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 γ-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 γ-rays and did not vary significantly. The incidence of DSBs and clustered lesions was higher for protons than for (137)Cs γ-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.