Impact of exercise on ovarian cancer prognosis

描述(申请人提供)：卵巢癌导致的死亡比女性生殖系统的任何其他癌症都多。然而，手术技术和化疗的改进导致5年存活率从1976年的37%上升到2006年的45%。由于治疗方法的进步，卵巢癌幸存者的主要目标是最大限度地提高无病生存率和维持生活质量(QOL)的人数正在增长。因此，生存问题正变得越来越重要。多项研究报告卵巢癌患者的生活质量较差。需要研究来开发和测试改善卵巢癌幸存者生活质量的干预措施。目前，美国癌症协会建议癌症幸存者采取积极运动的生活方式，以增加癌症和其他慢性病的无病生存率，并提高生活质量。在其他类型的癌症治疗后，体力活动对改善生活质量有很大益处的研究在文献中得到了很好的记录；然而，很少有关于卵巢癌诊断后体力活动和生活质量的研究发表。也没有公布的数据来检验体育锻炼是否可以改善卵巢癌的存活率或替代存活率的标记物。尽管运动对卵巢癌生存率的影响尚不清楚，但它可能通过控制体重发挥作用，因为一些研究(但不是全部)表明肥胖与生存率负相关。观察性研究的结果还表明，体力活动与患卵巢癌的风险呈负相关。肥胖和低运动量与卵巢癌风险和死亡率之间的关系可能的生物学解释包括雌激素、胰岛素、胰岛素样生长因子(IGFS)、C反应蛋白(CRP)、瘦素、CA-125、催乳素、骨桥蛋白和巨噬细胞抑制因子的潜在作用。鉴于我们对健康女性和乳腺癌幸存者进行的运动干预随机试验以及对卵巢癌幸存者的生活质量干预取得了令人振奋的结果，因此有必要进行一项试验，考察运动对改善卵巢癌幸存者的生活质量和替代预后标志物的影响。我们建议在230名被诊断为I-III期卵巢癌的久坐女性中，评估为期6个月的中等强度有氧运动干预与注意力控制对生活质量和替代预后标志物的影响。女性将被随机分配到锻炼计划或注意力控制组。被随机安排参加锻炼的女性将参加每周150分钟的有氧运动(例如，每周5次30分钟的锻炼)。我们将进行基线和6个月的临床访问，以评估锻炼对生活质量和替代指标的影响。我们的研究是对癌症幸存者进行的最大规模的运动试验，可能是一项“原则证明”，并将为理解体力活动可能影响卵巢癌风险和预后的潜在机制提供关键信息。与公共健康相关：尽管寿命延长，但卵巢癌的存活者往往会带来一系列令人不快的副作用和生活质量上的妥协。我们提议的试验将是第一次测试锻炼和注意力控制是否对生活质量、健康和预后的替代标记物产生有益影响的研究。我们的研究将检验锻炼对230名卵巢癌幸存者的生活质量和卵巢癌预后的替代标记物的影响。我们的研究是对卵巢癌幸存者进行的最大规模的锻炼试验，可能是一项“原则证明”，也将有助于制定数百万癌症幸存者的治疗后体力活动指南。

DESCRIPTION (provided by applicant): Ovarian cancer results in more deaths than any other cancer of the female reproductive system. However, improvements in surgical techniques and chemotherapy have led to an increase in the 5-year survival rate from 37 percent in 1976 to 45 percent in 2006. Because of advances in therapeutic modalities, the number of ovarian cancer survivors for whom primary goals are to maximize disease-free survival and maintain quality of life (QOL) is growing. As such, survivorship issues are becoming increasingly important. Various studies report poor QOL in ovarian cancer patients. Research is needed to develop and test interventions to improve QOL in ovarian cancer survivors. Currently, the American Cancer Society recommends a physically active lifestyle for cancer survivors to increase disease-free survival from cancer and other chronic diseases, and to improve quality of life. Studies of a strong benefit of physical activity on improving QOL following other types of cancer treatment, e.g., breast cancer, are well documented in the literature; yet very few studies of physical activity and QOL after a diagnosis of ovarian cancer have been published. There are also no published data examining whether physical activity may improve ovarian cancer survival or surrogate markers of survival. Although the impact of exercise on ovarian cancer survival is unknown, it may play a role via weight control, since obesity has been shown in some studies, but not all, to be negatively associated with survival. Results from observational studies also suggest an inverse association between physical activity and risk of ovarian cancer. Possible biological explanations for the associations between obesity and low levels of physical inactivity and ovarian cancer risk and mortality involve the potential role of estrogens, insulin, insulin-like growth factors (IGFs) C-reactive protein (CRP), leptin, CA-125, prolactin, osteopontin, and macrophage inhibitory factor. Given the promising results from our randomized trials of exercise interventions in healthy women and breast cancer survivors, and our QOL interventions in ovarian cancer survivors, a trial examining the impact of exercise in improving QOL and surrogate markers of prognosis in ovarian cancer survivors is warranted. We propose to evaluate, in 230 sedentary women diagnosed with Stage I-III ovarian cancer, the impact of a 6-month, moderate-intensity, aerobic exercise intervention vs. attention control upon QOL and surrogate markers of prognosis. Women will be randomized to an exercise program or attention control group. Women randomized to exercise will participate in 150 minutes of aerobic exercise per week (e.g., five 30-min sessions/wk). We will conduct baseline and 6-month clinic visits to evaluate the effect of exercise on QOL and surrogate markers. Our study, the largest exercise trial in cancer survivors, could be a "proof of principal" and will provide critical information in understanding the potential mechanisms through which physical activity may impact ovarian cancer risk and prognosis. PUBLIC HEALTH RELEVANCE: Despite an increase in longevity, surviving ovarian cancer often brings an array of unpleasant side effects and compromises in QOL. Our proposed trial will be the first study to test whether exercise compared with attention control has a beneficial impact on quality of life, fitness and surrogate markers of prognosis. Our study will examine the effect of exercise on QOL and surrogate markers of ovarian cancer prognosis in 230 ovarian cancer survivors. Our study, the largest exercise trial in ovarian cancer survivors, could be a "proof of principal" and will also help shape post-treatment physical activity guidelines for millions of cancer survivors.