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 Jr; 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

Science. 2018 Feb 23;359(6378):926-930. doi: 10.1126/science.aar3247. Epub 2018 Jan 18.

Authors

Joshua D Cohen^{1

2

3

4

5}, Lu Li⁶, Yuxuan Wang^{1

2

3

4}, Christopher Thoburn³, Bahman Afsari⁷, Ludmila Danilova⁷, Christopher Douville^{1

2

3

4}, Ammar A Javed⁸, Fay Wong^{1

3

4}, Austin Mattox^{1

2

3

4}, Ralph H Hruban^{3

4

9}, Christopher L Wolfgang⁸, Michael G Goggins^{3

4

9

10

11}, Marco Dal Molin⁴, Tian-Li Wang^{3

9}, Richard Roden^{3

9}, Alison P Klein^{3

4

12}, Janine Ptak^{1

2

3

4}, Lisa Dobbyn^{1

3

4}, Joy Schaefer^{1

3

4}, Natalie Silliman^{1

2

3

4}, Maria Popoli^{1

3

4}, Joshua T Vogelstein¹³, James D Browne¹⁴, Robert E Schoen^{15

16}, Randall E Brand¹⁵, Jeanne Tie^{17

18

19

20}, Peter Gibbs^{17

18

19

20}, Hui-Li Wong¹⁷, Aaron S Mansfield²¹, Jin Jen²², Samir M Hanash²³, Massimo Falconi²⁴, Peter J Allen²⁵, Shibin Zhou^{1

3

4}, Chetan Bettegowda^{1

3

4}, Luis A Diaz Jr^{1

3

4}, Cristian Tomasetti^{26

6

7}, Kenneth W Kinzler^{27

3

4}, Bert Vogelstein^{27

2

3

4}, Anne Marie Lennon^{26

4

8

10

11}, Nickolas Papadopoulos^{27

3

4}

Affiliations

¹ Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
² Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
³ Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁴ Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁵ Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁶ Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA.
⁷ Division of Biostatistics and Bioinformatics, Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
⁸ Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
⁹ Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
¹⁰ Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
¹¹ Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
¹² Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA.
¹³ Institute for Computational Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
¹⁴ Department of Computer Science, Johns Hopkins University Whiting School of Engineering, Baltimore, MD 21218, USA.
¹⁵ Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA.
¹⁶ Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
¹⁷ Division of Systems Biology and Personalized Medicine, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3021, Australia.
¹⁸ Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC 3010, Australia.
¹⁹ Department of Medical Oncology, Western Health, Melbourne, VIC 3021, Australia.
²⁰ Department of Medical Oncology, Peter MacCallum Cancer Center, Melbourne, VIC 3000, Australia.
²¹ Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, MN 55902, USA.
²² Division of Experimental Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55902, USA.
²³ Sheikh Ahmed Center for Pancreatic Cancer Research, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
²⁴ Division of Pancreatic Surgery, Department of Surgery, San Raffaele Scientific Institute Research Hospital, 20132 Milan, Italy.
²⁵ Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
²⁶ Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. [email protected] [email protected] [email protected] [email protected] [email protected].
²⁷ Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. [email protected] [email protected] [email protected] [email protected] [email protected].

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.

Publication types

Evaluation Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Circulating Tumor DNA / genetics*
Costs and Cost Analysis
Early Detection of Cancer / economics
Early Detection of Cancer / methods*
Hematologic Tests* / economics
Humans
Mutation
Neoplasm Proteins / blood*
Neoplasms / blood
Neoplasms / diagnosis*
Neoplasms / genetics
Neoplasms / surgery*
Polymerase Chain Reaction / methods

Substances

Circulating Tumor DNA
Neoplasm Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding