Does the effect of cognitive behavior therapy for chronic fatigue syndrome (ME/CFS) vary by patient characteristics? A systematic review and individual patient data meta-analysis.

Debate is ongoing on the efficacy of cognitive behavior therapy (CBT) for myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS). With an individual patient data (IPD) meta-analysis we investigated whether the effect of CBT varied by patient characteristics. These included post-exertional malaise (PEM), a central feature of ME/CFS according to many. We searched for randomized controlled trials similar with respect to comparison condition, outcomes and treatment-protocol. Moderation on fatigue severity (Checklist Individual Strength, subscale fatigue severity), functional impairment (Sickness Impact Profile-8) and physical functioning (Short Form-36, subscale physical functioning) was investigated using linear mixed model analyses and interaction tests. PROSPERO (CRD42022358245). Data from eight trials (n = 1298 patients) were pooled. CBT showed beneficial effects on fatigue severity (ß = -11.46, 95% CI -15.13 to -7.79); p < 0.001, functional impairment (ß = -448.40, 95% CI -625.58 to -271.23); p < 0.001; and physical functioning (ß = 9.64, 95% CI 3.30 to 15.98); p < 0.001. The effect of CBT on fatigue severity varied by age (pinteraction = 0.003), functional impairment (pinteraction = 0.045) and physical activity pattern (pinteraction = 0.027). Patients who were younger, reported less functional impairments and had a fluctuating activity pattern benefitted more. The effect on physical functioning varied by self-efficacy (pinteraction = 0.025), with patients with higher self-efficacy benefitting most. No other moderators were found. It can be concluded from this study that CBT for ME/CFS can lead to significant reductions of fatigue, functional impairment, and physical limitations. There is no indication patients meeting different case definitions or reporting additional symptoms benefit less from CBT. Our findings do not support recent guidelines in which evidence from studies not mandating PEM was downgraded.

Body composition and peri- and postoperative complications in patients with gynaecological malignancies: A systematic review.

BACKGROUND: In general abdominal surgery, the ratio of fat to muscle mass, or body composition measures, shows a stronger association with complications than body mass index. These studies include male and female patients. Women have a different body composition than men. Therefore, findings from general abdominal surgery cannot be extrapolated to women with cancer. The aim of this systematic review is to summarise the evidence on the association between body composition and peri- and postoperative complications in patients with gynaecological cancer. METHODS: Pubmed, Embase and the Cochrane Central databases were searched in June 2023. Studies were eligible if they included patients undergoing surgery for gynaecological cancer and reported on the association between body composition (muscle or fat mass) and surgical complications. The quality of the studies was assessed using the Newcastle-Ottawa quality assessment scale. A best-evidence synthesis was used to summarise the level of evidence. RESULTS: Fifteen studies were included that assessed muscle mass (n = 9) or fat mass (n = 6). We found strong evidence that there was no association between visceral fat and length of hospital stay. We found moderate evidence that a higher amount of good quality muscle was associated with a lower risk of postoperative complications. We found moderate evidence that there was no association between muscle or fat mass (i.e., muscle- or subcutaneous fat) and postoperative complications or fat mass and intraoperative complications. There was insufficient evidence for an association between visceral fat and intraoperative or postoperative complications, and for an association between muscle mass or -quality and length of hospital stay. There was high heterogeneity in the methods used to measure body composition, hampering meta-analyses. CONCLUSION: The association between body composition, particularly adipose tissue and muscle quality, and complications suggests that these measures may be of interest in determining postoperative risk in women undergoing surgery for gynaecological cancer.

Experiences, adherence and satisfaction with a combined exercise and dietary intervention for patients with ovarian cancer undergoing chemotherapy: A mixed-methods study.

OBJECTIVE: This study examined experiences, adherence and satisfaction with a combined exercise and dietary intervention in patients with ovarian cancer and their healthcare professionals (HCPs) as part of the randomized PADOVA trial. METHODS: A mixed-methods approach was used in 24 patients with ovarian cancer receiving first-line chemotherapy who were randomly allocated to a combined exercise and dietary intervention or usual care with counseling sessions post-treatment. Qualitative data on intervention experiences, adherence and satisfaction was collected using semi-structured interviews with patients and their HCPs (n = 18 physical therapists; n = 5 dietitians). Quantitative data on adherence and satisfaction was collected to provide context to qualitative data. RESULTS: Exercise relative dose intensity ranged from 36 to 100% (median 72%) and patients attended 33-133% (median 100%) of the prescribed dietary counseling sessions. Patients appreciated guidance on exercise and nutrition and perceived benefits including improved physical fitness, quality of life, peer support and recovery after surgery and/or chemotherapy cycles. Both patients and HCPs were satisfied with the intervention and perceived that participation exceeded prior expectations. Median patient satisfaction score with the intervention was 8.5 out of 10. Suggestions for improving the intervention included further personalization of the number, content and scheduling of the sessions to preferences of patients and HCPs. Patients in the usual care group reported counseling sessions post-chemotherapy to be too little too late. CONCLUSIONS: Patients with ovarian cancer adhered well to the intervention. Numerous perceived benefits of the intervention were reported by patients and HCPs. Good adherence and positive experiences support successful implementation in clinical practice.

Health-related quality of life and overall survival: a prospective study in patients with head and neck cancer treated with radiotherapy.

PURPOSE: We aimed to examine whether pre-treatment, post-treatment and change in health-related quality of Life (HRQoL) is associated with survival, in patients with head and neck cancer (HNC). METHODS: We included 948 newly diagnosed HNC patients treated with primary or adjuvant (chemo)radiotherapy with curative intent. The EORTC QLQ-C30 questionnaire was assessed pre-treatment and at 6 weeks, 6 months and 12 months post-treatment. Multivariable Cox regression analyses were performed to examine whether HRQoL at all time points and changes in HRQoL over time were associated with survival, after adjusting for demographic, clinical and lifestyle-related variables. RESULTS: Higher HRQoL scores were significantly associated with improved 5-year overall survival at all time points, except for the subscale global QoL at 6 weeks. Changes in HRQoL at 6 weeks post-treatment compared to pre-treatment were not significantly associated with survival. Changes in physical (HR: 0.88 95% CI: 0.82-0.96) and emotional functioning (HR: 0.90 95% CI: 0.85-0.96) from pre-treatment to 6 months post-treatment and changes in global QOL, and physical, emotional, and social functioning from pre-treatment to 12 months post-treatment were significantly associated with survival. CONCLUSION: Higher HRQoL reported pre-treatment and post-treatment (6 weeks, 6 months and 12 months) are significantly associated with improved survival, as well as changes in HRQoL at 6 and 12 months compared to pre-treatment. Our results highlight the value of monitoring HRQoL and to identify those patients that report decreased or deteriorated HRQOL. This may help to further improve cancer care in a timely and efficient manner.

Demographic, clinical and lifestyle-related correlates of accelerometer assessed physical activity and fitness in newly diagnosed patients with head and neck cancer.

Introduction: Objective measurements of levels of physical activity and fitness in patients with head and neck cancer (HNC) are lacking. Furthermore, demographic, clinical and lifestyle-related correlates of low levels of physical activity and fitness in patients with HNC are unknown. This study aims to investigate the levels of accelerometer that assessed physical activity and fitness in patients with HNC and to identify their demographical, clinical and lifestyle-related correlates.Methods: Two hundred and fifty-four patients who were recently diagnosed with HNC and participated in the NETherlands QUality of life and Biomedical cohort studies In head and neck Cancer (NET-QUBIC) study were included. Physical activity (accelerometer), cardiorespiratory fitness (Chester Step Test), hand grip strength (hand dynamometer) and lower body muscle function (30-second chair-stand test) were assessed. Multivariable linear regression analyses with a stepwise forward selection procedure were used.Results: Patients spent 229 min/d in physical activity of which 18 min/d in moderate-to-vigorous physical activity. The mean predicted VO2max was 27.9 ml/kg/min, the mean hand grip strength was 38.1 kg and the mean number of standings was 14.3. Patients with lower educational level, more comorbidity and higher tumor stage spent significantly less time in physical activity. Older patients, females and patients with a higher tumor stage had significantly lower cardiorespiratory fitness levels. Older patients, females, patients with more comorbidity, patients with normal weight and patients who have never smoked had significantly lower hand grip strength. Older patients, patients with lower educational level, smokers and patients with more comorbidity had a significantly lower function of lower body muscle.Conclusions: Pre-treatment levels of physical activity, cardiorespiratory fitness and lower body muscle function are low in patients with HNC. Based on this study, exercise programs targeted and tailored to patients with low levels of physical activity and fitness can be developed.

Which cancer survivors are at risk for a physically inactive and sedentary lifestyle? Results from pooled accelerometer data of 1447 cancer survivors.

BACKGROUND: Physical activity has beneficial effects on the health of cancer survivors. We aimed to investigate accelerometer-assessed physical activity and sedentary time in cancer survivors, and describe activity profiles. Additionally, we identify demographic and clinical correlates of physical activity, sedentary time and activity profiles. METHODS: Accelerometer, questionnaire and clinical data from eight studies conducted in four countries (n = 1447) were pooled. We calculated sedentary time and time spent in physical activity at various intensities using Freedson cut-points. We used latent profile analysis to identify activity profiles, and multilevel linear regression analyses to identify demographic and clinical variables associated with accelerometer-assessed moderate to vigorous physical activity (MVPA), sedentary time, the highly active and highly sedentary profile, adjusting for confounders identified using a directed acyclic graph. RESULTS: Participants spent on average 26 min (3%) in MVPA and 568 min (66%) sedentary per day. We identified six activity profiles. Older participants, smokers and participants with obesity had significantly lower MVPA and higher sedentary time. Furthermore, men had significantly higher MVPA and sedentary time than women and participants who reported less fatigue had higher MVPA time. The highly active profile included survivors with high education level and normal body mass index. Haematological cancer survivors were less likely to have a highly active profile compared to breast cancer survivors. The highly sedentary profile included older participants, males, participants who were not married, obese, smokers, and those < 12 months after diagnosis. CONCLUSIONS: Cancer survivors engage in few minutes of MVPA and spend a large proportion of their day sedentary. Correlates of MVPA, sedentary time and activity profiles can be used to identify cancer survivors at risk for a sedentary and inactive lifestyle.

Graded activity is an important component in cognitive behavioral therapy to reduce severe fatigue: results of a pragmatic crossover trial in cancer survivors.

Background: Fatigue is one of the most common and distressing long-term effects of cancer treatment. Cognitive behavioral therapy (CBT) is an evidence-based intervention for patients with severe post-cancer fatigue. CBT for fatigue is a complex intervention consisting of multiple elements like a graded activity program, regulation of the sleep-wake rhythm and reformulation of fatigue-related cognitions. The contribution of the separate elements to the positive effect of CBT on fatigue is unclear. The main objective of this pragmatic crossover trial was comparing the efficacy of graded activity with the other elements of CBT in reducing post-cancer fatigue.Material and methods: Severely fatigued cancer survivors were randomized to (i) graded activity followed by the other elements of CBT after crossover (n = 41), or (ii) the two components in reverse order (n = 48). Fatigue severity was measured at baseline, before crossover and after CBT (Checklist Individual Strength (CIS), Fatigue Severity subscale). Differences in effects on fatigue were examined with a linear regression analysis. Objective physical activity, perceived activity and self-efficacy were explored as mediators of the effect of graded activity.Results: Before crossover, the reduction in fatigue was significantly larger after graded activity than after the other elements (ß = 4.75, 95% confidence interval (95% CI) = -9.19; -0.32). An increase in perceived activity mediated this effect (ß = -4.17, 95% CI = -7.37; -1.37).Conclusions: Graded activity is an important component of CBT for post-cancer fatigue as it resulted in a larger reduction in fatigue compared with the other elements, mediated by an increased level of perceived activity. Results indicated that the other elements of CBT are of added value in reducing fatigue.

Return to work experiences of patients treated with stem cell transplantation for a hematologic malignancy.

PURPOSE: This qualitative study aimed to identify hematopoietic stem cell transplantation (HSCT) survivors' (1) work perceptions; (2) barriers to and facilitators of return to work (RTW); and (3) possible solutions to improve RTW. METHOD: Fifteen patients treated with HSCT 1-5 years ago participated in face-to-face semi-structured interviews. Interviews were analyzed following the steps of thematic content analyses. RESULTS: RTW was often characterized as a complex and prolonged trajectory, and it was frequently incomplete in working hours, tasks, and/or responsibilities. Work perceptions varied between patients; most valued work as positive, but some also reported a decline in work capacity and/or in importance. Perceived barriers included the duration and side effects of cancer treatment, the presence of comorbidity and poor health before diagnosis, having difficulties commuting and doing household tasks. Perceived facilitators were financial incentives, keeping in touch with the workplace, support of other patients and family, and looking after one's health. Proposed solutions to improve RTW included discussing RTW at the hospital, enhanced employer support, improved accessibility of rehabilitation programs, and more information about the consequences of being sick-listed. CONCLUSIONS: Many HSCT survivors value work as important and they are motivated to RTW. Insight in work perceptions, RTW barriers, and solutions might help researchers, healthcare professionals, and employers to develop and/or tailor individualized multidisciplinary care to facilitate RTW.

Effects and moderators of psychosocial interventions on quality of life, and emotional and social function in patients with cancer: An individual patient data meta-analysis of 22 RCTs.

OBJECTIVE: This individual patient data (IPD) meta-analysis aimed to evaluate the effects of psychosocial interventions (PSI) on quality of life (QoL), emotional function (EF), and social function (SF) in patients with cancer, and to study moderator effects of demographic, clinical, personal, and intervention-related characteristics. METHODS: Relevant studies were identified via literature searches in 4 databases. We pooled IPD from 22 (n = 4217) of 61 eligible randomized controlled trials. Linear mixed-effect model analyses were used to study intervention effects on the post-intervention values of QoL, EF, and SF (z-scores), adjusting for baseline values, age, and cancer type. We studied moderator effects by testing interactions with the intervention for demographic, clinical, personal, and intervention-related characteristics, and conducted subsequent stratified analyses for significant moderator variables. RESULTS: PSI significantly improved QoL (ß = 0.14,95%CI = 0.06;0.21), EF (ß = 0.13,95%CI = 0.05;0.20), and SF (ß = 0.10,95%CI = 0.03;0.18). Significant differences in effects of different types of PSI were found, with largest effects of psychotherapy. The effects of coping skills training were moderated by age, treatment type, and targeted interventions. Effects of psychotherapy on EF may be moderated by cancer type, but these analyses were based on 2 randomized controlled trials with small sample sizes of some cancer types. CONCLUSIONS: PSI significantly improved QoL, EF, and SF, with small overall effects. However, the effects differed by several demographic, clinical, personal, and intervention-related characteristics. Our study highlights the beneficial effects of coping skills training in patients treated with chemotherapy, the importance of targeted interventions, and the need of developing interventions tailored to the specific needs of elderly patients.

Lessons learnt from a process evaluation of an exercise intervention in patients treated with autologous stem cell transplantation.

This paper describes the process evaluation of an 18-week supervised exercise programme in 50 patients treated with high-dose chemotherapy followed by autologous stem cell transplantation. The intervention included 30 exercise sessions with six resistance exercises and interval training. We evaluated the context, dose delivered and received, and patients' and physiotherapists' satisfaction with the intervention. Ninety-two per cent of the patients trained within 15 km of their home address, with an average session attendance of 86%. Most patients trained at the prescribed intensity for four of the six resistance exercises, but the dose delivered and received of the two remaining resistance exercises and interval training could not be determined. Both patients and physiotherapists highly appreciated the programme (score of 8.3 and 7.9 out of 10 respectively). This process evaluation provided valuable lessons for future trials: (1) It is possible to deliver supervised exercise training to this patient group in local physiotherapy practices; (2) to determine dose received all intervention components should be standardised; and (3) to optimise data collection, all study materials should be tested more extensively prior to the start of the intervention.

Prevalence of depression in cancer patients: a meta-analysis of diagnostic interviews and self-report instruments.

OBJECTIVE: We aimed to investigate the prevalence of depression in cancer patients assessed by diagnostic interviews and self-report instruments, and to study differences in prevalence between type of instrument, type of cancer and treatment phase. METHODS: A literature search was conducted in four databases to select studies on the prevalence of depression among adult cancer patients during or after treatment. A total of 211 studies met the inclusion criteria. Pooled mean prevalence of depression was calculated using Comprehensive Meta-Analysis. RESULTS: Hospital Anxiety and Depression Scale-depression subscale (HADS-D) ≥ 8, HADS-D ≥11, Center for Epidemiologic Studies ≥ 16, and (semi-)structured diagnostic interviews were used to define depression in 66, 53, 35 and 49 studies, respectively. Respective mean prevalence of depression was 17% (95% CI = 16-19%), 8% (95% CI = 7-9%), 24% (95% CI = 21-26%), and 13% (95% CI = 11-15%) (p < 0.001). Prevalence of depression ranged from 3% in patients with lung cancer to 31% in patients with cancer of the digestive tract, on the basis of diagnostic interviews. Prevalence of depression was highest during treatment 14% (95% CI = 11-17%), measured by diagnostic interviews, and 27% (95% CI = 25-30%), measured by self-report instruments. In the first year after diagnosis, prevalence of depression measured with diagnostic interviews and self-report instruments were 9% (95% CI = 7-11%) and 21% (95% CI = 19-24%), respectively, and they were 8% (95% CI = 5-12%) and 15% (95% CI = 13-17%) ≥ 1 year after diagnosis. CONCLUSIONS: Pooled mean prevalence of depression in cancer patients ranged from 8% to 24% and differed by the type of instrument, type of cancer and treatment phase. Future prospective studies should disentangle whether differences in prevalence of depression are caused by differences in the type of instrument, type of cancer or treatment phase. © 2013 The Authors. Psycho-Oncology published by John Wiley & Sons, Ltd.

Mediators of physical exercise for improvement in cancer survivors' quality of life.

OBJECTIVE: Mediating mechanisms of a 12-week group-based exercise intervention on cancer survivors' quality of life (QoL) were examined to inform future exercise intervention development. METHODS: Two hundred nine cancer survivors ≥ 3 months posttreatment (57% breast cancer) aged 49.5 (± 10.4) years were assigned to physical exercise (n = 147) or wait-list control (n = 62). QoL, fatigue, emotional distress, physical activity, general self-efficacy and mastery were assessed at baseline and post-intervention using questionnaires. Path analysis was conducted using Mplus to explore whether improved physical activity, general self-efficacy and mastery mediated the effects of exercise on fatigue and distress and consequently QoL. RESULTS: The intervention was associated with increased physical activity (ß = 0.46, 95% confidence interval (CI) = 0.14;0.59), general self-efficacy (ß = 2.41, 95%CI = 0.35;4.73), and mastery (ß = 1.75, 95%CI = 0.36;2.78). Further, the intervention had both a direct effect on fatigue (ß = -1.09, 95%CI = -2.12;0.01), and an indirect effect (ß = -0.54, 95%CI = -1.00;-0.21) via physical activity (ß = -0.29, 95%CI = -0.64;-0.07) and general self-efficacy (ß = -0.25, 95%CI = -0.61;-0.05). The intervention had a borderline significant direct effect on reduced distress (ß = -1.32, 95%CI = -2.68;0.11), and a significant indirect effect via increased general self-efficacy and mastery (ß = -1.06, 95%CI = -1.89;-0.38). Reductions in fatigue (ß = -1.33, 95%CI =-1.85;-0.83) and distress (ß = -0.86, 95%CI = -1.25;-0.52) were associated with improved QoL. Further, increased physical activity was directly associated with improved QoL (ß = 3.37, 95%CI = 1.01;5.54). CONCLUSION: The beneficial effect of group-based physical exercise on QoL was mediated by increased physical activity, general self-efficacy and mastery, and subsequent reductions in fatigue and distress. In addition to physical activity, future interventions should target self-efficacy and mastery. This may lead to reduced distress and fatigue, and consequently improved QoL of cancer survivors.

Is the effect of cognitive behaviour therapy for chronic fatigue syndrome (ME/CFS) moderated by the presence of comorbid depressive symptoms? A meta-analysis of three treatment delivery formats.

OBJECTIVE: Cognitive behaviour therapy (CBT) for fatigue in chronic fatigue syndrome (ME/CFS) leads to a significant reduction of fatigue and disability and is available in different treatment delivery formats, i.e. internet-based, individual face-to-face and group face-to-face. The aim of this study was to investigate whether moderation of the effects of CBT by clinically relevant depressive symptoms varies between CBT delivery formats. METHODS: Data from six randomised controlled trials (n = 1084 patients) were pooled. Moderation of clinically relevant depressive symptoms (Brief Depression Inventory for Primary Care) in different treatment formats on fatigue severity (Checklist Individual Strength, subscale fatigue severity), functional impairment (Sickness Impact Profile-8) and physical functioning (Short Form-36, subscale physical functioning) was investigated using linear mixed model analyses and interaction tests. Differences in percentages of patients no longer severely fatigued post-CBT were studied by calculating relative risks. RESULTS: The moderator effect of depressive symptoms on fatigue severity varied by delivery format. In internet-based CBT, ME/CFS patients with depressive symptoms showed less reduction in fatigue, and were more often still severely fatigued post-treatment than patients without depressive symptoms. In individual and group face-to-face CBT, no significant difference in treatment effect on fatigue severity was found between patients with and without depressive symptoms. No moderation was found for the other outcomes. CONCLUSION: In internet-based CBT, ME/CFS patients with comorbid depressive symptoms benefit less, making face-to-face CBT currently the first-choice delivery format for these patients. Internet-based CBT should be further developed to improve its effectiveness for ME/CFS patients with depressive symptoms.

Physical activity at diagnosis is associated with tumor downstaging after neoadjuvant chemoradiotherapy in patients with rectal cancer.

BACKGROUND: Patients with rectal cancer are often treated with neoadjuvant chemoradiotherapy, followed by a waiting period and surgical resection. Good or complete response to neoadjuvant chemoradiotherapy might enable organ preservation, which highlights the need to increase response rates. Pre-clinical studies suggest that physical activity during neoadjuvant chemoradiotherapy may improve tumor downstaging. PURPOSE: To investigate whether physical activity and physical functioning of patients with rectal cancer at diagnosis are associated with tumor downstaging after neoadjuvant chemoradiotherapy. MATERIALS AND METHODS: Patients were included if they participated in the Dutch Prospective ColoRectal Cancer Cohort, a nationwide cohort providing an infrastructure for scientific research, and received neoadjuvant chemoradiotherapy for rectal cancer. Tumor downstaging was dichotomized into good/complete or moderate/poor downstaging. Physical activity (total physical activity, moderate-to-vigorous physical activity (MVPA), and Dutch physical activity guideline adherence) and physical functioning were assessed using questionnaires. Logistic regression analyses were performed to examine associations of physical activity and physical functioning with tumor downstaging, adjusted for relevant confounders. RESULTS: 268 patients (aged 62 ± 11 years, 33 % female) with rectal cancer were included. Patients with moderate (OR = 2.07; 95%CI = 1.07 - 4.07; p = 0.03) or high (OR = 2.05; 95%CI = 1.05 - 4.07; p = 0.04) levels of MVPA were more likely to have good/complete tumor downstaging than patients with low levels. No significant associations with tumor downstaging were found for total physical activity, Dutch physical activity guideline adherence, and physical functioning. CONCLUSIONS: We found augmented tumor downstaging in patients with rectal cancer with moderate or high levels of self-reported MVPA before the start of neoadjuvant chemoradiotherapy compared to patients with low levels.

Cancer patients' experiences with and perceived outcomes of yoga: results from focus groups.

PURPOSE: Yoga is a "mind-body" exercise, a combination of physical poses with breathing and meditation, and may have beneficial effects on physical and psychosocial symptoms. We aimed to explore cancer patients' motives for practicing yoga, experiences of practicing yoga, and perceived physical and psychosocial outcomes. METHODS: Participants (n = 45) following yoga classes for cancer patients were asked to participate in focus group interviews, of whom 29 participated. The focus groups (n = 5) were audio taped with prior consent and transcribed verbatim. Data were analyzed by two coders and independently coded into key issues and themes. RESULTS: Mean age of the participants was 53.8 (SD 10.8) years, of whom 25 were women, and 18 were diagnosed with breast cancer. Motives for participation in yoga were relaxation, the will to be physically active, the wish to pay more attention to one's body, coping with psychosocial symptoms, contributing to their cancer rehabilitation process, and combing physical and mental processes. Main physical and psychosocial experiences of yoga mentioned by patients were regaining body awareness, raising attention to the inner self, learning how to relax, enjoyment, and finding recognition and understanding. Increased physical fitness and function, mental strength and resilience, increased coping, being more relaxed, and happiness were frequently mentioned experiences of patients. CONCLUSIONS: Patients with different types of cancer perceived several benefits on physical and psychosocial outcomes by practicing yoga. Therefore, yoga can be a valuable form of supportive care for cancer patients.

Behavioral factors to modulate immunotherapy efficacy in cancer.

Immune checkpoint inhibitors, including anti-PD-1 and anti-CTLA-4 therapies, are used to (re)activate the immune system to treat cancer. Despite promising results, a large group of patients does not respond to checkpoint inhibition. In the vulnerability-stress model of behavioral medicine, behavioral factors, such as stress, exercise and classical pharmacological conditioning, predict cancer incidence, recurrence and the efficacy of conventional cancer treatments. Given the important role of the immune system in these processes, certain behavior may be promising to complement immune checkpoint inhibition therapy. Here, we discuss the preliminary evidence and suitability of three behavioral mechanisms, i.e. stress modulation, exercise and classical pharmacological conditioning for the benefit of immunotherapy. It is crucial to study the potential beneficial effects of behavioral strategies that support immunotherapeutic anti-tumor effects with rigorous experimental evidence, to exploit behavioral mechanisms in improving checkpoint inhibition efficacy.

Facilitators and barriers for the implementation of exercise are medicine in routine clinical care in Dutch university medical centres: a mixed methodology study on clinicians' perceptions.

OBJECTIVES: Despite the many proven advantages of a physically active lifestyle in patient populations, prescription of exercise is currently not widely implemented in routine clinical practice. The aims of this study were twofold: (1) to assess perceptions of clinicians on the current practice of exercise is medicine (E=M) prescription in two Dutch university medical centres and (2) to determine their perceived barriers and facilitators for the implementation of E=M in routine clinical care in Dutch university medical centres. DESIGN: A mixed methodologies study, using both online questionnaires and semi-structured interviews. SETTING: Dutch university medical centres. PARTICIPANTS: Clinicians working within the departments of medical oncology, orthopaedics and rehabilitation medicine of two university medical centres. RESULTS: Forty-five clinicians (response rate of 51%) completed the questionnaire, and 19 clinicians were interviewed. The results showed that even though clinicians had a positive attitude towards prescribing E=M, only a few reported to regularly prescribe E=M to their patients. The 52 identified facilitators and barriers for implementation of E=M were categorised into four main themes: (1) beliefs toward the implementation of E=M (eg, clinicians knowledge and skills, and social support), (2) factors related to the patient perspective (eg, patient priorities or motivation), (3) factors related to the referral options (eg, knowledge of and trust in local referral options) and (4) practical considerations when implementing E=M (eg, time constraints). CONCLUSIONS: Our study showed that even though many clinicians have a positive attitude toward an active lifestyle, many are not prescribing E=M on a regular basis. In order for clinicians to effectively implement E=M, strategies should focus on increasing clinicians E=M referral skills, improving clinicians knowledge of E=M referral options and develop a support system to ensure that E=M is high on the priority list of clinicians.

Rationale and study protocol of the Physical Activity and Dietary intervention in women with OVArian cancer (PADOVA) study: a randomised controlled trial to evaluate effectiveness of a tailored exercise and dietary intervention on body composition, physical function and fatigue in women with ovarian cancer undergoing chemotherapy.

INTRODUCTION: As a consequence of ovarian cancer and its treatment, many women with ovarian cancer have to deal with reduced physical function, fatigue, and loss of weight and/or muscle mass, compromising quality of life. Exercise and dietary interventions can positively influence body composition, physical fitness and function, and fatigue in patients with cancer. However, there are no data from randomised controlled trials on the effectiveness of exercise and dietary interventions in patients with ovarian cancer. Due to a complex disease trajectory, a relatively poor survival and distinct disease-induced and treatment-induced side effects, it is unclear whether exercise and dietary interventions that were shown to be feasible and effective in other types of cancer produce comparable results in patients with ovarian cancer. The aim of this article is to present the design of the multicentre randomised controlled Physical Activity and Dietary intervention in OVArian cancer trial and to describe how the exercise and dietary intervention is tailored to specific comorbidities and disease-induced and treatment-induced adverse effects in patients with ovarian cancer. METHODS AND ANALYSIS: Adult women with primary epithelial ovarian cancer who are scheduled to undergo first-line (neo)adjuvant chemotherapy (n=122) are randomly allocated to a combined exercise and dietary intervention or a usual care control group during chemotherapy. Primary outcomes are body composition, physical function and fatigue. Outcome measures will be assessed before the start of chemotherapy, 3 weeks after completion of chemotherapy and 12 weeks later. The exercise and dietary intervention was tailored to ovarian cancer-specific comorbidities and adverse effects of ovarian cancer and its treatment following the i3-S strategy. ETHICS AND DISSEMINATION: This study has been approved by the medical ethical committee of the Amsterdam UMC (reference: 018). Results of the study will be published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: Netherlands Trial Registry (NTR6300).

Effects and moderators of coping skills training on symptoms of depression and anxiety in patients with cancer: Aggregate data and individual patient data meta-analyses.

PURPOSE: This study evaluated the effects of coping skills training (CST) on symptoms of depression and anxiety in cancer patients, and investigated moderators of the effects. METHODS: Overall effects and intervention-related moderators were studied in meta-analyses of pooled aggregate data from 38 randomized controlled trials (RCTs). Patient-related moderators were examined using linear mixed-effect models with interaction tests on pooled individual patient data (n = 1953) from 15 of the RCTs. RESULTS: CST had a statistically significant but small effect on depression (g = -0.31,95% confidence interval (CI) = -0.40;-0.22) and anxiety (g = -0.32,95%CI = -0.41;-0.24) symptoms. Effects on depression symptoms were significantly larger for interventions delivered face-to-face (p = .003), led by a psychologist (p = .02) and targeted to patients with psychological distress (p = .002). Significantly larger reductions in anxiety symptoms were found in younger patients (pinteraction < 0.025), with the largest reductions in patients <50 years (ß = -0.31,95%CI = -0.44;-0.18) and no significant effects in patients ≥70 years. Effects of CST on depression (ß = -0.16,95%CI = -0.25;-0.07) and anxiety (ß = -0.24,95%CI = -0.33;-0.14) symptoms were significant in patients who received chemotherapy but not in patients who did not (pinteraction < 0.05). CONCLUSIONS: CST significantly reduced symptoms of depression and anxiety in cancer patients, and particularly when delivered face-to-face, provided by a psychologist, targeted to patients with psychological distress, and given to patients who were younger and received chemotherapy.

General practitioners' perceptions and practices of physical activity counselling: changes over the past 10 years.

OBJECTIVE: In this work, trends in general practitioners' (GP) knowledge, confidence and practices in promoting physical activity to patients over a 10-year period (1997-2007) were studied. DESIGN: Repeated cross-sectional population survey SETTING: General practice in New South Wales (Australia) PARTICIPANTS: 646 (40%), 747 (53%) and 511 (64%) GPs that were registered in a selection of urban and rural divisions in New South Wales participated in 2007, 2000 and 1997, respectively. MAIN OUTCOME MEASURES: Self-report questionnaire on the GP's knowledge, confidence, role perception, attendance of continuous professional development and counselling practice with regard to promoting physical activity in their patients were the main outcome measures. RESULTS: The majority of GPs felt confident in giving physical activity advice and saw it as their role to do so. The proportion of GPs with high confidence and role perception increased between 1997 and 2000 (p<0.001) but remained unchanged thereafter. In 1997, GPs were 0.54 times less likely (95% CI 0.42 to 0.69, p<0.001) to discuss physical activity with more than 10 patients per week than GPs in 2007. However, the percentage of new patients that were asked about their physical activity did not change over the last decade. CONCLUSIONS: Most increases in the proportion of GPs reporting high knowledge, role perception and confidence in giving physical activity advice to patients occurred between 1997 and 2000 and remained unchanged thereafter. In 2007, GPs appeared to give more physical activity advice, but Australian general practice is not yet living up to its potential with regard to physical activity promotion.