%0 Journal Article
%T Mutated KRAS Is an Independent Negative Prognostic Factor for Survival in NSCLC Stage III Disease Treated with High-Dose Radiotherapy
%A A. Hallqvist
%A F. Enlund
%A C. Andersson
%A H. Sj£¿gren
%A A. Hussein
%A E. Holmberg
%A J. Nyman
%J Lung Cancer International
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/587424
%X Background. The main attention regarding prognostic and predictive markers in NSCLC directs towards the EGFR-targeted pathway, where the most studied genetic alterations include EGFR mutations, EGFR copy number, and KRAS mutations. We wanted to explore the prognostic impact of mutated KRAS in the stage III setting treated with high-dose radiochemotherapy. Methods. Samples were obtained from patients participating in two prospective studies of locally advanced NSCLC receiving combined radiochemotherapy: the RAKET study, a randomized phase II study where patients were treated with induction chemotherapy (carboplatin/paclitaxel) followed by concurrent radiochemotherapy, and the Satellite trial, a phase II study with induction chemotherapy (cisplatin/docetaxel) followed by radiotherapy concurrent cetuximab. The samples were analysed regarding KRAS mutations, EGFR mutations, and EGFR FISH positivity. Results. Patients with mutated KRAS had a significantly inferior survival, which maintained its significance in a multivariate analysis when other possible prognostic factors were taken into account. The prevalence of KRAS mutations, EGFR mutations, and EGFR FISH positivity were 28.8%, 7.5%, and 19.7%, respectively. Conclusion. Mutated KRAS is an independent negative prognostic factor for survival in NSCLC stage III disease treated with combined radiochemotherapy. The prevalence of KRAS mutations and EGFR mutations are as expected in this Scandinavian population. 1. Introduction The importance of finding prognostic and predictive markers is an ongoing challenge in oncology. The main attention regarding NSCLC directs towards the epidermal growth factor receptor- (EGFR) targeted pathway, where the most studied genetic alterations include EGFR mutations, EGFR copy number, and KRAS mutations. KRAS mutations have been shown to be associated with worse survival in resected patients [1, 2] and have also been shown to be a negative prognostic factor regarding adjuvant chemotherapy [3], whereas the significance in the stage III (locally advanced) or stage IV (metastatic) setting still is unclear. In this study, we analysed tumour tissue samples regarding KRAS mutations, EGFR mutations, and EGFR positivity by FISH¡ªhigh polysomy and amplification as defined by Cappuzzo et al. [4]¡ªin patients with NSCLC stage III disease. The study population is represented by patients from two prospective trials who have received combined radiochemotherapy with curative intent: The RAKET study, a randomized three-armed phase II study where patients were treated with two cycles of induction
%U http://www.hindawi.com/journals/lci/2012/587424/