Universität zu Köln

Alakus, Hakan, Bollschweiler, Elfriede, Hoelscher, Arnulf H., Warnecke-Eberz, Ute, Frazer, Kelly A., Harismendy, Olivier, Lowy, Andrew M., Moenig, Stefan P., Eberz, Pascal M., Maus, Martin, Drebber, Uta, Siffert, Winfried and Metzger, Ralf (2014). Homozygous GNAS 393C-Allele Carriers with Locally Advanced Esophageal Cancer Fail to Benefit from Platinum-Based Preoperative Chemoradiotherapy. Ann. Surg. Oncol., 21 (13). S. 4375 - 4383. NEW YORK: SPRINGER. ISSN 1534-4681

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Abstract

Currently, patients with locally advanced esophageal cancer receive neoadjuvant chemoradiotherapy but only about half of these patients benefit from this treatment. GNAS T393C has been shown to predict the postoperative course in solid tumors and may therefore be useful for treatment stratification. The aim of the present study was to determine if the single-nucleotide polymorphism GNAS T393C can be used for treatment stratification in esophageal cancer patients. A total of 596 patients underwent surgical resection for esophageal carcinoma from 1996 to 2008; 279 patients received chemoradiotherapy prior to surgery (RTX-SURG group). All patients and a reference group of 820 healthy White individuals were genotyped for GNAS T393C. The 5-year-survival rate for the 317 patients who underwent esophagectomy as initial treatment (SURG group) was 57 % for homozygous C-allele carriers (n = 99) and 43 % for T-allele carriers (n = 218; log- rank test p = 0.025). Multivariate analysis revealed the GNAS T393C genotype (p = 0.034), pT (p < 0.001), pN (p < 0.001) and age (p < 0.001) as prognostic of survival. Homozygous C-allele carriers with a locally advanced tumor stage (cT3/T4, n = 129) in the SURG group had a 5-year survival rate of 37 %, which, remarkably, exceeded the 5-year survival rate of 30 % for the entire RTX-SURG group (n = 279). In the RTX-SURG group, the GNAS T393C genotype did not show any prognostic significance. Patients with a locally advanced esophageal cancer and an homozygous GNAS 393C genotype do not benefit from platinum-based neoadjuvant chemoradiotherapy, indicating that these patients should be treated by alternative treatment strategies.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Alakus, Hakan UNSPECIFIED UNSPECIFIED UNSPECIFIED Bollschweiler, Elfriede UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoelscher, Arnulf H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Warnecke-Eberz, Ute UNSPECIFIED UNSPECIFIED UNSPECIFIED Frazer, Kelly A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Harismendy, Olivier UNSPECIFIED UNSPECIFIED UNSPECIFIED Lowy, Andrew M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Moenig, Stefan P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Eberz, Pascal M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Maus, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Drebber, Uta UNSPECIFIED UNSPECIFIED UNSPECIFIED Siffert, Winfried UNSPECIFIED UNSPECIFIED UNSPECIFIED Metzger, Ralf UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-422195
DOI:	10.1245/s10434-014-3843-y
Journal or Publication Title:	Ann. Surg. Oncol.
Volume:	21
Number:	13
Page Range:	S. 4375 - 4383
Date:	2014
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1534-4681
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PHASE-III TRIAL; SQUAMOUS-CELL CARCINOMA; T393C POLYMORPHISM; NEOADJUVANT RADIOCHEMOTHERAPY; PITUITARY-TUMORS; GENE GNAS1; G-PROTEIN; SURGERY; SURVIVAL; ADENOCARCINOMA Multiple languages Oncology; Surgery Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42219