AI-REAL Study, St Mary's Hospital Lacor, Gulu& African Field Epidemiology Network, 180, Gulu-Uganda. African Field Epidemiology Network, 12874, Kampala, Uganda.
AI-REAL Study, Muhimbili University of Health and Allied Sciences, Dar es Salam, Tanzania.
BMC Cancer. 2022 May 2;22(1):484. doi: 10.1186/s12885-022-09553-w.
The capacity for invasive tissue biopsies followed by histopathology diagnosis in sub-Saharan Africa is severely limited. Consequently, many cancer patients are diagnosed late and outcomes are poor. Here, we propose to evaluate circulating tumour (ct) DNA analysis ("liquid biopsy"), a less invasive and faster approach to diagnose endemic EBV-driven lymphomas (EBVL) in East Africa.
We will evaluate the clinical utility of an already validated ctDNA test prospectively in a head-to-head comparison against histopathology. The primary endpoint is the time from presentation to the specialist centre to a final diagnosis of EBV- Lymphoma. Secondary endpoints include the sensitivity and specificity of liquid biopsy and health economic benefits over histopathology. One hundred forty-six patients will be recruited over 18 months. Patients will be eligible if they are 3-30 years of age and have provided written consent or assent as per IRB guidelines. Tissue and venous blood samples will be processed as per established protocols. Clinical data will be captured securely and in real-time into a REDCap database. The time from presentation to diagnosis will be documented. The sensitivity and specificity of the methods can be estimated within 5% error margin with 95% confidence level using 73 cases and 73 controls. Health-economic assessment will include micro-costing of ctDNA test and histopathology. All results will be reviewed in a multidisciplinary tumour board.
The study evaluates the clinical utility of ctDNA in improving the speed of diagnostic pathways for EBVL in sub-Saharan Africa. Our results would provide proof-of-principle that ctDNA can be used as a diagnostic tool in areas without access to regular pathology, that transfer of the tool is feasible, and that it leads to an earlier and faster diagnosis. The potential clinical and economic impact of this proposal is thus significant. If successful, this study will provide appropriate, and cost-effective diagnostic tools that will promote earlier diagnosis of EBVL and potentially other cancers in countries with restricted healthcare resources.
Pan African Clinical Trials Registry: PACTR202204822312651 , registered on 14th-April-2022.
在撒哈拉以南非洲地区，进行侵袭性组织活检并随后进行组织病理学诊断的能力受到严重限制。因此，许多癌症患者被诊断为晚期，预后较差。在这里，我们建议评估循环肿瘤（ct）DNA 分析（“液体活检”），这是一种侵入性较小、速度更快的方法，可用于诊断东非地方性 EBV 驱动的淋巴瘤（EBVL）。
我们将前瞻性地评估一种已验证的 ctDNA 检测的临床实用性，将其与组织病理学进行头对头比较。主要终点是从就诊到专科中心做出 EBV 淋巴瘤最终诊断的时间。次要终点包括液体活检的敏感性和特异性，以及相对于组织病理学的健康经济效益。在 18 个月内将招募 146 名患者。如果患者年龄在 3-30 岁之间，并按照 IRB 指南提供书面同意或同意，则符合入选条件。将按照既定方案处理组织和静脉血样本。临床数据将安全实时地记录到 REDCap 数据库中。将记录从就诊到诊断的时间。使用 73 例病例和 73 例对照，可以在 5%的误差范围内以 95%的置信水平估计方法的敏感性和特异性。健康经济学评估将包括 ctDNA 检测和组织病理学的微成本核算。所有结果将在多学科肿瘤委员会进行审查。
该研究评估了 ctDNA 提高撒哈拉以南非洲 EBVL 快速诊断途径的临床实用性。我们的结果将提供一个原理证明，即 ctDNA 可作为无常规病理学地区的诊断工具使用，该工具的转移是可行的，并且可以实现更早更快的诊断。因此，该提案具有重要的潜在临床和经济影响。如果成功，这项研究将提供适当且具有成本效益的诊断工具，可促进在医疗资源有限的国家更早诊断 EBVL 和潜在的其他癌症。
泛非临床试验注册处：PACTR202204822312651，注册于 2022 年 4 月 14 日。
