Abstract 57: Detection of cell-free circulating tumor DNA in plasma as a biomarker for treatment response, prognosis, and recurrence in head and neck squamous cell carcinoma

Abstract

Abstract Objective: Head and neck squamous cell carcinoma (HNSCC) affects approximately 500,000 people per year, with 50,000 affected in the United States. Depending on stage and pathologic features, treatment modalities consist of surgery with or without adjuvant therapy, or primary chemoradiation. However, monitoring with serial examination and imaging including CT or PET-CT has significant limitations with a delay between actual and detectable tumor response. Circulating cell-free tumor DNA (ctDNA) has shown promise as a biomarker for monitoring cancer treatment response, recurrence, and prognosis. We utilize a novel, barcoded next-generation sequencing approach called SimSen-Seq to facilitate ultrasensitive detection of ctDNA, and we are applying it to samples from patients with head and neck squamous cell carcinoma (HNSCC). The purpose of this study is to evaluate the feasibility of using tumor mutations that are detectable in ctDNA to monitor treatment response and recurrence in patients with HNSCC. Methods: Longitudinal blood samples were obtained from patients with Stage I-IV HNSCC, with the initial sample obtained immediately before surgery. Imaging studies and pathology reports were reviewed to determine disease stage. Tumor samples were obtained from surgical specimens, and tumor DNA was sequenced using a targeted panel to identify mutations. SimSen-Seq assays were developed for each patient and used to generate sequencing libraries from cell-free DNA isolated from plasma. Mutations in plasma were identified, quantified, and associations with disease stage and response to therapy were explored. Results: Preliminary results from 5 patients with HNSCC demonstrate detection of ctDNA, and correlation of ctDNA fraction with treatment response and recurrence. Four of these patients had stage IV disease, and ctDNA was detectable immediately preoperatively. One patient demonstrated positive ctDNA 3 weeks postoperatively, with no clinical evidence of residual disease, but subsequently recurred and died soon afterward. Two other patients demonstrated negative ctDNA at 3-week postoperative blood draws, but subsequently demonstrated metastatic recurrence over 6 months later. Conclusions: ctDNA can be detected in the plasma of HNSCC patients, and can be detected prior to clinical evidence of recurrence. Furthermore, positive detection early after surgery may suggest a poor prognosis. Additional samples have been collected, and more work to evaluate detection rates based on stage plus response to therapy and recurrence is ongoing. Citation Format: Stefanie S. Saunders, Matthew Egyud, Anand Devaiah, Scharukh Jalisi, Tony Godfrey. Detection of cell-free circulating tumor DNA in plasma as a biomarker for treatment response, prognosis, and recurrence in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 57.