Exercise during chemotherapy for ovarian cancer (ECHO) trial : design and implementation of a randomised controlled trial

Introduction Epidemiological evidence supports an association between higher levels of physical activity and improved cancer survival. Trial evidence is now needed to demonstrate the effect of exercise in a clinical setting. The Exercise during CHemotherapy for Ovarian cancer (ECHO) trial is a phase III, randomised controlled trial, designed to determine the effect of exercise on progression-free survival and physical well-being for patients receiving first-line chemotherapy for ovarian cancer. Methods and analysis Participants (target sample size n=500) include women with newly diagnosed primary ovarian cancer, scheduled to receive first-line chemotherapy. Consenting participants are randomly allocated (1:1) to either the exercise intervention (plus usual care) or usual care alone, with stratification for recruitment site, age, stage of disease and chemotherapy delivery (neoadjuvant vs adjuvant). The exercise intervention involves individualised exercise prescription with a weekly target of 150 minutes of moderate-intensity, mixed-mode exercise (equivalent to 450 metabolic equivalent minutes per week), delivered for the duration of first-line chemotherapy through weekly telephone sessions with a trial-trained exercise professional. The primary outcomes are progression-free survival and physical well-being. Secondary outcomes include overall survival, physical function, body composition, quality of life, fatigue, sleep, lymphoedema, anxiety, depression, chemotherapy completion rate, chemotherapy-related adverse events, physical activity levels and healthcare usage. Ethics and dissemination Ethics approval for the ECHO trial (2019/ETH08923) was granted by the Sydney Local Health District Ethics Review Committee (Royal Prince Alfred Zone) on 21 November 2014. Subsequent approvals were granted for an additional 11 sites across Queensland, New South Wales, Victoria and the Australian Capital Territory. Findings from the ECHO trial are planned to be disseminated via peer-reviewed publications and international exercise and oncology conferences

Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers

Purpose To determine whether adjuvant tamoxifen treatment for breast cancer (BC) is associated with reduced contralateral breast cancer (CBC) risk for BRCA1 and/or BRCA2 mutation carriers. Methods Analysis of pooled observational cohort data, self-reported at enrollment and at follow-up from the International BRCA1, and BRCA2 Carrier Cohort Study, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, and Breast Cancer Family Registry. Eligible women were BRCA1 and BRCA2 mutation carriers diagnosed with unilateral BC since 1970 and no other invasive cancer or tamoxifen use before first BC. Hazard ratios (HRs) for CBC associated with tamoxifen use were estimated using Cox regression, adjusting for year and age of diagnosis, country, and bilateral oophorectomy and censoring at contralateral mastectomy, death, or loss to follow-up. Results Of 1,583 BRCA1 and 881 BRCA2 mutation carriers, 383 (24%) and 454 (52%), respectively, took tamoxifen after first BC d

The psycho-analytical approach to juvenile delinquency : theory; case-studies; treatment /

Includes bibliographies and index

An exercise intervention during chemotherapy for women with recurrent ovarian cancer: A feasibility study

Objective: The aim of this study was to determine the feasibility of a combined supervised and home-based exercise intervention during chemotherapy for women with recurrent ovarian cancer. Secondary aims were to determine the impact of physical activity on physical and psychological outcomes and on chemotherapy completion rates.\ud \ud Methods: Women with recurrent ovarian cancer were recruited from 3 oncology outpatient clinics in Sydney and Canberra, Australia. All participants received an individualized exercise program that consisted of 90 minutes or more of low to moderate aerobic, resistance, core stability, and balance exercise per week, for 12 weeks. Feasibility was determined by recruitment rate, retention rate, intervention adherence, and adverse events. Aerobic capacity, muscular strength, fatigue, sleep quality, quality of life, depression, and chemotherapy completion rates were assessed at weeks 0, 12, and 24.\ud \ud Results: Thirty participants were recruited (recruitment rate, 63%), with a retention rate of 70%. Participants averaged 196 ± 138 min · wk of low to moderate physical activity throughout the intervention, with adherence to the program at 81%. There were no adverse events resulting from the exercise intervention. Participants who completed the study displayed significant improvements in quality of life (P = 0.017), fatigue (P = 0.004), mental health (P = 0.007), muscular strength (P = 0.001), and balance (P = 0.003) after the intervention. Participants completing the intervention had a higher relative dose intensity than noncompleters (P = 0.03).\ud \ud Conclusions: A program consisting of low to moderate exercise of 90 min · wk was achieved by two-thirds of women with recurrent ovarian cancer in this study, with no adverse events reported. Randomized control studies are required to confirm the benefits of exercise reported in this study

When will I feel normal again? Trajectories and predictors of persistent symptoms and poor wellbeing after primary chemotherapy for ovarian cancer

Objectives: After treatment for ovarian cancer, women want to know when they will feel ‘normal’ again. Our objective was to document the proportions of women with high levels of physical and emotional symptoms at the end of treatment, determine if/when they return to normal and identify groups at risk of persistent symptoms/delayed recovery. Methods: Women in the OPAL (Ovarian cancer Prognosis And Lifestyle) study who received ≥3 cycles of first-line chemotherapy and completed patient-reported outcome (PRO) questionnaires on or < 6 weeks after completing chemotherapy (baseline) were included in this analysis (n = 527). PRO measures included anxiety, depression, insomnia, fatigue and wellbeing (quality-of-life) at baseline, 3, 6, 9 and 18 months post-baseline. Group-based trajectory models identified clusters of individuals who followed similar patterns. Logistic and Cox regression identified factors associated with persistent symptoms and delayed recovery, respectively. Results: At baseline, 57% of women reported moderate-to-severe fatigue, 22% anxiety, 20% depression, 14% clinical insomnia and 45% had quality-of-life scores significantly lower than the general population. Between 50 and 75% of individual PRO scores normalised within six months, with the exception of emotional wellbeing (42%), but approximately two-in-five women still had at least one persistently poor PRO at 18 months. Women with more severe symptoms at baseline, who were younger, or had a history of anxiety/depression were more likely to have persistent symptoms or delayed recovery. Conclusions: Two-in-five women might never fully return to ‘normal’ after completing primary treatment for ovarian cancer. Those with risk factors should be triaged for early supportive interventions

OVQUEST – Life after the diagnosis and treatment of ovarian cancer - An international survey of symptoms and concerns in ovarian cancer survivors

Objectives: Our aim was to investigate the prevalence and potential risk factors for persistent and troublesome physical and psychological symptoms following treatment for ovarian cancer (OC). Methods: OvQuest is an international, internet-based, cross-sectional questionnaire which explored symptom burden and quality of life (QOL) after treatment for OC. Eligible women were aged 18 and over, diagnosed with OC at least 6 months previously and had received chemotherapy. Self-report data were collected including demographics, diagnosis and treatment, and standardised instruments for treatment-related toxicities, QOL, physical activity (PA) and supportive care needs. Results: The survey included 1360 patients, of whom 421 (31%) had been treated for recurrent OC. 78% reported symptoms of peripheral neuropathy, 60% significant fatigue, 48% mood disturbance and 59% moderate-severe insomnia. Rates of fatigue, mood disorders, neuropathy and insomnia did not differ between women with or without recurrence. The majority of respondents were overweight or obese (high BMI, 59%) and 35% reported low PA. Low PA and high BMI were associated with poorer QOL scores and higher symptom burden across a range of domains. Conclusion: Women living after a diagnosis of OC report a substantial and ongoing symptom burden which impacts significantly on their quality of life across multiple domains. The reported associations between obesity, physical inactivity and poor QOL warrant prospective evaluation of lifestyle interventions to improve QOL

Pre-existing immune status associated with response to combination of sipuleucel-T and ipilimumab in patients with metastatic castration-resistant prostate cancer

Background Sipuleucel-T is a US Food and Drug Administration-approved autologous cellular immunotherapy that improves survival in patients with metastatic castration-resistant prostate cancer (mCRPC). We examined whether administering ipilimumab after sipuleucel-T could modify immune and/or clinical responses to this treatment.Methods A total of 50 patients with mCRPC were enrolled into a clinical trial (NCT01804465, ClinicalTrials.gov) where they received ipilimumab either immediately or delayed 3 weeks following completion of sipuleucel-T treatment. Blood was collected at various timepoints of the study. Luminex assay for anti-prostatic acid phosphatase (PAP) and anti-PA2024-specific serum immunoglobulin G (IgG) and ELISpot for interferon-γ (IFN-γ) production against PAP and PA2024 were used to assess antigen-specific B and T cell responses, respectively. Clinical response was defined as &gt;30% reduction in serum prostate-specific antigen levels compared with pretreatment levels. The frequency and state of circulating immune cells were determined by mass cytometry by time-of-flight and statistical scaffold analysis.Results We found the combination to be well tolerated with no unexpected adverse events occurring. The timing of ipilimumab did not significantly alter the rates of antigen-specific B and T cell responses, the primary endpoint of the clinical trial. Clinical responses were observed in 6 of 50 patients, with 3 having responses lasting longer than 3 months. The timing of ipilimumab did not significantly associate with clinical response or toxicity. The combination treatment did induce CD4 and CD8 T cell activation that was most pronounced with the immediate schedule. Lower frequencies of CTLA-4 positive circulating T cells, even prior to treatment, were associated with better clinical outcomes. Interestingly, these differences in CTLA-4 expression were associated with prior localized radiation therapy (RT) to the prostate or prostatic fossa. Prior radiation treatment was also associated with improved radiographic progression-free survival.Conclusion Combining CTLA-4 blockade with sipuleucel-T resulted in modest clinical activity. The timing of CTLA-4 blockade following sipuleucel-T did not alter antigen-specific responses. Clinical responses were associated with both lower baseline frequencies of CTLA-4 expressing T cells and a history of RT. Prior cancer therapy may therefore result in long-lasting immune changes that influence responsiveness to immunotherapy with sipuleucel-T and anti-CTLA-4