{
  "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 ( Abscopal effects in metastasized cancer patients treated with RadioTherapy and Immune Checkpoint 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 ≥1 NIL 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.",
  "authors": [
    {
      "affiliations": [
        "Department of Radiation Oncology, Cyberknife and Radiotherapy, University Hospital Cologne, Cologne, Germany",
        "University Hospital Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, CIO ABCD, Cologne, Germany"
      ],
      "name": "Simone Ferdinandus"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany",
        "Department of Radiation Oncology, University of Leipzig Medical Center, Leipzig, Germany"
      ],
      "name": "Alexander Rühle"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany"
      ],
      "name": "Allison Lamrani"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany",
        "Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany"
      ],
      "name": "Charlotte Frei"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany"
      ],
      "name": "Justus Kaufmann"
    },
    {
      "affiliations": [
        "Department of Radiotherapy and Radiation Oncology, Jena University Hospital, Jena, Germany",
        "Clinician Scientist Program OrganAge, Jena University Hospital, Jena, Germany"
      ],
      "name": "Matthias Mäurer"
    },
    {
      "affiliations": [
        "Department of Radiotherapy and Radiation Oncology, Jena University Hospital, Jena, Germany",
        "Clinician Scientist Program, Interdisciplinary Center for Clinical Research (IZKF), Jena University Hospital, Jena, Germany"
      ],
      "name": "Georg Wurschi"
    },
    {
      "affiliations": [
        "Clinic for Radiation Oncology and Radiotherapy, Luedenscheid Clinic, Luedenscheid, Germany"
      ],
      "name": "Ping Jiang"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany",
        "German Cancer Consortium (DKTK), partner site Berlin, a partnership between DKFZ and Charité – Universitätsmedizin Berlin, Berlin, Germany"
      ],
      "name": "Felix Ehret"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, University Medical Hospital, Hamburg-Eppendorf, Hamburg, Germany"
      ],
      "name": "Andrea Baehr"
    },
    {
      "affiliations": [
        "Department of Radiotherapy and Radiation Oncology, Outpatient Center of the University Medical Hospital Hamburg-Eppendorf, Hamburg, Germany"
      ],
      "name": "Annika Hardt"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany",
        "Department of Radiation Oncology, University Hospital Tübingen, Tübingen, Germany"
      ],
      "name": "Raphael Bodensohn"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany"
      ],
      "name": "Lukas Käsmann"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, Hospital of Bolzano (SABES-ASDAA)",
        "Teaching Hospital of Paracelsus Meodical University Salzburg, Salzburg, Austria, Bolzano-Bozen, Italy"
      ],
      "name": "Maria Waltenberger"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, University Hospital Bonn, Bonn, Germany"
      ],
      "name": "Davide Scafa"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, University Hospital Bonn, Bonn, Germany",
        "Institute of Experimental Oncology, University Hospital Bonn, Bonn, Germany"
      ],
      "name": "Julian P Layer"
    },
    {
      "affiliations": [
        "OncoRay – National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany",
        "Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany"
      ],
      "name": "Esther G C Troost"
    },
    {
      "affiliations": [
        "OncoRay – National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany",
        "Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany"
      ],
      "name": "Sally A Elkhamisy"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, University Hospital Dusseldorf, Medical Faculty, Heinrich-Heine-University Dusseldorf, Dusseldorf, Germany"
      ],
      "name": "Danny Jazmati"
    },
    {
      "affiliations": [
        "University Hospital Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, CIO ABCD, Cologne, Germany",
        "Department of Dermatology and Venereology, Faculty of Medicine and University Hospital Cologne, Cologne, Germany"
      ],
      "name": "Cindy Franklin"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, Cyberknife and Radiotherapy, University Hospital Cologne, Cologne, Germany"
      ],
      "name": "Sebastian Neppl"
    },
    {
      "affiliations": [
        "Institute of Medical Statistics and Computational Biology, Medical Faculty and University Hospital, University of Cologne, Cologne, Germany"
      ],
      "name": "Anna Hagemeier"
    },
    {
      "affiliations": [
        "University Hospital Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, CIO ABCD, Cologne, Germany",
        "Department of Radiation Oncology, University Hospital Bonn, Bonn, Germany"
      ],
      "name": "Maike Trommer"
    }
  ],
  "title": "Abscopal effects in patients with malignant melanoma treated with radiotherapy and immune checkpoint inhibition: analysis of a large observational multicenter study",
  "uid": "e5c679b0-db32-54c3-b8c8-e63fed04fcd5"
}