Schmiegel Wolff, Scott Rodney J, Dooley Susan, Lewis Wendy, Meldrum Cliff J, Pockney Peter, Draganic Brian, Smith Steve, Hewitt Chelsee, Philimore Hazel, Lucas Amanda, Shi Elva, Namdarian Kateh, Chan Timmy, Acosta Danilo, Ping-Chang Su, Tannapfel Andrea, Reinacher-Schick Anke, Uhl Waldemar, Teschendorf Christian, Wolters Heiner, Stern Josef, Viebahn Richard, Friess Helmut, Janssen Klaus-Peter, Nitsche Ulrich, Slotta-Huspenina Julia, Pohl Michael, Vangala Deepak, Baraniskin Alexander, Dockhorn-Dworniczak Barbara, Hegewisch-Becker Susanne, Ronga Philippe, Edelstein Daniel L, Jones Frederick S, Hahn Stephan, Fox Stephen B
Department of Internal Medicine, Medical University of Bochum Hospital, Germany.
Pathology North, John Hunter Hospital, New Lambton Heights, Australia.
Mol Oncol. 2017 Feb;11(2):208-219. doi: 10.1002/1878-0261.12023. Epub 2017 Jan 20.
An accurate blood-based RAS mutation assay to determine eligibility of metastatic colorectal cancer (mCRC) patients for anti-EGFR therapy would benefit clinical practice by better informing decisions to administer treatment independent of tissue availability. The objective of this study was to determine the level of concordance between plasma and tissue RAS mutation status in patients with mCRC to gauge whether blood-based RAS mutation testing is a viable alternative to standard-of-care RAS tumor testing. RAS testing was performed on plasma samples from newly diagnosed metastatic patients, or from recurrent mCRC patients using the highly sensitive digital PCR technology, BEAMing (beads, emulsions, amplification, and magnetics), and compared with DNA sequencing data of respective FFPE (formalin-fixed paraffin-embedded) tumor samples. Discordant tissue RAS results were re-examined by BEAMing, if possible. The prevalence of RAS mutations detected in plasma (51%) vs. tumor (53%) was similar, in accord with the known prevalence of RAS mutations observed in mCRC patient populations. The positive agreement between plasma and tumor RAS results was 90.4% (47/52), the negative agreement was 93.5% (43/46), and the overall agreement (concordance) was 91.8% (90/98). The high concordance of plasma and tissue results demonstrates that blood-based RAS mutation testing is a viable alternative to tissue-based RAS testing.
一种准确的基于血液的RAS突变检测方法，用于确定转移性结直肠癌（mCRC）患者是否适合接受抗表皮生长因子受体（EGFR）治疗，这将通过在不依赖组织可用性的情况下更好地指导治疗决策，从而使临床实践受益。本研究的目的是确定mCRC患者血浆和组织RAS突变状态之间的一致性水平，以评估基于血液的RAS突变检测是否是标准护理RAS肿瘤检测的可行替代方法。使用高灵敏度数字PCR技术BEAMing（磁珠、乳液、扩增和磁性）对新诊断的转移性患者或复发性mCRC患者的血浆样本进行RAS检测，并与相应的福尔马林固定石蜡包埋（FFPE）肿瘤样本的DNA测序数据进行比较。如有可能，对不一致的组织RAS结果通过BEAMing进行重新检测。血浆（51%）和肿瘤（53%）中检测到的RAS突变发生率相似，这与mCRC患者群体中观察到的RAS突变已知发生率一致。血浆和肿瘤RAS结果之间的阳性一致性为90.4%（47/52），阴性一致性为93.5%（43/46），总体一致性（符合率）为91.8%（90/98）。血浆和组织结果的高一致性表明，基于血液的RAS突变检测是基于组织的RAS检测的可行替代方法。
