title: High VEGF-A level at baseline predicts poor treatment effect of bevacizumab-based chemotherapy in metastatic colorectal cancer: a meta-analysis.
abstract: BACKGROUND
  Bevacizumab (BEV) improves survival of metastatic colorectal cancer (mCRC) patients, but no specific biomarkers can predict which patients will benefit from bevacizumab (BEV). This meta-analysis aimed to evaluate the predictive significance of plasma/intratumoral vascular endothelial growth factor-A (VEGF-A) at baseline in the effectiveness of BEV-based treatment in mCRC.
  
  
  METHODS
  The PubMed, Medline, and Embase were searched to identify eligible studies. The association of high/low VEGF-A level at baseline with progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) were analyzed. Subgroup analysis based on sample and chemotherapy was also conducted. The pooled hazard ratio (HR), risk ratio (RR) and 95% confidence interval (95% CI) were calculated to estimate the effects.
  
  
  RESULTS
  Eleven eligible studies were included. This meta-analysis showed that high VEGF-A level at baseline was associated with poor PFS (HR=1.26, 95% CI [1.12, 1.42], P=0.0001) and OS (HR=1.30, 95% CI [1.15, 1.46], P<0.0001) of mCRC patients following BEV-based chemotherapy compared to low VEGF-A level. Subgroup analysis showed that the pooled results of PFS (blood and tumor tissue subgroup) and OS (blood subgroup) were similar to that of overall analysis. However, there was no significant difference in ORR between high and low VEGF-A level in tumor tissue subgroup (RR=0.95, 95% CI [0.53, 1.71], P=0.87). Moreover, the predictive role of high VEGF-A level at baseline was not impacted by various chemotherapies.
  
  
  CONCLUSIONS
  This meta-analysis indicated that high plasma/intratumoral VEGF-A level at baseline could predict poor treatment effect (depressed PFS and OS) of BEV-based chemotherapy in mCRC, although there was no correlation between intratumoral VEGF-A level and ORR following BEV-based treatment.
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China - taozhang66@outlook.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Dejun
authors.initials: D
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
authors.forename: Min
authors.initials: M
authors.lastname: Jin
authors.forename: Fang
authors.initials: F
authors.lastname: Huang
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage* / Q000009:adverse effects; D014408:Biomarkers, Tumor / Q000097:blood*; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D006801:Humans; D009362:Neoplasm Metastasis; D016017:Odds Ratio; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab