How a new blood test detects dozens of cancers

Researchers have developed a new, highly accurate blood test capable of detecting more than 50 types of cancer at various locations in the body, according to the results of a recent study published in the Annals of Oncology. 

The test employs next-generation sequencing to assess the arrangement of methyl groups on the DNA of cancer cells. Methyl groups attach to specific sections of DNA and help control the activation or inactivation of genes. (Methylation patterns are even more characteristic of cancer cells than are genetic mutations.) Dead tumor cells empty DNA with attached methyl groups into the blood, where they are detected by the test.

“Our results show that this approach to testing cell-free DNA (cfDNA) in blood can detect a broad range of cancer types at virtually any stage of the disease, with specificity and sensitivity approaching the level needed for population-level screening,” said co-lead author Geoffrey Oxnard, MD, Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, MA. “The test can be an important part of clinical trials for early cancer detection.”

Because early cancer detection is critical for optimal patient outcomes and screening is only available for a limited number of select cancer types, Dr. Oxnard and colleagues set out to determine the efficacy of targeted methylation analysis of circulating cfDNA to identify and localize several cancer types across all stages, at high specificity.  

For the prospective, multicenter, case-control, observational Circulation Cell-free Genome Atlas (CCGA) trial, they collected de-identified biospecimens from participants with and without cancer from 142 sites in North America. From each participant, up to 80 mL whole blood was collected. Participants with cancer submitted pre-treatment tumor tissue (when available). 

In this substudy of the CCGA trial, they used the test to assess cfDNA in 6,689 blood samples from 2,482 patients with cancer and 4,207 without cancer. Cancer types included breast, colorectal, esophageal, gallbladder, bladder, gastric, ovarian, head and neck, lung, lymphoid leukemia, multiple myeloma, and pancreatic cancer.

Using their novel blood test, Dr. Oxnard and fellow researchers detected more than 50 cancer types, including deadly cancers, and the targeted methylation approach localized the tissue of origin with > 90% accuracy.

For the 12 cancer types that account for nearly two-thirds of US cancer deaths—anus, bladder, colon/rectum, esophagus, head and neck, liver/bile-duct, lung, lymphoma, ovary, pancreas, plasma cell neoplasm, and stomach—the overall specificity of the test was 99.3%, and its sensitivity, 67.3%. 

Within this group, the sensitivity was 39% for patients with stage I cancer, 69% for those with stage II, 83% for those with stage III, and 92% for those with stage IV. The stage I-III sensitivity across all 50 cancer types was 43.9%. When cancer was detected, the test correctly identified the organ or tissue of cancer origin in more than 90% of cases—critical information for determining how the disease is diagnosed and managed.

“Our previous work indicated that methylation-based tests outperform traditional DNA-sequencing approaches to detecting multiple forms of cancer in blood samples. The results of this study suggest that such assays could be a feasible way of screening people for a wide variety of cancers,” concluded Dr. Oxnard.