Online Adaptive Radiotherapy in Pelvic and Thoracic Cancers - Comparing Toxicities, Clinical Outcomes and Technical Parameters between Conventional Image-Guided Radiotherapy and Online Adaptive Radiotherapy – The Study Protocol for the Prospective, Registry-Based, Phase II Trial (PRoART)
Authors: Fischer Laura Anna , Fischer Jann , Scheele Niklas Christian , Droege Leif Hendrik , Leu Martin , Guhlich Manuel , Oelmann-Avendano Jan Tobias , Hille Andrea , Bendrich Stephanie , Donath Sandra , Knaus Olga , Ziegler David Alexander , Zwerenz Carla Marie , Pagel Charlotta Friederike , Anczykowski Mahalia Zoe , Edelmann Marcus , Ammon Hanne Elisabeth , Bergau Pia Franziska Luise , Nitschmann Marc Juergen , Schirmer Markus Anton , Wenzel Alina Renata , Frohn Jasper , Bensberg Jona , Strauss Arne , Asendorf Thomas , Schmitt Daniela , Rieken Stefan , Shafie Rami Ateyah El 
Published: June 2024

Background
Conventional Radiotherapy (Image Guided Radiotherapy, IGRT) requires a computed tomography (CT)-based treatment planning (planning CT, pCT) process a priori. During this process, a treatment plan is calculated, which then is applied to the patient with a linear accelerator on a daily basis, possibly using image guidance to account for variability in patient position. However, daily changes of the anatomy of targets and organs at risk (OARs) can only be addressed by applying additional safety margins, resulting in larger irradiated volumes and possibly higher toxicity. A promising and innovative technique for margin and in consequence toxicity reduction is online Adaptive Radiotherapy (oART) using daily imaging to create a “plan of the day” aligned to the actual anatomy by means of artificial intelligence (AI) and with the patient on the treatment couch. Through daily image-guided re-optimization of the radiation treatment (RT) plan, the target coverage may also be improved. This approach is especially promising in the pelvic region due to the high anatomic variability, e.g. caused by peristalsis or volume changes of bladder and rectum.
Methods
This prospective registry-based trial will include patients with pelvic or thoracic tumors with an indication for RT treated with IGRT or oART using the Varian Ethos™ system. The primary endpoint is defined as a 10% reduction in the rate of acute RT related toxicity (≥ Common Terminology Criteria for Adverse Events (CTCAE) II°, v5.0) using oART. Secondary endpoints encompass clinical outcomes including late toxicities, tumor control rates, and patient-reported outcomes, as well as technical factors such as target volume, coverage, dose to OARs and anatomical variability score. While the trial compares IGRT versus oART for primary and secondary clinical endpoints, it also evaluates the real oART scenario against two hypothetical control scenarios for technical endpoints.
Discussion
The introduction of oART promises a reduction in toxicities and improved target volume coverage, potentially resulting in enhanced tumor control rates. It is poised to be a pioneering technology in the field of radiation oncology. Given the absence of a direct comparison between IGRT and oART thus far, the PRoART trial aims to address this gap.
Trial registration
Clinicaltrials.gov, NCT06185062. Registered 12/14/2023. Last update 02/06/2024.