Subproject 1: PUMA Trial and PUMA II Trial
PUMA Trial
The primary objective is to demonstrate the clinical feasibility of MR-guided online-adaptive radiotherapy of locally-advanced NSCLC (LA-NSCLC).
The primary endpoint is a combined endpoint with a two-step approach:
- Successfully completed online adapted treatment fractions: The binary outcome successful completion of the online adapted treatment fraction without prior abortion, e.g. due to clinical intolerability or exceeded maximum time will be documented.
- Online-adaptive treatment duration: Online-adaptive treatment duration is defined as the total time of the patient on the treatment couch during an online adapted treatment fraction, i.e. from the MRI of the day to completion of the RT.
The main secondary endpoints are: treatment safety, eligibility for consecutive immunotherapy, local/regional/distant tumor control, patterns of recurrence, progression-free and overall survival, technical analyses (e.g. dosimetry benefits of adaptive treatment plans compared to simulated non-adaptive standard treatment plans)
Methods: The first step of clinical feasibility assessment is to demonstrate that all but one online adapted fractions are successfully completed in ≥ 80% of patients (≤ 1 cancellations in ≥ 80% of patients). This proportion of patients is given together with the corresponding 95%-confidence interval with exact Clopper-Pearson boundaries. Secondly, the mean treatment duration should be < 90 minutes. For this purpose, the mean averaged on-table times of all patients will be calculated as point-estimate with a corresponding 95%-confidence interval for the mean of a normal distribution.
The data collected in the feasibility trial at stage I will support the hypothesis of PUMA II. Since the randomozation requires a statistical planning of case numbers, in order to be reasonable, we need the toxicity data from the first phase, to plan the second phase.