title: Decreased peritherapeutic VEGF expression could be a predictor of responsiveness to first-line FOLFIRI plus bevacizumab in mCRC patients.
abstract: OBJECTIVE
  Bevacizumab is the only anti-angiogenic agent approved in first-line therapy for metastatic colorectal cancer (mCRC). Although chemotherapy plus bevacizumab has led to improve outcomes for mCRC patients and is a common choice for first-line treatment of mCRC, previous research has established no prominent biomarker that can help to select patients who may benefit from bevacizumab in order to improve cost-effectiveness and therapeutic outcomes. The aim of this study was to compare pre- and post-therapeutic VEGF immunohistochemical (IHC) expression in mCRC patients treated with FOLFIRI plus bevacizumab to identify its potential role as a predictive biomarker.
  
  
  METHODS
  A total of 57 mCRC patients who underwent FOLFIRI combined with bevacizumab chemotherapy as a first-line neoadjuvant regimen were enrolled and clinical outcome data analyzed.
  
  
  RESULTS
  Low post-therapeutic VEGF expression (P < 0.001) and decreased peri-therapeutic VEGF expression (P < 0.001) were significantly predictive factors of responders. Furthermore, the 6-month progression-free survival (PFS) rate in mCRC patients with decreased peri-therapeutic VEGF expression was significantly better than the rate for those patients with no peri-therapeutic VEGF expression alterations (P = 0.033).
  
  
  CONCLUSIONS
  Decreased peri-therapeutic VEGF expression in mCRC patients could probably be used to predict responsiveness to bevacizumab and subsequent PFS in clinical practice.
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University Kaohsiung, Taiwan ; Division of General Surgery Medicine, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung, Taiwan ; Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung, Taiwan ; Program of Bachelor of Health Beauty, School of Medical and Health Sciences, Fooyin University Kaohsiung, Taiwan ; Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University Kaohsiung, Taiwan ; Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University Kaohsiung, Taiwan.
authors.forename: Hsiang-Lin
authors.initials: HL
authors.lastname: Tsai
authors.affiliation: Deaprtment of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung, Taiwan.
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University Kaohsiung, Taiwan ; Division of Gastrointestinal and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung, Taiwan ; Department of Surgery, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University Kaohsiung, Taiwan.
authors.forename: Ching-Wen
authors.initials: CW
authors.lastname: Huang
authors.affiliation: Department of Nursing, Shu-Zen College of Medicine and Management Kaohsiung, Taiwan.
authors.forename: I-Ping
authors.initials: IP
authors.lastname: Yang
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University Kaohsiung, Taiwan ; Division of Trauma, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung, Taiwan.
authors.forename: Yung-Sung
authors.initials: YS
authors.lastname: Yeh
authors.affiliation: Division of Gastroenterology, Department of Internal medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung, Taiwan ; Department of Internal medicine, College of Medicine, Kaohsiung Medical University Kaohsiung, Taiwan.
authors.forename: Wen-Hung
authors.initials: WH
authors.lastname: Hsu
authors.affiliation: Division of Gastroenterology, Department of Internal medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung, Taiwan ; Department of Internal medicine, College of Medicine, Kaohsiung Medical University Kaohsiung, Taiwan.
authors.forename: Jeng-Yih
authors.initials: JY
authors.lastname: Wu
authors.affiliation: Division of Gastroenterology, Department of Internal medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung, Taiwan ; Department of Internal medicine, College of Medicine, Kaohsiung Medical University Kaohsiung, Taiwan.
authors.forename: Chao-Hung
authors.initials: CH
authors.lastname: Kuo
authors.affiliation: Division of General Surgery, Department of Surgery, Ten Chan General Hospital Chung-Li, Taiwan.
authors.forename: Fan-Ying
authors.initials: FY
authors.lastname: Tseng
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University Kaohsiung, Taiwan ; Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung, Taiwan ; Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University Kaohsiung, Taiwan ; Division of Gastrointestinal and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung, Taiwan ; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University Kaohsiung, Taiwan ; Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University Kaohsiung, Taiwan.
authors.forename: Jaw-Yuan
authors.initials: JY
authors.lastname: Wang
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D015536:Down-Regulation; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis; D011237:Predictive Value of Tests; D013997:Time Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: Vascular endothelial growth factor; bevacizumab; metastatic colorectal cancer; peri-therapeutic VEGF expression; response