The abscopal effect of local radiotherapy: using immunotherapy to make a rare event clinically relevant

  • Kobe Reynders
    Correspondence
    Corresponding author at: Experimental Radiation Oncology, Herestraat 49, Postbus 815, B-3000 Leuven, Belgium. Tel.: +32 16346282, +32 16372142.
    Affiliations
    KU Leuven – University of Leuven, Department of Oncology, Experimental Radiation Oncology, University Hospitals Leuven, Department of Radiation Oncology, B-3000 Leuven, Belgium
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  • Tim Illidge
    Affiliations
    Institute of Cancer Sciences, University of Manchester, Christie NHS Foundation Trust, Manchester Academic Health Sciences Centre, Wilmslow Road, Withington M20 4BX, United Kingdom
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  • Shankar Siva
    Affiliations
    Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne 3002, Australia

    Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville 8006, Australia
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  • Joe Y. Chang
    Affiliations
    Department of Radiation Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
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  • Dirk De Ruysscher
    Affiliations
    KU Leuven – University of Leuven, Department of Oncology, Experimental Radiation Oncology, University Hospitals Leuven, Department of Radiation Oncology, B-3000 Leuven, Belgium
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Published:March 28, 2015DOI:https://doi.org/10.1016/j.ctrv.2015.03.011

      Highlights

      • Current clinical and preclinical data of the abscopal effect is summarized.
      • The abscopal effect is linked with the immunogenic properties of irradiation.
      • Radiotherapy has a potential synergy with immune agents.
      • The issues that come with combining radiotherapy and immune agents are addressed.

      Abstract

      Background

      Recently, immunologic responses to localized irradiation are proposed as mediator of systemic effects after localized radiotherapy (called the abscopal effect). Here, we give an overview of both preclinical and clinical data about the abscopal effect in particular and link them with the immunogenic properties of radiotherapy.

      Methods

      We searched Medline and Embase with the search term “abscopal”, “(non-targeted irradiation) OR (non-targeted radiotherapy)” and “distant bystander” from 1960 until July, 2014. Only papers that cover radiotherapy in an oncological setting were selected and only if no concurrent cytotoxic treatment was given. Targeted immune therapy was allowed.

      Results

      Twenty-three case reports, one retrospective study and 13 preclinical papers were selected. Eleven preclinical papers used a combination of immune modification and radiotherapy to achieve abscopal effects. Patient age range (28–83 years) and radiation dose (median total dose 32 Gy) varied. Fractionation size ranged from 1.2 Gy to 26 Gy. Time to documented abscopal response ranged between less than one and 24 months, with a median reported time of 5 months. Once an abscopal response was achieved, a median time of 13 months went by before disease progression occurred or the reported follow-up ended (range 3–39 months).

      Conclusion

      Preclinical data points heavily toward a strong synergy between radiotherapy and immune treatments. Recent case reports already illustrate that such a systemic effect of radiotherapy is possible when enhanced by targeted immune treatments. However, several issues concerning dosage, timing, patient selection and toxicity need to be resolved before the abscopal effect can become clinically relevant.

      Keywords

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