Cell biological basis for combination radiotherapy using heavy-ion beams and high-energy X-rays q Yusuke Demizu a, * , Kazufumi Kagawa b , Yasuo Ejima a , Hideki Nishimura a , Ryohei Sasaki a , Toshinori Soejima a , Toshihiro Yanou b , Masakazu Shimizu b , Yoshiya Furusawa c , Yoshio Hishikawa b , Kazuro Sugimura a a Division of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan b Department of Radiology, Hyogo Ion Beam Medical Center, Hyogo, Japan c Heavy-ion Radiobiology Research Group, National Institute of Radiological Sciences, Chiba, Japan Received 3 November 2003; received in revised form 23 February 2004; accepted 4 March 2004 Abstract We investigated the biological effect of combining carbon-beam and X-ray in vitro. The results showed that when we employed Gray equivalent as the indication of therapeutic dose, the effects could be explained with simple additive way in the treatment plan. This fact provides important information about the combined therapy of carbon-beam and X-ray. q 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Carbon-beam; X-ray; Combination; Linear energy transfer; Irradiation; Radiosensitivity 1. Introduction Carbon-beam therapy is a promising cancer treatment with superb biological effects and excellent dose distri- bution. Carbon-beam is a high-linear energy transfer (LET) radiation characterized by a higher relative biological effectiveness (RBE) than low-LET radiation and it pene- trates the body losing its energy and forms a Bragg peak with the maximum ionization when it stops. By using these precious characteristics of carbon-beam, favorable anti- tumor effects can be achieved with few effects on critical normal organs. Efficacy of carbon-beam therapy has been shown in the clinical trials at the National Institute of Radiological Sciences (NIRS), Japan since 1994 [7,9,10] and at the Heavy Ion Research Center (GSI), Germany since 1997 [12–16]. Experience of NIRS for more than 1600 cases helps to identify that the carbon-beam therapy achieves excellent tumor controllability even for radioresistant tumors, and that the carbon-beam therapy causes minimal complications. These advantages have been shown in bone and soft tissue sarcomas, stage I non-small cell lung cancers, and various other types of cancers [7,9]. A combined therapy of carbon-beam and photon may be a more useful strategy with photon for clinical target volume and with carbon-beam for gross tumor volume. Actually, this strategy has been tried for patients with locally advanced adenoid cystic carcinomas or skull base tumors at GSI [12,15,16]. Their study included comparatively small number of cases and the results were still preliminary, but the strategy was promising. Although there are a number of papers reporting cytotoxicity by combination of different LET radiations [1 – 3,5,8,11,17 – 19], as far as we searched, this is the first study to investigate the biological effect of combining carbon-beam and X-ray experimentally. The purpose of this study is to clarify whether these different LET radiations can act as a simple additive way when the doses are expressed with Gray equivalent (GyE) unit and to assess that this combination can be a promising strategy. 0167-8140/$ - see front matter q 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.radonc.2004.03.008 Radiotherapy and Oncology 71 (2004) 207–211 www.elsevier.com/locate/radonline q This study was presented at the 12th ECCO (the European Cancer Conference) meeting, Copenhagen, Denmark, September 21–25, 2003. * Corresponding author.