Subproject 1: PUMA Trial and PUMA II Trial

• PUMA Trial
• PUMA II Trial
• Image-Guided Adaptive Radiotherapy (IGART)
• Contact

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: 

1. 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.
2. 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.

In stage II (PUMA II Trial), a prospective clinical trial will be carried out, which aims at a reduction of cardiac, esophageal and pulmonary toxicity ≥ grade III (according to Common Terminology Criteria for Adverse Events, version 5) compared to the standard, conventional, non-adaptive treatment.

Further information will be given by the end of 2024.

In our collaborative study and clinical trial, two different image-guided adaptive radiotherapy (IGART) technologies are applied:

(1) Magnetic resonance guided radiotherapy (MRgRT):

The modern hybrid device consists of an magnetic resonance imaging (MRI) scanner and a linear accelerator. The combination of both devices allows MR imaging to be carried out before and during each radiotherapy treatment. This allows to adapt the radiotherapy plan to anatomical changes of the patient on a daily basis. Breathing movements are also visualised during radiotherapy so that patients can be instructed to hold their breath in a targeted manner. Overall, this results in a particularly precise and individualised radiotherapy treatment.

Systems, used at UKHD, LMU & UKT: MRIdian® from ViewRay, and ELEKTA

(2) ETHOS with offline MRI image guidance:

The ETHOS is a hybrid device consisting of a cone-beam computer tomography (CT) and a linear accelerator. It enables daily online adaptive radiotherapy. The low-dose CT, which was previously only used for pure positioning, is now also used to develop a daily customised radiation plan. This enables more precise radiotherapy. At the DKFZ Heidelberg, the ETHOS device is also connected to the neighbouring MRI device by a shuttle. The MRI delivers more precise images due to its significantly higher soft tissue contrast. Thanks to the shuttle, patients do not have to stand up after the MRI examination, but are brought to the device in their irradiation position. This is done with the help of an inflatable air cushion. This procedure is also known as "offline MRI image guidance". The benefits of additional MRI imaging using the shuttle system are currently being investigated in studies at the DKFZ.

System, used at DKFZ: ETHOS® from VARIAN

Subproject Leaders: 

Prof. Dr. Dr. Jürgen Debus

Head of the Department of Radiation Oncology and Radiation Therapy, Heidelberg University Hospital

Prof. Dr. Juliane Hörner-Rieber

Senior Physician in the Department of Radiation Oncology and Radiation Therapy, Heidelberg University Hospital

Dr. Sebastian Regnery 

Assistant Physician in the Department of Radiation Oncology and Radiation Therapy, Heidelberg University Hospital

E-Mail: sebastian.regnery@med.uni-heidelberg.de

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