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Title: EGF61 polymorphism predicts complete pathologic response to cetuximab-based chemoradiation independent of KRAS status in locally advanced rectal cancer patients
Authors: Hu-Lieskovan, Siwen ×
Vallbohmer, Daniel
Zhang, Wu
Yang, Dongyun
Pohl, Alexandra
Labonte, Melissa J
Grimminger, Peter
Holscher, Arnulf H
Semrau, Robert
Arnold, Dirk
Dellas, Kathrin
Debucquoy, Annelies
Haustermans, Karin
Machiels, Jean-Pascal H
Sempoux, Christine
Rodel, Claus
Bracko, Matej
Velenik, Vaneja
Lenz, Heinz-Josef #
Issue Date: 1-Aug-2011
Publisher: Association for Cancer Research
Series Title: Clinical Cancer Research vol:17 issue:15 pages:5161-5169
Abstract: PURPOSE: Cetuximab has demonstrated significant clinical activity in metastatic colon cancer. However, cetuximab-containing neoadjuvant chemoradiation has not been shown to improve tumor response in locally advanced rectal cancer patients in recent phase I/II trials. We evaluated functional germline polymorphisms of genes involved in EGFR pathway, angiogenesis, ADCC, DNA repair, and drug metabolism, for their potential role as molecular predictors for clinical outcome in locally advanced rectal cancer patients treated with preoperative cetuximab-based chemoradiation. EXPERIMENTAL DESIGN: 130 patients (74 men and 56 women) with locally advanced rectal cancer (4 with stage II, 109 with stage III and 15 with stage IV, 2 unknown) who were enrolled in phase I/II clinical trials treated with cetuximab-based chemoradiation in European cancer centers were included. Genomic DNA was extracted from formalin-fixed paraffin-embedded tumor samples and genotyping was performed using PCR-RFLP assays. Fisher's exact test was used to examine associations between polymorphisms and complete pathologic response (pCR) that was determined by a modified Dworak classification system (grade 0-III vs grade IV: complete response)RESULTS: Patients with the EGF 61 G/G genotype had pCR of 45% (5/11), compared with 21% (11/53) in patients heterozygous, and 2% (1/54) in patients homozygous for the A/A allele (P {less than} 0.001). In addition, this association between EGF 61 G allele and pCR remained significant (p=0.019) in the 59 patients with wild type KRAS.CONCLUSIONS: This study suggests EGF A+61G polymorphism to be a predictive marker for pCR, independent of KRAS mutation status, to cetuximab-based neoadjuvant chemoradiation of patients with locally advanced rectal cancer.
URI: 
ISSN: 1078-0432
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Experimental Radiotherapy
× corresponding author
# (joint) last author

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