Understanding Treatment Tolerability in Older Patients with Cancer

项目总结 代表罗切斯特大学提交的这项赠款提案补编的首要目标 NCI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)，是：继续评估项目是否来自患者报告的结果 不良事件通用术语标准(PRO-CTCAE)的版本与 老年患者对晚期癌症治疗的耐受性(即， 残疾、共病和老年综合征)。不断增长的老年患者人数仍在增加 在制定癌症护理标准的研究中代表性不足，导致结果存在显著差异。 在我们的初步研究中，我们发现：1)近60%的老年患者出现3-5级毒性(AS 由NCI的CTCAE衡量)在开始新的治疗方案后三个月内；来自老年人的项目 评估(GA)与毒性显著相关；2)老年患者经常患有晚期癌症 经历干扰功能和生活质量(QOL)的多种症状；3)老年患者经常 经历导致过早停止治疗、住院和死亡的毒性。我们有一个 前所未有的机会，继续利用现有的多站点集群随机研究，该研究已经 已完成登记70岁以上年龄相关疾病的成年人，并开始新的治疗 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、生物统计学和数据科学、PRO测量以及与 CAG和患者权益倡导者(由Canin领导的记分板)是唯一适合进行这项研究的人。这 研究将解决患者报告的毒性如何影响耐受性的知识差距 治疗患有晚期癌症和年龄相关疾病的老年患者。

PROJECT SUMMARY The overarching goal of this grant proposal supplement, 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), is: to continue 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 continue to leverage an existing multi-site cluster randomized study that has completed 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, biostatistics and data science, PRO measurement, and collaborations with CARG 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.