RADIOBIOLOGICAL CHARACTERIZATION OF TWO THERAPEUTIC PROTON BEAMS WITH DIFFERENT INITIAL ENERGY SPECTRA USED AT THE INSTITUT CURIE PROTON THERAPY CENTER IN ORSAY

Purpose: Treatment planning in proton therapy uses a generic value for the relative biological efficiency (RBE) of 1.1 throughout the spread-out Bragg peak (SOBP) generated. In this article, we report on the variation of the RBE with depth in the SOBP of the 76- and 201-MeV proton beams used for treatment at the Institut Curie Proton Therapy Center in Orsay. Methods and Materials: The RBE (relative to (137)Cs gamma-rays) of the two modulated proton beams at three positions in the SOBP was determined in two human tumor cells using as endpoints clonogenic cell survival and the incidence of DNA double-strand breaks (DSBs) as measured by pulse-field gel electrophoresis without and with enzymatic treatment to reveal clustered lesions. Results: The RBE for induced cell killing by the 76-MeV beam increased with depth in the SOBP. However for the 201-MeV protons, it was close to that for (137)Cs gamma-rays and did not vary significantly. The incidence of DSBs and clustered lesions was higher for protons than for (137)Cs gamma-rays, but did not depend on the proton energy or the position in the SOBP. Conclusions: Until now, little attention has been paid to the variation of RBE with depth in the SOBP as a function of the nominal energy of the primary proton beam and the molecular nature of the DNA damage. The RBE increase in the 76-MeV SOBP implies that the tumor tissues at the distal end receives a higher biologically equivalent dose than at the proximal end, despite a homogeneous physical dose. This is not the case for the 201-MeV energy beam. The precise determination of the effects of incident beam energy, modulation, and depth in tissues on the linear energy transfer RBE relationship is essential for treatment planning. (C) 2011 Elsevier Inc.