An Uncertainty Estimation Framework for Dose Accumulation in Adaptive Radiotherapy: Application to CBCT-Guided Radiotherapy for Cervical Cancer
Authors: Cedric Hemon, Delphine Lebret, Jean-Claude Nunes, Valentin Boussot, Karine Peignaux, Nathalie Mesgouez-Nebout, Chantal Hanzen, Antoine Simon, +3 more
Organizations: Univ. Rennes, CLCC Eugène Marquis, INSERM, LTSI - UMR 1099, F-35000 Rennes, France · Department of Radiation Oncology, Centre Georges-Francois Leclerc, F-21000 Dijon, France · Institut de Cancérologie de l’Ouest–Site Paul Papin, F-49000 Angers, France · CLCC Henri Becquerel, Rouen, France, F-76000 Rouen, France
Abstract
Background and purpose: oART enables daily plan adaptation to interfraction anatomical variations, but cumulative dose estimation remains limited by DIR, segmentation, and anatomical uncertainties. We introduce IMPACT-DoseAcc, an uncertainty-aware dose accumulation framework, within IMPACT for semantic feature-driven image analysis. The framework is modality- and disease-agnostic and is applied to CBCT-guided oART for cervical cancer (LACC). Material and Methods: Nine LACC patients were retrospectively analyzed using daily CBCT-derived virtual CTs for dose recalculation. IMPACT-DoseAcc focuses on uncertainty from DIR, without modeling vCT-generation uncertainty. Two DIR uncertainty strategies were tested within IMPACT-Reg: a Bayesian segmentation-guided approach using one probabilistic model to quantify anatomical uncertainty, and an ensemble of segmentation models targeting structures to capture epistemic variability. Voxel-wise uncertainty maps were propagated through dose warping and accumulation to generate probabilistic dose-volume histograms. Ensemble uncertainty was quantified from voxel-wise standard deviation across deformation fields, and geometric error was assessed using surface distance between warped and validated contours. Anatomical-variability weighting refined aggregation. Results: Ensemble DIR uncertainty correlated with geometric error, with Pearson coefficients of 0.63 for CTVt and 0.66 for bladder. For CTVt, pDVHs achieved 96.3 +/- 3.9% coverage, showing calibration of propagated uncertainty. Weighting stabilized estimates across fractions and organs. Conclusions: IMPACT-DoseAcc propagates registration-driven uncertainty to cumulative dose metrics, improving interpretation of accumulated dose under anatomical variations. Its 3DSlicer integration supports reproducible, uncertainty-informed ART workflows.
Deformable image registration (DIR) is widely used in radiotherapy for dose propagation and accumulation, but uncertainty in the underlying deformation can substantially affect clinically relevant dose estimates. We present a practical probabilistic framework for propagating DIR uncertainty to voxel-wise dose statistics and dose-volume histograms (DVHs). The method models the mapped correspondence at each voxel as a random variable governed by a transparent local certainty map that can be defined by simple safety margins, structure-boundary mismatch, or structure-wise conservative uncertainty values. This yields interpretable quantities such as dose probabilities, expected dose, confidence bounds, and induced DVH envelopes. The framework is designed to remain lightweight and interpretable: it avoids complex biomechanical or ensemble-based uncertainty models and instead emphasizes simple parameterization, computational feasibility, and transparent dose metrics. We further introduce a structure-guided in/out strategy as an optional refinement that restricts mapping probabilities to anatomically plausible target regions. The approach is demonstrated on a prostate radiotherapy case study and used to compare different certainty-map strategies and probability kernels. The experiments show that the certainty-map design has a stronger effect on resulting dose and DVH uncertainty bounds than the specific kernel choice, while the additional benefit of the in/out strategy is case-dependent and modest in the present example. Overall, the proposed framework provides a transparent way to incorporate DIR uncertainty into radiotherapy dose assessment and to study how modelling choices affect propagated dose metrics.
Most radiotherapy dose-prediction models use only CT images and anatomical structures, although intensity-modulated proton therapy (IMPT) dose also depends strongly on beam geometry and available clinical datasets are often small. We present DoseBridge, a denoising diffusion bridge model that uses the patient CT as a structured bridge endpoint and encodes plan-specific beam geometry in a spatially aligned beam mask. Multiscale fusion combines CT, target, organ-at-risk, and beam-mask representations with 1.95% additional parameters. DoseBridge was retrospectively evaluated on single-institution CT images and treatment plans from 52 patients with advanced-stage lung cancer treated with 60 Gy in 30 fractions; 42 cases were used for training and 10 for testing. Performance was assessed using image-similarity, dose-volume, and Lyman-Kutcher-Burman normal-tissue complication probability (NTCP) metrics and compared with two deep-learning models. On the test cohort, DoseBridge achieved a mean absolute error of 4.170 Gy, peak signal-to-noise ratio of 23.06 dB, and structural similarity index of 0.798, outperforming both comparison models on these metrics. Clinical target volume D95 differed from the reference dose by 0.62 +/- 1.6 Gy; signed organ-at-risk mean-dose differences ranged from -0.32 to 0.24 Gy, and NTCP differences were -0.40 +/- 2.2 and 0.52 +/- 3.4 percentage points for acute esophagitis and radiation pneumonitis, respectively. Changing only the beam mask redirected predicted low-dose entrance regions while preserving the high-dose target region. To our knowledge, DoseBridge is the first denoising diffusion bridge model for radiotherapy dose prediction. These results support its feasibility as a beam-aware planning prior for lung IMPT, pending evaluation in larger external cohorts.
We present a clinically deployed end-to-end auto-contouring system for cervical cancer radiotherapy planning, anchored by the Boundary-Aware Transformer with Region-Aware Mamba (BAT-RM), a hybrid architecture that integrates Sobel-gated boundary attention, a linear-time, multi-directional Mamba module for long-range context, and a boundary-skeleton-guided fusion gate. This design achieves linear-time complexity for long-range context modeling, avoiding the quadratic cost of full spatial self-attention. The full pipeline spans multi-institutional data collection, rigorous inter-rater quality assurance, external validation in an independent cohort, and a web-based clinical interface natively compatible with Varian, RayStation, and Monaco. Against four baselines, BAT-RM achieves superior performance across seven anatomical classes, with statistically significant improvements in target volumes, including GTV and CTV, and in organs at risk such as the rectum and bladder. A prospective multi-center reader study involving 13 radiation oncologists demonstrated that AI assistance elevates junior oncologists' IoU from 0.899 to 0.965, approaching senior-level accuracy, while reducing contouring time by more than 80%. The system also reduced expert consultation rates and improved inter-reader consistency, reflecting gains in both efficiency and quality assurance. Following clinical deployment at a partner hospital, the system reduced patient wait times from days to hours without additional staffing, enabling same-day or next-day initiation of treatment for routine cases. BAT-RM demonstrates that a rigorous research pipeline, from data curation to clinical deployment, can translate directly into measurable patient benefit in resource-constrained settings where the demand for radiotherapy far exceeds specialist capacity.
Istiak Ahmed, Kazi Shahriar Sanjid, Galib Ahmed +16