CBCT-Based Online Adaptive, Ultra-Hypofractionated Radiotherapy for Prostate Cancer: First Clinical Experiences

<i>Background and Objectives</i>: Ultra-hypofractionated radiotherapy (uhRT) is increasingly used for low- and intermediate-risk localized prostate cancer, necessitating exceptional precision compared to conventional fractionation. CBCT-based online-adaptive uhRT may help mitigate pelvic organ motion but has not yet been established in clinical routine. We report initial clinical experiences focusing on the feasibility and technical aspects of treatment delivery. <i>Materials and Methods</i>: Seven patients (35 fractions) with low- or intermediate-risk prostate cancer were treated with online-adaptive uhRT on the Varian Ethos^® system within routine clinical care. The target included the prostate and proximal seminal vesicles (CTV1, 5 × 7.25 Gy), with an integrated boost to the prostate (CTV2, 5 × 8.00 Gy). For each fraction, dose-volume histogram (DVH) parameters for targets and organs at risk (OARs) were recorded retrospectively for both scheduled and adaptive plans, along with the plan selection decision. Plan quality was evaluated per clinical DVH constraints and target coverage. The treatment time was recorded. <i>Results</i>: Online-adaptive uhRT was successfully delivered every day in 5 patients and on alternate days in 2 patients. Mean treatment time was 30:17 (±05:49 SD) minutes per fraction. The median recorded change in target and OAR volumes was <10%. Adaptive plans resulted in a statistically significantly improved target coverage for CTV1 (V100%, <i>p</i> = 0.01), PTV1 (D98%, <i>p</i> < 0.001), PTV2 boost (D98%, <i>p</i> < 0.001) in Wilcoxon signed-rank tests. OAR dose reduction was limited, with a small improvement in bladder V40Gy (<i>p</i> = 0.02). Adaptive plans were applied in 32/35 fractions (91.4%). To encompass intra-fractional motion in 95% of fractions, positional adjustments up to 0.77 cm (longitudinal), 0.37 cm (lateral), and 0.59 cm (sagittal) were required. <i>Conclusions</i>: Online-adaptive uhRT appears feasible, leading to optimized target volume coverage. Considerable treatment times must be taken into account. A second CBCT is recommended to compensate for intra-fractional motion. Further research regarding patient-related endpoints and cost-effectiveness is highly needed.