Any2Any 3D Diffusion Models with Knowledge Transfer: A Radiotherapy Planning Study

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 provides a robust and generalizable solution for RT planning across various clinical scenarios.