Understanding Treatment Tolerability in Older Patients with Cancer

项目摘要 本补助金申请补充的总体目标，代表罗切斯特大学提交 NCI社区肿瘤学研究计划（UR NCORP）研究基地与癌症和衰老 研究小组（CARG）的主要任务是：继续评估患者报告结局中的项目是否 不良事件通用术语标准（PRO-CTCAE）版本与 在具有年龄相关病症的老年患者中治疗晚期癌症的耐受性（即， 残疾、合并症和老年综合征）。不断增长的老年患者人数仍然是 在制定癌症护理标准的研究中代表性不足，导致结果的显著差异。 在我们的初步研究中，我们发现：1）接近60%的老年患者发生3-5级毒性（如 通过NCI的CTCAE测量）;来自老年组的项目 评估（GA）与毒性显著相关; 2）老年晚期癌症患者经常 出现多种干扰功能和生活质量（QoL）的症状; 3）老年患者经常 经历导致早期停止治疗、住院和死亡的毒性。我们有一个 这是一个前所未有的机会，可以继续利用现有的多中心随机分组研究， 已完成入组年龄>70岁、患有年龄相关疾病且正在开始新治疗的成人 UR NCORP网络中晚期癌症的治疗方案（URCC 13059/“GAP”）（n=700）。除了 基线、第4周、第3周时临床医生评定的CTCAE、GAP采集PRO指标（PRO-CTCAE、GA、满意度） 个月，以及新治疗方案开始后6个月。收集了大量临床数据， 耐受性指标，包括治疗剂量调整、住院和死亡率。我们将合作 与U 01联盟合作，以：1）开发并比较PRO-CTCAE评分和临床医生评定的 年龄相关疾病老年患者CTCAE 2-5级; 2）评价PRO-1与年龄相关疾病之间的相关性。 CTCAE评分和临床医师评定的CTCAE等级与临床耐受性指标; 3）评价相关性 PRO-CTCAE评分和临床医生评定的CTCAE等级与PRO终点（例如，功能，生活质量， 满意度）;以及4）验证一个模型，该模型识别出患有与年龄相关的疾病的老年患者， 晚期癌症治疗耐受性差的风险。与利益相关者一起开发，我们的运营 耐受性的定义是新的;它包括临床结局和PRO终点。该小组 包括临床试验，生物统计学和数据科学，PRO测量以及与 CARG和患者倡导者（由Canin领导的SCOREBoard）非常适合进行这项研究。这 研究将解决患者报告的毒性如何告知耐受性的知识方面的关键差距， 治疗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.