A protocol to clinically evaluate liquid biopsies as a tool to speed up diagnosis of children and young adults with aggressive infection-related lymphoma in East Africa “(AI-REAL)”

Abstract

Background 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. Methods 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. Discussion 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. Trial registration Pan African Clinical Trials Registry: PACTR202204822312651, registered on 14th-April-2022.

Diagnostic validation of a portable whole slide imaging scanner for lymphoma diagnosis in resource-constrained setting: A cross-sectional study

“…The detailed design and study setting are described elsewhere. 10 For the portable WSI scanner validation, study pathologists evaluated 105 initially confirmed by gold standard pathology between February 2021 and December 2021. The sites included Kilimanjaro Christian Medical Centre (KCMC), Muhimbili National Hospital (MNH) in Tanzania, and St. Mary’s Hospital Lacor, Gulu, Uganda.…”

“…Formalin-fixed and paraffin-embedded (FFPE) tissue blocks of the identified cases were previously processed according to standard study protocol. 10 Specialist pathological assessment included a full immunohistochemistry (IHC) panel performed on the automated Roche Ventana Benchmark platform (Ventana Medical Systems Inc, USA) . For suspected Burkitt’slymphoma (BL) cases, c-MYC staining was performed in addition to using the Naresh algorithm Fig.…”

“…11 For Hodgkin’s Lymphoma (HL), the diagnosis included the presence of Reed-Sternberg cells expressing CD30 and CD15, occasional CD20 positivity, but the absence of CD45 by IHC or as described in the study protocol. 10 …”

Clinical application of circulating cell-free lymphoma DNA for fast and precise diagnosis of Burkitt lymphoma: Precision medicine for sub-Saharan Africa

“…Finally, because interaction with more established centres in HICs is critical, we recommend training for laboratory scientists through short courses to introduce specific technical skills and fellowships for more long-term mentoring with experts in centres of excellence situated in HICs. We acknowledge that achieving these goals goes beyond science and public health because it 2024 (Legason et al, 2022). In addition to a technical and clinical validation, the study addresses the need for regional multi-disciplinary diagnostic capacity building, laboratory quality control and health-economic evidence to achieve long-term sustainability and patient benefit that will ultimately catalyse multi-cancer early detection more generally.…”

“…In conclusion, cfDNA promises earlier and more precise diagnosis of eBL in SSA. The UK’s National Institute of Health Research (NIHR) has funded a multicentre study in Uganda and Tanzania that evaluates this promise with initial results expected to be published in 2024 (Legason et al, 2022 ). In addition to a technical and clinical validation, the study addresses the need for regional multi-disciplinary diagnostic capacity building, laboratory quality control and health-economic evidence to achieve long-term sustainability and patient benefit that will ultimately catalyse multi-cancer early detection more generally.…”