101. EGF61 polymorphism predicts complete pathologic response to cetuximab-based chemoradiation independent of KRAS status in locally advanced rectal cancer patients
- Author
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UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (SLuc) Unité d'oncologie médicale, UCL - (SLuc) Service d'anatomie pathologique, UCL - (SLuc) Centre du cancer, Hu-Lieskovan, Siwen, Vallbohmer, Daniel, Zhang, Wu, Yang, Dongyun, Pohl, Alexander, Labonte, Melissa J, Grimminger, Peter P, Hölscher, Arnulf H, Semrau, Robert, Arnold, Dirk, Dellas, Kathrin, Debucquoy, Annelies, Haustermans, Karin, Machiels, Jean-Pascal, Sempoux, Christine, Rödel, Claus, Bracko, Matej, Velenik, Vaneja, Lenz, Heinz-Josef, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (SLuc) Unité d'oncologie médicale, UCL - (SLuc) Service d'anatomie pathologique, UCL - (SLuc) Centre du cancer, Hu-Lieskovan, Siwen, Vallbohmer, Daniel, Zhang, Wu, Yang, Dongyun, Pohl, Alexander, Labonte, Melissa J, Grimminger, Peter P, Hölscher, Arnulf H, Semrau, Robert, Arnold, Dirk, Dellas, Kathrin, Debucquoy, Annelies, Haustermans, Karin, Machiels, Jean-Pascal, Sempoux, Christine, Rödel, Claus, Bracko, Matej, Velenik, Vaneja, and Lenz, Heinz-Josef
- Abstract
BACKGROUND: Cetuximab has shown 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 epidermal growth factor receptor pathway, angiogenesis, antibody-dependent cell-mediated cytotoxicity, 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. METHODS: 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 done by 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 III vs. grade IV: complete response). RESULTS: Patients with the epidermal growth factor (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 < 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. CONCLUSION: This study suggested 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.
- Published
- 2011