ESTRO 38 Abstract book

S1196 ESTRO 38

Tamaki 1 , Y. Morokoshi 5 , S. Hasegawa 5 , H. Ohgaki 6 , H. Yokoo 7 , T. Nakano 3 1 Fukushima Medical University School of Medicine, Department of Radiation Oncology, Fukushima-City, Japan; 2 National Institute of Radiological Sciences- National Institutes for Quantum and Radiological Science and Technology, Hospital, Chiba, Japan; 3 Gunma University Graduate School of Medicine, Department of Radiation Oncology, Maebashi, Japan; 4 Fukushima Medical University School of Medicine, Department of Gastrointestinal Tract Surgery, Fukushima-City, Japan ; 5 National Institute of Radiological Sciences- National Institutes for Quantum and Radiological Science and Technology, Radiation and cancer biology team, Chiba, Japan ; 6 International Agency for Research on Cancer, Section of Molecular Pathology, Lyon, France; 7 Gunma University Graduate School of Medicine, Department of Human Pathology, Maebashi, Japan Purpose or Objective Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, accounting for approximately 70% of high-grade gliomas. The current standard of care is based on maximal safe surgical resection with concurrent chemoradiotherapy using temozolomide followed by 6 months of maintenance chemotherapy, resulting in median survival time of approximately just 15 months. Microglia are immune effector cells that play an important role in processes such as phagocytosis and antigen presentation in the CNS. The aim of this study was to investigate the efficacy of combination therapy with intravenously injected microglia (MI) and radiation therapy (RT) for malignant glioma in rats. Material and Methods Transgenic rats expressing v-erbB and spontaneously developing malignant glioma were used. The rats were divided into 4 groups: control (n = 19), RT alone (n = 10), MI alone (n = 9), and combination MI and RT (MI + RT) (n = 10). Cranial x-ray irradiation (8 Gy per fraction; once per week) was performed at 50 and 51 weeks of age. Cultured rat microglial cells (5 × 10 6 cells/rat) were intravenously injected via the tail vein within 30 minutes after RT. Results No evidence of side effects, including thrombosis or graft- versus-host disease, was noted. Rats treated with RT alone, MI alone, MI + RT, and control survived 60.9, 56.3, 66.0, and 56.1 weeks, respectively. The survival period of MI + RT was significantly longer than that of control (P = .014), MI alone (P = .027), and RT alone (P = .049). Immunohistochemical analysis showed a significantly higher number of tumor-infiltrated MI in the RT alone (P = .041) and MI + RT groups (P = .014) compared with the control. Significantly more CD8-positive lymphocytes were observed in the MI + RT group (P = .049) compared with the control. A positive correlation was found between the number of MI and CD8-positive lymphocytes (R 2 = 0.556). A positive correlation was also found between CD8-positive lymphocytes and survival periods (R 2 = 0.460).

Conclusion MI + RT increased infiltrated MI and CD8-positive T cells and prolonged survival in transgenic rats that spontaneously developed malignant glioma. Combined immunocellular therapy and RT may provide a novel treatment strategy for malignant glioma. EP-2164 Pilot Study: Systemic response after lung SBRT analyzing immune Cells phenotyping A. Navarro-Martin 1 , I. Linares 2 , M.A. Berenguer 2 , R. Cañas 3 , F. Guedea 4 1 Instituto Catalan De Oncologia, Radiation Oncology Department, Hospitalet De Llobregat, Spain; 2 Instituto Catalan de Oncologia, Radiation Oncology Department, Barcelona, Spain; 3 ONCOBELL Program/IDIBELL, Radiation Oncology Department Barcelona, Barcelona, Spain; 4 Instituto Catalan de Oncologia, Radiation Oncology Department, Barcelona, Spain Purpose or Objective To investigate changes of immune-phenotyping values in patients treated with Stereotactic Body Radiation Therapy (SBRT) over the lung in order to evaluate the immune response after radiation therapy. Material and Methods From November 2016 to May 2018, 7 patients (p) with 7 lung lesions were enrolled in a translational sub-study. All of them underwent SBRT treatment. Peripheral blood samples prior to the treatment for each patient (1month, 3 months and 6 months) were collected and analyzed. Peripheral mononuclear cells (PBMCs) were isolated from a heparinized venous blood sample by density gradient centrifugation. After centrifugation, PBMCs were collected from the plasma–Ficoll interphase and used for flow cytometry. Three panels were used: - Lymphocyte Phenotyping DuracloneTM, Beckman Coulter: CD16 Ab , CD56 Ab, CD19 Ab, CD14 Ab, CD4 Ab, CD8 Ab, CD3 Ab, CD45 Ab - Regulatory T cells DuracloneTM, BeckmanCoulter: CD45RA Ab, CD25 Ab, CD39 Ab, CD4 Ab, Intracellular FOXP3 Ab, CD3 Ab, Helios Ab, CD45 Ab - Myeloid Derived Supressor Cells (MDSC) DuracloneTM, BeckmanCoulter: CD45, HLA-DR, CD14, CD33, CD11b. Cell surface and intracellular staining were performed according to the manufacturer’s protocols. Cell phenotypes were evaluated using the FACS Navios system (BeckmanCoulter). Results Median age was 73r (65-80). 5 Males and 2 females. Primary lung tumor 5 cases, 1 CRC and 1 breast primary. None were a candidate to undergo surgery after evaluation in a multidisciplinary tumor board. Locations were: 2p right upper lobe, 3p right inferior lobe and 2p right medium lobe. Following the clinical protocol doses delivered were 60Gy (7.5Gy x 8fr) in 3p y 50Gy (12.5Gy x 4 fr) in 4 p. Mean follow up of 16 months r(2- 20), 1p incomplete response, 2p in partial response and 4 in stable .