Integration of Geriatric Measures Alongside Disease-Based Measures to Advance Precision Oncology for Older Veterans with Multiple Myeloma

虽然领先的癌症组织，如美国临床医学会， 肿瘤学现在建议对所有患有癌症的老年人进行老年评估， 由于以下方面的限制，评估尚未在VA和其他地方广泛采用 资源、老年医学专业知识和在忙碌的肿瘤诊所的时间。国家精密 肿瘤学项目正在分析骨髓瘤和其他癌症的肿瘤遗传学， 疾病和个性化治疗以前所未有的方式。然而，真正个性化的癌症 老年退伍军人的治疗不仅必须基于肿瘤的“基因型”，而且还必须基于老年人 “显型”Clark DuMontier博士是一位老年病学家和临床研究者，专注于整合 将老年医学纳入肿瘤学。为CDA-2提出的研究将促进博士。 DuMontier的长期目标是开发可行有效的工具，帮助VA肿瘤学家整合 脆弱性和多发性骨髓瘤以及骨髓瘤特异性因素，以推进精确的肿瘤学， 患有骨髓瘤的老兵本申请的目的是电子测量 在VA新治疗的5000多名年龄≥ 65岁的骨髓瘤退伍军人中的虚弱和多发性骨髓瘤 从2004年至今，使用VA全国综合医疗保健数据， 卫生系统。初步研究结果表明，虚弱和多发性硬化可以迅速 使用诊断和程序代码以及电子健康记录中的数据进行评估 （EHR）。目标1将确定电子脆弱指数VA-FI是否能独立预测 患有骨髓瘤的老年退伍军人的死亡率和住院率，以及它是否改变了 对这些结果的影响。分析将包括重要的骨髓瘤特异性因素 如三联或双联化疗、分期和细胞遗传学、社会人口学变量 和预后实验室目标2将确定多模态模式是否独立预测 骨髓瘤的死亡率和住院率，以及它们是否改变了特定方案的效果 这些结果。机器学习分析将应用于67种慢性疾病 在VA数据库中进行测量，以定义这些模式及其对老年退伍军人的影响， 骨髓瘤目标3将开发和验证死亡率的预测风险模型， 虚弱和多发性骨髓瘤特异性因子。一旦验证，该模型将 翻译成嵌入在VA EHR中的临床决策支持工具。该工具将帮助 肿瘤学家快速评估虚弱和多发性硬化，并提高个体化预后 和治疗决策的老年退伍军人骨髓瘤。受指导的研究和培训 该CDA-2中描述的计划将加速DuMontier博士发展成为一个独立的 退伍军人事务部老年肿瘤学研究员。他的导师团队包括Jane Driver博士、Nikhil Munshi、Michael Gaziano和玛丽布罗菲--老年医学、肿瘤学和大数据科学领域的领导者 来自新英格兰老年医学研究教育临床中心（GRECC）， 马萨诸塞州退伍军人流行病学研究和信息中心（MAVERIC），以及 VA国家精确肿瘤学计划。在这些导师的指导下， 与MAVERIC合作，DuMontier博士将继续接受培训，提供（1）经验 具有大型数据库调查;（2）高级统计分析和机器方面的专业知识 学习;（3）项目管理和多学科合作;（4）沟通， 领导技能和专业发展。这项培训和指导研究将为 他是竞争的VA优秀奖走向独立作为VA临床研究者。

Although leading cancer-focused organizations such as the American Society of Clinical Oncology now recommend geriatric assessments for all older adults with cancer, these assessments have not been widely adopted within VA and elsewhere due to limitations in resources, geriatrics expertise, and time in busy oncology clinics. The VA National Precision Oncology Program is profiling tumor genetics in myeloma and other cancers to characterize disease and personalize therapy in unprecedented fashion. However, truly personalized cancer treatment for older Veterans must be based not only on tumor “genotype,” but also on older adult “phenotype.” Dr. Clark DuMontier is a geriatrician and clinical investigator focused on integrating geriatric measures into oncology. The research proposed for this CDA-2 will advance Dr. DuMontier’s long-term goal of developing feasible and valid tools to help VA oncologists integrate frailty and multimorbidity alongside myeloma-specific factors to advance precision oncology for older Veterans with myeloma. The objectives of this application are to electronically measure frailty and multimorbidity in over 5000 Veterans age ³ 65 years with myeloma newly treated in VA from 2004-present using healthcare data that is readily available within VA’s nationally integrated health system. Preliminary findings demonstrate that frailty and multimorbidity can be rapidly assessed using diagnostic and procedural codes and data from the electronic health record (EHR). Aim 1 will determine whether an electronic frailty index, the VA-FI, independently predicts mortality and hospitalizations in older Veterans with myeloma, and whether it modifies the effect of initial therapy on these outcomes. Analyses will include important myeloma-specific factors such as triplet or doublet chemotherapy, stage and cytogenetics, sociodemographic variables, and prognostic labs. Aim 2 will determine whether multimorbidity patterns independently predict mortality and hospitalizations in myeloma, and whether they modify the effect of specific regimens on these outcomes. A machine learning analysis will be applied to 67 chronic conditions measured within the VA database to define these patterns and their impact in older Veterans with myeloma. Aim 3 will develop and validate a predictive risk model for mortality that incorporates frailty and multimorbidity with myeloma-specific factors. Once validated, this model will be translated into a clinical decision support tool embedded in the VA EHR. This tool will help VA oncologists to rapidly estimate frailty and multimorbidity and enhance individualized prognosis and treatment decisions for older Veterans with myeloma. The mentored research and training program described in this CDA-2 will accelerate Dr. DuMontier’s development into an independent VA investigator in geriatric oncology. His mentorship team includes Drs. Jane Driver, Nikhil Munshi, Michael Gaziano, and Mary Brophy—leaders in geriatrics, oncology, and big data science from the New England Geriatric Research Education Clinical Center (GRECC), the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), and the VA National Precision Oncology Program. Under the guidance of these mentors and in collaboration with MAVERIC, Dr. DuMontier will pursue training that will provide (1) experience with large database investigation; (2) expertise in advanced statistical analyses and machine learning; (3) project management and multidisciplinary collaboration; and (4) communication, leadership skills, and professional development. This training and mentored research will prepare him to be competitive for a VA Merit Award toward independence as a VA clinician investigator.