Sarcopenia and Treatment Tolerability in Older Patients with Advanced Cancer

老年晚期癌症患者的肌肉减少症和治疗耐受性

• 批准号: 10164990
• 负责人: Richard F Dunne
• 金额: $ 15万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-20 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10164990
• 关键词: Address; Adult; Advanced Malignant Neoplasm; Adverse event; American Society of Clinical Oncology; Applications Grants; Biometry; Body Composition; Clinical; Clinical Trials; Common Terminology Criteria for Adverse Events; Data; Data Science; Dose; Elderly; Enrollment; Fatty acid glycerol esters; Funding; Geriatric Assessment; Goals; Health; Height; Impairment; Intervention; Knowledge; Lead; Malignant Neoplasms; Measurement; Measures; Muscle; Muscular Atrophy; Older Population; Oncologist; Oncology; Outcome; Patient Outcomes Assessments; Patients; Pharmaceutical Preparations; Population; Populations at Risk; Prevalence; Reporting; Research; Sample Size; Scanning; Science; Skeletal Muscle; Social Well-Being; Syndrome; Time; Toxic effect; Toxicity due to chemotherapy; Treatment Protocols; Vulnerable Populations; Weight; Well in self; X-Ray Computed Tomography; adverse outcome; age related; aged; anticancer research; base; cancer care; cancer therapy; chemotherapy; dosage; experience; functional disability; group intervention; high risk; improved; innovation; interest; mortality; muscle form; novel; older patient; overtreatment; primary outcome; randomized trial; reduced muscle mass; response; sarcopenia; secondary analysis; sex; skeletal muscle wasting; survival outcome; systematic review; treatment as usual

Project Summary: This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA- 20-036. The overarching goal of this one-year supplement grant proposal is: to evaluate whether sarcopenia is associated with tolerability of treatment for advanced cancer in older patients with age-related conditions. 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 clinician-rated Common Terminology Criteria for Adverse Events [CR-CTCAE]); impairment in geriatric assessment (GA) domains were significantly associated with toxicity; 2) 29% of older adults with cancer received chemotherapy at significantly reduced relative dose intensity (RDI); and 3) sarcopenia is highly prevalent (58%) in the geriatric oncology population. U01CA233167 funds secondary analyses of a completed clinical trial to understand how toxicities inform treatment tolerability as part of a NCI U01 tolerability consortium. The operational definition of tolerability we proposed in the U01 is novel because it includes not only adverse outcomes such as toxicity, but also patient-reported outcomes (PROs) valued by older patients. Our analyses utilize data from a completed randomized trial, the GAP study (URCC 13059, clinicaltrials.gov NCT02054741), which evaluated whether provision of a GA summary to oncologists would improve clinical outcomes in adults aged 70+ with advanced cancer receiving treatment (i.e., chemotherapy or other drugs with high risk of toxicity). In this U01 supplement proposal, we will evaluate whether muscle mass (determined by Computed Tomography [CT] scan body composition analysis) is independently associated with treatment tolerability. Our tolerability endpoints include not only toxicity, but also dose intensity, survival, and PROs. Only patients in usual care enrolled to GAP will be included for these analyses (n=369), because many in the intervention group had initial treatment dosages altered based on the GA summary. We will collaborate with Voronoi Health Analytics to accurately measure skeletal muscle mass via CT scan body composition analysis: 1) to determine if sarcopenia is associated with an increased prevalence of grade 3-5 toxicity (CR-CTCAE v4); 2) to determine if sarcopenia is associated with cancer treatment RDI; and 3) to determine if sarcopenia is associated with mortality. Exploratory aims will evaluate if change in muscle mass is associated with clinical outcomes and patient-reported adverse events (as measured by PRO-CTCAE). The team, which includes expertise in clinical trials (Mohile, Mustian, Hezel, Linehan), sarcopenia (Dunne, Hezel, Linehan, Voronoi Health Analytics), geriatric oncology (Mohile and Loh), biostatistics and data science (Culakova, Xu), and PRO measurement (Mohile, Culakova, Loh) is uniquely suited to conduct this research. This research will address a critical gap in knowledge of sarcopenia and its relationship with tolerability of treatment in older patients with advanced cancer and age-related conditions.

项目摘要： 该申请是为了响应特殊利益通知（NOSI）而提交 20-036。这项为期一年的补充赠款提案的总体目标是：评估肌肉减少症是否 与年龄相关的老年患者的治疗耐受性有关 状况。在研究癌症的研究中，老年患者人口不断增长的人数仍然不足 护理标准导致结果差异很大。在我们的初步研究中，我们发现：1） 接近60％的老年患者患有3-5级毒性（如NCI的临床医生评级共同测量 不良事件的术语标准[CR-CTCAE]）;老年评估（GA）领域的损害为 与毒性显着相关； 2）29％的癌症老年人接受了化学疗法 相对剂量强度降低（RDI）； 3）肌肉减少症在老年肿瘤学中高度普遍（58％） 人口。 U01CA233167资金对完成的临床试验进行了二级分析，以了解毒性如何 作为NCI U01耐受性财团的一部分，告知治疗耐受性。耐受性的操作定义 我们在U01中提出的是新颖的，因为它不仅包括毒性等不良结果，还包括 老年患者对患者报告的结果（PRO）。我们的分析利用已完成的数据 随机试验，GAP研究（URCC 13059，ClinicalTrials.gov NCT02054741），该研究评估了是否是否评估 向肿瘤学家提供GA摘要将改善70岁以上成年人的临床结果 接受治疗的癌症（即化学疗法或其他高毒性风险）。在本u01补充中 提案，我们将评估肌肉质量是否（通过计算机断层扫描[CT]扫描体确定 组成分析）与治疗耐受性独立相关。我们的耐受性终点包括 不仅毒性，而且剂量强度，生存和优点。只有接受差距的常规护理患者才会 包括这些分析（n = 369），因为干预组中的许多都有初始治疗剂量 根据GA摘要更改。我们将与Voronoi Health Analytics合作，以准确测量 骨骼肌质量通过CT扫描身体组成分析：1）确定肌肉减少症是否与 3-5级毒性的患病率增加（CR-CTCAE V4）； 2）确定肌肉减少症是否与 癌症治疗RDI； 3）确定肌肉减少症是否与死亡率有关。探索目的会 评估肌肉质量的变化是否与临床结果和患者报告的不良事件有关 （通过Pro-CTCAE衡量）。该团队包括临床试验方面的专业知识（Mohile，Mustian，Hezel， Linehan），肌肉减少症（Dunne，Hezel，Linehan，Voronoi Health Analytics），老年肿瘤学（Mohile and Loh）， 生物统计学和数据科学（Culakova，XU）和Pro测量（Mohile，Culakova，Loh）是独特的 适合进行这项研究。这项研究将解决有关肌肉减少症及其知识的关键差距 在患有晚期癌症和年龄有关的老年患者中，与治疗的耐受性的关系。