Introduction:
Circulating cell-free methylated tumor DNA in blood from tumor patients is suitable
for minimal-invasive diagnostics. In the current study, we tested the application
of plasma methylation for detection of post-surgical residual tumor (primary tumor/metastasis)
in patients primarily treated with curative intent and for therapy response monitoring
in palliatively treated patients.
Methods:
Patients were prospectively enrolled who underwent surgical tumor excision with curative
intent (A, n = 100) or received palliative chemo- or immunotherapy (B, n = 20). Blood
was withdrawn prior to therapy start (A and B), 3 to 10 days after surgical resection
(A), and longitudinally during each systemic therapy cycle (B). Plasma methylation
of SHOX2 and SEPT9 was measured using qPCR and correlated with therapy response and
clinical course.
Results:
Plasma methylation correlated significantly with tumor burden and decreased to normal
level (≤0.16%) after tumor excision. Postoperatively elevated plasma methylation was
associated with an early relapse and poor prognosis. Rapid clearance of plasma methylation
in palliatively treated patients was associated with response to chemo- or immunotherapy.
Conclusions:
Postoperatively elevated plasma methylation is associated with the existence of residual
tumor and allows for the identification of patients who would potentially benefit
from an intensified aftercare or adjuvant treatment. In palliatively treated patients,
dynamic plasma methylation changes were associated with response to medical therapy
and might be used to individualize therapy regimen.
