• Elfriede Bollschweiler, Arnulf H Hölscher, Till Herbold, Ralf Metzger, Hakan Alakus, Henner Schmidt, Uta Drebber, and Ute Warnecke-Eberz.
• Department of General, Visceral and Cancer Surgery, University Hospital of Cologne, Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
• Ann. Surg. 2016 Nov 1; 264 (5): 839-846.

ObjectiveThe 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.Summary Of Background DataPatients without response to neoadjuvant chemoradiation for esophageal cancer have no prognostic benefits, but experience time delays and risk side effects.MethodsInclusion 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.ResultsFrom 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.ConclusionERCC1-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.

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