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

PaulT. Spellman¹  Christopher Boniface¹  Carol Halsey²  Taylor Kelley²  MichaelB. Heskett²  Christopher Deig³  Nima Nabavizadeh³  CharlesR. Thomas³ 

[1] Cancer Early Detection Advanced Research (CEDAR) Center, Division of Oncological Sciences, Knight Cancer Institute, Oregon Health & Science University (OHSU), 2720 SW Moody Ave., Portland, OR 97201, USA;Department of Molecular and Medical Genetics, Oregon Health & Science University (OHSU) School of Medicine, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA;Department of Radiation Medicine, Oregon Health & Science University (OHSU), 3181 SW Sam Jackson Park Rd, KPV4, Portland, OR 97239, USA;

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

DOI  :  10.3390/diagnostics11010073

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown