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Experimental Radiotherapy for Malignant Brain Tumours

Final Report Summary - ERTMABTU (Experimental Radiotherapy for Malignant Brain Tumours)

The scientific aims of this project, supported by an international Marie Curie Reintegration Grant to Dr. Elisabeth Schültke, included the assessment of radiobiological consequences and adverse effects of monoplanar microbeam radiation therapy (MRT) with view towards future clinical trials and to drive the early development phase of a micro-pencilbeam radiation technique with respect to its use for whole brain irradiation therapy in patients with highly infiltrating malignant brain tumors or multiple brain metastases. Both experimental techniques are developed and tested at the European Synchrotron radiation Facility (ESRF) in Grenoble. At the current stage of development, the availability of a dedicated biomedical synchrotron facility is prerequisite for this type of research. We hope, however, that some of the compact X-ray sources under development will allow the transfer of MRT into the hospital environment within the next decade.

Monoplanar MRT and micro-pencilbeam irradiation are currently used in the preclinical research phase, in cell culture studies (in-vitro) and small animal models of malignant brain tumor (in-vivo). Our research group has obtained first in-vivo data with the micro-pencilbeam technique. Following the irradiated animals for a period of six months, during which several tests for motor and memory performance were conducted, we have identified the technical and physiological limitations of the new technique. We have provided the proof that micro-pencilbeam irradiation at the synchrotron is a feasible solution for whole brain irradiation, at least in a small animal model. Analyzing the results of those first experiments we found that the technical solution we had used resulted was not optimal, because the irradiation period was too long for high quality work. One requirement for the precise administration of microbeams, whether monoplanar or pencilbeams, is the very fast administration of a very high irradiation dose, even within fractions of a second. Only a short irradiation time assures that little or no blurring of the microbeam edges occurs and, as a consequence, normal tissue will stay functionally intact. With the results of our experiments we supported the decision to design, produce and install a new collimator that is especially suited for work with this technique.

The research results from this and other groups show that MRT induces tissue reactions which are significantly different from those seen after broad beam irradiation with regard to proteomic and genetic expression. It is likely that part of the therapeutic effect of MRT results from secondary effects rather than direct cell kill as consequence of the irradiation process. We believe that it is very likely that future MRT research will be extended to other organ systems (outside the central nervous system).

With the transfer of MRT from bench to bedside within the next decade, this technique has a large potential to increase the quality of life for patients with malignant brain tumours. The two most important aspects in this regard are a significantly reduced hospitalization period from four to six weeks to less than one week for radiotherapy and a low rate of irradiation-induced adverse effects. Especially in young children, where radiotherapy can be conducted only when they are anaesthetized, a shortening of the therapy cycle would significantly increase the quality of life for patients and care givers.
During the 4-year period of this grant, already existing international collaborations have been extended with colleagues in France and Canada. In three of the four years, we have hosted an exchange student from the Laboratory of Radiobiology at McMaster University in Canada. New collaborations have been started with colleagues in Switzerland and Italy. Out of those collaborations have resulted already 5 publications, with more manuscripts still in preparation.