S2536
Radiobiology – Immuno-radiobiology
ESTRO 2026
stable Amyloid β 1–42 levels. Complement factor H declined from baseline to 6 months in NCF ( Δ = − 0.0247 mg/ml, p = 0.020) but not in non-NCF. Other analytes showed non-significant fluctuations. Conclusion: Post-HA-WBRT dynamics of BDNF, Amyloid β 1–42, and complement factor H distinguished patients with NCF from those without. These circulating biomarkers may serve as minimally invasive indicators of neurocognitive vulnerability after HA-WBRT and warrant validation in larger cohorts. References: 1. Brown PD, Gondi V, Pugh S et al. Hippocampal Avoidance During Whole-Brain Radiotherapy Plus Memantine for Patients With Brain Metastases: Phase III Trial NRG Oncology CC001. J Clin Oncol. 2020 Apr 1;38(10):1019-1029.2. Yang WC, Chen YF, Yang CC et al. Hippocampal avoidance whole-brain radiotherapy without memantine in preserving neurocognitive function for brain metastases: a phase II blinded randomized trial. Neuro Oncol. 2021 Mar 25;23(3):478- 486. Keywords: HA-WBRT, neuroinflammatory biomarkers Digital Poster 3243 Experimental investigation of lung toxicity after radiation therapy combined with immune checkpoint inhibition Andreas Zoeschg 1 , Laura L. Rotgerink 1 , Florian T. Gassert 2 , Tanja Groll 3 , Sarah Diederich 1 , Sophie M. Nefzger 1 , Rico Burkhardt 1 , Ziyi Huang 1 , Maximilian Giller 1 , Nicole A. Schmid 1 , Caroline N. Walther 1 , Christin Weiß 4 , Kilian Kirmes 5 , Hannah Felchle 1 , Lina Felsner 6 , Dario Biongiovanni 7 , Katja Steiger 3 , Thomas E. Schmid 1 , Stephanie E. Combs 1 , Julius C. Fischer 1 1 Department of Radiation Oncology, TUM School of Medicine and Health, Munich, Germany. 2 Institute of Diagnostic and Interventional Radiology, TUM University Hospital, Munich, Germany. 3 Comparative Experimental Pathology, TUM School of Medicine and Health, Munich, Germany. 4 Institute of Clinical Chemistry and Pathobiochemistry, TUM School of Medicine and Health, Munich, Germany. 5 Department of Internal Medicine I, TUM School of Medicine and Health, Munich, Germany. 6 School of Computation, Information & Technology, Technical University of Munich, Munich, Germany. 7 Department of Internal Medicine I, University Hospital Augsburg, Augsburg, Germany Purpose/Objective: Combining radiation therapy (RT) and immune checkpoint inhibition (ICI) has revolutionized the treatment of many thoracic tumors, including lung cancer. However, it remains unclear whether such a
Digital Poster 3038 Dynamics of Serum Neuroinflammatory Biomarkers Associated With Neurocognitive Failure After Hippocampal Avoidance Whole-Brain Radiotherapy Wen-Chi Yang 1,2 , Shao-Lun Lu 1,2 , Shih-Fan Lai 1,2 , Feng- Ming Hsu 1,2 1 Radiation Oncology, National Taiwan University Cancer Center, Taipei, Taiwan. 2 Oncology, National Taiwan University Hospital, Taipei, Taiwan Purpose/Objective: Hippocampal avoidance whole brain radiotherapy (HA- WBRT) has been shown to mitigate neurocognitive decline in patients with multiple brain metastases. Our prior randomized trial demonstrated that unilateral (left-sided) hippocampal avoidance provided neurocognitive protection comparable to bilateral avoidance. Building on that study, this secondary analysis investigated whether serial changes in serum neuroinflammatory biomarkers were associated with subsequent neurocognitive failure (NCF). Material/Methods: Serum biomarkers—including α -synuclein, Amyloid beta1–40, Amyloid beta1–42, apolipoprotein E (ApoE4), brain-derived neurotrophic factor (BDNF), clusterin (ApoJ), complement factor H, fetuin-A, glial cell line- derived neurotrophic factor (GDNF), S100B, phosphorylated tau (pT231), and total tau—were measured at baseline (0 months), 4 months, and 6 months after treatment in a clinical trial comparing unilateral versus bilateral HA-WBRT. Biomarkers were assayed using ProcartaPlex™ immunoassays (Thermo Fisher Scientific, Waltham, MA, USA). Neurocognitive function was assessed with the Hopkins Verbal Learning Test–Revised (HVLT-R). NCF was defined as a decline in any HVLT-R domain based on the Reliable Change Index. Paired t tests evaluated within-group changes, and Welch t tests assessed between-group differences. Results: From March 2021 to April 2024, 73 patients were enrolled, and 68 (33 unilateral, 35 bilateral) completed treatment (median follow-up, 13.2 months). Among 38 patients with complete serial samples, 31 experienced NCF and 7 remained non-NCF. BDNF levels were slightly higher in NCF than in non-NCF patients (mean +13.96 pg/mL, p = 0.065). In NCF, BDNF declined from baseline to 4 months ( Δ = − 14.35 pg/mL, p = 0.002) and partially rebounded by 6 months ( Δ = +7.51 pg/mL, p = 0.134), whereas non-NCF patients showed no significant change across time (p all > 0.2). Amyloid β 1–42 increased from 0 to 4 months ( Δ = +0.126 pg/mL, p = 0.012) and remained elevated at 6 months compared with baseline ( Δ = +0.125 pg/mL, p = 0.019) in the NCF group, while the non-NCF group maintained
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