Understanding Treatment Tolerability in Older Patients with Cancer

项目总结 代表罗切斯特NCI大学提交的这份为期五年的拨款提案的总体目标是 社区肿瘤学研究计划(UR NCORP)研究基地与癌症和老龄化研究 组(CAG)对RFA-CA-17-052的响应是：评估是否来自患者报告的项目 不良事件通用术语标准(PRO-CTCAE)的结果版本为 与老年晚期癌症患者对治疗的耐受性有关 疾病(即残疾、共病和老年综合征)。不断增长的老年患者人数 在制定癌症护理标准的研究中仍然代表不足，导致在 结果。在我们的初步研究中，我们发现：1)近60%的老年患者发展为3-5级 毒性(以NCI的CTCAE衡量)在开始新的治疗方案后三个月内； 老年评估(GA)与毒性显著相关；2)老年晚期癌症患者 经常出现干扰功能和生活质量(QOL)的多种症状；以及3)年龄较大 患者经常会经历毒副作用，导致提前停止治疗、住院和 死亡率。我们有一个前所未有的机会来利用现有的多站点集群随机研究 目前正在招募70岁的患有年龄相关疾病的成年人，他们正在开始一种新的治疗方法 UR NCORP网络中晚期癌症的治疗方案(URCC 13059/“GAP”)(n=700)。除了……之外 临床医生评级的CTCAE，GAP捕获基线、4周、3周的PRO指标(PRO-CTCAE、GA、满意度) 在新的治疗方案开始后6个月。收集了大量关于临床的数据 耐受性指标包括治疗剂量修改、住院和死亡率。我们将合作 与U01联盟合作：1)开发和比较CTCAE前评分和临床医生评级的轨迹 有年龄相关性疾病的老年患者的CTCAE评分为2-5级；2)评估与年龄相关疾病的相关性 CTCAE评分和临床医生评定的CTCAE等级与临床耐受性指标；3)评估相关性 在PRO-CTCAE评分和具有PRO终点的临床医生评级的CTCAE评分之间(例如，功能、QOL、 满意度)；以及4)验证一个模型，该模型识别具有与年龄相关的疾病的老年患者处于高 晚期癌症治疗的耐受性差的风险。与利益相关者共同开发，我们的运营 耐受性的定义是新的；它既包括临床结果，也包括PRO终点。这支球队， 包括临床试验(Mohile、Morrow、Janelsins、Kamen)、生物统计学和数据科学方面的专业知识 (Culakova，Heckler，Pandya，Ramsdale，Zand)，专业测量(Mohile，Duberstein，Chapman，Flannery)， 与Carg(Hurria，Dale)和患者权益倡导者(由Canin领导的记分板)的合作是独一无二的 适合进行这项研究。这项研究将解决关于患者如何报告的知识的一个关键差距 毒性可告知患有晚期癌症和年龄相关疾病的老年患者的治疗耐受性。

PROJECT SUMMARY The overarching goal of this five-year grant proposal, submitted on behalf of the University of Rochester NCI Community Oncology Research Program (UR NCORP) Research Base and the Cancer and Aging Research Group (CARG), in response to RFA-CA-17-052, is: to evaluate whether items from the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) are associated with tolerability of treatment for advanced cancer in older patients with age-related conditions (i.e., disability, comorbidity, and geriatric syndromes). The growing population of older patients remains underrepresented in research that sets cancer care standards leading to significant disparities in outcomes. In our preliminary research, we found that: 1) close to 60% of older patients develop grade 3-5 toxicity (as measured by NCI's CTCAE) within three months of starting a new treatment regimen; items from geriatric assessment (GA) were significantly associated with toxicity; 2) older patients with advanced cancer frequently experience multiple symptoms that interfere with function and quality of life (QoL); and 3) older patients often experience toxicities that lead to early discontinuation of treatment, hospitalizations, and mortality. We have an unprecedented opportunity to leverage an existing multi-site cluster randomized study that is currently enrolling adults aged >70 years with age-related conditions who are starting a new treatment regimen for advanced cancer in the UR NCORP network (URCC 13059/“GAP”) (n=700). In addition to clinician-rated CTCAE, GAP captures PRO measures (PRO-CTCAE, GA, satisfaction) at baseline, 4 weeks, 3 months, and 6 months after the start of the new treatment regimen. Extensive data are collected on clinical tolerability metrics including treatment dose modifications, hospitalizations, and mortality. We will collaborate with the U01 consortium to: 1) develop and compare the trajectories of PRO-CTCAE scores and clinician-rated CTCAE grades 2-5 in older patients with age-related conditions; 2) evaluate associations between PRO- CTCAE scores and clinician-rated CTCAE grades with clinical tolerability metrics; 3) evaluate associations between PRO-CTCAE scores and clinician-rated CTCAE grades with PRO endpoints (e.g., function, QoL, satisfaction); and 4) validate a model that identifies older patients with age-related conditions who are at high risk for poor tolerability from treatment for advanced cancer. Developed with stakeholders, our operational definition of tolerability is novel; it includes both clinical outcomes and PRO endpoints. The team, which includes expertise in clinical trials (Mohile, Morrow, Janelsins, Kamen), biostatistics and data science (Culakova, Heckler, Pandya, Ramsdale, Zand), PRO measurement (Mohile, Duberstein, Chapman, Flannery), and collaborations with CARG (Hurria, Dale) and patient advocates (SCOREBoard led by Canin) is uniquely suited to conduct this research. This research will address a critical gap in knowledge of how patient-reported toxicity informs tolerability of treatment in older patients with advanced cancer and age-related conditions.