TY - JOUR
T1 - Detection of Circulating Tumor DNA in Plasma
T2 - A Potential Biomarker for Esophageal Adenocarcinoma
AU - Egyud, Matthew
AU - Tejani, Mohamedtaki
AU - Pennathur, A.
AU - Luketich, J.
AU - Sridhar, Praveen
AU - Yamada, E.
AU - Ståhlberg, Anders
AU - Filges, Stefan
AU - Krzyzanowski, Paul
AU - Jackson, Jennifer
AU - Kalatskaya, I.
AU - Jiao, Wei
AU - Nielsen, Gradon
AU - Zhou, Zhongren
AU - Litle, Virginia
AU - Stein, Lincoln
AU - Godfrey, Tony
N1 - Funding Information:
The authors wish to acknowledge two grants from NIH/NCI awarded to Boston University: 1R21CA172999 and 5R01CA208599.
Funding Information:
The authors wish to acknowledge two grants from NIH/NCI awarded to Boston University: 1R21CA172999 and 5R01CA208599.
Publisher Copyright:
© 2019 The Society of Thoracic Surgeons
PY - 2019/8
Y1 - 2019/8
N2 - 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. Results: Plasma samples from a final cohort of 38 patients were evaluated. Baseline plasma samples were ctDNA positive for 18 patients (47%) overall, with tumor allele frequencies ranging from 0.05% to 5.30%. Detection frequency of ctDNA and quantity of ctDNA increased with stage. Data from longitudinal samples indicate that ctDNA levels correlate with and precede evidence of response to therapy or recurrence. Conclusions: ctDNA can be detected in plasma of EAC patients and correlates with disease burden. Detection of ctDNA in early-stage EAC is challenging and may limit diagnostic applications. However, our data demonstrate the potential of ctDNA as a dynamic biomarker to monitor treatment response and disease recurrence in patients with EAC.
AB - 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. Results: Plasma samples from a final cohort of 38 patients were evaluated. Baseline plasma samples were ctDNA positive for 18 patients (47%) overall, with tumor allele frequencies ranging from 0.05% to 5.30%. Detection frequency of ctDNA and quantity of ctDNA increased with stage. Data from longitudinal samples indicate that ctDNA levels correlate with and precede evidence of response to therapy or recurrence. Conclusions: ctDNA can be detected in plasma of EAC patients and correlates with disease burden. Detection of ctDNA in early-stage EAC is challenging and may limit diagnostic applications. However, our data demonstrate the potential of ctDNA as a dynamic biomarker to monitor treatment response and disease recurrence in patients with EAC.
UR - http://www.scopus.com/inward/record.url?scp=85064953005&partnerID=8YFLogxK
U2 - 10.1016/j.athoracsur.2019.04.004
DO - 10.1016/j.athoracsur.2019.04.004
M3 - Article
C2 - 31059681
AN - SCOPUS:85064953005
SN - 0003-4975
VL - 108
SP - 343
EP - 349
JO - Annals of Thoracic Surgery
JF - Annals of Thoracic Surgery
IS - 2
ER -