Study of biomarkers in ovarian cancer: modulation by activity & diet intervention

描述（由申请人提供）：卵巢癌在美国每年造成超过18，000例死亡，4年后疾病进展率估计为60-70%。目前正在对1070名既往患有浸润性疾病的女性进行一项假设驱动、随机、注意力控制研究，以检验体力活动+饮食干预在这一弱势人群中增加无进展生存期（PFS）的疗效[（妇科肿瘤组（GOG）0225研究（生活方式干预对卵巢癌增强生存期-（LIVES）试验）]。在这里，我们建议利用试验基础设施和收集重复血液样本的能力来评估可能解释治疗组随时间推移健康指数变化的机制基础。总体假设是，参与者的代谢和炎症状态的变化，预计将证明干预组参与者的炎症和代谢失调的减少比注意力控制组更明显，将与PFS增加相关。拟议工作的第二个重点将是与中心性肥胖症的相互作用。具体目标包括：确定LIVES干预是否改变先前接受过II-IV期卵巢癌治疗的女性中代谢失调的生物标志物;目的2：确定干预对生物标志物的任何影响是否由中心性肥胖的变化介导;目的3：确定干预对生物标志物的任何影响是否由基线中心性肥胖改变，包括 使用计算机断层扫描（CT）检查中枢性肥胖。我们的长期目标是确定中心性肥胖、胰岛素/脂质代谢或炎症的变化是否与无进展生存期相关。

DESCRIPTION (provided by applicant): Ovarian cancer accounts for over 18,000 deaths each year in the U.S. with disease progression rates estimated at 60-70% after 4 years. The efficacy of a physical activity + dietary intervention to increase progression-free survival (PFS) in this vulnerable population is currently being tested in a hypothesis-driven, randomized, attention-control study of 1070 women with prior invasive disease [(Gynecological Oncology Group (GOG) 0225 study (Lifestyle Intervention for oVarian cancer Enhanced Survival- (LIVES) Trial]. Here, we propose to take advantage of the trial infrastructure and capacity to collect repeat blood samples to evaluate the mechanistic underpinnings that might explain any changes in health indices by treatment arm over time. The overarching hypothesis is that change in metabolic and inflammatory status of participants, that is expected to demonstrate a reduction in inflammation and metabolic deregulation in the intervention group participants more so than the attention-control group, will be associated with increased PFS. A secondary focus of the proposed work will be the interaction with central adiposity. The Specific Aims include: To determine if the LIVES intervention alters biomarkers of metabolic deregulation in women previously treated for stage II-IV ovarian cancer; Aim 2: To determine if any effect of the intervention on biomarkers is mediated by change in central adiposity; and Aim 3: To determine if any effect of the intervention on biomarkers is modified by baseline central adiposity including exploration of central adiposity using Computerized Tomography (CT) scans. Our longer term goal is to determine whether change in central adiposity, insulin/lipid metabolism or inflammation is associated with progression free survival.