Journal of Pain and Symptom Management
Volume 39, Issue 2 , Pages 197-210, February 2010

Fatigue in Gynecological Cancer Patients During and After Anticancer Treatment

  • Gillian Prue, PhD

      Affiliations

    • Institute of Nursing Research, University of Ulster, Newtownabbey, United Kingdom
    • Health and Rehabilitation Sciences Research Institute, University of Ulster, Newtownabbey, United Kingdom
    • Corresponding Author InformationAddress correspondence to: Gillian Prue, PhD, Institute of Nursing Research, University of Ulster, Shore Road, Newtownabbey, Co. Antrim, BT37 0QB, United Kingdom.
    • ,
  • James Allen, PhD

      Affiliations

    • Health and Rehabilitation Sciences Research Institute, University of Ulster, Newtownabbey, United Kingdom
    • ,
  • Jacqueline Gracey, PhD

      Affiliations

    • Health and Rehabilitation Sciences Research Institute, University of Ulster, Newtownabbey, United Kingdom
    • ,
  • Jane Rankin, MSc

      Affiliations

    • Northern Ireland Cancer Centre, Belfast Health and Social Care Trust, Belfast, United Kingdom
    • ,
  • Fiona Cramp, PhD

      Affiliations

    • Department of Allied Health Professions, Faculty of Health and Life Sciences, University of the West of England, Bristol, United Kingdom

Accepted 13 July 2009. published online 08 December 2009.

Article Outline

Abstract 

Context

Research has indicated that individuals with gynecological cancer experience severe fatigue.

Objectives

This longitudinal survey aimed to analyze the fatigue experienced over the course of one year by a gynecological cancer population, to determine if the fatigue was more severe than that reported by females without cancer, and to identify variables associated with cancer-related fatigue (CRF).

Methods

Data were collected over a 12-month period before, during, and after anticancer treatment. Fatigue was assessed using the Multidimensional Fatigue Symptom Inventory-Short Form. Participants with cancer also completed the Rotterdam Symptom Checklist.

Results

Sixty-five cancer patients (mean age = 57.4 years, standard deviation [SD] = 13.9) and 60 control subjects (mean age = 55.4 years, SD = 13.6) participated. Descriptive analysis and repeated measurements modeling indicated that the cancer participants reported worse fatigue than the noncancer individuals before, during, and after anticancer treatment (P < 0.001) and that the level of fatigue in persons with cancer changed with time (P = 0.02). A forward stepwise regression demonstrated that psychological distress level was the only independent predictor of CRF during anticancer treatment (P < 0.00), explaining 44% of the variance in fatigue. After treatment, both psychological distress level (P < 0.00) and physical symptom distress (P = 0.03) were independent predictors of fatigue, accounting for 81% of the variance.

Conclusion

Psychological distress level is an important indicator of CRF in gynecological cancer. Interventions focused on the reduction of psychological distress may help alleviate CRF.

Key Words: Fatigue, neoplasm, gynecological, symptoms, adult

 

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Introduction 

Cancer-related fatigue (CRF) is an almost universal symptom in patients receiving anticancer therapy.1 CRF can have a phenomenal impact on a patient's life2 and can hinder the chance of remission or even cure owing to the direct influence it can have on the individual's desire to continue with treatment.3 Research has indicated that individuals with gynecological cancer experience more severe fatigue than those with other cancer diagnoses.4 In a U.K. multicenter survey of 576 cancer patients with varying diagnoses, half of whom were currently receiving anticancer treatment, more than 50% reported fatigue as their biggest problem.5 Furthermore, a pilot study indicated that fatigue is a significant problem for females with gynecological cancer at various stages of their disease and treatment process.6 It was, therefore, deemed appropriate and necessary to further examine fatigue in gynecological cancer.

A number of methodological limitations have been highlighted in the research to date.7, 8, 9 Three main problems have been emphasized. First, there is a degree of uncertainty surrounding the best approach for CRF assessment, and a variety of self-report measures exist. Many of these measures are single item, which are inadequate to measure fatigue as a multidimensional construct. The most appropriate and valid approach would be to use a multidimensional measure.8 Second, a number of investigations are cross-sectional in design, which has restricted the conclusions that can be drawn with regard to fatigue as an ongoing symptom. A more methodologically sound approach is to undertake a longitudinal survey to enable fatigue to be charted accurately over time. Finally, fatigue is a common complaint among the general population that must be taken into consideration when reporting the prevalence of symptoms among cancer patients.9

Theoretical Framework 

The fatigue model used as the conceptual framework for the study was the Winningham Psychobiological-Entropy Model (PEM). The PEM describes fatigue as an “energy deficit” and suggests variables that could contribute to the development and persistence of the condition.10 This model correlates fatigue, the disease, any antineoplastic treatment, any other symptoms, activity, and functional status.11 The model suggests that fatigue is not only a primary symptom of cancer but can also occur as a secondary symptom, as a result of the individual's response to other symptoms, including psychological symptoms.12 For this study, the PEM was used to identify the appropriate variables to be examined and measured, specifically fatigue, symptom experience, activity level, and tumor- and treatment-related variables, such as tumor site and stage and treatment received.

Aims 

The study aimed to answer three questions. First, do individuals with gynecological cancer experience a more severe fatigue than matched noncancer volunteers? Second, does the profile of fatigue in gynecological cancer change over time and, if so, in what way? Finally, which variables (as identified by the PEM) are associated with CRF before, during, and after anticancer treatment, and which are associated with more severe fatigue in gynecological cancer?

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Methods 

A multiple point, prospective, longitudinal survey was implemented involving gynecological cancer patients from the Belfast City Hospital (BCH), Southampton General Hospital (SGH), and United Bristol Healthcare Trust (UBHT). Ethical approval was obtained from the Central Office of Research Ethics Committees (January 2005). The cancer participants were identified and recruited through their consultant at an outpatient review appointment at either the chemotherapy clinic or radiotherapy planning clinic before they commenced anticancer treatment. The nonprobability sampling technique of consecutive convenience sampling was used; hence, every available individual with a diagnosis of gynecological cancer attending the BCH, SGH, and UBHT and who met the inclusion criteria was approached. This has been described as the best approach for nonrandom sampling.13

The study sample included cancer subjects who were newly diagnosed with any gynecological cancer having no treatment except surgery for their disease to date and with no previous diagnosis of cancer. They had to be fully informed of their diagnosis, had to be 18 years or older, had to be English speaking, and should have provided informed consent. Individuals attending a clinical psychologist or psychiatrist, with cognitive impairment or incompetence, with a chronic disease in which fatigue was a prominent symptom, or with a serious underlying medical condition, were excluded. Written informed consent was obtained from each participant on enrollment. Cancer patients completed three questionnaires that collected data on 1) fatigue, 2) symptom experience and activity level, and 3) demographics and disease-related information.

Fatigue 

The fatigue questionnaire used for the study was the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF). The 30-item MFSI-SF has five subscales: general (GF), physical (PF), emotional (EF), and mental fatigue (MF), and vigor (V). The respondent indicates the extent to which he or she has experienced each symptom during the preceding week (0 = not at all; 4 = extremely).14 Ratings are summed to obtain scores for each of the subscales detailed previously. In addition, a total fatigue (TF) score can be generated by summing the four fatigue subscales and subtracting the vigor subscale.14

Symptom Experience and Activity Level 

The Rotterdam Symptom Checklist (RSCL) was used to provide a measure of other symptoms experienced and the activity level. This is a 30-item, cancer-specific tool that assesses four domains: physical symptom distress, psychological distress, overall valuation of life, and activity level over the past week on a 5-point Likert scale.15 According to the PEM, activity level is an important variable in the development and persistence of CRF; thus, it was considered to be an essential factor to measure in the longitudinal survey. For this reason, the RSCL was chosen, as it provides an indication of not only symptom experience but also activity level. Its use would reduce participant burden by minimizing the number of questionnaires to be used in the longitudinal survey. Despite assessing a number of domains, the RSCL takes only eight minutes to complete,15 and therefore, it was anticipated that its completion would not prove too burdensome for participants.

Demographics and Disease/Treatment-Related Information 

Information on age, marital status, number of dependents, employment status, and normal activity levels was obtained. Relevant medical data, such as tumor site and stage, and information on anticancer treatment received were obtained from medical records.

Data were collected over a 12-month period. This commenced after surgical management, if indicated, before the initiation of any antineoplastic treatment. A baseline point postsurgery was decided on after a feasibility study, where it became apparent that an attempt to recruit patients before surgery would be fruitless, as patients at that time were either unaware of their diagnosis or not emotionally fit to undertake such a study. During the treatment phase, it was unknown exactly how the participants' fatigue would behave. As the chemotherapy cycles were administered either weekly or every three weeks and radiotherapy lasted approximately five to six weeks, it was felt most appropriate to invite participants to complete the MFSI-SF weekly based on each participant's own weekly treatment schedule. It was expected that some cancer participants would receive treatment for a period up to six months, and it was felt to be unrealistic to expect the subjects to complete the MFSI-SF every week for this time period. Therefore, a cutoff point of 12 weeks was decided on for weekly questionnaire completion. Once a participant had completed treatment or reached the 12-week cutoff point, they moved on to monthly completion of the MFSI-SF until the 12-month endpoint. The RSCL was completed by the cancer participants on a monthly basis for the 12 months. The RSCL was completed monthly and not weekly, as it was felt that weekly completion of the RSCL in addition to the MFSI-SF would be too burdensome for a fatigued individual.

Data for comparison purposes were collected from a group of age-matched females, with no history of cancer. Participants in the noncancer group were recruited by means of a peer nomination process.16, 17 This process was chosen because it has been demonstrated in the literature to be a successful method of recruiting a group of healthy volunteers who are similar demographically to the cancer participants.17, 18, 19 The process involved the cancer subject nominating a suitable friend or relative, who was not her primary carer, to participate.16, 17 Once nominated and informed of the study by the person with cancer, the potential recruit was contacted by telephone to obtain consent to participate. When the cancer subject could not nominate a suitable match within one month of her own recruitment, a control was assigned to her from a list of eligible volunteers created before the commencement of the survey. This list was devised as a result of an e-mail circulated among University of Ulster staff requesting suitable volunteers. Friends and family of the research team were also invited to participate. This was to ensure that a diverse list with respect to age and occupation was available. This approach has been used in previous research and has been shown to be an adequate method of recruitment.20, 21 The included noncancer females were 18 years or older and were within five years of their matched cancer subject. They had to be English speaking and had to have provided fully informed written consent. The exclusion criteria were as for the cancer participants; in addition, the cancer participant's primary carer was excluded.

The noncancer comparison group was required to complete the initial demographic questionnaire and the MFSI-SF. The fatigue questionnaire was completed on a monthly basis for the 12-month duration. Any individual who did not wish to participate or withdrew was invited to score her fatigue verbally on a numerical rating scale1, 2, 3, 4, 5, 6, 7, 8, 9, 10 (NRS-F) as a one off record.

Statistical Analysis 

Data analysis was performed using the Statistical Package for the Social Sciences (SPSS) Version 11 for Windows (SPSS Inc., Chicago, IL). Repeated measurements modeling (RMM) was conducted to address the first two aims of the study: to determine whether or not females with gynecological cancer had more severe fatigue than those with no history of cancer and to examine the change in fatigue in those with gynecological cancer with time. RMM computes estimated marginal means of the dependent variable that show the effect being studied without the error, not the actual observed means.22 The RMM was chosen as it can be used to describe the temporal changes of a dependent variable in a data set with missing data, and it is capable of treating time as a categorical variable or a continuous variable.23

To address the final aim of the study to examine the variables associated with fatigue in gynecological cancer and identify those associated with more severe CRF, a forward stepwise regression with fatigue as the dependent variable was conducted. Initially, a univariate analysis was undertaken to identify the individual predictors of the dependent variable. Independent variables included were tumor related, treatment related, and demographic. Those that were identified as significant were entered into a forward stepwise regression with baseline TF as the dependent variable. Independent variables were entered and removed until the independent variables that remained in the model were all significant in the presence of each other.

This analysis was conducted three times using baseline TF, Month 2 TF (during treatment), and Month 12 TF (end of follow-up) as the dependent variables to determine if the variables associated with CRF differed before, during, and after anticancer treatment.

To detect selection bias, a univariate analysis (t-test) was used to compare the difference in NRS-F scores in those who agreed to participate and those who did not and for those who withdrew and those who completed the study.

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Results 

Participants 

Over the course of 12 months, 92 individuals with gynecological cancer were identified as being eligible to participate. Twenty-seven of the 92 declined involvement. There was no significant difference in NRS-F scores for participants (mean = 4.13, standard deviation [SD] = 2.49) and nonparticipants (mean = 3.44, SD = 3.65; t = 0.886, P = 0.38). Over the same time frame, 60 females with no history of cancer were recruited.

The demographic characteristics of the 65 participants with gynecological cancer and the 60 noncancer females are summarized in Table 1. The mean age of the cancer group was 57.4 years (SD = 13.9), ranging from 23 to 86 years. Most of the cancer participants were married (n = 35, 54%); not working (n = 57, 88%), with 28 (49%) citing their cancer as their reason for not working; and had a low activity level (n = 46, 71%). Regarding the noncancer group, the mean age of this cohort was 55.4 years (SD = 13.6), ranging from 24 to 86 years. Most of them were married (n = 39, 65%), currently working (n = 38, 63%), and had a subjectively low activity level (n = 34, 57%). There was no significant difference in age (P = 0.43) or marital status (P = 0.26) of those who had cancer and those who did not have cancer (P = 0.43).

Table 1. Cancer and Noncancer Participant Demographics
DemographicsCancer (n)Noncancer (n)
Total number of participants6560

Age, years
Mean (SD)57.38 (13.85)55.41 (13.60)

Marital status
Married3539
Living with partner13
Single133
Divorced24
Widowed129
Unknown22

Employment status
Working638
Not working5720
Unknown22

Reason for not working
Because of illness28—
Not because of illness28—
Unknown2—

Activity level
Low4634
Moderate1113
High24
Unknown4a3b

Have activity levels changed since diagnosis?
Increased4—
Decreased50—
Stayed the same8—
Unknown1a—

aTotals 63, as two participants did not consider themselves to be active people.

bDoes not total 60, as six participants did not consider themselves to be active people.

Medical oncology data are summarized in Table 2. The most common malignancy was ovarian cancer (n = 35, 54%), with most tumors being Stage 1 (n = 27, 42%). The sample was heterogeneous regarding antineoplastic treatment received. There was no significant difference in fatigue between those who had undergone surgery before baseline (mean = 7.00, SD = 15.81) and those who had not undergone surgery before baseline (mean = 9.57, SD = 19.97; t = −0.394, P = 0.70).

Table 2. Gynecological Cancer Oncology Data
Oncology Datan
Total number of participants65

Tumor type
Ovarian35
Endometrial16
Cervix7
Uterus1
Ovarian and uterine1
Endometrial and ovarian3
Vulva1
Fallopian tube1

Tumor stage
127
210
318
44
Unknown6

Did patient have surgery?
Yes56
No8
Unknown1

Treatment
Chemotherapy5
Radiotherapy1
Chemotherapy and radiotherapy3
Surgery and chemotherapy34
Surgery and radiotherapy16
Surgery, chemotherapy, and radiotherapy6

Chemotherapy regime
Paclitaxel/carboplatin28
Carboplatin9
Carbocockcroft2
Cisplatin/5FU1
5FU2
Weekly cisplatin (short course of chemotherapy)4
Unknown2

Number of chemotherapy cycles
11
22
42
52
640
Unknown1

Radiotherapy dose
45 Gy; 23 fractionation5
50.4 Gy; 28 fractionation3
45 Gy; 25 fractionation15
60 Gy; 33 fractionation1
Unknown2

Duration of radiotherapy, weeks
31
4.52
513
5.52
67
6.51

Completion Rates 

Of the 65 individuals with gynecological cancer who agreed to participate, 15 withdrew over the course of the 12 months. The most common reasons given were that they no longer wished to participate because they had finished treatment (n = 5), and disease progression (n = 7). A further 25 failed to complete the final 12-month questionnaire. Of this 25, eight had died, six had disease progression, and two had been admitted to hospital. Consequently, only 25 individuals completed the final questionnaire. A comparison of the final NRS-F of those who completed the study and the last available NRS-F of those who dropped out indicated that there was no significant difference in NRS-F scores between those who completed (mean = 4.57, SD = 2.12) and those who did not (mean = 5.64, SD = 2.41; t = −1.82, P = 0.07). Forty-two of the 60 healthy volunteers completed the study.

Do Individuals with Cancer Have a Higher Level of Fatigue Than Noncancer Females? 

The monthly TF scores for the cancer and noncancer participants are presented in Table 3. Descriptively, the scores for the noncancer participants were much lower than those reported by the individuals with gynecological cancer, indicating that the females with gynecological cancer suffered a higher level of fatigue. This was reflected statistically through the RMM. The RMM concluded that there was a significant difference in GF, PF, EF, MF, V, and TF scores between those with cancer and those without, with those who had cancer having significantly higher fatigue (P < 0.001).

Table 3. Cancer and Noncancer Participants' Monthly TF Scores
CancerNoncancer
TF ScoresTF Mean (SD)TF Mean (SD)
Baseline7.30 (16.03)−1.21 (10.69)
Month 116.91 (22.40)0.44 (13.97)
Month 215.89 (23.62)−0.63 (13.09)
Month 314.85 (21.77)−0.17 (13.78)
Month 412.34 (24.94)0.13 (14.06)
Month 510.60 (22.67)0.65 (15.36)
Month 67.79 (17.58)−0.58 (14.51)
Month 78.03 (19.55)−3.04 (12.14)
Month 87.26 (19.29)−2.06 (13.75)
Month 95.70 (19.55)0.12 (16.05)
Month 102.96 (17.74)−0.63 (14.33)
Month 116.52 (19.09)0.19 (13.64)

How Does Fatigue in Gynecological Cancer Change with Time? 

The change in CRF over time is summarized in Fig. 1. The level of GF and PF peaked during treatment and returned to approximately baseline level by the 12-month endpoint. The level of EF declined with time. The level of MF remained relatively stable. TF peaked during treatment and gradually declined after anticancer treatment. The first and last TF measurements were similar. The RMM validated this finding statistically. With GF (P = 0.038) and PF (P < 0.00), time was significant as a factor, which indicated that there were peaks and/or troughs in fatigue with time. Time was significant as a covariate for EF and TF (P = 0.03 and 0.02, respectively), which was indicative of a linear downward trend, that is, an improvement in fatigue levels with time. The level of both MF and V remained constant at all time points.

As a heterogeneous sample with regard to anticancer treatment was recruited, it was possible to compare descriptively the impact of treatment received on the pattern of fatigue during and after therapy. During chemotherapy, TF peaked at the time of each infusion (Fig. 2a). However, during radiotherapy, there was a gradual increase in the level of CRF with time (Fig. 2b). After treatment, in both chemotherapy and radiotherapy, a drop in the level of TF was noted.

Which Variables Are Associated with Cancer-Related Fatigue Before, During, and After Anticancer Treatment? 

Before Anticancer Treatment 

The independent variables included in the univariate analysis were as follows: demographics; disease- and treatment-related variables; and indications of baseline psychological distress level, baseline physical symptom distress level, baseline overall valuation of life, and baseline activity level, as measured by the RSCL. Significant variables were subsequently included in a forward stepwise regression with baseline TF as the dependent variable. These were baseline psychological distress level (t = 7.83, P < 0.00), baseline overall valuation of life (t = 6.62, P < 0.00), baseline physical symptom distress level (t = 8.15, P < 0.00), and baseline activity level (t = 2.21, P = 0.03). Following the forward stepwise regression, baseline psychological distress level, baseline physical symptom distress level, and baseline overall valuation of life were revealed as the three independent predictors of baseline TF, explaining 68% (adjusted r2) of the variance.

During Anticancer Treatment 

The independent variables considered in the univariate analysis were as follows: baseline TF, demographics, disease- and treatment-related variables, and indications of Month 2 psychological distress level, Month 2 physical symptom distress level, Month 2 overall valuation of life, and Month 2 activity level as measured by the RSCL. The variables that were significant and thus included in the forward stepwise regression were baseline fatigue (t = 3.78, P < 0.00), Month 2 psychological distress level (t = 6.19, P < 0.00), Month 2 overall valuation of life (t = 3.26, P < 0.00), Month 2 physical symptom distress level (t = 3.30, P < 0.00), and Month 2 activity level (t = 2.08, P = 0.04). Following the forward stepwise regression, Month 2 psychological distress level as measured by the RSCL was the only independent predictor of Month 2 TF, explaining 44% (adjusted r2) of the variance.

After Anticancer Treatment 

The independent variables considered in the univariate analysis were as follows: baseline TF, demographics, disease- and treatment-related variables, and indications of Month 12 psychological distress level, Month 12 physical symptom distress level, Month 12 overall valuation of life, and Month 12 activity level as measured by the RSCL. The variables entered into the forward stepwise regression were baseline TF (t = 3.24, P < 0.00), Month 12 psychological distress level (t = 8.33, P < 0.00), Month 12 overall valuation of life (t = 4.20, P < 0.00), and Month 12 physical symptom distress level (t = 6.17, P < 0.00). Following the forward stepwise regression, Month 12 psychological distress level and Month 12 physical symptom distress level were the independent predictors of Month 12 TF, explaining 81% (adjusted r2) of the variance.

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Discussion 

A longitudinal survey accumulating fatigue data from a group of newly diagnosed gynecological cancer patients before, during, and after anticancer treatment was conducted. The methodology permitted the investigation of the pattern of fatigue both during and after treatment and facilitated comparison of this fatigue with that reported by females with no history of cancer. Without this comparison, it would be unknown what proportion of the fatigue experienced by the individuals with cancer was a result of having cancer and receiving cancer treatment.

Do Individuals with Cancer Have a Higher Level of Fatigue Than Noncancer Females? 

The gynecological cancer participants included in the study had more severe fatigue than the noncancer females before, during, and after anticancer treatment. These findings are reflected in the CRF literature.19, 24, 25, 26, 27, 28, 29, 30 The raised baseline fatigue could be attributed to undergoing surgery.19 However, in this sample, there was no significant difference in the level of fatigue reported by those who had undergone surgery and those who had not. The increase in baseline fatigue could be because of the effects of the tumor itself and the psychological impact of receiving a cancer diagnosis.19 To investigate this issue further, it would be useful to assess fatigue levels before surgery. However, as demonstrated in an earlier pilot study, it is difficult to obtain fatigue scores at this stage, as the individual may not be emotionally fit to participate and may be unaware of her diagnosis.6

How Does Fatigue in Gynecological Cancer Change with Time? 

Banthia et al. recommended that it was important to identify which dimensions of CRF were problematic and more sensitive to change over time to effectively guide treatment interventions.31 In this survey, the level of general and physical fatigue reported by the cancer participants changed over the course of the 12 months and was highest during anticancer treatment. In comparison, the MF subscale remained at a constant level over the course of the 12 months. The different profiles of the MFSI-SF subscales over time underscore the importance of measuring the different dimensions of fatigue, as it would appear that each dimension behaves differently over time. A number of studies have reported that CRF increases significantly during treatment,24, 32, 33, 34, 35, 36, 37, 38, 39 but this is not verified by all investigations.40, 41, 42 This inconsistency could be the result of methodological flaws, such as fatigue not being assessed frequently enough to detect fluctuations.

Which Variables Are Associated with Cancer-Related Fatigue Before, During, and After Treatment? 

Before commencement of anticancer treatment, the regression analysis suggested that surgery and tumor-related variables, such as tumor site and stage, were not related to fatigue. Increased psychological distress level was associated with raised baseline fatigue, which is likely to be a result of receiving a diagnosis of cancer and feeling anxious about starting anticancer treatment. Reduced quality of life and a raised physical symptom distress level also were related to fatigue, indicating that suffering from other symptoms leads to an increase in fatigue. During treatment, psychological distress level was the sole independent predictor of CRF. A strong relationship has been noted in the literature between CRF during treatment and anxiety and depression.5, 9, 16, 24, 37, 38, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55 In this longitudinal survey, demographic variables and factors associated with the tumor and anticancer treatment were unrelated to the fatigue. A large body of evidence exists to support the finding that CRF during anticancer treatment is not associated with tumor stage16, 17, 32, 34, 39, 44, 48, 56, 57, 58 or any demographic16, 17, 24, 32, 37, 43, 44, 48, 50, 52, 54, 55, 56, 57, 58, 59 or treatment-related variables.16, 17, 18, 32, 34, 39, 42, 43, 48, 52, 56, 57, 58, 59

After treatment, psychological distress level was again an independent predictor of fatigue, as was physical symptom distress level. Tumor- and treatment-related variables were not associated with the persistence of fatigue after anticancer therapy. Previous research also has indicated strong relationships between anxiety and depression and CRF in cancer survivors.20, 24, 26, 27, 29, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74 In agreement with the current findings, most of the previous researches have found no relationship between diagnosis and fatigue.19, 20, 29, 30, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 75, 76, 77 Studies investigating CRF in survivors of cancer have also reported no association between treatment-related variables and fatigue,19, 26, 27, 28, 29, 30, 60, 61, 62, 63, 64, 65, 66, 69, 70, 71, 72, 74, 76, 77, 78, 79 which concurs with the current findings. These findings, in conjunction with the outcome of this longitudinal survey, lead to the conclusion that, in cancer survivors, psychological factors are related to CRF, whereas tumor and type of treatment are not.

Psychological distress level was an independent predictor of fatigue before, during, and after anticancer treatment. Throughout this survey, fatigue has been demonstrated as a symptom of cancer, but it is also reported to be a symptom of depressive disorders.80 The symptoms associated with fatigue are similar to those reported by individuals with depression.81 As a result of this, some items included in an assessment scale for CRF would be incorporated into an assessment scale for psychological impairment. It would be acceptable to assume some level of correlation between the two phenomena, and thus, they would appear related in a regression analysis. A relationship between depression and fatigue has frequently been reported. However, there is evidence that CRF may increase during treatment with no concurrent increase in anxiety and depression.44, 82 Furthermore, Jacobsen et al.80 reported a correlation between fatigue and depression that remained even when items included in both assessment scales were removed. This indicated that a relationship might exist that was not because of the overlap in the two assessment scales.80 The causal relationship between the two phenomena remains to be determined. In an attempt to combat the overlap in measurement, a clinical syndrome approach has been suggested as a more appropriate method of assessing CRF.80, 81

Limitations 

The problem of attrition affected the study, as only 25 of the original 65 cancer participants completed the final assessment. However, the comparison of the fatigue levels, as measured by the NRS-F, of those who completed the study and those who dropped out demonstrated that there was no difference in the level of fatigue between the two at the time of withdrawal. It cannot, however, be presumed that the level of fatigue reported by those who withdrew stayed at a similar level as those who completed the study. Every attempt was made to minimize the attrition rate; however, because of the nature of the disease and the severity of treatment, dropouts, as in many studies, were inevitable.83

Not all cancer participants had a matched control, largely because of the fact that they were elderly participants, and it was difficult to source a match that met the inclusion/exclusion criteria. However, the fact that more than 90% of cancer participants were matched would indicate that the results are more than likely the true outcome.

The data on CRF were only recorded up to 12 months from baseline. It is, therefore, unknown how long CRF persists in survivors of gynecological cancer. Future research should focus on investigating this fatigue persistence.

Although the change in MFSI-SF scores over time was statistically significant, the increase in fatigue may not have been substantial enough to have a negative impact on quality of life. Including the noncancer group of females provided an indication that the fatigue was worse than the “norm,” but a more suitable method for determining clinical significance is the use of minimal clinically important differences (MCIDs).84 Unfortunately, there are currently no MCIDs available for the MFSI-SF. The National Comprehensive Cancer Network (NCCN) recommendations for the management of CRF suggest that anyone scoring 4 or more on an NRS should have their fatigue investigated further.1 In this survey, the overall mean NRS score for all of the cancer participants was 4.6. This would suggest that most of the gynecological cancer patients in this study had fatigue that was severe enough to warrant further investigation.

Implications for Practice 

This study suggests that all females with a diagnosis of gynecological cancer, regardless of their tumor site, tumor stage, or treatment regimen, should be informed that they may experience CRF during their treatment and that it may persist for many months once their treatment is complete.85 This would enable the individual to provide fully informed consent to treatments, such as chemotherapy. Research also has suggested that if an individual is told what to expect, they are not as likely to experience the stress of unexpected problems.86

To fulfill the National Institute of Health and Clinical Excellence recommendations that all patients should be offered optimal symptom control if they require it,87 individuals with gynecological cancer should be screened for high fatigue levels before commencement of anticancer treatment. This screening should become a routine part of each clinical visit for the duration of the anticancer treatment and continue at regular intervals once treatment is complete. Frequent assessment at each clinical visit will help to ensure that appropriate interventions are made available to the patient as soon as they require them.

The outcomes of this longitudinal survey demonstrate that the various dimensions of CRF behave differently. This confirms that the ideal approach for the measurement of CRF is with a multidimensional assessment tool. Clinically, however, it is acknowledged that, because of time restrictions, it may not be possible for each individual to complete a lengthy multidimensional fatigue questionnaire. Where this is not achievable, it is suggested that individuals are screened with a single-item scale, such as an NRS-F, to identify those that require more complete CRF assessment. The subsequent in-depth assessment with those persons who have shown to be suffering from a raised level of fatigue should measure all the dimensions of CRF with a multidimensional assessment tool. This comprehensive assessment should identify the source of the fatigue, thereby ensuring that it is managed appropriately. This recommendation has been discussed further by the NCCN.1

The apparent association between fatigue in individuals with gynecological cancer and psychological distress would indicate that managing actual and potential psychological distress may preempt a degree of fatigue. A number of pharmacological and nonpharmacological approaches aimed at alleviating psychological distress have been discussed in the literature. Pharmacological interventions, such as antidepressants, have been used for fatigue that is related to depression, but there is currently minimal research evidence to support their use.88, 89 Nonpharmacological interventions, for example, exercise, support groups, psychotherapy, relaxation therapy, cognitive behavioral therapy, and distraction techniques, such as reading and listening to music, have also been investigated and shown to be beneficial.89, 90, 91, 92 A recent Cochrane review, however, concluded that there was limited evidence that psychosocial interventions are effective in reducing fatigue.93

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Conclusions 

Fatigue is a problem in gynecological cancer patients both during and after anticancer treatment. Fatigue should, therefore, be assessed before (to establish baseline fatigue levels), during, and after anticancer treatment, and routinely after end of treatment. From this longitudinal survey, it would appear that tumor- and treatment-related variables are not associated with CRF in gynecological cancer. Individuals with gynecological cancer should be reassured that the experience of severe fatigue is not indicative of disease progression.1 They should be offered education regarding effective fatigue management, for example, energy conservation techniques, such as delegation, pacing, and prioritizing, as recommended by the NCCN.1 The strong association presented between CRF and psychological distress in gynecological cancer is an important finding and indicates that interventions focused on the amelioration of psychological distress may reduce the perception of CRF in this patient population. Future research should focus on the investigation of the optimum management strategy for CRF in gynecological cancer.

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Acknowledgments 

Statistical advice was provided by Dr. Ian Bradbury.

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References 

  1. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: cancer-related fatigue v.1. 2006 [online]. Available from http://www.nccn.org/professionals/physician_gls/PDF/fatigue.pdf/. Accessed October 10, 2006.
  2. Flechtner H, Bottomley A. Fatigue assessment in cancer clinical trials. Expert Rev Pharmacoecon Outcomes Res. 2002;2:67–76
  3. Morrow GR, Andrews PLR, Hickok JT, Roscoe JA, Matteson S. Fatigue associated with cancer and its treatment. Support Care Cancer. 2002;10:389–398
  4. Payne JK. The trajectory of fatigue in adult patients with breast and ovarian cancer receiving chemotherapy. Oncol Nurs Forum. 2002;29:1334–1340
  5. Stone P, Richardson A, Ream E, et al. Cancer-related fatigue: inevitable, unimportant and untreatable? Results of a multi-centre patient survey. Ann Oncol. 2000;11:971–975
  6. Prue G, Rankin J, Cramp F, Allen J, Gracey J. Fatigue in gynaecological cancer patients: a pilot study. Support Care Cancer. 2006;14:78–83
  7. Sadler IJ, Jacobsen PB. Progress in understanding fatigue associated with breast cancer treatment. Cancer Invest. 2001;19:723–731
  8. Jacobsen PB, Thors CL. Fatigue in the radiation therapy patient: current management and investigations. Semin Radiat Oncol. 2003;13:372–380
  9. Stone P, Richards M, A'Hern R, Hardy J. Fatigue in patients with cancers of the breast and prostate undergoing radical radiotherapy. J Pain Symptom Manage. 2001;22:1007–1015
  10. Winningham ML, Nail LM, Barton-Burke M, et al. Fatigue and the cancer experience: the state of the knowledge. Oncol Nurs Forum. 1994;21:23–36
  11. Nail LM, Winningham ML. Fatigue. In:  Groenwald SL,  Hansen Frogge M,  Goodman M,  Yarbo CH editor. Cancer nursing: Principles and practice. 3rd ed. London, United Kingdom: Jones and Bartlett; 1993;p. 609–617
  12. Winningham ML. How exercise mitigates fatigue: implications for people receiving cancer therapy. In:  Johnson RM editors. The biotherapy of cancer V. Pittsburgh, PA: Oncology Nursing Press; 1992;p. 16–20
  13. Endacott R, Botti M. Clinical research 3: sample selection. Intensive Crit Care Nurs. 2005;21:51–55
  14. Stein KD, Jacobsen PB, Blanchard CM, Thors C. Further validation of the multidimensional fatigue symptom inventory-short form. J Pain Symptom Manage. 2004;27:14–23
  15. De Haes JCJM, Olschewski M, Fayers P, et al. Measuring the quality of life of cancer patients with the Rotterdam Symptom Check List: A manual. Groningen, The Netherlands: Northern Center for Healthcare Research, University of Groningen; 1996;
  16. Hann DM, Garovoy N, Finkelstein B, et al. Fatigue and quality of life in breast cancer patients undergoing autologous stem cell transplantation: a longitudinal comparative study. J Pain Symptom Manage. 1999;17:311–319
  17. Jacobsen PB, Hann DM, Azzarello LM, et al. Fatigue in women receiving adjuvant chemotherapy for breast cancer: characteristics, course, and correlates. J Pain Symptom Manage. 1999;18:233–242
  18. Tchen N, Juffs HG, Downie FP, et al. Cognitive function, fatigue, and menopausal symptoms in women receiving adjuvant chemotherapy for breast cancer. J Clin Oncol. 2003;22:4175–4183
  19. Mar Fan HG, Houede-Tchen N, Yi Q, et al. Fatigue, menopausal symptoms, and cognitive function in women after adjuvant chemotherapy for breast cancer: 1- and 2- year follow-up of a prospective controlled study. J Clin Oncol. 2005;23:8025–8032
  20. Brown DJ, McMillan DC, Milroy R. The correlation between fatigue, physical function, the systemic inflammatory response, and psychological distress in patients with advanced lung cancer. Cancer. 2005;103:377–382
  21. Payne JK, Piper BF, Rabinowitz I, Zimmerman MB. Biomarkers, fatigue, sleep, and depressive symptoms in women with breast cancer: a pilot study. Oncol Nurs Forum. 2006;33:775–783
  22. Statistical Package for the Social Sciences (SPSS). Available from: http://www.spss.com/. Accessed June 2009.
  23. Krueger C, Tian L. A comparison of the general linear model and repeated measures ANOVA using a dataset with multiple missing data points. Biol Res Nurs. 2004;6:151–157
  24. Fleer J, Sleijfer DT, Hoekstra HJ, Tuinman MA, Hoekstra-Weebers JE. Prevalence, changes in and correlates of fatigue in the first year after diagnosis of testicular cancer. Anticancer Res. 2005;25:4647–4653
  25. Stone PC, Abdul-Wahab A, Gibson JS, Wright RJ, Andrews PL. Fatigue in cancer patients is not related to changes in oxyhaemoglobin dissociation. Support Care Cancer. 2005;13:854–858
  26. Servaes P, Verhagen C, Bleijenberg G. Determinants of chronic fatigue in disease-free breast cancer patients: a cross-sectional study. Ann Oncol. 2002;13:589–593
  27. Fossa SD, Dahl AA, Loge JH. Fatigue, anxiety, and depression in long-term survivors of testicular cancer. J Clin Oncol. 2003;21:1249–1254
  28. Hjermstad MJ, Fossa SD, Oldervoll L, et al. Fatigue in long-term Hodgkin's disease survivors: a follow-up study. J Clin Oncol. 2005;23:6587–6595
  29. Ng AK, Li S, Recklitis C, et al. A comparison between long-term survivors of Hodgkin's disease and their siblings on fatigue level and factors predicting for increased fatigue. Ann Oncol. 2005;16:1949–1955
  30. Hjermstad MJ, Oldervoll L, Fossa SD, et al. Quality of life in long-term Hodgkin's disease survivors with chronic fatigue. Eur J Cancer. 2006;42:327–333
  31. Banthia R, Malcarne VL, Roesch SC, et al. Correspondence between daily and weekly fatigue reports in breast cancer survivors. J Behav Med. 2006;29:269–279
  32. Poirier P. The relationship of sick leave benefits, employment patterns, and individual characteristics to radiation therapy-related fatigue. Oncol Nurs Forum. 2006;33:593–601
  33. Ahlberg K, Ekman T, Gaston-Johansson F. The experience of fatigue, other symptoms and global quality of life during radiotherapy for uterine cancer. Int J Nurs Stud. 2005;42:377–386
  34. Liu L, Marler MR, Parker BA, et al. The relationship between fatigue and light exposure during chemotherapy. Support Care Cancer. 2005;13:1010–1017
  35. Mills PJ, Parker B, Dimsdale JE, Sadler GR, Ancoli-Israel S. The relationship between fatigue and quality of life and inflammation during anthracycline-based chemotherapy in breast cancer. Biol Psychol. 2005;69:85–96
  36. Monga U, Kerrigan AJ, Thornby J, Monga TN, Zimmermann KP. Longitudinal study of quality of life in patients with localized prostate cancer undergoing radiotherapy. J Rehabil Res Dev. 2005;42:391–400
  37. Shun S-C, Lai Y-H, Jing T-T, et al. Fatigue patterns and correlates in male liver cancer patients receiving transcatheter hepatic arterial chemoembolization. Support Care Cancer. 2005;13:311–317
  38. Byar KL, Berger AM, Bakken SL, Cetak MA. Impact of adjuvant breast cancer chemotherapy on fatigue, other symptoms and quality of life. Oncol Nurs Forum. 2006;33:E18–E26
  39. Lavdaniti M, Patiraki E, Dafani U, et al. Prospective assessment of fatigue and health status in Greek patients with breast cancer undergoing adjuvant radiotherapy. Oncol Nurs Forum. 2006;33:603–610
  40. Geinitz H, Zimmermann FB, Stoll P, et al. Fatigue, serum cytokine levels and blood cell counts during radiotherapy of patients with breast cancer. Int J Radiat Oncol Biol Phys. 2001;51:691–698
  41. Jacobsen PB, Garland LL, Booth-Jones M, et al. Relationship of hemoglobin levels to fatigue and cognitive functioning among cancer patients receiving chemotherapy. J Pain Symptom Manage. 2004;28:7–18
  42. De Jong N, Candel MJJM, Schouten HC, Abu-Saad HH, Courtens AM. Course of mental fatigue and motivation in breast cancer patients receiving adjuvant chemotherapy. Ann Oncol. 2005;16:372–382
  43. Smets EMA, Visser MRM, Willems-Groot AFMN, et al. Fatigue and radiotherapy: (A) experience in patients undergoing treatment. Br J Cancer. 1998;78:899–906
  44. Stone P, Hardy J, Huddart R, A'Hern R, Richards M. Fatigue in patients with prostate cancer receiving hormone therapy. Eur J Cancer. 2000;36:1134–1141
  45. Ahsberg E, Furst CJ. Dimensions of fatigue during radiotherapy: an application of the Swedish Occupational Fatigue Inventory (SOFI) on cancer patients. Acta Oncol. 2001;40:37–43
  46. Kallich JD, Tchekmedyian NS, Damiano AM, et al. Psychological outcomes associated with anaemia-related fatigue in cancer patients. Oncology. 2002;16:117–124
  47. Roscoe JA, Morrow GR, Hickok JT, et al. Temporal interrelationships among fatigue, circadian rhythm and depression in breast cancer patients undergoing chemotherapy treatment. Support Care Cancer. 2002;10:329–336
  48. Haghighat S, Akbari ME, Holakouei K, Rahimi A, Montazeri A. Factors predicting fatigue in breast cancer patients. Support Care Cancer. 2003;11:533–538
  49. Hwang SS, Chang VT, Rue M, Kasimis B. Multidimensional independent predictors of cancer-related fatigue. J Pain Symptom Manage. 2003;26:604–614
  50. Respini D, Jacobsen PB, Thors C, Tralongo P, Balducci L. The prevalence and correlates of fatigue in older cancer patients. Crit Rev Oncol Hematol. 2003;47:273–279
  51. Ahlberg K, Ekman T, Wallgren A, Gaston-Johansson F. Fatigue, psychological distress, coping and quality of life in patients with uterine cancer. J Adv Nurs. 2004;45:205–213
  52. Geinitz H, Zimmermann FB, Thamm R, et al. Fatigue in patients with adjuvant radiation therapy for breast cancer: long-term follow-up. J Cancer Res Clin Oncol. 2004;130:327–333
  53. Ahlberg K, Ekman T, Gaston-Johansson F. Levels of fatigue compared to levels of cytokines and haemoglobin during pelvic radiotherapy: a pilot study. Biol Res Nurs. 2004;5:203–210
  54. Porock D, Beshears B, Hinton P, Anderson C. Nutritional, functional and emotional characteristics related to fatigue in patients during and after biochemotherapy. Oncol Nurs Forum. 2005;32:661–667
  55. Munch TN, Stromgren AS, Pedersen L, et al. Multidimensional measurement of fatigue in advanced cancer patients in palliative care: an application of the multidimensional fatigue inventory. J Pain Symptom Manage. 2006;31:533–541
  56. Donovan KA, Jacobsen PB, Andrykowski MA, et al. Course of fatigue in women receiving chemotherapy and/or radiotherapy for early stage breast cancer. J Pain Symptom Manage. 2004;28:373–380
  57. Jacobsen PB, Andrykowski MA, Thors CL. Relationship of catastrophizing to fatigue among women receiving treatment for breast cancer. J Consult Clin Psychol. 2004;72:355–361
  58. Wratten C, Kilmurray J, Nash S, et al. Fatigue during breast radiotherapy and its relationship to biological factors. Int J Radiat Oncol Biol Phys. 2004;59:160–167
  59. Can G, Durna Z, Aydiner A. Assessment of fatigue in and care needs of Turkish women with breast cancer. Cancer Nurs. 2004;27:153–161
  60. Hann DM, Jacobsen PB, Martin SC, et al. Fatigue in women treated with bone marrow transplantation for breast cancer: a comparison with women with no history of cancer. Support Care Cancer. 1997;5:44–52
  61. Andrykowski MA, Curran SL, Lightner R. Off-treatment fatigue in breast cancer survivors: a controlled comparison. J Behav Med. 1998;21:1–18
  62. Broeckel JA, Jacobsen PB, Horton J, Balducci L, Lyman GH. Characteristics and correlates of fatigue after adjuvant chemotherapy for breast cancer. J Clin Oncol. 1998;16:1689–1696
  63. Hann DM, Jacobsen PB, Martin S, Azzarello L, Greenberg H. Fatigue and quality of life following radiotherapy for breast cancer: a comparative study. J Clin Psychol Med Settings. 1998;5:19–33
  64. Smets EMA, Visser MRM, Willems-Groot AFMN, et al. Fatigue and radiotherapy: (B) experience in patients 9 months following treatment. Br J Cancer. 1998;78:907–912
  65. Loge JH, Abrahamsen AF, Ekeberg O, Kaasa S. Hodgkin's disease survivors more fatigued than the general population. J Clin Oncol. 1999;17:253–261
  66. Howell SJ, Radford JA, Smets EMA, Shalet SM. Fatigue, sexual function and mood following treatment for haematological malignancy: the impact of mild Leydig cell dysfunction. Br J Cancer. 2000;82:789–793
  67. Loge JH, Abrahamsen AF, Ekeberg O, Kaasa S. Fatigue and psychiatric morbidity among Hodgkin's disease survivors. J Pain Symptom Manage. 2000;19:91–99
  68. Okuyama T, Akechi T, Kugaya A, et al. Factors correlated with fatigue in disease-free breast cancer patients: an application of the Cancer Fatigue Scale. Support Care Cancer. 2000;8:215–222
  69. Servaes P, van der Werf S, Prins J, Verhagen S, Bleijenberg G. Fatigue in disease-free cancer patients compared with fatigue in chronic fatigue syndrome. Support Care Cancer. 2000;9:11–17
  70. Bower JE, Ganz PA, Aziz N, Fahey JL. Fatigue and proinflammatory cytokine activity in breast cancer survivors. Psychosom Med. 2002;64:604–611
  71. Barstch HH, Weis J, Moser MT. Cancer-related fatigue in patients attending oncological rehabilitation programs: prevalence, patterns and predictors. Onkologie. 2003;26:51–57
  72. Dimeo F, Schmittel A, Fietz T. Physical performance, depression, immune status and fatigue in patients with haematological malignancies after treatment. Ann Oncol. 2004;15:1237–1242
  73. Gelinas C, Fillion L. Factors related to persistent fatigue following completion of breast cancer treatment. Oncol Nurs Forum. 2004;31:269–278
  74. Young KE, White CA. The prevalence and moderators of fatigue in people who have been successfully treated for cancer. J Psychosom Res. 2006;60:29–38
  75. Servaes P, Verhagen C, Schreuder B, Veth RPH, Bleijenberg G. Fatigue after treatment for malignant and benign bone and soft tissue tumors. J Pain Symptom Manage. 2003;26:1113–1122
  76. Knobel H, Loge JH, Nordoy T, et al. High level of fatigue in lymphoma patients treated with high dose therapy. J Pain Symptom Manage. 2000;19:446–456
  77. Okuyama T, Tanaka K, Akechi T, et al. Fatigue in ambulatory patients with advanced lung cancer: prevalence, correlated factors, and screening. J Pain Symptom Manage. 2001;22:554–564
  78. Sugawara Y, Akechi T, Okuyama T, et al. Occurrence of fatigue and associated factors in disease-free breast cancer patients without depression. Support Care Cancer. 2005;13:628–636
  79. Knobel H, Loge JH, Lund MB, et al. Late medical complications and fatigue in Hodgkin's disease survivors. J Clin Oncol. 2001;19:3226–3233
  80. Jacobsen PB, Donovan KA, Weitzner MA. Distinguishing fatigue and depression in patients with cancer. Semin Clin Neuropsychiatry. 2003;8:229–240
  81. Reuter K, Harter M. The concepts of fatigue and depression in cancer. Eur J Cancer Care. 2004;13:127–134
  82. Visser MRM, Smets EMA. Fatigue, depression and quality of life in cancer patients: how are they related?. Support Care Cancer. 1998;6:101–108
  83. Wisniewski SR, Leon AC, Otto MW, Trivedi MH. Prevention of missing data in clinical research studies. Biol Psychiatry. 2006;59:997–1000
  84. Cella D, Hahn EA, Dineen K. Meaningful change in cancer-specific quality of life scores: difference between improvement and worsening. Qual Life Res. 2002;11:201–221
  85. Ahlberg K, Ekman T, Gaston-Johansson F. Fatigue, psychological distress, coping resources, and functional status during radiotherapy for uterine cancer. Oncol Nurs Forum. 2005;32:633–640
  86. Ahlberg K, Ekman T, Gaston-Johansson F, Mock V. Assessment and management of cancer-related fatigue in adults. Lancet. 2003;362:640–650
  87. National Institute for Health and Clinical Excellence. Guidance on cancer services: Improving supportive and palliative care for adults with cancer: The manual. London, United Kingdom: National Institute for Clinical Excellence; 2004;
  88. Stasi R, Abriani L, Beccaglia P, Terzoli E, Amadori S. Cancer-related fatigue: evolving concepts in evaluation and treatment. Cancer. 2003;98:1786–1801
  89. Mock V. Evidence-based treatment for cancer-related fatigue. J Natl Cancer Inst Monogr. 2004;32:112–118
  90. Manzullo E, Liu W, Escalante C. Treatment for cancer-related fatigue: an update. Expert Rev Anticancer Ther. 2003;3:99–106
  91. Lawrence DP, Kupelnick B, Miller K, Devine D, Lau J. Evidence report on the occurrence, assessment, and treatment of fatigue in cancer patients. J Natl Cancer Inst Monogr. 2004;32:40–50
  92. Ream E, Richardson A, Alexander-Dann C. Supportive intervention for fatigue in patients undergoing chemotherapy: a randomised controlled trial. J Pain Symptom Manage. 2006;31:148–161
  93. Goedendorp MM, Gielissen MFM, Verhagen CAHHVM, Bleijenberg G. Psychosocial interventions for reducing fatigue during cancer treatment in adults. Cochrane Database Syst Rev. 2009;(Issue 1):

 Financial support was provided by the Northern Ireland Cancer Recognized Research Group.

PII: S0885-3924(09)00844-6

doi:10.1016/j.jpainsymman.2009.06.011

Journal of Pain and Symptom Management
Volume 39, Issue 2 , Pages 197-210, February 2010

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