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Clinical Significance and Role of Lymphatic Vessel Invasion as a Major Prognostic Implication in Non-Small Cell Lung Cancer: A Meta-Analysis
Authors:Jun Wang  Baocheng Wang  Weipeng Zhao  Yan Guo  Hong Chen  Huili Chu  Xiuju Liang  Jingwang Bi
Institution:1. Department of Oncology, General Hospital, Jinan Command of the People’s Liberation Army, Jinan, China.; 2. Tianjin Cancer Hospital and Institute, Tianjin Medical University, Tianjin, China.; 3. Department of Outpatient, Military Command of Shandong Province, Jinan, China.; 4. Department of Chinese Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.; Roswell Park Cancer Institute, United States of America,
Abstract:

Background

Lymphatic vessel invasion (LVI) exerts an important process in the progression and local spread of cancer cells. However, LVI as a prognostic factor for survival in non-small cell lung cancer (NSCLC) remains controversial.

Methodology/Principal Findings

A meta-analysis of published studies from PubMed and EMBASE electronic databases was performed to quantity the effects of LVI on both relapse-free survival and overall survival for patients with NSCLC. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used to assess the strength of these effects. This meta-analysis included 18,442 NSCLC patients from 53 eligible studies. LVI appeared in 32.1% (median; range, 2.8% to 70.9%) of tumor samples. In all, patients with LVI were 2.48 times more likely to relapse by univariate analysis (95% CI: 1.92–3.22) and 1.73 times by multivariate analysis (95% CI: 1.24–2.41) compared with those without LVI. For the analyses of LVI and overall survival, the pooled HR estimate was 1.97 (95% CI: 1.75–2.21) by univariate analysis and 1.59 (95% CI: 1.41–1.79) by multivariate analysis. Multivariate analysis showed a risk was 91% higher for recurrence (HR  = 1.91, 95% CI: 1.14–2.91) and 70% higher for mortality (HR = 1.70, 95% CI: 1.38–2.10) in LVI-positive I stage patients compared with LVI-negative I stage patients. Subgroup analyses showed similar significant adjusted risks for recurrence and death in adenocarcinomas, and a significant adjusted risk for death in studies that utilized elastic staining with or without immunohistochemistry in defining LVI.

Conclusions/Significance

The present study indicates that LVI appears to be an independent poor prognosticator in surgically managed NSCLC. NSCLC patients with LVI would require a more aggressive treatment strategy after surgery. However, large, well-designed prospective studies with clinically relevant modeling and standard methodology to assess LVI are required to address some of these important issues.
Keywords:
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