Journal Article

DKFZ-2026-00093

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 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.DKFZ* ; Baehr, A. ; Hardt, A. ; Bodensohn, R. ; Käsmann, L. ; Waltenberger, M. ; Gkika, E. ; Layer, J. P. ; Scafa, D. ; Troost, E. G. C. ; Elkhamisy, S. A. ; Jazmati, D. ; Popp, I. ; Neppl, S. ; Hagemeier, A. ; Ferdinandus, S.

2026
Taylor & Franics Abingdon

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.

Keyword(s): Humans (MeSH) ; Male (MeSH) ; Female (MeSH) ; Immune Checkpoint Inhibitors: therapeutic use (MeSH) ; Middle Aged (MeSH) ; Aged (MeSH) ; Retrospective Studies (MeSH) ; Neoplasms: pathology (MeSH) ; Neoplasms: radiotherapy (MeSH) ; Neoplasms: mortality (MeSH) ; Neoplasms: therapy (MeSH) ; Aged, 80 and over (MeSH) ; Adult (MeSH) ; Neoplasm Metastasis (MeSH) ; Abscopal effect ; immune checkpoint inhibitor resistance ; immunotherapy ; metastatic cancer ; radiotherapy ; Immune Checkpoint Inhibitors

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Berlin (BE01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

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Database coverage:
; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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