Abstract
Background: Role of tumor-stroma ratio (TSR) as a predictor of survival in patients with non-small cell lung cancer (NSCLC) remains not clear. A systematic review and meta-analysis was conducted to summarize current evidence for the role of TSR in NSCLC. Methods: Relevant cohort studies were retrieved via search of Medline, Embase, and Web of Science databases. The data was combined with a random-effect model by incorporating the between-study heterogeneity. Specifically, subgroup and meta-regression analyses were performed to explore the association between TSR and survival in patients with squamous cell carcinoma (SCC) or adenocarcinoma (AC). Results: Nine cohort studies with 2031 patients with NSCLC were eligible for the meta-analysis. Pooled results showed that compared to those stroma-poor tumor, patients with stroma rich NSCLC were associated with worse recurrence-free survival (RFS, hazard ratio [HR] = 1.52, 95% confidence interval [CI]: 1.07 to 2.16, p = 0.02) and overall survival (OS, HR = 1.48, 95% CI: 1.20 to 1.82, p < 0.001). Subgroup analyses showed that stroma-rich tumor may be associated with a worse survival of SCC (HR = 1.89 and 1.47 for PFS and OS), but a possibly favorable survival of AC (HR = 0.28 and 0.69 for PFS and OS). Results of meta-regression analysis also showed that higher proportion of patients with SCC was correlated with higher HRs for RFS (Coefficient = 0.012, p = 0.03) and OS (Coefficient = 0.014, p = 0.02) in the included patients, while higher proportion of patients with AC was correlated with lower HRs for RFS (Coefficient = −0.012, p = 0.03) and OS (Coefficient = −0.013, p = 0.04), respectively. Conclusion: Tumor TSR could be used as a predictor of survival in patients with NSCLC. The relative proportion of patients with SCC/AC in the included NSCLC patients may be an important determinant for the association between TSR and survival in NSCLC. Stroma richness may be a predictor of poor survival in patients with lung SCC, but a predictor of better survival in patients with lung AC.
Highlights
Among various solid tumors, lung cancer is a common malignancy and a leading cause of cancer-specific mortality [1]
Pooled results showed that compared to those stroma-poor tumor, patients with stroma rich non-small cell lung cancer (NSCLC) were associated with worse recurrence-free survival (RFS, hazard ratio [HR] 1.52, 95% confidence interval [confidence intervals (CIs)]: 1.07 to 2.16, p 0.02) and overall survival (OS, HR 1.48, 95% CI: 1.20 to 1.82, p < 0.001)
Results of meta-regression analysis showed that higher proportion of patients with squamous cell carcinoma (SCC) was correlated with higher HRs for RFS (Coefficient 0.012, p 0.03) and OS (Coefficient 0.014, p 0.02) in the included patients, while higher proportion of patients with AC was correlated with lower HRs for RFS (Coefficient −0.012, p 0.03) and OS (Coefficient −0.013, p 0.04), respectively
Summary
Lung cancer is a common malignancy and a leading cause of cancer-specific mortality [1]. A previous meta-analysis showed that higher proportion of stroma in primary cancer tissue was associated with poor prognosis of the patients, studies with various types of cancer were included and a site-specific association between TSR and survival in patients with solid tumor was suggested [13]. Role of tumor-stroma ratio (TSR) as a predictor of survival in patients with non-small cell lung cancer (NSCLC) remains inconsistent according to previous studies [14,15,16,17,18,19,20,21,22]. Role of tumor-stroma ratio (TSR) as a predictor of survival in patients with non-small cell lung cancer (NSCLC) remains not clear. A systematic review and metaanalysis was conducted to summarize current evidence for the role of TSR in NSCLC
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