Stage III Non–Small-Cell Lung Cancer Treated With Concurrent Chemoradiation Followed or Not by Consolidation Chemotherapy: A Survival Analysis From a Brazilian Multicentric Cohort

Lima, Vladmir Cláudio Cordeiro de; Baldotto, Clarissa; Barrios, Carlos H.; Mascarenhas, Eldsamira; Zukin, Mauro; Mathias, Clarissa; Zaffaroni, Facundo; Nery, Rodrigo; Madeira, Gabriel; Amadio, Alex Vieira; Coelho, Juliano Cé; Geib, Guilherme; Simões, M.F.; Castro, Gilberto de

doi:10.1200/jgo.17.00214

“…Urvay et al retrospectively reviewed the clinical records of 148 patients with advanced inoperable stage IIIA or IIIB NSCLC diagnosed from 2007 through 2015 in Turkey, who had undergone concurrent or sequential chemoradiation, and estimated median survival as being 19 months and overall 3-year survival as being 27% (57). Similar results were obtained after the analysis of a retrospective cohort that comprised 165 Brazilian patients treated with chemoradiation therapy followed by consolidated chemotherapy, in which the median OS was 9 months, and the 1-, 2-and 3-year survival rates were 64.8%, 45.5% and 32.2%, respectively (58). OS did not differ among patients who received consolidated therapy (23 vs. 18 months; P=0.128).…”

Section: Stage III Lung Cancer: 1- 3-and 5-year Survivalsupporting

confidence: 77%

Epidemiology of stage III lung cancer: frequency, diagnostic characteristics, and survival

Casal-Mouriño¹,

Ruano-Raviña²,

Lorenzo-González³

et al. 2021

Transl Lung Cancer Res

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Stage III non-small cell lung cancer (NSCLC) includes a highly heterogeneous group of patients with differences in the extent and localization of disease. Many aspects of stage III disease are controversial. The data supporting treatment approaches are often subject to a number of limitations, due to the heterogeneous patient populations involved in the trials. Furthermore, the definition of stage III disease has changed over time, and early studies were frequently inadequately powered to detect small differences in therapeutic outcome, were not randomized, or had a limited follow-up times. Major improvements in therapy, including the use of more active chemotherapy agents and refinements in radiation and surgical techniques, also limit the interpretation of earlier clinical trials. Lastly, improvements in pretreatment staging have led to reclassification of patients with relatively minimal metastatic disease as stage IV rather than stage III, leading to an apparent increase in the overall survival of both stage III and IV patients. Median overall stage III NSCLC survival ranges from 9 to 34 months. Higher survival rates are observed in younger Caucasian women with good performance status, adenocarcinoma, mutations, stage IIIA, and in patients with multidisciplinary-team-based diagnoses.

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“…Globally, pulmonary carcinoma exhibits the highest incidence and mortality rate [ 1 , 2 ]. Non-small cell lung cancer (NSCLC) accounts for between 80 and 85% of all pulmonary carcinoma [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

“…Globally, pulmonary carcinoma exhibits the highest incidence and mortality rate [ 1 , 2 ]. Non-small cell lung cancer (NSCLC) accounts for between 80 and 85% of all pulmonary carcinoma [ 1 ]. Recent advances in the diagnosis and treatment of NSCLC have been remarkable, however, the 5-year overall survival (OS) rate remains below 21% [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

EZH2 as a prognostic-related biomarker in lung adenocarcinoma correlating with cell cycle and immune infiltrates

Fan¹,

Zhang²,

Han

³

et al. 2023

BMC Bioinformatics

5

0

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Backgrounds It has been observed that high levels of enhancer of zeste homolog 2 (EZH2) expression are associated with unsatisfactory prognoses and can be found in a wide range of malignancies. However, the effects of EZH2 on Lung Adenocarcinoma (LUAD) remain elusive. Through the integration of bioinformatic analyses, the present paper sought to ascertain the effects of EZH2 in LUAD. Methods The TIMER and UALCAN databases were applied to analyze mRNA and protein expression data for EZH2 in LUAD. The result of immunohistochemistry was obtained from the HPA database, and the survival curve was drawn according to the library provided by the HPA database. The LinkedOmics database was utilized to investigate the co-expressed genes and signal transduction pathways with EZH2. Up- and down-regulated genes from The Linked Omics database were introduced to the CMap database to predict potential drug targets for LUAD using the CMap database. The association between EZH2 and cancer-infiltrating immunocytes was studied through TIMER and TISIDB. In addition, this paper explores the relationship between EZH2 mRNA expression and NSCLC OS using the Kaplan–Meier plotter database to further validate and complement the research. Furthermore, the correlation between EZH2 expression and EGFR genes, KRAS genes, BRAF genes, and smoking from the Cancer Genome Atlas (TCGA) database is analyzed. Results In contrast to paracancer specimens, the mRNA and protein levels of EZH2 were higher in LUAD tissues. Significantly, high levels of EZH2 were associated with unsatisfactory prognoses in LUAD patients. Additionally, the coexpressed genes of EZH2 were predominantly associated with numerous cell growth-associated pathways, including the cell cycle, DNA replication, RNA transport, and the p53 signaling pathway, according to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. The results of TCGA database revealed that the expression of EZH2 was lower in normal tissues than in lung cancer tissues (p < 0.05). Smoking was associated with elevated EZH2 expression (p < 0.001). EZH2 was highly expressed in lung cancers with positive KRAS expression, and the correlation was significant in lung adenocarcinoma (r = 0.3129, p < 0.001). CMap was applied to determine the top 15 positively correlated drugs/molecules and the top 15 negatively correlated drugs/molecules. MK-1775, MK-5108, fenbendazole, albendazole, BAY-K8644, evodiamine, purvalanol-a, mycophenolic-acid, PHA-793887, and cyclopamine are potential drugs for patients with lung adenocarcinoma and high EZH2 expression. Conclusions Highly expressed EZH2 is a predictor of a suboptimal prognosis in LUAD and may serve as a prognostic marker and target gene for LUAD. The underlying cause may be associated with the synergistic effect of KRAS, immune cell infiltration, and metabolic processes.

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“…Lung cancer is the cancer that has the highest incidence and mortality rate worldwide [ 1 , 2 ]. NSCLC accounts for 80% to 85% of all lung cancer cases [ 3 ]. In recent years, great progress in the diagnosis and treatment of NSCLC has been achieved, yet the overall five-year survival rate is still less than 21% [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Prognostic Value of EZH2 in Non-Small-Cell Lung Cancers: A Meta-Analysis and Bioinformatics Analysis

Fan

¹

,

Zhang

²

,

Qi

³

et al. 2020

BioMed Research International

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Background. The prognosis of non-small-cell lung cancer (NSCLC) has not been significantly improved. In the past several years, research on epigenetics is in full swing. There is a focus on the gene EZH2; however, its role as a predictor of the prognosis of NSCLC is in the debate. Objective. To clarify if the expression level of EZH2 can influence the prognosis of NSCLC and explain its prognostic value. Methods. We have systematically searched PubMed, Web of Science, and Cochrane library, screened relevant articles, and conducted a meta-analysis on the expression level of EZH2 in NSCLC. We collected the hazard ratio (HR) and the 95% confidence interval (CI) and used STATA 12.0 to calculate the combined result of EZH2 overall survival. In addition, we conducted subgroup analyses, a sensitivity analysis, and a funnel plot to test the reliability of the results. We further validated these meta-analysis results using the Kaplan-Meier plotter database and The Cancer Genome Atlas (TCGA) database. In addition, we have investigated the correlation between EZH2 expression and EGFR expression, KRAS expression, BRAF expression, and smoking in TCGA database to further explore the mechanism behind the influence of high EZH2 expression on lung cancer prognosis. Results. 13 studies including 2180 participants were included in the meta-analysis. We found that high expression of EZH2 indicates a poor prognosis of NSCLC ( HR = 1.65 and 95% CI 1.16-2.35; p ≤ 0.001 ). Subgroup analyses showed high heterogeneity in stages I-IV ( I 2 = 85.1 % and p ≤ 0.001 ) and stages I-III ( I 2 = 66.9 % and p = 0.029 ) but not in stage I ( I 2 = 0.00 % and p = 0.589 ). In the Kaplan-Meier plotter database, there was a high expression in 963 cases and low expression in 964 cases ( HR = 1.31 and 95% CI 1.15-1.48; p < 0.05 ). Further analysis found that the high expression of EZH2 was statistically significant in lung adenocarcinoma ( HR = 1.27 and 95% CI 1.01−1.6; p = 0.045 ), but not in lung squamous cell carcinoma ( HR = 1.03 and 95% CI 0.81−1.3; p = 0.820 ). The results of the TCGA database showed that the expression of EZH2 in normal tissues was lower than that in lung cancer tissues ( p < 0.05 ). Smoking was associated with high expression of EZH2 ( p < 0.001 ). EZH2 was also highly expressed in lung cancers with positive KRAS expression, and the correlation was positive in lung adenocarcinoma ( r = 0.3129 and p < 0.001 ). The correlation was also positive in lung squamous cell carcinoma ( r = 0.3567 and p < 0.001 ). EZH2 expression was positively correlated with BRAF expression ( r = 0.2397 and p < 0.001 ), especially in lung squamous cell carcinoma ( r = 0.3662 and p < 0.001 ). In lung squamous cell carcinoma, a positive yet weak correlation was observed between EZH2 expression and EGFR expression ( r = 0.1122 and p < 0.001 ). Conclusions. The high expression of EZH2 indicates a poor prognosis of NSCLC, which may be related to tumor stage or cancer type. EZH2 may be an independent prognostic factor for NSCLC. EZH2 high expression or its synergistic action with KRAS and BRAF mutations affects the prognosis of non-small-cell lung cancer.

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Stage III Non–Small-Cell Lung Cancer Treated With Concurrent Chemoradiation Followed or Not by Consolidation Chemotherapy: A Survival Analysis From a Brazilian Multicentric Cohort

Cited by 3 publications

References 22 publications

Epidemiology of stage III lung cancer: frequency, diagnostic characteristics, and survival

Epidemiology of stage III lung cancer: frequency, diagnostic characteristics, and survival

EZH2 as a prognostic-related biomarker in lung adenocarcinoma correlating with cell cycle and immune infiltrates

Prognostic Value of EZH2 in Non-Small-Cell Lung Cancers: A Meta-Analysis and Bioinformatics Analysis

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