PURPOSE:Locoregional failures after (chemo)radiation therapy for primary lung cancer account for 30% of relapses. Reirradiation in this setting is challenging. To evaluate the outcome after thoracic reirradiation with radical doses, a prospective phase 2 trial was conducted for marginal or in-field recurrences of lung cancer. METHODS AND MATERIALS:The goal of this study was to treat recurrent lung cancer with high-dose (chemo)radiation therapy to reach a median overall survival (OS) of 12 months. Patients with recurrent lung cancer in the thorax (tumor <5 cm from 50 Gy10 Equivalent Dose of 2 Gy per fraction [EQD2] isodose line of previous radiation therapy) were reirradiated with ≥45 Gy10 EQD2. The secondary endpoints were local control (LC), disease-free survival (DFS), and toxicity. RESULTS:From 2018 to 2022, 64 patients were included, of whom 60 were analyzed. The median dose of the first radiation therapy course was 68 Gy10 EQD2. All patients were reirradiated using image guided intensity modulated radiation therapy or volumetric modulated arc therapy: 38 patients (63%) using conventional fractionated radiation therapy (median dose 53 Gy10) and 22 (37%) using stereotactic body radiation treatment (median dose 77 Gy10). Median reirradiation planning target volume (PTV) was 106 cc. In 50 patients, the current PTV overlapped with the previous PTV. After a median follow-up of 26.5 months, median OS was 30.1 months, LC was 28.2 months, and DFS was 13.6 months. No grade 4-5 toxicities were registered. Grade 3 toxicities occurred in 12 patients (20%); the most common was pneumonitis (12%). CONCLUSIONS:This trial showed that high-dose thoracic reirradiation for recurrent lung cancer is effective and achieved a good OS higher than our null hypothesis. It resulted in good LC and DFS with low toxicity.

Background and purpose: To evaluate the performance of automated surface-guided gating for left-sided breast cancer with DIBH and VMAT. Materials and methods: Patients treated in the first year after introduction of DIBH with VMAT were retrospectively considered for analysis. With automated surface-guided gating the beam automatically switches on/off, if the surface region of interest moved in/out the gating tolerance (+/- 3 mm, +/- 3 degrees). Patients were coached to hold their breath as long as comfortably possible. Depending on the patient's preference, patients received audio instructions during treatment delivery. Real-time positional variations of the breast/chest wall surface with respect to the reference surface were collected, for all three orthogonal directions. The durations and number of DIBHs needed to complete dose delivery, and DIBH position variations were determined. To evaluate an optimal gating window threshold, smaller tolerances of +/- 2.5 mm, +/- 2.0 mm, and +/- 1.5 mm were simulated. Results: 525 fractions from 33 patients showed that median DIBH duration was 51 s (range: 30-121 s), and median 4 DIBHs per fraction were needed to complete VMAT dose delivery. Median intra-DIBH stability and intrafractional DIBH reproducibility approximated 1.0 mm in each direction. No large differences were found between patients who preferred to perform the DIBH procedure with (n = 21) and without audio-coaching (n = 12). Simulations demonstrated that gating window tolerances could be reduced from +/- 3.0 mm to +/- 2.0 mm, without affecting beam-on status. Conclusion: Independent of the use of audio-coaching, this study demonstrates that automated surface-guided gating with DIBH and VMAT proved highly efficient. Patients' DIBH performance far exceeded our expectations compared to earlier experiences and literature. Furthermore, gating window tolerances could be reduced.

This Roadmap paper covers the field of precision preclinical x-ray radiation studies in animal models. It is mostly focused on models for cancer and normal tissue response to radiation, but also discusses other disease models. The recent technological evolution in imaging, irradiation, dosimetry and monitoring that have empowered these kinds of studies is discussed, and many developments in the near future are outlined. Finally, clinical translation and reverse translation are discussed.

Purpose To determine the dosimetric impact of using unedited autocontours in daily plan adaptation of patients with locally advanced pancreatic cancer (LAPC) treated with stereotactic body radiotherapy using tumor tracking. Materials and Methods The study included 98 daily CT scans of 35 LAPC patients. All scans were manually contoured (MAN), and included the PTV and main organs-at-risk (OAR): stomach, duodenum and bowel. Precision and MIM deformable image registration (DIR) methods followed by contour propagation were used to generate autocontour sets on the daily CT scans. Autocontours remained unedited, and were compared to MAN on the whole organs and at 3, 1 and 0.5 cm from the PTV. Manual and autocontoured OAR were used to generate daily plans using the VOLO™ optimizer, and were compared to non-adapted plans. Resulting planned doses were compared based on PTV coverage and OAR dose-constraints. Results Overall, both algorithms reported a high agreement between unclipped MAN and autocontours, but showed worse results when being evaluated on the clipped structures at 1 cm and 0.5 cm from the PTV. Replanning with unedited autocontours resulted in better OAR sparing than non-adapted plans for 95% and 84% plans optimized using Precision and MIM autocontours, respectively, and obeyed OAR constraints in 64% and 56% of replans. Conclusion For the majority of fractions, manual correction of autocontours could be avoided or be limited to the region closest to the PTV. This practice could further reduce the overall timings of adaptive radiotherapy workflows for patients with LAPC.

Key Points Question Can modern radiation techniques reduce the risk of radiation-associated esophageal adverse effects in patients with advanced lung cancer? Findings In this phase 3 randomized clinical trial of esophageal-sparing intensity-modulated radiotherapy (ES-IMRT) or standard palliative radiotherapy for 90 patients with stage III/IV incurable non–small cell lung cancer, ES-IMRT significantly reduced symptomatic esophagitis (24% [n = 11] vs 2% [n = 1]), but did not significantly improve esophageal-related quality of life. Meaning In this trial, the use of ES-IMRT did not definitively improve esophageal quality of life but reduced symptomatic esophagitis in patients with advanced lung cancer who were receiving palliative thoracic radiotherapy; this technique holds merit for translation into clinical practice.

Purpose: To study the trade-offs of three online strategies to adapt treatment plans of patients with locally advanced pancreatic carcinoma (LAPC) treated using the CyberKnife with tumor tracking. Methods and Materials: A total of 35 planning computed tomography scans and 98 daily in-room computed tomography scans were collected from 35 patients with LAPC. Planned dose distributions, optimized with VOLO, were evaluated on manually contoured daily anatomies to collect daily doses. Three strategies were tested to adapt treatment plans: (1) unrestricted full replanning using a patient-specific plan template, (2) time-restricted replanning on organs at risk (OARs) within 3 cm from the planning target volume (PTV) structure, and (3) dose realignment optimization to stay within OAR constraints. Dose distributions resulting from each plan adaptation strategy were dosimetrically compared by means of gross tumor volume (GTV), PTV coverage, and OAR tolerances. Results: Planned doses did not result in dose-constraint violations for 28 of 98 daily anatomies. None of the suggested plan adaptation strategies improved planned doses significantly for this subset. For 70 of the 98 reported violations, the median (interquartile range) PTV coverage of the planned dose was 84% (76% to 86%). After plan adaptation, unrestricted replanning achieved clinically acceptable plans in 93% of these fractions, time-restricted replanning in 90%, and dose realignment in 74%, at median computational times of 8.5, 3, and 0.5 minutes. Over all 98 fractions, PTV coverage was reduced: -1% (-3% to 1%), -2% (-5% to 0%), and -2% (-8% to 0%) after each strategy, respectively. In 3 of 70 fractions, none of the suggested strategies achieved clinically acceptable OAR dose volumes. Conclusions: Unrestricted replanning was the most time-consuming method but reached the highest number of successfully adapted plans. Time-restricted replanning and dose realignment resulted in a high number of plans within dose constraints. Depending on the resources available, an adaptive strategy can be selected for each patient to address the specific anatomic challenges on the treatment day. The increase in the complexity of the strategy corresponds with an increasing number of successfully adapted plans. (C) 2021 Elsevier Inc. All rights reserved.

Background: Stereotactic body radiation therapy (SBRT) results in high local control (LC) rates in patients with non-small cell lung cancer (NSCLC). For central lung tumors, risk-adapted fractionation schedules are used and underdosage to the Planned Target Volume (PTV) is often accepted to respect the dose constraints of the organs at risk in order to avoid high rates of toxicity. The purpose of this study was to analyze the effect of PTV underdosage and other possible prognostic factors on local- and disease control after SBRT in patients with central lung tumors. Material and Methods: Patients with centrally located NSCLC treated with SBRT were included. The doses were converted into biologically equivalent dose using alpha/beta-value of 10 Gy (BED10). Underdosage to the PTV was defined as the (percentage of) PTV receiving less than 100 Gy BED10; (%)PTV < 100 BED10. Potential prognostic factors for LC and Disease Free Survival (DFS) were evaluated using Cox regression analysis. Results: Two hundred and twenty patients received <= 12 fractions of SBRT. LC-rates were 88% at 2 years and 81% at 3 years. Twenty-seven patients developed a local recurrence. Both the PTV < 100 BED(10)and %PTV < 100 BED(10)were not prognostic for LC. Tumor size and forced expiratory volume in 1 second (FEV1) were independently prognostic for LC. Disease progression was reported in 75 patients with DFS-rates of 66% at 2 years and 56% at 3 years. Disease recurrence was independent significantly associated with larger tumor diameter, lower lobe tumor location and decreased FEV1. Grade 4-5 toxicity was reported in 10 patients (8 with ultra-central tumors) and was fatal in at least 3 patients. Conclusion: Decrease in tumor coverage was not correlated with the local recurrence probability. The LC and DFS were promising after SBRT of centrally located NSCLC with tumor size, FEV(1)and tumor location (for DFS only) as prognostic factors.

Purpose: To characterize daily geometrical variations of gastrointestinal organs with respect to pancreatic tumors, through a population-based statistical model. Materials and methods: The study included 131 CT scans from 35 pancreatic cancer patients treated with Stereotactic Body Radiotherapy (SBRT). For each patient, day-to-day anatomical variations of the stomach, the duodenum and the bowel were assessed from the deformation vector fields (DVF) obtained by non-rigidly registering the contours of the fractions to the planning CT scans. For the whole population, day-to-day motion-deformation patterns were abstracted using principal component analysis (PCA) on the set of DVFs mapped on a reference patient. Based on these geometrical variations, anatomies were generated to create population-based dose-volume histograms (DVH) per patient, which were also compared to clinical values. Results: Through PCA, the most dominant directions of daily deformations were localized in the abdominal organs. Common patterns were found, such as stomach contraction-expansion in the anterior-posterior direction ranging from 5 to 13 mm, and superior-inferior deformations on the bowel from 7 to 14 mm. The duodenum resulted to move laterally, but in a lesser extent (4-8 mm). The population-based DVHs derived from the model mostly included the daily DVHs observed in the clinic (in >90% of the cases). Conclusions: Anatomical variations influence the delivered doses to healthy organs during SBRT. A motion model was successfully built and explored to extract the larger directions of movement of the gastrointestinal organs. Day-to-day motion modeling can potentially be used to account for geometrical uncertainties in future plan optimization and in online adaptive strategies. (C) 2019 Elsevier B.V. All rights reserved.

S3ESTRO 38 important for RT planning.A baseline pre-treatment PET/CT is recommended.Smaller nodes that are not FDGavid but seen on CT adjacent to FDG-avid nodes should be included.In masses seen on CT with partial FDG-uptake the entire mass should be included.Breathing control techniques are recommended for mediastinal treatment to reduce the doses to the critical structures. TeachingLecture: The role of postoperative radiotherapy in endometrial cancer: what have we learned of the PORTEC trials?SP-0005 The role of postoperative radiotherapy in endometrial cancer: what have we learned of the PORTEC trials?C. Creutzberg

Purpose: Locally advanced pancreatic cancer (LAPC) patients are prone to experience daily anatomical variations, which can lead to additional doses in organs-at-risk (OAR) during SBRT. A patient selection tool was developed to identify who may be at risk of exceeding dose tolerances, by quantifying the dosimetric impact of daily variations using an OAR motion model. Materials and methods: The study included 133 CT scans from 35 LAPC patients. By following a leave-one-out approach, an OAR motion model trained with the remaining 34 subjects variations was used to simulate organ deformations on the left-out patient planning CT anatomy. Dose-volume histograms obtained from planned doses sampled on simulated organs resulted in the probability of exceeding OAR dose-constraints due to anatomical variations. Simulated probabilities were clustered with a threshold per organ according to clinical observations. If the prediction of at least one OAR was above the established thresholds, the patient was classified as being at risk. Results: Clinically, in 20/35 patients at least one OAR exceeded dose-constraints in the daily CTs. The model-based prediction had an accuracy of 89%, 71%, 91% in estimating the risk of exceeding dose tolerances for the duodenum, stomach and bowel, respectively. By combining the three predictions, our approach resulted in a correct patient classification for 29/35 patients (83%) when compared with clinical observations. Conclusions: Our model-based patient selection tool is able to predict who might be at risk of exceeding dose-constraints during SBRT. It is a promising tool to tailor LAPC treatments, e.g. by employing online adaptive SBRT; and hence, to minimize toxicity of patients being at risk. (C) 2019 Elsevier B.V. All rights reserved.