ESTRO 2020 Abstract book

S289 ESTRO 2020

PH-0477 Effectiveness of fractionated carbon ion treatments in three rat prostate tumors C. Glowa 1,2,3 , P. Peschke 2,3 , S. Brons 2,4 , J. Debus 1,2,5 , C.P. Karger 2,3 1 University Hospital Heidelberg, Department of Radiation Oncology and Radiotherapy, Heidelberg, Germany ; 2 Heidelberg Institute for Radiation Oncology HIRO, National Center for Radiation Research in Oncology NCRO, Heidelberg, Germany ; 3 German Cancer Research Center, Department of Medical Physics in Radiation Oncology, Heidelberg, Germany ; 4 Heidelberg Ion Beam Therapy Center HIT, Heidelberg Institute for Radiation Oncology HIRO- National Center for Radiation Research in Oncology NCRO, Heidelberg, Germany ; 5 German Cancer Research Center DKFZ, Clinical Cooperation Unit Radiation Therapy, Heidelberg, Germany Purpose or Objective Carbon ions ( 12 C-ions) show an increased relative biological effectiveness (RBE) relative to photons. To compare the impact of intra- and intertumor heterogeneity on the RBE, dose-response curves for fractionated photon and 12 C-ion treatments were determined for three sublines of a syngeneic rat prostate adenocarcinoma. Material and Methods Tumor fragments from three sublines (AT1, HI and H) of the Dunning prostate tumor R3327 were transplanted subcutaneously into the right thigh of male Copenhagen rats. Tumors were treated 6 times on consecutive days with increasing doses of either 12 C-ions or 6 MeV photons. Primary endpoint was local tumor control within 300 days. For the H-tumor, histological tumor control, defined as absence of proliferation (BrdU-injection) in the remaining fibrotic nodules (Hematoxylin/Eosin staining) was used as secondary endpoint. RBE-values were calculated by the ratio of TCD 50 -values (dose to achieve 50% tumor control probability) for photons and 12 C-ions, respectively. Results For all tumors an increased effectiveness of 12 C-ions was observed. The RBE for local tumor control increased from minimal 1.8 for single fraction irradiation to 2.6 for 6 fraction irradiation and was only weakly dependent on the tumor subline. For 12 C-ion irradiations the variation of TCD 50 -values between tumor sublines (TCD 50 : 35.8 - 44.4 Gy) was significantly smaller than after photons (TCD 50 : 91.3 - 117.3 Gy). Additionally 12 C-ion dose-response curves were much steeper compared to photons indicating a smaller intra-tumor heterogeneity for 12 C-ions. The biggest fractionation effect was found for photon treated H- tumors resulting in the smallest α/β – ratio. Conclusion The study confirms the increased relative biological effectiveness of fractionated 12 C-ions in tumors, which is comparable for all three tumor sublines. After single dose irradiation there was a clear RBE-dependence on tumor differentiation, which diminished at six fractions. 12 C-ions reduce the radiation response heterogeneity between the three tumor sublines as well as within each subline relative to photons, independently of fractionation. The dose- dependence of the RBE varies between tumors of different histology, which has to be considered, when changing fractionation schemes in patients. PH-0478 HPV pos HNSCC cells show strong radiosensitivity after photon but not after carbon ion irradiation S. Lerch 1 , S. Berthold 1 , F. Ziemann 1 , K. Dreffke 1 , F. Subtil 1 , A. Jensen 1 , R. Engenhart-Cabillic 1 , E. Dikomey 1,2 , A. Wittig 3 , F. Eberle 1 , U. Schötz 1

1 Philipps-University Marburg- University Hospital Gießen and Marburg, Department of Radiotherapy and Radiooncology, Marburg, Germany ; 2 University Medical Center Hamburg Eppendorf, Laboratory for Radiobiology & Experimental Radiooncology, Hamburg, Germany ; 3 Friedrich-Schiller-University, Department of Radiation Oncology, Jena, Germany Purpose or Objective Head and neck squamous cell carcinoma (HNSCC) comprises two tumor entities according to pathogenesis. Beneath abuse of alcohol and tobacco (HPV neg.), another risk factor is infection with HPV of high-risk genotypes (HPV pos.). HPV-status is a prognostic factor, since HPV pos. tumors exhibit a very good treatment response. Preclinical studies revealed a higher radiosensitivity due to inefficient DNA repair mechanisms, especially homologous recombination, in HPV pos. cell lines. For HPV neg., tumor control is feasible only for 35%, despite application of maximum irradiation doses. Carbon ion (12C) irradiation could be a promising alternative treatment option. It is unknown, whether HPV pos. and HPV neg. tumors show the same variations in radiosensitivity after 12C. The following preclinical study tested under both 2D and 3D culture conditions whether such a difference was also apparent when HNSCC cells Five HPV pos. (UD-SCC-2, UM-SCC-47, UM-SCC-104, 93VU147T, UPCI:SCC-154) and five HPV neg. (FaDu, UM- SCC-3, UM-SCC-6, UM-SCC-11b, UTSCC-33) HNSCC cell lines were exposed either to photon or 12C irradiation using both 2D and 3D cell culture conditions. Cell survival was determined by colony formation assay using isoeffective doses. DSBs were evaluated by immunofluorescent co- staining of γH2AX/53BP1 foci. Results The great difference in radiosensitivity seen between HPV pos. and HPV neg. HNSCC cells when irradiated with photons under 2D cell culture conditions was strongly reduced when exposed under 3D conditions. 12C irradiation of 2D cell cultures strongly increases the cellular radiosensitivity of both, HPV pos. (UPCI:SCC-154) and HPV neg. (UM-SCC-6) cell lines. However, increase was more pronounced for HPV neg. cells as for HPV pos. cells with an RBE of either 2.81 or 2.14. As a consequence, after exposure to 3Gy 12C there was almost no difference in cell survival between HPV pos. and neg. HNSCC cell lines (HPV neg., SF6=0.045±0.018; HPV pos., SF6=0.031±0.012; P=0.529). In line with this, no difference in DSB repair efficiency was observed for these two entities after irradiation with 12C, in contrast to a significant difference measured after photon irradiation. Conclusion The preclinical study shows for the first time that irradiation response of HNSCC cell lines differs strongly for photons and 12C. While HPV pos. cells are significantly more radiosensitive to photons than HPV neg. cells, almost no difference was seen after 12C irradiation. This pronounced difference between photon and 12C irradiation needs to be considered when planning new protocols for the treatment of HPV pos. tumors with 12C. Acknowledgement: The project was funded by Kempkes- Stiftung and MIT-Forschung, Philipps-University Marburg were exposed to 12C. Material and Methods