ESTRO 2020 Abstract book

S683 ESTRO 2020

20 fractions) with concurrent gemcitabine (100mg/m 2 ) as per institutional protocol (NCT01343121). Forty-eight tumour tissue sample blocks were available for analysis. Next generation sequencing of transcriptomic RNA was performed evaluating the expression of 395 immune response genes. Gene expression was categorised relative to validated house-keeping genes and analysed with respect to patients who had relapsed with distant metastases. Results After 3 years of follow up, 6 patients had developed distant metastases. In these patients, CD3 and IL10 expression was reduced indicating a low T-cell and monocyte infiltrate. M- TOR, PIK3CA and PTPN11 were elevated suggesting activation of signalling pathways often found in aggressive cancers. Conclusion This study is hypothesis generating, but provides data supporting a relationship between the immune tumour microenvironment and poor response to treatment and development of distant metastases. With the PIK3CA- MTOR-AKT and RAS-MAPK pathways implicated with an increased aggressive phenotype and resistance to anti- PD1/PDL1 therapy, immune response gene signatures should be investigated as both prognostic and predictive biomarkers in bladder cancer. PO-1207 Exploring molecular subtype as a biomarker of radiation response in muscle-invasive bladder cancer M. Tan 1,2 , G. Nyamundanda 3 , E. Fontana 3 , S. Hazell 4 , C. Ragulan 3 , K. Jones 5 , B. Abah 5 , T. Jacobs 5 , J. Bowes 5 , A. Sadanandam 3 , R. Huddart 1,2 1 The Institute of Cancer Research, Radiotherapy and Imaging, Sutton, United Kingdom ; 2 The Royal Marsden NHS Foundation Trust, Academic Urology Unit, Sutton, United Kingdom ; 3 The Institute of Cancer Research, Systems and Precision Cancer Medicine, Sutton, United Kingdom ; 4 The Royal Marsden NHS Foundation Trust, Department of Histopathology, London, United Kingdom ; 5 The Royal Marsden NHS Foundation Trust, Bob Champion Unit, Sutton, United Kingdom Purpose or Objective Muscle-invasive bladder cancer (MIBC) can be divided into molecular subtypes based on RNA expression profiles. Data suggests that subtype may be a biomarker of response to neoadjuvant chemotherapy in MIBC, but its role as a biomarker of radiotherapy response has been less explored. We therefore aimed to investigate whether molecular subtype might be associated with response to In this retrospective pilot study, RNA was extracted from diagnostic formalin-fixed paraffin-embedded tumour tissue, from patients with MIBC treated in a single UK centre with radical radiotherapy +/- chemotherapy. Patient tumour samples and data were obtained from our institution’s MIBC biobank. Samples were interrogated by a custom-designed Nanostring panel which included TCGA MIBC subtype genes and radiosensitivity genes. Expression data underwent non-negative matrix factorisation (NMF) to determine subtypes present. The resulting classifier was also applied to publically available data sets. Kaplan-Meier analysis was performed to examine clinical endpoints including invasive locoregional relapse-free survival (invLR_RFS) and overall survival (OS). Data was analysed using R and SPSS. Results Expression data was successfully generated for 43/44 (98%) patients tested. The mean age was 71.9 years and 79% were male. At presentation, 29/43 (67%) had T2-4 N0 M0 disease, 11/43 (26%) had locoregional nodal involvement and 3/43 (7%) had para-aortic nodal involvement. 37/43 (86%) had predominantly transitional cell carcinoma radiotherapy in MIBC. Material and Methods

reviewed. Canadian Institute of Health Information (CIHI) database was used to extract additional SCUC patients treated with upfront cystectomy. Patients with distant metastatic diseases at diagnosis and/or palliative intent therapy were excluded. Stage was converted to AJCC 8th edition staging for clinical staging for both surgical and non-surgical cohorts. Multivariate analysis (MVA) was performed to compare overall survival (OS) and cancer specific survival (CSS) between surgical vs non-surgical groups Results 79 patients were identified: 42 chemoRT, 35 in surgical. Median RT dose was 50Gy (EQD2 52 using a/b ratio of 10).On regression analysis, surgery cohort tended to be younger (OR 0.93, p = 0.04, CI 0.87 – 1.0), lower clinical stage (OR 0.14, p < 0.01, CI 0.04 – 0.56), diagnosed later years (OR 4.8, p = 0.03, CI 1.2 – 20). 5 year OS for CRT and surgery arm were 38% and 33% respectively (p = 0.69). 5 year CSS were 52% and 36% respectively (p=0.22). On MVA, higher ECOG, younger age, and lack of chemotherapy were associated with worse OS.

Conclusion Population-based retrospective chart review suggests no significant difference in CSS and OS between the surgical and chemoRT groups for curative small cell bladder cancer. Younger age, worse ECOG, and lack of chemotherapy are associated with worse OS and CSS. This is the largest series comparing surgery and CRT for localized SCUC in North America to this date. PO-1206 Immune response gene expression analysis and response to radical chemoradiation in bladder cancer M. Anjanappa 1 , D. Roberts 2 , K. Reeves 2 , Y.P. Song 1 , N. Akturk 3 , A. Choudhury 2 1 The Christie NHS Foundation Trust, Clinical Oncology, Manchester, United Kingdom ; 2 University of Manchester, Division of Cancer Sciences, Manchester, United Kingdom ; 3 Dokuz Eylül University Medical School, Oncology, İzmir, Turkey Purpose or Objective The presence of tumour infiltrating lymphocytes (TILs) is prognostic in a number of solid tumours such as colon, lung and breast. An immune supressed tumour microenvironment is a poor prognostic factor thought to be due to a limited host response to cancer cell death. The immune response gene analysis enables characterisation of the TILs and the responsible pathways. Bladder cancer is known to be influenced by immune modulation. We hypothesised that the immune genotype of muscle- invasive bladder cancers treated with radical chemoradiotherapy would stratify for distant failure. Material and Methods Between 2012 and 2014, fifty patients with muscle invasive bladder cancer underwent radical radiotherapy (52.5Gy in