Cargando…

The Feasibility of Patient-Specific Circulating Tumor DNA Monitoring throughout Multi-Modality Therapy for Locally Advanced Esophageal and Rectal Cancer: A Potential Biomarker for Early Detection of Subclinical Disease

As non-operative management (NOM) of esophageal and rectal cancer is becoming more prevalent, blood-biomarkers such as circulating tumor DNA (ctDNA) may provide clinical information in addition to endoscopy and imaging to aid in treatment decisions following chemotherapy and radiation therapy. In th...

Descripción completa

Detalles Bibliográficos
Autores principales: Boniface, Christopher, Deig, Christopher, Halsey, Carol, Kelley, Taylor, Heskett, Michael B., Thomas, Charles R., Spellman, Paul T., Nabavizadeh, Nima
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824834/
https://www.ncbi.nlm.nih.gov/pubmed/33466369
http://dx.doi.org/10.3390/diagnostics11010073
_version_ 1783640174169686016
author Boniface, Christopher
Deig, Christopher
Halsey, Carol
Kelley, Taylor
Heskett, Michael B.
Thomas, Charles R.
Spellman, Paul T.
Nabavizadeh, Nima
author_facet Boniface, Christopher
Deig, Christopher
Halsey, Carol
Kelley, Taylor
Heskett, Michael B.
Thomas, Charles R.
Spellman, Paul T.
Nabavizadeh, Nima
author_sort Boniface, Christopher
collection PubMed
description As non-operative management (NOM) of esophageal and rectal cancer is becoming more prevalent, blood-biomarkers such as circulating tumor DNA (ctDNA) may provide clinical information in addition to endoscopy and imaging to aid in treatment decisions following chemotherapy and radiation therapy. In this feasibility study, we prospectively collected plasma samples from locally advanced esophageal (n = 3) and rectal cancer (n = 2) patients undergoing multimodal neoadjuvant therapy to assess the feasibility of serial ctDNA monitoring throughout neoadjuvant therapy. Using the Dual-Index Degenerate Adaptor-Sequencing (DIDA-Seq) error-correction method, we serially interrogated plasma cell-free DNA at 28–41 tumor-specific genomic loci throughout therapy and in surveillance with an average limit of detection of 0.016% mutant allele frequency. In both rectal cancer patients, ctDNA levels were persistently elevated following total neoadjuvant therapy with eventual detection of clinical recurrence prior to salvage surgery. Among the esophageal cancer patients, ctDNA levels closely correlated with tumor burden throughout and following neoadjuvant therapy, which was associated with a pathologic complete response in one patient. In this feasibility study, patient- and tumor-specific ctDNA levels correlated with clinical outcomes throughout multi-modality therapy suggesting that serial monitoring of patient ctDNA has the potential to serve as a highly sensitive and specific biomarker to risk-stratify esophageal and rectal cancer patients eligible for NOM. Further prospective investigation is warranted.
format Online
Article
Text
id pubmed-7824834
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-78248342021-01-24 The Feasibility of Patient-Specific Circulating Tumor DNA Monitoring throughout Multi-Modality Therapy for Locally Advanced Esophageal and Rectal Cancer: A Potential Biomarker for Early Detection of Subclinical Disease Boniface, Christopher Deig, Christopher Halsey, Carol Kelley, Taylor Heskett, Michael B. Thomas, Charles R. Spellman, Paul T. Nabavizadeh, Nima Diagnostics (Basel) Article As non-operative management (NOM) of esophageal and rectal cancer is becoming more prevalent, blood-biomarkers such as circulating tumor DNA (ctDNA) may provide clinical information in addition to endoscopy and imaging to aid in treatment decisions following chemotherapy and radiation therapy. In this feasibility study, we prospectively collected plasma samples from locally advanced esophageal (n = 3) and rectal cancer (n = 2) patients undergoing multimodal neoadjuvant therapy to assess the feasibility of serial ctDNA monitoring throughout neoadjuvant therapy. Using the Dual-Index Degenerate Adaptor-Sequencing (DIDA-Seq) error-correction method, we serially interrogated plasma cell-free DNA at 28–41 tumor-specific genomic loci throughout therapy and in surveillance with an average limit of detection of 0.016% mutant allele frequency. In both rectal cancer patients, ctDNA levels were persistently elevated following total neoadjuvant therapy with eventual detection of clinical recurrence prior to salvage surgery. Among the esophageal cancer patients, ctDNA levels closely correlated with tumor burden throughout and following neoadjuvant therapy, which was associated with a pathologic complete response in one patient. In this feasibility study, patient- and tumor-specific ctDNA levels correlated with clinical outcomes throughout multi-modality therapy suggesting that serial monitoring of patient ctDNA has the potential to serve as a highly sensitive and specific biomarker to risk-stratify esophageal and rectal cancer patients eligible for NOM. Further prospective investigation is warranted. MDPI 2021-01-05 /pmc/articles/PMC7824834/ /pubmed/33466369 http://dx.doi.org/10.3390/diagnostics11010073 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Boniface, Christopher
Deig, Christopher
Halsey, Carol
Kelley, Taylor
Heskett, Michael B.
Thomas, Charles R.
Spellman, Paul T.
Nabavizadeh, Nima
The Feasibility of Patient-Specific Circulating Tumor DNA Monitoring throughout Multi-Modality Therapy for Locally Advanced Esophageal and Rectal Cancer: A Potential Biomarker for Early Detection of Subclinical Disease
title The Feasibility of Patient-Specific Circulating Tumor DNA Monitoring throughout Multi-Modality Therapy for Locally Advanced Esophageal and Rectal Cancer: A Potential Biomarker for Early Detection of Subclinical Disease
title_full The Feasibility of Patient-Specific Circulating Tumor DNA Monitoring throughout Multi-Modality Therapy for Locally Advanced Esophageal and Rectal Cancer: A Potential Biomarker for Early Detection of Subclinical Disease
title_fullStr The Feasibility of Patient-Specific Circulating Tumor DNA Monitoring throughout Multi-Modality Therapy for Locally Advanced Esophageal and Rectal Cancer: A Potential Biomarker for Early Detection of Subclinical Disease
title_full_unstemmed The Feasibility of Patient-Specific Circulating Tumor DNA Monitoring throughout Multi-Modality Therapy for Locally Advanced Esophageal and Rectal Cancer: A Potential Biomarker for Early Detection of Subclinical Disease
title_short The Feasibility of Patient-Specific Circulating Tumor DNA Monitoring throughout Multi-Modality Therapy for Locally Advanced Esophageal and Rectal Cancer: A Potential Biomarker for Early Detection of Subclinical Disease
title_sort feasibility of patient-specific circulating tumor dna monitoring throughout multi-modality therapy for locally advanced esophageal and rectal cancer: a potential biomarker for early detection of subclinical disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824834/
https://www.ncbi.nlm.nih.gov/pubmed/33466369
http://dx.doi.org/10.3390/diagnostics11010073
work_keys_str_mv AT bonifacechristopher thefeasibilityofpatientspecificcirculatingtumordnamonitoringthroughoutmultimodalitytherapyforlocallyadvancedesophagealandrectalcancerapotentialbiomarkerforearlydetectionofsubclinicaldisease
AT deigchristopher thefeasibilityofpatientspecificcirculatingtumordnamonitoringthroughoutmultimodalitytherapyforlocallyadvancedesophagealandrectalcancerapotentialbiomarkerforearlydetectionofsubclinicaldisease
AT halseycarol thefeasibilityofpatientspecificcirculatingtumordnamonitoringthroughoutmultimodalitytherapyforlocallyadvancedesophagealandrectalcancerapotentialbiomarkerforearlydetectionofsubclinicaldisease
AT kelleytaylor thefeasibilityofpatientspecificcirculatingtumordnamonitoringthroughoutmultimodalitytherapyforlocallyadvancedesophagealandrectalcancerapotentialbiomarkerforearlydetectionofsubclinicaldisease
AT heskettmichaelb thefeasibilityofpatientspecificcirculatingtumordnamonitoringthroughoutmultimodalitytherapyforlocallyadvancedesophagealandrectalcancerapotentialbiomarkerforearlydetectionofsubclinicaldisease
AT thomascharlesr thefeasibilityofpatientspecificcirculatingtumordnamonitoringthroughoutmultimodalitytherapyforlocallyadvancedesophagealandrectalcancerapotentialbiomarkerforearlydetectionofsubclinicaldisease
AT spellmanpault thefeasibilityofpatientspecificcirculatingtumordnamonitoringthroughoutmultimodalitytherapyforlocallyadvancedesophagealandrectalcancerapotentialbiomarkerforearlydetectionofsubclinicaldisease
AT nabavizadehnima thefeasibilityofpatientspecificcirculatingtumordnamonitoringthroughoutmultimodalitytherapyforlocallyadvancedesophagealandrectalcancerapotentialbiomarkerforearlydetectionofsubclinicaldisease
AT bonifacechristopher feasibilityofpatientspecificcirculatingtumordnamonitoringthroughoutmultimodalitytherapyforlocallyadvancedesophagealandrectalcancerapotentialbiomarkerforearlydetectionofsubclinicaldisease
AT deigchristopher feasibilityofpatientspecificcirculatingtumordnamonitoringthroughoutmultimodalitytherapyforlocallyadvancedesophagealandrectalcancerapotentialbiomarkerforearlydetectionofsubclinicaldisease
AT halseycarol feasibilityofpatientspecificcirculatingtumordnamonitoringthroughoutmultimodalitytherapyforlocallyadvancedesophagealandrectalcancerapotentialbiomarkerforearlydetectionofsubclinicaldisease
AT kelleytaylor feasibilityofpatientspecificcirculatingtumordnamonitoringthroughoutmultimodalitytherapyforlocallyadvancedesophagealandrectalcancerapotentialbiomarkerforearlydetectionofsubclinicaldisease
AT heskettmichaelb feasibilityofpatientspecificcirculatingtumordnamonitoringthroughoutmultimodalitytherapyforlocallyadvancedesophagealandrectalcancerapotentialbiomarkerforearlydetectionofsubclinicaldisease
AT thomascharlesr feasibilityofpatientspecificcirculatingtumordnamonitoringthroughoutmultimodalitytherapyforlocallyadvancedesophagealandrectalcancerapotentialbiomarkerforearlydetectionofsubclinicaldisease
AT spellmanpault feasibilityofpatientspecificcirculatingtumordnamonitoringthroughoutmultimodalitytherapyforlocallyadvancedesophagealandrectalcancerapotentialbiomarkerforearlydetectionofsubclinicaldisease
AT nabavizadehnima feasibilityofpatientspecificcirculatingtumordnamonitoringthroughoutmultimodalitytherapyforlocallyadvancedesophagealandrectalcancerapotentialbiomarkerforearlydetectionofsubclinicaldisease