ESTRO 2024 - Abstract Book

S5361

Radiobiology - Tumour biology

ESTRO 2024

Emily Durie 1,2 , Megan Morris 1,3 , Selvakumar Anbalagan 1 , Ritika Chauhan 4 , Daniel Price 4 , Ioannis Roxanis 5 , Nina Tunariu 6 , Victoria Sinnett 6 , Seema Salehi-Bird 7 , Nuala Healy 8 , Archana Seth 9 , Steven Allen 6 , Lone Gothard 1,2 , Justine Hughes 1,2 , Kevin Harrington 1,10 , Sylvain Ladame 3 , Joerg Mansfeld 11 , Meng-Xing Tang 3 , Matthew Blackledge 1 , Navita Somaiah 1,2 1 The Institute of Cancer Research, Division of Radiotherapy and Imaging, Sutton, United Kingdom. 2 The Royal Marsden NHS Foundation Trust, Division of Radiotherapy and Imaging, Sutton, United Kingdom. 3 Imperial College London, Department of Bioengineering, London, United Kingdom. 4 The Institute of Cancer Research, Genomics Facility, Sutton, United Kingdom. 5 The Institute of Cancer Research, The Breast Cancer Now Toby Robins Research Centre, London, United Kingdom. 6 The Royal Marsden NHS Foundation Trust, Radiology, Sutton, United Kingdom. 7 University Hospitals North Midlands, Radiology, Stoke-on-trent, United Kingdom. 8 Cambridge University Hospitals NHS trust, Radiology, Cambridge, United Kingdom. 9 NHS Greater Glasgow and Clyde, Radiology, Glasgow, United Kingdom. 10 The Royal Marsden NHS Foundation Trust, Division of Radiotherapy and Imaging, London, United Kingdom. 11 The Institute of Cancer Research, Division of Cancer Biology, Sutton, United Kingdom The ongoing KORTUC phase 2 multicentre randomised clinical trial (NCT03946202) is testing a novel radiosensitiser (intra-tumoural hydrogen peroxide) in locally advanced breast tumours treated with hypofractionated (36Gy/6# twice weekly) radiotherapy (RT). Hydrogen peroxide results in increased free radical generation, oxidative stress, DNA damage and release of molecular oxygen (when broken down by tumour catalases/peroxidases), thereby potentially reversing tumour hypoxia which is a well-known mechanism of radio resistance 1 . The patients undergo paired pre- and 2-weeks post-RT biopsies and longitudinal dynamic contrast-enhanced and diffusion-weighted MRI (DCE/DW MRI) to assess response. Super-resolution ultrasound (SRUS) scans of tumours are also performed, allowing visualisation of the microvasculature down to micrometre resolution 2 . This enables us to observe microvasculature changes in response to RT to a level of detail not seen before, while extracting quantitative biomarkers like vessel density and diameter. This trial gives us a unique opportunity to understand the radiation-induced changes in the tumour immune microenvironment and its relationship with hypoxia and angiogenesis. Here, we present a pilot study (n=10 patients) investigating transcriptomic changes in the tumour pre- and post-RT and correlate these with immunohistochemical (IHC) markers and novel imaging biomarkers of response. Purpose/Objective:

Material/Methods:

Serial sections from formalin-fixed paraffin-embedded biopsies were stained for vascular and hypoxia IHC markers (GLUT1, CD31, CAIX) and blind-scored by a histopathologist. RNA was extracted, libraries constructed with Agilent SureSelect XT HS2 RNA Library and finally sequenced using the Illumina Novaseq. Analysis was carried out using DESeq2 and clusterProfiler. DCE/DW-MRI and contrast-enhanced SRUS scans were performed at baseline, 2 weeks, 6- & 12-months post-RT to assess response. Complete response (CR) on MRI was defined as no tumour enhancement above background or minimal enhancement in keeping with fibrosis. Due to the ongoing nature of this trial, we remain blinded to the trial intervention and so all data has been analysed to investigate changes and response post RT.