Optimizing Treatment of Prostate Cancer in Men living with HIV

优化男性艾滋病毒感染者前列腺癌的治疗

基本信息

批准号：
10771784
负责人：
Elizabeth Chiao
金额：
$ 72.05万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-01 至 2028-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10771784
关键词：
Acquired Immunodeficiency Syndrome Adverse event Age Aging American Society of Clinical Oncology CD4 Lymphocyte Count Calibration Cancer Control Cause of Death Clinical Clinical Management Clinical Trials Cohort Studies Data Decision Aid Decision Making Diagnosis Disease Disease Outcome Disease Progression Disseminated Malignant Neoplasm Event Goals HIV HIV Infections HIV diagnosis Harm Reduction Health Health system Immune System Diseases Life Expectancy Malignant Neoplasms Malignant neoplasm of prostate Medicare Modality Modeling Morbidity - disease rate Natural History Outcome Pathway interactions Persons Population Premature aging syndrome Process Prostate Prostate Cancer therapy Prostatectomy Quality of Life Assessment Quality of life Radiation Radiation therapy Recommendation Recording of previous events Regional Cancer Risk Role Second Primary Cancers Selection for Treatments Source Stage at Diagnosis Subgroup Surgical complication Texas Therapeutic Toxic effect Treatment Protocols Treatment outcome Treatment-related toxicity Uncertainty Veterans aging population antiretroviral therapy cancer diagnosis cancer therapy carcinogenesis chemotherapy clinical decision-making cohort common treatment comorbidity comparative comparative effectiveness analysis data integration disorder risk experience functional status high risk hormone therapy improved men models and simulation mortality mortality risk neoplasm registry novel prostate cancer model prostate cancer progression prostate cancer risk prostate cancer survivors simulation surgical risk therapy outcome treatment disparity treatment optimization treatment risk tumor tumor progression

项目摘要

SUMMARY Cancer is a leading cause of morbidity and mortality among aging people with HIV (PWH) and prostate cancer is now one of the most common cancers among PWH. Despite this, prostate cancer remains the least studied tumor in terms of its natural history and clinical outcomes in the context of HIV. Our findings suggest that HIV infection is associated with rapid carcinogenesis, increased adverse treatment events, and elevated mortality risk. However, there are very limited data on the impact of HIV on treatment selection (versus active surveillance) on key short- and long-term outcomes, including cancer control, quality of life, and mortality particularly for PWH with clinically localized prostate cancer (the most commonly diagnosed stage). These include tradeoffs in toxicity profiles and oncologic control among therapeutic modalities, as well as competing risks of death from non-cancer causes. Quantifying the downstream harms and benefits of different management strategies for localized prostate cancers is critical to aid decision-making, maximize treatment benefits, and reduce harms. Despite compelling need, treatment of localized prostate cancer has never been investigated in the context of HIV in clinical trials, and extrapolating results from clinical trials in HIV uninfected persons is inappropriate due to differences in treatment complications and tolerability. Furthermore, unique HIV-related factors may substantially alter prostate cancer natural history, comorbidities, functional status, risk of second primary cancers, life expectancy, and quality of life. This project will determine the role of HIV on localized prostate cancer natural history and outcomes. We will synthesize a disease simulation that will be used to perform comparative assessment of common treatment pathways to guide treatment decision-making. Our Specific Aims are: (1) To evaluate the impact of immune dysfunction and specific ART regimens on a) active surveillance (AS) for low-risk disease, and definitive treatment for intermediate- and high-risk disease and b) outcomes and adverse treatment events for all stages of prostate cancer among PWH; (2) To create and validate a microsimulation model (HIv Prostate Treatment [HIPR-T]) of prostate cancer natural history and treatment outcomes for localized prostate cancer in PWH; and (3) To use the HIPR-T model to compare the benefits vs harms of optimized AS and definitive treatment for localized prostate cancer over the lifetime of PWH. To achieve these aims, we will use data from large, representative HIV/cancer cohorts (>3,000 PWH prostate cancer survivors) and a validated HIV natural history simulation framework. We will synthesize and validate a novel prostate cancer-HIV simulation model capturing AS, treatment initiation and definitive therapy outcomes. Then, we will use the enhanced model to assess the optimal management of PWH with localized prostate cancer that will maximize survival and quality of life. The findings from this study will transform the clinical decision-making process for early-stage prostate cancer, maximize benefits and reduce harms, reduce uncertainties and treatment disparities, and will inform treatment recommendations for managing prostate cancer among PWH.

概括癌症是艾滋病毒（PWH）和前列腺癌老龄化患者发病率和死亡率的主要原因现在是PWH中最常见的癌症之一。尽管如此，前列腺癌仍然是研究最少的肿瘤就其自然史和临床结果而言。我们的发现表明艾滋病毒感染与癌变快速，不良治疗事件增加和死亡率升高有关风险。但是，关于艾滋病毒对治疗选择的影响的数据非常有限（与主动监测）有限关于关键的短期和长期结果，包括癌症控制，生活质量和死亡率，尤其是PWH 患有临床局部的前列腺癌（最常见的阶段）。这些包括毒性方面的权衡治疗方式之间的概况和肿瘤控制以及非癌症的死亡风险原因。量化不同管理策略的下游危害和益处前列腺癌对于帮助决策，最大化治疗益处并减少危害至关重要。尽管迫切的需求，在HIV的背景下从未研究过局部前列腺癌的治疗由于临床试验，并推断出艾滋病毒未感染患者的临床试验的结果是不合适的治疗并发症和耐受性的差异。此外，独特的HIV相关因素可能基本上改变前列腺癌的自然史，合并症，功能状况，第二次主要癌症的风险，生命期待和生活质量。该项目将确定艾滋病毒对局部前列腺癌的作用历史和结果。我们将合成一个疾病模拟，该模拟将用于进行比较评估通用治疗途径以指导治疗决策。我们的具体目的是：（1）评估免疫功能障碍和特定ART方案对A）主动监视（AS）的影响疾病，以及对中等和高风险疾病以及b）结局和不良治疗的明确治疗 PWH中前列腺癌的所有阶段的事件；（2）创建和验证微仿真模型（HIV 前列腺癌自然病史和局部前列腺治疗结果的前列腺治疗[HIPR-T]） PWH中的癌症；（3）使用HIPR-T模型比较优化AS和在PWH的一生中，对局部前列腺癌的明确治疗。为了实现这些目标，我们将使用来自大型代表性艾滋病毒/癌症队列（> 3,000个PWH前列腺癌幸存者）和经过验证的HIV的数据自然历史模拟框架。我们将合成并验证新的前列腺癌HIV模拟捕获AS的模型，治疗开始和确定的治疗结果。然后，我们将使用增强模型用局部前列腺癌评估PWH的最佳管理，以最大化生存和质量生活。这项研究的发现将改变早期前列腺的临床决策过程癌症，最大化福利并减少危害，减少不确定性和治疗差异，并将告知在PWH中管理前列腺癌的治疗建议。