ESTRO 2023 - Abstract Book

S199

Saturday 13 May

ESTRO 2023

Conclusion The inclusion of at least one NITDLN station within the CTV (NILN-R+) was an independent factor for poor PFS in the context of CCRT and durvalumab consolidation for locally advanced NSCLC. Therefore, the optimal sparing of immune structures might be of interest in order to achieve a better synergy between radiotherapy and immunotherapy in this indication. OC-0262 The longitudinal effect of neoadjuvant radiotherapy on lymphocytes in primary breast cancer M. Yoneyama 1 , K. Zormpas-Petridis 1 , R. Robinson 1,2 , F. Sobhani 3 , I. Roxanis 4 , E. Provenzano 5 , H. Steel 1 , S. Lightowlers 6 , M. Murthy 7 , C. Philpot 6 , S.P. Castillo 3 , T. Lund 8 , E. Wennerberg 1 , A. Melcher 1 , C. Coles 6 , Y. Yuan 3 , N. Somaiah 1,2 1 The Institute of Cancer Research, Division of Radiotherapy and Imaging, London, United Kingdom; 2 The Royal Marsden NHS Foundation Trust, Breast Unit, London, United Kingdom; 3 The Institute of Cancer Research, Division of Molecular Pathology, London, United Kingdom; 4 The Institute of Cancer Research, The Breast Cancer Now Toby Robins Research Centre, London, United Kingdom; 5 Cambridge University Hospitals NHS Foundation Trust, Pathology, Cambridge, United Kingdom; 6 University of Cambridge, Department of Oncology, Cambridge, United Kingdom; 7 University of Cambridge, Department of Medicine, Cambridge, United Kingdom; 8 The Institute of Cancer Research, Integrated Pathology Unit, London, United Kingdom Purpose or Objective Despite the growing interest in combining radiotherapy (RT) with immune checkpoint blockers (ICB), there is a lack of understanding on the effect of RT itself on the human tumour-immune microenvironment (TIME) and thus the anti-tumour immune response. The PRADA (NCT02771938) and Neo-RT (NCT03818100) trials, which tested feasibility and safety of neoadjuvant RT (NRT) in breast cancer patients, represent a unique opportunity to study novel in vivo longitudinal radiobiological data from the treatment-naïve TIME. We characterised NRT-induced changes to stromal tumour-infiltrating lymphocytes (sTILs) and peripheral blood lymphocytes in these cohorts. Materials and Methods PRADA cases (n=30) received pre-operative locoregional RT (40Gy/15F) following neoadjuvant chemotherapy (NACT). Contemporaneous case-matched controls for PRADA (n=30) received NACT alone. Neo-RT (n=13) received pre-operative locoregional RT (40Gy/15F, with simultaneous integrated boost of 48Gy/15F to primary tumour where possible) followed by 20 weeks of pre-operative endocrine therapy. FFPE samples were obtained from primary tumour at diagnosis (T0), after one fraction of NRT (T1), after final fraction of NRT (T2), and at surgery (T3). H&E-stained sections were manually scored by a breast pathologist blinded to clinical context, following the International TILs Working Group guidelines. Digitised H&E sections were also scored using artificial intelligence (AI) methods for comparison. Absolute lymphocyte count (ALC) from full blood count data at relevant timepoints was evaluated for a subset of patients from PRADA. Results PRADA cases experienced a significant and uniform decrease in sTILs between T0 and subsequent timepoints, with no recovery by T3 (Fig.1A). This was not seen in PRADA controls following NACT alone. sTILs also showed a trend towards decreasing infiltration in Neo-RT. Both NACT and NRT contributed to significant decreases in ALC (Fig.1B). High sTILs at T0 was associated with pathological complete response (pCR) in PRADA cases only, but a relationship between sTILs at T3 and relapse-free survival was seen in both PRADA cases and controls (Fig.2A,B). AI-TILs analysis using a novel approach combining cell classification with the SuperHistopath pipeline showed superior concordance with manual scores when compared with other AI methods. A model using combined manual-AI scores had greater AUC for prediction of pCR compared to models using either parameter alone.