Liquid biopsy-based early-detection test for multiple cancers may find early-stage cancers and cancers with low DNA shedding

Joe Cavallo

Posted: 2023/04/18 11:09:00 AM

Last update: Apr 18, 2023 12:31:56 PM

Plasma cell-free DNA (cfDNA) testing is a promising approach for cancer screening, but methodologies vary in performance, with many liquid biopsy tests performing poorly in detecting early-stage or low-shedding DNA tumors. is shown. However, the results of a retrospective case-control study evaluating the performance of a novel genome-wide methylome-enrichment platform for liquid biopsy-based early detection of multiple cancers showed that the test detected 12 types of cancer, including early and low-grade cancers. I have found that it is possible to detect DNA shedding cancer.

Additional studies will be needed to confirm these findings before the blood test is ready for clinical use. A study by Park et al. will be presented at the 2023 American Association for Cancer Research (AACR) Annual Meeting (Abstract 1030/7).

Survey method

The researchers analyzed blood samples from 4,322 patients, including newly diagnosed cancer-naïve patients and age- and sex-matched non-cancer controls. Samples were analyzed on a bisulfite-free, non-degrading, genome-wide DNA methylation enrichment platform using cfDNA isolated from plasma. The samples were split into separate sets and a machine learning classifier composed of differently methylated regions was trained and tested to distinguish between cases and controls. Approximately 50% of patients had early-stage (defined as stage I and II) cancer.

In this initial analysis, researchers used 80% and 20% of the sample to evaluate the performance of a machine learning algorithm designed to distinguish patients from non-cancer controls in a training cohort. reported findings from cross-validation within a subset of 1,903 samples of . for training and testing respectively.

result

The researchers distinguished patients from controls with an area under the curve (AUC) measurement of 0.94 (0.93, 0.96), with AUCs for individual cancer types ranging from 0.91 to 0.97. AUC was 0.94 (0.92, 0.95) for stage I/II cancer and 0.95 (0.94, 0.96) for stage III/IV cancer. A subset of cancers generally considered to have low dropout rates, including bladder, breast, renal, prostate, and endometrial cancers, had an AUC of 0.92 (0.91, 0.94) and stage I /II (0.91; 0.89, 0.93) and stage III showed similar performance. /IV (0.93; 0.91, 0.95) disease in that subset.
“Initial analysis of case-control data demonstrated the feasibility of MCED’s genome-wide methylome enrichment platform. [multicancer early detection]High detection rates for low-shedding and early-stage cancers are promising for MCED applications, as this is essential for screening to identify cancers for which treatment may be more effective,” said the study. the authors conclude.

Promising clinical implications

“This platform enabled a higher signal-to-noise ratio, leading to improved performance in more challenging applications with the lowest cfDNA load,” said the authors of the presented study. Ben Ho Park, MD, PhD, Benjamin F. Byrd, Jr. Professor of Oncology, Director of the Vanderbilt Ingram Cancer Center, Professor of Medicine, Department of Hematology and Oncology, Vanderbilt University Medical Center. “Cancer that sheds large amounts of cfDNA performed best, but even cancers that are normally difficult to detect with the cfDNA assay were detected with high performance at this preliminary readout. At this stage, the robust detection of early-stage and low-shedding cancers using this genome-wide methylome-enrichment platform is very promising.”

But this is an early development study, and prospective studies are needed to confirm these findings before the liquid biopsy test is ready for clinical use, Dr. Park noted.

Disclosure: This research was sponsored by Adela Inc. There was no direct funding other than a sample acquisition fee as part of this study. For full disclosure of the study authors, please see: Abstractsonline.com.

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

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