Background <p>Conventional image-guided radiotherapy (IGRT) typically relies on a computed tomography (CT)-based treatment planning process (planning CT, pCT) performed prior to the start of treatment. During this process, a patient-specific treatment plan is generated, which is then delivered to the patient with a linear accelerator on a daily basis, usually with image guidance to compensate for variations in patient setup. However, daily interfractional anatomical variations in target position, shape, and volume, as well as in surrounding organs at risk (OARs), can only be addressed indirectly by adding safety margins, resulting in larger irradiated volumes and potentially increased toxicity. Online adaptive radiotherapy (oART) is a promising and innovative technique to reduce such margins and, consequently, treatment-related toxicity. It uses daily imaging to generate a “plan of the day” that is aligned with the current patient anatomy, often supported by artificial intelligence (AI), while the patient remains on the treatment couch. Through daily image-guided re-optimization of the radiation treatment (RT) plan on the anatomy of the day, target coverage may also be improved. This approach is particularly attractive in the pelvic region, where high interfractional anatomical variability, for example due to peristalsis or changes in bladder and rectal filling, is frequently observed.</p> Methods <p>This prospective registry-based cohort study 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 (PROs), as well as technical factors such as target volume, coverage, dose to OARs and anatomical variability score. While the cohort study 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.</p> Discussion <p>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 prospective registry-based cohort study PRoART aims to address this gap.</p> Trial registration <p>Clinical trial number NCT06185062, Clinicaltrials.gov. Registered 12/14/2023. Last update 07/29/2026. </p>