AbstractIntroductionUsing diagnostic CT for radiotherapy (RT) planning can bypass traditional CT simulation but introduces challenges in patient positioning and Hounsfield unit (HU) fidelity, affecting dose accuracy. Here a Varian Ethos adaptive‐driven CT direct‐to‐treatment (DtT) multi‐fraction stereotactic body radiation therapy (SBRT) workflow is presented.MethodsThis study employed institutional diagnostic PET‐CT images to generate an initial reference Ethos treatment plan. HU and dosimetric accuracy were validated for PET‐CT, Ethos CBCT images (with and without Hypersight (HS), and the gold‐standard helical CT simulators). Following the SBRT reference plan creation on the low dose diagnostic PET‐CT, the first fraction was delivered with a newly generated adaptive plan calculated on the HS CBCT (Ethos) images. For multi‐fraction treatments, the first day CBCT images and adaptive plan become the reference for subsequent IGRT treatments. This study includes workflow validation and initial three patient experience.ResultsThe DtT adaptive SBRT workflow was successfully implemented, with initial end‐to‐end testing demonstrating feasibility. In‐house solutions were introduced to facilitate the adaptive to IGRT plan conversion. The Ethos system, especially with HS, maintained HU fidelity and dose calculation accuracy comparable to helical CTs. On‐table adaptive sessions were within 37–51 min, aligning with single‐fraction palliative studies. Subsequent non‐adaptive IGRT fractions were efficiently completed within 7–27 min.ConclusionsThis study demonstrates the feasibility of DtT adaptive‐driven multifraction SBRT using diagnostic PET‐CT. This approach reduces the need for on‐site patient presence prior to treatment, expands planning lead times, and improves overall efficiency in radiotherapy for well selected patients.