The minipig experiment: a last major milestone prior clinical trials in MRT?
Résumé
Microbeam Radiation Therapy (MRT) has made considerable advances in all domains over the last 2 decades. By now, we have a better understanding of the underlying biological processes and in particular solid proof by scientists from different laboratories of the extraordinary normal tissue sparing of MRT as well as its differential effect between the tumour vasculature and the normal tissue vasculature, inducing hypoxia in preclinical tumour models when high-dose, spatially fractionated microbeams are applied in preclinical research[1]. Further milestones include the development of a dosimetry protocol, benchmarking of Monte Carlo dose calculations using several high resolution dosimeters, the development of a treatment planning system and the development of a MRT Patient Safety system to control dose delivery at high dose rates around 8000 Gy/sec.
Prior a successful translation of the biological findings into an optimized treatment plan for humans, larger animals than rodents should be treated in MRT, which is one of the aims of the veterinary trials. A realistic scenario for a clinical trial phase I could be an MRT treatment delivered as a boost in order to delay tumor growth and increase the lifespan. The plan to irradiate landrace pigs in such a regim using 3 x 11Gy as in conventional RT in 1 week compared to 2 x 11Gy plus 1 MRT irradiation at 11Gy in the valley at the tumour site is being proposed. This project represents one of the last steps towards clinical application of MRT where microbeam radiation therapy would be applied as a relevant and efficient therapeutic boost for brain tumor management. A phase I clinical trial should first demonstrate the normal tissue tolerance in humans applying a simple cross-fired microbeam array from a maximum of 3 ports prior moving to more sophisticated irradiation geometries. Such potentially interesting irradiation geometries could keep the normal tissue at very low dose values applying a large centre to centre distance of 1200 μm, and in combination with a horizontal microbeam dose delivery from several ports, tumor control could be improved using intersperced beams to deliver a radiotherapeutic relevant valley dose only at the tumour site at tighter ctc spacing.
References
[1] – A. Bouchet et al., “Synchrotron microbeam radiation therapy induces hypoxia in intracerebral gliosarcoma but not in
the normal brain“ Radiotherapy and Oncology 108 (2013) 143-14