ESTRO 2020 Abstract Book

S269 ESTRO 2020

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 were exposed to 12C. Material and Methods

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 PH-0479 The influence of the tissue specific parameter α/β on the RBE of protons E. Mara 1 , S. Khachonkham 2 , M. Clausen 3 , P. Kuess 3 , C. Pessy 3 , W. Dörr 3 , D. Georg 3 , S. Gruber 3 1 University of Applied Science, Biomedical Science, Wiener Neustadt, Austria ; 2 Faculty of Medicine Ramathibodi Hospital- Mahidol University, Department of Diagnostic and Therapeutic Radiology, Bangkok, Thailand ; 3 Department of Radiotherapy, Department of Radiation Oncology, Vienna, Austria Purpose or Objective Particle radiotherapy is used to treat an increasing number of patients worldwide. Clinical proton facilities use a generic RBE of 1.1, i.e. protons are assumed being 10 % more effective than photons. Recent research increasingly challenged the concept of a static RBE in proton therapy. In this study, the RBE of scanned protons was studied in- vitro for head-and-neck squamous cell carcinoma-, prostate carcinoma- and melanoma cells as well as normal keratinocytes. Furthermore, RBE correlations with the LET (linear energy transfer) and the intrinsic radiosensitivity factor α/β were evaluated. Material and Methods Cells were irradiated at different positions within a 8 cm long SOPB (proximal, middle and distal position) using two different target depths (Figure 1). Both, target A, covered by lower energies (66 – 136 MeV) and target B, covered by higher energies (137 – 180 MeV) were irradiated with physical doses of 0.5, 1, 2, 4 and 6 Gy. The treatment planning system (TPS) RayStation (V5.99, Raysearch Laboratories, Sweden) was used. Corresponding dose averaged LET (LET d ) was derived using the Monte Carlo algorithm provided in the TPS. As reference irradiation, 200 kV X-rays were used. A negative control was conduct and handled as the irradiated samples only without the irradiation treatment. The LQ model was applied to the in vitro data.