Preclinical biological assessment of proton and carbon ion beams at hyogo ion beam medical center

Abstract

Purpose: To assess the biological effects of proton and carbon ion beams and to decide clinical RBE values before clinical use. Materials and methods: Cultured cells from human salivary gland cancer (HSG) were irradiated at 5 points along a 190MeV proton beam and along a 320MeV carbon ion beam, with its Bragg peak modulated to 6cm widths (P190/6-SOBP and C320/6-SOBP), and a linac 4MV X-ray (X4) was used as a reference. Survival curves were obtained by colony formation assay. RBE values at each point was calculated when D10 or D50 doses were given to the center of each SOBP beam. Cells were also irradiated in a cell-stack phantom to identify that presumed cell deaths were observed at predefined depth in a setting of single fractional irradiation. To represent in vivo biological effects, total body irradiation of C3H/He mice was performed at 4 points along both P190/6-SOBP and C320/6-SOBP. The number of regenerating crypts per jejunal section was compared between P190/6-SOBP or C320/6-SOBP and referential X4 to calculate intestinal RBE values. Mice right legs were also irradiated at 2 points along a C320/6-SOBP beam by 4-fractional treatment and the irradiated areas were followed-up for a month by means of skin reaction scoring. Results: RBE values for P190/6-SOBP calculated from cell survival curves ranged from 1.01 to 1.05 at D10 level and from 1.01 to 1.07 at D50 level, and the values for C320/6-SOBP ranged from 1.23 to 2.56 and from 1.21 to 3.47, respectively (Table). The biological doses in the SOBP portion were flat enough with the uniformity of }2.5% for P190/6-SOBP and }5.0% for C320/6-SOBP. The cell-stack phantom irradiation revealed the flatness of the biological doses of both SOBP beams with the same accuracy as anticipated. The intestinal RBE values ranged from 1.01 to 1.08 for P190/6-SOBP and from 1.15 to 1.18 for C320/6-SOBP at the dose level that the number of jejunal crypts decreases to be 10 per circumference. The skin RBE value calculated from 4-fractional treatment of mice right legs was 1.30 at 5 mm depth and 2.16 at the SOBP center. We adopted the clinical RBE value of 1.1 at the center of SOBP for modulated proton beams. A comparative biological study with the other 6cm-SOBP beam generated from a 290MeV carbon beam demonstrated that carbon beams at the two different facilities had the same biological effect when the dose-averaged LET was the same (46.6 keV/μm). Thus the clinical RBE value of 2.23 was assigned at the 46.6 keV/μm point in the modulated carbon ion beam (SOBP center of C320/6-SOBP) to share a clinical dose-response evaluation system between the two facilities. Conclusion: Expected biological depth-dose distributions were observed on both P190/6-SOBP and C320/6-SOBP beams. The clinical RBE value was decided as 1.1 at the center of SOBP for modulated proton beams and 2.23 at 46.6keV/μm point in modulated carbon ion beams. Tabled 1Biological systemEnd pointX4 dose levelRBE values of proton P190/6-SOBPRBE values of carbon ion C320/6-SOBPHSG cell10% survival5.23Gy1.01 – 1.051.23 – 2.56HSG cell50% survival2.33Gy1.01 – 1.071.21 – 3.46Mouse jejunal crypt10 crypts/section14.70Gy1.00 – 1.081.15 – 1.88Mouse skin reactionPeak score = 2.541.6GyNot assessed1.30 (entrance), 2.16 (SOBP center) Open table in a new tab