Universität zu Köln

Bollschweiler, Elfriede, Hoelscher, Arnulf H., Herbold, Till, Metzger, Ralf, Alakus, Hakan, Schmidt, Henner, Drebber, Uta and Warnecke-Eberz, Ute (2016). Molecular Markers for the Prediction of Minor Response to Neoadjuvant Chemoradiation in Esophageal Cancer: Results of the Prospective Cologne Esophageal Response Prediction (CERP) Study. Ann. Surg., 264 (5). S. 839 - 847. PHILADELPHIA: LIPPINCOTT WILLIAMS & WILKINS. ISSN 1528-1140

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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.Summary of Background Data: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.Conclusion: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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bollschweiler, Elfriede UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoelscher, Arnulf H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Herbold, Till UNSPECIFIED UNSPECIFIED UNSPECIFIED Metzger, Ralf UNSPECIFIED UNSPECIFIED UNSPECIFIED Alakus, Hakan UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmidt, Henner UNSPECIFIED UNSPECIFIED UNSPECIFIED Drebber, Uta UNSPECIFIED UNSPECIFIED UNSPECIFIED Warnecke-Eberz, Ute UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-257358
DOI:	10.1097/SLA.0000000000001911
Journal or Publication Title:	Ann. Surg.
Volume:	264
Number:	5
Page Range:	S. 839 - 847
Date:	2016
Publisher:	LIPPINCOTT WILLIAMS & WILKINS
Place of Publication:	PHILADELPHIA
ISSN:	1528-1140
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MESSENGER-RNA EXPRESSION; HISTOPATHOLOGICAL RESPONSE; THYMIDYLATE SYNTHASE; GENE POLYMORPHISMS; PROGNOSTIC IMPACT; RADIOCHEMOTHERAPY; ERCC1; THERAPY; CHEMORADIOTHERAPY; ADENOCARCINOMA Multiple languages Surgery Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/25735