MR-guided biologically individualized real-time adaptive high-precision radiotherapy (bio-iMRgRT)

• Applicant: Professor Dr. Daniel Zips
• Subject Area: Nuclear Medicine, Radiotherapy, Radiobiology ; Medical Physics, Biomedical Technology
• Term: from 2016 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 281568919

Combination of magnetic resonance imaging (MRI) with a linear accelerator (MRL) in a single device represents a straight forward technology development to improve outcome compared to current state of the art image guided radiotherapy (IGRT). In theory, MRL offers not only higher geometric precision due to its higher soft tissue contrast allowing for higher doses to the tumour and sparing normal tissues by closer margins but synergistically also the opportunity for real-time integration of biological imaging and subsequent treatment adaptation (biologically individualized MR-guided adaptive RT, bio-iMRgRT). The MRL technology is highly innovative but also very challenging for research and development and therefore requires thorough clinical evaluation of the potential benefit for patients over existing technologies. We have established an interdisciplinary clinical research group MR-guided Radiotherapy in Tübingen bringing together expertise in experimental and clinical research in the field of MR, medical physics, preclinical imaging, technology development and radiation oncology. Tübingen in co-operation with our national and international partners offers excellent infrastructure and expertise for MRL technology development, research and clinical evaluation. We hypothesize that the hybrid MRL allows novel dose-painting strategies with biological and geometrical precision superior to current state of the art off-line MR/PET imaging merged into CBCT IGRT. We envision in our interdisciplinary research proposal the development and evaluation of innovative applications towards bio-iMRgRT. We propose an interdisciplinary research and development program including basic and clinical dosimetry, MR-only RT planning, image registration and dose accumulation, development and validation of response models, validation of MRL treatment planning, development of dedicated imaging and treatment protocols as well as QA procedures. In the clinical phase we will enrol patients with head and neck, prostate, rectal and oesophageal cancer to explore the MRL in comparison with state of the art CBCT IGRT. Our large prospective database including external data will allow planning studies comparing off-line and on-line bio-iMRgRT. In the second phase we will enrol patients in prospective interventional trials exploring feasibility, safety and early clinical efficacy of bio-iMRgRT for model-based dose escalation, novel dose-fractionation schedules and organ- and functional sparing approaches. In parallel, we will further develop and clinically evaluate novel methods in functional MR and explore links to FDG, PSMA and Misonidazole MR/PET. Focus will be given to changes of functional imaging parameters during radiotherapy including their prognostic and predictive value. Our project is embedded in our BSc/MSc courses Medical Technology/ Medical Radiation Sciences and the PhD program at the Medical Faculty.

• DFG Programme: Major Instrumentation Initiatives
• Major Instrumentation: MR-Linearbeschleuniger
• Instrumentation Group: 3250 Beschleuniger (Medizin)
• Cooperation Partners: Professor Dr. Michael Baumann; Professorin Dr. Ulrike Ernemann; Professor Dr. Dietmar Georg, Ph.D.; Professor Dr. Konstantin Nikolaou; Professor Dr. Bernd Pichler; Professor Dr. Björn Poppe; Professor Dr. Richard Pötter; Professor Klaus Scheffler, Ph.D.; Professor Dr. Fritz Schick; Professor Marcel Verheij, Ph.D.
• Co-Investigator: Professorin Dr. Daniela Thorwarth