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Factors associated with distant recurrence following R0 lobectomy for pN0 lung adenocarcinoma.

ABSTRACT: OBJECTIVE:We investigated factors associated with distant recurrence, disease-free survival (DFS), and overall survival (OS) following R0 lobectomy for pathologic node-negative (pN0) lung adenocarcinoma. METHODS:We performed a retrospective analysis of a prospectively maintained database of patients with pT1-3N0M0 non-small cell lung cancer. Exclusion criteria included metachronous lung cancer, sublobar/incomplete resection, nonadenocarcinoma histology, and induction/adjuvant therapy. The primary outcome was distant recurrence; secondary outcomes were DFS and OS. Associations between variables and outcomes were assessed by Fine-Gray competing-risk regression for distant recurrence and Cox proportional hazard models for DFS and OS. RESULTS:Of 2392 patients identified with pT1-3N0M0 lung adenocarcinoma, 893 met the inclusion criteria. Median follow-up was 35.0 months (range, 0.1-202 months). Thirteen percent of patients developed recurrence (n = 115), of which 86% (n = 99) were distant. The 5-year cumulative incidence of distant recurrence was 14% (95% confidence interval [CI], 11%-17%). On multivariable analysis, pT2a (hazard ratio [HR], 2.84; 95% CI, 1.56-5.16; P = .001) and pT2b/3 (HR, 6.53; 95% CI, 3.17-13.5; P < .001) tumors were associated with distant recurrence. Recent surgery was associated with decreased distant recurrence (HR, 0.43; 95% CI, 0.20-0.91; P = .028), and lymphovascular invasion was strongly associated with distant recurrence (HR, 1.62; 95% CI, 1.00-2.63; P = .05). DFS was independently associated with pT stage (P < .001) and lymphovascular invasion (P = .004). CONCLUSIONS:In patients undergoing R0 lobectomy with pN0 lung adenocarcinoma, pT stage and lymphovascular invasion were associated with distant recurrence and decreased DFS. These observations support the inclusion of these patients in future clinical trials investigating adjuvant targeted and immunotherapies.

SUBMITTER: Brandt WS

PROVIDER: S-EPMC5816702 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Factors associated with distant recurrence following R0 lobectomy for pN0 lung adenocarcinoma.

Brandt Whitney S WS Bouabdallah Ilies I Tan Kay See KS Park Bernard J BJ Adusumilli Prasad S PS Molena Daniela D Bains Manjit S MS Huang James J Isbell James M JM Bott Matthew J MJ Jones David R DR

The Journal of thoracic and cardiovascular surgery 20171113 3

<h4>Objective</h4>We investigated factors associated with distant recurrence, disease-free survival (DFS), and overall survival (OS) following R0 lobectomy for pathologic node-negative (pN0) lung adenocarcinoma.<h4>Methods</h4>We performed a retrospective analysis of a prospectively maintained database of patients with pT1-3N0M0 non-small cell lung cancer. Exclusion criteria included metachronous lung cancer, sublobar/incomplete resection, nonadenocarcinoma histology, and induction/adjuvant ther ...[more]

PMID: 29246549

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Project description:Acute lung injury following lung resection surgery is not rare and often related to mortality. Although it has been a significant clinical and economic impact associated with increased intensive care unit (ICU) utilization, length of hospital stay, and associated cost, it is unpredictable. Aims of this study were to identify the modifiable risk factors of postoperative acute lung injury (PALI) following lung cancer surgery.We retrospectively analyzed medical records of 354 cases of lung cancer surgery in the tertiary university hospital from January 2012 to December 2015. PALI was defined as bilateral diffuse pulmonary infiltration on chest radiography, oxygenation failure (PaO2/FiO2 < 300), and absence of sign of left ventricular failure within a week from operation. We classified patients into either PALI group or non-PALI group and compared clinical characteristics of two groups. Logistic regression model was fitted to evaluate the risk factor of PALI.Among 354 cases of lung cancer surgeries, 287 lobectomies were analyzed. The overall incidence of PALI was 2.79% (8/287); four patients developed pneumonia with acute respiratory distress syndrome, and four patients developed ALI without clinical infection sign. There was no difference in baseline characteristics between PALI group and non-PALI group, but in operative parameters, a larger amount of fluid infusion was observed in PALI group. Logistic regression model showed underlying ischemic heart disease (OR 7.67, 95% CI 1.21-47.44, P = .03), interstitial lung disease (OR 30.36, 95% CI 2.30-401.52, P = .01), intravascular crystalloid fluid during surgery (OR 1.10, 95% CI 1.00-1.20, P = .04), and intraoperative transfusion (OR 56.4, 95% CI 3.53-901.39, P < .01) were risk factors of PALI. PALI increases ICU admission, use of mechanical ventilator, duration of hospital stay, and mortality.The clinical impact of PALI is marked. Significant independent risk factors have been identified in underlying ischemic heart disease, interstitial lung disease, intravascular crystalloid fluid, and transfusion during surgery.

Project description:The aim of this study was to clarify the significance of DNA methylation alterations at precancerous stages of lung adenocarcinoma. Using single-CpG resolution Infinium array, genome-wide DNA methylation analysis was performed in 36 samples of normal lung tissue obtained from patients without any primary lung tumor, 145 samples of non-cancerous lung tissue (N) obtained from patients with lung adenocarcinomas, and 145 samples of tumorous tissue (T). Stepwise progression of DNA methylation alterations from normal lung tissue to non-cancerous lung tissue obtained from patients with lung adenocarcinomas, and then tumorous tissue samples, was observed at 3,270 CpG sites, suggesting that non-cancerous lung tissue obtained from patients with lung adenocarcinomas was at precancerous stages with DNA methylation alterations. At CpG sites of 2,083 genes, DNA methylation status in samples of non-cancerous lung tissue obtained from patients with lung adenocarcinomas was significantly correlated with recurrence after establishment of lung adenocarcinomas. Among such recurrence-related genes, 28 genes are normally unmethylated (average ?-values based on Infinium assay in normal lung tissue samples was less than 0.2) and their DNA hypermethylation at precancerous stages was strengthened during progression to lung adenocarcinomas (??(T-N)>0.1). Among these 28 genes, we focused on 6 for which implications in transcription regulation, apoptosis or cell adhesion had been reported. DNA hypermethylation of the ADCY5, EVX1, GFRA1, PDE9A, and TBX20 genes resulted in reduced mRNA expression in tumorous tissue samples. 5-Aza-2'-deoxycytidine treatment of lung cancer cell lines restored the mRNA expression levels of these 5 genes. Reduced mRNA expression in tumorous tissue samples was significantly correlated with tumor aggressiveness. These data suggest that DNA methylation alterations at precancerous stages determine tumor aggressiveness and outcome through silencing of specific genes.

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Factors associated with distant recurrence following R0 lobectomy for pN0 lung adenocarcinoma.

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Factors associated with distant recurrence following R0 lobectomy for pN0 lung adenocarcinoma.

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