Arenz, A.

Bischoff, B.

Engenhart-Cabillic, R.

Fournier, C.

Hänze, J.

Rose, F.

Scheel, S.

Scholz, M.

Subtil, F.

Taucher-Scholz, G.

GSI Repository

Increased RBE of carbon ions in tumor growth inhibition using an in vivo lung adenocarcinoma model F. Subtil1, S. Scheel1, B. Bischoff1, F. Rose1, R. Engenhart-Cabillic1, A. Arenz1, M. Scholz2, C. Fournier2, G. Taucher-Scholz2, and J. Hänze3 1Dept. of Radiotherapy and Radiooncology, University of Marburg, Germany; 2GSI, Darmstadt, Germany; 3Department of Urology and Pediatric Urology, University of Marburg, Germany   Carbon ion irradiation is an emerging therapy option for various tumor entities, including lung cancer [1]. This irradiation quality with a high linear energy transfer (LET) induces more complex and irreparable clustered DNA damage. Compared with low-LET photons and pro-tons, carbon ions have a higher relative biological effec-tiveness (RBE) with less oxygen-dependent radiosensitiv-ity [2]. Based on the colony formation assay we previ-ously revealed a RBE of 3 for 10% cell survival in A549 cells [3].  Here we compared the effect of different irradiation quali-ties (carbon ions (12C) and photon irradiations) on the tumor growth using a mouse tumor model of the human non small lung adenocarcinoma cell line (A549). Adult BALBc nu/nu mice were maintained under patho-gen-free conditions and handled in accordance with the recommendations for animal experimentation of Euro-pean Community. After subcutaneous tumor initiation and a starting tumor volume of 200 mm³, local tumor irradia-tion with biologically equivalent doses of 12C (LET 50-70 keV/µm, energy 122.36-183.74 MeV/u on target, 40 mm spread out bragg peak [SOBP]) and photons (6 MV-X) were performed. The tumor volumes were measured 3 times per week until reaching a target tumor volume of 400 mm³ or after an observation time of 40 days. The tumor volume (TV) was calculated by the formula: TV [mm ³] = (L x W²)/2; where L is the longest dimen-sion of the tumor [mm], and W is the shortest dimension of the tumor [mm].  We found a tumor volume doubling time of 37.8 ± 1.6 days in the carbon ion irradiated group compared to 18.3 ± 1.2 days in the photon irradiated group and 11.9 ± 1.0 days in the unirradiated control group (Figure 1). Thus, the RBE of in vivo tumor growth is above 3 and clearly greater than for cell survival measurements, providing further support for a clinical application. However, it should be mentioned that 3 of 6 carbon ion irradiated tu-mors did not reach the target tumor volume of 400 mm³ within the observation time of 40 days.  In further experiments, we will focus on the analysis of the effects of carbon ion irradiation on the tumor micro-environment. These experiments will consider effects on tumor cells, tumor vasculature as well as distribution of immune cells.    Figure 1: Growth curves of A549 tumors after irradiation with carbon ions (12C SOBP) or photons. All data repre-sent the means ± S.E.M.  References [1] Miyamoto, T., Baba, M., Sugane, T., Nakajima, M., Yashiro, T., Kagei, K., Hirasawa, N., Sugawara, T., Yamamoto, N., Koto, M., Ezawa, H., Kadono, K., Tsujii, H., Mizoe, J. E., Yoshikawa, K., Kandatsu, S., and Fujisawa, T. (2007) Carbon ion radiotherapy for stage I non-small cell lung cancer using a regi-men of four fractions during 1 week. J Thorac Oncol 2, 916-926 [2] Weber, U., and Kraft, G. (2009) Comparison of car-bon ions versus protons. Cancer J 15, 325-332  [3] Kamlah, F., Hänze, J., Arenz, A., Seay, U., Hasan, D., Juricko, J., Bischoff, B., Gottschald, O. R., Fournier, C., Taucher-Scholz, G., Scholz, M., See-ger, W., Engenhart-Cabillic, R., and Rose, F. (2011) Comparison of the effects of carbon ion and photon irradiation on the angiogenic response in human lung adenocarcinoma cells. Int J Radiat Oncol Biol Phys 80, 1541-1549 GSI SCIENTIFIC REPORT 2012 HEALTH-23447

Increased RBE of carbon ions in tumor growth inhibition using an in vivo lung adenocarcinoma model

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Increased RBE of carbon ions in tumor growth inhibition using an in vivo lung adenocarcinoma model

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