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]的常见原因，超过三分之二的老年人

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.