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.

Study protocol of the CORRECT multicenter trial: the efficacy of blended cognitive behavioral therapy for reducing psychological distress in colorectal cancer survivors.

BACKGROUND: Approximately one third of the colorectal cancer survivors (CRCS) experience high levels of psychological distress. Common concerns experienced by CRCS include distress related to physical problems, anxiety, fear of cancer recurrence (FCR) and depressive symptoms. However, psychological interventions for distressed CRCS are scarce. Therefore, a blended therapy was developed, combining face-to-face cognitive behavioral therapy (CBT) with online self-management activities and telephone consultations. The aim of the study is to evaluate the efficacy and cost-effectiveness of this blended therapy in reducing psychological distress in CRCS. METHODS/DESIGN: The CORRECT study is a two-arm multicenter randomized controlled trial (RCT). A sample of 160 highly distressed CRCS (a score on the Distress Thermometer of 5 or higher) will be recruited from several hospitals in the Netherlands. CRCS will be randomized to either the intervention condition (blended CBT) or the control condition (care as usual). The blended therapy covers approximately 14 weeks and combines five face-to-face sessions and three telephone consultations with a psychologist, with access to an interactive self-management website. It includes three modules which are individually-tailored to patient concerns and aimed at decreasing: 1) distress caused by physical consequences of CRC, 2) anxiety and FCR, 3) depressive symptoms. Patients can choose between the optional modules. The primary outcome is general distress (Brief Symptom Inventory-18). Secondary outcomes are quality of life and general psychological wellbeing. Assessments will take place at baseline prior to randomization, after 4 and 7 months. DISCUSSION: Blended CBT is an innovative and promising approach for providing tailored supportive care to reduce high distress in CRCS. If the intervention proves to be effective, an evidence-based intervention will become available for implementation in clinical practice. TRIAL REGISTRATION: This trial is registered in the Netherlands Trial Register ( NTR6025 ) on August 3, 2016.

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.

The Distress Thermometer for screening for severe fatigue in newly diagnosed breast and colorectal cancer patients.

OBJECTIVE: Internationally, the Distress Thermometer and associated Problem List are increasingly used in oncology as screening tools for psychological distress. Cancer-related fatigue is common but often overlooked in clinical practice. We examined if severe fatigue in cancer patients can be identified with the fatigue item of the Problem List. METHODS: Newly diagnosed breast (N = 334) and colorectal (N = 179) cancer patients were screened for severe fatigue, which was defined as having a positive score on the fatigue item of the Problem List. The Fatigue Severity subscale of the Checklist Individual Strength was used as gold standard measure for severe fatigue. RESULTS: In total, 78% of breast cancer patients and 81% of colorectal cancer patients were correctly identified with the fatigue item. The sensitivity was 89% in breast cancer patients and 91% in colorectal cancer patients. The specificity was 75% in breast cancer patients and 77% in colorectal cancer patients. The positive predictive value was 53% in breast cancer patients and 64% in colorectal cancer patients, whereas the negative predictive value was 95% in both tumor types. CONCLUSIONS: The fatigue item of the Problem List performs satisfactorily as a quick screening tool for severe fatigue. However, a positive screen should be followed up with a more thorough assessment of fatigue, ie, a questionnaire with a validated cutoff point. Given time pressure of clinicians, this already implemented and brief screening tool may prevent severe fatigue from going undetected in clinical practice.

Risk factors, prevalence, and course of severe fatigue after breast cancer treatment: a meta-analysis involving 12 327 breast cancer survivors.

BACKGROUND: This meta-analysis aimed to (i) examine demographic, disease-related, and treatment-related risk factors, (ii) estimate the prevalence, and (iii) describe the course of severe fatigue following breast cancer (BC) treatment. METHODS: PubMed, PsycINFO, Cochrane, CINAHL, and Web of Science were systematically searched from inception up to 23 November 2015. Risk factors and prevalence rates were analyzed with inverse variance random-effects analyses. Heterogeneity was studied with sensitivity analyses. RESULTS: Twenty-seven studies were included (N = 12 327). Breast cancer survivors (BCS) with a partner were at lower risk for severe fatigue than survivors without a partner [risk ratio (RR) 0.96, 95% confidence interval (CI) 0.93-0.98]. Survivors with stage II or III cancer, and survivors treated with chemotherapy were at higher risk for severe fatigue than survivors with stage 0 or I cancer and without chemotherapy (RR respectively 1.18, 95% CI 1.08-1.28; 1.12, 95% CI 1.06-1.19). Survivors treated with surgery, radiotherapy, and chemotherapy, and survivors with this combination plus hormone therapy were at higher risk than survivors with other treatment combinations (RR respectively 1.18, 95% CI 1.05-1.33; 1.38, 95% CI 1.15-1.66). Survivors treated with surgery and surgery plus radiotherapy were at lower risk than survivors with additional treatments (RR respectively 0.83, 95% CI 0.70-0.98; 0.87, 95% CI 0.78-0.96). Hormone and targeted therapy were no significant risk factors. The pooled prevalence of severe fatigue was 26.9% (95% CI 23.2-31.0), but this should be interpreted with caution because of high heterogeneity. A relatively large decrease in the prevalence of severe fatigue seemed to occur in the first half year after treatment completion. CONCLUSIONS: Approximately one in four BCS suffer from severe fatigue. Risk factors of severe fatigue were higher disease stages, chemotherapy and receiving the combination of surgery, radiotherapy, and chemotherapy, both with and without hormone therapy. Having a partner, receiving only surgery, and surgery plus radiotherapy decreased the risk.

A randomized controlled trial of web-based cognitive behavioral therapy for severely fatigued breast cancer survivors (CHANGE-study): study protocol.

BACKGROUND: About one third of breast cancer survivors suffer from persistent severe fatigue after completion of curative cancer treatment. Face-to-face cognitive behavioral therapy (F2F CBT), especially designed for fatigue in cancer survivors, was found effective in reducing fatigue. However, this intervention is intensive and treatment capacity is limited. To extend treatment options, a web-based version of CBT requiring less therapist time was developed. This intervention is aimed at changing fatigue-perpetuating cognitions and behaviors. The efficacy of web-based CBT will be examined in a multicenter randomized controlled trial. METHODS: In total, 132 severely fatigued breast cancer survivors will be recruited and randomized to either an intervention condition or care as usual (ratio 1:1). Participants will be assessed at baseline and 6 months thereafter. The intervention group will receive web-based CBT, consisting of three F2F sessions and maximally eight web-based modules over a period of 6 months. The care as usual group will be on a waiting list for regular F2F CBT. The total duration of the waiting list is 6 months. The primary outcome of the study is fatigue severity. Secondary outcomes are functional impairments, psychological distress and quality of life. DISCUSSION: If web-based CBT is effective, it will provide an additional treatment option for fatigue in breast cancer survivors. Web-based CBT is expected to be less time-consuming for therapists than regular F2F CBT, which would result in an increased treatment capacity. Moreover, the intervention would become more easily accessible for a larger number of patients, and patients can save travel time and costs. TRIAL REGISTRATION: Dutch Trial Registry--NTR4309.

Selective attention and fear of cancer recurrence in breast cancer survivors.

BACKGROUND: Anxious people show an attentional bias towards threatening information. PURPOSE: It was investigated whether an attentional bias exists for cancer-related stimuli in breast cancer survivors and if different levels of fear of cancer recurrence would lead to different patterns of selective attention. METHODS: Breast cancer survivors with high (n = 35) and low (n = 32) fear of cancer recurrence were compared to 40 healthy female hospital employees. Specificity of attentional biases was investigated using a modified Emotional Stroop Task. Self-report measures were used to assess depression and anxiety, feelings of fatigue, and experienced traumas. RESULTS: Compared to control participants, breast cancer survivors with both high and low levels of fear of cancer recurrence showed increased interference for cancer-related words, but not for other word types. CONCLUSIONS: The findings suggest a specific attentional bias for cancer-related words in breast cancer survivors that is independent of level of fear of cancer recurrence.

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.

Severe fatigue and related factors in cancer patients before the initiation of treatment.

It is generally known that fatigue is a common symptom during cancer treatment, and in cancer survivors. However, fatigue was never studied after diagnosis, before cancer treatment was initiated. This study investigated the prevalence of severe fatigue, and related factors, in cancer patients before the initiation of treatment. One hundred and seventy-nine patients with various malignancies were assessed before start of treatment with curative intention, including the Checklist Individual Strength, Sickness Impact Profile, Beck Depression Inventory Primary Care, Symptom Checklist-90, and six Numeric Rating Scales to measure fatigue, pain and physical activity. To test which factors contributed to severe fatigue a logistic regression analysis was performed. In total 23.5% patients were severely fatigued, varying between diagnoses; prostate cancer (14.3%), breast cancer (20.3%), and gastrointestinal cancer (28.1%). Currently lower physical activity (P=0.013), more depressive mood (P=0.014), impaired sleep and rest during the day and night (P=0.045), and fatigue 1 year before diagnosis (P=0.005) contributed to severe fatigue. Relatively large numbers of cancer patients already experience severe fatigue before initiation of treatment, varying between 14-28%. The factors that contributed to severe fatigue at this stage were physical activity, depressive mood, impaired sleep and rest, and fatigue 1 year before diagnosis.

The relationship of fatigue in breast cancer survivors with quality of life and factors to address in psychological interventions: A systematic review.

Severe fatigue occurs in one in four breast cancer survivors (BCS). Quality of life (QOL) and psychological factors are important in fatigue-oriented interventions for BCS, but an up-to-date overview is lacking. The aims of this review were to (i) provide a comprehensive overview of the relationship of fatigue with QOL and factors that can be addressed in psychological interventions for fatigue in BCS and (ii) determine the strength of evidence for these relationships. A systematic literature search was conducted to find studies on fatigue in BCS who had completed curative breast cancer treatment. Fatigue-related factors of 57 eligible studies were extracted and the level of evidence was determined. Factors regarding QOL (ie, general QOL, functioning, work ability, and mental health) had a negative relationship with fatigue (moderate to strong evidence). Target factors for psychological interventions were divided into the subcategories emotional problems, sleep disturbances, physical activity, pain, coping with cancer, dysfunctional cognitions, and social support. Moderate to strong evidence appeared for a relationship of fatigue with depressive symptoms, anxiety, distress, sleep disturbances, lower physical activity levels, pain, difficulties with coping with cancer, and catastrophizing about symptoms. These factors are points of attention for existing and future psychological interventions for fatigue in BCS.

Experience of severe fatigue in long-term survivors of stem cell transplantation.

The literature suggests that cancer survivors with more aggressive treatments are more at risk for postcancer fatigue. In this study, we investigated the prevalence of fatigue after completion of stem cell transplantation (SCT). Furthermore, we studied if medical variables are associated with fatigue and if the model of perpetuating factors of postcancer fatigue derived from previous studies in cancer survivors, without SCT, is applicable in SCT survivors. Ninety-eight patients treated with autologous or allogeneic SCT filled out several questionnaires. Medical characteristics were obtained from the medical charts. All patients had to be in persistent complete remission for at least 1 year. Thirty-five per cent of the patients experienced severe fatigue. The percentage of patients with severe fatigue remained stable during the years after transplantation. Several psychosocial factors, but no medical factors, were associated with fatigue. The model of perpetuating factors appeared to be applicable. Contrary to cancer survivors without SCT, we found no decrease in fatigue complaints during the first years after SCT. Cognitive behaviour therapy (CBT) is a general form of psychotherapy directed at changing condition-related cognitions and behaviours. CBT especially designed for postcancer fatigue, aimed at perpetuating factors, can also be used to manage fatigue in cancer survivors treated with SCT.

Severe fatigue after treatment of ductal carcinoma in situ: A comparison with age-matched breast cancer survivors and healthy controls.

PURPOSE: Severe fatigue after treatment of ductal carcinoma in situ (DCIS) has not been studied before. The current study examined (i) the prevalence of severe fatigue in DCIS patients versus breast cancer survivors (BCS) and healthy controls (HC), (ii) quality of life and functioning of severely versus non-severely fatigued DCIS patients and BCS, and (iii) the association of fatigue with psychosocial and behavioral factors in DCIS patients. METHODS: 89 patients treated for DCIS were matched on age and gender to 67 BCS and 178 HC (ratio 1:1:2). Fatigue was measured with the Fatigue Severity subscale of the Checklist Individual Strength. RESULTS: 23% of DCIS patients, 25% of BCS, and 6% of HC were severely fatigued (DCIS versus HC: p < 0.001). Severely fatigued DCIS patients had a lower quality of life and were more impaired in all domains of functioning than non-severely fatigued DCIS patients. Sleep problems, dysfunctional cognitions regarding fatigue, avoidance of activities, all-or-nothing behavior, perceived lack of social support, DCIS-related coping problems, and fear of future cancer occurrence were related to fatigue. CONCLUSIONS: The prevalence of severe fatigue in DCIS patients was similar to BCS, but higher than in HC. Severely fatigued DCIS patients had a lower quality of life and more functional impairments. The psychosocial and behavioral fatigue-related factors in DCIS patients are known to perpetuate fatigue in BCS. These factors can be targeted in interventions for cancer-related fatigue. Our findings suggest that the same treatment elements might be applicable to severely fatigued DCIS patients.

The course of severe fatigue in disease-free breast cancer patients: a longitudinal study.

BACKGROUND: We investigated whether fatigue is a persistent problem, and whether persistent fatigue is related to former treatment modalities. In addition, we studied the predictors of persistent fatigue. METHODS: At baseline (n=150, mean time since cancer treatment=29 months) patients were asked to fill out several questionnaires on psychological, physical, social, cognitive and behavioral aspects (Ann. Oncol. 2002;13:589-598). During the 2 years after baseline patients were asked to fill out monthly a fatigue questionnaire (CIS-fatigue). Hundred-twenty-one patients completed the study, 10 dropped out and 19 had a disease recurrence. RESULTS: Twenty-four percent of the patients experienced persistent severe fatigue complaints during the 2-year observation period. Persistent fatigue seemed to be related to the duration of former treatment but unrelated to type of surgery, type of adjuvant therapy and time since treatment finished. High anxiety, high impairment in role functioning and low sense of control over fatigue symptoms at baseline were predictors of persistent fatigue. CONCLUSION: Fatigue appears to be a persistent problem for a quarter of a sample of disease-free breast cancer patients during a 2-year period. The predictors of persistent fatigue found in this study can be helpful for the development of interventions to reduce post-treatment fatigue.

Cognitive behaviour therapy for fatigued cancer survivors: long-term follow-up.

An earlier randomised-controlled trial demonstrated the positive effects of cognitive behaviour therapy (CBT), especially designed for fatigued cancer survivors in reducing fatigue, functional impairments and psychological distress. In the current prospective study, we were able to examine the long-term effect of CBT in patients who completed the therapy. Predictors of fatigue severity at follow-up were exploratory investigated. Sixty-eight patients who completed CBT were assessed at pretreatment, post-treatment and at follow-up (mean follow-up 1.9 years (s.d. 1.0), range: 1-4 years). To analyse possible predictors of treatment outcome a linear regression (enter) was carried out. Improvements on fatigue severity, functional impairment and psychological distress after CBT appeared to remain stable during a follow-up period. Patients who were not fatigued anymore at follow-up were not different from a reference group of non-fatigued cancer survivors. The explorative regression analysis showed that fatigue severity, psychological distress and somatic attributions at pretreatment contributed to persistent fatigue severity at follow-up. Cognitive behaviour therapy, especially designed for post-cancer fatigue, is successful in reducing fatigue and functional impairment in cancer survivors. Moreover, these positive effects were maintained at about 2 years after finishing CBT.