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  • Perspective
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OPINION

Time to abandon single-site irradiation for inducing abscopal effects

Nature Reviews Clinical Oncology volume 16, pages 123–135 (2019)Cite this article

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Abstract

Considerable interest is being directed toward combining immune-checkpoint inhibition (ICI) with radiotherapy to improve response rates to ICI, which have been disappointingly low at around 15–30% among patients with advanced-stage cancers other than melanoma. Since a case report published in 2012, in which authors described the resolution of metastatic disease after irradiation of a single lesion in a patient who had been receiving ICI, hundreds of clinical trials have been launched with the aim of testing the safety and/or efficacy of radiotherapy in combination with immunotherapy, nearly all of which use this single-site irradiation, or ‘abscopal’, approach. However, emerging preclinical and clinical evidence suggests that this approach likely produces suboptimal results. In this Perspective, we describe this evidence and provide a biological rationale supporting the abandonment of the single-site abscopal approach. We instead advocate exploring comprehensive irradiation of multiple/all lesions in order to enhance the likelihood of obtaining meaningful clinical outcomes — if such a clinical synergy between radiation and ICI does exist — before the failure of the current, single-site approach leads to the potential premature and inappropriate abandonment of radiotherapy in combination with ICI altogether.

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Fig. 1: Radiation activates the host immune system.
Fig. 2: Irradiation of all disease sites, rather than just one.
Fig. 3: Multisite radiation is safe and feasible with state-of-the-art radiotherapy techniques.

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Acknowledgements

The work of the authors is supported in part by Cancer Center Support (Core) Grant CA016672 from the National Institutes of Health to The University of Texas MD Anderson Cancer Center, and by the Joan and Herb Kelleher Charitable Foundation. The authors gratefully acknowledge the editorial contributions of C. F. Wogan, MS, ELS, of the MD Anderson Division of Radiation Oncology in developing this report.

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  1. Department of Radiation Oncology, Unit 97, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Eric D. Brooks & Joe Y. Chang

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J.Y.C. reports receiving financial support from Varian for travel to meetings in the past 3 years, grants from Bristol-Myers Squibb, being a shareholder of Global Oncology One (in unrelated work), and participating in advisory scientific discussions supported by AstraZeneca. E.D.B. declares no competing interests.

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Brooks, E.D., Chang, J.Y. Time to abandon single-site irradiation for inducing abscopal effects. Nat Rev Clin Oncol 16, 123–135 (2019). https://doi.org/10.1038/s41571-018-0119-7

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