Preoperative anemia as a prognostic factor in patients with lung cancer: a systematic review and meta-analysis of epidemiological studies

Abstract

The evidence of current epidemiological studies investigating the relationship between preoperative anemia and progression of lung cancer (LC) patients remains controversial. The PubMed, EMBASE, and Web of Science databases were comprehensively searched by two independent authors to identify related epidemiological studies from inception through January 31, 2019. Similarly, two researchers separately extracted data and any differences were resolved by discussion. Summarized hazard ratios (HRs) and 95% confidence intervals (CIs) were summarized with inverse variance weighted random effects meta-analysis. Heterogeneity among studies was assessed with the I² statistic. Twenty-two studies were included in this meta-analysis. As compared with LC patients without anemia, those with pre-operative anemia were at a 1.6-fold greater risk of death (summarized HR = 1.58; 95% CI = 1.44-1.75), with moderate heterogeneity (I ² = 53.1%). Funnel plot and statistical analyses showed no evidence of publication bias. Associations between pre-operative anemia and OS were broadly consistent across numerous subgroups analyses stratified by the study design, geographic location, number of cases, tumor, node, and metastasis (TNM) stage, histology, quality, and adjustment for potential confounders (age, sex, body mass index, TNM stage, histology, performance status, surgery, blood transfusion, and systemic inflammatory response markers). Similar patterns were observed in the sensitivity analyses. The results of meta-regression analysis suggested no evidence of significant heterogeneity between subgroups. In conclusion, pre-operative anemia was associated with poorer overall survival among LC patients.

Keywords: lung cancer (LC) patients; meta-analysis; overall survival; pre-operative anemia.

Figure 1

Selection of studies for inclusion in this meta-analysis.

Figure 2

Forest plot (random effects model) of pre-operative anemia and OS of LC patients. The squares indicate study-specific hazard ratios (size of the square reflects the study-specific statistical weight); the horizontal lines indicate 95% CIs; and the diamond indicates the summary hazard ratio estimate with its 95% CI.

Figure 3

Test for publication bias for OS through Begg's funnel plot. HR, hazard ratio; SE, standard error. The circles alone are real studies. The vertical lines represent the summary effect estimates and the dashed lines represent pseudo-95% CI limits.

Figure 4

Sensitivity plot corresponding to the relationship between pre-operative anemia and OS of LC patients. The circle indicates the study-specific hazard ratio after excluding the present study; the horizontal dotted lines indicate 95% CIs.