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, 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

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.

Figures

Fig. 1. Development of a PCR-based assay… — **Fig. 1. Development of a PCR-based assay to identify tumor-specific mutations in plasma samples**
Colored curves indicate the proportion of cancers of the eight types evaluated in this study that can be detected with an increasing number of short (

**Fig. 2. Performance of CancerSEEK**

( A…

**Fig. 2. Performance of CancerSEEK**

( A ) ROC curve for CancerSEEK. The red point…

**Fig. 2. Performance of CancerSEEK**
(A) ROC curve for CancerSEEK. The red point on the curve indicates the test’s average performance (62%) at >99% specificity. Error bars represent 95% confidence intervals for sensitivity and specificity at this particular point. The median performance among the eight cancer types assessed was 70%. (B) Sensitivity of CancerSEEK by stage. Bars represent the median sensitivity of the eight cancer types, and error bars represent standard errors of the median. (C) Sensitivity of CancerSEEK by tumor type. Error bars represent 95% confidence intervals.

**Fig. 3. Identification of cancer type by…**

**Fig. 3. Identification of cancer type by supervised machine learning for patients classified as positive…**

**Fig. 3. Identification of cancer type by supervised machine learning for patients classified as positive by CancerSEEK**
Percentages correspond to the proportion of patients correctly classified by one of the two most likely types (sum of light and dark blue bars) or the most likely type (light blue bar). Predictions for all patients for all cancer types are provided in table S8. Error bars represent 95% confidence intervals.

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**Fig. 2. Performance of CancerSEEK**
(A) ROC curve for CancerSEEK. The red point on the curve indicates the test’s average performance (62%) at >99% specificity. Error bars represent 95% confidence intervals for sensitivity and specificity at this particular point. The median performance among the eight cancer types assessed was 70%. (B) Sensitivity of CancerSEEK by stage. Bars represent the median sensitivity of the eight cancer types, and error bars represent standard errors of the median. (C) Sensitivity of CancerSEEK by tumor type. Error bars represent 95% confidence intervals.

Fig. 3. Identification of cancer type by… — **Fig. 3. Identification of cancer type by supervised machine learning for patients classified as positive by CancerSEEK**
Percentages correspond to the proportion of patients correctly classified by one of the two most likely types (sum of light and dark blue bars) or the most likely type (light blue bar). Predictions for all patients for all cancer types are provided in table S8. Error bars represent 95% confidence intervals.

Source: PubMed

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

Abstract

Figures

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