Plasma circulating tumor DNA as a potential tool for disease monitoring in head and neck cancer

Abstract

Background: Recommendations for perioperative therapy in head and neck cancer are not explicit and recurrence occurs frequently. Circulating tumor DNA is an emerging cancer biomarker, but has not been extensively explored for detection of recurrence in head and neck cancer.

Methods: Patients diagnosed with head and neck squamous cell carcinoma were recruited into the study protocol. Tumors were sequenced to identify patient-specific mutations. Mutations were then identified in plasma circulating tumor DNA from pre-treatment blood samples and longitudinally during standard follow-up. Circulating tumor DNA status during follow-up was correlated to disease recurrence.

Results: Samples were taken from eight patients. Tumor mutations were verified in seven patients. Baseline circulating tumor DNA was positive in six patients. Recurrence occurred in four patients, two of whom had detectable circulating tumor DNA prior to recurrence.

Conclusion: Circulating tumor DNA is a potential tool for disease and recurrence monitoring following curative therapy in head and neck cancer, allowing for better prognostication, and/or modification of treatment strategies.

Keywords: cancer biomarker; cancer diagnostics; cell-free DNA; circulating tumor DNA; liquid biopsy.

Figure 1

Consort diagram for eight patients diagnosed with head and neck cancer who were enrolled in this study

Figure 2

Raw positive result for plasma circulating tumor DNA. The baseline plasma sample in patient HN01 is represented in the bottom plot compared to the actual mutational frequency following correction by Debarcer (consensus data). This patient had a missense mutation at position chr17:7578406 in the tumor DNA (top) corresponding with the same mutation seen in the plasma circulating tumor DNA (bottom) [Color figure can be viewed at wileyonlinelibrary.com]

Figure 3

Treatment and surveillance for patients with diagnosed recurrence. (A) Patient HN01 had a TP53 tumor mutation detectable in baseline circulating tumor DNA which was not seen postoperatively. The patient was found to have no detectable recurrence on imaging and plasma until clinical and radiographic recurrence was found 384 days post‐operatively. Plasma circulating tumor DNA was positive at the next subsequent blood draw 13 days after diagnosed recurrence. (B) Patient HN02 was found to have a lack of clearance of plasma circulating tumor DNA at blood draw 3 weeks post operatively. Clinical exam, imaging, and biopsy confirmed recurrence at the next postoperative visit. (C) Patient HN04 was found to have two tumor mutations which were not detectable in baseline plasma just prior to resection, but both of which were detectable prior to recurrence diagnosed on clinical exam and imaging [Color figure can be viewed at wileyonlinelibrary.com]