Relative Biological Effectiveness of Proton Therapy on Tumor and Lung Tissues

Particle therapy is the new direction of radiotherapy. Proton, the most widely used particle therapy, hoses different interactions with matter from photon. Protons relief most of the residual energy close to their range-end, which is called Bragg peak. There is an increased linear energy transfer in the Bragg peak that is linked with increased cell killing and RBE (relative biological effectiveness). Dose in proton therapy is defined in terms of an effective dose, which is the physical dose multiplied by a RBE. In clinical practice, a single generic RBE of 1.1 is applied to all proton beam therapy. However, the RBE around Bragg peak is different from the one in high-energy regions. The value of RBE also depends on the study endpoint. Due to the lack of accurate dose measurement, most of the previous reports studied the proton RBE at the middle of the proton tract. The data of proton RBE in vivo are relatively few. In this project, with delicate dose simulations and measurements, we would like to explore the proton RBE on the endpoints which are rarely discussed. Both in vitro and in vivo models are included in this project. Because it is easy to determine the accurate dose in the in vitro system, the RBE of proton will be examined in details. We will compare the responses to proton beams among photon-sensitive and photon-resistant GBM cell lines. DNA damages and loss of the clonogenic capabilities are the endpoints of these models in the monolayer culture. In order to study the impacts of cell-to-cell interactions, hypoxia, and nutrition stress on proton treatment, we will establish the spheroid model to simulate these conditions in vitro. The in vivo studies of proton RBE include a lung metastasis model and a window chamber model. The development of microCT makes the observation of lung tumor formation and regression after irradiation much easier than that before. Another study endpoint, radiation-induced pneumonitis, can also be followed by the microCT scan. We will use the window chamber system to analyze the effects of proton and photon beams on the tumor cells and their microenvironments, especially the vasculature. This observation will be performed continuously by both fluorescent microscopy and OCT (optical coherent tomography). Furthermore, this system could be used to study the RBE of proton beam in the Bragg peak region in vivo.

Project ID:PC10308-1225
External Project ID:MOST103-2314-B182-055