Evaluation of the relative biological effectiveness of spot-scanning proton irradiation in vitro

Journal of Radiation Research, Vol. 57, No. 3, 2016, pp. 307–311 doi: 10.1093/jrr/rrv101 Advance Access Publication: 1 February 2016 Evaluation of the relative biological effectiveness of spot-scanning proton irradiation in vitro Kenichiro Maeda1, Hironobu Yasui2, Taeko Matsuura3, Tohru Yamamori2, Motofumi Suzuki2, Masaki Nagane2, Jin-Min Nam1,4, Osamu Inanami2 and Hiroki Shirato1,4* 1 Department of Radiation Medicine, Graduate School of Medicine, Hokkaido University Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University 3 Department of Medical Physics, Proton Beam Therapy Center, Hokkaido University Hospital 4 Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education, Hokkaido University *Corresponding author. Department of Radiation Medicine, Graduate School of Medicine, Hokkaido University, Kita 15 Nishi 7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan. Tel: +81-11-706-5977; Fax: +81-11-706-7876; Email address: Received August 18, 2015; Revised December 2, 2015; Accepted December 7, 2015 2 A B S T R AC T Variations in relative biological effectiveness (RBE) from a fixed value of 1.1 are critical in proton beam therapy. To date, studies estimating RBE at multiple positions relative to the spread-out Bragg peak (SOBP) have been predominantly performed using passive scattering methods, and limited data are available for spot-scanning beams. Thus, to investigate the RBE of spot-scanning beams, Chinese hamster fibroblast V79 cells were irradiated using the beam line at the Hokkaido University Hospital Proton Therapy Center. Cells were placed at six different depths, including the entrance of the proton beam and the proximal and distal part of the SOBP. Surviving cell fractions were analyzed using colony formation assay, and cell survival curves were obtained by the curve fitted using a linear–quadratic model. RBE10 and RBE37 were 1.15 and 1.21 at the center of the SOBP, respectively. In contrast, the distal region showed higher RBE values (1.50 for RBE10 and 1.85 for RBE37). These results are in line with those of previous studies conducted using passive scattering proton beams. Taken together, these data strongly suggest that variations in RBE should be considered during treatment planning for spot-scanning beams as well as for passive scattering proton beams. KE YWOR DS: relative biological effectiveness, spot scanning, radiotherapy, proton therapy I N T RO D U C T I O N Proton therapy allows the delivery of high-radiation doses to tumors without damaging the surrounding healthy organs [1], and an increasing number of patients have been treated using this therapy [2]. Although most patients are treated using passive scattering methods, modern proton therapy centers often adopt pencil beam scanning because it offers more flexible and conformal dose distributions compared with passive scattering methods, and minimizes overall exposure. Hokkaido University Hospital started spot-scanning proton therapy (SSPT), a type of pencil beam scanning proton therapy, in March 2014. During SSPT, several thousand small-sized, nearly mono-energetic proton beams are used to administer a planned dose to the target volume. The depth position of the spots are adjusted by changing the acceleration energy, whereas their lateral positions are moved using a pair of scanning magnets [3, 4]. This technique does not require collimators or compensators, and can thus reduce neutron contamination from interactions of protons with these materials. Relative biological effectiveness (RBE) is defined as the ratio of the absorbed dose of a reference radiation to that of a test radiation that produces the same biological effect, and RBE is an essential consideration during treatment planning for proton therapy. Treatment planning in proton therapy is generally based on a constant RBE of 1.1, according to Report 78 of the International Commission on Radiation Units and Measurements (ICRU78). In line with ICRU78, determinations of RBE have been performed widely, using passive scattering methods [5, 6], and show RBE values ranging from 1.1 to © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/bync/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact • 307 308 • K. Maeda et al. 1.2 at the beginning of the flat top portion of the spread-out Bragg peak (SOBP). However, recent studies warrant cautious use of this RBE value for treatment planning because it may lead to lower estimates of biological doses in organs at risk (OARs) that are located close to the distal fall-off of SOBP [7–9]. Many studies have revealed that RBE tends to increase with increasing linear energy transfer (LET) towards the distal region of the SOBP [10, 11], and Paganetti reviewed this RBE characteristic of proton beam comprehensively [12]. However, it remains unclear whether these RBE values for passive scattering methods are relevant to spot-scanning systems. This is because, first, the proton energy spectra, the fluence, and the LET of SSPT proton beams may differ from those of conventional passive scattering systems, resulting in differences in the RBE [13]. Second, smaller neutron contamination from SSPT may contribute to differences in RBE between these systems [14]. While Gueulette et al. determined RBE for SSPT at three depth positions according to the intestinal crypt regeneration in mice and showed RBE values of 1.11 for the initial plateau, 1.16 for the center, and 1.21 for the distal region of the SOBP [15], RBE values could not be estimated at positions with high-dose gradients, such as the distal fall-off of the SOBP, reflecting poor estimates of precise positions with in vivo experiments. The goal of this study is to derive an RBE suitable for SSPT, including the value at the distal fall-off of the SOBP. We performed a clonogenic survival assay using a V79 cell line and estimated the RBE values at six different depths (a 5 mm depth point from the primary plane, three points in the SOBP plateau and two points in the distal fall-off ). Proton beams were generated using a ProBeat RT (Hitachi, Tokyo, Japan), with an SOBP width of 6 cm, an energy range of 156.7–182.8 MeV, spot spacing of 5 mm and a field size of 10 × 10 cm. The isocenter plane was matched with the center of the SOBP, and dose flatness of the SOBP was ±2.5% compared with the center of the SOBP in the depth direction. The average dose rate was 2.68 Gy/min. As reference photon beams, 6 MV X-rays were generated using a linear accelerator (Mitsubishi Elec (...truncated)