Biomarker Approaches to Individualizing Systemic Therapy for High Risk Prostate Cancer

高危前列腺癌个体化系统治疗的生物标志物方法

基本信息

批准号：
10310721
负责人：
Felix Yi-Chung Feng
金额：
$ 7.18万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10310721
关键词：
Address African African American Androgens Biological Markers CLIA certified Cancer Patient Cardiovascular system Clinical Clinical Research Cost Effectiveness Analysis Data Decision Analysis Decision Making Diagnosis Disease Disease Management Effectiveness European Event Exclusion Exposure to External Beam Radiation Therapy Fracture Future Gene Expression Profile Genomics Gleason Grade for Prostate Cancer Goals Grant Guidelines Health Benefit Impaired cognition Intervention Malignant Neoplasms Malignant neoplasm of prostate Mental Depression National Comprehensive Cancer Network Oligonucleotide Microarrays Operative Surgical Procedures Outcome Parents Pathologic Patients Performance Phase Population Prognosis Prognostic Marker Prostate Prostate-Specific Antigen Publishing Race Racial Equity Radiation Therapy Oncology Group Radiation therapy Recommendation Recurrence Risk Role Sampling Selection Criteria Sexual Dysfunction Systemic Therapy Therapeutic Tissues Toxic effect Tumor stage Use Effectiveness androgen deprivation therapy arm base biomarker panel cancer health disparity chemotherapy clinical predictors clinical translation cohort cost cost effective cost effectiveness density deprivation genetic signature genomic signature health equity high risk hormone therapy improved innovation lens markov model men molecular marker new therapeutic target novel parent grant personalized medicine phase III trial predicting response predictive marker predictive modeling predictive signature prognostic prognostic performance prognostic signature prognostic tool prognostic value prostate cancer risk randomized trial research clinical testing response risk stratification side effect specific biomarkers standard of care therapy duration tool treatment strategy tumor

项目摘要

PROJECT SUMMARY Despite the advancement of risk stratification tools on disease management for men with prostate cancer (PCa), there is still a paucity of prognostic tools aimed at identifying African American men (AAM) at increased risk for lethal prostate cancer in the setting of radiation therapy (RT) and androgen deprivation hormone therapy (ADT). Prognostic biomarker panels, such as Decipher, which have been developed and validated in surgical cohorts, have not been systematically validated for prognostic performance after RT+ADT. Furthermore, the cohorts used to derive and validate these prognostic tools have been, on the whole, made up of European-descendent patients. This has limited the prognostic ability in patients of African-descent, who have been shown to have worse prostate cancer-specific outcomes based on clinicopathologic factors including prostate-specific antigen (PSA), Gleason score, and tumor stage. Prognostic tools have not been developed with a racial equity lens, and the role of race and ancestry have only been an afterthought in the treatment recommendation guidelines resulting from Eurocentrically derived clinical studies. As of yet, race has remained on the sidelines without contributing in a clinically meaningful way to the identification, prognosis, treatment recommendations, and cost- effectiveness analysis for men of African-descent. This has limited our ability to identify non-white men at increased risk for lethal PCa, making treatment intensification less precise, limiting the effectiveness of more intense treatment interventions, and contributing to the widening of existing disparities. To address the lack of routine use of molecular biomarkers for therapeutic decision making in men with high-risk PCa, treated with definitive RT, the parent grant proposes to “develop and validate clinically useful and cost-effective prognostic and predictive biomarkers for high-risk PCa patients treated with RT.” This supplement seeks to expand the parent grant, by utilizing principles of health equity, to extend the reach of the findings beyond the traditional Eurocentric population, and in doing so improve the generalizability of the R01 findings to include AAM. This will be accomplished by: (1) comparing the clinical performance of the best prognostic signature and subsequent best prognostic tool, derived from integration of the genomic and clinicopathologic data, from parent grant Aim 1, between AAM and White men (WM) with PCa treated with RT, and (2) determine whether biomarker-based assignment to short-term ADT (STADT) vs. long-term ADT (LTADT) vs. LTADT+intensification, is cost-effective in AAM compared to WM with high-risk PCa, from parent grant Aim 3. Successful completion of this supplement will expand the findings of the parent R01 grant to focus specifically at AAM. Extending the reach of the findings beyond the traditional Eurocentric population.

项目概要尽管前列腺癌 (PCa) 男性疾病管理的风险分层工具取得了进步，仍然缺乏旨在识别非洲裔美国男性 (AAM) 患病风险增加的预测工具放射治疗（RT）和雄激素剥夺激素治疗（ADT）中的致命性前列腺癌。预后生物标志物组合，例如已在外科队列中开发和验证的 Decipher， RT+ADT 后的预后表现尚未得到系统验证。此外，所使用的队列。总的来说，推导和验证这些预测工具是由欧洲人后裔组成的这限制了非洲裔患者的预后能力，而非洲裔患者已被证明患有这种疾病。基于包括前列腺特异性抗原在内的临床病理因素，癌症特异性结果更差 (PSA)、格里森评分和肿瘤分期尚未在种族公平的情况下开发出来。种族和血统的作用只是治疗建议指南中的事后考虑来自以欧洲为中心的临床研究的结果到目前为止，种族仍然处于观望状态。以具有临床意义的方式为识别、预后、治疗建议和成本做出贡献对非洲裔男性的有效性分析这限制了我们识别非白人男性的能力。致命性 PCa 的风险增加，使得治疗强化不太精确，限制了更多治疗的有效性加强治疗干预措施，并导致现有差距的扩大。常规使用分子生物标志物为患有高危 PCa 的男性患者制定治疗决策，并接受最终 RT，母基金提议“开发和验证临床上有用且具有成本效益的预后以及接受 RT 治疗的高危 PCa 患者的预测生物标志物。” 家长资助，利用健康公平原则，将研究结果的影响范围扩大到传统之外以欧洲为中心的人口，这样做可以提高 R01 研究结果的普遍性，将 AAM 纳入其中。通过以下方式完成：（1）比较最佳预后特征和后续特征的临床表现最佳预后工具，源自基因组和临床病理数据的整合，来自家长资助 Aim 1，在 AAM 和接受 RT 治疗的 PCa 白人 (WM) 之间，以及 (2) 确定是否基于生物标志物短期 ADT (STADT) 与长期 ADT (LTADT) 与 LTADT+强化的分配是具有成本效益的在 AAM 中与患有高风险 PCa 的 WM 进行比较，来自家长补助金目标 3。成功完成本补充将扩大母公司 R01 拨款的调查结果，专门关注 AAM 扩大调查结果的范围。超越了传统的以欧洲为中心的人口。