The relative biological effectiveness of proton and carbon ion beams in photon-sensitive and resistant nasopharyngeal cancer cells

Abstract

Background: Approximately 10–15% of all nasopharyngeal carcinoma (NPC) cases will develop local recurrence (LR) after definitive radiation therapy. Clinical data has demonstrated a decreased treatment-related toxicities and a potential improved local control rate with carbon ion radiotherapy (CIRT) as compared to photon-based intensity-modulated radiotherapy (IMRT) for LR-NPC. However, the relative biological effectiveness (RBE) for NPC cells, especially the photon-radioresistant nasopharyngeal carcinoma (prNPC) cells within recurrent tumors, have not been determined. Methods: An established prNPC cell line (CNE-2R), which represents a cell model for extremely photon resistant NPC, and its parental cell line, CNE-2 were irradiated by photons or protons (energy, 74.55– 95.8 MeV; LET, ~3.125 keV/μm) with doses of 2, 4, 6, 8 and 10 Gy or by carbon ion pencil beam (energy, 148.3–180.3 MeV/u; LET, ~315.7 keV/μm) with physical doses of 2, 4, 6 and 8 Gy. Clonogenic survival was studied by analyzing the macrocolony formation and RBE values were at 10% (D 10 ) and 37% (D 37 ) survival. Results: For photon response, the α/β ratio for CNE-2 cells is higher compared to CNE-2R cells. The proton-treated cell survival curves demonstrated similar profiles to those of X-rays for CNE-2 and CNE-2R cell lines. The RBE of proton beam at 10% survival (D 10 ) was 0.95 for CNE-2 cells as compared with 0.98 for CNE-2R cells. The surviving fraction (SF) at 2 Gy, after exposure to photons, ~3.125 keV/μm protons and 315.7 keV/μm carbon ions, were 0.547, 0.566 and 0.166 for CNE-2 and 0.686, 0.750 and 0.310 for CNE-2R cells, respectively. The CNE-2R cells were less sensitive to carbon ions than CNE-2 cells. The RBE for carbon at 10% and 37% survival levels were 2.46 and 2.90 for CNE-2 cells compared with 1.95 and 2.53 for CNE-2R cells, respectively. Therefore, the RBEs in the photon-resistant CNE-2R cells were relatively lower than those in photon-sensitive CNE-2 cells following X-ray or carbon ion irradiation at 315.7 keV/μm. Conclusions: Compared with photons and protons, carbon ion shows better cell inactivation capability in both CNE-2 cells and photon resistant CNE-2R cells. The RBE values of NPC cells can help in making strategic decisions on the design of clinical trials using carbon ion therapy.