Head-and-neck cancer (HNC) planning is difficult because multiple critical organs-at-risk (OARs) are close to complex targets. Intensity-modulated carbon-ion therapy (IMCT) offers superior dose conformity and OAR sparing but remains slow due to relative biological effectiveness (RBE) modeling, leading to laborious, experience-based, and often suboptimal tuning of many treatment-planning parameters (TPPs). Recent deep learning (DL) methods are limited by data bias and plan feasibility, while reinforcement learning (RL) struggles to efficiently explore the exponentially large TPP search space. We propose a scalable multi-agent RL (MARL) framework for parallel tuning of 45 TPPs in IMCT. It uses a centralized-training decentralized-execution (CTDE) QMIX backbone with Double DQN, Dueling DQN, and recurrent encoding (DRQN) for stable learning in a high-dimensional, non-stationary environment. To enhance efficiency, we (1) use compact historical DVH vectors as state inputs, (2) apply a linear action-to-value transform mapping small discrete actions to uniform parameter adjustments, and (3) design an absolute, clinically informed piecewise reward aligned with plan scores. A synchronous multi-process worker system interfaces with the PHOENIX TPS for parallel optimization and accelerated data collection. On a head-and-neck dataset (10 training, 10 testing), the method tuned 45 parameters simultaneously and produced plans comparable to or better than expert manual ones (relative plan score: RL $85.93\pm7.85%$ vs Manual $85.02\pm6.92%$), with significant (p-value $<$ 0.05) improvements for five OARs. The framework efficiently explores high-dimensional TPP spaces and generates clinically competitive IMCT plans through direct TPS interaction, notably improving OAR sparing.

The field of simulation optimization (SO) encompasses various methods developed to optimize complex, expensive-to-sample stochastic systems. Established methods include, but are not limited to, ranking-and-selection for finite alternatives and surrogate-based methods for continuous domains, with broad applications in engineering and operations management. The recent advent of large language models (LLMs) offers a new paradigm for exploiting system structure and automating the strategic selection and composition of these established SO methods into a tailored optimization procedure. This work introduces SOCRATES (Simulation Optimization with Correlated Replicas and Adaptive Trajectory Evaluations), a novel two-stage procedure that leverages LLMs to automate the design of tailored SO algorithms. The first stage constructs an ensemble of digital replicas of the real system. An LLM is employed to implement causal discovery from a textual description of the system, generating a structural `skeleton' that guides the sample-efficient learning of the replicas. In the second stage, this replica ensemble is used as an inexpensive testbed to evaluate a set of baseline SO algorithms. An LLM then acts as a meta-optimizer, analyzing the performance trajectories of these algorithms to iteratively revise and compose a final, hybrid optimization schedule. This schedule is designed to be adaptive, with the ability to be updated during the final execution on the real system when the optimization performance deviates from expectations. By integrating LLM-driven reasoning with LLM-assisted trajectory-aware meta-optimization, SOCRATES creates an effective and sample-efficient solution for complex SO optimization problems.

The conditional average treatment effect (CATE) is widely used in personalized medicine to inform therapeutic decisions. However, state-of-the-art methods for CATE estimation (so-called meta-learners) often perform poorly in the presence of low overlap. In this work, we introduce a new approach to tackle this issue and improve the performance of existing meta-learners in the low-overlap regions. Specifically, we introduce Overlap-Adaptive Regularization (OAR) that regularizes target models proportionally to overlap weights so that, informally, the regularization is higher in regions with low overlap. To the best of our knowledge, our OAR is the first approach to leverage overlap weights in the regularization terms of the meta-learners. Our OAR approach is flexible and works with any existing CATE meta-learner: we demonstrate how OAR can be applied to both parametric and non-parametric second-stage models. Furthermore, we propose debiased versions of our OAR that preserve the Neyman-orthogonality of existing meta-learners and thus ensure more robust inference. Through a series of (semi-)synthetic experiments, we demonstrate that our OAR significantly improves CATE estimation in low-overlap settings in comparison to constant regularization.

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.

Seed implant brachytherapy (SIBT) is an effective cancer treatment modality; however, clinical planning often relies on manual adjustment of objective function weights, leading to inefficiencies and suboptimal results. This study proposes an adaptive weight optimization framework for SIBT planning, driven by large language models (LLMs). A locally deployed DeepSeek-R1 LLM is integrated with an automatic planning algorithm in an iterative loop. Starting with fixed weights, the LLM evaluates plan quality and recommends new weights in the next iteration. This process continues until convergence criteria are met, after which the LLM conducts a comprehensive evaluation to identify the optimal plan. A clinical knowledge base, constructed and queried via retrieval-augmented generation (RAG), enhances the model's domain-specific reasoning. The proposed method was validated on 23 patient cases, showing that the LLM-assisted approach produces plans that are comparable to or exceeding clinically approved and fixed-weight plans, in terms of dose homogeneity for the clinical target volume (CTV) and sparing of organs at risk (OARs). The study demonstrates the potential use of LLMs in SIBT planning automation.

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.

Office Assistant Robots (OARs) offer a promising solution to proactively provide in-situ support to enhance employee well-being and productivity in office spaces. We introduce OfficeMate, a social OAR designed to assist with practical tasks, foster social interaction, and promote health and well-being. Through a pilot evaluation with seven participants in an office environment, we found that users see potential in OARs for reducing stress and promoting healthy habits and value the robot's ability to provide companionship and physical activity reminders in the office space. However, concerns regarding privacy, communication, and the robot's interaction timing were also raised. The feedback highlights the need to carefully consider the robot's appearance and behaviour to ensure it enhances user experience and aligns with office social norms. We believe these insights will better inform the development of adaptive, intelligent OAR systems for future office space integration.