Tan W Keith, Ross-Innes Caryn S, Somerset Timothy, Markert Greta, Markowetz Florian, O'Donovan Maria, di Pietro Massimiliano, Sasieni Peter, Fitzgerald Rebecca C
Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge, UK; Department of Gastroenterology, Addenbrookes Hospital, Cambridge University NHS Foundation Trust, Cambridge, UK.
Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge, UK.
Lancet. 2025 Jul 19;406(10500):271-282. doi: 10.1016/S0140-6736(25)01021-9. Epub 2025 Jun 23.
Endoscopic surveillance is the clinical standard for Barrett's oesophagus, but its effectiveness is inconsistent. We have developed a test comprising a pan-oesophageal cell collection device coupled with biomarkers to stratify patients into three risk groups. We aimed to prospectively evaluate the prespecified risk stratification tool to establish whether it can identify those at highest risk of dysplasia or cancer to prioritise the timing of endoscopy; and safely be used to follow up the low-risk group, thus sparing patients from unnecessary endoscopies.
Participants were recruited as part of two multicentre, prospective, pragmatic implementation studies from 13 hospitals in the UK. Patients with non-dysplastic Barrett's oesophagus had a capsule-sponge test which was assessed in an ISO-accredited laboratory. Patients were included if they were aged at least 18 years with a non-dysplastic Barrett's oesophagus diagnosis at their last endoscopy who were undergoing surveillance according to the published UK guidelines. Patients were assigned as low (clinical and capsule-sponge biomarkers negative), moderate (negative for capsule-sponge biomarkers, positive clinical biomarkers-age, sex, and segment length), or high risk (p53 abnormality or glandular atypia regardless of clinical biomarkers, or both). The primary outcome was a diagnosis of high-grade dysplasia or cancer necessitating treatment, according to the risk group assignment.
910 patients recruited between August, 2020, and December, 2024 participated, of whom 138 (15%) were classified as high risk, 283 (31%) moderate risk and 489 (54%) low risk. The positive predictive value for any dysplasia or worse in the high-risk group was 37·7% (95% CI 29·7-46·4). Patients with both atypia and aberrant p53 had the highest risk of high-grade dysplasia or cancer (relative risk 135·8 [95% CI 32·7-564·0] relative to the low-risk group). The prevalence of high-grade dysplasia or cancer in the low-risk group was 0·4% (95% CI 0·1-1·6); the negative predictive value for any dysplasia or cancer was 97·8% (95% CI 95·9-98·8). Applying a machine learning algorithm as part of a digital-pathology workflow reduces the proportion needing p53 pathology review to 32% without missing any positive cases.
The risk-panel substantially enriches for dysplasia and capsule-sponge-based surveillance could be used in low-risk Barrett's oesophagus in lieu of endoscopy.
Innovate UK, Cancer Research UK, National Health Service England Cancer Alliance.
内镜监测是巴雷特食管的临床标准，但其有效性并不一致。我们开发了一种检测方法，包括一个全食管细胞采集装置和生物标志物，可将患者分为三个风险组。我们旨在对预先设定的风险分层工具进行前瞻性评估，以确定它是否能够识别发育异常或癌症风险最高的患者，从而确定内镜检查的时机；并安全地用于低风险组的随访，从而避免患者接受不必要的内镜检查。
参与者是从英国13家医院进行的两项多中心、前瞻性、务实实施研究中招募的。非发育异常的巴雷特食管患者接受了胶囊海绵检测，并在一家获得ISO认可的实验室进行评估。纳入标准为年龄至少18岁，在上次内镜检查时被诊断为非发育异常的巴雷特食管，且正在按照英国已发表的指南接受监测。患者被分为低风险（临床和胶囊海绵生物标志物均为阴性）、中度风险（胶囊海绵生物标志物为阴性，临床生物标志物——年龄、性别和节段长度为阳性）或高风险（无论临床生物标志物如何，p53异常或腺体异型增生，或两者皆有）。主要结局是根据风险组分配诊断出需要治疗的高级别发育异常或癌症。
2020年8月至2024年12月期间招募了910名患者，其中138名（15%）被归类为高风险，283名（31%）为中度风险，489名（54%）为低风险。高风险组中任何发育异常或更严重情况的阳性预测值为37.7%（95%CI 29.7 - 46.4）。既有异型增生又有p53异常的患者发生高级别发育异常或癌症的风险最高（相对于低风险组，相对风险为135.8[95%CI 32.7 - 564.0]）。低风险组中高级别发育异常或癌症的患病率为0.4%（95%CI 0.1 - 1.6）；任何发育异常或癌症的阴性预测值为97.8%（95%CI 95.9 - 98.8）。将机器学习算法作为数字病理学工作流程的一部分应用，可将需要进行p53病理学检查的比例降至32%，且不会遗漏任何阳性病例。
风险评估小组能显著富集发育异常情况，基于胶囊海绵的监测可用于低风险的巴雷特食管患者以替代内镜检查。
英国创新署、英国癌症研究中心、英国国家医疗服务体系英格兰癌症联盟
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