Systemic Immunostimulatory Effects of Radiation Therapy Improves the Outcomes of Patients With Advanced NSCLC Receiving Immunotherapy

The understanding of localized radiation therapy's immunostimulatory properties combined with its well-known effects on the cell cycle and insights into the immunomodulation mechanisms that occur at the molecular and cellular levels has changed our traditional view of the anticancer effects of ionizing radiation. The potential interactions between the tumor's immune system and radiation therapy have revealed that local radiation has the ability to induce systemic antitumor responses in patients with advanced cancers. The recognition of systemic antitumor effects of radiation therapy has allowed investigators to begin uncovering the integral players in these pathways. Parallel to this, there has been progress in understanding how tumor immunology leads to the development of novel immunotherapies using immune checkpoint blockade therapies in the treatment of advanced cancers. To date there has been limited success in this benefiting only a small fraction of patients. The concept of priming the body's immune system by radiation to make less responsive tumors more responsive to immunotherapy provides an opportunity to explore the use of the combination of radiation therapy and immunotherapy for the treatment of advanced non-small cell lung cancer and other cancers. This article provides an overview of the current state of knowledge of the clinical experience using radiation therapy in combination with immune therapy and discusses the rationale for integrating these 2 modalities in the treatment of advanced non-small cell lung cancer. Available data supports the use of radiation therapy in combination with immunotherapy to achieve improved local and systemic tumor control. Evidence from the early clinical trials has shown that using radiation therapy and immune checkpoint blockade therapies together produces a greater clinical effect than using either modality alone. To maximize the clinical benefit and successful integration of these two modalities as well as optimizing radiation therapy dosing and its schedule, improvement in its field design and the development of reliable predictors of clinical tumor response needs to be established.