Roswell Park-Led Research Shows Muscle & Fat Strongly Linked to Survival in Epithelial Ovarian Cancer

Rikki Cannioto, PhD, EdD, MS

Researchers from Roswell Park Comprehensive Cancer Center and five partner institutions are shedding light on how body composition at the time of diagnosis relates to mortality in patients with epithelial ovarian cancer (EOC), a subject about which little is known. The team’s findings are reported in a new study published in the Journal of the National Cancer Institute.

Led by principal investigator and senior author Rikki Cannioto, PhD, EdD, MS, Assistant Professor of Oncology, Department of Cancer Prevention & Control, the study analyzed pre-chemotherapy clinical data and CT image-based body composition data from 500 EOC patients in the ongoing Body Composition and Epithelial Ovarian Cancer Survival (BComES) study at Roswell Park, also led by Dr. Cannioto.

While adiposity, or obesity, increases the risk of developing at least 13 types of cancer — including EOC — some data from previous studies suggested that obese patients with ovarian cancer tended to survive longer than their non-obese peers — an obesity paradox. This work calls into question the conclusions of previous ovarian cancer studies on obesity and survival that reported either no association between the two or an “overweight or obesity paradox.”

But Dr. Cannioto points out that the results of previous studies may be skewed, because they did not account for skeletal muscle mass when gauging the impact of excess adiposity on patient survival. “It is likely that in prior reports, many patients in the healthy-weight comparison group also had low muscle mass, or sarcopenia — an age-related condition known to be associated with increased mortality in cancer patients,” she says. “As a result, both skeletal muscle mass and adiposity need to be considered to disentangle the association between high versus low adiposity and cancer outcomes.”

To solve the problem, she and her colleagues assigned patients to one of four body phenotype categories based on their body imaging records. Each category factored in both high or low skeletal muscle index (SMI) and high or low adiposity, making it easier to identify those who had low SMI (sarcopenia) so their higher mortality rates could be considered separately. “We compared patients with any combination of excess adiposity and/or low muscle mass to patients who had low adiposity but normal skeletal muscle mass,” adds Dr. Cannioto. “That’s what’s unique about it.”

The four body phenotype categories and percentage of patients in each included:

• Fit/reference (normal SMI/low adiposity) — 16.2%
• Overweight/obese (normal SMI/high adiposity) — 51.2%
• Sarcopenia/overweight-obese (low SMI/high adiposity) — 15.6%
• Sarcopenia/cachexia (low SMI/low adiposity) — 17%

“Our work, which accounts for both skeletal muscle mass and adiposity, shows no evidence of an overweight or obesity paradox when patients with low muscle mass are removed from the healthy comparison group. Rather, we show that EOC patients with any combination of high adiposity and/or low muscle had up to a twofold increased risk of mortality in comparison with patients with optimal muscle and low adiposity — a “fit” phenotype, with the greatest increases in mortality seen in patients with high-grade serous ovarian cancer (HGSOC), the most common and fatal EOC tumor,” says Dr. Cannioto.

Mortality rates were recorded for each category, both for EOC overall and HGSOC, which has a median overall survival of only 40 months.

Data analysis showed that when compared to the Fit/reference group:

• Overweight/obesity was associated with up to 51% higher mortality for EOC and 104% higher mortality for HGSOC.
• Sarcopenia/overweight-obesity was associated with up to 66% higher mortality for EOC and 67% higher mortality for HGSOC.
• Sarcopenia/cachexia was associated with up to 73% higher mortality for EOC and 109% higher mortality for HGSOC.

Authors of the study note that the strong association of overweight and obesity with increased mortality in EOC and HGSOC correlates with preclinical evidence linking obesity to worse tumor outcomes, and that obesity and physical inactivity may be associated with a suppressed tumor immune microenvironment, resulting in increased tumor aggressiveness.

Results of the study could lay the foundation for future research to determine whether interventional exercise programs and nutritional evaluations might help improve survival in patients after an ovarian cancer diagnosis. “Body composition can be modified through lifestyle,” says Dr. Cannioto. “Targeted lifestyle interventions for patients with high adiposity or low muscle phenotypes may be safe and feasible approaches for mitigating the deleterious changes in body composition that occur as a result of aging, inactivity or a cancer diagnosis and its treatment.”

The research team also included collaborators from the Lake Erie College of Osteopathic Medicine in Elmira, New York; the Jacobs School of Medicine and Biomedical Sciences, University at Buffalo; the University of Utah School of Medicine; Huntsman Cancer Institute at the University of Utah; and the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida.

The research was supported with funding from the National Cancer Institute, the Roswell Park/University of Pittsburgh Cancer Institute Ovarian Cancer Specialized Program of Research Excellence (SPORE) grant and the Roswell Park/University of Chicago Ovarian Cancer SPORE.