lunes, 9 de noviembre de 2015

Clinical utility of KRAS status in circulating plasma DNA compared to archival tumour tissue from patients with metastatic colorectal cancer treate... - PubMed - NCBI

2015 Oct 24. pii: S0959-8049(15)00644-9. doi: 10.1016/j.ejca.2015.06.118. [Epub ahead of print]

Clinical utility of KRAS status in circulating plasma DNA compared to archival tumour tissue from patients with metastatic colorectal cancer treated with anti-epidermal growth factor receptor therapy.

Spindler KG1, Pallisgaard N2, Appelt AL3, Andersen RF2, Schou JV4, Nielsen D5, Pfeiffer P6, Yilmaz M7, Johansen JS5, Hoegdall EV8, Jakobsen A3, Jensen BV4.

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Abstract

BACKGROUND:

Circulating cell-free DNA (cfDNA) in plasma is a mixture of DNA from malignant and normal cells, and can be used as a liquid biopsy to detect and quantify tumour specific mutations e.g. KRAS. We investigated the clinical value of KRAS mutations when detected in plasma compared to tumour in patients from metastatic colorectal cancer (mCRC) prior to anti-epidermal growth factor receptor (anti-EGFR) therapy. Secondly, we investigated the concentration of total cfDNA in relation to clinical outcome.

PATIENTS AND METHODS:

Patients were resistant to 5-FU, oxaliplatin and irinotecan and treated with 3rd line irinotecan (180mg/m2) and cetuximab (500mg/m2) q2w in a prospective phase II trial. The study was conducted prior to implementation of KRAS as selection criteria. Plasma was obtained from a pre-treatment EDTA blood-sample, and the total cfDNA, and KRAS mutations were quantified by an in-house qPCR method. Results are presented according to REMARK.

RESULTS:

One-hundred-and-forty patients were included. Thirty-four percent had detectable KRAS mutations in the tumour, compared to 23% in plasma. KRAS detection in archival tumour tissue showed no correlation to survival, whereas plasma KRAS status remained a strong predictive and prognostic factor in multivariate analysis (Hazard Ratio (HR)=2.98 (95% CI 1.53-5.80, p=0.001) and 2.84 (1.46-5.53, p=0.002), for OS and PFS, respectively). Combining the information of total cell free DNA levels and plasma KRAS mutation status, produced an additional prognostic effect.