ESTRO 2020 Abstract Book

S268 ESTRO 2020

for treatment of multiple metastases show single isocentre plans may have reduced accuracy in the treatment of off- axis target volumes.

growing tumor. 12 C-ion treated tumors showed earlier vascular changes in perfusion/permeability indicated by an increase in K trans and v e at day 3 while the response of photon treated tumors was prolonged until day 21. The vascular fraction v p exhibited reasonable values but no significant temporal changes. Histological results revealed that photon RT led to more heterogeneous tissue structures than 12 C-ion irradiation which was also reflected in the broader distribution of v e values for photon treated tumors after 21 days. Quantitative analysis showed lower vascular density and lower rates of proliferative active cells in 12 C-ion treated tumors than in photon treated tumors 21 days after RT. No dose dependency was found neither in the DCE-MRI data nor in the quantitative histology results. Conclusion 12 C-ions evoked an early and strong vascular treatment response compared to photons. As no dose-dependency was found in the results, the initial vascular response can only have a minor effect on local tumor control. 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

Poster Highlights: Poster highlights 15: Particles and microbeams

PH-0476 Impact of single dose photon or 12C-ion irradiation on rat prostate tumors assessed by DCE-MRI A. BENDINGER 1,2 , L. Seyler 3 , M. Saager 1,4 , C. Debus 5,6 , P. Peschke 1,4 , D. Komljenovic 2 , J. Debus 4,7,8 , J. Peter 2 , R. Floca 4,9 , C. Karger 1,4 , C. Glowa 1,4,8 1 German Cancer Research Center, Medical Physics in Radiation Oncology, Heidelberg, Germany ; 2 German Cancer Research Center, Medical Physics in Radiology, Heidelberg, Germany ; 3 University Hospital Erlangen- Friedrich-Alexander-Universität Erlangen-Nürnberg, Radiology, Erlangen, Germany ; 4 Heidelberg Institute for Radiation Oncology HIRO and National Center for Radiation Research in Oncology NCRO, HIRO and NCRO, Heidelberg, Germany ; 5 German Aerospace Center DLR, Department of High-Performance Computing- Simulation and Software Technology, Köln, Germany ; 6 National Center for Tumor Diseases NCT- German Cancer Research Center DKFZ, Department of Translational Radiation Oncology, Heidelberg, Germany ; 7 German Cancer Research Center, Clinical Cooperation Unit Radiation Therapy, Heidelberg, Germany ; 8 University Hospital Heidelberg, Department of Radiation Oncology and Radiotherapy, Heidelberg, Germany ; 9 German Cancer Research Center, Department of Medical Image Computing, Heidelberg, Germany Purpose or Objective 12 C-ion radiotherapy (RT) holds great potential for the treatment of radioresistant tumors, however its differential effects on tumor vasculature compared to photons are still not fully understood. We used dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and pharmacokinetic modelling to quantify vascular changes after 12 C-ion and photon irradiation at therapeutic and subtherapeutic doses of the anaplastic experimental prostate tumor R3327-AT1. Material and Methods The anaplastic prostate tumor subline Dunning R3327-AT1 was transplanted subcutaneously on both thighs of 12 male Copenhagen rats. When tumors reached diameters of 9 mm, the rats’ right tumor was irradiated with single doses of either photons (6 MeV) or 12 C-ions (20 mm spread-out Bragg-peak), while the tumor on the left leg served as an untreated control. Tumors were irradiated in four dose groups: with curative doses of 37 Gy 12 C-ions and 85 Gy photons leading to local tumor control and with sub- curative doses of 16 Gy 12 C-ions and 37 Gy photons not leading to local tumor control. DCE-MRI was performed one day prior to and 3, 7, 14, and 21 days after irradiation. DCE-MRI data was analyzed voxel-wise by pharmacokinetic modelling using the extended Tofts model (ETM). The image based arterial input function was extracted individually for each animal from the left ventricle. After the last imaging time point, tumors were dissected and histologically analyzed to assess quantitative information on the tumor morphology (H&E), vasculature (CD31), and proliferation (bromodeoxyuridine (BrdU)). Results Non-irradiated control tumors showed a decrease in all ETM parameters ( K trans , v e , v p ) over the observation period due to the progressive decline in perfusion in this rapidly