Radiotherapy-induced abscopal effects in immune checkpoint inhibitor-refractory metastatic disease: results from a large multicenter real-world cohort study
Year: 2026
Type: article
Study design: Observational Study
Abstract: Combining radiotherapy with immune checkpoint inhibitors (RT-ICI) triggers systemic antitumor responses, such as abscopal effects (AbE). Predictors of AbE and its impact on survival in real-world settings remain poorly defined. This multicenter, retrospective cohort study assessed the prevalence of AbE in ICI-refractory progressive metastatic patients by evaluating the additive effect of RT on nonirradiated lesions (NIL). We screened 3773 cases to identify patients with stage IV tumors receiving RT during/after ICI. Abscopal benefit (AB) was defined as abscopal response (AR) or control (AC) by measuring NILs according to iRECIST. AB was observed in 61.3% of 142 included patients and associated with improved median overall survival (18 vs. 8 months, p < 0.01) and progression-free survival (7 vs. 3 months, p < 0.01). Logistic regression identified younger age (OR = 0.951, 95% CI: 0.903–0.995, p = 0.039) and longer ICI-RT intervals (OR = 1.077, 95% CI: 1.019–1.171, p = 0.027) as predictors of AB. There was no association between radiation dose or tumor volume and AB. Cox regression identified BMI ≥ 25 kg/m2 (HR = 3.348, 95% CI: 1.557–7.202, p = 0.002) and CRP ≥ 5 mg/l (HR = 3.058, 95% CI: 1.211–7.724, p = 0.016) as independent negative prognostic factors for survival in this RT-ICI cohort. Median survival was significantly higher among patients receiving ultrahypofractionated RT, compared to other fractions (21 vs. 11 months; p = 0.024). AbE seems to occur reliably and is prognostically relevant in ICI-refractory patients receiving RT. Patient- and timing-related factors were more predictive than RT details in our cohort. Our findings enhance the understanding of tailored RT-ICI approaches and lay the groundwork for targeted radioimmunotherapy strategies and personalized clinical trial designs.
Source: OncoImmunology
Authors: Maike Trommer, Alexander Rühle, Allison Lamrani, Charlotte Frei, Justus Kaufmann, Matthias Mäurer, Georg Wurschi, Ping Jiang, Felix Ehret, Andrea Baehr, Annika Hardt, Raphael Bodensohn, Lukas Käsmann, Maria Waltenberger, Eleni Gkika, Julian P. Layer, Davide Scafa, Esther G. C. Troost, Sally A. Elkhamisy, Danny Jazmati, Ilinca Popp, Sebastian Neppl, Anna Hagemeier, Simone Ferdinandus
Institutions: University Hospital Bonn, University Hospital Cologne, Olivia Newton-John Cancer Wellness & Research Centre, Austin Health, University of Freiburg, University Medical Center Freiburg, University Hospital Leipzig, Leipzig University, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Comprehensive Cancer Center Erlangen, University Medical Center of the Johannes Gutenberg University Mainz, Jena University Hospital, Klinikum Lüdenscheid, Humboldt-Universität zu Berlin, Deutsches Konsortium für Translationale Krebsforschung, Charité – Universitätsmedizin Berlin, University Medical Center Hamburg-Eppendorf, LMU Klinikum, Universitätsklinikum Tübingen, Ludwig-Maximilians-Universität München, Paracelsus Medical University, TUM Klinikum, Ospedale di Bolzano, Azienda Sanitaria dell'Alto Adige, Technical University of Munich, German Cancer Research Center, Helmholtz-Zentrum Dresden-Rossendorf, National Center for Tumor Diseases, OncoRay, University Hospital Carl Gustav Carus, Nationales Centrum für Tumorerkrankungen Dresden, Technische Universität Dresden, Düsseldorf University Hospital, Heinrich Heine University Düsseldorf, University of Cologne
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,913
Awards: G3433373831, G3643674569
OpenAlex ID: W7122391144