title: Molecular Markers for the Prediction of Minor Response to Neoadjuvant Chemoradiation in Esophageal Cancer: Results of the Prospective Cologne Esophageal Response Prediction (CERP) Study.
abstract: OBJECTIVE
  The aim of this study was to evaluate the predictive value of a single or combination of biomarker(s) for histopathologic non-response to neoadjuvant chemoradiation in esophageal cancer.
  
  
  BACKGROUND
  Patients without response to neoadjuvant chemoradiation for esophageal cancer have no prognostic benefits, but experience time delays and risk side effects.
  
  
  METHODS
  Inclusion criteria for this prospective diagnostic study were patients with cT3,Nx,M0, esophageal squamous cell or adenocarcinoma and planned neoadjuvant chemoradiation (5- fluorouracil, cisplatin, 40Gy) followed by 2-field transthoracic esophagectomy. From pretherapeutic endoscopic tumor biopsies, ERCC1 rs11615 single-nucleotide polymorphism (ERCC1-SNP) and a combination of gene expression marker mRNA (ERCC1, DPYD, ERBB2) were analyzed. ERCC1-SNP was subdifferentiated into homozygous C-allele (CC) and T-allele (TT), and heterozygous C/T carriers. The primary endpoint was the prediction of histopathological minor response (≥10% vital tumor cells in the primary tumor) relative to marker levels.
  
  
  RESULTS
  From 2009 until 2013, 320 patients were screened, and 85 patients (SCC n = 29, AC n = 56) were included in the study. Forty-one patients (48%) had major response with 3-year survival rate (3-YSR) of 57% compared with 44 patients with minor response and 3-YSR of 25% (P = 0.001). Patients with ERCC1-SNP CC (n = 8) and TT (n = 37) had similar rates of minor response of 70% and 75%, and a positive predictive value (PPV) of 71% [95% confidence interval (CI 56%-84%)]. PPV increased to 89% (95% CI 73%-96%) when ERCC1-SNP was combined with mRNA markers.
  
  
  CONCLUSIONS
  ERCC1-SNP in combination with mRNA ERCC1, DPYD, and ERBB2 from pretherapeutic endoscopic biopsies can predict minor response to chemoradiation, as a basis for individualized therapy of advanced esophageal cancer.
authors.affiliation: Department of General, Visceral and Cancer Surgery, University Hospital of Cologne, Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Elfriede
authors.initials: E
authors.lastname: Bollschweiler
authors.forename: Arnulf H
authors.initials: AH
authors.lastname: Hölscher
authors.forename: Till
authors.initials: T
authors.lastname: Herbold
authors.forename: Ralf
authors.initials: R
authors.lastname: Metzger
authors.forename: Hakan
authors.initials: H
authors.lastname: Alakus
authors.forename: Henner
authors.initials: H
authors.lastname: Schmidt
authors.forename: Uta
authors.initials: U
authors.lastname: Drebber
authors.forename: Ute
authors.initials: U
authors.lastname: Warnecke-Eberz
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D059248:Chemoradiotherapy; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; D042943:Dihydrouracil Dehydrogenase (NADP); D004720:Endonucleases; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human; C071447:ERCC1 protein, human