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WP-3 Radiobiology and modeling for innovative radiotherapies

The technological innovations needed to treat resistant radio tumors depend on the combination of better targeting and increased toxic effect on the tumor. Among the innovative radiotherapies, carbon ion hadrontherapy entered the clinical trial phase in Germany and Japan, and the PAT-Z (Radiation Therapy by Photoactivation of High-Z-elements) and MRT (Microbeam Radiation Therapy) techniques are currently in the preclinical phase.

A beam of carbon ion
abruptly deposits a maximum of energy at the end of the course (= Bragg peak) which makes it possible to treat deep tumors while delivering minimal doses of energy to the surrounding tissues. In addition, at equivalent physical dose, carbon ions induce much more severe intracellular lesions than photons such as complex damage to DNA, leading to greater destruction of cancer cells.

The carbon ions also have the paricularity of increasing destruction of hypoxic tumors, and of showing a suppressive effect of angiogenesis and cell migration (metastases).

Higher relative biological effectiveness (GBR) and finer targeting, allow for hypo-fractionated treatment and improved life expectancy as observed in preliminary clinical studies. The PAT-Z technique is based on the local increase of the dose of radiation delivered to the tumor, after interaction with absorbing elements such as platinium salts, gold or gadolinium particles previously injected into the body. At the same time, the MRT technique uses a very thin X-ray beam that delivers doses of several octagray in a fraction of a second while sparing healthy tissue. It is a promising alternative to radio surgery in neuro-oncology. Two models are currently being incorporated into treatment planning systems (TPS) for carbon therapy: the Local Effect Model (LEM) in Germany and the MKM model (Microdosimetrik Kinetic Model) in Japan. So far, no model has been developed for PAT-Z and MRT techniques.

The objectives of this WP are to elucidate, quantify and predict cell events generated by high energy carbon ions, by PAT-Z and MRT techniques and at different levels (from femtosecond to several months, and from the molecule to tissues) to optimize the transfer of these innovative radiotherapies to clinical applications. In parallel with experiments in living systems, radiobiology includes the development of irradiation platforms, methodologies and simulations for data analysis, acquisition and prediction.