People diagnosed with cancer or undergoing cancer treatment experience a wide range of symptoms. One of the most common symptoms experienced by cancer patients today is cancer-related fatigue. Cancer-related fatigue is a complex condition, recognised as a multidimensional construct and thought to be associated with a cluster of symptoms rather than occurring in isolation. Cancer-related fatigue is distressing and can persist beyond the treatment phase or the disease itself. Current understanding of cancer-related fatigue and its management is limited. Further developing our knowledge of cancer-related fatigue may lead to innovative means of improving the identification, prediction and management of this troublesome symptom. To this end, this thesis aims to: I) identify factors reported to have a relationship with cancer-related fatigue; II) examine the course of cancer-related fatigue during and after radiotherapy; III) determine a method of detecting clinically meaningful change in fatigue; IV) examine whether correlates of fatigue are consistent across all fatigue dimensions or whether each dimension has its own unique pattern of correlates; and, V) develop and trial a group-based educational intervention to target cancer-related fatigue. To address Aim I in this thesis, relevant literature was reviewed to identify factors which potentially influence cancer-related fatigue. Factors identified include underlying medical factors (biomedical mechanisms, disease-related factors, treatment-related factors and comorbid conditions); physical or behavioural factors (poor nutrition, decreased activity, sleep disturbance, pain); psychological factors (anxiety and depression); and sociodemographic factors (social support, employment and education). The range of inter-related factors identified makes cancer-related fatigue a challenging condition to manage. The factors associated with cancer-related fatigue were synthesized into the Fatigue Framework to provide a clinically useful format for health professionals working with people with cancer. The Fatigue Framework was used to guide the remainder of the research into cancer-related fatigue presented in this thesis. This research consists of two main studies; a prospective longitudinal cohort study (to address Aims II, III, IV) and a randomised controlled trial (to address Aim V). The first study in this research examined the factors and effects associated with cancer-related fatigue in a radiotherapy population (n=210). Patients undergoing radiotherapy were recruited for a single-centre prospective longitudinal cohort study. Participants were assessed using a battery of assessments at three time points, at the start of radiotherapy, the end of radiotherapy and six weeks after radiotherapy completion. The results of this study were used to address Aim II, to identify the pattern of fatigue over the course of radiotherapy. The level of fatigue reported was shown to significantly increase from start to the end of radiotherapy and then significantly decrease from the end of radiotherapy to six weeks post-treatment for each subscale of the MFI. The results of this study were also used to address Aim III, to determine a method of detecting clinically meaningful change in fatigue. Whilst there are many tools used to assess cancer-related fatigue, the Multidimensional Fatigue Inventory (MFI) was the assessment chosen for use in this research study and throughout this thesis. The MFI is one of the few fatigue assessments that takes the various clinical dimensions of fatigue into account and has established reliability and validity. However, unlike other fatigue assessments, there were no published minimal clinically important difference (MCID) criteria for its use in cancer populations. MCID criteria determine the smallest change in scores that can be regarded as important, allowing clinicians and researchers to interpret the meaning of changes in patients’ fatigue scores. Determination of the MCID was based on the relationship of MFI scores to four clinically relevant constructs: (1) treatment impact on fatigue, (2) health-related quality of life, (3) performance status and (4) occupational productivity. These constructs were used as external or anchor-based measures to determine a MCID for each sub-scale of the MFI. Multiple MCID criteria were identified through the first study, each from a different perspective based on the anchor-based construct used. However, a two-point reference for each MFI sub-scale was suggested as a generic MCID as it was most consistent across the anchors examined. The MCID criteria validated in this study allow better interpretation of changes in MFI sub-scale scores and allow effect size calculations for determining sample size in future studies. The MFI allows assessment of multiple dimensions of fatigue (general fatigue, physical fatigue, reduced activity, reduced motivation and mental fatigue). Minimal previous research had considered the differential effect of symptom correlates on individual dimensions of fatigue. The data of the prospective cohort study were further utilised to address Aim IV, to determine whether correlates of fatigue were consistent across all dimensions or whether each fatigue dimension had its own unique pattern of correlates. Results indicated that each dimension of fatigue was associated with a different pattern of correlates supporting the concept of multiple dimensions of fatigue. This enhanced understanding of fatigue could be used to guide the development of individually tailored interventions to target specific correlates of fatigue in affected domains, or group interventions to address all relevant fatigue correlates. Because fatigue is associated with multiple symptom correlates, it requires multi-focused symptom management. Education is a commonly recommended fatigue management strategy which can be used to target multiple symptoms simultaneously. There is a lack of information about the content and format used in education programs and the effectiveness of education in managing fatigue. The second study in this thesis addressed Aim V, to develop and trial a group-based educational intervention to target cancer-related fatigue. The study examined a group-based educational intervention (CAN-FIT) targeting cancer-related fatigue in radiotherapy patients. A pilot study of the intervention’s feasibility and acceptability indicated the intervention was acceptable to participants and its operation was feasible. Small modifications to program components were made based on participant feedback. A randomised controlled trial was then conducted to examine effectiveness of the CAN-FIT program and to ascertain the most effective timing for such an educational intervention. The study employed a factorial design and recruited 110 participants. Assessments were conducted at three time points, the start of radiotherapy, the end of radiotherapy and six weeks after the completion of radiotherapy. Results of the randomised controlled trial of CAN-FIT did not show a significant effect of the program on cancer-related fatigue levels, however the pre-radiotherapy education sessions were associated with significant increases in physical activity participation. Furthermore, the study demonstrated the delivery of education prior to radiotherapy was more effective than delivery after radiotherapy. This thesis successfully addresses its stated aims and provides a greater understanding of the concept of cancer-related fatigue. The results more clearly describe the course and correlates of fatigue and their relationship with the dimensions of fatigue. The MCID criteria for the MFI can be used in future research to evaluate outcomes and determine sample size in power calculations. The intervention trialled can be used in clinical practice to provide a low-resource intervention to improve activity levels without any subsequent change in fatigue in radiotherapy patients. Together these studies build upon current knowledge and provide directions for future research to address this difficult symptom.

Background: Stroke is the leading cause of disability in the United States. Physical therapists treating patients post acute stroke use measurement tools specifically designed to measure gait and balance ability. People with sub-acute stroke typically have rapid and large changes in gait and balance ability while undergoing inpatient physical therapy. There is a lack of information about how much change in gait speed is needed in hospitalized people with sub-acute stroke to be considered an important amount. There is no information regarding the validity, and reliability of the Tinetti Performance Oriented Mobility Assessment (POMA) to measure balance ability in people with stroke or how much change is needed to be important to people in the sub acute phases of stroke. Objective: The purpose of this study was to 1) estimate minimal clinically important difference (MCID) for comfortable gait speed in persons who have experienced stroke and are undergoing inpatient physical therapy using 3 different anchors of change; 2) estimate minimal clinically important difference (MCID) for Tinetti POMA in persons who have experienced stroke and are undergoing inpatient physical therapy using 3 different anchors of change; 3) determine the test retest reliability and minimal detectable change (MDC) for the Tinetti POMA; and 4) explore the construct validity of the Tinetti POMA for use in people with stroke undergoing inpatient physical therapy. Study Design: This study was a prospective, longitudinal study, which followed a cohort of patients who were undergoing inpatient physical therapy post acute stroke. Methods: Participants were recruited if they had a first documented stroke and were receiving physical therapy during inpatient rehabilitation. Participants were excluded from the study if they had a history of a previous stroke, were medically unstable, were non-English speaking or were unable to walk without assistance prior to the current stroke event. Comfortable gait speed measured by a 5-meter walk test, Tinetti POMA scores and motor Functional Independence Measure (FIMTM) scores were collected at admission to and discharge from inpatient rehabilitation. To determine test re-test reliability, two trials of comfortable gait speed were administered during the same treatment session and two trials of Tinetti POMA were performed one day apart. Global Rating of Change (GROC) scores were collected at discharge from inpatient rehabilitation. A score of 6 (¡°a great deal better, an important amount¡±) on a Global Rating of Change scale and achievement of ¡Ý17 point change on the motor FIM was used to dichotomize participants into those who had important change in walking and balance ability and those who did not. Receiver operator characteristic (ROC) curves were constructed to estimate important change values for gait speed using the three anchors. Effect Size (ES) index was used to determine the responsiveness of gait speed and the Tinetti POMA, Intraclass Correlation Coefficient (ICC2,1) was used to determine test re-test reliability and MDC values for gait speed and Tinetti POMA and Spearman¡¯s Rho (rs) was used to explore the construct validity of the Tinetti POMA. Results: The participants in this study were 43 people with average age of 76¡À11 years who had experienced first documented stroke, began inpatient physical therapy at a mean of 8¡À5 days post stroke and were discharged from the hospital at an average of 38¡À11 days post stroke. The mean length of stay for all participants was 23¡À11 days. MCID of comfortable gait speed was estimated to be 0.24 m/s (AUC= 0.644 , sn/sp=66%/64%, LR+=1.83, LR-0.54) anchored to motor FIM change scores. Test re-test reliability of gait speed was ICC2,1=0.931 at admission and ICC2,1=0.987 at discharge. MDC of comfortable gait speed was 0.12 m/s at admission and 0.08 m/s at discharge. MCID of the Tinetti POMA was 7 points (AUC=0.743, sn/sp=79%/64%, LR+=2.18, LR-=0.32) anchored to motor FIM change. Test re-test reliability of the Tinetti POMA was ICC2,1 0.859 and MDC was 5 points. Tinetti POMA scores were moderately correlated to motor FIM and gait speed scores at admission (rs=0.74 and 0.67) and discharge (rs=0.60 and 0.76) to gait speed and motor FIM scores. Conclusions: People with stroke who experience a 7 point change on the Tinetti POMA during inpatient rehabilitation are likely to experience an important change in functional mobility. The Tinetti POMA demonstrates validity and reliability to measure balance ability people with stroke. More research is needed to estimate meaningful change people with sub-acute stroke using larger cohorts with similar characteristics.