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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 13/2014

01-12-2014 | Thoracic Oncology

Homozygous GNAS 393C-Allele Carriers with Locally Advanced Esophageal Cancer Fail to Benefit from Platinum-Based Preoperative Chemoradiotherapy

Authors: Hakan Alakus, MD, Elfriede Bollschweiler, MD, PhD, Arnulf H. Hölscher, MD, Ute Warnecke-Eberz, PhD, Kelly A. Frazer, PhD, Olivier Harismendy, PhD, Andrew M. Lowy, MD, Stefan P. Mönig, MD, Pascal M. Eberz, MS, Martin Maus, MD, Uta Drebber, MD, Winfried Siffert, MD, Ralf Metzger, MD

Published in: Annals of Surgical Oncology | Issue 13/2014

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.
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Metadata
Title
Homozygous GNAS 393C-Allele Carriers with Locally Advanced Esophageal Cancer Fail to Benefit from Platinum-Based Preoperative Chemoradiotherapy
Authors
Hakan Alakus, MD
Elfriede Bollschweiler, MD, PhD
Arnulf H. Hölscher, MD
Ute Warnecke-Eberz, PhD
Kelly A. Frazer, PhD
Olivier Harismendy, PhD
Andrew M. Lowy, MD
Stefan P. Mönig, MD
Pascal M. Eberz, MS
Martin Maus, MD
Uta Drebber, MD
Winfried Siffert, MD
Ralf Metzger, MD
Publication date
01-12-2014
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue 13/2014
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-014-3843-y

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