A biological and dosimetric study of hadrontherapy on tumor and normal cells. (PhD)

It is the goal of any tumour therapy to deliver a sufficiently high dose to kill all tumour cells and to spare normal tissue to a maximum extend.

Consequently, progress in radiotherapy has been driven in the past 100 years by the search for greater precision and higher biological effectiveness. Radiotherapy using protons and carbon ions (also named hadrontherapy) represents the closest approach to this goal: ion beams have millimeter precision and an inverse depth-dose profile with an increase of the dose with depth. In addition, for carbon ions, the radiobiological effectiveness (RBE) is higher at the position of the tumour than in the surrounding normal tissue. Therefore heavy charged-particle beams have the capacity to deliver safely (i.e. with a very low complication risk) a dose to the tumour sufficient to eliminate it, with greater efficacy than conventional (i.e. megavoltage bremsstrahlung) radiotherapy beams. Furthermore, this method has demonstrated the advantages of these ions, in particular carbon ions, for the very accurate treatment of deep-seated tumours which are inoperable and radioresistant. Hadrontherapy has been tested in Japan (Chiba) and Germany (Darmstadt) for several years, following the pioneering work initially carried out at Berkeley. Furthermore, several treatment centers are under construction: two in Germany, one in Italy and one in France.

It is the general goal of this PhD project to gain more information at the biological and at the dosimetric level on the (heavy) particle radiation response of normal and cancer tissues such as within the central nervous system, the lung, the rectum/gastro-intestinal tract and the  hematopoietic system. Minimizing uncertainty on healthy tissue response to protons and carbon ions is also necessary to expand the applications of hadrontherapy in curing cancer. Therefore, it is planned, in a first instance, to compare the biological effects at the morphological, cellular, biochemical and molecular levels of protons and carbon ions with X-rays using in vitro normal and cancerous cell lines; and to then transfer the experimental and dosimetric results in mathematical models used in the treatment planning for protons and carbon ions. In vitro experiments coupled with dosimetry are necessary to understand the biological mechanisms involved in the effects of protons and carbon ions.

In a second phase, animal experiments using existing mouse models spontaneously developing cancer will be studied through in vivo experiments with ion beams.

It is intended that the knowledge generated within this PhD will be hopefully useful and transferred to treatment planning for patients.