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.
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.
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.
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.
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.
•Fatigue in breast cancer survivors is related to a lower quality of life•Fatigue has a negative relationship with functioning, work ability and pain•Strong evidence exists for a relationship of fatigue with psychological factors•Most evidence appears for sleep, emotions, coping, activity and catastrophizing•The identified factors should be addressed in interventions for fatigue
Early identification of palliative patients is challenging. The Surprise Question (SQ1; Would I be surprised if this patient were to die within 12 months?) is widely used to identify palliative ...patients. However, its predictive value is low. Therefore, we added a second question (SQ2) to SQ1: 'Would I be surprised if this patient is still alive after 12 months?' We studied the accuracy of this double surprise question (DSQ) in a general practice.
We performed a prospective cohort study with retrospective medical record review in a general practice in the eastern part of the Netherlands. Two general practitioners (GPs) answered both questions for all 292 patients aged ≥75 years (mean age 84 years). Primary outcome was 1-year death, secondary outcomes were aspects of palliative care.
SQ1 was answered with 'no' for 161/292 patients. Of these, SQ2 was answered with 'yes' in 22 patients. Within 12 months 26 patients died, of whom 24 had been identified with SQ1 (sensitivity: 92%, specificity: 49%). Ten of them were also identified with SQ2 (sensitivity: 42%, specificity: 91%). The latter group had more contacts with their GP and more palliative care aspects were discussed.
The DSQ appears a feasible and easy applicable screening tool in general practice. It is highly effective in predicting patients in high need for palliative care and using it helps to discriminate between patients with different life expectancies and palliative care needs. Further research is necessary to confirm the findings of this study.
Cancer-related fatigue remains a prevalent and burdensome symptom experienced by patients with advanced cancer. Our aim was to assess the effects of cognitive behavioral therapy (CBT) or graded ...exercise therapy (GET) on fatigue in patients with advanced cancer during treatment with palliative intent.
A randomized controlled trial was conducted from 1 January 2013 to 1 September 2017. Adult patients with locally advanced or metastatic cancer who reported severe fatigue during treatment Checklist Individual Strength, subscale fatigue severity (CIS-fatigue) ≥35 were accrued across nine centers in The Netherlands. Patients were randomly assigned to either 12 weeks of CBT or GET, or usual care (1 : 1: 1, computer-generated sequence). Primary outcome was CIS-fatigue at 14 weeks. Secondary outcomes included fatigue measured with the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ-C30), quality of life, emotional functioning, physical functioning, and functional impairments at baseline, 14, 18, and 26 weeks.
Among 134 participants randomized, the mean age was 63 (standard deviation 9) years and 77 (57%) were women. Common diagnoses included: breast (41%), colorectal (28%), and prostate cancer (17%). A total of 126 participants completed assessment at 14 weeks. Compared with usual care, CBT significantly reduced fatigue difference −7.2, 97.5% confidence interval (CI) −12.7 to −1.7; P = 0.003, d = 0.7, whereas GET did not (−4.7, 97.5% CI −10.2 to 0.9; P = 0.057, d = 0.4). CBT significantly reduced EORTC-QLQ-C30 fatigue (−13.1, 95% CI −22.1 to −4.0; P = 0.005) and improved quality of life (10.2, 95% CI 2.4 to 17.9; P = 0.011) and physical functioning (7.1, 95% CI 0.5 to 13.7; P = 0.036) compared with usual care. Improvement in emotional functioning and decrease in functional impairments failed to reach significance. GET did not improve secondary outcomes compared with usual care.
Among advanced cancer patients with severe fatigue during treatment, a CBT intervention was more effective than usual care for reducing fatigue. Following GET, patients reported lower fatigue, but results were not significant, probably due to a smaller sample size and lower adherence than anticipated.
Netherlands National Trial Register, identifier: NTR3812.
•Cognitive behavioral therapy (CBT) reduced fatigue in severely fatigued patients receiving cancer treatment with palliative intent.•CBT aimed at fatigue also improved quality of life and physical functioning.•Positive effects of CBT were sustained for 3 months after the intervention.•CBT is recommended as a supportive care approach for patients with advanced cancer and severe cancer-related fatigue.
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.
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.
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.
Dutch Trial Registry--NTR4309.
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.
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.
Tumor markers that are related to hypoxia, proliferation, DNA damage repair and stem cell-ness, have a prognostic value in advanced stage HNSCC patients when assessed individually. Here we aimed to ...evaluate and validate this in a multifactorial context and assess interrelation and the combined role of these biological factors in determining chemo-radiotherapy response in HPV-negative advanced HNSCC.
RNA sequencing data of pre-treatment biopsy material from 197 HPV-negative advanced stage HNSCC patients treated with definitive chemoradiotherapy was analyzed. Biological parameter scores were assigned to patient samples using previously generated and described gene expression signatures. Locoregional control rates were used to assess the role of these biological parameters in radiation response and compared to distant metastasis data. Biological factors were ranked according to their clinical impact using bootstrapping methods and multivariate Cox regression analyses that included clinical variables. Multivariate Cox regression analyses comprising all biological variables were used to define their relative role among all factors when combined.
Only few biomarker scores correlate with each other, underscoring their independence. The different biological factors do not correlate or cluster, except for the two stem cell markers CD44 and SLC3A2 (
= 0.4,
< 0.001) and acute hypoxia prediction scores which correlated with T-cell infiltration score, CD8
T cell abundance and proliferation scores (
= 0.52, 0.56, and 0.6, respectively with
< 0.001). Locoregional control association analyses revealed that chronic (Hazard Ratio (HR) = 3.9) and acute hypoxia (HR = 1.9), followed by stem cell-ness (CD44/SLC3A2; HR = 2.2/2.3), were the strongest and most robust determinants of radiation response. Furthermore, multivariable analysis, considering other biological and clinical factors, reveal a significant role for EGFR expression (HR = 2.9,
< 0.05) and T-cell infiltration (CD8
T-cells: HR = 2.2,
< 0.05; CD8
T-cells/Treg: HR = 2.6,
< 0.01) signatures in locoregional control of chemoradiotherapy-treated HNSCC.
Tumor acute and chronic hypoxia, stem cell-ness, and CD8
T-cell parameters are relevant and largely independent biological factors that together contribute to locoregional control. The combined analyses illustrate the additive value of multifactorial analyses and support a role for EGFR expression analysis and immune cell markers in addition to previously validated biomarkers. This external validation underscores the relevance of biological factors in determining chemoradiotherapy outcome in HNSCC.
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.
Head and neck squamous cell carcinoma (HNSCC) is characterized by the frequent manifestation of DNA crosslink repair defects. We established novel expression-based DNA repair defect markers to ...determine the clinical impact of such repair defects. Using hypersensitivity to the DNA crosslinking agents, mitomycin C and olaparib, as proxies for functional DNA repair defects in a panel of 25 HNSCC cell lines, we applied machine learning to define gene expression models that predict repair defects. The expression profiles established predicted hypersensitivity to DNA-damaging agents and were associated with mutations in crosslink repair genes, as well as downregulation of DNA damage response and repair genes, in two independent datasets. The prognostic value of the repair defect prediction profiles was assessed in two retrospective cohorts with a total of 180 patients with advanced HPV-negative HNSCC, who were treated with cisplatin-based chemoradiotherapy. DNA repair defects, as predicted by the profiles, were associated with poor outcome in both patient cohorts. The poor prognosis association was particularly strong in normoxic tumor samples and was linked to an increased risk of distant metastasis.
, only crosslink repair-defective HNSCC cell lines are highly migratory and invasive. This phenotype could also be induced in cells by inhibiting rad51 in repair competent and reduced by DNA-PK inhibition. In conclusion, DNA crosslink repair prediction expression profiles reveal a poor prognosis association in HNSCC. SIGNIFICANCE: This study uses innovative machine learning-based approaches to derive models that predict the effect of DNA repair defects on treatment outcome in HNSCC.
http://cancerres.aacrjournals.org/content/canres/79/21/5597/F1.large.jpg.
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