ESTRO 37 Abstract book

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ESTRO 37

OC-0050 Clinical significance of soluble PD-L1 level in hepatocellular carcinoma patients treated with RT H.J. Kim 1 , S. Park 1 , K.J. Kim 1 , J. Seong 1 1 Yonsei University, Radiation Oncology, SEOUL, Korea Republic of Purpose or Ojective Efforts to find an optimal combination with immune checkpoint inhibitors are underway to further increase the therapeutic effect. This study was performed to investigate the clinical implications of soluble PD-L1 (sPD-L1) level in hepatocellular carcinoma (HCC) patients treated with radiotherapy (RT). Material and Methods HCC patients treated with RT between June 2011 and March 2015 were prospectively recruited and sPD-L1 levels were analyzed. RT was performed using either stereotactic body radiotherapy (SBRT) or conventional fractionated RT. Blood samples were obtained at the each day of RT start, RT end and 1 month follow-up, respectively. sPD-L1 was measured using an enzyme- linked immunosorbent assay (ELISA) in plasma. The association between the amount of sPD-L1 and both of the clinical features and treatment outcome was analyzed. Results Fifty-three patients with HCC were included. Thirty-four patients received a conventional fractionated RT with a median dose of 45 Gy, while 19 patients received SBRT with 60 Gy in 4 fractions. Median follow-up period was 21.3 months. Initial sPD-L1 level increased as the BCLC stage increased (P = 0.047), which was also same in the mUICC stage (P = 0.015). Moreover, initial sPD-L1 level was significantly associated with portal vein tumor thrombosis (P = 0.001), vein invasion (P = 0.006), and tumor size (r = 0.279, P = 0.043). The overall-survival was significantly poor in patients with higher sPD-L1 (≥ 1.315 pg/ml). Furthermore, the higher level of sPD-L1 at 1 month follow-up (≥ 12.9 pg/ml) was significantly related to early lung metastasis within 4 months after RT (P = 0.015). sPD-L1 level was significantly increased after RT. It continued to increase until 1 month follow-up in SBRT group, while it decreased at 1 month in conventional group compared to immediately after RT. Conclusion The level of sPD-L1 was associated with tumor aggressiveness, suggesting its role as a possible biomarker predicting outcome. The increases in PD-L1 after RT suggests that combined treatment with RT and immune checkpoint inhibitors may be a promising therapeutic strategy in HCC. OC-0051 Radiotherapy causes long-lasting antitumor immunological memory when combined with immunotherapy V. Olivo Pimentel 1 , N.H. Rekers 1 , A. Yaromina 1 , N.G. Lieuwes 1 , R. Biemans 1 , C.M.L. Zegers 1 , W.T.V. Germeraad 2 , E.J. Van Limbergen 1 , D. Neri 3 , L.J. Dubois 1 , P. Lambin 1 1 Dept. of Radiotherapy, GROW - School for Oncology and Developmental Biology- Maastricht Comprehensive Cancer Centre- Maastricht University Medical Centre, Maastricht, The Netherlands 2 Dept. of Internal Medicine, GROW - School for Oncology and Developmental Biology- Maastricht Comprehensive Cancer Centre- Maastricht University Medical Centre, Maastricht, The Netherlands 3 Dept. of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, Zürich, Switzerland Purpose or Objective Radiotherapy (RT) induces DNA damage lethal to cancer cells, but also immunogenic cell death by releasing tumor associated-antigens and danger signals, thus enhancing immunity against cancer. We have shown that the

outweighed by the potential side effects? The current challenge in radiation oncology is therefore to improve the patient selection, towards identifying those patients who have an expected benefit from radiation, from those patients with no added radiation benefit but who only gets added a risk of late side effects.

Proffered Papers: RB 1: Joint efforts in Immuno- radiobiology

OC-0049 Genomic profiling of muscle invasive bladder cancer to predict response to chemoradiation therapy D. Miyamoto 1 , E. Gibb 2 , K. Mouw 3 , Y. Liu 2 , C. Wu 1 , M. Drumm 1 , J. Lehrer 2 , H. Ashab 2 , N. Erho 2 , M. Du Plessis 2 , K. Ong 2 , W. Shipley 1 , E. Davicioni 2 , J. Efstathiou 1 1 Massachusetts General Hospital, Radiation Oncology, Boston, USA 2 GenomeDx Biosciences, Inc, Vancouver, Canada 3 Dana Farber / Brigham & Women's Hospital, Radiation Oncology, Boston, USA Purpose or Objective Bladder-sparing trimodality therapy with maximal transurethral resection of bladder tumor (TURBT) followed by chemoradiation therapy is an acceptable alternative to radical cystectomy for selected patients with muscle invasive bladder cancer (MIBC). Genomic profiling has demonstrated MIBC can be divided into molecular subtypes with differing responses to chemotherapy. We explored the utility of genomic data to select patients for bladder-sparing trimodality therapy. Material and Methods Transcriptome wide gene expression profiles were generated for 189 MIBC TURBT samples from patients treated with bladder-sparing trimodality therapy at a single institution. Of these, 103 passed microarray quality control. Molecular subtype and expression of bladder cancer genes were assessed for association with overall and disease-specific survival. Transcriptome wide differential gene expression analysis was used to explore gene set enrichment in trimodality therapy response The chemoradiation cohort (n=103) had a median followup of 6.9 years for alive patients, and was classified into four subtypes: basal (n=44), basal claudin- low (n=12), infiltrated luminal (n=17) and luminal tumors (n=30). There was no significant difference in overall or disease-specific survival by subtype. However, higher expression of the luminal-associated PPARG was correlated with increased survival after adjusting for subtype and clinical factors (HR=0.52, p=0.002). In contrast, a p53 signature predicted worse survival after adjusting for clinical factors (HR=1.92, p=0.022). Elevated mRNA expression of the DNA damage repair gene MRE11 was associated with improved survival in the trimodality cohort (HR=0.69, P=0.031), consistent with its potential role as a predictive biomarker for radiation response. Gene set enrichment revealed differential regulation of immune pathways in trimodality therapy responders relative to non-responders, including enrichment of interferon gamma signaling (p=0.01) and CXCL9 (p=0.031), suggestive of an interplay between tumor immunologic microenvironment and response to chemoradiation. Conclusion Transcriptional profiling of MIBC revealed gene signatures correlated with response to chemoradiation, suggesting the potential of genomics to guide use of bladder-sparing trimodality therapy. groups. Results