Preserving Physical Function in Older Adults with Cancer: Impact of an Optimizing Nutrition Intervention Applied Before and After Surgery

癌症是老年人[功能衰退和发病率]的常见原因，超过三分之二的 新病例发生在60岁或以上的成年人中。手术是最有效的癌症治疗方法，但它 带来了许多威胁老年患者身体功能恢复的风险。需要手术的老年人 治疗面临与年龄相关的肌肉丧失[质量、力量和耐力、营养不良]的威胁 (包括与癌症相关的营养影响)]、炎症和恶病质[由癌症及其 处理]。此外，老年人经常经历明显的功能能力下降和减少 身体储备，并可能永远不会恢复他们的身体机能的基线水平。这项建议解决了 围手术期干预知识，最大限度地恢复功能能力，最大限度减少肌肉损失 由于分解代谢的情况，并防止这些患者营养不良。因为一种治疗方法使用几种 针对多种机制(靶点)的营养素有望大大优于单一营养素。 治疗方面，我们将使用这种方法来针对与癌症恶病质有关的一些因素，包括 厌食症，脂肪和蛋白质代谢的改变，全身炎症，以及预防或纠正 营养不良。我们希望这项干预措施能提供更好的身体功能恢复，并 改善[生理、代谢]和以退伍军人为中心的结果，而不是[典型]治疗。因此，在一个 务实的临床试验，我们将测试一种多靶点的营养干预，以两相模式应用(Pre-Pre 和手术后)在新转诊为外科癌症治疗的老年退伍军人中。 在一项双臂1：1随机对照试验中，我们将测试这种针对老年人健康的营养优化治疗。 (NOSH)，一种分两期(前8周和后24周)提供的多靶点治疗 手术后出院)，并就(主要)与[典型营养方案(典型)]进行比较 目标1)身体功能、[(次级目标2)生理和代谢结果]和(探索性目标3) 以退伍军人为中心的结果，包括生活质量(QOL)、与癌症相关的营养影响症状以及 术后转归指标。老年退伍军人接近胃肠道或胃肠道[II-III期]手术 在治疗过程中体能明显下降的高危泌尿生殖道癌患者 将被纳入并随机分配到Nosh或[典型方案]，两组都规定低强度 每周进行三次抗阻练习。点心干预将包括慷慨的优质蛋白质(30 G/餐；1.5g/kg/d)和其他与肌肉保存有关的关键营养物质，即b-羟基-b- 丁酸甲酯，一种氨基酸亮氨酸(HMB；3g/d)的代谢物，维生素D和每日一种复合维生素 补充到每天800IU的维生素D水平)。目标1将评估小吃中身体功能的变化 相对于[典型方案]的干预组。我们的工作假设是，小吃干预将 改善身体功能(目标1)和[生理和代谢结果(目标2)] 典型的养生法。]我们还预测以退伍军人为中心的结果会有所改善(目标3)。 这项研究解决了虚弱老年人营养护理最佳实践证据方面的一个重要空白。 接近外科癌症治疗的成年人。如果这项研究的假设是正确的，那么将有很强的 有证据表明，迄今为止被忽视的高危人群的治疗方法发生了重大变化 患有癌症的老年人。更重要的是，癌症治疗的这种改进将导致更强大、更 快速的身体恢复和更好的生活质量。这些发现还将使退伍军人管理局受益于 通过减少术后并发症和加速手术减少对卫生保健系统的需求 身体机能的恢复。

Cancer is a common cause of [functional decline and morbidity] in older adults, with more than two-thirds of new cases occurring in adults aged 60 years or more. Surgery is the most effective cancer treatment, but it brings many risks that threaten recovery of physical function in older patients. Older adults needing surgical treatment face the threats of age-related loss of muscle [quality, strength and endurance, malnutrition (including cancer-related nutrition impact)], inflammation, and cachexia [caused by cancer and its treatments]. Further, older adults often experience marked deterioration of functional abilities and reduced physical reserve and may never regain their baseline level of physical function. This proposal addresses a gap in knowledge on perioperative interventions to maximize restoration of functional capacity, minimize muscle loss due to catabolic circumstances, and prevent malnutrition for these patients. Because a treatment using several nutrients aimed at multiple mechanisms (targets) is expected to be strongly superior to single nutrient treatment, we will use this approach to target a number of factors involved in cancer cachexia, including anorexia, alterations in fat and protein metabolism, and systemic inflammation, as well as to prevent or correct nutritional deficiencies. We expect this intervention to provide superior recovery of physical function and to improve [physiologic, metabolic] and Veteran-centered outcomes versus a [typical] treatment. Thus, in a pragmatic clinical trial, we will test a multi-targeted nutrition intervention, applied in a biphasic pattern (pre- and post-operatively) in older Veterans newly referred for surgical cancer treatment. In a two-armed 1:1 randomized controlled trial, we will test this nutrition-optimized treatment for senior health (NOSH), a multi-targeted treatment provided in biphasic intervals (8 weeks before and 24 weeks after discharge from surgery), and compare it to a [typical nutrition regimen (Typical )] with regards to (Primary Aim 1) physical function, [(Secondary Aim 2) physiologic and metabolic outcomes], and (Exploratory Aim 3) Veteran-centered outcomes, including quality of life (QoL), cancer-related nutrition impact symptoms, and postoperative outcome measures. Older Veterans approaching surgery for [Stage II-III] gastrointestinal or genitourinary cancer who are at high risk for having their physical abilities markedly decline during treatment will be enrolled and randomized to NOSH or the [Typical regimen], with both groups prescribed low-intensity resistance exercise thrice weekly. The NOSH intervention will include generous high-quality protein (30 g/meal; 1.5 g/kg/d) and other key nutrients linked with muscle preservation, namely b-hydroxy-b- methylbutyrate, a metabolite of the amino acid leucine (HMB; 3 g/d), and vitamin D and a daily multivitamin supplemented to a vitamin D level of 800 IU/d). Aim 1 will evaluate changes in physical function in the NOSH intervention arm relative to the [Typical regimen]. Our working hypothesis is that the NOSH intervention will result in improved physical function (Aim 1) and [physiologic and metabolic outcomes (Aim 2) relative to the Typical regimen.] We also predict improvements in Veteran-centered outcomes (Aim 3). This research addresses an important gap in the evidence for best practice of nutritional care for frail older adults approaching surgical cancer treatment. If the hypotheses of this study are correct, there will be strong evidence for a major change in treatment approaches for a heretofore mostly neglected population of high-risk older adults with cancer. More importantly, this improvement in cancer treatment will lead to stronger, more rapid physical recoveries and better quality of life for this population. The findings will also benefit the VA by decreasing demands on the health care system via reductions in postoperative complications and the hastening of recovery of physical function.