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OC-085 Circulating tumour markers can discriminate between patients with and without oesophageal neoplasia
  1. R J Mead1,
  2. M Duku1,
  3. I Cree2,
  4. P Bhandari1
  1. 1Department of Gastroenterolgy, Queen Alexandra Hospital, NHS, Portsmouth
  2. 2Department of Pathology, Warwickshire NHS Foundation Trust, NHS, Warwick, UK

Abstract

Introduction Oesophageal cancer is the fastest rising cause of gastro-intestinal cancer in the UK, and associated with a poor prognosis. Early diagnosis represents the best opportunity for cure, but early disease is often asymptomatic. Current surveillance programs improve outcome, but rely on two yearly endoscopic screening of previously identified Barrett's oesophagus patients. This has limited sensitivity and acceptability to patients. New endoscopic treatments for oesophageal dysplasia can avoid major surgery, but discriminating between patients with and without invasive disease can be challenging. A discriminating diagnostic blood test may offer improved patient outcome.

Methods In this study, we optimised a series of promising diagnostic markers utilising circulating free DNA (cfDNA), with a preparation method allowing small DNA fragments to be purified. cfDNA was isolated from 115 patients including a “normal” population of 44 patients (Barrett's oesophagus or normal endoscopic findings). Twenty-five patients had high grade dysplasia (HGD) or intra-mucosal cancer (IMC), and 46 patients had invasive cancer. In each case real time quantitative polymerase chain reaction (RT-PCR) was performed for Line 1 79 bp (quantitative total DNA marker), Line 1 300 bp, Alu 115 bp, Alu 247 bp and mitochondrial primers. Each marker was analysed for differences between normal, HGD and IMC, and invasive cancer populations using Mann–Whitney U tests and ROC curves. The best performing were analysed in combination by logistic regression. A Bonferroni correction was applied.

Results The average age of the normal population group was 56.1 years, the HGD and IMC population group 70.0 years, and the cancer population group 68.9 years. The mean total DNA (ng/ml) was 10.8, 14.1, and 19.2 respectively. Mean DNA marker levels ng/ml. Analysing total DNA, mitochondrial DNA and Line 1 300bp fragment DNA levels, there were highly significant differences between the normal group vs all dysplastic and cancerous patients (p ≤ 0.003).

Conclusion The combination DNA marker was able to discriminate the normal population from all dysplasia and cancer patients with a ROC curve of 0.778. This may offer the prospect of a simple blood test to stratify patients and improve surveillance for dysplasia and early cancer. The same model was able to discriminate the normal population from invasive cancer patients with a ROC curve of 0.847. This may help in the rapid identification of patients who require surgery.

Abstract OC-085 Table 1

Competing interests None declared.

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