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53; 95% CI, 1.31-1.79) and SR similar OS (hazard ratio, 1.20; 95% CI, 0.87-1.67) compared with LB. SR was associated with similar survival compared with LB in a propensity score-matched multivariable analysis as well. WR was also associated with greater odds of >R0 resection compared with LB. CONCLUSIONS In this study, patients with limited-stage SCLC undergoing WR experienced worse survival compared with those undergoing LB; survival was similar between segmentectomy and LB. Immune checkpoint inhibitors have recently been demonstrated to improve survival in metastatic and locally advanced non-small cell lung cancer (NSCLC). Radiation therapy has a well-established role in the treatment of NSCLC and has more recently been shown to be immunostimulatory, with the potential to enhance the efficacy of immunotherapy. This comprehensive review details the current roles of radiation therapy and immune checkpoint inhibitors in NSCLC, discusses the intersection of these two modalities and their potential to have combined synergistic responses, and highlights existing preclinical and clinical data and ongoing clinical trials of combined immunotherapy and radiotherapy across all NSCLC stages. The advent of immune checkpoint blockade has revolutionized the management of advanced non-small cell lung cancer (NSCLC). Impressive results in the metastatic setting have prompted substantial interest in the application of these agents in earlier-stage disease. Applications of checkpoint blockade in the adjuvant setting are under investigation in several clinical trials. Early trials have demonstrated the safety and feasibility of the administration of checkpoint inhibitors in the neoadjuvant setting. Resection specimens demonstrate encouraging rates of pathologic response. There are several ongoing phase 3 studies comparing neoadjuvant combination chemotherapy and checkpoint blockade to chemotherapy alone in patients with resectable NSCLC. Immune checkpoint inhibitor (ICI) therapy has been approved for several solid tumors, including non-small cell lung cancer. ICIs have shown unprecedented durable responses and higher response rates than chemotherapy in selected patients. The development of biomarkers that serve as predictors of response is crucial for treatment selection. Evidence suggests that the response to immunotherapy depends on tumor genomics and the interactions with the immune system and the tumor microenvironment. This article reviews the data supporting the use of these biomarkers to optimize patient selection for these therapies and explores biomarkers that are the focus of ongoing research. Over the past year, the combination of platinum-based chemotherapy and immunotherapy has become the standard of care for patients with metastatic non-small-cell lung cancer with any programmed death ligand 1 tumor proportion score. There is preclinical evidence demonstrating potential synergistic immunomodulation with combination therapy by enhancing immune-mediated tumor death and by disrupting the immunosuppressive tumor microenvironment that prevents immune detection. This potential synergy or complementary activity has been demonstrated in clinical trials showing improved and durable responses with chemo-immunotherapy. Immunotherapy has transformed the treatment of many tumors. Robust data demonstrating improved overall survival and progression-free survival in patients treated with monoclonal antibodies have established immune checkpoint inhibitors as standard of care in stages III and IV non-small cell lung cancer. Nivolumab is effective in previously treated patients with metastatic non-small cell lung cancer. Pembrolizumab and atezolizumab are approved as monotherapy and in combination with other therapies. Ongoing trials investigate the potential role of immunotherapy in earlier disease settings. Identifying predictive biomarkers of response will further amplify the impact of immune checkpoint inhibitors in the treatment of non-small cell lung cancer. Five-year survival rates for patients with early-stage non-small cell lung cancer have room for improvement. Adjuvant chemotherapy results in a small but significant increase in overall survival at 5 years. Efforts to improve outcomes by intensifying adjuvant treatment, utilizing cancer-specific vaccines or tyrosine kinase inhibitors in unselected patients, have been unsuccessful. In addition to research with immune checkpoint inhibitors that are addressed in a separate article, ongoing studies to personalize adjuvant therapy either by selecting only patients with evidence of minimal residual disease or targeting tumor driver mutations are promising. Liquid biopsies for the diagnosis and treatment of lung cancer have developed rapidly, driven primarily by technical advances in sensitivity to detect circulating tumor DNA (ctDNA). Still, technical limitations such as the challenge of detecting low-level ctDNA variants and distinguishing tumor-related variants from clonal hematopoiesis remain. Sodium acrylate research buy With further technical advancements, new applications for ctDNA analysis are emerging including detection of post-treatment molecular residual disease (MRD), clinical trial selection, and early cancer detection. This chapter reviews the current state of ctDNA testing in NSCLC, the underlying technological advances enabling ctDNA detection, and the potential to expand ctDNA analysis to new applications. Lung cancer is a heterogeneous genomic disease. Smoking remains the primary cause. Genetic susceptibility and environmental exposures are responsible for 10% to 15% of cases. Targeted therapies improve survival in patients with tumors with oncogenic drivers. It is critical to expand our understanding of genetic alterations in non-small cell lung cancer to increase the available targeted therapies. Alterations beyond epidermal growth factor receptor (EGFR), ALK, and ROS1 exemplify lung cancer's complexity and the need for investments in precision therapy to extend patient survival and improve outcomes. This article covers genetic targets beyond EGFR, ALK and ROS1, their novel agents, challenges, and future directions.