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

项目3：为艾滋病毒相关疾病儿童的临床改善建立一个平台 撒哈拉以南非洲的恶性肿瘤 撒哈拉以南非洲（SSA）癌症儿童的预后差得令人无法接受， 被诊断为幸存者。相比之下，在美国，超过85%的癌症儿童存活。艾滋病毒 流行病使SSA的儿科恶性肿瘤的情况复杂化。在南苏丹， HIV感染与卡波西肉瘤（KS）之间的关联，儿童KS发病率增加40倍 在乌干达。虽然不太明显，艾滋病毒和成熟B细胞非霍奇金淋巴瘤之间的联系 （MB-NHL）已在整个地区建立。艾滋病毒不仅影响了癌症的发病率， SSA，与未感染艾滋病毒的同龄人相比，感染艾滋病毒的儿童的结局较差。过去 十五年来，一直在共同努力，使艾滋病毒感染的儿童在撒哈拉以南非洲的治疗， 抗逆转录病毒疗法（ART）。通过与SSA的合作者合作，Global HOPE旨在为 国际合作临床试验网络：儿科艾滋病毒/艾滋病和预防相关肿瘤 撒哈拉以南非洲研究联盟（PARCA）。SSA面临的核心问题是 儿童中HIV相关恶性肿瘤的负担以及这些患者的生存率低。的总目标 该项目旨在建立一个标准化的多地点战略，以提供安全有效的疾病特异性和 对SSA的KS和MB-NHL儿童进行风险分层护理。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PARCA中心儿童癌症治疗的现行做法和结果， 并解决实施标准化治疗方案的障碍。我们将进行评估 SSA治疗HIV相关和HIV阴性KS和MB-NHL儿童的当前临床实践， 风险分层，治疗和支持性护理。根据这些结果，我们将确定和解决 在执行标准化治疗方案方面存在差距。 目的2：确定对儿童KS实施标准化治疗方案的可行性， PARCA研究中心的MB-NHL。我们将测试实施标准化的、基于证据的、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。 该方法的可行性将通过评估风险分层的准确性、 处方方案、毒性、放弃治疗和1年无事件生存期和总生存期。 目的3：研究与儿童临床结局相关的临床和生物学特征 KS和MB-NHL患者接受标准PARCA治疗方案治疗。为了识别临床和 生物学因素，可能会告知未来的风险分层策略，我们将评估的临床意义， 基线分期方法，HIV状态，肿瘤生物标志物，并探索血浆细胞因子预测 对治疗的反应。

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.