Detection of Circulating Tumor DNA in Plasma: A Potential Biomarker for Esophageal Adenocarcinoma

Abstract

Background. Recent literature has demonstrated the potential of "liquid biopsy" and detection of circulating tumor (ct)DNA as a cancer biomarker. However, to date there is a lack of data specific to esophageal adenocarcinoma (EAC). This study was conducted to determine how detection and quantification of ctDNA changes with disease burden in patients with EAC and evaluate its potential as a biomarker in this population.Methods. Blood samples were obtained from patients with stage I to IV EAC. Longitudinal blood samples were collected from a subset of patients. Imaging studies and pathology reports were reviewed to determine disease course. Tumor samples were sequenced to identify mutations. Mutations in plasma DNA were detected using custom, barcoded, patient-specific sequencing libraries. Mutations in plasma were quantified, and associations with disease stage and response to therapy were explored.

Detection of somatic mutations in circulating cell-free DNA from patients with esophageal squamous cell carcinoma

“…In total, there were 14 mutations with VAFs of >5% detected in cfDNA. The results showed ESCC had low ctDNA in the blood, which was similar to one previous study on EAC [34]. Moreover, the variants called from cfDNA were much more than the ones called from solid tumor tissues.…”

“…Recently, data from one study with longitudinal EAC samples indicated that ctDNA levels correlate with and precede evidence of response to therapy, which demonstrated that the potential of ctDNA as a dynamic biomarker to monitor treatment response in patients with EAC. Moreover, the VAFs of some mutations were lower or equaled zero in postoperative plasma from ESCC patients [34]. Similarly, somatic mutations can be detected in preoperative cfDNA from patients with ESCC at stage IIA to IIIB , and at a lower frequency in postoperative cfDNA in another study [44].…”

“…Together with the possibility of multiple assessments over time, the use of cfDNA may be able to predict response to treatment and patterns of therapeutic resistance earlier and more accurately than radiological imaging [34,36]. The ability to analyze tumor-derived DNA from a routine blood draw without the need for an invasive tumor biopsy represents a critical advance with potentially transformative clinical applications.…”

“…First, it provides physicians with a rapid assessment of the success of the treatment choice and may allow for modi cation of therapeutic regimens if inadequate response is noted. Second, poor clinical response to neoadjuvant treatment may be identi ed early during therapy, thereby allowing changes in the treatment plan, including surgical management [34]. Therefore, as a repeat or serial testing tool, cfDNA testing for treatment selection and tracking therapeutic response is increasingly used as an alternative to repeat invasive biopsy and may reveal actionable mutations that guide treatment decisions in these patients [22].…”

Don’t Anger the Host: New Etiquette in Standard Cancer Assessment?

“…Circulating tumor studies are showing promise yet not with high throughput. 14 McSorley et al should be commended for introducing a scoring system based on a blood draw, as it allows us to learn to look beyond the misbehaving tumor and to engage with the host and their guests. In the age of immunomodulatory therapies, the host immune/inflammatory response is a continually important aspect of treating the patient.…”