Cancer is responsible for 25% of deaths in Europe and radiation therapy (RT) has a key role in its treatment. At least 50 % of cancer patients receive RT in the course of their illness. Optimising benefit/risk ratio in RT requires novel treatment protocols that maximise tumour control while reducing therapy-related toxicities. Normal tissue tolerances still compromise an effective treatment of many late stage tumours, radio-resistant bulky tumours, recurring tumours and some paediatric cancers, in current clinical. The main objective of this project is to investigate the biological effects of spatial variations in dose delivery to reduce the normal tissue toxicities of those treatments.
Radiotherapy (RT) is a cornerstone of cancer treatment. However, the dose tolerances of normal tissues continue to be the main limitation in RT. Finding novel approaches leading to healthy tissues protection is of utmost importance. This is the case of minibeam radiation therapy (MBRT), an innovative RT approach. MBRT employs strong spatial dose modulation: the irradiation is performed by means of an array of sub-millimetric beams. The distinct radiobiological mechanisms activated by MBRT results in a remarkable reduction of normal tissue radiation toxicities. Numerous preclinical experiments and the outcome of the two first patients’ treatments indicate that MBRT offers promise for the treatment of hopeless cases today, such as some bulky and radioresistant tumours. To make future patients optimally profit from the healthy tissue preservation offered by MBRT, a deeper understanding of the underlying biology and its relationship with the complex dosimetry of MBRT is needed. Along this line, the BIOMBRT project aims at providing a deep understanding of the potential differential immune and vascular effects (major players) after MBRT with respect to conventional RT involved in normal tissue sparing.
With that aim we will perform a series of preclinical experiments. We will investigate the effect of MBRT on two different (radiosensitive) organs (brain and lung), impacted in two oncological diseases associated with high mortality: gliomas and advanced lung cancer. Doseescalation studies will be performed to assess the gain of normal tissue complication probability with respect to conventional RT. A longitudinal imaging study will be carried out to get an understanding on how different MBRT configurations impact on both normal vasculature. An extensive -omics study including single cell RNA sequencing, spatial transcriptomics and proteomics would provide a holistic vision on the differential pathways being activated in MBRT. Finally, multiplexing immunochemistry evaluations would complement the previous evaluations. The knowledge acquired would allow unleashing the full potential of MBRT and optimally design future clinical trials. Therefore, BIOMBRT fits within one of the major goals of PIANOFORTE: Investigating the effects of temporal and spatial variations in dose delivery on the risk of health effects.
