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Review
. 2015 Jun;41(6):503-10.
doi: 10.1016/j.ctrv.2015.03.011. Epub 2015 Mar 28.

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

Kobe Reynders  1 , Tim Illidge  2 , Shankar Siva  3 , Joe Y Chang  4 , Dirk De Ruysscher  5
Affiliations
Review

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

Kobe Reynders et al. Cancer Treat Rev. 2015 Jun.

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 (28-83years) and radiation dose (median total dose 32Gy) varied. Fractionation size ranged from 1.2Gy to 26Gy. Time to documented abscopal response ranged between less than one and 24months, with a median reported time of 5months. Once an abscopal response was achieved, a median time of 13months went by before disease progression occurred or the reported follow-up ended (range 3-39months).

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: Abscopal effect; Immune therapy; Irradiation; Radiotherapy.

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Figures

Figure 1
Figure 1. Immunogenic cell death
Endoplasmatic reticulum stress induced by radiotherapy leads to apoptotic release of DAMPs such as ATP (find-me signal) and membrane blebs with the CRT/ERp57 complex (eat-me signal).
Figure 2
Figure 2. Search results
Breakdown of the number of papers identified according to the search strategy and selection criteria.
See this image and copyright information in PMC

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