A review of radiation induced abscopal effect: combining radiotherapy and immunotherapy to treat the untreated distant metastatic tumours

Abstract Background: Radiotherapy is an effective and significant mode of definitive cancer treatment with well-established local tumour control success, especially in the treatment of localised tumours. Although, for metastatic disease, the role of radiotherapy has generally been limited to palliation of symptoms. In the treatment of metastatic diseases settings, the radiation therapy technique has always been confronted with the challenge of the simultaneous treatment of all of the various distant metastatic tumour sites, however, some recent evidence suggests that radiotherapy can potentially induce anticancer immune responses whose effectors potentially migrate to distant metastatic tumours to provoke their regression in cancer patients. Thus, unirradiated distant metastatic tumour sites can exhibit a delayed therapeutic response termed the abscopal effect. Materials and methods: This paper reports on a review of the abscopal effect, including its biological mechanism, the effect of radiation dose and fractionation regime and the timing of immunotherapy administration on radiotherapy-induced abscopal effect, the enhancement of radiotherapy-induced abscopal effects with immunotherapy, the effect of the location of the irradiated tumour and the radiotherapy of multiple tumour sites on the likelihood and effectiveness of inducing abscopal responses in the preclinical and clinical settings and also reports on some evidence of clinical observations in patients. Conclusions: Although abscopal effects of radiotherapy are still relatively rare in patients, it has gained a lot of interest due to recent development and use of immunotherapy strategies incorporating combinations of targeted immunomodulators and immune checkpoint blockade with radiation therapy. The enhancement of cancer immunotherapy could potentially enable the translation of the concept of abscopal effect into the clinics as a new strategy to induce therapeutically effective anti-tumour immune responses in cancer patients. The combination of radiotherapy and immunotherapy has the potential to expand the role of radiotherapy from a purely local tumour control treatment to play a significant role in advanced and metastatic tumour control and this could likely lead to a paradigm shift in the treatment of patients with metastatic cancer.