Radiotherapy-induced abscopal effects in immune checkpoint inhibitor-refractory metastatic disease: results from a large multicenter real-world cohort study

Trommer M, Rühle A, Lamrani A, Frei C, Kaufmann J, Mäurer M, Wurschi G, Jiang P, Ehret F, Baehr A, Hardt A, Bodensohn R, Käsmann L, Waltenberger M, Gkika E, Layer JP, Scafa D, Troost EG, Elkhamisy SA, Jazmati D, Popp I, Neppl S, Hagemeier A, Ferdinandus S (2026)

Publication Type: Journal article

Publication year: 2026

Journal

OncoImmunology Taylor & Francis

Book Volume: 15

Article Number: 2610529

Journal Issue: 1

DOI: 10.1080/2162402X.2025.2610529

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.

Authors with CRIS profile

Allison Lamrani Department of Radiation Oncology Charlotte Frei Department of Radiation Oncology

Involved external institutions

Universitätsmedizin der Johannes Gutenberg-Universität Mainz DE Germany (DE) Universitätsklinikum Düsseldorf DE Germany (DE) Universitätsklinikum Freiburg DE Germany (DE) Universitätsklinikum Bonn DE Germany (DE) Märkische Kliniken (Klinikum Lüdenscheid, Stadtklinik Werdohl) DE Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden DE Germany (DE) Universitätsklinikum Köln DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE) Universitätsklinikum Jena DE Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) Klinikum der Universität München (LMU Klinikum) DE Germany (DE)

How to cite

APA:

Trommer, M., Rühle, A., Lamrani, A., Frei, C., Kaufmann, J., Mäurer, M.,... Ferdinandus, S. (2026). Radiotherapy-induced abscopal effects in immune checkpoint inhibitor-refractory metastatic disease: results from a large multicenter real-world cohort study. OncoImmunology, 15(1). https://doi.org/10.1080/2162402X.2025.2610529

MLA:

Trommer, Maike, et al. "Radiotherapy-induced abscopal effects in immune checkpoint inhibitor-refractory metastatic disease: results from a large multicenter real-world cohort study." OncoImmunology 15.1 (2026).

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