Radiotherapy for non-small cell lung cancer in the immunotherapy era: the opportunity and challenge—a narrative review

Immunotherapy has radically changed the clinical management of patients with cancer in recent years. Immune checkpoint inhibitors (ICIs) reversing the immunosuppressive effects of the tumor microenvironment are one type of immunotherapy, several of which are approved by the US Food and Drug Administration (FDA) as first-line treatments for patients with non-small cell lung cancer (NSCLC). However, response rates to ICIs are around 19–47% among patients with advanced NSCLC. As a result, the development of combined ICI and radiotherapy has begun with the aim of strengthening patients’ antitumor immunity. Radiotherapy with substantial technological improvements not only achieves local tumor control through the induction of deoxyribonucleic acid (DNA) damage in irradiated regions, but also has the potential to mediate immunostimulatory effects that could result in tumor regression beyond irradiated regions. At present, numerous preclinical and clinical research are investigating the efficiency and safety of combining ICI with radiotherapy. The PACIFIC trial showed that combining chemoradiotherapy with ICI could improve clinical outcomes. In this review, we summarize the rationale for combining radiotherapy with immunotherapy. We also discuss the opportunities and challenges of combination therapy, including the timing of radiotherapy, optimal dose and fractionations, radiotherapy target and target volume, acquired resistance, patient selection, and radioimmunotherapy toxicity.