Detection and localization of surgically resectable cancers with a multi-analyte blood test

Joshua D. Cohen; Lu Li; Yuxuan Wang; Christopher Thoburn; Bahman Afsari; Ludmila Danilova; Christopher Douville; Ammar A. Javed; Fay Wong; Austin Mattox; Ralph H. Hruban; Christopher L. Wolfgang; Michael G. Goggins; Marco Dal Molin; Tian Li Wang; Richard Roden; Alison P. Klein; Janine Ptak; Lisa Dobbyn; Joy Schaefer; Natalie Silliman; Maria Popoli; Joshua T. Vogelstein; James D. Browne; Robert E. Schoen; Randall E. Brand; Jeanne Tie; Peter Gibbs; Hui Li Wong; Aaron S. Mansfield; Jin Jen; Samir M. Hanash; Massimo Falconi; Peter J. Allen; Shibin Zhou; Chetan Bettegowda; Luis A. Diaz; Cristian Tomasetti; Kenneth W. Kinzler; Bert Vogelstein; Anne Marie Lennon; Nickolas Papadopoulos

doi:10.1126/science.aar3247

Detection and localization of surgically resectable cancers with a multi-analyte blood test

Joshua D. Cohen, Lu Li, Yuxuan Wang, Christopher Thoburn, Bahman Afsari, Ludmila Danilova, Christopher Douville, Ammar A. Javed, Fay Wong, Austin Mattox, Ralph H. Hruban, Christopher L. Wolfgang, Michael G. Goggins, Marco Dal Molin, Tian Li Wang, Richard Roden, Alison P. Klein, Janine Ptak, Lisa Dobbyn, Joy SchaeferNatalie Silliman, Maria Popoli, Joshua T. Vogelstein, James D. Browne, Robert E. Schoen, Randall E. Brand, Jeanne Tie, Peter Gibbs, Hui Li Wong, Aaron S. Mansfield, Jin Jen, Samir M. Hanash, Massimo Falconi, Peter J. Allen, Shibin Zhou, Chetan Bettegowda, Luis A. Diaz, Cristian Tomasetti, Kenneth W. Kinzler, Bert Vogelstein, Anne Marie Lennon, Nickolas Papadopoulos

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Abstract

Earlier detection is key to reducing cancer deaths. Here, we describe a blood test that can detect eight common cancer types through assessment of the levels of circulating proteins and mutations in cell-free DNA. We applied this test, called CancerSEEK, to 1005 patients with nonmetastatic, clinically detected cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast. CancerSEEK tests were positive in a median of 70% of the eight cancer types. The sensitivities ranged from 69 to 98% for the detection of five cancer types (ovary, liver, stomach, pancreas, and esophagus) for which there are no screening tests available for average-risk individuals. The specificity of CancerSEEK was greater than 99%: only 7 of 812 healthy controls scored positive. In addition, CancerSEEK localized the cancer to a small number of anatomic sites in a median of 83% of the patients.

Original language	English (US)
Pages (from-to)	926-930
Number of pages	5
Journal	Science
Volume	359
Issue number	6378
DOIs	https://doi.org/10.1126/science.aar3247
State	Published - Feb 23 2018

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Cohen, J. D., Li, L., Wang, Y., Thoburn, C., Afsari, B., Danilova, L., Douville, C., Javed, A. A., Wong, F., Mattox, A., Hruban, R. H., Wolfgang, C. L., Goggins, M. G., Molin, M. D., Wang, T. L., Roden, R., Klein, A. P., Ptak, J., Dobbyn, L., ... Papadopoulos, N. (2018). Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science, 359(6378), 926-930. https://doi.org/10.1126/science.aar3247

Cohen, JD, Li, L, Wang, Y, Thoburn, C, Afsari, B, Danilova, L, Douville, C, Javed, AA, Wong, F, Mattox, A, Hruban, RH, Wolfgang, CL, Goggins, MG, Molin, MD, Wang, TL, Roden, R, Klein, AP, Ptak, J, Dobbyn, L, Schaefer, J, Silliman, N, Popoli, M, Vogelstein, JT, Browne, JD, Schoen, RE, Brand, RE, Tie, J, Gibbs, P, Wong, HL, Mansfield, AS, Jen, J, Hanash, SM, Falconi, M, Allen, PJ, Zhou, S, Bettegowda, C, Diaz, LA, Tomasetti, C, Kinzler, KW, Vogelstein, B, Lennon, AM & Papadopoulos, N 2018, 'Detection and localization of surgically resectable cancers with a multi-analyte blood test', Science, vol. 359, no. 6378, pp. 926-930. https://doi.org/10.1126/science.aar3247

@article{2ae36224c7e54f7aa62af969947bc9ad,

title = "Detection and localization of surgically resectable cancers with a multi-analyte blood test",

abstract = "Earlier detection is key to reducing cancer deaths. Here, we describe a blood test that can detect eight common cancer types through assessment of the levels of circulating proteins and mutations in cell-free DNA. We applied this test, called CancerSEEK, to 1005 patients with nonmetastatic, clinically detected cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast. CancerSEEK tests were positive in a median of 70% of the eight cancer types. The sensitivities ranged from 69 to 98% for the detection of five cancer types (ovary, liver, stomach, pancreas, and esophagus) for which there are no screening tests available for average-risk individuals. The specificity of CancerSEEK was greater than 99%: only 7 of 812 healthy controls scored positive. In addition, CancerSEEK localized the cancer to a small number of anatomic sites in a median of 83% of the patients.",

author = "Cohen, {Joshua D.} and Lu Li and Yuxuan Wang and Christopher Thoburn and Bahman Afsari and Ludmila Danilova and Christopher Douville and Javed, {Ammar A.} and Fay Wong and Austin Mattox and Hruban, {Ralph H.} and Wolfgang, {Christopher L.} and Goggins, {Michael G.} and Molin, {Marco Dal} and Wang, {Tian Li} and Richard Roden and Klein, {Alison P.} and Janine Ptak and Lisa Dobbyn and Joy Schaefer and Natalie Silliman and Maria Popoli and Vogelstein, {Joshua T.} and Browne, {James D.} and Schoen, {Robert E.} and Brand, {Randall E.} and Jeanne Tie and Peter Gibbs and Wong, {Hui Li} and Mansfield, {Aaron S.} and Jin Jen and Hanash, {Samir M.} and Massimo Falconi and Allen, {Peter J.} and Shibin Zhou and Chetan Bettegowda and Diaz, {Luis A.} and Cristian Tomasetti and Kinzler, {Kenneth W.} and Bert Vogelstein and Lennon, {Anne Marie} and Nickolas Papadopoulos",

note = "Funding Information: Career Award for Medical Scientists; The Doris Duke Charitable Foundation (2014107); and National Institutes of Health grants P50-CA62924, P50-CA102701, CA06973, CA152753, GM-07309, U01CA200469, and U01CA152753. N.P., S.Z., K.W.K., L.D., and B.V. are founders of Personal Genome Diagnostics and PapGene. B.V. and K.W.K are on the Scientific Advisory Board of Sysmex-Inostics. B.V. is also on the Scientific Advisory Boards of Exelixis GP. R.H.H. is on the Board of Directors of MiDiagnostics. These companies and others have licensed technologies from Johns Hopkins, and N.P., K.W.K., L.D., B.V, and R.H.H. receive equity or royalties from these licenses. The terms of these arrangements are being managed by Johns Hopkins University in accordance with its conflict of interest policies. L.D. is on the Board of Directors of Jounce Therapeutics and is a Scientific Advisor for Genocea, Cell Design Labs, and Merck. A.S.M. is a consultant for Abbvie, Genentech, Bristol-Myers Squibb, and Trovagene. B.V., N.P., and K.W.K. are inventors on a patent (U.S. 20140227705 A1) held by Johns Hopkins University that covers basic aspects of the SafeSeqS technology used in this paper. B.V., K.W.K., N.P., J.D.C., C.T., and A.M.L. are inventors on a patent application to be submitted by Johns Hopkins University that covers other aspects of SafeSeqS as well as the multi-analyte approach described in this paper. All data needed to evaluate the conclusions in the paper are present in the paper and/or the supplementary materials. Contact C.T. for questions about the algorithms; A.M.L. for questions about clinically related issues; K.W.K about the sequencing analyses; B.V. about experimental procedures; and N.P. about the overall design of the study. Funding Information: We thank our patients for their courage and generosity. We are grateful to C. Blair and K. Judge for expert technical and administrative assistance. We thank H. Ren, J. Olson, M. Hathcok, H. Zeh, A. Singhi, S. Crippa, M. Ryan, and L. Ryan for their assistance with this study. This work was supported by the Lustgarten Foundation for Pancreatic Cancer Research; The Virginia and D. K. Ludwig Fund for Cancer Research; The Conrad N. Hilton Foundation; The Commonwealth Fund; The John Templeton Foundation; the Clinomics Program; Mayo Clinic Center for Individualized Medicine; the Mayo Clinic Biobank; The Sol Goldman Center for Pancreatic Cancer Research; The Michael Rolfe Pancreatic Cancer Research Foundation; The Benjamin Baker Scholarship; The Gray Foundation; S. Wojcicki and D. Troper; The Marcus Foundation; The Honorable Tina Brozman Foundation; The Burroughs Wellcome Publisher Copyright: {\textcopyright} 2017 The Authors.",

year = "2018",

month = feb,

day = "23",

doi = "10.1126/science.aar3247",

language = "English (US)",

volume = "359",

pages = "926--930",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6378",

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TY - JOUR

T1 - Detection and localization of surgically resectable cancers with a multi-analyte blood test

AU - Cohen, Joshua D.

AU - Li, Lu

AU - Wang, Yuxuan

AU - Thoburn, Christopher

AU - Afsari, Bahman

AU - Danilova, Ludmila

AU - Douville, Christopher

AU - Javed, Ammar A.

AU - Wong, Fay

AU - Mattox, Austin

AU - Hruban, Ralph H.

AU - Wolfgang, Christopher L.

AU - Goggins, Michael G.

AU - Molin, Marco Dal

AU - Wang, Tian Li

AU - Roden, Richard

AU - Klein, Alison P.

AU - Ptak, Janine

AU - Dobbyn, Lisa

AU - Schaefer, Joy

AU - Silliman, Natalie

AU - Popoli, Maria

AU - Vogelstein, Joshua T.

AU - Browne, James D.

AU - Schoen, Robert E.

AU - Brand, Randall E.

AU - Tie, Jeanne

AU - Gibbs, Peter

AU - Wong, Hui Li

AU - Mansfield, Aaron S.

AU - Jen, Jin

AU - Hanash, Samir M.

AU - Falconi, Massimo

AU - Allen, Peter J.

AU - Zhou, Shibin

AU - Bettegowda, Chetan

AU - Diaz, Luis A.

AU - Tomasetti, Cristian

AU - Kinzler, Kenneth W.

AU - Vogelstein, Bert

AU - Lennon, Anne Marie

AU - Papadopoulos, Nickolas

N1 - Funding Information: Career Award for Medical Scientists; The Doris Duke Charitable Foundation (2014107); and National Institutes of Health grants P50-CA62924, P50-CA102701, CA06973, CA152753, GM-07309, U01CA200469, and U01CA152753. N.P., S.Z., K.W.K., L.D., and B.V. are founders of Personal Genome Diagnostics and PapGene. B.V. and K.W.K are on the Scientific Advisory Board of Sysmex-Inostics. B.V. is also on the Scientific Advisory Boards of Exelixis GP. R.H.H. is on the Board of Directors of MiDiagnostics. These companies and others have licensed technologies from Johns Hopkins, and N.P., K.W.K., L.D., B.V, and R.H.H. receive equity or royalties from these licenses. The terms of these arrangements are being managed by Johns Hopkins University in accordance with its conflict of interest policies. L.D. is on the Board of Directors of Jounce Therapeutics and is a Scientific Advisor for Genocea, Cell Design Labs, and Merck. A.S.M. is a consultant for Abbvie, Genentech, Bristol-Myers Squibb, and Trovagene. B.V., N.P., and K.W.K. are inventors on a patent (U.S. 20140227705 A1) held by Johns Hopkins University that covers basic aspects of the SafeSeqS technology used in this paper. B.V., K.W.K., N.P., J.D.C., C.T., and A.M.L. are inventors on a patent application to be submitted by Johns Hopkins University that covers other aspects of SafeSeqS as well as the multi-analyte approach described in this paper. All data needed to evaluate the conclusions in the paper are present in the paper and/or the supplementary materials. Contact C.T. for questions about the algorithms; A.M.L. for questions about clinically related issues; K.W.K about the sequencing analyses; B.V. about experimental procedures; and N.P. about the overall design of the study. Funding Information: We thank our patients for their courage and generosity. We are grateful to C. Blair and K. Judge for expert technical and administrative assistance. We thank H. Ren, J. Olson, M. Hathcok, H. Zeh, A. Singhi, S. Crippa, M. Ryan, and L. Ryan for their assistance with this study. This work was supported by the Lustgarten Foundation for Pancreatic Cancer Research; The Virginia and D. K. Ludwig Fund for Cancer Research; The Conrad N. Hilton Foundation; The Commonwealth Fund; The John Templeton Foundation; the Clinomics Program; Mayo Clinic Center for Individualized Medicine; the Mayo Clinic Biobank; The Sol Goldman Center for Pancreatic Cancer Research; The Michael Rolfe Pancreatic Cancer Research Foundation; The Benjamin Baker Scholarship; The Gray Foundation; S. Wojcicki and D. Troper; The Marcus Foundation; The Honorable Tina Brozman Foundation; The Burroughs Wellcome Publisher Copyright: © 2017 The Authors.

PY - 2018/2/23

Y1 - 2018/2/23

N2 - Earlier detection is key to reducing cancer deaths. Here, we describe a blood test that can detect eight common cancer types through assessment of the levels of circulating proteins and mutations in cell-free DNA. We applied this test, called CancerSEEK, to 1005 patients with nonmetastatic, clinically detected cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast. CancerSEEK tests were positive in a median of 70% of the eight cancer types. The sensitivities ranged from 69 to 98% for the detection of five cancer types (ovary, liver, stomach, pancreas, and esophagus) for which there are no screening tests available for average-risk individuals. The specificity of CancerSEEK was greater than 99%: only 7 of 812 healthy controls scored positive. In addition, CancerSEEK localized the cancer to a small number of anatomic sites in a median of 83% of the patients.

AB - Earlier detection is key to reducing cancer deaths. Here, we describe a blood test that can detect eight common cancer types through assessment of the levels of circulating proteins and mutations in cell-free DNA. We applied this test, called CancerSEEK, to 1005 patients with nonmetastatic, clinically detected cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast. CancerSEEK tests were positive in a median of 70% of the eight cancer types. The sensitivities ranged from 69 to 98% for the detection of five cancer types (ovary, liver, stomach, pancreas, and esophagus) for which there are no screening tests available for average-risk individuals. The specificity of CancerSEEK was greater than 99%: only 7 of 812 healthy controls scored positive. In addition, CancerSEEK localized the cancer to a small number of anatomic sites in a median of 83% of the patients.

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ER -

Detection and localization of surgically resectable cancers with a multi-analyte blood test

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