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 i nclude: 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.
Women treated for invasive ovarian cancer are at a high risk for disease progression making ovarian cancer the most fatal gynecological cancer. Little is known about the biological mechanisms by which progression may be modified. General knowledge of cancer suggests inflammation and metabolic abnormalities, both of which are altered with obesity, may play a role in ovarian cancer progression. Importantly, these mechanisms have been shown to improve with lifestyle modifications such as increased physical activity or healthy dietary selections. The ongoing GOG 0225 physical activity + diet trial affords a unique opportunity to study blood samples to advance our understanding of mechanisms associated with ovarian cancer survival.
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