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Journal of Thoracic Oncology:
doi: 10.1097/01.JTO.0000283363.42687.c5
Poster Discussion Abstracts: Session PD2: Tuesday, September 4, Cancer Genetics and Tumor Biology: Molecular Targets and Prognostic Factors, Tue, 16:00 - 17:30

Prognostic significance and origin of plasma KRAS mutations in patients with non-small cell lung cancer (NSCLC): PD2-3-1

Gautschi, Oliver1; Ziegler, Annemarie2; Huegli, Barbara1; Gugger, Mathias3; Ratschiller, Daniel4; Mack, Philip C.5; Kung, Hsing-Jien5; Stahel, Rolf A.2; Gandara, David R.5; Betticher, Daniel C.6

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1University Hospital Bern, Medical Oncology, Bern, Switzerland 2University Hospital Zurich, Medical Oncology, Zurich, Switzerland 3University of Bern, Institute of Pathology, Bern, Switzerland 4University Hospital, Medical Oncology, Bern, Switzerland 5University of California Davis Cancer Center, Sacramento, CA, USA 6Hospital of Fribourg, Medical Oncology, Fribourg, Switzerland

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Background:

KRAS codon 12 mutations occur in about 30% of non-small cell lung cancer (NSCLC) tissue and are associated with adenocarcinoma histology, poor survival and resistance to erlotinib or gefitinib. In this study, we evaluated the reliability and clinical significance of plasma KRAS mutations in NSCLC patients.

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Patients and Methods:

180 Swiss patients with NSCLC were screened for KRAS mutations in plasma and matched peripheral blood mononuclear cells (PBMC) using a combined restriction fragment-length polymorphism and polymerase chain reaction (RFLP-PCR) assay. Survival analysis was performed using the Kaplan-Meier method and the Cox multivariate model. KRAS mutations were validated in a second laboratory by DNA sequencing, using matched plasma, serum, PBMC and tumor tissue.

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Results:

Baseline characteristics: 69% male, 69% smokers, 86% stage IIIB/IV and 44% adenocarcinoma. Median age at diagnosis was 61 years and median survival was 12 months. Chemotherapy was given to 78% of the patients, 27% had surgical resection and 12% radiation. Mutation screening revealed KRAS mutations in 16/180 (9%) plasma and 0/180 (0%) PBMC samples. Plasma KRAS mutations (P = 0.014), tumor stage (P ≤ 0.001) and surgical resection (P ≤ 0.001) were independent predictors of prognosis in the multivariate model. No significant associations were found between plasma KRAS mutations and baseline characteristics or response to chemotherapy. DNA sequencing confirmed circulating KRAS mutations in 11/15 evaluable cases. KRAS codon 12 sequences matched between blood and tumors in 7/9 evaluable cases.

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Conclusions:

Plasma KRAS mutations were associated with poor survival and concordant with tumor KRAS mutations. Further studies are warranted to test if plasma KRAS mutations predict resistance to erlotinib or gefitinib in NSCLC patients.

Copyright © 2007 by the European Lung Cancer Conference and the International Association for the Study of Lung Cancer.

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