We sequenced 245 plasma samples from 97 patients with oesophageal adenocarcinoma using a 77 gene pan-cancer ctDNA panel. 2/8
Variants derived from previously characterised driver oesophageal adenocarcinoma genes had a significantly higher VAF than variants from other genes, indicating selection. 3/8
Peripheral blood cell samples were also sequenced for 78/97 patients. CHIP mutations were identified in 23% of cases, longitudinal tracking of CHIP variants suggested these variants were dynamic over time. 4/8
We found patients that were ctDNA positive post-surgery had a significantly poorer survival than ctDNA negative patients, and the elimination of CHIP variants improved the positive predictive value. 5/8
In summary, we demonstrate in a large, national, prospectively-collected dataset that ctDNA in plasma following surgery for EAC is prognostic for relapse. Inclusion of peripheral blood cell samples can reduce or eliminate false positives from CHIP. 6/8
In the future, post-operative ctDNA could be used to risk stratify patients into high- and low-risk groups for intensification or de-escalation of adjuvant chemotherapy. 7/8
DNA from patients with Barrett’s oesophagus can show who is most likely at risk to develop oesophageal cancer up to *8 years* before cancer is diagnosed, improving detection and decreasing overdiagnosis. (2/8)
Using a low resolution whole genome sequencing method, we looked for signals of copy number changes in the DNA. This is common in tumours and important in oesophageal cancer. Samples from patients with early cancer showed more changes than samples from patients who had not. (3/8)