Dimo Dietrich (Bonn), Franz-Georg Bauernfeind (Bonn), Moritz Färber (Bonn), Peter Brossart (Bonn), Sebastian Strieth (Bonn), Alina Franzen (Bonn)
Introduction: Anti-PD-1-targeted immunotherapy has shown efficacy in the palliative treatment of recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Adjuvant treatment of locally advanced HNSCC after surgery with curative intent is tested in ongoing clinical trials. Liquid biopsy biomarkers, e.g., circulating cell-free DNA (ccfDNA), might aid monitoring of response to palliative treatment or disease recurrence during adjuvant treatment. In the present study, we tested the utility of SEPT9 ccfDNA methylation for response and recurrence monitoring in adjuvant and palliative anti-PD-1-treated locally advanced and R/M HNSCC.
Material and methods: We included N = 25 HNSCC patients treated with adjuvant or palliative anti-PD-1 immune checkpoint blockade. We applied quasi-digital methylation-specific real-time PCR to determine SEPT9 ccfDNA methylation levels in blood plasma prior to and ~ 40 days after palliative treatment initiation with regard to outcome (objective response, progression-free survival, and overall survival). In the adjuvant setting, we associated longitudinal SEPT9 ccfDNA methylation levels with disease recurrence.
Results: Low SEPT9 ccfDNA methylation levels at baseline or rapid ccfDNA methylation clearance during palliative treatment was strongly associated with beneficial survival of R/M HNSCC patients. Low SEPT9 ccfDNA methylation during adjuvant treatment was associated with recurrence-free survival.
Conclusion: Our study suggests SEPT9 ccfDNA methylation to be an early predictor of outcome in anti-PD-1-treated HNSCC patients. SEPT9 ccfDNA methylation testing may aid individualized treatment decision making.
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