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

  • Thoracic Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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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Acknowledgment

This study was supported by the Köln Fortune Program of the Faculty of Medicine, University of Cologne and The German Cancer Aid, Bonn.

Conflict of interest

Hakan Alakus, Elfriede Bollschweiler, Arnulf H. Hölscher, Ute Warnecke-Eberz, Kelly A. Frazer, Olivier Harismendy, Andrew M. Lowy, Stefan P. Mönig, Pascal M. Eberz, Martin Maus, Uta Drebber, Winfried Siffert, and Ralf Metzger declare no financial and personal relationships with other people or organizations that could inappropriately influence (bias) their work.

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Authors and Affiliations

  1. Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany

    Hakan Alakus MD, Elfriede Bollschweiler MD, PhD, Arnulf H. Hölscher MD, Ute Warnecke-Eberz PhD, Stefan P. Mönig MD, Martin Maus MD & Ralf Metzger MD

  2. Center for Integrated Oncology Cologne-Bonn, University of Cologne, Cologne, Germany

    Hakan Alakus MD & Ralf Metzger MD

  3. Division of Genome Information Sciences, Department of Pediatrics and Rady Children’s Hospital, University of California San Diego, La Jolla, CA, USA

    Hakan Alakus MD, Kelly A. Frazer PhD & Olivier Harismendy PhD

  4. Moores UCSD Cancer Center, University of California San Diego, La Jolla, CA, USA

    Hakan Alakus MD, Kelly A. Frazer PhD, Olivier Harismendy PhD & Andrew M. Lowy MD

  5. Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA

    Kelly A. Frazer PhD

  6. Division of Surgical Oncology, Department of Surgery, University of California San Diego, La Jolla, CA, USA

    Andrew M. Lowy MD

  7. Université Joseph Fourier, Grenoble, France

    Pascal M. Eberz MS

  8. Institute of Pathology, University of Cologne, Cologne, Germany

    Uta Drebber MD

  9. Institute of Pharmacogenetics, University Hospital Essen, Essen, Germany

    Winfried Siffert MD

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  1. Hakan Alakus MD
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Correspondence to Hakan Alakus MD.

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Supplementary Fig. 1

Kaplan–Meier Survival curve for 408 patients with locally advanced esophageal cancer based on their treatment (TIFF 2724 kb)

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Alakus, H., Bollschweiler, E., Hölscher, A.H. et al. Homozygous GNAS 393C-Allele Carriers with Locally Advanced Esophageal Cancer Fail to Benefit from Platinum-Based Preoperative Chemoradiotherapy. Ann Surg Oncol 21, 4375–4382 (2014). https://doi.org/10.1245/s10434-014-3843-y

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