Detecting and Localizing Eight Cancer Types With One Multianalyte Blood Test

Key Points

  • The test had greater than 99% specificity for cancer.
  • The median overall sensitivity was 70% and ranged from a high of 98% for ovarian cancer to a low of 33% for breast cancer.
  • For the five cancers that have no screening tests—ovarian, liver, stomach, pancreatic, and esophageal cancers—sensitivity ranged from 69% to 98%. 

Johns Hopkins Kimmel Cancer Center researchers developed a single blood test that screens for eight common cancer types and also helps identify the location of the cancer.

The test, called CancerSEEK, is a unique noninvasive, multianalyte test that simultaneously evaluates levels of eight cancer proteins and the presence of cancer gene mutations from circulating DNA in the blood. The test is aimed at screening for eight common cancer types that account for more than 60% of cancer deaths in the Uniuted States. Five of the cancers covered by the test currently have no screening test.

Findings from the use of CancerSEEK were published by Cohen et al in Science.

Development of the Panel

“Circulating tumor DNA mutations can be highly specific markers for cancer. To capitalize on this inherent specificity, we sought to develop a small yet robust panel that could detect at least one mutation in the vast majority of cancers,” explained Joshua Cohen, an MD/PhD student at the Johns Hopkins University School of Medicine and the paper’s first author. “In fact, keeping the mutation panel small is essential to minimize false-positive results and keep such screening tests affordable.”

The investigators initially explored several hundred genes and 40 protein markers, whittling the number down to segments of 16 genes and 8 proteins. They point out that this molecular test is solely aimed at cancer screening and, therefore, is different from other molecular tests that rely on analyzing large numbers of cancer-driving genes to identify therapeutically actionable targets.

In this study, the test had greater than 99% specificity for cancer. “Very high specificity was essential, because false-positive results can subject patients to unnecessary invasive follow-up tests and procedures to confirm the presence of cancer,” said Kenneth Kinzler, PhD, Professor of Oncology and Co-Director of the Ludwig Center. The test was used on 812 healthy controls and produced only 7 false-positive results.

Study Findings

The test was evaluated on 1,005 patients with nonmetastatic, stage I to III cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast. The median overall sensitivity was 70% and ranged from a high of 98% for ovarian cancer to a low of 33% for breast cancer. For the five cancers that have no screening tests—ovarian, liver, stomach, pancreatic, and esophageal cancers—sensitivity ranged from 69% to 98%.

“A novelty of our classification method is that it combines the probability of observing various DNA mutations together with the levels of several proteins in order to make the final call,” says Cristian Tomasetti, PhD, Associate Professor of Oncology and Biostatistics, who developed the algorithm. “Another new aspect of our approach is that it uses machine learning to enable the test to accurately determine the location of a tumor down to a small number of anatomic sites in 83% of patients.”

Although the current test does not pick up every cancer, it identifies many cancers that would likely otherwise go undetected. To zero in on the analytes they included in their CancerSEEK test, the research team pulled data from more than 3 decades of cancer genetics research generated at their Ludwig Center at Johns Hopkins, as well as data from many other institutions.

To precisely determine the optimal number of DNA bases to assess in the CancerSEEK test, the researchers used a method based on diminishing returns. “The more DNA bases you assay, the more mutations you are capable of finding, but eventually you reach a point of diminishing returns,” explained Dr. Cohen. “We designed our test to reflect this point of diminishing returns, including the DNA markers that were useful in detecting the cancers and eliminating those that did not add benefit.” The result was a relatively small panel of highly selective DNA markers.

CancerSEEK is noninvasive and can, in principle, be administered by primary care providers at the time of other routine blood work.

The investigators feel that a test that will be used routinely for cancer screening must have a cost in line with or less than other currently available screening tests for single cancers, such as colonoscopy. They envision that the CancerSEEK test will eventually cost less than $500.

Larger studies of the test are currently underway.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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