Blood-based detection of RAS mutations to guide anti-EGFR therapy in colorectal cancer patients: concordance of results from circulating tumor DNA and tissue-based RAS testing

被引：115

作者：

Schmiegel, Wolff ^{[1
]}

Scott, Rodney J. ^{[2
,3
,4
]}

Dooley, Susan ^{[2
]}

Lewis, Wendy ^{[2
]}

Meldrum, Cliff J. ^{[2
]}

Pockney, Peter ^{[4
,5
]}

Draganic, Brian ^{[4
,5
]}

Smith, Steve ^{[4
,5
]}

Hewitt, Chelsee ^{[6
,7
]}

Philimore, Hazel ^{[6
,7
]}

Lucas, Amanda ^{[6
,7
]}

Shi, Elva ^{[6
,7
]}

Namdarian, Kateh ^{[6
,7
]}

Chan, Timmy ^{[6
,7
]}

Acosta, Danilo ^{[6
,7
]}

Ping-Chang, Su ^{[6
,7
]}

Tannapfel, Andrea ^{[8
]}

Reinacher-Schick, Anke ^{[9
]}

Uhl, Waldemar ^{[10
]}

Teschendorf, Christian ^{[11
]}

Wolters, Heiner ^{[12
]}

Stern, Josef ^{[12
]}

Viebahn, Richard ^{[13
]}

Friess, Helmut ^{[14
]}

Janssen, Klaus-Peter ^{[14
]}

Nitsche, Ulrich ^{[14
]}

Slotta-Huspenina, Julia ^{[15
]}

Pohl, Michael ^{[1
]}

Vangala, Deepak ^{[1
,16
]}

Baraniskin, Alexander ^{[1
]}

Dockhorn-Dworniczak, Barbara ^{[17
,18
]}

Hegewisch-Becker, Susanne ^{[19
]}

Ronga, Philippe ^{[20
]}

Edelstein, Daniel L. ^{[21
]}

Jones, Frederick S. ^{[21
]}

Hahn, Stephan ^{[16
]}

Fox, Stephen B. ^{[6
,7
]}

机构：

[1] Med Univ, Bochum Hosp, Dept Internal Med, Bochum, Germany

[2] John Hunter Hosp, Pathol North, New Lambton Hts, Australia

[3] Hunter Med Res Inst, Newcastle, NSW, Australia

[4] Univ Newcastle, Fac Med & Hlth, Newcastle, NSW, Australia

[5] John Hunter Hosp, Div Surg, New Lambton Hts, Australia

[6] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia

[7] Univ Melbourne, Melbourne, Vic, Australia

[8] Univ Bochum Hosp, Inst Pathol, Bochum, Germany

[9] Ruhr Univ Bochum, St Josef Hosp, Dept Internal Med, Div Hematol & Oncol, Bochum, Germany

[10] Ruhr Univ Bochum, St Josef Hosp, Dept Visceral & Gen Surg, Bochum, Germany

[11] St Josefs Hosp, Dept Internal Med, Dortmund, Germany

[12] St Josephs Hosp, Dept Visceral & Gen Surg, Dortmund, Germany

[13] Med Univ, Bochum Hosp, Dept Visceral & Gen Surg, Bochum, Germany

[14] Univ Hosp, Tech Univ Munich, Klinikum Rechts Isar, Dept Surg, Munich, Germany

[15] Tech Univ Munich, Dept Pathol, Munich, Germany

[16] Univ Bochum Hosp, Dept Mol GI Oncol, Bochum, Germany

[17] Ctr Pathol, Kempten, Germany

[18] MVZ Humangenet & Lab Med, Martinsried, Germany

[19] Ctr Haematooncol, Hamburg, Germany

[20] Merck KGAa, Global Med Affairs Oncol, Darmstadt, Germany

[21] Sysmex Inostics Inc, Med Sci Affairs, Mundelein, IL USA

来源：

MOLECULAR ONCOLOGY | 2017年 / 11卷 / 02期

关键词：

anti-EGFR therapy; CRC; ctDNA; plasma; RAS mutations; PLUS CETUXIMAB TREATMENT; PHASE-III TRIAL; 1ST-LINE TREATMENT; AMERICAN SOCIETY; PREDICT RESPONSE; OPEN-LABEL; KRAS; FLUOROURACIL; LEUCOVORIN; PANITUMUMAB;

D O I：

10.1002/1878-0261.12023

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 tissuebased RAS testing.

引用

页码：208 / 219

页数：12

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