Improving the Accuracy of Diagnosis of Cancer in Children with HIV Infection

提高 HIV 感染儿童癌症诊断的准确性

• 批准号: 10427346
• 负责人: Julie M Gastier-Foster
• 金额: $ 13.17万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-25 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10427346
• 关键词: AIDS related cancer; AIDS/HIV problem; Address; Adult; Africa South of the Sahara; Algorithms; Antibodies; Archives; Biological Assay; Biopsy; Botswana; Burkitt Lymphoma; Chest; Child; Childhood; Clinical; Clinical Pathology; Color; Cytogenetics; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Ensure; Evidence based treatment; Fine needle aspiration biopsy; Flow Cytometry; Foundations; Goals; Gold; HIV; HIV Infections; HIV diagnosis; Health Personnel; Hematoxylin and Eosin Staining Method; Hospitals; Human Resources; Image; Immunohistochemistry; Incisional Biopsy; Infection; Infrastructure; Laboratories; Left; Lesion; Link; Lymphoma; Malawi; Malignant Childhood Neoplasm; Malignant Neoplasms; Molecular; Morphology; Needle biopsy procedure; Operative Surgical Procedures; Opportunistic Infections; Pathologist; Pathology; Peripheral; Predictive Value; Preparation; Procedures; Process; Protocols documentation; Recording of previous events; Reporting; Reproducibility; Research; Sedation procedure; Site; Specificity; Stains; Standardization; Superficial Lesion; System; Tanzania; Testing; Time; Tissues; Training; Translational Research; Uganda; United States; base; cancer diagnosis; cancer therapy; cost; design; diagnostic accuracy; diagnostic algorithm; diagnostic assay; diagnostic biomarker; diagnostic platform; diagnostic strategy; experience; improved; infection related cancer; leukemia/lymphoma; lymph nodes; lymphadenopathy; molecular diagnostics; novel; novel diagnostics; novel strategies; pediatric human immunodeficiency virus; recruit; research facility; skills; skin lesion; success; treatment research; treatment site; tumor; ultrasound; virtual

Project 2: Improving the Accuracy of Diagnosis of Cancer in Children with HIV Infection The goal of Project 2 is to evaluate and implement novel strategies that are reproducible and sustainable across treatment sites in sub-Saharan Africa (SSA) to improve real-time diagnosis of HIV-associated pediatric cancers, because this is a prerequisite for evidence-based treatment and clinical/translational research. Diagnosis of cancer in children in SSA is a major challenge because of scarcity of local skilled personnel, facilities for obtaining tissue biopsies, and laboratory platforms for pathology analysis. The result is that for many children with suspected cancer a diagnosis is made based on clinical features only. If a biopsy is obtained, morphological examination using Hematoxylin & Eosin (H&E) stain is often the only test performed. In our study of 324 with HIV infection and diagnosed with KS at BIPAI centers in Uganda, Malawi, Tanzania and Botswana from 2008 – 2014, 141 (43%) of the children were diagnosed based on clinical history and examination only. The overarching aim of this project is to implement and evaluate harmonized diagnostic strategies in PARCA sites. Aim 1: Evaluate the adequacy of biopsies and diagnostic accuracy of the current Global HOPE Uganda diagnostic strategy for pediatric cancer tumors. We will retrospectively assess the proportion of adequate biopsies, and repeat or escalation to open surgical biopsy among 400 children with HIV-associated cancers. To determine the accuracy of the current diagnostic strategy, we will perform gold-standard diagnostic assays by United States standards on archived FFPE tissues from these 400 cases. Aim 2: Determine the feasibility of standardizing the diagnostic algorithm across multiple sites by implementing a similar algorithm in Malawi. We will implement a similar diagnostic approach in Malawi by training medical personnel to use a similar biopsy strategy and expanding the flow cytometry and IHC antibody panels to mimic those performed in Uganda. To ensure accuracy and consistency across sites in preparation for implementation of standardized cancer treatment and research protocols across SSA sites, we will implement a virtual pathology platform to enable sharing and central review of images. The virtual pathology network will also serve as a platform for ongoing training of pediatric pathologists and technicians. Aim 3: Improve accuracy of cancer diagnosis at SSA sites by designing, testing, and implementing novel diagnostic methods. We will test and validate novel molecular assays of established diagnostic biomarkers to improve timeliness and specificity of the diagnosis using platforms and procedures that are sustainable in the SSA setting. Consideration will be given to cost, complexity, and turnaround time.

项目2：提高HIV感染儿童癌症诊断的准确性 项目2的目标是评估和实施可重复且可持续的新型策略 撒哈拉以南非洲（SSA）的治疗部位，以改善与艾滋病毒相关的儿科的实时诊断 癌症，因为这是循证治疗和临床/转化研究的先决条件。 SSA儿童诊断癌症是一个主要挑战，因为当地熟练的人员缺乏 获得组织活检的设施和用于病理分析的实验室平台。结果是 许多怀疑癌症的儿童仅根据临床特征进行诊断。如果活检是 获得的，使用苏木精和曙红（H＆E）染色的形态检查通常是进行的唯一测试。 在我们对324例HIV感染的研究中 2008年至2014年的博茨瓦纳（Botswana），根据临床病史和 仅考试。该项目的总体目的是实施和评估统一的诊断 PARCA网站的策略。 目标1：评估活检的充分性和当前全球希望乌干达的诊断准确性 小儿癌肿瘤的诊断策略。我们将回顾性评估适当的比例 活检，重复或升级以在400名与HIV相关癌症的儿童中打开手术活检。 为了确定当前诊断策略的准确性，我们将执行金标准的诊断测定 按照这400例归档的FFPE组织的美国标准。 AIM 2：确定通过多个站点站立诊断算法的可行性 在马拉维实施类似的算法。我们将在马拉维实施类似的诊断方法 培训医务人员使用类似的活检策略并扩大流式细胞术和IHC抗体 模仿乌干达演出的人的面板。确保准备站点的准确性和一致性 为了实施跨SSA站点的标准化癌症治疗和研究方案，我们将 实施一个虚拟病理平台，以启用图像的共享和中央审查。虚拟病理 网络还将作为持续培训儿科病理学家和技术人员的平台。 AIM 3：通过设计，测试和实施，提高SSA网站上癌症诊断的准确性 新型诊断方法。我们将测试和验证已建立诊断的新型分子测定 使用平台和程序来提高诊断的及时性和特异性的生物标志物 在SSA环境中可持续。将考虑成本，复杂性和周转时间。