Doctor of Philosophy in Rehabilitation Sciences (PhD) 
Exercise Cardio-protection from Chemotherapy for Breast Cancer
Postdoctoral Research Fellow
University of Alberta
The role of exercise and physical therapy in oncology treatment and oncology care.
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There is a growing population of breast cancer survivors world-wide due to an ageing population, improved early detection, treatment advances and longer survival. Breast cancer survivors experience persistent upper-body issues following surgery and adjuvant treatment. Physical rehabilitation is known to improve outcomes in upper-body functioning. Strategies to improve reach and access of physical rehabilitation interventions and early detection of upper-body issues are needed to prevent the development of chronic issues. This dissertation aims to develop and test new delivery approaches to surveillance and physical rehabilitation by employing a variety of research methodologies. The first study was a development and feasibility study of the Breast Cancer Online Rehabilitation (BRECOR) program, consisting of a clinical assessment tool, a pamphlet and website to inform and support 12-week self-managed upper-body rehabilitation. This program was found to be feasible for use in community-based centres with preliminary evidence of efficacy. The second study was cross-sectional and tested the reliability and validity of self-measured arm circumference, as well as attitudes towards self-managed surveillance for breast cancer-related lymphedema. The third study was prospective and tested the feasibility and reliability of self-managed surveillance for upper-body issues as part of a hospital-based program. The fourth study aimed to understand experiences and preferences for surveillance and rehabilitation services using qualitative research methods among breast cancer survivors, rehabilitation professionals and breast surgeons from across British Columbia. Participants reported that current services did not enable early detection and were in need of revamping to increase equity of care. Suggestions included providing multimodal self-management resources. In summary, these studies propose new delivery approaches to enable timely and support evidence-based upper-body rehabilitation. The studies lay the groundwork for future randomized controlled trials to determine the magnitude of the effect that self-managed surveillance and rehabilitation may have on the prevalence of chronic breast cancer-related upper-body issues.
One in nine women in Canada will be diagnosed with breast cancer during their lifetime, yet 88% will live for at least five years after diagnosis. Cardiovascular disease has become the most common cause of death of older breast cancer survivors, and breast cancer survivors are more likely to die of cardiovascular disease than women who have not had breast cancer. One of the contributing factors to the increased cardiovascular morbidity and mortality is anthracycline chemotherapy-related cardiotoxicity, or damage to the myocardium. The need for balance of oncological efficacy with cardiotoxicity of anthracycline chemotherapy has driven the active investigation of cardio-protective strategies. Exercise, an accessible and inexpensive intervention with numerous other health benefits, has demonstrated efficacy for attenuating cardiotoxicity in numerous preclinical (i.e. animal model) studies; a finding yet to be confirmed by clinical research. This dissertation investigated the potential for exercise cardio-protection from anthracycline chemotherapy in women diagnosed with breast cancer in three studies. The primary findings are: 1) during anthracycline treatment, adherence to supervised exercise training following the guidelines for cancer survivors varies widely; 2) the primary reason for withdrawal, missed exercise sessions, and non-adherence to prescribed intensity and/or duration was treatment-related symptoms; 3) despite low and variable adherence, women who enrolled in an exercise training program during anthracycline chemotherapy for breast cancer did not experience a clinically relevant deterioration of echocardiography-derived systolic global longitudinal strain or strain rate, which are both established predictive markers of cardiotoxicity; 4) global longitudinal strain has excellent intra-observer reliability and is consistently measurable in breast cancer patients, making it an excellent option for an outcome measure to assess cardio-protection; 5) performance of a single vigorous intensity aerobic exercise bout performed 24 hours prior to anthracycline treatment attenuates the acute NT-proBNP myocardial injury marker response to the first treatment, and alters hemodynamic regulation and cardiac structure after completion of treatment, but has no effect on longitudinal strain or strain rate or treatment symptoms. Overall this dissertation provides proof-of-principal for exercise cardio-protection, and contributes novel findings regarding exercise prescription and outcome measure assessment for future exercise cardio-protection studies during anthracycline treatment for breast cancer.
There is growing evidence that shift workers are at increased risk of cancer and a number of chronic diseases. As the prevalence of shift work is unlikely to decrease, an understanding of the factors that contribute to, and strategies that can be used to mitigate this risk are needed. Physical activity is known to improve health, and reduce chronic disease risk. However, evidence suggests that women shift workers may be less likely than other women to be sufficiently physically active. This dissertation aims to examine the effect that physical activity may have on improving health and reducing breast cancer risk in shift workers, by employing a variety of research methodologies. The first study is a systematic review of the literature on interventions aimed at improving the health of shift workers. This was conducted to understand what strategies have been most effective, as well as to identify gaps in the literature. The second study used cross- sectional data from the Canadian Health Measures Survey to understand patterns of physical activity and sedentary time in shift workers compared to day workers, as well as objective measures of physical fitness and obesity. The third and fourth studies aimed to understand women shift workers’ perspectives on physical activity, particularly barriers to and preferences for physical activity programming, using quantitative and qualitative research methods respectively. Findings from these four studies led to the development of a distance-based physical activity intervention, consisting of behavioural counselling sessions, and use of an activity tracker to encourage participants to meet Canada’s physical activity guidelines of 150 minutes per week of moderate-vigorous physical activity. This intervention was found to be feasible to implement in women shift workers, with preliminary evidence of efficacy. In summary, these studies highlight the important role that physical activity may play in improving health and reducing breast cancer risk in women shift workers. The intervention developed lays the groundwork for future randomized-controlled trials to determine the magnitude of the effect that regular physical activity may have on shift workers’ risk of breast cancer and other chronic diseases.
As many breast cancer survivors (BCS) in British Columbia report difficulties accessing physiotherapy (PT), which increases their risk of developing chronic shoulder and arm issues, strategies are needed to inform effective PT program design. This thesis project used sequential mixed methods to develop a pilot discrete choice experiment (DCE) to understand the feasibility of using DCE methodology to elicit BCSs’ preferences for PT services. Methods: First, focus groups were held with BCS (n=35) to identify key attributes and levels of PT care: timing of education, method of PT referral, timing of first PT appointment, physiotherapist expertise level, treatment frequency, treatment format, and out-of-pocket cost. Second, think aloud interviews were conducted with BCS (n=5) to explore attribute and level relevance and task comprehension. Third, an experimental design of 32 choice tasks (separated into two blocks) was created from the identified attributes and levels, quantitatively pilot tested with BCS, and fit using an error-component mixed logit model to estimate preference data. Feasibility was assessed based on: (i) response rate; (ii) completion rate; and (iii) respondent diversity. Results: The pilot DCE had a 21% response rate and 17% of respondents completed the entire questionnaire and provided usable data. All respondents identified as female and were mean of 9.1 years post-diagnosis. Most received PT treatment for breast cancer-related issues (69%), completed post-secondary education (77%), and had annual family incomes of at least $80,000 (69%). Preliminary preference data indicate, on average, respondents preferred breast surgeon referral to PT, less time between surgery completion and receipt of first PT appointment, a physiotherapist with greater breast cancer-specific expertise, and to pay less out-of-pocket for PT treatment. Conclusion: Given the low response and completion rates and respondent homogeneity, alternative recruitment strategies and choice task instruction and presentation should be explored before beginning a full-scale DCE. As this DCE was a pilot study, preference data should be interpreted with caution and not inferred to reflect the preferences of the wider population of BCS. Preference data from the full-scale DCE may be incorporated into exploratory policy analyses and programming for breast cancer-specific PT services in British Columbia.
Exercise has been shown to be an effective strategy to enhance survivorship and improve quality of life in individuals with prostate cancer. However, the majority of men with prostate cancer do not meet the exercise guidelines for cancer survivors that recommend achieving a minimum of 150-minutes of moderate-to-vigorous aerobic exercise and two resistance exercise sessions weekly. To assist in the adoption and maintenance of exercise behaviours, the Prostate Cancer Supportive Care (PCSC) program implemented an exercise clinic that included group education and individualized exercise counselling delivered by an exercise physiologist. The primary aim of this dissertation was to evaluate the feasibility of the delivery of the exercise clinic and to understand the preliminary effect of this clinic at changing exercise behaviours over a 3-month period. A retrospective chart review was performed on data collected from attendees of the PCSC Program Exercise Clinic version 2.0 protocol from June 11 2018 to April 10 2019 from four appointment sessions: Education session, exercise clinic session 1 (first in-person exercise clinic session), exercise clinic session 2 (telephone follow-up session) and exercise clinic session 3 (3-month in-person follow-up session). Feasibility was defined a priori and measured by attendance, attrition, session timing, intervention delivery fidelity and intervention component fidelity. Self-reported aerobic and resistance exercise levels were evaluated at each session. The results show that this study exceeded feasibility targets for attendance, attrition, intervention fidelity and in-person session timing. There was intervention component fidelity in 38 of 39 components. Aerobic exercise levels at 3-months had increased by 83198 minutes per week of moderate-to-vigorous aerobic exercise with a moderate effect (ES 0.54, 95% CI 0.3-0.5) and resistance exercise increased by 2.03.1 sessions per week with a large effect (ES 0.77, 95% CI 0.3-1.3). Overall, this intervention was feasible to deliver to individuals with prostate cancer in a real-world clinical setting by exercise physiologists. The exercise counselling intervention elicited a moderate effect, showing improvements in aerobic and resistance exercise levels across 3-months. Future work should explore if this behaviour change can be sustained longer-term.
Computed tomography (CT) imaging presents an accurate and readily available method to quantify changes in body composition within colon cancer patients. Unwanted changes in body composition is one pathway in which cancer outcomes, particularly survival, may be altered in this population. Sarcopenic cancer patients consistently exhibit poorer overall survival compared to non-sacropenic cancer patients. Physical activity is associated with favourable changes in body composition, namely through promoting reductions in visceral adipose tissue and increases in muscle mass. The purpose of this feasibility study is to evaluate the practicality of using CT scans to quantify changes in body composition over time between colon cancer patients who had completed primary cancer treatment randomized to a physical activity intervention (intervention group) or usual care (control group). Eighteen participants who had completed a minimum of 12 months of the CO.21 Trial from the Vancouver CO.21 Trial center were included. Body composition outcomes were measured at baseline, 6 months and 12 months using CT scans taken as part of routine practice. Manual image analysis time took on average longer (17min:20sec) then automated analysis (57sec). Image retention rate was high (97.9%), and only a small proportion of images were deemed as having major quality issues (5.9%). All but one quantified body composition outcome had excellent measured inter- and intra-rater reliability (ICC >0.9). There were no significant time and group effect (p
Background: Cancer survivors report unique health complications associated with their treatment. Common symptoms include pain, compromised physical functioning, and lymphedema. Although these complications are highly responsive to physical therapy, many cancer survivors do not receive adequate physical therapy care. Furthermore, the delivery of physical therapy services for cancer survivors in British Columbia (BC) has not yet been investigated, warranting an inquiry specific to BC.Purpose: To develop an accurate description of the physical therapy services and programs currently accessible to oncology patients within BC’s public health care system.Methods: A standardized survey was used to investigate the provision of physical therapy to cancer survivors across BC. Public health care sites offering physical therapy services were identified through a comprehensive list of BC hospitals and out-patient health centres. Public practice health care professionals responsible for overseeing physical therapy at each site were requested to complete a survey regarding the physical therapy care provided to cancer survivors at their respective location. Results: Of the 98 sites contacted, surveys were collected for 92 for an overall response rate of 94%. Seventy-one (77%) of sites offered physical therapy to oncology patients, and two (2%) reported having an oncology-specific rehabilitation program, both of which were exclusive to breast cancer survivors and located in the lower mainland (Vancouver and Surrey). Thirty-one (44% of) participants agreed that the services currently being offered at their site were meeting the needs of their patients, 15 (21%) did not consider current services to be adequately meeting the needs of their oncology population, and 25 (35%) were unsure. The most common reasons for not meeting patient needs was lack of funding (83%), lack of professionals experienced in oncology rehabilitation (73%), and lack of resources (e.g., equipment) (70%).Conclusion: In BC, only two public health care sites deliver oncology-specific rehabilitation programs. The remaining sites offer services to oncology patients based on need. A minority of sites report meeting patient rehabilitation needs, with primary barriers being lack of funding, resources, and specialized health care professionals.
Taxane-based chemotherapy is frequently administered to treat breast cancer. However, side effects of taxanes include chemotherapy-induced peripheral neuropathy (CIPN) and cardiovascular complications, which negatively impact patient quality of life and long-term health. Exercise can significantly reduce cancer treatment side effects. However, information on exercise’s influence on taxane-specific side effects is limited. The primary aim of this dissertation was to evaluate the effect of exercise on taxane side effects, including CIPN and cardiovascular outcomes, in women with breast cancer. METHODS: Women with early-stage breast cancer were randomized to thrice-weekly exercise (EX) or usual care (UC) during taxane chemotherapy (4 cycles, 2-3 weeks apart). Patient-reported CIPN symptoms and quality of life (EORTC QLQ-C30 + CIPN20 subscale), clinical CIPN tests (vibration sensation and pinprick), patient-reported pain (Brief Pain Inventory) and cardiovascular outcomes, including heart rate and blood pressure at rest, and during and after submaximal exercise testing, were evaluated at baseline (pre-taxane chemotherapy) and end of chemotherapy. CIPN symptoms and quality of life were also evaluated at 0-3 days pre-chemotherapy cycle 4. RESULTS: Twenty-four women enrolled (EX: n=11, UC: n=13). Patient-reported CIPN symptoms were significantly worse by the end of chemotherapy in both groups for sensory (p
Background: Following chemotherapy, it is estimated that up to 95% of all cancer patients report cognitive changes such as complaints with memory and difficulty concentrating. This condition is referred to as chemotherapy-associated cognitive dysfunction or “chemo brain”. In addition, deficits in physical function are observed among those undergoing cancer treatment, as well as, long-term cancer survivors. While a decrease in physical activity participation has been shown among colorectal cancer patients over the course of chemotherapy, to date, changes in functional mobility over the course of chemotherapy has not been assessed in colon cancer patients using objective validated mobility tests. Furthermore, the association of cognitive and functional mobility dysfunction has not been explored. Purpose: To examine the effect of chemotherapy treatment on cognitive function, functional mobility and physical activity from baseline, to 6 months (end of chemotherapy) in individual being treated for colon cancer. Methods: At baseline and end of chemotherapy, participant completed a neuropsychological test battery, which included the Stroop, Hopkins Verbal Learning Test-Revised (HVLT-R), and Trail Making A & B (TMT A&B), a 6-minute walk test (6MWT), a measure of physical function, and a functional mobility testing battery, which included timed up and go (TUG) and gait speed. Demographic information and self-reported physical activity, using the International Physical Activity Questionnaire (IPAQ), were also collected at these time points. For the analysis of neuropsychological and mobility test scores, the paired t-test was used to test for the differences and assess the change in the mean scores from the baseline to 6-months. Results: No significant changes were noted in the HVLT-R, Stroop, and TMT-A and -B mean scores after completion of chemotherapy compared to baseline. Compared to baseline, no significant changes were observed for 6MWT, TUG, GS, or leisure-time physical activity after completion of chemotherapy. Conclusions: There were no significant changes in chemotherapy-associated cognitive, physical function, or functional mobility noted from baseline to the end of chemotherapy. In addition, physical activity levels and average time spent sitting did no change significantly. No definitive statements can be provided since the results are based on a small sample size.
INTRODUCTION: Physical activity (PA) levels in children who have completed treatment for acute lymphoblastic leukemia (ALL) have been shown to be lower than their healthy peers. Obesity and related health concerns have been recognized as long-term side-effect of cancer treatment. Motor performance and physical function have been shown to be lower in these children compared with children who have not had a cancer diagnosis. Whether or not these two physical factors are related to PA levels in these children is unknown. PURPOSE: To determine if motor performance and physical function are associated with PA in children who have completed treatment for ALL. METHODS: PA was measured using the Physical Activity Questionnaire for Older Children (PAQ-C); motor performance was measured using the Bruininks-Oseretsky Test of Motor Proficiency, Second Edition, Short Form (BOT-2 SF); and physical function was measured using the Six-Minute Walk Test (6MWT). RESULTS: Thirteen participants were recruited. PAQ-C scores were not related to standardized scores from the BOT-2 SF (Spearman’s rho, rs = 0.282, p = 0.35) and 6-minute walk distance (6MWD) (rs = -0.429, p = 0.14) and 6MWD Standard Deviation Score (SDS) (rs = -0.094, p = 0.76). Only 1/13 participants performed below average in the BOT-2 SF, and 11/13 participants walked shorter distances compared with published data from healthy children in the 6MWT (mean 6MWD SDS: -1.62). Body mass index SDS were significantly associated with measured 6MWD (rs = 0.602, p = 0.03) and 6MWD SDS (rs = -0.691 p = 0.01). CONCLUSION: PA was not associated with motor performance or physical function. Physical function was poorer compared with healthy children in 11/13 participants. Healthcare professionals can focus on improving physical function and improving weight management to help reduce risk of obesity and associated health consequences in children who have completed treatment for ALL. Future research should include a larger sample size and include psychosocial factors, such as self-efficacy and parental influence, in exploring factors related to PA childhood ALL survivors.
Fatigue is one of the most commonly reported side effects during treatment for breast cancer, andfor some individuals can continue for an extended period following treatment completion.Cancer-related fatigue is multi-factorial in nature, and one hypothesized mechanism of bothdevelopment and persistence of cancer-related fatigue following treatment is cardiorespiratoryand muscular deconditioning. The purpose of this study is to compare lactate threshold, VO₂peak and central vs. peripheral causes of muscular fatigue in breast cancer survivors withpersistent cancer-related fatigue (FG) and the control group (CG), breast cancer survivorswithout persistent cancer-related fatigue following treatment for breast cancer. METHODS:During first testing visit, power output at lactate threshold, lactate threshold as a percentageof peak power output, and absolute and relative VO₂ peak were determined using a gradedincremental maximal exercise test on a cycle ergometer. During the second testing visit centraland peripheral muscle fatigue following a sustained contraction of the right quadriceps wereassessed using the twitch interpolation technique and measurement of voluntary activation,control twitch, maximum voluntary contraction and endurance time. RESULTS: There were nosignificant differences in age, body weight, or time since completion of treatment betweengroups. There were no significant differences between groups in power output at lactatethreshold (FG 60.7±17.0 vs. CG 73.3±22.2 W, p=0.14), lactate threshold as a percentage of peakpower output (FG 46.8±8.6 vs. CG 55.0±14.7%, p=0.11), peak power output (FG132.12±38.2vs. CG 140.6±5.9 W, p=0.66), absolute VO2 peak (FG 1.51±0.39 vs. CG 1.74±0.38 L/min,p=0.19), or relative VO2 peak (FG 22.4±4.9 vs. CG 23.6±7.1 ml/kg/min, p=0.62). Results didapproach significance for power output at lactate threshold (p=0.10) and absolute VO₂ peak(p=0.08) when adjusted for age. Central fatigue was responsible for muscular fatigue in theivcontrol group, while muscular fatigue in the cancer-related fatigue group was more due toperipheral mechanisms. CONCLUSION: While no statistically significant differences werefound between groups, results suggest that deconditioning may play a role in cancer-relatedfatigue. Future research into the use of exercise training as a tool to improve deconditioning andthereby reduce this proposed aspect of cancer-related fatigue is warranted.