Abscopal effects in patients with malignant melanoma treated with radiotherapy and immune checkpoint inhibition: analysis of a large observational multicenter study

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Simone Ferdinandus - , University of Cologne (Author)
  • Alexander Rühle - , University Medical Center Freiburg, Leipzig University (Author)
  • Allison Lamrani - , Friedrich-Alexander University Erlangen-Nürnberg (Author)
  • Charlotte Frei - , Friedrich-Alexander University Erlangen-Nürnberg, University Hospital at the Friedrich-Alexander University Erlangen-Nürnberg (Author)
  • Justus Kaufmann - , University Medical Center Mainz (Author)
  • Matthias Mäurer - , Friedrich Schiller University Jena (Author)
  • Georg Wurschi - , Friedrich Schiller University Jena (Author)
  • Ping Jiang - , Hospital Lüdenscheid (Author)
  • Felix Ehret - , Charité – Universitätsmedizin Berlin (Author)
  • Andrea Baehr - , University Hospital Hamburg Eppendorf (Author)
  • Annika Hardt - , University of Hamburg (Author)
  • Raphael Bodensohn - , Ludwig Maximilian University of Munich, University Hospital Tübingen (Author)
  • Lukas Käsmann - , Ludwig Maximilian University of Munich (Author)
  • Maria Waltenberger - , Regional Hospital of Bolzano, Paracelsus Private Medical University (Author)
  • Davide Scafa - , University of Bonn (Author)
  • Julian P. Layer - , University of Bonn (Author)
  • Esther G.C. Troost - , Department of Radiotherapy and Radiooncology, OncoRay - National Center for Radiation Research in Oncology (Author)
  • Sally A. Elkhamisy - , Department of Radiotherapy and Radiooncology, OncoRay - National Center for Radiation Research in Oncology (Author)
  • Danny Jazmati - , University Hospital Duesseldorf (Author)
  • Cindy Franklin - , University of Cologne (Author)
  • Sebastian Neppl - , University of Cologne (Author)
  • Anna Hagemeier - , University of Cologne (Author)
  • Maike Trommer - , University of Cologne, University of Bonn (Author)

Abstract

Background Abscopal effect (AbE), the regression of non-irradiated metastatic lesions (NILs) following radiotherapy (RT), is relevant in patients with malignant melanoma (MM) with progressive disease (PD) under immune checkpoint inhibition (ICI) as resistance to immunotherapy. In the “ARTIC” trial, we assessed the incidence of AbE in patients with progressive MM by evaluating the effect of RT on NILs. Methods ARTIC (<ani:underline>A</ani:underline>bscopal effects in metastasized cancer patients treated with <ani:underline>R</ani:underline>adio<ani:underline>T</ani:underline>herapy and <ani:underline>I</ani:underline>mmune <ani:underline>C</ani:underline>heckpoint inhibition) (ARO (Arbeitsgemeinschaft Radiologische Onkologie) 2022–10, DRKS00032390) retrospectively screened clinical records of patients with stage IV MM with PD under ICI. Patients received RT for metastases and had ≥1NIL outside the RT field (=control lesion). NILs were evaluated according to iRECIST (immune Response Evaluation Criteria in Solid Tumors): abscopal response (AR): size reduction ≥30%, abscopal progression (AP): size increase ≥20%, abscopal control (AC): all others. Patients with AR and/or AC were categorized as abscopal benefit (AB), patients with AP and/or mixed response=no AB. RT details and factors influencing AR were analyzed. Results After screening clinical records of 3773 patients with stage IV tumor from 12 oncological centers in Germany, we identified 47 patients with MM with 115 NILs. RT targeted metastases in brain (38.3%) and lung (19.1%), primarily using stereotactic RT (29.8%). The mean time interval between the end of ICI and RT was 3.53±5.67 months. AR was achieved in 19.1% of patients and 29.1% of lesions. Compared with stereotactic RT, normofractionated or other (non-stereotactic) RT regimens significantly reduced the probability of AB (OR=0.092, p=0.04, 95%CI: (0.007 to 0.758)). Longer ICI-to-RT intervals were associated with reduced mortality risk (HR=0.703, p=0.007, 95%CI: (0.544 to 0.908)). Patients with AB had a longer median overall (17 vs 9 months) and a longer median progression-free survival (4 vs 2 months). Conclusions RT can induce AR in patients with MM with PD under ICI, particularly with hypofractionated regimens and long ICI-to-RT intervals. Our findings can serve as a reference for designing prospective trials.

Details

Original languageEnglish
Article numbere012717
JournalJournal for immunotherapy of cancer
Volume13
Issue number10
Publication statusPublished - 2 Oct 2025
Peer-reviewedYes

External IDs

PubMed 41043856

Keywords

Sustainable Development Goals

Keywords

  • Abscopal, Immune modulatory, Immunotherapy, RADIOTHERAPY, Solid tumor