Understanding the Role of Diet, Body Composition, and Exercise across the Ovarian Cancer Control Continuum
Date of Award
Spring 2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Public Health
First Advisor
Ferrucci, Leah
Abstract
Background:Ovarian cancer is the fifth leading cause of cancer-related death in women in the United States. The high mortality rate for ovarian cancer can be attributed to a lack of effective screening tools and relatively limited treatment options. Energy balance factors, including diet, physical activity, and body composition, have been studied as potential intervention targets for cancer prevention and to complement current treatments for cancer outcomes in many cancer types, but research is much more limited for ovarian cancer. For example, there are few studies on diet quality and ovarian cancer risk and survival, and results have been mixed. The existing diet quality studies have also not dealt with the issue of semi-competing events which could lead to biased effect estimates for these associations. In addition, there are only four studies of body mass index (BMI) and chemotherapy adherence in ovarian cancer patients. While obesity has been identified as risk factor for non-adherence to guidelines-recommended chemotherapy, most of the existing datasets were from an era in which there was a dose-capping recommendation for high body surface area, which is associated with high BMI, thus examinations in the current treatment era are needed. Higher physical activity has been inversely associated with chemotherapy-induced peripheral neuropathy (CIPN), a common side effect of chemotherapy in women with ovarian cancer, in observational studies, but intervention studies directly assessing the effect of exercise on CIPN are lacking for not only ovarian cancer, but all cancer types. Therefore, high-quality research on lifestyle factors across the cancer control continuum is needed to better inform lifestyle recommendations for both ovarian cancer prevention and survivorship. Methods:This dissertation includes three studies that assessed: the associations between diet quality and ovarian cancer risk and survival; the relationship between BMI at ovarian cancer diagnosis in relation to chemotherapy adherence; and the effect of an aerobic exercise intervention on CIPN after completing ovarian cancer treatment. For the first study (Chapter 2), we used a semi-Markov multistate model to assess the association between prediagnosis diet quality, assessed via the Healthy Eating Index-2015 (HEI-2015), the alternate Mediterranean diet score (aMED), and the Dietary Approaches to Stop Hypertension score (DASH), in relation to ovarian cancer risk (N=150,643) and survival (N=1,107) in the large, prospective National Institutes of Health-AARP (NIH-AARP) Diet and Health Study. For the second study (Chapter 3), among patients who received curative intent, first-line carboplatin plus paclitaxel chemotherapy for ovarian cancer at Yale-Smilow Cancer Hospital Network from 2012 to 2022 (N=327), we examined the association between BMI at diagnosis and relative dose intensity (RDI), defined as the ratio of completed chemotherapy dose intensity to the guidelines recommended dose intensity, as well as common chemotoxicities and hospitalizations during treatment using multivariable logistic and linear regression. In the final study (Chapter 4), we conducted a secondary data analysis in a randomized clinical trial of a six-month aerobic exercise intervention versus attention-control among 134 patients who were treated for ovarian cancer to assess the effect of exercise on self-reported CIPN via mixed-effects models. Results:In Chapter 2, we found better diet quality, according to the HEI-2015 (quintile 5 versus quintile 1: Hazard Ratio (HR) = 0.75, 95% confidence interval (CI): 0.60 to 0.93) and aMED (quintile 5 versus quintile 1: HR = 0.68, 95% CI: 0.53 to 0.87), was associated with lower all-cause mortality among ovarian cancer patients. There was no evidence of an association between diet quality and ovarian cancer risk. In Chapter 3, the average RDI was 78.1%, and 47.1% of the patients had a low RDI (defined as <85%). BMI was not associated with RDI (between group difference versus BMI<25kg/m2: 25≤BMI<30: 5.05±3.06%; BMI≥30: 3.19±3.00%; P=0.24) or other chemotherapy adherence related outcomes. An average initial prescribed dose intensity of 95.9±9.0% of the NCCN recommended intensity and an average adherence of 81.8±25.7% to one’s oncologist-prescribed dose intensity indicated most dose modifications occurred during treatment. In Chapter 4, self-reported CIPN was reduced by 1.3 points in the exercise arm compared to a 0.4-point increase in the attention-control arm after 6 months, with a between-group difference of -1.6 points (95% CI: -3.1 to -0.2). The point estimate was larger among the 127 patients with CIPN symptoms at enrollment (-2.0, 95% CI: -3.6 to -0.5). Conclusion:Overall, our findings support the importance of a healthy lifestyle in ovarian cancer survivorship. We found that higher quality diet prediagnosis was associated with lower all-cause mortality after ovarian cancer diagnosis, suggesting that maintaining or improving one’s diet quality from diagnosis could be important for survival. Additional observational and intervention research on post-diagnosis diet quality is essential to understand if better diet quality after diagnosis could improve outcomes in women with ovarian cancer. Importantly, in patients with ovarian cancer treated since 2012, BMI was not associated with completing a lower chemotherapy dose intensity and dose-capping for high BMI was not common. As dose modifications were common during treatment, developing interventions that maximize chemotherapy adherence for patients with ovarian cancer is critical. Additionally, studies with other measures of body composition (e.g., muscle mass, fat mass) are warranted to further explore body composition and chemotherapy adherence and inform clinical decision making. Finally, since aerobic exercise improved CIPN among patients who had completed ovarian cancer treatment, this points toward exercise being a potential treatment for CIPN among those who had developed CIPN during treatment. Future research could help to illuminate if exercise interventions delivered during chemotherapy could prevent the development of CIPN. This dissertation has helped to expand the knowledge base on lifestyle factors and body composition across the ovarian cancer control continuum and laid the groundwork for future interventions targeting diet quality and exercise to potentially improve cancer outcomes for patients diagnosed with ovarian cancer. Implementation science studies that evaluate the integration of lifestyle interventions in tandem with standard oncology care in diverse settings are needed, so that if effective, patients diagnosed with ovarian cancer can have access to these supportive care services that may improve outcomes.
Recommended Citation
Cao, Anlan, "Understanding the Role of Diet, Body Composition, and Exercise across the Ovarian Cancer Control Continuum" (2024). Yale Graduate School of Arts and Sciences Dissertations. 1311.
https://elischolar.library.yale.edu/gsas_dissertations/1311
