In the realm of metastatic cancer surveillance, monitoring circulating tumor DNA (ctDNA) levels has emerged as a critical component in assessing disease progression. A recent study published in The Journal of Molecular Diagnostics by Elsevier introduces a novel dual threshold model that could significantly enhance cancer surveillance, patient stratification, and personalized treatment approaches.
Lead investigator Geert A. Martens, MD, PhD, from the Department of Laboratory Medicine at AZ Delta General Hospital and the Department of Biomolecular Medicine at Ghent University in Belgium, explains the current limitations of monitoring methods: “Currently, medical imaging is the primary tool for tracking metastatic breast cancer progression, supplemented by less precise biomarkers like CA15-3. Liquid biopsy, which involves monitoring tumor-specific mutations in circulating DNA, offers a superior approach but lacks standardized interpretation guidelines for clinicians.” The team aimed to address this gap with their innovative dual threshold model.
Researchers conducted an extensive longitudinal study involving two years of frequent (every five weeks) ctDNA level measurements in advanced breast cancer patients. Utilizing various techniques such as targeted deep sequencing and digital PCR, they found a perfect correlation between the methods. The choice of technique would depend on factors like cost and turnaround times within each pathology laboratory.
Dr. Martens highlights their findings: “We have confirmed that ctDNA levels are more accurate than traditional biomarkers like CA15-3 in identifying tumor progression, with earlier detection (within three months) achieved through frequent measurements. Moreover, we developed a simple dual threshold classifier—what we call the ‘0/10/100 copy model’—that provides clear results 90% of the time. Levels below 10 mutant copies/mL suggest little risk of progression, while those above 100 copies/mL indicate at least a 90% chance.”
Advocating for a shift in clinical practice, Dr. Martens recommends that advanced cancer centers adopt patient-specific digital PCR tests focused on mutation detection and implement regular ctDNA monitoring for enhanced surveillance and early disease recognition. This approach offers several benefits: increased sensitivity and specificity, optimized use of radiology resources, reduced hospital visits, diminished anxiety, and potential health-economic advantages.
Furthermore, the study confirmed that similar thresholds can be applied to metastatic non-small-cell lung cancer patients. Dr. Martens emphasizes the practicality of their model beyond traditional survival curve analyses: “Our concept provides a robust statistical framework for reproducibility and retrospective application to any dataset with registered progression outcomes. We hope our work will inspire further research into ctDNA concentration-guided care schedules in advanced cancers.”
By focusing on actual ctDNA concentrations through relatively inexpensive PCR tests, doctors can better manage retesting intervals for tumors or liquid biopsies using Comprehensive Genomic Profiling, paving the way for more targeted and effective cancer management strategies.
