ESTRO 2020 Abstract Book

S39 ESTRO 2020

Based on preliminary results of the ImmunoSABR phase 1 trial (NCT02086721), 15 Mio IU L19-IL2 are safe after SABR. Treatment response was seen in 50% of patients with PFS and OS of >2 years. A phase 2 trial (NCT03705403) has been approved by the medical ethical board and is currently recruiting patients.

The study aims were (1) signature validation in a new whole transcriptome cohort (2) assay development for pre- treatment biopsies (3) assay validation. Material and Methods Three cohorts were used (1) VorteX n=203 (2) single centre retrospective n=165 (3) MCRC Biobank n=28. VorteX was a randomised phase III trial comparing radiotherapy volumes in adults with localised extremity STS. Validation cohorts included mainly high-risk patients (85% high-grade). Whole transcriptome RNA-sequencing data (Illumina HiSeq4000) were generated from fresh frozen tumour samples for VorteX. Two targeted assays (Taqman® array cards and nanoString®) were compared in formalin-fixed, paraffin-embedded (FFPE) biopsies. Prognostic validation of the nanoString® assay was performed in FFPE samples from the retrospective and VorteX cohorts. Intra-tumour heterogeneity was assessed in patients (n=10) with multiple biopsies and compared with CAIX expression. Results In the RNA-sequencing VorteX cohort, data were generated for 125/140 patients with available tissue. There was a trend towards poor disease-free survival (DFS) in patients with hypoxic tumours (HR 1.68 95% CI 0.95-2.98 p=0.061). Taqman® array cards and nanoString® demonstrated excellent pass rates and reproducibility. The nanoString® was more sensitive, required lower input and can measure more genes simultaneously. The gene signature showed considerably less intra-tumour heterogeneity than a single marker (figure 1). The nanoString® assay produced a result for 126/127 (99.2%) and 154/159 (96.9%) of patients with sufficient RNA yield and classified 41.3% and 44.8% of samples as hypoxic from the retrospective and VorteX cohorts, respectively. In a univariate analysis patients with hypoxic tumours had worse disease free survival in both cohorts (retrospective HR 2.302 95% CI 1.182-4.486 p=0.0083, VorteX HR 1.687 95% CI 1.013-2.81 p=0.0377) (figure 2).

Conclusion Our results suggest that radiotherapy would better synergize with immunocytokines than checkpoint inhibitors, and that triple combination with aPDL1 is able to make a tumour immune-permissive. Combining the knowledge gained from the successful phase 1 trial and pre-clinical evidence we expect prolonged PFS and OS in the multicentric ImmunoSABR phase 2 trial. OC-0085 Fractionated Radiosurgery plus Check Point Blockade is a Novel Paradigm for Treating Glioblastoma

Abstract withdrawn from presentation

Proffered Papers: Proffered papers 3: Sarcoma

OC-0086 A sarcoma hypoxia signature (nanoString® assay) validates in the phase III VorteX radiotherapy trial L. Forker 1 , B. Bibby 1 , L. Yang 1 , J. Irlam 1 , H. Valentine 1 , P. Shenjere 2 , J. Wylie 3 , M. Leahy 4 , P. Gaunt 5 , L. Billingham 5 , M. Robinson 6 , A. Choudhury 1 , C. West 1 1 University of Manchester, Translational Radiobiology, Manchester, United Kingdom ; 2 The Christie NHS Foundation Trust, Histopathology, Manchester, United Kingdom ; 3 The Christie NHS Foundation Trust, Clinical Oncology, Manchester, United Kingdom ; 4 The Christie NHS Foundation Trust, Medical Oncology, Manchester, United Kingdom ; 5 University of Birmingham, Cancer Research UK Clinical Trials Unit, Birmingham, United Kingdom ; 6 University of Sheffield, Academic Unit of Clinical Oncology, Sheffield, United Kingdom Purpose or Objective Soft tissue sarcomas (STS) are a rare group of tumours encompassing ~50 malignant, heterogeneous subtypes. Localised disease is managed with surgery ± radiotherapy. Neoadjuvant radiotherapy response is varied and despite high metastatic recurrence rates, there is no definite overall survival benefit from the addition of systemic chemotherapy. Each subtype is very rare; therefore, biomarkers of adverse biological features present across subtypes might be more successful in selecting high-risk patients for clinical trials. Tumour hypoxia is associated with poor radiotherapy response and metastasis. We previously derived a 24-gene STS hypoxia signature that was prognostic in two independent cohorts.