S2625
Radiobiology - Translational radiobiology
ESTRO 2026
chemotherapy and RT to a total dose of 60 Gy in 30 fractions of 2 Gy each, delivered with photons or protons, with or without adjuvant durvalumab. Plasma samples were collected at four key timepoints: prior to RT initiation, before the fourth and before the last fraction of RT (end of cCRT), and 3 months after the start of durvalumab treatment. Protein profiling was performed using the OLINK Target 48 Cytokine and OLINK Target 48 Immune Surveillance panels, enabling the detection of proteins covering key immunological processes. Differential protein expression across timepoints was assessed using a linear mixed model approach. Results: A total of 38 patients have been included (mean age 66.4 yrs ±8.6; 57.9% male). Twenty-eight patients were treated with adjuvant durvalumab, of whom 5 prematurely stopped the treatment. The top 12 proteins that were significantly differentially expressed between all timepoints included FASLG, EPO, IL15, OLR1, IL32, IL16, PDCD1, TREM1, MMP12, GZMA, GZMAB, and IL17D. Notably, the absolute plasma concentration of EPO and IL15 significantly increased from baseline towards the end of cCRT. Erythropoietin (EPO) is a hormone that promotes erythropoiesis and increased EPO levels may be associated with the development of anemia during cCRT. The plasma levels normalized during adjuvant durvalumab. In contrast, the absolute plasma concentration of FASLG, PDCD1, MMP12, GZMA, GZMB, and IL17D gradually decreased during cCRT. Granzymes, in particular, are key immunological regulators and a decrease in absolute concentration may reflect impaired immunity
individual risk factor for OS. The most discriminating immune biomarkers for OS were IFN- γ , IP-10, MCP-1, sPD-L1, and RANTES. Log-Rank statistics revealed significant differences in the median OS in the low vs high expression groups (IFN- γ : 27.0 months, 95%CI: 7.4-46.6 vs. 16.0 months, 95%CI: 12.1-27.2, p=0.1; IP- 10: 25.0 months, 95%CI: 14.0-36.0 vs. 16.0 months, 95%CI: 10.7-21.3, p=0.06; MCP-1: 21.0 months, 95%CI: 13.3-27.7 vs. 10.0 months, 95%CI: 4.2-15.8, p=0.008; sPD-L1: 90.0 months, 95%CI: 0.0-236.1 vs. 19.0 months, 95%CI: 13.5-24.5, p=0.008; RANTES: 24.0 months, 95% CI: 10.1-37.9 vs. 13.0 months, 95% CI: 10.9-15.1, p=0.007). Conclusion: Both clinical- and peripheral immunological parameters have been identified that can identify the patients who are at high risk of early mortality during and after cCRT. These patients may benefit from alternative treatment strategies. Keywords: Immune profiling; small cell lung cancer Peripheral blood immune profiling of patients with stage III non-small cell lung cancer treated with concurrent chemoradiation and adjuvant durvalumab Rianne D.W. Vaes 1 , Iris E.W.G. Laven 1 , Tessa T.J. Welbers 1 , Marijana Rucevic 2 , Lizza E.L. Hendriks 3 , Dirk De Ruysscher 1 1 Department of Radiation Oncology (Maastro Clinic), GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, Netherlands. 2 Olink Proteomics Sciences, part of Thermo Fisher Scientific, Uppsala, Sweden. 3 Department of Pulmonary Diseases, GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, Netherlands Purpose/Objective: The standard of care for fit patients with unresectable stage III non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy (cCRT) followed by adjuvant durvalumab for 12 months. Preserving the immune competence during cCRT is considered essential for maximizing the therapeutic benefit of the treatment. This study aimed to profile the dynamic changes of the systemic immune status of patients with stage III NSCLC before, during and after treatment. Material/Methods: In this prospective observational phase II trial Digital Poster 4401 (NCT04432142 / METC20-062), patients with stage III NSCLC were enrolled between May 2021 and June 2024. Patients were treated with standard of care cCRT, consisting of platinum-based doublet
during cCRT. Conclusion:
Preliminary results of this prospective phase II trial revealed significant changes in immunological plasma proteins during and after cCRT and adjuvant durvalumab. These changes are indicative for an immunocompromised state of these patients during cCRT. The association thereof with treatment outcome and treatment-related toxicity will be further explored. Keywords: Immune profiling; non-small cell lung cancer
Proffered Paper 4976
Rapid ex vivo chemoradiotherapy assessment in human precision cut organotypic tumour slices can guide treatment selection in colorectal cancer. Jayant K Rane 1,2 , Juan Jose Garcia-Gomez 1 , Cenk Celik 3 , Reem Ahmad 1 , Eloise Withnell 3 , Stephen Turnock 1 , Imran Uddin 1 , Gordon Beatie 1 , Hou Wang Lam 3 , Alex McLatchie 1 , Samuel Marguerat 1 , Maria Secrier 3 , Maria Hawkins 4,2
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