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all of which can be detected in the circulation [ 3 – 5 ]. The use of
liquid biopsy thus provides a minimally invasive way to assess can-
cer capabilities for better diagnosis and management in cancer
patients. Indeed, there has been interest in using liquid biopsy as a
method for surveillance for esophageal adenocarcinoma, particu-
larly in the conversion from Barrett’s esophagus, using either cir-
culating tumor cells or cell-free DNA, where studies have
successfully identified cancer-associated mutations from patient
samples [ 1 , 2 ].
A 2014 study by Sclafani et al. examined the role of circulating
tumor cells in patients with esophageal or gastric adenocarcinoma
[ 6 ]. Using the CellSearch system, based on detecting CD45− cells
expressing cytokeratin, Sclafani and coworkers determined that
patients with more than two circulating tumor cells per sample at a
pretreatment collection have a worse progression free survival and
4 months shorter median overall survival than patients with less
than two circulating tumor cells [ 6 ]. Samples taken at later time
points during treatment also showed a decline in detectable circu-
lating tumor cells.
An alternative approach for liquid biopsy is to examine bio-
chemical markers of cancer, particularly in the form of metabolites.
Zhang et al. attempted this form of liquid biopsy in esophageal
adenocarcinoma in 2015. This group collected blood plasma from
esophageal adenocarcinoma patients, patients with high-risk pre-
adenocarcinoma lesions (high-grade glandular dysplasia and
Barrett’s esophagus), and healthy controls [ 7 ]. These plasma sam-
ples were subjected to mass spectrometry and nuclear magnetic
resonance spectroscopy, identifying panels of metabolites with a
peak sensitivity and specificity of 91% for differentiating esophageal
adenocarcinoma patients from controls and 83% sensitivity and
80% specificity for differentiating high-risk pre-adenocarcinoma
lesions from adenocarcinoma [ 7 ].
A more recent study by Boldrin and colleagues examined the
role of cell-free DNA (cfDNA) derived from patient plasma in the
surveillance of Barrett’s esophagus for transition to esophageal
adenocarcinoma [ 2 ]. Although this study was carried out in only
two patients, it was a longitudinal study, combining plasma collec-
tion and time-matched formalin-fixed paraffin-embedded collec-
tion of tissue biopsies. Examination of DNA was centered on loss
of heterozygosity events for TP53, and in both patients, tumor-
specific mutations were detected in cfDNA, mirroring the results
and timing of their appearance in the time-matched tissue biopsies.
Simple Sanger DNA sequencing was able to detect these variants
and high sensitivity or next generation DNA sequencing methods
were not required [ 2 ]. This result clearly indicates that the use of
liquid biopsy may be extremely useful as a minimally invasive tech-
nique for surveillance of malignant transformation of suspect
benign lesions such as Barrett’s esophagus, aiding in theRobert A. Smith and Alfred K. Lam