Muscle morphology and function in women with advanced-stage ovarian cancer: Relevance in care and response to exercise medicine
Date of Award
Doctor of Philosophy
School of Medical and Health Sciences
Paul A. Cohen
Background: Women with ovarian cancer (OC) often have suboptimal muscle morphology (i.e., low muscle mass and density) at diagnosis, irrespective of their body mass index (BMI). Emerging OC research suggests an association between low pre-treatment muscle mass and density, and poorer treatment and survival outcomes. However, little is known about changes in muscle morphology during first-line OC treatment or muscle morphology differences between women undergoing primary cytoreductive surgery and adjuvant chemotherapy versus neoadjuvant chemotherapy and interval cytoreductive surgery. Additionally, there is currently no established process for screening patients to identify those with suboptimal muscle morphology for supportive care. Resistance exercise has the potential to counteract detrimental cancer-related changes in muscle morphology and function. However, the effects of this exercise modality in women diagnosed with OC are not yet well understood.
Purpose: The overall purpose of this doctoral research was to examine the clinical relevance of muscle morphology in women diagnosed with OC and, further, to explore the effect of supervised resistance exercise on muscle morphology and muscle function in women who had completed first-line treatment for advanced-stage OC.
Methods: This thesis comprises four studies. Study One (Chapter Two) is a systematic review with meta-analyses to investigate the association of BMI, body composition, diet and activity behaviours with survival and treatment-related outcomes in OC patients. In Study Two (Chapter Three) routine computed tomography (CT) scans of 88 patients were used to retrospectively examine muscle morphology change during first-line treatment and differential changes in muscle morphology based on treatments received. Study Three (Chapter Four) was an exploration of the application of a recommended algorithm (i.e., the European Working Group on Sarcopenia in Older People algorithm; EWGSOP2) for the screening and diagnosis of sarcopenia in a case series of six advanced stage OC patients undergoing neoadjuvant chemotherapy. Study Four (Chapter Five) was a prospective single-arm study examining the effects of a 12-week supervised resistance exercise intervention on muscle mass and density (dualenergy x-ray absorptiometry and peripheral quantitative computed tomography), muscle strength (1-repetition maximum [1RM] chest press and 5-RM leg press, handgrip strength), physical function (400-meter walk and Timed Up and Go), quality of life (EORTC QLQ-C30 questionnaire) and self-reported pelvic floor function (Australian pelvic floor questionnaire) in fifteen advanced-stage OC survivors who had completed first-line treatment.
Results: Findings from Study One showed that BMI is not associated with survival outcomes in OC, but that muscle mass and density at diagnosis have prognostic value for progression-free and overall survival. In Study Two suboptimal muscle morphology was prevalent at OC diagnosis. Patients from both treatment groups experienced further muscle mass loss during treatment. However, patients who underwent primary cytoreductive surgery experienced significantly greater pre- to post-treatment reductions in muscle density compared to patients who received neoadjuvant chemotherapy. Muscle density loss during treatment and low post-treatment muscle density were associated with worse overall survival. In Study Three the EWGSOP2 sarcopenia algorithm was found to be unsuitable for the identification of OC patients with low muscle mass. In Study Four a 12-week supervised resistance exercise intervention improved lean body mass and muscle density, upper and lower body strength, and physical function in women who had recently completed first-line OC treatment.
Conclusion: This work provides a better understanding of the clinical relevance of skeletal muscle in OC care and highlights the need for early identification of suboptimal morphology. Preliminary evidence indicates resistance exercise to be an effective supportive care intervention to maintain or increase muscle morphology and muscle function in this cancer population. Research is urgently needed to establish strategies for the effective and timely screening and diagnosis of OC patients with suboptimal morphology. Individualized and targeted resistance exercise interventions should be recommended in OC supportive care to counteract the detrimental impact of cancer and treatment on skeletal muscle.
Access to this thesis is embargoed until 30th November 2023.
Schofield, C. (2022). Muscle morphology and function in women with advanced-stage ovarian cancer: Relevance in care and response to exercise medicine. https://ro.ecu.edu.au/theses/2601