Establishing a Platform for Clinical Improvement for Children with HIV-Associated Malignancies in Sub-Saharan Africa

为撒哈拉以南非洲地区患有艾滋病毒相关恶性肿瘤的儿童建立临床改进平台

• 批准号: 10657505
• 负责人: CARL E ALLEN
• 金额: $ 14.79万
• 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/10657505
• 关键词: AIDS related cancer; Acquired Immunodeficiency Syndrome; Address; Adopted; Adoption; Affect; Africa South of the Sahara; Awareness; B-Cell NonHodgkins Lymphoma; Biologic Characteristic; Biology; Bone Marrow; Botswana; Caring; Central Africa; Cerebrospinal Fluid; Child; Child Care; Childhood; Clinical; Clinical Research; Clinical Treatment; Clinical Trials Network; Collaborations; Complex; Conduct Clinical Trials; Development; Diagnosis; Diagnostic Imaging; Disease; Eastern Africa; Epidemic; Evaluation; Event; Foundations; Frequencies; Future; Goals; HIV; HIV Infections; HIV Seronegativity; HIV/AIDS; Health; Hematology; Hospitals; Human Herpesvirus 4; Human Herpesvirus 8; Human Resources; Incidence; Inferior; Infrastructure; International; Kaposi Sarcoma; Lactate Dehydrogenase; Malawi; Malignant Childhood Neoplasm; Malignant Neoplasms; Malnutrition; Mature B-Lymphocyte; Medicine; Methods; Modeling; Outcome; Pathology; Patients; Pediatric Hospitals; Pediatric Oncology; Pediatric Oncology Group; Phenotype; Plasma; Poverty; Prediction of Response to Therapy; Regimen; Research; Risk; Site; Staging; Standardization; Supportive care; Texas; Toxic effect; Treatment Protocols; Tumor Markers; Uganda; United States; antiretroviral therapy; chronic infection; clinical care; clinical center; clinical practice; clinically significant; college; comorbidity; cytokine; evidence base; experience; feasibility testing; high risk; implementation barriers; improved; improved outcome; infection related cancer; multidisciplinary; novel strategies; pediatric human immunodeficiency virus; programs; response; risk stratification; skills; standardized care; survival outcome; treatment strategy; tumor

PROJECT 3: Establishing a Platform for Clinical Improvement for Children with HIV-Associated Malignancies in Sub-Saharan Africa Outcomes for children with cancer in sub-Saharan Africa (SSA) are unacceptably poor, with fewer than 20% of those diagnosed surviving. By contrast, over 85% of children with cancer in the United States survive. The HIV epidemic complicates the landscape of pediatric malignancies in SSA. In SSA, there has been an emphatic association between HIV infection and Kaposi sarcoma (KS), with a 40-fold increase in KS incidence in children in Uganda. And although less pronounced, associations between HIV and mature B cell non-Hodgkin lymphoma (MB-NHL) have been established throughout the region. Not only has HIV impacted the frequency of cancer in SSA, children with HIV have inferior outcomes compared to their HIV-uninfected contemporaries. Over the past fifteen years, there has been a concerted effort to enable treatment of HIV-infected children in SSA with antiretroviral therapy (ART). In partnership with collaborators in SSA, Global HOPE aims to lay the foundation for an international collaborative clinical trial network: Pediatric HIV/AIDS & Infection-Related Malignancies Research Consortium for Sub-Saharan Africa (PARCA). The central problem faced in SSA is the significant burden of HIV-associated malignancies in children and the poor survival of these patients. The overall goal of this project is to establish a standardized multi-site strategy to deliver safe and effective disease-specific and risk-stratified care to children with KS and MB-NHL in SSA. We plan to achieve this goal through the following specific aims: Aim 1: Evaluate current practices and outcomes of children treated for cancer at PARCA sites to identify and address barriers to implementation of standardize treatment regimens. We will perform assessments of current clinical practices in SSA for children with HIV-associated and HIV-negative KS and MB-NHL with focus on risk-stratification, delivery of therapy, and supportive care. Based on these results, we will identify and address gaps in implementation of standardized regimens. Aim 2: Determine the feasibility of implementing standardized treatment regimens for pediatric KS and MB-NHL across PARCA sites. We will test the feasibility of implementing standardized, evidence-based, risk- stratified treatment regimens for HIV-associated and HIV-negative KS and MB-NHL in Uganda and Malawi. Feasibility of this approach will be determined by evaluating accuracy of risk-stratification, completion of prescribed regimen, toxicity, treatment abandonment, and 1-year event-free and overall survival. Aim 3: Investigate clinical and biological characteristics associated with clinical outcomes of children with KS and MB-NHL treated on standardized PARCA treatment regimens. In order to identify clinical and biology factors that may inform future risk-stratification strategies, we will evaluate the clinical significance of baseline staging methods, HIV status, tumor biomarkers and explore potential for plasma cytokines to predict response to therapy.

项目3：为与艾滋病毒相关的儿童建立临床改进平台 撒哈拉以南非洲的恶性肿瘤 撒哈拉以南非洲(SSA)患有癌症的儿童的结果令人无法接受地糟糕，只有不到20% 那些被确诊的人活了下来。相比之下，美国超过85%的癌症儿童存活下来。艾滋病病毒 流行病使SSA儿童恶性肿瘤的情况变得更加复杂。在SSA中，一直有一个强调 HIV感染与Kaposi肉瘤(KS)之间的相关性，儿童KS发病率增加40倍 在乌干达。尽管不那么明显，艾滋病毒和成熟B细胞性非霍奇金淋巴瘤之间的联系 (MB-NHL)已在整个区域建立。艾滋病毒不仅影响了中国的癌症发病率 SSA，与同时代未感染艾滋病毒的儿童相比，感染艾滋病毒的儿童的预后较差。在过去的时间里 15年来，一直在共同努力，使感染艾滋病毒的儿童能够在SSA接受治疗 抗逆转录病毒疗法(ART)。通过与SSA的合作者合作，Global Hope旨在奠定基础 国际协作性临床试验网络：儿科艾滋病毒/艾滋病和感染相关恶性肿瘤 撒哈拉以南非洲研究联盟(PARCA)。SSA面临的中心问题是重要的 儿童中艾滋病毒相关恶性肿瘤的负担和这些患者的低存活率。的总目标是 该项目旨在建立标准化的多站点战略，以提供安全有效的针对特定疾病的 对SSA中KS和MB-NHL儿童的风险分层护理。我们计划通过以下方式实现这一目标 具体目标： 目标1：评估目前在PARCA地点接受癌症治疗的儿童的做法和结果，以确定 并解决实施标准化治疗方案的障碍。我们将进行评估 目前SSA治疗HIV相关和HIV阴性KS和MB-NHL儿童的临床实践 关于风险分层、治疗的提供和支持性护理。根据这些结果，我们将确定和解决 在实施标准化养生方案方面存在差距。 目的2：确定儿童KS和KS实施标准化治疗方案的可行性 跨PARCA站点的MB-NHL。我们将测试实施标准化、循证、风险- 乌干达和马拉维HIV相关和HIV阴性KS和MB-NHL的分层治疗方案。 这种方法的可行性将通过评估风险分层的准确性、完成 处方方案，毒性，放弃治疗，以及1年无事件和总体生存。 目的3：调查与儿童临床结局相关的临床和生物学特征 KS和MB-NHL采用标准化的PARCA治疗方案。为了辨别临床和 可能影响未来风险分层策略的生物学因素，我们将评估 基线分期方法、HIV状态、肿瘤生物标志物和探索血浆细胞因子预测的可能性 对治疗的反应。