Impact of exercise on ovarian cancer prognosis

描述（由申请人提供）：卵巢癌比女性生殖系统的任何其他癌症导致更多的死亡。然而，手术技术和化疗的改进使得五年生存率从 1976 年的 37% 提高到 2006 年的 45%。由于治疗方式的进步，以最大限度地提高无病生存率和维持生活质量 (QOL) 为主要目标的卵巢癌幸存者数量正在不断增加。因此，生存问题变得越来越重要。各种研究报告卵巢癌患者的生活质量较差。需要进行研究来开发和测试干预措施，以改善卵巢癌幸存者的生活质量。目前，美国癌症协会建议癌症幸存者采取积极锻炼的生活方式，以提高癌症和其他慢性疾病的无病生存率，并提高生活质量。文献中有大量研究表明，在其他类型的癌症治疗（例如乳腺癌）后，体力活动对改善生活质量有很大好处；然而，关于卵巢癌诊断后体力活动和生活质量的研究很少发表。也没有已发表的数据检验体力活动是否可以提高卵巢癌的生存率或生存的替代标志物。尽管运动对卵巢癌生存的影响尚不清楚，但它可能通过体重控制发挥作用，因为一些研究（但并非全部）表明肥胖与生存呈负相关。观察性研究的结果还表明体力活动与卵巢癌风险之间呈负相关。肥胖和低水平缺乏身体活动与卵巢癌风险和死亡率之间关系的可能生物学解释涉及雌激素、胰岛素、胰岛素样生长因子 (IGF)、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的有希望的结果，有必要开展一项试验来检验运动对改善卵巢癌幸存者的生活质量和预后替代标志物的影响。我们建议在 230 名被诊断患有 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预后替代标志物的影响。女性将被随机分配到锻炼计划组或注意力对照组。随机参加运动的女性每周将参加 150 分钟的有氧运动（例如，每周 5 次每次 30 分钟的运动）。我们将进行基线和 6 个月的临床访问，以评估运动对生活质量和替代指标的影响。我们的研究是癌症幸存者中最大规模的运动试验，可以成为“原理证明”，并将为了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。公共卫生相关性：尽管寿命有所延长，但存活的卵巢癌通常会带来一系列令人不快的副作用和生活质量下降。我们提出的试验将是第一项测试运动与注意力控制相比是否对生活质量、健康和预后替代指标产生有益影响的研究。我们的研究将检查运动对 230 名卵巢癌幸存者的生活质量和卵巢癌预后替代标志物的影响。我们的研究是对卵巢癌幸存者进行的最大规模的运动试验，可以成为“原则证明”，也将有助于为数百万癌症幸存者制定治疗后身体活动指南。

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.