Working Paper Article Version 1 This version is not peer-reviewed

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

Version 1 : Received: 8 December 2020 / Approved: 10 December 2020 / Online: 10 December 2020 (12:52:27 CET)

A peer-reviewed article of this Preprint also exists.

Boniface, C.; Deig, C.; Halsey, C.; Kelley, T.; Heskett, M.B.; Thomas, C.R., Jr.; Spellman, P.T.; Nabavizadeh, N. 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. Diagnostics 2021, 11, 73. Boniface, C.; Deig, C.; Halsey, C.; Kelley, T.; Heskett, M.B.; Thomas, C.R., Jr.; Spellman, P.T.; Nabavizadeh, N. 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. Diagnostics 2021, 11, 73.

Journal reference: Diagnostics 2021, 11, 73
DOI: 10.3390/diagnostics11010073

Abstract

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 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.

Keywords

liquid biopsy; ctDNA; cell free DNA; non-operative management; neoadjuvant therapy

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