Circulating cell-free methylated DNA in blood from head and neck squamous cell carcinoma patients for post-surgical residual tumor detection and therapy response monitoring

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 Blood was withdrawn prior to therapy start (A and B), 3 to 10 days after surgical resection (A), and longitudinally during each systemic therapy cycle (B).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.

Publication History

Publication Date:
23 April 2019 (online)