Although plasma cell-free DNA (cfDNA) tests represent a promising approach for cancer screening, different methodologies vary in performance and many liquid biopsy tests show decreased performance in detecting early-stage or low-shedding DNA tumors. However, the results from a retrospective case-control study evaluating the performance of a novel genome-wide methylome enrichment platform for a liquid biopsy–based multicancer early detection test found that the test could detect 12 types of cancers, including early-stage and low DNA–shedding cancers.
Additional studies will be needed to confirm these findings before the blood test is ready for clinical use. The study by Park et al was presented during the American Association for Cancer Research (AACR) Annual Meeting 2023 (Abstract 1030/7).
Study Methodology
The researchers analyzed blood samples from 4,322 patients, including treatment-naive patients with newly diagnosed cancer, and age- and gender-matched noncancer controls. Samples were analyzed with a bisulfite-free, nondegradative genome-wide DNA methylation enrichment platform using cfDNA isolated from plasma. The samples were split into distinct sets to train and test a machine-learning classifier consisting of differentially methylated regions to distinguish cases from controls. Approximately 50% of the patients had early-stage— defined as stage I and II—cancers.
For this initial analysis, researchers reported findings from cross-validation within a subset of 1,903 samples in the training cohort to assess the performance of a machine-learning algorithm designed to distinguish patients from the noncancer controls, using 80% and 20% of the samples for training and testing, respectively.
Results
The researchers distinguished the patients from the controls with an area under the curve (AUC) measure of 0.94 (0.93, 0.96), with AUCs for individual cancer types ranging from 0.91 to 0.97. The AUC was 0.94 (0.92, 0.95) for stage I/II cancers and 0.95 (0.94, 0.96) for stage III/IV cancers. The AUC was 0.92 (0.91, 0.94) in the subset of cancers typically considered low shedding, including bladder, breast, renal, prostate, and endometrial cancers, with similar performance for stage I/II (0.91; 0.89, 0.93) and stage III/IV (0.93; 0.91, 0.95) disease in that subset.
“Initial analysis of case-control data demonstrates feasibility of a genome-wide methylome enrichment platform for MCED [multicancer early detection]. The high detection of low-shedding and early-stage cancers is promising for MCED applications, as this will be critical for screening to identify cancers for which treatment may be more effective,” concluded the study authors.
Promising Clinical Significance
“This platform allowed for a higher signal-to-noise ratio and led to increased performance in the more challenging applications where the cfDNA burden is the lowest,” said presenting study author Ben Ho Park, MD, PhD, Benjamin F. Byrd, Jr Professor of Oncology, Director of the Vanderbilt-Ingram Cancer Center, and Professor of Medicine in the Division of Hematology and Oncology at Vanderbilt University Medical Center. “Cancers that shed a high amount of cfDNA had the best performance, but even cancers that are typically difficult to detect with cfDNA assays were detected with high performance in this interim readout. At this early stage in development, the robust detection of early-stage and low-shedding cancers with this genome-wide methylome enrichment platform is very promising.”
However, Dr. Park noted that this was an early development study, and that prospective studies will be needed to confirm these findings and before the liquid biopsy test is ready for use in the clinic.
Disclosure: This study was sponsored by Adela Inc. No direct funding was provided as part of this study outside of sample acquisition fees. For full disclosures of the study authors, visit abstractsonline.com.
