The Use of Biomarkers to Guide Management of Patients Treated With Radiofrequency Ablation for Early Oesophageal Neoplasia (PROBAN)

University of Cambridge

Status: Enrolling

Conditions: Barrett's Oesophagus

Treatments: Diagnostic Test: Oesophagogastroduodenoscopy; Diagnostic Test: Assessment of the panel of molecular biomarkers: IM-SCORE, TFF3 protein expression, methylation panel, p53 mutation; Diagnostic Test: Cytosponge test

Study type: Interventional

Funder types: Other

Identifiers

NCT04155242

ISRCTN12730505

Details and patient eligibility

About

This prospective cohort study aims to assess the utility of a panel of molecular biomarkers for predicting the risk of relapse of Barrett's Oesophagus after endoscopic treatment of early oesophageal neoplasia with RadioFrequency Ablation (RFA). Patients who received endoscopic treatment of early oesophageal neoplasia with RFA and achieved endoscopic remission will be recruited. During the surveillance visits patients will receive a Cytosponge test followed by an endoscopy with Narrow Band Imaging (NBI) magnification and biopsies. Patients will receive an endoscopy every 6 months and Cytosponge every 12 months for at least 2 years. Molecular biomarkers including a methylation panel on DNA and immunohistochemical markers on formalin fixed paraffin embedded samples. After 2 years of intensive endoscopic follow up, patients will be prospectively tracked for up to 3 years.

The investigators will also evaluate:

• The risk of progression to dysplasia or oesophageal intestinal metaplasia (IM) in patients with IM at the GOJ post RFA in the absence of retreatment
• the diagnostic accuracy of NBI for IM/dysplasia at the GOJ .

Full description

The panel of predetermined molecular biomarkers includes:

IM-SCORE - a score quantifying the extent of intestinal metaplasia at GOJ, which uses a 4-tier system based on the number of glands and the number of biopsies with features of IM. The score has been developed in a pilot study (manuscript under submission) and will be validated in this study Methylation markers- assessed by a PCR-based method (Methylight) on Cytosponge samples. P53 status. TFF3 protein expression.

Enrollment: 147 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

1. Previous RFA for dysplastic BE or following EMR for BE-related neoplasia
2. No definite endoscopic evidence of BE defined as at least 1cm tongue of columnar oesophagus or oesophageal BE islands larger than 5mm.
3. No histological evidence of oesophageal IM including buried BE at first post RFA follow up. GOJ IM is allowed
4. No evidence of suspicious lesions with dysplasia at the GOJ.

Exclusion criteria

1. Evidence of BE requiring additional RFA
2. Anticoagulant or antiplatelet therapy for high risk conditions, whereby discontinuation of the treatment is not recommended.
3. Individuals with a diagnosis of an oro-pharynx, oesophageal or gastro-oesophageal tumour (T2 staging and above), or symptoms of dysphagia,
4. Oesophageal varices, stricture or requiring dilatation of the oesophagus
5. Individuals who have had a myocardial infarction or any cardiac event less than six months ago
6. Patients whose primary previous ablative treatment was different from RFA, such as Photodynamic therapy (PDT), APC or Cryotherapy
7. Participants who are unable to provide informed consent.
8. Participants under age 18.
9. Endoscopy is generally avoided in pregnant women and therefore it is unlikely that any pregnant women will be included although pregnancy would not be an absolute contraindication. Pregnancy/ pregnancy test will not be recorded as part of the trial.

Trial design

Primary purpose: Diagnostic

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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147 participants in 1 patient group

Study group

Experimental group

Description:

As part of the post RFA treatment follow up patients will receive a Cytosponge test followed by an endoscopy with NBI magnification and biopsies. Four endoscopies will be performed during 2 years of active follow up together with up to 2 Cytosponge procedures. Molecular biomarkers including a methylation panel on DNA and immunohistochemical markers on formalin fixed paraffin embedded samples obtained during the examinations will be assessed. Patients will be then followed up for up to 3 years with standard endoscopy to assess for relapse of Barrett's oesophagus/IM/dysplasia.

Treatment:

Diagnostic Test: Cytosponge test

Diagnostic Test: Oesophagogastroduodenoscopy

Diagnostic Test: Assessment of the panel of molecular biomarkers: IM-SCORE, TFF3 protein expression, methylation panel, p53 mutation