ESTRO 2026 Responders exhibited preserved and resilient CD4 ⁺ TEMRA populations, suggesting that maintenance of helper T-cell memory may support durable tumor control. Peripheral immune signatures could serve as early, noninvasive biomarkers of benefit from immunoradiotherapy. Keywords: Immunophenotype, immunoradiotherapy, phase 2, SBRT Digital Poster Highlight 2206 Plasma proteomic profile as prognostic tool in oligorecurrent prostate cancer after SBRT: updated results Ombretta Repetto 1 , Giulia Brisotto 1 , Mariangela De Zorzi 1 , Matteo Turetta 1 , Fabio Del Ben 1 , Elena Muraro 1 , Alessandra Donofrio 2 , Francesca Gessoni 2 , Martina Zanchetta 3 , Agostino Steffan 1 , Fabio Matrone 2 1 Immunopathology and Cancer Biomarkers Unit, Department of Cancer Research and Advanced Diagnostics, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy. 2 Department of Radiation Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy. 3 Clinical Trial Office, Scientific Direction, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy Purpose/Objective: Improving prognostic stratification in patients (pts) with oligorecurrent hormone-sensitive prostate cancer (orHSPC) treated with Stereotactic Body Radiation Therapy (SBRT) remains an unmet clinical need. Circulating proteins have emerged as promising, minimally invasive biomarkers [1-2]. We previously presented preliminary results of this prospective trial at ESTRO 2025 [3]; here we report an updated analysis with extended follow-up. Material/Methods: Thirty-five orHSPC pts with 1–3 nodal and/or bone metastases treated with SBRT were prospectively enrolled. After a median follow-up of 41 months (previously 25.6 months), pts were stratified by biochemical progression (BP) into “early-BP” (BP-free survival < 6 months; n = 7) and “late-BP” (> 24 months; n = 9) subgroups, and by distant progression (DP) into “no-DP” (n = 7) and “polymetastatic-DP” (n = 7). Plasma-EDTA was collected before SBRT. Plasma peptides were separated by liquid chromatography tandem mass spectrometry (LC-MS/MS) based proteomics. Relative amount of identified proteins across our samples was determined through label-free quantification (LFQ). Differentially abundant proteins (adjusted p ≤ 0.05) were validated using immunoblotting. Results: Distinct proteomic signatures were observed
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Clinical - Biomarkers of clinical response
3 Inserm US23, Gustave Roussy, Villejuif, France. 4 DITEP, Gustave Roussy, Villejuif, France
Purpose/Objective: Predictive biomarkers for immunoradiotherapy remain lacking. Peripheral blood offers an accessible means to monitor systemic immunity. While radiation- induced lymphopenia is a known negative prognostic factor, its impact on specific immune subsets is unclear. This translational substudy of the ABIMMUNE trial (durvalumab ± tremelimumab plus stereotactic body radiotherapy [SBRT]) used large-scale immunophenotyping to identify systemic immune correlates of response in advanced squamous cell carcinoma (SCC). Material/Methods: Patients with pretreated advanced SCC of the head and neck, lung, esophagus, cervix, vagina, vulva, or anus received durvalumab ± tremelimumab with SBRT (9 Gy × 3 fractions from C1D15, with ≥ 1 unirradiated lesion). Peripheral blood was collected at baseline, before SBRT (C1D15), and after SBRT (C2D15). Multiparametric flow cytometry quantified ~300 circulating immune cell subsets across innate and adaptive compartments. Responders were defined as progression-free survival (PFS) ≥ 120 days. Group comparisons used Mann–Whitney and Kruskal–Wallis tests, and logistic regression identified clinical predictors of response. Significant immune subsets (2– 3 features) were combined and evaluated by leave- one-out (LOO) cross-validation (n = 47 at baseline). Results: Forty-eight patients and 119 samples were analyzed, including 20 responders (42%) and 28 non-responders (58%). Median age was 59 years (range 27–80); 56% were female, and 67% had ECOG 0. The main primary sites were esophagus (42%) and anal canal (33%). SBRT most often targeted the lung (40%), and 92% received durvalumab plus tremelimumab. Grade 3 lymphopenia occurred in 8–9 patients across timepoints. At C1D15, non-responders showed a greater decline in total lymphocytes (880.7 vs 1190.1 cells/µL, p = 0.037) and CD4 ⁺ T cells (354.4 vs 472.6 cells/µL, p = 0.027). Differences were most marked in CD4 ⁺ effector-memory T cells re-expressing CD45RA (TEMRA). Responders had higher baseline activated CD4 ⁺ TEMRA (CD95 ⁺ , 13.9 vs 7.4 cells/µL; p = 0.0015) and retained more long-lived memory CD4 ⁺ TEMRA (CD127 ⁺ , 6.3 vs 2.2 cells/µL; p = 0.0024) after SBRT. On multivariate analysis, female sex (OR = 4.74, 95% CI 1.14–24.73, p = 0.04) and younger age (OR = 0.94, 95% CI 0.89–0.99, p = 0.04) were independently associated with PFS ≥ 120 days. The best immune model, combining CD4 ⁺ TEMRA and CD4 ⁺ TEMRA CD95 ⁺ cells, achieved an AUC of 0.89 [95% CI 0.78–0.99] after LOO validation. Conclusion:
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