanced with radiomic and dosiomic features provide better predictions by incorporating spatial information beyond DVHs. However, to improve the clinical decision process, we propose to use uncertainty quantification (UQ) to improve the confidence in model prediction. This study evaluates the impact of post hoc UQ methods on the discriminative performance and calibration of ML models for RP prediction. Methods: This study evaluated four ML models: logistic regression (LR), support vector machines (SVM), extreme gradient boosting (XGB), and random forest (RF), using radiomic, dosiomic, and dosimetric features to predict RP. We applied UQ methods, including Patt scaling, isotonic regression, Venn-ABERS predictor, and Conformal Prediction, to quantify uncertainty. Model performance was assessed through Area Under the Receiver Operating Characteristic curve (AUROC), Area Under the Precision-Recall Curve (AUPRC), and Adaptive Calibration Error (ACE) using Leave-One-Out Cross-Validation (LOO-CV). Results: UQ methods enhanced predictive performance, particularly for high-certainty predictions, while also improving calibration. Radiomic and dosiomic features increased model accuracy but introduced calibration challenges, especially for non-linear models like XGB and RF. Performance gains from UQ methods were most noticeable at higher certainty thresholds. Conclusion: Integrating UQ into ML models with radiomic and dosiomic features improves both predictive accuracy and calibration, supporting more reliable clinical decision-making. The findings emphasize the value of UQ methods in enhancing applicability of predictive models for RP in healthcare settings.

Deep learning-based automated contouring and treatment planning has been proven to improve the efficiency and accuracy of radiotherapy. However, conventional radiotherapy treatment planning process has the automated contouring and treatment planning as separate tasks. Moreover in deep learning (DL), the contouring and dose prediction tasks for automated treatment planning are done independently. In this study, we applied the multi-task learning (MTL) approach in order to seamlessly integrate automated contouring and voxel-based dose prediction tasks, as MTL can leverage common information between the two tasks and be able able to increase the efficiency of the automated tasks. We developed our MTL framework using the two datasets: in-house prostate cancer dataset and the publicly available head and neck cancer dataset, OpenKBP. Compared to the sequential DL contouring and treatment planning tasks, our proposed method using MTL improved the mean absolute difference of dose volume histogram metrics of prostate and head and neck sites by 19.82% and 16.33%, respectively. Our MTL model for automated contouring and dose prediction tasks demonstrated enhanced dose prediction performance while maintaining or sometimes even improving the contouring accuracy. Compared to the baseline automated contouring model with the dice score coefficients of 0.818 for prostate and 0.674 for head and neck datasets, our MTL approach achieved average scores of 0.824 and 0.716 for these datasets, respectively. Our study highlights the potential of the proposed automated contouring and planning using MTL to support the development of efficient and accurate automated treatment planning for radiotherapy.

Dose prediction plays a key role in knowledge-based planning (KBP) by automatically generating patient-specific dose distribution. Recent advances in deep learning-based dose prediction methods necessitates collaboration among data contributors for improved performance. Federated learning (FL) has emerged as a solution, enabling medical centers to jointly train deep-learning models without compromising patient data privacy. We developed the FedKBP framework to evaluate the performances of centralized, federated, and individual (i.e. separated) training of dose prediction model on the 340 plans from OpenKBP dataset. To simulate FL and individual training, we divided the data into 8 training sites. To evaluate the effect of inter-site data variation on model training, we implemented two types of case distributions: 1) Independent and identically distributed (IID), where the training and validating cases were evenly divided among the 8 sites, and 2) non-IID, where some sites have more cases than others. The results show FL consistently outperforms individual training on both model optimization speed and out-of-sample testing scores, highlighting the advantage of FL over individual training. Under IID data division, FL shows comparable performance to centralized training, underscoring FL as a promising alternative to traditional pooled-data training. Under non-IID division, larger sites outperformed smaller sites by up to 19% on testing scores, confirming the need of collaboration among data owners to achieve better prediction accuracy. Meanwhile, non-IID FL showed reduced performance as compared to IID FL, posing the need for more sophisticated FL method beyond mere model averaging to handle data variation among participating sites.