HighlightsTreatment de-escalation in HPV+ oropharynx cancer is an active area of research.A Bayesian phase II trial of MR-guided radiotherapy dose adaptation is proposed.High dose volume will be adapted on weekly MRI based on tumor response.The non-inferiority of dose adaptation compared to standard IMRT will be assessed.

Purpose: Response assessment of radiotherapy for the treatment of intrahepatic cholangiocarcinoma (IHCC) across longitudinal images is challenging due to anatomical changes. Advanced deformable image registration (DIR) techniques are required to correlate corresponding tissues across time. In this study, the accuracy of five commercially available DIR algorithms in four treatment planning systems (TPS) was investigated for the registration of planning images with posttreatment follow-up images for response assessment or re-treatment purposes. Methods: Twenty-nine IHCC patients treated with hypofractionated radiotherapy and with pretreatment and posttreatment contrast-enhanced computed tomography (CT) images were analyzed. Liver segmentations were semiautomatically generated on all CTs and the posttreatment CT was then registered to the pretreatment CT using five commercially available algorithms (Demons, B-splines, salient feature-based, anatomically constrained and finite element-based) in four TPSs. This was followed by an in-depth analysis of 10 DIR strategies (plus global and liver-focused rigid registration) in one of the TPSs. Eight of the strategies were variants of the anatomically constrained DIR while the two were based on a finite element-based biomechanical registration. The anatomically constrained techniques were combinations of: (a) initializations with the two rigid registrations; (b) two similarity metricscorrelation coefficient (CC) and mutual information (MI); and (c) with and without a controlling region of interest (ROI)the liver. The finite element-based techniques were initialized by the two rigid registrations. The accuracy of each registration was evaluated using target registration error (TRE) based on identified vessel bifurcations. The results were statistically analyzed with a one-way analysis of variance (ANOVA) and pairwise comparison tests. Stratified analysis was conducted on the inter-TPS data (plus the liver-focused rigid registration) using treatment volume changes, slice thickness, time between scans, and abnormal lab values as stratifying factors. Results: The complex deformation observed following treatment resulted in average TRE exceeding the image voxel size for all techniques. For the inter-TPS comparison, the Demons algorithm had the lowest TRE, which was significantly superior to all the other algorithms. The respective mean (standard deviation) TRE (in mm) for the Demons, B-splines, salient feature-based, anatomically constrained, and finite element-based algorithms were 4.6 (2.0), 7.4 (2.7), 7.2 (2.6), 6.3 (2.3), and 7.5 (4.0). In the follow-up comparison of the anatomically constrained DIR, the strategy with liverfocused rigid registration initialization, CC as similarity metric and liver as a controlling ROI had the lowest mean TRE -6.0 (2.0). The maximum TRE for all techniques exceeded 10 mm. Selection of DIR strategy was found to be a statistically significant factor for registration accuracy. Tumor volume change had a significant effect on TRE for finite element...

PurposeThis study aimed to analyze the potential clinical impact of the differences between planned and accumulated doses on the development and use of normal tissue complication probability (NTCP) models.Methods and MaterialsThirty patients who were previously treated with stereotactic body radiation therapy for liver cancer and for whom the accumulated dose was computed were assessed retrospectively. The linear quadratic equivalent dose at 2 Gy per fraction and generalized equivalent uniform dose were calculated for planned and accumulated doses. Stomach and duodenal Lyman-Kutcher-Burman NTCP models (α/β = 2.5; n = .09) were developed on the basis of planned and accumulated generalized equivalent uniform doses and the differences between the models assessed. In addition, the error in determining the probability of toxicity on the basis of the planned dose was evaluated by comparing planned doses in the NTCP model that were created from accumulated doses.ResultsThe standard, planned-dose NTCP model overestimates toxicity risk for both the duodenal and stomach models at doses that are below approximately 20 Gy (6 fractions) and underestimates toxicity risk for doses above approximately 20 Gy (6 fractions). Building NTCP models with accumulated rather than planned doses changes the predicted risk by up to 16% (mean: 6%; standard deviation: 7%) for duodenal toxicity and 6% (mean: 2%; standard deviation: 2%) for stomach toxicity. For a protocol that plans a 10% iso-toxicity risk to the duodenum, a 15.7 Gy (6 fractions) maximum dose constraint would be necessary when using standard NTCP models on the basis of a planned dose and a 17.6 Gy (6 fractions) maximum dose would be allowed when using NTCP models on the basis of accumulated doses.ConclusionsAssuming that accumulated dose is a more accurate representation of the true delivered dose than the planned dose, this simulation study indicates the need for prospective clinical trials to evaluate the impact of building NTCP models on the basis of accumulated doses.

Purpose: To improve the understanding of deviations between planned and accumulated dose and establish metrics to predict for clinically significant dosimetric deviations midway through treatment to evaluate the potential need to replan during fractionated radiation therapy (RT). Methods and Materials: 100 head and neck cancer patients were retrospectively evaluated. Contours were mapped from the planning CT to each fraction CBCT via deformable image registration (DIR). The dose was calculated on each CBCT and evaluated based on the mapped contours. The mean dose at each fraction was averaged to approximate the accumulated approximate the accumulated dose for structures with max dose constraints. A threshold dose for structures with mean dose constraints and the daily max dose was summed to deviation value was calculated to predict for patients needing mid-treatment replanning. This predictive model was applied to 52 patients treated at a separate institution. Results: Dose was accumulated on 10 organs over 100 patients. To generate a threshold deviation that predicted the need to replan with 100% sensitivity, the submandibular glands required replanning if the delivered dose was at least 3.5Gy higher than planned by fraction 15. This model predicts the need to replan the submandibular glands with 98.7% specificity. On the independent evaluation cohort, this model predicts the need to replan the submandibular glands with 100% sensitivity and 98.0% specificity. The oral cavity, intermediate CTV, left parotid, and inferior constrictor patients each had one patient exceeding the threshold deviation by the end of