Prospective Characterization of Circulating Tumor Cell Kinetics in Patients with Locoregional Head and Neck Cancer Receiving Definitive Therapy

Abstract

<h3>Purpose/Objective(s)</h3> To characterize circulating tumor cell (CTC) kinetics in response to definitive or adjuvant therapy in patients with locoregional head and neck cancer and identify a profile of CTC kinetics that is associated with favorable disease response. <h3>Materials/Methods</h3> Patients with head and neck cancer of any subsite, excluding cutaneous malignancies, receiving definitive or post-operative adjuvant radiotherapy (RT) with or without concurrent chemotherapy were included. Induction chemotherapy was also permitted. Blood specimens were collected at baseline, during RT, and at routine follow-up visits. CTCs were captured and quantified using a nanotechnology-based assay functionalized with aEpCAM, aHER-2, and aEGFR to facilitate biomimetic cell rolling and dendrimer-mediated multivalent binding. Disease status was assessed per RECIST 1.1 criteria. CTC counts were reported and compared at various follow-up intervals for groups with and without complete response and progression. CTC counts were compared using the Wilcoxon signed rank test. <h3>Results</h3> 33 patients were enrolled with a median follow up of 15 months and median 6 CTC measurements per patient (range, 3-12). Histologies included squamous cell carcinoma (n=30), sinonasal undifferentiated carcinoma (n=1), high grade carcinoma with neuroendocrine features (n=1), and mucoepidermoid carcinoma (n=1). Subsites included the oropharynx (n=23), sinonasal (n=3), larynx (n=2), oral cavity (n=3), nasopharynx (n=1), and unknown primary (n=1). Of 23 oropharyngeal malignancies, 20 were HPV-associated. 25 patients received definitive chemoradiation (CRT), while 8 patients received surgical resection followed by risk-adapted adjuvant RT +/- chemotherapy. For patients treated with definitive CRT, median pre-treatment and end of treatment CTC counts were 77 CTCs/mL (range 7-849) and 22 CTCs/mL (range 2-209), respectively (P = 0.01). For patients treated with post-operative therapy, median pre-treatment and end of treatment CTC counts were 63 CTCs/mL (range 13-182) and 43 CTCs/mL (range 27-150), respectively (P = 0.17). Of 7 patients who developed disease progression and had CTC data available prior to the diagnosis of recurrence, 4 exhibited an increase in CTC counts near the time of progression. In comparison, 85% (17/20) of patients without evidence of disease progression had continued decline or stability of CTC counts following treatment, while the remaining 3 patients exhibited a transient increase in CTC counts. <h3>Conclusion</h3> Our data suggest that CTCs may serve as a biomarker for response to therapy in patients being treated for definitive management of locoregional head and neck cancer. Additional studies are warranted to further characterize their predictive and prognostic value.