Search

Objectives: Comprehensive cross-interaction of multiple programmed cell death (PCD) patterns in the patients with lung adenocarcinoma (LUAD) have not yet been thoroughly investigated., Methods: Here, we collected 19 different PCD patterns, including 1911 PCD-related genes, and developed an immune-derived multiple programmed cell death index (MPCDI) based on machine learning methods., Results: Using the median MPCDI scores, we categorized the LUAD patients into two groups: low-MPCDI and high-MPCDI. Our analysis of the TCGA-LUAD training cohort and three external GEO cohorts (GSE37745, GSE30219, and GSE68465) revealed that patients with high-MPCDI experienced a more unfavorable prognosis, whereas those with low-MPCDI had a better prognosis. Furthermore, the results of both univariate and multivariate Cox regression analyses further confirmed that MPCDI serves as a novel independent risk factor. By combining clinical characteristics with the MPCDI, we constructed a nomogram that provides an accurate and reliable quantitative tool for personalized clinical management of LUAD patients. The findings obtained from the analysis of C-index and the decision curve revealed that the nomogram outperformed various clinical variables in terms of net clinical benefit. Encouragingly, the low-MPCDI patients are more sensitive to commonly used chemotherapy drugs, which suggests that MPCDI scores have a guiding role in chemotherapy for LUAD patients., Conclusion: Therefore, MPCDI can be used as a novel clinical diagnostic classifier, providing valuable insights into the clinical management and clinical decision-making for LUAD patients., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Background: The prognostic impact and clinicopathological characteristics of extracapsular lymph node involvement (ECLNI) in patients with surgically resected lung adenocarcinoma (LUAD) remain unknown in the context of the eighth edition N classification., Patients and Methods: We retrospectively reviewed 279 patients with stage II-IIIA LUAD who underwent lobectomy and lymphadenectomy. The correlations of ECLNI presence and clinicopathological profiles were analyzed. We also assessed the impact of ECLNI on the postoperative survival of pN1 and pN2 LUAD patients., Results: ECLNI-positive status was more common in patients with high lymph node yield and in patients with multiple stations involved. The logistic regression model identified tumor spread through air spaces, micropapillary component, cribriform component, and nodal stage as predictive factors for ECLNI presence. LUAD patients with ECLNI presence had an increased risk of locoregional recurrence compared with those without (p < 0.001). Presence of ECLNI was confirmed as an independent risk factor for worse recurrence-free survival (RFS) (p < 0.001) and overall survival (OS) (p < 0.001) in the entire cohort. Among the 61 patients with ECLNI(+)pN2 disease, our analysis revealed that adjuvant radiation was a significant predictor of improved RFS and OS. In addition, ECLNI status provides additional precision in stratifying pN1 and pN2 patients with significantly different RFS and OS., Conclusions: Our data suggest that ECLNI remains a strong prognosticator of unfavorable OS and RFS for LUADs in the context of the eighth edition N classification. Adjuvant radiation should be actively considered for pN1b and pN2 LUAD patients with ECLNI presence.

Background: This study sought to determine the optimal number of examined lymph nodes (ELNs) and examined node stations (ENSs) in patients with radiologically pure-solid non-small cell lung cancer (NSCLC) who underwent lobectomy and ipsilateral lymphadenectomy by investigating the impact of ELNs and ENSs on accurate staging and long-term survival., Materials and Methods: Data from 6 institutions in China on resected clinical stage I-II (cI-II) NSCLCs presenting as pure-solid tumors were analyzed for the impact of ELNs and ENSs on nodal upstaging, stage migration, recurrence-free survival (RFS), and overall survival (OS). Correlations between different endpoints and ELNs or ENSs were fitted with a LOWESS smoother, and the structural break points were determined by Chow test., Results: Both ELNs and ENSs were identified as independent prognostic factors for OS (ENS hazard ratio [HR], 0.690; 95% CI, 0.597-0.797; P<.001; ELN HR, 0.950; 95% CI, 0.917-0.983; P=.004) and RFS (ENS HR, 0.859; 95% CI, 0.793-0.931; P<.001; ELN HR, 0.960; 95% CI, 0.942-0.962; P<.001), which were also associated with postoperative nodal upstaging (ENS odds ratio [OR], 1.057; 95% CI, 1.002-1.187; P=.004; ELN OR, 1.186; 95% CI, 1.148-1.226; P<.001). A greater number of ELNs and ENSs correlated with a higher accuracy of nodal staging and a lower probability of stage migration. Cut-point analysis revealed an optimal cutoff of 18 LNs and 6 node stations for stage cI-II pure-solid NSCLCs, which were validated in our multi-institutional cohort., Conclusions: Extensive examination of LNs and node stations seemed crucial to predicting accurate staging and survival outcomes. A threshold of 18 LNs and 6 node stations might be considered for evaluating the quality of LN examination in patients with stage cI-II radiologically pure-solid NSCLCs.

Objectives: Conflicting results have been reported about the prognostic value of programmed death ligand 1 (PD-L1) protein and gene expression in lung adenocarcinoma., Methods: We performed a comprehensive online search to explore the association between PD-L1 expression (protein and messenger RNA) and overall survival (OS) or disease-free survival. Outcomes also included pooled rates of high PD-L1 protein expression in different cell types, per threshold used and per antibody used. A pooled gene expression analysis was also performed on 3 transcriptomic data sets that were obtained from The Cancer Genome Atlas database and the Gene Expression Omnibus database., Results: A total of 6488 patients from 25 studies were included. The pooled results suggested that high PD-L1 expression was associated with shorter OS [hazard ratio (HR) 1.57; P < 0.001] and disease-free survival (HR 1.341; P = 0.037) in the overall population. The overall pooled rate of high PD-L1 protein expression was 29% (95% confidence interval 23-34%) in tumour cells. In subgroup analysis, high PD-L1 protein expression in tumour cells predicted worse OS and disease-free survival. A pooled analysis of The Cancer Genome Atlas and Gene Expression Omnibus data sets revealed that higher levels of PD-L1 messenger RNA predicted poorer OS in the entire population., Conclusions: This study is, to our knowledge, the largest pooled analysis on the subject to shed light on the high expression rate of PD-L1 and the prognostic value of high PD-L1 expression in resected lung adenocarcinomas. PD-L1 gene expression is a promising prognostic factor for patients with surgically resected lung adenocarcinoma. Standardization of staining should be underscored prior to routine implementation., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: A series of studies have assessed the clinicopathological features and prognostic impact of spread through air spaces (STAS) in non-small cell lung cancer (NSCLC) bringing conflicting findings so far. We performed a systematic review and meta-analysis to synthesize the available evidence regarding to the prognostic value of STAS in NSCLCs., Methods: Studies were identified by searching databases including PubMed, EMBASE, Web of Science, and Cochrane Library up to August 2018 without language restrictions. Results of these searches were filtered according to a set of eligibility criteria and analyzed in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines., Results: A total of 3,754 patients from 14 studies were selected for the present study. The pooled results suggested that presence of STAS was associated with worse recurrence-free survival (hazard ratio [HR], 1.975; 95% confidence interval [CI], 1.691 to 2.307; p < 0.001) and overall survival (HR, 1.75; 95% CI, 1.375 to 2.227; p < 0.001) in NSCLCs. Subgroup analysis by histology type indicated the presence of STAS was significantly associated with inferior recurrence-free survival in resected lung adenocarcinoma (n = 7; HR, 2.288; 95% CI, 1.843 to 2.840; I 2  = 7.80%), lung squamous cell carcinoma (n = 3; HR, 1.622; 95% CI, 1.279 to 2.056; I 2  = 0%), and lung pleomorphic carcinoma (n = 1; HR, 4.76; 95% CI, 1.168 to 19.398). Additionally, a number of clinicopathological characteristics indicating STAS in NSCLCs are summarized., Conclusions: Our study indicates that tumor STAS was a potentially significant prognostic predictor for surgical patients with NSCLCs. The prognostic impact of STAS present in the resection margin remains undetermined. Further large-scale prospective studies are warranted to confirm the prognostic significance of STAS in patients with NSCLCs., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)