Learning the Dose Manifold: A Latent Diffusion Framework for Volumetric Dose Prediction in Automated Radiotherapy Treatment Planning
Automated treatment planning (ATP) aims to reduce the unwarranted inter-planner variability of manual planning, while improving treatment quality and efficiency. Most ATP pipelines rely on the prediction of the achievable three-dimensional dose distribution for a given anatomy and the subsequent optimization of machine parameters to reproduce it. Diffusion-based methods are largely slice-wise due to the high dimensionality of radiotherapy data, and assume a one-to-one mapping between anatomy and optimal dose despite the multi-objective nature of treatment planning. They are evaluated on their ability to match reference doses and rarely on their integration in ATP frameworks. We present LaDose, a latent diffusion framework for fully volumetric dose prediction. An autoencoder learned on dose distributions, trained so that perturbed latents decode to plausible doses, compresses dose maps 128-fold and enables 3D diffusion on a single GPU. Prescription values are represented as exact scalar vectors that bypass the image encoder, avoiding resampling and latent compression. Multiscale classifier-free guidance allows for the modulation of clinical trade-offs at inference, without retraining or additional labeled data. On 900 clinically delivered head-and-neck volumetric modulated arc therapy plans from five centers, LaDose reached a median absolute error of 1.18 Gy (1.4--1.8% of the prescription) and was the only one of six frameworks free of systematic bias with respect to the reference distribution. Guidance scales acted predictably on target coverage and organ-at-risk sparing. Integrated with direct aperture optimization, the pipeline generated plans in 15.2 minutes; in a blinded review, senior clinicians rated 14 of 15 plans acceptable without editing.