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Objective: The goal of this study is to determine if cancer can be detected, and treatment response and recurrence can be monitored with plasma-based assays to detect circulating tumor DNA (ctDNA). Multiple studies to date have demonstrated utility of detection of ctDNA as a diagnostic and prognostic biomarker. However, little literature exists on liquid biopsy for esophageal adenocarcinoma (EAC) and head and neck squamous cell carcinoma (HNSCC), thus this remains an unmet need with significant therapeutic implications. We developed a novel approach using molecular barcodes to detect mutant alleles with frequencies below 1%, and are using this to evaluate liquid biopsy for monitoring treatment response and post-surgical recurrence of EAC and HNSCC.

Design: Cohort Study - DNA from patients with EAC and HNSCC was sequenced using targeted gene panels to identify tumor mutations. Assays with molecular barcodes were designed to identify these mutations in plasma, and sequencing libraries subsequently prepared and analyzed.

Setting: General community

Participants: Patients with evidence of EAC and HNSCC were identified for study. 74 patients with EAC and 13 patients with HNSCC consented to participate. 25 EAC and 13 HNSCC patients had blood collected longitudinally throughout treatment, while 49 EAC patients had blood collected at a single time point. Patients from both cancer groups were classified by AJCC7 stage at the time of diagnosis, and patients from all stages were enrolled.

Outcome: Identification of, and quantification, among plasma DNA, mutations of interest found in the primary tumor.

Results: Actionable mutations were identified in tumor samples from 42 EAC patients and 5 HNSCC patients. To date, plasma from 34 EAC and 5 HNSCC patients has been analyzed. Of these, 17 EAC patients and 4 HNSCC patients have positive detections in their initial sample. Mutations in plasma DNA can be identified in all stages of EAC, with increasing detection rates with more advanced stage. Two EAC and three HNSCC patients have longitudinal samples analyzed. Of the EAC patients, one demonstrates detectable ctDNA prior to clinical recurrence, and a second undergoing chemoradiation demonstrates correlation of amount of ctDNA to changes in imaging findings. Of the HNSCC patients, one patient demonstrated detectable ctDNA three weeks after surgery, which preceded recurrence and rapid clinical decline. Two others demonstrated undetectable ctDNA post-op and remained disease-free for over one year.

Conclusions: Tumor DNA can be detected in plasma of patients with EAC using ultra-sensitive sequencing. Early results in EAC and HNSCC show applications for rapid monitoring of response to therapy, monitoring for recurrence, and prognostication. Additional patient samples have been collected, enrollment continues, and work to elaborate on these findings is ongoing.