Strategies to Improve Pediatric Cancer Pathology and Tissue Handling for Clinical Care and Research in Low-Resource Settings

Abstract

PURPOSE Evidence-based pediatric cancer control is dependent on accurate, timely cancer diagnosis, as well as maintenance of tissue integrity and annotation for clinical diagnosis and clinical/translational research. Scarcity of cancer pathology infrastructure and the delinkage of clinical pathology and research workflows in low- and middle-income countries thwarts real-time, high-resolution diagnosis, risk stratification, and maintenance of tissue integrity for future research. This renders the application of evidence-based treatments and conduct of translational research and clinical trials, particularly across multiple centers in low- and middle-income countries, impractical. We present the innovative approach and impact of a Texas Children’s Global HOPE model designed to overcome these systemic obstacles in a sub-Saharan Africa setting. METHODS We designed a pathology algorithm at Mulago Hospital Complex in Uganda with the following goals: integrate clinical and research workflows, ensure safe and optimal tissue biopsies, and maintain tissue integrity for clinical and research assays. We introduced new assays built on locally available technology platforms for anatomic pathology and immunophenotyping. RESULTS The novel workflow and assays enabled consistent real-time hematoxylin and eosin microscopy, immunohistochemistry, and multiparametric flow cytometry. The proportion of cancer diagnoses based on tissue pathology increased from 67.5% to 100%. Streamlined pathology processes improved the timeliness of commencement of treatment from 4 to 6 weeks to 24 hours in the case of acute leukemias. The refined diagnosis process has enabled implementation of risk-adapted treatment regimens. Overall, these strategies contributed to improved overall survival from 30% to 85% at 1 month, and have revealed hitherto unrecognized clinical patterns of pediatric cancers in sub-Saharan Africa. CONCLUSION Accurate real-time pathology for pediatric cancers improves survival. Improvements should aim at enhancing the capabilities of existing in-country platforms and skilled personnel. Future efforts will focus on scaling up these practices to other sites and integrating molecular diagnostics that reduce overall cost and improve diagnostic accuracy or risk stratification.