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Gastrointestinal Neoplasms

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Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Blood DNA will be isolated from plasma. Tumor DNA will be purified with a kit and amplified regions of 10 genes discovered to by mutated in whole exome sequencing.

Blood and Tissue Collection

Shanda Blackmon, MD, MPH

To prospectively collect blood and tumor tissue from esophageal cancer patients to identify specific esophageal cancer mutations that can be measured in the blood (cell free DNA) during the course of treatment as a marker of response and recurrence.

Esophageal carcinoma is an aggressive malignancy and about a third of patients present with distant metastatic disease. While survival is slowly improving with better diagnostic tools and therapy, the overall 5-year survival remains low at 18%. Unlike other malignancies, such as colon cancer and prostate cancer, there is no peripheral blood marker of response or recurrence during treatment in esophageal cancer. However, quantifying cfDNA is a unique and tumor specific avenue that may allow real time response to treatment in esophageal cancer.

To identify esophageal cancer specific mutations, tumor samples will undergo whole exome sequencing. From this data, the investigators will select 10-15 genes to focus their efforts. PCR primers will be designed to detect these tumor specific mutations in the cell-free component of peripheral blood samples over the course of treatment for esophageal cancer.

The investigators will obtain baseline blood (before treatment) and then collect blood after neoadjuvant treatment, after surgery, and then at subsequent visits from the participants.

Patients will have blood drawn prior to any neoadjuvant treatment or surgery. Tumor tissue will be collected and stored after pathologic evaluation has been completed. Blood collections will then be drawn at every subsequent follow up visit at Mayo Clinic for surveillance.

Measuring Cell Free DNA During the Course of Treatment for Esophageal Cancer as a Marker of Response and Recurrence

To identify specific esophageal cancer mutations that can be measured in the blood (cell free DNA) during the course of treatment as a marker of response and recurrence.

To validate cfDNA as a marker of recurrence of esophageal cancer.

Mayo Clinic

Ear, Nose, and Throat Diseases

Adenocarcinoma

Gastroesophageal Reflux

Esophagitis

Barrett Esophagus

Hyperplasia

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Esophageal Motility Disorders

Esophageal Spasm, Diffuse

Deglutition Disorders

Gastroenteritis

Precancerous Conditions

Individuals who underwent endoscopy and were found to only have one of the following:

* Esophageal adenocarcinoma of any stage
* Esophageal adenocarcinoma confined to the mucosa (stage Tis)

Individuals who underwent endoscopy and were found to only have one of the following:

* Barrett's Esophagus, with high-grade dysplasia, independently of Barrett's segment length
* Esophageal adenocarcinoma of any stage
* Esophageal adenocarcinoma confined to the mucosa (stage Tis)

Individuals who underwent endoscopy and were found to only have Barrett's Esophagus, with one of the following:

* Craniocaudal maximal extension of 3 cm or more
* Low-grade dysplasia at most, independently of Barrett's segment length

Individuals who underwent endoscopy and were found not to have any Barrett's Esophagus or adenocarcinoma.

A panel of circulating microRNA, whose expression level is tested in cell-free derived samples.

EMERALD (Esophageal MicroRNAs for BaRRett's esophagus, Adenocarcinoma, and Dysplasia)

Ajay Goel, PhD

This study aims to develop a highly sensitive, specific, and cost-effective blood assay for the early detection of esophageal adenocarcinoma and its precursor lesions, using advanced machine learning and state-of-the-art biological analyses.

Esophageal adenocarcinoma (EAC) is a significant global health concern, ranking second in lethality (after pancreatic cancer). Despite being potentially preventable, it remains a leading cause of cancer-related deaths. Traditional screening methods have relied on an endoscopy-first approach to screen for the precursor of EAC, which is Barrett's esophagus (BE). After BE detection, BE is then regularly surveiled to monitor the development of dysplasia, which can be treated to prevent malignant transformation. An endoscopy-first approach is sensitive BE and, therefore, it lowers the risk of developing EAC but it also faces challenges such as invasiveness, cost, and patient compliance.

Non-invasive tests are more appealing to patients than invasive tests and can increase participation rates. Biomarker studies have shown promise, but existing tests lack sensitivity for early-stage EAC and, most importantly, to its precursor lesion BE. This is likely because they over-sampled analytes that are primarily expressed at the EAC end of the spectrum, but not in BE yet during the BE to EAC sequence.

This study proposes developing an innovative liquid biopsy test tailored for EAC and BE to address this. An ideal screening test should be minimally invasive, highly sensitive, and cost-effective. This test would optimize patient compliance and resource allocation by detecting both conditions from a single blood draw. More specifically, circulating microRNA (miRNA) analysis shows promise: tests based on cell-free microRNA (cf-miRNA) have demonstrated high sensitivity.

This study will develop a non-invasive blood test for BE and EAC in four phases:

1. In silico genome-wide profiling of tissue miRNA to select the best candidates for biomarker panels.
2. Prioritization of the biomarkers that are differentially expressed across the entire continuum of BE to EAC sequence, compared to the normal mucosa
3. Transition of these biomarkers to a liquid biopsy assay, confirming their detectability in blood as well as their differential expression in cases compared to controls
4. Utilizing machine learning to identify the most promising candidates and train algorithms for detecting EAC and BE, based on results from quantitative polymerase chain reaction (qPCR) analysis.
5. Independently validating these signatures using diverse cohorts to ensure broad applicability and compare the effectiveness of the blood assay to standard care through retrospective and prospective studies.

This study aims to develop a highly sensitive, specific, and cost-effective liquid biopsy for early detection of BE and EAC. Success could transform clinical practice by preventing EAC through early detection of pre-malignant lesions. Innovations include incorporating pre-malignant lesions into screening. This approach could potentially reduce EAC mortality and incidence and pave the way for new clinical trials.

A Liquid Biopsy for High-risk Pre-cancer Screening of Esophageal Adenocarcinoma

A Liquid Biopsy to Screen for Barrett's Esophagus, Dysplasia, and Esophageal Adenocarcinoma: the EMERALD Multi-center Study.

Data collected for the study will be made available to others, including de-identified participant data, at publication, via a signed data access agreement and at the discretion of the investigators' approval of the proposed use of such data.

True positive rate: the probability of a positive test result, conditioned on the individual truly being positive

True negative rate: the probability of a negative test result, conditioned on the individual truly being negative

A measure of trueness: proportion of correct predictions (both true positives and true negatives) among the total number of cases examined

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Measuring Cell Free DNA During the Course of Treatment for Esophageal Cancer as a Marker of Response and Recurrence	NCT03108885	Esophageal Neop... Esophageal Neop... Esophageal Neop... Cancer of Esoph... Cancer of the E... Esophageal Canc... Esophagus Cance... Neoplasm, Esoph...	Blood and Tissu...	19 Years -	Mayo Clinic
A Liquid Biopsy for High-risk Pre-cancer Screening of Esophageal Adenocarcinoma	NCT06381583	Esophagus Cance... Esophageal Canc... Esophageal Canc... Esophageal Neop... Esophagus Adeno... Esophagus, Barr... Barrett Esophag... Barrett Adenoca... Barrett Epithel... Barretts Esopha... Barrett's Esoph... Barretts Esopha... Barretts Esopha... Barrett Esophag... Barrett's Esoph... Barrett's Esoph... Gastroesophagea... Reflux Disease Esophageal Aden... Esophageal Dysp... Esophageal Neop...	EMERALD (Esopha...	18 Years -	City of Hope Medical Center

Spots Global Cancer Trial Database for esophageal neoplasms malignant