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BackgroundQualitative analysis of circulating DNA in the blood is a promising non-invasive diagnostic and prognostic tool. Our aim was to study the association between the presence of KRAS mutations at codon 12 and several clinical variables in advanced non-small cell lung cancer (NSCLC) patients.MethodsWe examined 308 stage IIIB and IV NSCLC patients who were treated with cisplatin and docetaxel. Blood samples were collected before chemotherapy, and circulating DNA was extracted from the plasma using commercial adsorption columns. The KRAS mutational status was determined by an RT-PCR method that is based on allelic discrimination.ResultsThe median age of the patients was 60 years [31-80], 84% were male, 98% had a performance status of 0-1 and 84% of the patients were in stage IV. The histological subtypes were as follows: 30% squamous cell carcinoma (SCC), 51% adenocarcinoma (ADC) and 19% others. Of the 277 response-evaluated patients, 1% achieved a complete response (CR), 26% achieved a partial response (PR), 34% had stable disease (SD) and 39% had progressive disease (PD). Additionally, 27 (8.8%) patients had KRAS mutations; 26 had a KRAS codon 12 TGT mutation, and 1 had a codon 12 GTT mutation. Plasmatic KRAS mutations were found in patients presenting SCC or ADC. Patients with KRAS mutations in plasma DNA had a median progression free survival (PFS) of 5.77 months [3.39-8.14], whereas for patients with wild-type (wt) KRAS, the PFS was 5.43 months [4.65-6.22] (p=0.277). The median overall survival (OS) in KRAS-mutated patients was 9.07 months [4.43-13.70] vs 10.03 months [8.80-11.26] in wt patients (p=0.514).ConclusionsIn advanced NSCLC patients, there were no significant differences between patients with or without KRAS mutations in plasma-free DNA with respect to the baseline characteristics, response rates, PFS or OS.

Original publication

DOI

10.1016/j.lungcan.2010.09.005

Type

Journal article

Journal

Lung cancer (Amsterdam, Netherlands)

Publication Date

06/2011

Volume

72

Pages

365 - 369

Addresses

Servicio de Oncología Médica, Hospital General Universitario, Valencia, Spain.

Keywords

Humans, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Disease Progression, ras Proteins, Proto-Oncogene Proteins, DNA, Neoplasm Staging, Prognosis, Survival Analysis, Follow-Up Studies, Predictive Value of Tests, DNA Mutational Analysis, Mutation, Aged, Middle Aged, Female, Male, Proto-Oncogene Proteins p21(ras), Genetic Association Studies