Pre-post feasibility trial of a telephone-delivered exercise intervention for patients during chemotherapy for recurrent ovarian cancer: the ECHO-R trial protocol.

INTRODUCTION: The benefits of exercise in reducing treatment-related morbidity and improving quality of life following a primary diagnosis of cancer have been well documented and have led to exercise being recommended by oncology societies for all people with a cancer diagnosis. However, these recommendations are derived from research typically involving cohorts with more common cancers and relatively good prognosis, such as breast and prostate. Evidence from these cancers may not apply to women with recurrent ovarian cancer. Therefore, the primary objective of this trial is to evaluate the feasibility and safety of a home-based, telephone-delivered exercise intervention for women undergoing chemotherapy for recurrent ovarian cancer. METHODS AND ANALYSIS: The Exercise During Chemotherapy for Recurrent Ovarian Cancer (ECHO-R) trial is a single-arm, phase II, pre/postintervention trial of a 6-month, telephone-delivered exercise intervention (consistent with recommended exercise oncology prescription). The target sample size is 80 women who are currently undergoing (or are scheduled to receive) chemotherapy for recurrent ovarian cancer. Recruitment is through participating hospital sites in Queensland, Australia, or via self-referral. The exercise intervention comprises 12 telephone sessions over a 6-month period delivered by trial-trained exercise professionals and supplemented (where feasible) by five sessions face to face. Exercise prescription is individualised and works towards an overall goal of achieving a weekly target of 150 min of moderate-intensity, mixed-mode exercise. Assessments via self-administered survey and physical fitness and function tests occur at baseline and then at 6 and 9 months postbaseline. Data to inform feasibility and safety are recorded as case notes by the exercise professional during each session. ETHICS AND DISSEMINATION: Ethics approval for the ECHO-R trial was granted by the Metro North Human Research Ethics Committee (HREC/2020/QRBW/67223) on 6 November 2020. Findings from the trial are planned to be disseminated via peer-reviewed publications and both national and international exercise and oncology conferences. TRIAL REGISTRATION NUMBER: ACTRN12621000042842.

Is Vitamin D Level at Melanoma Diagnosis Associated With Stage Of Tumor? An Observational Study of Melanoma Patients Living in a High Ultraviolet Radiation Environment.

OBJECTIVES: This study will assess the relationship between vitamin D concentration at melanoma diagnosis and melanoma tumor characteristics, in individuals in a high ultraviolet radiation (UVR) environment. METHODS: We aim to recruit 600 recently diagnosed melanoma patients from Queensland, Australia, a high UVR location with one of the world's highest melanoma incidence rates. Patients are recruited through general practitioner, skin cancer specialist, dermatological and hospital-based practices. As close as possible to diagnosis, participants provide a blood sample for vitamin D analysis and have their sun exposure/sun protection behavior, melanoma risk factors and dietary vitamin D intake assessed by questionnaire and phone interview. Details of tumor pathology, including tumor level, thickness, and ulceration, are abstracted from cancer registry records. Here, we describe the study methods and present preliminary findings from early participants. RESULTS: As of December 2017, we have recruited 128 participants (48% male, mean age 60.2 years, mean Breslow thickness 0.63 mm). CONCLUSIONS: When complete, this study will give insights into the association between vitamin D at diagnosis and melanoma tumor characteristics whilst adjusting for recent sun exposure and sun protection use. This study may impact military sun exposure and nutrition policies as vitamin D may play a role in melanomagenesis.

Weight and weight change following breast cancer: evidence from a prospective, population-based, breast cancer cohort study.

BACKGROUND: While weight gain following breast cancer is considered common, results supporting these findings are dated. This work describes changes in body weight following breast cancer over 72 months, compares weight with normative data and explores whether weight changes over time are associated with personal, diagnostic, treatment or behavioral characteristics. METHODS: A population-based sample of 287 Australian women diagnosed with early-stage invasive breast cancer was assessed prospectively at six, 12, 18 and 72 months post-surgery. Weight was clinically measured and linear mixed models were used to explore associations between weight and participant characteristics (collected via self-administered questionnaire). Those with BMI changes of one or more units were considered to have experienced clinically significant changes in weight. RESULTS: More than half (57%) of participants were overweight or obese at 6 months post-surgery, and by 72 months post-surgery 68% of women were overweight or obese. Among those who gained more weight than age-matched norms, clinically significant weight gain between 6 and 18 months and 6 and 72 months post-surgery was observed in 24% and 39% of participants, respectively (median [range] weight gain: 3.9 kg [2.0-11.3 kg] and 5.2 kg [0.6-28.7], respectively). Clinically-significant weight losses were observed in up to 24% of the sample (median [range] weight loss between 6 and 72 months post-surgery: -6.4 kg [-1.9--24.6 kg]). More extensive lymph node removal, being treated on the non-dominant side, receiving radiation therapy and lower physical activity levels at 6 months was associated with higher body weights post-breast cancer (group differences >3 kg; all p < 0.05). CONCLUSIONS: While average weight gain among breast cancer survivors in the long-term is small, subgroups of women experience greater gains linked with adverse health and above that experienced by age-matched counterparts. Weight change post-breast cancer is a contemporary public health issue and the integration of healthy weight education and support into standard breast cancer care has potential to significantly improve the length and quality of cancer survivorship.

Changes in outdoor workers' sun-related attitudes, beliefs, and behaviors: a pre-post workplace intervention.

OBJECTIVE: To evaluate changes in outdoor workers' sun-related attitudes, beliefs, and behaviors in response to a health promotion intervention using a participatory action research process. METHODS: Fourteen workplaces across four outdoor industry types worked collaboratively with the project team to develop tailored sun protection action plans. Workers were assessed before and after the 18-month intervention. RESULTS: Outdoor workers reported increases in workplace support for sun protection (P < 0.01) and personal use of sun protection (P < 0.01). More workers reported seeking natural shade (+20%) and wearing more personal protective equipment, including broad-brimmed hats (+25%), long-sleeved collared shirts (+19%), and long trousers (+16%). The proportion of workers reporting sunburn over the past 12 months was lower at postintervention (-14%) (P = 0.03); however, the intensity of reported sunburn increased. CONCLUSIONS: This intervention was successful in increasing workers' sun protective attitudes, beliefs, and behaviors.

Incidence of unilateral arm lymphoedema after breast cancer: a systematic review and meta-analysis.

BACKGROUND: The body of evidence related to breast-cancer-related lymphoedema incidence and risk factors has substantially grown and improved in quality over the past decade. We assessed the incidence of unilateral arm lymphoedema after breast cancer and explored the evidence available for lymphoedema risk factors. METHODS: We searched Academic Search Elite, Cumulative Index to Nursing and Allied Health, Cochrane Central Register of Controlled Trials (clinical trials), and Medline for research articles that assessed the incidence or prevalence of, or risk factors for, arm lymphoedema after breast cancer, published between Jan 1, 2000, and June 30, 2012. We extracted incidence data and calculated corresponding exact binomial 95% CIs. We used random effects models to calculate a pooled overall estimate of lymphoedema incidence, with subgroup analyses to assess the effect of different study designs, countries of study origin, diagnostic methods, time since diagnosis, and extent of axillary surgery. We assessed risk factors and collated them into four levels of evidence, depending on consistency of findings and quality and quantity of studies contributing to findings. FINDINGS: 72 studies met the inclusion criteria for the assessment of lymphoedema incidence, giving a pooled estimate of 16.6% (95% CI 13.6-20.2). Our estimate was 21.4% (14.9-29.8) when restricted to data from prospective cohort studies (30 studies). The incidence of arm lymphoedema seemed to increase up to 2 years after diagnosis or surgery of breast cancer (24 studies with time since diagnosis or surgery of 12 to <24 months; 18.9%, 14.2-24.7), was highest when assessed by more than one diagnostic method (nine studies; 28.2%, 11.8-53.5), and was about four times higher in women who had an axillary-lymph-node dissection (18 studies; 19.9%, 13.5-28.2) than it was in those who had sentinel-node biopsy (18 studies; 5.6%, 6.1-7.9). 29 studies met the inclusion criteria for the assessment of risk factors. Risk factors that had a strong level of evidence were extensive surgery (ie, axillary-lymph-node dissection, greater number of lymph nodes dissected, mastectomy) and being overweight or obese. INTERPRETATION: Our findings suggest that more than one in five women who survive breast cancer will develop arm lymphoedema. A clear need exists for improved understanding of contributing risk factors, as well as of prevention and management strategies to reduce the individual and public health burden of this disabling and distressing disorder. FUNDING: The National Breast Cancer Foundation, Australia.

Exercise for health: a randomized, controlled trial evaluating the impact of a pragmatic, translational exercise intervention on the quality of life, function and treatment-related side effects following breast cancer.

Exercise for Health was a randomized, controlled trial designed to evaluate two modes of delivering (face-to-face [FtF] and over-the-telephone [Tel]) an 8-month translational exercise intervention, commencing 6-weeks post-breast cancer surgery (PS). Outcomes included quality of life (QoL), function (fitness and upper body) and treatment-related side effects (fatigue, lymphoedema, body mass index, menopausal symptoms, anxiety, depression and pain). Generalised estimating equation modelling determined time (baseline [5 weeks PS], mid-intervention [6 months PS], post-intervention [12 months PS]), group (FtF, Tel, Usual Care [UC]) and time-by-group effects. 194 women representative of the breast cancer population were randomised to the FtF (n = 67), Tel (n = 67) and UC (n = 60) groups. There were significant (p < 0.05) interaction effects on QoL, fitness and fatigue with differences being observed between the treatment groups and the UC group. Trends observed for the treatment groups were similar. The treatment groups reported improved QoL, fitness and fatigue over time and changes observed between baseline and post-intervention were clinically relevant. In contrast, the UC group experienced no change, or worsening QoL, fitness and fatigue, mid-intervention. Although improvements in the UC group occurred by 12-months post-surgery, the change did not meet the clinically relevant threshold. There were no differences in other treatment-related side effects between groups. This translational intervention trial, delivered either FtF or Tel, supports exercise as a form of adjuvant breast cancer therapy that can prevent declines in fitness and function during treatment and optimise recovery post-treatment.

Prevalence of breast cancer treatment sequelae over 6 years of follow-up: the Pulling Through Study.

BACKGROUND: There is a need to better describe and understand the prevalence of breast cancer treatment-related adverse effects amenable to physical therapy and rehabilitative exercise. Prior studies have been limited to single issues and lacked long-term follow-up. The Pulling Through Study provides data on prevalence of adverse effects in breast cancer survivors followed over 6 years. METHODS: A population-based sample of Australian women (n = 287) diagnosed with invasive, unilateral breast cancer was followed for a median of 6.6 years and prospectively assessed for treatment-related complications at 6, 12, and 18 months and 6 years after diagnosis. Assessments included postsurgical complications, skin or tissue reaction to radiation therapy, upper-body symptoms, lymphedema, 10% weight gain, fatigue, and upper-quadrant function. The proportion of women with positive indication for each complication and 1 or more complication was estimated using all available data at each time point. Women were only considered to have a specific complication if they reported the highest 2 levels of the Likert scale for self-reported issues. RESULTS: At 6 years after diagnosis, more than 60% of women experienced 1 or more side effects amenable to rehabilitative intervention. The proportion of women experiencing 3 or more side effects decreased throughout follow-up, whereas the proportion experiencing no side effects remained stable around 40% from 12 months to 6 years. Weight gain was the only complication to increase in prevalence over time. CONCLUSIONS: These data support the development of a multidisciplinary prospective surveillance approach for the purposes of managing and treating adverse effects in breast cancer survivors.

Prevalence and prognostic significance of secondary lymphedema following breast cancer.

BACKGROUND: The adverse consequences of lymphedema following breast cancer in relation to physical function and quality of life are clear; however, its potential relationship with survival has not been investigated. Our purpose was to determine the prevalence of lymphedema and associated upper-body symptoms at 6 years following breast cancer and to examine the prognostic significance of lymphedema with respect to overall 6-year survival (OS). METHODS AND RESULTS: A population-based sample of Australian women (n = 287) diagnosed with invasive, unilateral breast cancer was followed for a median of 6.6 years and prospectively assessed for lymphedema (using bioimpedance spectroscopy [BIS], sum of arm circumferences [SOAC], and self-reported arm swelling), a range of upper-body symptoms, and vital status. OS was measured from date of diagnosis to date of death or last follow-up. Kaplan-Meier methods were used to calculate OS and Cox proportional hazards models quantified the risk associated with lymphedema. Approximately 45% of women had reported at least one moderate to extreme symptom at 6.6 years postdiagnosis, while 34% had shown clinical evidence of lymphedema, and 48% reported arm swelling at least once since baseline assessment. A total of 27 (9.4%) women died during the follow-up period, and lymphedema, diagnosed by BIS or SOAC between 6-18 months postdiagnosis, predicted mortality (BIS: HR = 2.5; 95% CI: 0.9, 6.8, p = 0.08; SOAC: 3.0; 95% CI: 1.1, 8.7, p = 0.04). There was no association (HR = 1.2; 95% CI: 0.5, 2.6, p = 0.68) between self-reported arm swelling and OS. CONCLUSIONS: These findings suggest that lymphedema may influence survival following breast cancer treatment and warrant further investigation in other cancer cohorts and explication of a potential underlying biology.

Design and implementation of the Exercise for Health trial -- a pragmatic exercise intervention for women with breast cancer.

BACKGROUND: Exercise for Health was a pragmatic, randomised, controlled trial comparing the effect of an eight-month exercise intervention on function, treatment-related side effects and quality of life following breast cancer, compared with usual care. The intervention commenced six weeks post-surgery, and two modes of delivering the same intervention was compared with usual care. The purpose of this paper is to describe the study design, along with outcomes related to recruitment, retention and representativeness, and intervention participation. METHODS: Women newly diagnosed with breast cancer and residing in a major metropolitan city of Queensland, Australia, were eligible to participate. Consenting women were randomised to a face-to-face-delivered exercise group (FtF, n = 67), telephone-delivered exercise group (Tel, n = 67) or usual care group (UC, n = 60) and were assessed pre-intervention (5-weeks post-surgery), mid-intervention (6 months post-surgery) and 10 weeks post-intervention (12 months post-surgery). Each intervention arm entailed 16 sessions with an Exercise Physiologist. RESULTS: Of 318 potentially eligible women, 63% (n = 200) agreed to participate, with a 12-month retention rate of 93%. Participants were similar to the Queensland breast cancer population with respect to disease characteristics, and the randomisation procedure was mostly successful at attaining group balance, with the few minor imbalances observed unlikely to influence intervention effects given balance in other related characteristics. Median participation was 14 (min and max: 0 and 16) and 13 (min and max: 3 and 16) intervention sessions for the FtF and Tel, respectively, with 68% of those in Tel and 82% in FtF participating in at least 75% of sessions. DISCUSSION: Participation in both intervention arms during and following treatment for breast cancer was feasible and acceptable to women. Future work, designed to inform translation into practice, will evaluate the quality of life, clinical, psychosocial and behavioural outcomes associated with each mode of delivery.

Upper-body morbidity following breast cancer treatment is common, may persist longer-term and adversely influences quality of life.

BACKGROUND: Impairments in upper-body function (UBF) are common following breast cancer. However, the relationship between arm morbidity and quality of life (QoL) remains unclear. This investigation uses longitudinal data to describe UBF in a population-based sample of women with breast cancer and examines its relationship with QoL. METHODS: Australian women (n=287) with unilateral breast cancer were assessed at three-monthly intervals, from six- to 18-months post-surgery (PS). Strength, endurance and flexibility were used to assess objective UBF, while the Disability of the Arm, Shoulder and Hand questionnaire and the Functional Assessment of Cancer Therapy-Breast questionnaire were used to assess self-reported UBF and QoL, respectively. RESULTS: Although mean UBF improved over time, up to 41% of women revealed declines in UBF between six- and 18-months PS. Older age, lower socioeconomic position, treatment on the dominant side, mastectomy, more extensive lymph node removal and having lymphoedema each increased odds of declines in UBF by at least two-fold (p<0.05). Lower baseline and declines in perceived UBF between six- and 18-months PS were each associated with poorer QoL at 18-months PS (p<0.05). CONCLUSIONS: Significant upper-body morbidity is experienced by many following breast cancer treatment, persisting longer term, and adversely influencing the QoL of breast cancer survivors.