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Spindler, Karen-Lise Garm; Pallisgaard, Niels; Vogelius, Ivan; Jakobsen, Anders

Quantitative Cell-Free DNA, KRAS, and BRAF Mutations in Plasma from Patients with Metastatic Colorectal Cancer during Treatment with Cetuximab and Irinotecan

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  • Media type: E-Article
  • Title: Quantitative Cell-Free DNA, KRAS, and BRAF Mutations in Plasma from Patients with Metastatic Colorectal Cancer during Treatment with Cetuximab and Irinotecan
  • Contributor: Spindler, Karen-Lise Garm; Pallisgaard, Niels; Vogelius, Ivan; Jakobsen, Anders
  • imprint: American Association for Cancer Research (AACR), 2012
  • Published in: Clinical Cancer Research
  • Language: English
  • DOI: 10.1158/1078-0432.ccr-11-0564
  • ISSN: 1078-0432; 1557-3265
  • Keywords: Cancer Research ; Oncology
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title> <jats:p>Purpose: The present study investigated the levels of circulating cell-free DNA (cfDNA) in plasma from patients with metastatic colorectal cancer (mCRC) in relation to third-line treatment with cetuximab and irinotecan and the quantitative relationship of cfDNA with tumor-specific mutations in plasma.</jats:p> <jats:p>Experimental Design: Inclusion criteria were histopathologically verified chemotherapy-resistant mCRC, adequate Eastern Cooperative Oncology Group performance status, and organ function. Treatment consisted of irinotecan being administered at 350 mg/m2 for 3 weeks and weekly administration of 250 mg/m2 cetuximab until progression or unacceptable toxicity. A quantitative PCR method was developed to assess the number of cfDNA alleles and KRAS and BRAF mutation alleles in plasma at baseline.</jats:p> <jats:p>Results: The study included 108 patients. Only three patients were positive for BRAF mutations. The majority of KRAS mutations detected in tumors were also found in the plasma [32 of 41 (78%)]. Plasma cfDNA and plasma mutant KRAS levels (pmKRAS) were strongly correlated (r = 0.85, P &amp;lt; 10−4). The disease control rate was 77% in patients with low cfDNA (&amp;lt;25% quartile) and 30% in patients with high cfDNA [&amp;gt;75% quartile (P = 0.009)]. Patients with pmKRAS levels higher than 75% had a disease control rate of 0% compared with 42% in patients with lower pmKRAS (P = 0.048). Cox analysis confirmed the prognostic importance of both cfDNA and pmKRAS. High levels were clear indicators of a poor outcome.</jats:p> <jats:p>Conclusions: KRAS analysis in plasma is a viable alternative to tissue analysis. Quantitative levels of cfDNA and pmKRAS are strongly correlated and hold promise of clinical application. Clin Cancer Res; 18(4); 1177–85. ©2012 AACR.</jats:p>
  • Access State: Open Access