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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 12/2007

01-12-2007 | Gastrointestinal Oncology

Pretreatment Gene Expression Profiles Can Be Used to Predict Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer

Authors: Cuong Duong, Danielle M. Greenawalt, Adam Kowalczyk, Marianne L. Ciavarella, Garvesh Raskutti, William K. Murray, Wayne A. Phillips, Robert J. S. Thomas

Published in: Annals of Surgical Oncology | Issue 12/2007

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Abstract

Background

The use of neoadjuvant therapy, in particular chemoradiotherapy (CRT), in the treatment of esophageal cancer (EC) remains controversial. The ability to predict treatment response in an individual EC patient would greatly aid therapeutic planning. Gene expression profiles of EC were measured and relationship to therapeutic response assessed.

Methods

Tumor biopsy samples taken from 46 EC patients before neoadjuvant CRT were analyzed on 10.5K cDNA microarrays. Response to treatment was assessed and correlated to gene expression patterns by using a support vector machine learning algorithm.

Results

Complete clinical response at conclusion of CRT was achieved in 6 of 21 squamous cell carcinoma (SCC) and 11 of 25 adenocarcinoma (AC) patients. CRT response was an independent prognostic factor for survival (P < .001). A range of support vector machine models incorporating 10 to 1000 genes produced a predictive performance of tumor response to CRT peaking at 87% in SCC, but a distinct positive prediction profile was unobtainable for AC. A 32-gene classifier was produced, and by means of this classifier, 10 of 21 SCC patients could be accurately identified as having disease with an incomplete response to therapy, and thus unlikely to benefit from neoadjuvant CRT.

Conclusions

Our study identifies a 32-gene classifier that can be used to predict response to neoadjuvant CRT in SCC. However, because of the molecular diversity between the two histological subtypes of EC, when considering the AC and SCC samples as a single cohort, a predictive profile could not be resolved, and a negative predictive profile was observed for AC.
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Metadata
Title
Pretreatment Gene Expression Profiles Can Be Used to Predict Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer
Authors
Cuong Duong
Danielle M. Greenawalt
Adam Kowalczyk
Marianne L. Ciavarella
Garvesh Raskutti
William K. Murray
Wayne A. Phillips
Robert J. S. Thomas
Publication date
01-12-2007
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 12/2007
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-007-9550-1

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