Physical models in the form of partial differential equations serve as important priors for many under-constrained problems. One such application is tumor treatment planning, which relies on accurately estimating the spatial distribution of tumor cells within a patient's anatomy. While medical imaging can detect the bulk of a tumor, it cannot capture the full extent of its spread, as low-concentration tumor cells often remain undetectable, particularly in glioblastoma, the most common primary brain tumor. Machine learning approaches struggle to estimate the complete tumor cell distribution due to a lack of appropriate training data. Consequently, most existing methods rely on physics-based simulations to generate anatomically and physiologically plausible estimations. However, these approaches face challenges with complex and unknown initial conditions and are constrained by overly rigid physical models. In this work, we introduce a novel method that integrates data-driven and physics-based cost functions, akin to Physics-Informed Neural Networks (PINNs).

Recent advances in psychotherapy have focused on treatment personalization, such as by selecting treatment modules based on personalized networks. However, estimating personalized networks typically requires intensive longitudinal data, which is not always feasible. A solution to facilitate scalability of network-driven treatment personalization is leveraging LLMs. In this study, we present an end-to-end pipeline for automatically generating client networks from 77 therapy transcripts to support case conceptualization and treatment planning. We annotated 3364 psychological processes and their corresponding dimensions in therapy transcripts. Using these data, we applied in-context learning to jointly identify psychological processes and their dimensions. The method achieved high performance even with a few training examples. To organize the processes into networks, we introduced a two-step method that grouped them into clinically meaningful clusters. We then generated explanation-augmented relationships between clusters. Experts found that networks produced by our multi-step approach outperformed those built with direct prompting for clinical utility and interpretability, with up to 90% preferring our approach. In addition, the networks were rated favorably by experts, with scores for clinical relevance, novelty, and usefulness ranging from 72-75%. Our findings provide a proof of concept for using LLMs to create clinically relevant networks from therapy transcripts. Advantages of our approach include bottom-up case conceptualization from client utterances in therapy sessions and identification of latent themes. Networks generated from our pipeline may be used in clinical settings and supervision and training. Future research should examine whether these networks improve treatment outcomes relative to other methods of treatment personalization, including statistically estimated networks.

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.

Radiation therapy treatment planning is an iterative, expertise-dependent process, and the growing burden of cancer cases has made reliance on manual planning increasingly unsustainable, underscoring the need for automation. In this study, we propose a workflow that leverages a large language model (LLM)-based agent to navigate inverse treatment planning for intensity-modulated radiation therapy (IMRT). The LLM agent was implemented to directly interact with a clinical treatment planning system (TPS) to iteratively extract intermediate plan states and propose new constraint values to guide inverse optimization. The agent's decision-making process is informed by current observations and previous optimization attempts and evaluations, allowing for dynamic strategy refinement. The planning process was performed in a zero-shot inference setting, where the LLM operated without prior exposure to manually generated treatment plans and was utilized without any fine-tuning or task-specific training. The LLM-generated plans were evaluated on twenty head-and-neck cancer cases against clinical manual plans, with key dosimetric endpoints analyzed and reported. The LLM-generated plans achieved comparable organ-at-risk (OAR) sparing relative to clinical plans while demonstrating improved hot spot control (Dmax: 106.5% vs. 108.8%) and superior conformity (conformity index: 1.18 vs. 1.39 for boost PTV; 1.82 vs. 1.88 for primary PTV). This study demonstrates the feasibility of a zero-shot, LLM-driven workflow for automated IMRT treatment planning in a commercial TPS. The proposed approach provides a generalizable and clinically applicable solution that could reduce planning variability and support broader adoption of AI-based planning strategies.

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.

Objective: This study aims to uncover the opaque decision-making process of an artificial intelligence (AI) agent for automatic treatment planning. Approach: We examined a previously developed AI agent based on the Actor-Critic with Experience Replay (ACER) network, which automatically tunes treatment planning parameters (TPPs) for inverse planning in prostate cancer intensity modulated radiotherapy. We selected multiple checkpoint ACER agents from different stages of training and applied an explainable AI (EXAI) method to analyze the attribution from dose-volume histogram (DVH) inputs to TPP-tuning decisions. We then assessed each agent's planning efficacy and efficiency and evaluated their policy and final TPP tuning spaces. Combining these analyses, we systematically examined how ACER agents generated high-quality treatment plans in response to different DVH inputs. Results: Attribution analysis revealed that ACER agents progressively learned to identify dose-violation regions from DVH inputs and promote appropriate TPP-tuning actions to mitigate them. Organ-wise similarities between DVH attributions and dose-violation reductions ranged from 0.25 to 0.5 across tested agents. Agents with stronger attribution-violation similarity required fewer tuning steps (~12-13 vs. 22), exhibited a more concentrated TPP-tuning space with lower entropy (~0.3 vs. 0.6), converged on adjusting only a few TPPs, and showed smaller discrepancies between practical and theoretical tuning steps. Putting together, these findings indicate that high-performing ACER agents can effectively identify dose violations from DVH inputs and employ a global tuning strategy to achieve high-quality treatment planning, much like skilled human planners. Significance: Better interpretability of the agent's decision-making process may enhance clinician trust and inspire new strategies for automatic treatment planning.

Anatomical changes during intensity-modulated proton therapy (IMPT) for head-and-neck cancer (HNC) can shift Bragg peaks, risking tumor underdosing and organ-at-risk overdosing. Treatment replanning is often required to maintain clinically acceptable treatment quality. However, current manual replanning processes are resource-intensive and time-consuming. We propose a patient-specific deep reinforcement learning (DRL) framework for automated IMPT replanning, with a reward-shaping mechanism based on a $150$-point plan quality score addressing competing clinical objectives. We formulate the planning process as a reinforcement learning problem where agents learn control policies to adjust optimization priorities, maximizing plan quality. Unlike population-based approaches, our framework trains agents for each patient using their planning Computed Tomography (CT) and augmented anatomies simulating anatomical changes (tumor progression and regression). This patient-specific approach leverages anatomical similarities along the treatment course, enabling effective plan adaptation. We implemented two DRL algorithms, Deep Q-Network and Proximal Policy Optimization, using dose-volume histograms (DVHs) as state representations and a $22$-dimensional action space of priority adjustments. Evaluation on eight HNC patients using actual replanning CT data showed that both agents improved initial plan scores from $120.78 \pm 17.18$ to $139.59 \pm 5.50$ (DQN) and $141.50 \pm 4.69$ (PPO), surpassing the replans manually generated by a human planner ($136.32 \pm 4.79$). Clinical validation confirms that improvements translate to better tumor coverage and OAR sparing across diverse anatomical changes. This work highlights DRL's potential in addressing geometric and dosimetric complexities of adaptive proton therapy, offering efficient offline adaptation solutions and advancing online adaptive proton therapy.

Focused Ultrasound Ablation Surgery (FUAS) has emerged as a promising non-invasive therapeutic modality, valued for its safety and precision. Nevertheless, its clinical implementation entails intricate tasks such as multimodal image interpretation, personalized dose planning, and real-time intraoperative decision-making processes that demand intelligent assistance to improve efficiency and reliability. We introduce FUAS-Agents, an autonomous agent system that leverages the multimodal understanding and tool-using capabilities of large language models (LLMs). By integrating patient profiles and MRI data, FUAS-Agents orchestrates a suite of specialized medical AI tools, including segmentation, treatment dose prediction, and clinical guideline retrieval, to generate personalized treatment plans comprising MRI image, dose parameters, and therapeutic strategies. We evaluate the system in a uterine fibroid treatment scenario. Human assessment by four senior FUAS experts indicates that 82.5%, 82.5%, 87.5%, and 97.5% of the generated plans were rated 4 or above (on a 5-point scale) in terms of completeness, accuracy, fluency, and clinical compliance, respectively. These results demonstrate the potential of LLM-driven agents in enhancing decision-making across complex clinical workflows, and exemplify a translational paradigm that combines general-purpose models with specialized expert systems to solve practical challenges in vertical healthcare domains.

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.