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

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.