ROAR-A: re-optimization based Online Adaptive Radiotherapy of anal cancer, a prospective phase II trial protocol.

BACKGROUND: Chemo-radiotherapy with curative intent for anal cancer has high complete remission rates, but acute treatment-related gastrointestinal (GI) toxicity is significant. Toxicity occurs due to irradiation of surrounding normal tissue. Current radiotherapy requires the addition of large planning margins to the radiation field to ensure target coverage regardless of the considerable organ motion in the pelvic region. This increases the irradiated volume and radiation dose to the surrounding normal tissue and thereby toxicity. Online adaptive radiotherapy uses artificial intelligence to adjust the treatment to the anatomy of the day. This allows for the reduction of planning margins, minimizing the irradiated volume and thereby radiation to the surrounding normal tissue.This study examines if cone beam computed tomography (CBCT)-guided oART with daily automated treatment re-planning can reduce acute gastrointestinal toxicity in patients with anal cancer. METHODS/DESIGN: The study is a prospective, single-arm, phase II trial conducted at Copenhagen University Hospital, Herlev and Gentofte, Denmark. 205 patients with local only or locally advanced anal cancer, referred for radiotherapy with or without chemotherapy with curative intent, are planned for inclusion. Toxicity and quality of life are reported with Common Terminology Criteria of Adverse Events and patient-reported outcome questionnaires, before, during, and after treatment. The primary endpoint is a reduction in the incidence of acute treatment-related grade ≥ 2 diarrhea from 36 to 25% after daily online adaptive radiotherapy compared to standard radiotherapy. Secondary endpoints include all acute and late toxicity, overall survival, and reduction in treatment interruptions. RESULTS: Accrual began in January 2022 and is expected to finish in January 2026. Primary endpoint results are expected to be available in April 2026. DISCUSSION: This is the first study utilizing online adaptive radiotherapy to treat anal cancer. We hope to determine whether there is a clinical benefit for the patients, with significant reductions in acute GI toxicity without compromising treatment efficacy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05438836. Danish Ethical Committee: H-21028093.

Online adaptive radiotherapy of anal cancer: Normal tissue sparing, target propagation methods, and first clinical experience.

BACKGROUND AND PURPOSE: Online adaptive radiotherapy (oART) potentially spares OARs as PTV margins are reduced. This study evaluates dosimetric benefits, compared to standard non-adaptive radiotherapy (non-ART), target propagation methods, and first clinical treatments of CBCT-guided oART of anal cancer. MATERIALS AND METHODS: Treatment plans with standard non-ART and reduced oART PTV margins were retrospectively generated for 23 consecutive patients with anal cancer. For five patients randomly selected among the 23 patients, weekly CBCT-guided oART sessions were simulated, where the targets were either deformed or rigidly propagated. Preferred target propagation method and dose to OARs were evaluated. Ten consecutive patients with anal cancer were treated with CBCT-guided oART. Target propagation methods and oART procedure time were evaluated. RESULTS: For the retrospective treatment plans, oART resulted in median reductions in bowel bag V45Gy of 11.4 % and bladder V35Gy of 16.1%. Corresponding values for the simulated sessions were 7.5% and 27.1%. In the simulated sessions, 35% of all targets were deformed while 65% were rigidly propagated. Manual editing and rigid propagation were necessary to obtain acceptable target coverage. In the clinical treatments, the primary and some elective targets were rigidly propagated, while other targets were deformed. The median oART procedure time, measured from CBCT acquisition to completion of plan review and QA, was 23 min. CONCLUSIONS: Simulated oART reduced the dose to OARs, indicating potential reduction in toxicity. Rigid propagation of targets was necessary to reduce the need for manual edit. Clinical treatments demonstrated that oART of anal cancer is feasible but time-consuming.

Evaluation of an automated template-based treatment planning system for radiotherapy of anal, rectal and prostate cancer.

Background and purpose: The Ethos system has enabled online adaptive radiotherapy (oART) by implementing an automated treatment planning system (aTPS) for both intensity-modulated radiotherapy (IMRT) and volumetric modulated arc radiotherapy (VMAT) plan creation. The purpose of this study is to evaluate the quality of aTPS plans in the pelvic region. Material and Methods: Sixty patients with anal (n = 20), rectal (n = 20) or prostate (n = 20) cancer were retrospectively re-planned with the aTPS. Three IMRT (7-, 9- and 12-field) and two VMAT (2 and 3 arc) automatically generated plans (APs) were created per patient. The duration of the automated plan generation was registered. The best IMRT-AP and VMAT-AP for each patient were selected based on target coverage and dose to organs at risk (OARs). The AP quality was analyzed and compared to corresponding clinically accepted and manually generated VMAT plans (MPs) using several clinically relevant dose metrics. Calculation-based pre-treatment plan quality assurance (QA) was performed for all plans. Results: The median total duration to generate the five APs with the aTPS was 55 min, 39 min and 35 min for anal, prostate and rectal plans, respectively. The target coverage and the OAR sparing were equivalent for IMRT-APs and VMAT-MPs, while VMAT-Aps.demonstrated lower target dose homogeneity and higher dose to some OARs. Both conformity and homogeneity index were equivalent (rectal) or better (anal and prostate) for IMRT-APs compared to VMAT-MPs. All plans passed the patient-specific QA tolerance limit. Conclusions: The aTPS generates plans comparable to MPs within a short time-frame which is highly relevant for oART treatments.

Online adaptive radiotherapy of urinary bladder cancer with full re-optimization to the anatomy of the day: Initial experience and dosimetric benefits.

BACKGROUND AND PURPOSE: Online adaptive radiotherapy (oART) potentially reduces the dose to organs at risk (OARs) as the planning target volume (PTV) margins are reduced compared to a non-adaptive approach (non-ART). This study evaluates the feasibility and dosimetric impact of cone-beam computed tomography (CBCT)-guided oART of urinary bladder cancer for the first patients treated, using patient-specific margins. MATERIALS AND METHODS: Sixteen consecutive patients with muscle-invasive bladder cancer received two or more (median = 23) fractions as oART, and remaining fractions as non-ART. The non-ART fractions were delivered with standard population-based margins, while reduced patient-specific margins based on intra-fractional variations extracted from 2-4 fractions were applied to the primary PTV (PTV-T) during the oART fractions. Target volume and coverage, and dose to OARs were compared between non-ART and oART plans, and the oART procedure time was recorded. RESULTS: In total, 297/512 fractions were delivered as oART with full re-optimization to the anatomy of the day. The median (interquartile range, IQR) oART procedure time, measured from the end of CBCT generation to completion of plan review, and quality assurance was 13.9 (11.9;16.6) min. The median (IQR) volume reduction in PTV-T volume was 33.9 (24.2;45.0)%, comparing oART and non-ART plans, resulting in median (IQR) reductions in bowel bag V45Gy of 18.8 (12.7;27.9)% and rectum V50Gy of 70.7 (35.9;94.8)%. By re-optimizing the plan to the daily anatomy, full target coverage was achieved at all oART fractions. CONCLUSIONS: oART resulted in large reductions in treatment volumes and doses to OARs, compared to non-ART, while ensuring target coverage. This indicates potential reductions in gastrointestinal toxicity.