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Systemic Effects of Radiation Therapy-Induced Abscopal Responses in Patients with Advanced Lung Cancer

Background: Out-of-field tumor regression effects of radiation therapy (abscopal response) have been sporadically observed in the past, but they have only recently gained significant importance due to the use of innovative high-precision radiation delivery devices for the treatment of various cancers including non-small cell lung cancer (NSCLC). In this study, we provide a detailed overview of the current state of knowledge and clinical experience of radiation therapy-induced abscopal effects in patients with advanced NSCLC. Summary: Peer-reviewed published clinical evidence on the abscopal effect of radiation therapy was collected using electronic databases such as MEDLINE via PubMed and Google Scholar. The clinical data on the abscopal effect of radiation therapy were reviewed and the outcomes have been summarized. Most studies describing the abscopal effects of radiation therapy in patients with advanced NSCLC have been in the form of either case reports or small cohort studies. Although the exact molecular mechanisms for the abscopal effect are yet to be established, current evidence indicates that tumor cell destruction induced by local radiation therapy releases tumor antigens, which stimulate the immune system of the host to activate the body’s immune effector cells systemically and trigger the regression of distant nonirradiated cancer cells. These off-target antitumor effects of radiation therapy provide an opportunity to explore the use of the radiation therapy in combination with novel immunotherapy agents to maximize treatment outcomes in patients with advanced NSCLC and other cancers. Key Message: The findings suggest that radiation therapy has the ability to induce abscopal effects with an increased potential to boost these effects when it is used in combination with immunotherapy for the treatment of patients with advanced NSCLC and other cancers. Clinical trials investigating radiation therapy-induced abscopal effects may lead to a dramatic change in its use especially when it is combined with immunotherapy for the treatment of patients with advanced NSCLC.