ESTRO 38 Abstract book

S597 ESTRO 38

PO-1074 Radiotherapy and immuno-check point inhibitors for brain metastases. A mono-institutional analysis. C. Di Carlo 1 , F. Patani 1 , D. Fasciolo 1 , S. Di Biase 1 , C. Rosa 1 , A. Allajbej 1 , L. Gasparrini 1 , P. Di Marino 2 , M. De Tursi 2 , L. Caravatta 1 , M. Trignani 1 , D. Genovesi 1 1 Department of Rdiation Oncology- SS Annunziata Hospital, G. D'Annunzio University, Chieti, Italy ; 2 Medical Oncology Unit- SS Annunziata Hospital- Chieti, Department of Medical- Oral and Biotechnological Sciences- University G. D'Annunzio, Chieti-Pescara, Italy Purpose or Objective As suggested by the literature, immunotherapy (IT) combined with radiotherapy (RT) could be a promising strategy to enhance treatment efficacy, but the safety and timing of their association remains unclear. The aim of our analysis is to assess the safety of IT concomitant or close to RT in patients with brain metastases. Material and Methods From November 2016 to September 2018, 13 patients with brain metastases from renal cells carcinoma (2 patients), non-small cell lung cancer (6 patients) and melanoma (5 patients) were treated in our Institute and retrospectively analyzed. The radiation treatment was defined concomitant when it was performed after the beginning of IT course. Acute and late toxicities were evaluated according to CTCAE v 4.0 scale. After RT, patients were revaluated with total body CT scan. MRI was also performed in case of FSRT after 3 months from RT. Results Median age was 71 years (range: 54-78 years). All patients reported a performance status ≥ 70% according to Karnofsky scale, except one with 60%. Median follow up was 12 weeks (range: 2-60 weeks). Patients received IT with anti-PDL1 (12 patients) or anti-CTLA4 (1 patients) that was concomitant in 10 cases, while 2 patients started immunotherapy within two months from RT. Whole brain radiotherapy (WBRT) with a total dose of 20 Gy (4 Gy/fraction) was administered in 11 patients, while the remaining 2 patients underwent fractionated stereotactic radiotherapy (FSRT) with a total dose of 24 Gy (8Gy/ fraction). Median number of IT cycles was 9 and it is still ongoing in 3 cases. All patients received concomitant corticosteroids therapy (dexamethasone, at ranging dose between 2 mg/die and 12 mg/die). Combination IT-RT was well tolerated without unexpected toxicities. The 92% of patients had G0 acute toxicities according to CTCAE scale. Only in one case, radiotherapy was interrupted for poor clinical condition. Late toxicities were collected in 7/13 patients and it was G0 in the 70%. The remaining 30% of patients, showed G1-G2 neurological toxicity. No case of radionecrosis was detected. At the time of analysis, 5 patients were died for disease complications, non-related to the treatment. Conclusion From our data, IT resulted to be safe in patients treated with concomitant RT for brain metastases without G3-G4 acute toxicities and radionecrosis. Longer follow-up and a higher number of patients are necessary to confirm these data.

Purpose or Objective We investigated the effects of Chromobox 4 (CBX4) in esophageal squamous cell carcinoma (ESCC) and its role in radiosensivity. Material and Methods We used quantitative real-time polymerase chain reaction and immunohistochemistry analyses to compare expression of CBX4 between radioresistant and radiosensitive ESCC samples. Lentivirus was used to knockdown of CBX4 gene and stable transmitted cell line of KYSE150 and TE13 were made. In vitro cell counting kit 8 and clone formation assay were used to detect cell viability and proliferation. Radioresponse was primary examined by clone formation assay after exposure of 0, 2, 4, 6, 8 Gy X-ray by a medical accelerator of different stable cell lines. Then autophagy as well as apoptosis, cell- cycle arrest, and γ-H2AX expression were examined in 0 Gy and 8 Gy by flow cytometer and immunoflourence. Gene-chips and western blot were used to investigate molecular mechanism. In vivo experiments of xenografts were used to confirm the results. Results Levels of eEF2K were increased in redioresistant ESCC samples compared with radiorensitive tissues, as well as ESCC cell lines. Increased levels of CBX4 were associated with ESCC survival times of patients (P<0.05). CBX4 promotes ESCC proliferation and tumorgeneity in vitro and in vivo. An improved radioresponse was detected in CBX4 knockdown cells. Affymetrix GeneChip was used in CBX4 knockdown TE13 and control cells in normal conditions and 8 Gy of irradiation and autophagy pathways were detected by bioinformatic analysis. Improved protein expression of Atg5, mTOR, LC3, and TP53 were confirmed by western blot. In xengraft radiosensivity experiments, improved radioresponse with a reduction of tumor doubling time was observed. Immunohistochemistry and immunofluorescence of tumor tissue confirmed the molecular mechanism of autophagy pathway. Conclusion CBX4 is overexpressed in ESCC and associated with progression and shorter survival times of patients. Decreased expression of CBX4 correlated with a reduction of malignancy in biological behavior and an improvement of radioresistance in ESCC, which may be mediated by autophagy signaling pathway. Targeting CBX4 may be a potential therapeutic approach of ESCC in the future. PO-1076 Concomitant association of T-DM1 and radiation: An in vitro study on HER2 breast cancer cells M. Fabien 1 , Y. Kirova 1 , P. Verrelle 1 , M. Teulade-Fichou 2 , F. Mégnin-Chanet 2 1 Institut Curie, Radiotherapy, Paris, France ; 2 Institut Curie-Recherche, inserm U1196/CNRS UMR 9187 - CMIB, Orsay, France Purpose or Objective The better understanding of the EGFR receptors involved in the oncogenesis of HER2 positive breast cancers has led to the emergence of new therapeutic classes: the Antibodies Drug-Conjugate (ADC). T-DM1 is an ADC combining the anti-HER2 monoclonal antibody trastuzumab with molecules of DM1, a powerful mitotic spindle inhibitor. In HER2 positive breast cancer, T-DM1 is a validated treatment but the effects of concomitant association with radiation are not known. The objective of this study is to determine in vitro the effects of concomitant irradiation with T-DM1 on five different HER2 positive breast cancer cell lines. Material and Methods Five cell lines of human breast cancer with different levels of HER2 expression (HCC-1954, BT-474, SKBR-3, MDA-MB- 453, ZR-75). T-DM1 was provided by Roche®/Genetech upon MTA. Expression levels were determined by western blot. T-DM1 toxicity was assessed using the CellTiter-Glo®

Poster: Radiobiology track: Radiation and tumour metabolism

PO-1075 CBX4 contributes to radioresistence of esophageal squamous cell carcinoma by targeting autophagy H. Zhu 1 , L. Chu 1 , Q. Liu 1 , H. Zhu 1 , S. Lai 1 , K. Zhao 1 1 Fudan University Shanghai Cancer Center, Radiation Oncology, Shanghai, China