S1119
Clinical – Upper GI
ESTRO 2026
Statistics, Medical Center - University of Freiburg, Freiburg, Germany. 5 Department of Radiation Oncology, Frei, Freiburg, Germany. 6 Department of Radiation Oncology, University Hospital Leipzig, Leipzig, Germany. 7 Department of Radiation Oncology, University of Washington School of Medicine, Seattle, USA. 8 Transplant Oncology and Therapeutics, Department of Surgery, Houston Methodist Academic Institute,, Houston, USA Purpose/Objective: Stereotactic body radiotherapy (SBRT) is increasingly used for metastatic lesions and can induce systemic immune modulation. The immunologic impact of combining SBRT with systemic therapy remains unclear. This prospective, non-interventional study analysed longitudinal immune cell changes in patients with metastatic liver disease treated with SBRT with or without concomitant systemic treatment. Material/Methods: Peripheral blood was collected before and at the end of treatment, and during follow-up visits at 6 weeks (FU1) and 3 months (FU2). We used flow cytometry to assess T-cell subsets, including by using markers of proliferation (Ki67), immune checkpoints (PD-1, Tim-3, CTLA-4), costimulatory molecules (ICOS), chemokine receptor CXCR3, and cytokine production following in vitro stimulation. Patients were treated in 3 to 12 fractions, aiming at a BED of 100 Gy. Results: A total of 92 patients were evaluated. Patients receiving systemic treatment (n=51) showed stronger and more sustained CD8 ⁺ and CD4 ⁺ T-cell depletion with concomitant increases in Ki67 ⁺ proliferating T-cell fractions up to FU2, compared to patients without systemic treatment (n=41). PD-1 expression was comparable between groups, suggesting non-terminal exhaustion, but PD-1 intensity increased only after systemic therapy. Activated PD-1 ⁺ Tim-3 ⁻ T-cells expanded after SBRT alone, whereas ICOS upregulation was seen only after combined treatment. CXCR3 ⁺ T-cells decreased in both groups, more prominently after systemic therapy. Cytokine (IFN- γ , TNF- α , IL-17A) production was transiently reduced under systemic therapy, indicating diminished effector function. NK/NKT cell depletion and loss of naïve/memory T-cells were more pronounced after combination therapy. Tregs increased in both groups, but absolute counts rose only after systemic treatment. MDSCs were unaffected. Conclusion: Systemic therapy combined with SBRT induces stronger lymphodepletion and rebound T cell proliferation but attenuated effector function of circulating T-cells compared to SBRT alone. These findings may guide optimal integration and sequencing of systemic therapy with SBRT in
Conclusion: Distant metastasis remains the primary challenge in cervical esophageal carcinoma management, accounting for over half of all failures and highlighting the need for effective systemic therapy including immunotherapy. Local failure still represents a substantial concern which can potentially be addressed with radiation dse escalation. However, prospective studies with larger sample size and longer follow-up are required to validate this. Keywords: Chemoradiation, Squamous cell carcinoma Immunomodulatory effects of SBRT with or without concomitant systemic treatment in metastatic liver disease: Results from the prospective LAPIS study Eleni Gkika 1,2 , Elke Firat 3 , Sonja Adebahr 1 , Erika Graf 4 , Ilinca Popp 1 , Alexandra Eichhorst 5 , Gianluca Radicioni 1 , Simon S. Spohn 1 , Nils H. Nicolay 6 , Andreas Rimner 1 , Simon Kirste 1 , Simon S. Lo 7 , Gabriele Niedermann 1 , Dan G. Duda 8 , Anca-Ligia Grosu 1 1 Department of Radiation Oncology, Medical Center - University of Freiburg, Freiburg, Germany. 2 Department of Radiation Oncology, University Hospital Bonn, Bonn, Germany. 3 Department of Radiation Oncology, University Hospital Bonn, Freiburg, Germany. 4 Institute of Medical Biometry and Mini-Oral 4684
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