RECRUITINGINTERVENTIONAL

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

Prospective Study on the Use of Biomarkers to Guide Management of Patients Treated With Radiofrequency Ablation for Early Oesophageal Neoplasia

About This Trial

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 .

Who May Be Eligible (Plain English)

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 willing to sign a consent form. 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. Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

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.

Treatments Being Tested

DIAGNOSTIC_TEST

Cytosponge test

The Cytosponge will be administered by the study nurse prior to the participant having the endoscopy, usually as part of the same visit to hospital. The capsule along with the string is swallowed by drinking a small glass of water. The participant is asked to hold the Cytosponge in situ for 5 minutes. The sponge contained within expands and is then drawn back by the research nurse up the oesophagus by the attached string, collecting cells as it moves upwards. This device received a letter of no objection by the MHRA for use in the BEST pilot trial (LRQ 0939857) but it is not CE marked. Cytosponge and research endoscopic biopsies will be couriered to the Fitzgerald laboratory, at the MRC Cancer Cell Unit on a regular basis. The specimens will be processed in conjunction with the Cambridge University Hospitals' NHS Foundation Trust tissue bank which is accredited to GLP standards.

DIAGNOSTIC_TEST

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

Molecular analysis of the specimen obtained by Cytosponge or endoscopic biopsies - TFF3 protein expression, methylation panel, p53 mutation. Endoscopic biopsies will be assessed for the presence of IM (according to the IM-score).

DIAGNOSTIC_TEST

Oesophagogastroduodenoscopy

* Endoscopy will be carried out with white light and NBI with optical magnification or near focus to inspect oesophagus and GOJ. * NBI magnification will be used to assess systematically the mucosal pit pattern at the GOJ and to look for light blue crest (LBC) sign. * Targeted biopsies will be taken from either areas with LBC or irregular pit pattern on NBI, followed by random biopsies as per clinical standard. A maximum of 6 biopsies will be taken at the GOJ (maximum 4 targeted and 4 random.. During the first 2 post RFA follow up, at discretion of the endoscopists, neo-suqamous biopsies can be taken in line with local policies. * Argon plasma coagulation ablation is allowed in a single island up to 5mm or up to 3 islands \<3mm within the study endoscopy as long as this does not represent an obstacle to GOJ biopsies.

Locations (1)

MRC Cancer Unit

Cambridge, United Kingdom