Glasgow Pleural Disease Unit, Queen Elizabeth University Hospital Campus, Glasgow, UK.
School of Cancer Sciences, University of Glasgow, Glasgow, UK.
BMJ Open. 2023 Aug 8;13(8):e067780. doi: 10.1136/bmjopen-2022-067780.
To assess key elements of the design for Meso-ORIGINS (Mesothelioma Observational study of RIsk prediction and Generation of paired benign-meso tissue samples, Including a Nested MRI Substudy), an ambitious, UK-wide, prospective study that will collect ≥63 matched benign-mesothelioma tissue pairs through longitudinal surveillance and repeat biopsy of patients with asbestos-associated pleural inflammation (AAPI).
A multicentre, mixed-methods feasibility study, comprising a prospective observational element, evaluating recruitment feasibility, technical feasibility of repeat local anaesthetic thoracoscopy (LAT) and patient acceptability, and a retrospective cohort study focused on AAPI-mesothelioma evolution rate, informing sample size.
4 UK pleural disease centres (February 2019-January 2020).
Patients with AAPI (history or typical imaging plus appropriate pleural histology) were eligible for both elements. In August 2019, eligibility for the prospective element was broadened, including addition of radiological AAPI for technical feasibility and patient acceptability endpoints only. Retrospective cases required ≥2 years follow-up.
A prospective recruitment target was set a priori at 27 histological AAPI cases (or 14 in any 6 months). Technical feasibility and patient acceptability were determined at 6-month follow-up by thoracic ultrasound surrogates and questionnaires, respectively. Retrospective malignant pleural mesothelioma evolution rate was defined by proportion (95% CI). Baseline predictors of evolution were identified using logistic regression.
296 patients with AAPI (39 prospective, 257 retrospective) were recruited/selected. 21/39 prospective recruits were histologically diagnosed (target n=27). Repeat LAT was technically feasible and acceptable in 13/28 (46%) and 24/36 (67%) cases with complete follow-up data. Mesothelioma evolution was confirmed histologically in 36/257 retrospective cases (14% (95% CI 10.3% to 18.8%)) and associated with malignant CT features (OR 4.78 (95% CI 2.36 to 9.86)) and age (OR 1.06 (95% CI 1.02 to 1.12)).
Our initial eligibility criteria were too narrow. Meso-ORIGINS will recruit a broader cohort, including prevalent cases, any biopsy type and patients with malignant CT features. A range of rebiopsy techniques will be allowed, accounting for technical and patient factors. The sample size has been reduced to 500.
ISRCTN12840870.
评估 Meso-ORIGINS（间皮瘤风险预测和生成配对良性间皮组织样本的观察性研究，包括嵌套 MRI 子研究）的设计的关键要素，这是一项雄心勃勃的英国前瞻性研究，将通过纵向监测和对石棉相关胸膜炎症（AAPI）患者进行重复活检来收集≥63 对匹配的良性-间皮瘤组织。
一项多中心、混合方法可行性研究，包括前瞻性观察元素，评估招募可行性、局部麻醉性胸腔镜（LAT）重复的技术可行性和患者可接受性，以及一项聚焦于 AAPI-间皮瘤演变率的回顾性队列研究，为样本量提供信息。
4 个英国胸膜疾病中心（2019 年 2 月-2020 年 1 月）。
有 AAPI（病史或典型影像学加适当的胸膜组织学）的患者有资格参加这两个元素。2019 年 8 月，前瞻性元素的资格标准放宽，仅包括增加放射学 AAPI 以评估技术可行性和患者可接受性终点。回顾性病例需要≥2 年的随访。
前瞻性招募目标预先设定为 27 例组织学 AAPI 病例（或任何 6 个月内 14 例）。技术可行性和患者可接受性分别在 6 个月随访时通过胸腔超声替代物和问卷调查来确定。回顾性恶性胸膜间皮瘤的演变率通过比例（95%CI）来定义。使用逻辑回归识别演变的基线预测因子。
共招募/选择了 296 例 AAPI 患者（39 例前瞻性，257 例回顾性）。27 例目标病例中，有 21 例（39 例前瞻性病例）经组织学诊断。在有完整随访数据的 28 例（46%）和 36 例（67%）病例中，重复 LAT 是可行且可接受的。在 257 例回顾性病例中，有 36 例（14%（95%CI 10.3%至 18.8%））经组织学证实发生间皮瘤，与恶性 CT 特征相关（OR 4.78（95%CI 2.36 至 9.86））和年龄（OR 1.06（95%CI 1.02 至 1.12））。
我们最初的纳入标准过于严格。Meso-ORIGINS 将招募更广泛的队列，包括现患病例、任何活检类型和有恶性 CT 特征的患者。将允许使用多种再活检技术，考虑到技术和患者因素。样本量已减少至 500 例。
ISRCTN84500424。
