ESTRO 36 Abstract Book

S543 ESTRO 36 2017 _______________________________________________________________________________________________

Purpose or Objective External beam radiotherapy (EBRT) treats gross tumors and local microscopic diseases. Radionuclide therapy by isotopes can control tumors systemically. Rhenium 188 ( 188 Re)-liposome, a nanoparticle undergoing clinical trials, emits gamma rays for imaging validation and beta rays for therapy with biodistribution profiles preferential to tumors. We designed a unique combinatory treatment and examined its effects on lung metastasis from esophageal cancer, a malignancy with poor prognosis. Material and Methods Human esophageal cancer BE-3 cells with luciferase gene for optical imaging were injected into tail vein of nude mice to induce lung metastasis. The radiochemical purity of 188 Re-liposome exceeded 95%. Molecular imaging by NanoSPECT/CT (NanoSPECT/CT PLUS, Mediso, Alsotorokvesz, Budapest, Hungary) showed that lung metastatic lesion could uptake the 188 Re-liposome. For biodistribution, the radioactivity of 188 Re-liposome was detected by Auto-Gamma counter (Packard Cobra II, Canberra, Germany), and the uptake of 188 Re-liposome in each organ was expressed as the percentage of injected dose per gram of tissue (% ID/g). Low-dose whole lung EBRT with 3 consecutive daily fractions of 1 Gy was delivered by linear accelerator with 6-MV photon (Clinac iX, Varian Medical Systems, USA) followed by intravenous 188 Re-liposome (250 µCi) administration 2-h after last teletherapy. Flow cytometry was used to estimate the amount of myeloid derived suppressor cells and macrophages. Results The combination of EBRT and 188 Re-liposome inhibited tumor burden of lung metastasis faster and better than each treatment alone (Figure 1 and 2). Combination treatment did no cause additive adverse effects on white blood cell counts, body weight, or liver and renal functions. EBRT significantly reduced the uptake of 188 Re- liposome in lung, kidney, bone marrow and blood. In spleen, 188 Re-liposome administration declined the amount of myeloid derived suppressor cells and increased the amount of M1 and M2 macrophages.

Figure 2. The therapeutic efficacy of 188 Re-liposome combined with EBRT on lung metastasis from esophageal cancer. Low-dose whole lung EBRT with 3 consecutive daily fractions of 1 Gy was delivered followed by intravenous 188 Re-liposome (250 µCi) administration in combination group. N=3 for each group. Conclusion The combination of low-dose whole lung EBRT with systemic 188 Re-liposome administration might be a potential treatment modality for lung metastasis from esophageal cancer. Modulation of tumor microenvironment by the combination treatment is warranted in translational research. This proof-of-concept study needs to be validated by clinical investigation. PO-0993 Influence of radiotherapy on differentiation, maturation and functionality of dendritic cells L. König 1 , A. Gardyan 2 , J. Hörner-Rieber 1 , P. Huber 2 , K. Herfarth 1 , S. Rieken 1 Purpose or Objective Primary purpose of radiotherapy (RT) is elimination of cancer cells by inducing DNA-damage that either causes induction of tumor cell death or inhibition of the proliferating capacity of these cells. In addition, considerable evidence emerges that antineoplastic effects extend beyond these mechanisms. These secondary effects can contribute to anti-tumor responses in a local but also systemic manner via activation of the immune system: The role of dendritic cells (DCs) is well described to be essential for priming effective radiation-induced adaptive immunity. Through increased release of tumor- associated antigens (TAA) after RT, DCs are recruited and cross-presentation of TAA leads to activation of B- and T- lymphocytes, therefore playing a pivotal role in adaptive immune response and immunogenic cell death. However, there are still many hypotheses regarding the influence of RT on activation of the immune system. The aim of our experiments is to further characterize the impact of different radiation types and dosages on differentiation and functionality of DCs. Material and Methods Human CD14-positive monocytes were isolated from peripheral blood mononuclear cell samples of six individuals. In the presence of appropriate cytokine stimulation with Interleukin-4 (IL-4) and granulocyte macrophage colony-stimulating factor (GM-CSF) monocytes were induced into immature DCs (iDCs) and later mature DCs (mDCs). Monocytes were irradiated with different photon radiation doses (1x15Gy, 5x2Gy, 1x0.5Gy) on day 0. Maturation to mDCs was induced on day 7 by adding tumor necrosis factor alpha (TNFα) to the culture medium. Differentiation and maturation of DCs was assessed on day 2, 9 and 12 by staining of the cell 1 University Hospital Heidelberg, Department of Radiation Oncology, Heidelberg, Germany 2 German Cancer Research Center- Heidelberg, Clinical Cooperation Unit Molecular Radiooncology-, Heidelberg, Germany

Figure 1. The therapeutic efficacy of 188 Re-liposome combined with EBRT on lung metastasis from esophageal cancer. The representative optical images show lung metastatic burden detected by D-luciferin assay.