Activity behavior and physiological profile of advanced-stage ovarian cancer survivors

Background: Advanced-stage ovarian cancer survivors (OCS) often experience a multitude of disease symptoms and treatment-related side-effects. Additionally, most OCS are older, have comorbidities, are overweight or obese, and report being insufficiently physically active. Ovarian cancer survivors may benefit from exercise oncology interventions to reduce symptom-burden, manage comorbidities, minimize functional decline and maximize health-related quality of life (HRQoL). However, current knowledge gaps regarding the physiological characteristics of OCS throughout the entire survivorship spectrum challenge the development of tailored exercise interventions. Purpose: The overall purpose of this thesis was to provide a more comprehensive physiological and activity behavior profile of post-treatment advanced-stage OCS. Specifically, a cross-sectional research study was conducted to compare objectively measured activity behavior and physical function, body composition and musculoskeletal morphology, self-reported pelvic floor dysfunction (PFD) and HRQoL of OCS with age-matched controls. Associations between activity behavior, physiological characteristics, PFD and HRQoL for OCS were also investigated. Methods: Twenty stage III-IV OCS and 20 age-matched controls underwent objective assessments of activity behavior (physical activity and sedentary time via 7-day accelerometry), physical function (400-meter walk to assess cardiorespiratory fitness, repeated chair rise to assess lower extremity function, 6-meter walking tests to assess gait speed and dynamic balance), muscle strength (1-repetition maximum chest press and single leg extension, and handgrip strength), body composition (dual-energy x-ray absorptiometry) and musculoskeletal morphology (peripheral quantitative computed tomography), and completed questionnaires assessing HRQoL (SF-36) and PFD (Australian Pelvic Floor Questionnaire). Results: Compared to controls, OCS spent more time/day in prolonged sedentary bouts (i.e., uninterrupted sedentary bouts of ≥30 min; p = 0.039), had lower cardiorespiratory fitness (p =0.041) and upper body strength (p = 0.023), had higher areal bone mineral content (p = 0.047) and volumetric trabecular density (p = 0.048), but were not different in other measures of body composition or musculoskeletal morphology (i.e., all p-values \u3e 0.050). Compared to controls, OCS had equivalent self-reported PFD as indicated by combined bladder, bowel and pelvic organ prolapse symptoms (p = 0.277), but worse physical HRQoL indicated by a physical composite score (p = 0.013). Only 20% (n = 4) of OCS accrued ≥150 minutes/week moderate-and-vigorous physical activity (MVPA) in ≥10 min bouts. MVPA time/day in ≥10 min bouts was positively associated with cardiorespiratory fitness (p = 0.001), lower extremity function, (p = 0.019), muscle crosssectional area (p = 0.035), less PFD (p = 0.038) and physical HRQoL (p = 0.003). Decreased physical HRQoL was associated with less MVPA (p = 0.005), more sedentary time (p = 0.047), decreased objective physical function (p-values \u3c 0.050) and greater PFD (p = 0.043). Conclusion: Post-treatment advanced-stage OCS spent more time in prolonged sedentary bouts, had lower cardiorespiratory fitness, upper body strength and physical HRQoL compared to agematched controls. The decreased physical HRQoL of this sample of OCS compared to controls and its associations with modifiable factors such as MVPA, sedentary time, objective physical function and PFD highlights the need for ongoing supportive care and the importance of multidisciplinary interventions, including exercise oncology interventions, beyond the completion of first-line ovarian cancer treatment

Supervised resistance exercise for women with ovarian cancer who have completed first-line treatment: a pragmatic study

Objectives: In ovarian cancer (OC), suboptimal muscle morphology (i.e., low muscle mass and density) is associated with poor clinical outcomes, yet little is known about the effect of interventions aimed at improving these measures. We investigated the effect of resistance exercise after first-line treatment on muscle mass and density, muscle strength and physical function, health-related quality of life (QoL), and pelvic-floor function in advanced-stage OC survivors. Methods: Fifteen OC survivors participated in supervised resistance exercise twice weekly for 12 weeks (in-clinic or by telehealth). Assessments included muscle mass and density (dual-energy X-ray absorptiometry, peripheral quantitative computed tomography), muscle strength (1-repetition maximum [1RM] chest press, 5RM leg press, handgrip strength), physical function (400-m walk, timed up-and-go [TUG]), QoL (QLQ-C30 questionnaire), and self-reported pelvic floor function (Australian Pelvic Floor Questionnaire). Results: The median age was 64 (range 33–72) years, 10 women underwent neoadjuvant chemotherapy and five underwent adjuvant chemotherapy. All participants completed the intervention (median attendance = 92%; range 79–100%). Post-intervention improvements were observed for whole-body lean mass (1.0 ± 1.4 kg, p = 0.015), appendicular lean mass (0.6 ± 0.9 kg, p = 0.013), muscle density (p = 0.011), upper and lower body strength (p ≤ 0.001), 400-m walk (p = 0.001), TUG (p = 0.005), and social and cognitive QoL domains (p = 0.002 and 0.007), with no change to pelvic floor symptoms (p \u3e 0.05). Conclusion: In this study, supervised resistance exercise effectively improved muscle mass and density, muscle strength, and physical functioning without deleterious effects on the pelvic floor. Considering the prognostic value of these outcomes, larger studies are needed to confirm the benefits of resistance exercise in OC supportive care

The effects of home-based exercise therapy for breast cancer-related fatigue induced by radical radiotherapy

Background: Radiotherapy (RT) can lead to cancer-related fatigue (CRF) and decreased health-related quality of life (HRQoL) in breast cancer patients. The purpose of this trial was to examine the feasibility and efficacy of a home-based resistance and aerobic exercise intervention for reducing CRF and improving HRQoL in breast cancer patients during RT. Methods: Women with breast cancer (N = 106) commencing RT were randomized to 12 weeks of home-based resistance and aerobic exercise (EX) or usual care/control (CON). The primary endpoint was CRF, with secondary endpoints of HRQoL, sleep duration and quality, and physical activity. Measurements were undertaken prior to RT, at completion of RT (~ 6 weeks), at completion of the intervention (12 weeks), and 6 and 12 months after RT completion, while CRF was also measured weekly during RT. Results: Eighty-nine women completed the study (EX = 43, CON = 46). Over the 12-week intervention, EX completed 1 – 2 resistance training sessions and accumulated 30–40 min of aerobic exercise weekly. For CRF, EX had a quicker recovery both during and post-RT compared to CON (p \u3c 0.05). Moreover, there was a significant difference in HRQoL between groups at RT completion, with HRQoL unchanged in CON and higher in EX (p \u3c 0.05). There was no change in sleep duration or quality for either group and there were no exercise-related adverse effects. Conclusions: Home-based resistance and aerobic exercise during RT is safe, feasible, and effective in accelerating CRF recovery and improving HRQoL. Improvements in CRF and HRQoL for these patients can be achieved with smaller exercise dosages than stated in the generic recommendations for breast cancer

Association between energy balance-related factors and clinical outcomes in patients with ovarian cancer: A systematic review and meta-analysis

Background: This systematic review and meta-analysis synthesized evidence in patients with ovarian cancer at diagnosis and/or during first-line treatment on; (i) the association of body weight, body composition, diet, exercise, sedentary behavior, or physical fitness with clinical outcomes; and (ii) the effect of exercise and/or dietary interventions. Methods: Risk of bias assessments and best-evidence syntheses were completed. Meta-analyses were performed when ≥ 3 papers presented point estimates and variability measures of associations or effects. Results: Body mass index (BMI) at diagnosis was not significantly associated with survival. Although the following trends were not supported by the best-evidence syntheses, the meta-analyses revealed that a higher BMI was associated with a higher risk of post-surgical complications (n = 5, HR: 1.63, 95 % CI: 1.06 – 2.51, p = 0.030), a higher muscle mass was associated with a better progression-free survival (n = 3, HR: 1.41, 95 % CI: 1.04 – 1.91, p = 0.030) and a higher muscle density was associated with a better overall survival (n = 3, HR: 2.12, 95 % CI: 1.62 – 2.79, p \u3c 0.001). Muscle measures were not significantly associated with surgical or chemotherapy-related outcomes. Conclusions: The prognostic value of baseline BMI for clinical outcomes is limited, but muscle mass and density may have more prognostic potential. High-quality studies with comprehensive reporting of results are required to improve our understanding of the prognostic value of body composition measures for clinical outcomes. Systematic review registration number: PROSPERO identifier CRD42020163058

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Muscle morphology and function in women with advanced-stage ovarian cancer: Relevance in care and response to exercise medicine

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

A physiological profile of ovarian cancer survivors to inform tailored exercise interventions and the development of exercise oncology guidelines

Physical activity has become increasingly important in supportive cancer care. However, physical activity and exercise guidelines for ovarian cancer survivors remain generic. The aim of this narrative review is to summarize existing data regarding the physiological characteristics (treatment-related adverse effects, concurrent comorbidities, body weight and composition, physical fitness and function, and physical activity behavior) of ovarian cancer survivors to further understanding of their cancer-specific physical activity and exercise needs. We also highlight gaps in the current knowledge base.We undertook a narrative review of current literature on the physiological status of ovarian cancer survivors. We defined physiological status as treatment-related adverse effects, concurrent comorbidities, body weight and composition, physical fitness and function, and physical activity behavior.In addition to disease- and treatment-related symptoms and adverse effects, the majority of ovarian cancer survivors have comorbidities, which may adversely affect treatment effectiveness and safety, as well as survival. Despite high overweight and obesity rates, a large percentage of women are malnourished at diagnosis, with potentially compromised muscle mass and muscle density. Low muscle density at diagnosis and loss of muscle mass during treatment may be associated with worse survival outcomes. A small number of studies have observed impaired physical function and cardiorespiratory fitness in ovarian cancer survivors. The majority of ovarian cancer survivors are insufficiently active or sedentary.Our review suggests that ovarian cancer survivors could benefit from physical activity and exercise oncology interventions aimed at addressing detrimental changes to physiological status due to disease and treatment. However, current knowledge gaps regarding the physiological characteristics of ovarian cancer survivors throughout the entire survivorship spectrum challenge the development of tailored exercise intervention studies and exercise oncology guidelines