S2541
Radiobiology – Immuno-radiobiology
ESTRO 2026
Conclusion: Preliminary multimodal results from a novel
Significant differential gene expression was defined as an absolute log2 fold change (log2FC) of ≥ 1 and adjusted p-value <0.05. Results: Post-radiotherapy, 68.2% (15/22) of PRADA patients had ≥ 1 axillary TDLN with fibrotic treatment effect (partial/complete replacement of a tumour-containing area6). Versus baseline tumour-containing TDLN regions and post-RT normal TDLN regions, these areas were significantly enriched for CD8+ T-cells and non- lymphoid cells, alongside depletion of CD20+ B cells (Fig1). 687 genes were differentially expressed in post- radiotherapy TDLNs versus baseline. 425 genes were upregulated, including chemokines (e.g. CXCL2; log2FC 5.86, CCL21; log2FC 1.14) and interleukins (e.g. IL-1 β ; log2FC 1.49, IL-21; log2FC 3.71).GSEA analysis indicated 15 significantly upregulated Hallmark pathways including epithelial-mesenchymal transition, inflammatory signalling axes and apoptosis (Fig2). Upregulated Gene Ontology pathways included leucocyte migration, antigen binding and extracellular matrix deposition. Immune cell deconvolution also highlighted an increased TDLN stromal population post-radiotherapy, alongside increased antigen- presenting cells and CD4+ memory T-cells.
translational dataset suggest radiotherapy influences TDLN stromal populations, whilst inducing some transcriptomic changes in TDLNs that could promote anti-tumour immune responses. Ongoing work is dissecting whether this is specific to tumour- containing TDLNs (versus tumour-free), which will have important implications for optimal nodal radiotherapy strategies, particularly in the context of increasing immunotherapy use. Fibrotic treatment effect areas in post-radiotherapy TDLNs represent a distinct immune microenvironment warranting further characterisation. References: 1.Marciscano AE et al. Clin Cancer Res. 2018. PMID 29898992.2.Darragh LB et al. Nat Commun. 2022. PMID 36385142.3.Telarovic I et al. Nat Commun. 2024. PMID 38951172.4.Thiruchelvam PTR et al. Lancet Oncol. 2022. PMID 35397804.5.Lightowlers SV et al. Clin Oncol (R Coll Radiol). 2024. PMID 39561627.6.Newman LA et al. Ann Surg Oncol. 2003. PMID 12900363. Keywords: lymph node, breast cancer, neo-adjuvant Impact of Radiotherapy Fractionation on Immune Activation in Adrenal Oligometastases (IM-SABR study) Nora D Purcell 1 , Linda R Beeloo 1 , Peter S.N. van Rossum 1 , Suresh Senan 1 , Tanja D de Gruijl 2 , Famke L Schneiders 1 1 Radiation Oncology, Amsterdam UMC, Amsterdam, Netherlands. 2 Medical Oncology, Amsterdam UMC, Amsterdam, Netherlands Purpose/Objective: Stereotactic MR-guided adaptive radiotherapy (SMART) is an effective treatment for adrenal metastases, providing a good local control1. Beyond direct tumor ablation, stereotactic ablative radiotherapy (SABR) may also stimulate systemic immune activation, potentially enhancing efficacy of immune checkpoint inhibition (ICI). However, the character of the immune responses Proffered Paper 4583 may vary depending on radiation dose and fractionation schedule. This study investigates systemic immune effects of different SABR fractionation schemes for adrenal metastases, with and without concurrent ICI. Material/Methods: The study was approved by the Institutional Review Board of Amsterdam UMC (NL77647.029.21). The planned accrual was 30 patients. Between April 2022 and November 2025, patients with adrenal metastases treated with SMART received one of three SABR
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