Learning to Optimize Radiotherapy Plans via Fluence Maps Diffusion Model Generation and LSTM-based Optimization

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.

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.

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.