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OBJECTIVE: The objective of this article is to review the efficacy, safety, and evidence for current use and potential future uses of immune-checkpoint inhibitors (ICIs) in the management of resectable non-small cell lung cancer (NSCLC). DATA SOURCES: A literature review was carried out through PubMed to identify completed and ongoing clinical trials evaluating the use, efficacy, and safety of ICIs in the management of resectable NSCLC. DATA SUMMARY: To date, four phase 3 trials have emerged that have changed our treatment practice concerning the utilization of ICIs during the adjuvant and neoadjuvant settings. The IMpower010 and KEYNOTE-091 trials examined the application of adjuvant atezolizumab and pembrolizumab, respectively, following surgical resection and adjuvant chemotherapy. In the CheckMate 816 trial, the combination of nivolumab and chemotherapy as a neoadjuvant therapy received approval for patients with resectable NSCLC. Also, for patients with resectable NSCLC, the use of a pembrolizumab and chemotherapy combination as a perioperative therapy received approval based on the results of the KEYNOTE-671 trial. Apart from these trials, there are numerous phase 2 and phase 3 trials, some of which have been published while others are still in progress. CONCLUSION: Despite the promising outcomes from these trials there remain several unanswered questions. In this review, we will assess clinical trials involving adjuvant, neoadjuvant, and perioperative ICIs, aiming to address the unresolved questions related to these therapeutic approaches.
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OBJECTIVE: Systemic inflammatory indices and CD8(+) tumor infiltrating lymphocytes (TILs) in the tumor microenvironment are highly prognostic in colon cancer (CC) but combined assessment is less well studied. The purpose of this study was to investigate the prognostic and predictive value of CD8(+) TILs in combination with systemic inflammatory indices in patients with resected stage II-III colon cancer. PATIENTS AND METHODS: Patients with stage II-III CC (n = 304) diagnosed between 2008 and 2016 were included. Pan-immune inflammation value (PIV) was used as a comprehensive inflammatory index and was calculated as: [neutrophil count × platelet count × monocyte count]/lymphocyte count. The mean density of CD8+ TILs in the periphery and center of the tumor was assessed and dichotomized at the 75th percentile. Combined inflammation score (CIS) was classified as "high" in patients with high PIV (>median) plus low mean CD8(+) TILs density, and CIS "low" in the remaining patients. RESULTS: 5-year DFS was 71% (78% in stage II, 63.4% in stage III). PIV was higher in right colon tumors, T4 tumors and in patients with obstruction / perforation. CD8(+) TIL density was lower in node positive tumors. High PIV and low CD8(+) TILs were associated with shorter disease-free survival (DFS). In multivariate analysis; age > 65 years, stage III disease and high CIS (PIVhigh / CD8low) were associated with shorter DFS. Among patients with stage II disease, patients with high CIS (PIVhigh / CD8low) derived significant benefit from adjuvant chemotherapy while those with low CIS derived no benefit. CONCLUSION: Combined inflammation score may represent a new prognostic factor for localized colon cancer and predictor of chemotherapy response in patients with stage II disease.