Clinical utility of circulating tumor DNA in patients with head and neck cancers.

Abstract

e18003 Background: Globally, head and neck cancers (HNCs) account for over 900,000 cases annually with a meager overall survival rate of 50%. While early-stage HNCs may be amenable to surgery, advanced disease is treated with systemic therapy or chemoradiation. For localized disease, chemo-radiation is often curative, but is associated with severe toxicity. Assessment of systemic treatment in the era of immunotherapy is often challenging due to the pseudoprogression phenomenon. In general, surveillance is limited to clinical follow-up and radiological imaging due to the lack of a sensitive and specific biomarker to assess treatment response and disease progression. Circulating tumor DNA (ctDNA) has shown promise as a reliable marker of disease activity in several solid tumors. In this study we evaluated the clinical utility of ctDNA for monitoring of therapeutic response and disease progression in patients with HNCs. Methods: ctDNA analysis was performed utilizing a personalized, tumor-informed ctDNA assay (Signatera™ bespoke mPCR NGS assay) in patients with advanced stage (III, IV) HNC who underwent chemoradiation or systemic therapy. ctDNA levels were measured at diagnosis, throughout treatment and during remission. The primary endpoint was correlation of ctDNA kinetics with radiological response. The secondary endpoint was the rate of ctDNA positivity during remission. Additional data collected included patient demographics and tumor clinicopathologic characteristics. Analysis was conducted using descriptive statistics. Results: ctDNA kinetics from 15 patients with squamous HNCs were analyzed. Due to insufficient time points, 5 five patients were excluded from this analysis. At diagnosis, 9/10 (90%) patients were ctDNA-positive, with baseline ctDNA levels ranging from 0.2 to 8500 mean tumor molecules (MTM)/mL of plasma. Patients received either chemoradiation (7/10) or (chemo)immunotherapy (3/10). Among patients who received chemoradiation, 4 out of 7 cleared ctDNA in less than 40 days, while 2 out of 7 had persistent ctDNA after 40 days. Those who showed ctDNA clearance had a continued response at 3-6 month follow-up both by ctDNA and by standard of care imaging. The 2 patients that did not clear ctDNA by day 40 ultimately relapsed on imaging and had rising ctDNA levels within 3 months of completion of chemoradiation. The patient who was ctDNA negative at baseline remained negative throughout the treatment and follow up. Of the patients who received chemo(immunotherapy), 2/3 cleared ctDNA after 2 cycles of therapy and continued to be in remission. The remaining patient who did not show ctDNA clearance became refractory to treatment. Conclusions: Our study demonstrates the feasibility of personalized and tumor-informed ctDNA in patients with advanced HNCs. Monitoring of ctDNA kinetics during therapy may enable prediction of therapeutic response and early disease progression to guide clinical decision-making.