The following article features coverage from the American Association for Cancer Research (AACR) 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

A plasma cfDNA test was able to detect cancer in patients who had a high suspicion of cancer, and was able to predict tissue of origin among patients with confirmed cancer, according to results presented at the American Association for Cancer Research (AACR) Virtual Annual Meeting I 2020.1

“Our thought was that a simple and noninvasive multicancer early-detection test could potentially decrease mortality,” David D. Thiel, MD, of the Mayo Clinic in Jacksonville, Florida, and lead author and presenter of the study, said.

Although there are screening protocols for several cancer types, adherence is often suboptimal, and many cancer types do not have a screening test. This test uses a single blood sample collected at the point of care, Dr Thiel said, and is being developed to identify multiple cancer types before metastatic disease develops.

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The cfDNA test is being developed as part of the Circulating Cell-Free Genome Atlas (CCGA) Study, which is fully enrolled with 15,254 participants with or without cancer from 142 sites. Blood samples were collected from all participants, and tissue samples were collected from the tumors of patients with cancer. The follow-up of the study is 5 years.

The CCGA study participants were separated into 3 substudies: substudy 1 for discovery analyses of independent assays; substudy 2 for assay refinement, and substudy 3 for further validation.

In substudy 1, “whole-genome methylation outperformed others and was selected for further development,” Dr Thiel said. Substudy 2 used targeted methylation for training and validation of the targeted methylation classifier.

Dr Thiel said that methylation can “identify patterns that differentiate cancer vs noncancer, and predicts tissue of origin.”

In this analysis, samples of 303 patients with a high suspicion of cancer (HCS) were analyzed for training or validation and then patients were classified as having confirmed cancer or confirmed noncancer. The group with confirmed cancer represented multiple cancer types and stages I through IV.

In the overall substudy 2 cohort, the cfDNA test had 99.8% and 99.3% specificity for detecting cancer in training and validation, respectively. In the HCS subgroup from substudy 2, the specificity increased to 100% for both training and validation.

This suggests “utility of the test in patients with symptoms,” Dr Thiel said.

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Sensitivity was similar between the overall substudy 2 cohort and the HCS subset. The sensitivity for detecting all cancers in the training set was 40.2% and 46.7% in the validation set. When kidney cancer was excluded, this increased to 50.4% and 59.3% for training and validation, respectively. According to Dr Thiel, the reason for this difference is that cfDNA is not very present in kidney cancer for currently unknown reasons.

Accuracy of tissue-of-origin prediction by the cfDNA test was 85.5% in the training set and 97.1% in the validation set for multiple cancer types, which was similar between the overall substudy 2 cohort and the HCS subset.

“This targeted methylation-based multicancer early-detection test shows the potential to detect cancer and predict [tissue of origin] in individuals with high clinical suspicion of cancer ahead of confirmed pathologic diagnosis,” Dr Thiel said.

He said the test “could potentially be utilized to accelerate the diagnostic workup of individuals with high suspicion of cancer.”

Read more of Cancer Therapy Advisor‘s coverage of AACR 2020 meeting by visiting the conference page.


Thiel DD, Chen X, Kurtzman KN, et al. Prediction of cancer and tissue of origin in individuals with suspicion of cancer using a cell-free DNA multi-cancer early detection test. Presented at: American Association for Cancer Research (AACR) Virtual Annual Meeting I; April 27-28, 2020. Abstract CT021.