Prognostic Significance of Blood-Based Multi-cancer Detection in Plasma Cell-Free DNA.

Area of Science:

• Oncology
• Genomics
• Biomarkers

Background:

• Cell-free DNA (cfDNA) targeted methylation (TM) sequencing is a novel approach for multi-cancer early detection (MCED).
• MCED tests aim to detect cancer and predict its origin, offering potential for improved patient outcomes.

Purpose of the Study:

• To evaluate the prognostic significance of cancer detection by an MCED test using longitudinal follow-up data.
• To assess if MCED test results provide prognostic information beyond established clinical factors.

Main Methods:

• Plasma cfDNA samples were analyzed using a TM sequencing approach within a Circulating Cell-free Genome Atlas (CCGA) substudy.
• Machine learning classifiers predicted cancer status and origin, and overall survival (OS) was analyzed in relation to MCED test results.
• Statistical models accounted for clinical stage, diagnosis method, age, and cancer type (SEER data) for robust analysis.

Main Results:

• Cancers not detected by the MCED test demonstrated significantly better OS (P < 0.0001) compared to detected cancers.
• The MCED test's prognostic value extended beyond clinical stage and diagnosis method.
• Detected cancers showed better OS than expected based on SEER data, and the MCED test differentiated aggressive from less aggressive cancers (P < 0.0001).

Conclusions:

• MCED test cancer detection is a significant prognostic factor, independent of clinical stage and diagnosis method.
• The MCED test identifies cancers with a better prognosis compared to detected cancers and SEER-based survival expectations.
• Tumor fraction in cfDNA may link MCED test results to cancer prognosis.