title: Predicting the pathologic response of locally advanced rectal cancer to neoadjuvant concurrent chemoradiation using enzyme-linked immunosorbent assays (ELISAs) for biomarkers.
abstract: OBJECTIVE
  To investigate the role of biomarkers including serum tissue inhibitor of metalloproteinases-1 (TIMP-1), urokinase plasminogen activator receptor, vascular endothelial growth factor, and epidermal growth factor receptor in predicting pathologic response to neoadjuvant chemoradiation (NACRT) for rectal cancer.
  
  
  METHODS
  Between 2007 and 2009, 50 clinical TNM stage II or III patients were analyzed in this prospective study. Pre- and post-NACRT serum levels of biomarkers were assessed using ELISAs. The primary and secondary endpoints were pathologic complete response (pCR) and Mandard regression grade (MRG).
  
  
  RESULTS
  The pCR was reported in 5 patients (10.0%). According to the MRG, fifteen patients (30.0%) were divided into group A (Grade I-II), the others in group B (Grade III-V). On univariate analysis, post-NACRT TIMP-1 showed notable significance with pCR (P = 0.092) and significant correlation with MRG group A (P = 0.003). Post-NACRT TIMP-1 ≤ 204.5 ng/mL as cut-off value by ROC curve was associated with more pCR and MRG group A patients (P = 0.016 and 0.002). Interval between NACRT and surgery was related to pCR with approached trend levels of significance (P = 0.05) and to MRG group A significantly on univariate analysis of clinical factors (P = 0.031). On multivariate analysis, post-NACRT TIMP-1 was not significantly related to pCR (P = 0.187), while it was significantly associated with MRG (P = 0.009). Among clinical responders, post-NACRT TIMP-1 level ≤ 204.5 ng/mL was significantly associated with pCR (P = 0.021) and MRG group A (P = 0.003).
  
  
  CONCLUSIONS
  Post-NACRT serum TIMP-1 could be used as a predictive marker of pathologic response to NACRT in rectal cancer, even in patients with clinical response.
authors.affiliation: Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea.
authors.forename: Hong In
authors.initials: HI
authors.lastname: Yoon
authors.forename: Woong Sub
authors.initials: WS
authors.lastname: Koom
authors.forename: Yong Bae
authors.initials: YB
authors.lastname: Kim
authors.forename: Byung Soh
authors.initials: BS
authors.lastname: Min
authors.forename: Kang Young
authors.initials: KY
authors.lastname: Lee
authors.forename: Nam Kyu
authors.initials: NK
authors.lastname: Kim
authors.forename: Sang Joon
authors.initials: SJ
authors.lastname: Shin
authors.forename: Joong Bae
authors.initials: JB
authors.lastname: Ahn
authors.forename: Ki Chang
authors.initials: KC
authors.lastname: Keum
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D002272:Carcinoembryonic Antigen / Q000097:blood; D059186:Chemoradiotherapy, Adjuvant / Q000009:adverse effects; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011446:Prospective Studies; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood; D012004:Rectal Neoplasms / Q000097:blood / Q000473:pathology* / Q000628:therapy*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; C524898:PLAUR protein, human; D055293:Receptors, Urokinase Plasminogen Activator; D019715:Tissue Inhibitor of Metalloproteinase-1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D066246:ErbB Receptors