Impact of exercise on ovarian cancer prognosis

描述（由申请人提供）：卵巢癌导致的死亡人数超过任何其他女性生殖系统癌症。然而，手术技术和化疗的进步使5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和维持生活质量（QOL）为主要目标的卵巢癌幸存者的数量正在增加。因此，幸存者问题变得越来越重要。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的生活方式，以增加癌症和其他慢性疾病的无病生存率，并提高生活质量。研究表明，在其他类型的癌症治疗（如乳腺癌）后，体育活动对改善生活质量有很强的好处，这在文献中有很好的记录；然而，很少有关于卵巢癌诊断后身体活动和生活质量的研究发表。也没有公布的数据表明体育锻炼是否可以提高卵巢癌患者的生存率或替代生存率。虽然运动对卵巢癌存活的影响尚不清楚，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）显示肥胖与存活呈负相关。观察性研究的结果也表明，体力活动与卵巢癌风险呈负相关。对于肥胖和低水平缺乏运动以及卵巢癌风险和死亡率之间的关联，可能的生物学解释涉及雌激素、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。考虑到我们对健康女性和乳腺癌幸存者的运动干预的随机试验以及我们对卵巢癌幸存者的生活质量干预的有希望的结果，一项研究运动对改善卵巢癌幸存者生活质量和预后替代标志物的影响的试验是有必要的。我们建议评估230名确诊为I-III期卵巢癌的久坐女性，6个月的中等强度有氧运动干预与注意控制对生活质量和预后替代指标的影响。女性将被随机分配到锻炼计划组或注意力控制组。随机分配到运动组的女性将参加每周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。我们的研究是对癌症幸存者进行的最大规模的运动试验，可能是“原理证明”，并将为理解体育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：尽管卵巢癌患者寿命延长，但存活下来的患者往往会带来一系列令人不快的副作用和生活质量的降低。我们提出的试验将是第一个测试运动与注意控制相比是否对生活质量、健康和预后替代指标有有益影响的研究。本研究将探讨运动对230例卵巢癌幸存者生活质量和卵巢癌预后替代指标的影响。我们的研究是卵巢癌幸存者中规模最大的运动试验，可能是“主要证据”，也将有助于为数百万癌症幸存者制定治疗后的体育活动指南。

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.