Fatigue-Related Cognitive-Behavioral Factors in Survivors of Childhood Cancer: Comparison with Chronic Fatigue Syndrome and Survivors of Adult-Onset Cancer

Abstract

Purpose:

Cancer-related fatigue is a burdensome late effect of cancer treatment. A pilot study showed the effectiveness of cognitive-behavioral therapy (CBT) in fatigued survivors of childhood cancer (CCS). The aim of this study is to investigate whether the six cognitive-behavioral factors that are addressed during CBT differ in CCS compared with patients with chronic fatigue syndrome (CFS) and survivors of adult-onset cancer (ACS). Levels of self-esteem, optimism, and depressive symptoms, variables that are also related to fatigue, were also compared between groups.

Methods:

Retrospective analyses were performed on 34 CCS (ages 11–42 years), 102 patients with CFS, and 95 ACS who were referred for evaluation of severe fatigue. Fatigue severity, possible cognitive-behavioral fatigue maintaining factors, depressive symptoms, self-esteem, and optimism were assessed using questionnaires and actigraphy.

Results:

No significant differences were found in the factors coping with the experience of having had cancer, fear of cancer recurrence, physical activity, and in levels of self-esteem and optimism. CCS attributed their fatigue significantly more often to psychosocial causes and reported fewer problems in sleep/rest compared with patients with CFS. Compared with ACS, CCS reported significantly more social support, more problems in sleep/rest, and more depressive symptoms.

Conclusions:

There is substantial overlap in cognitive-behavioral factors that can maintain fatigue between CCS and CFS patients or ACS. Also differences were found regarding attribution of fatigue, the sleep/rest pattern, social support, and depressive symptoms that might have clinical implications when CBT for fatigue is provided to CCS.

Introduction

Survival rates of childhood cancer are steadily increasing. About 80% of children diagnosed with cancer survive 5 years postdiagnosis.¹ Therefore, attention is frequently focused on late effects of cancer and its treatment. Cancer-related fatigue, defined as “a distressing, persistent, subjective sense of physical, emotional and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning,” is a commonly described symptom in cancer survivors, and can have a negative impact on quality of life.^2–5

An effective treatment for fatigue is cognitive-behavioral therapy (CBT).^6–8 According to the cognitive-behavioral model of fatigue in survivors of adult-onset cancer (ACS), cancer and its treatment trigger fatigue, whereas cognitions and behavior can maintain fatigue.⁶ Treatment with CBT focuses on the maintaining factors for fatigue. The cognitive-behavioral model of fatigue discerns six fatigue maintaining factors in ACS: inadequate coping with the experience of cancer, excessive fear of cancer recurrence, dysfunctional beliefs related to fatigue, sleep disturbances, deregulated and lower level of physical activity, and perceived lack of social support.^2,6,9 Based on this model, CBT, aimed at changing these cognitions and behaviors, has been proven to be an effective treatment for fatigue in ACS. In a recent pilot study, we showed that CBT was also effective in severely fatigued survivors of childhood cancer (CCS).¹⁰

The model underlying CBT for fatigue is based on the cognitive-behavioral model of fatigue in patients with chronic fatigue syndrome (CFS).¹¹ Adjustments were made to address specific issues related to cancer, that is, fear of disease recurrence, coping with the experience of having had cancer and perceived lack of social support.¹² Although CBT addresses all six fatigue maintaining factors, the therapy is tailored to the maintaining factors that are relevant for an individual patient.⁶

Apart from the six maintaining factors addressed by CBT, depression, low optimism, and low self-esteem have also been associated with fatigue in cancer survivors.^2,3,13,14 CCS differ from patients with CFS and ACS as treatment for cancer during childhood or adolescence might disrupt the development into adulthood, which could negatively influence emotional functioning, optimism, and self-esteem.¹⁵ These psychosocial variables could be additional maintaining factors in CCS.

In this study, we investigated similarities and differences in fatigue-related cognitive-behavioral factors between severely fatigued CCS and patients with CFS and severely fatigued ACS. The results of this study can aid in the tailoring of treatment of fatigue in CCS using CBT.

Materials and Methods

Study population

Fatigue severity was assessed in all three study populations with the fatigue severity subscale of the checklist individual strength.¹⁶ All patients included in the study scored 35 of higher, being the validated cutoff point for severe fatigue.¹⁷

Survivors of childhood cancer

The data of the CCS population originate from a pilot study investigating the efficacy of CBT in this group.¹⁰ CCS were referred for evaluation and treatment of fatigue to a tertiary treatment center for chronic fatigue at the Radboud University Medical Centre.¹⁰ Inclusion criteria were CCS of any age at referral, diagnosed with cancer before the age of 18 years, free of cancer at time of referral, a follow-up from cancer diagnosis of at least 5 years, and suffering from severe fatigue. Before the referral for the treatment of fatigue, the referring physician screened the participant for medical conditions that could explain fatigue, such as hypothyroidism, cardiovascular, or pulmonary disorders.

CFS patients

An age- and gender-matched noncancer control group of CFS patients originates from a study investigating the role of partners during CBT for fatigue (adults; age ≥18 years at referral)¹⁸ and from the database of a tertiary treatment center for fatigue (adolescent; age <18 years at referral). CFS is characterized by persistent medically unexplained fatigue that causes disability in daily life.¹⁹ Inclusion criteria were referred for therapy to a tertiary treatment center for chronic fatigue, meeting criteria for CFS according to the U.S. Centers for Disease Control case definition revised in 2003.²⁰ CFS patients were matched to the CCS based on gender and age at start of therapy with three controls per CCS.

Survivors of adult-onset cancer

Data from ACS were from an intervention study that evaluated the efficacy of CBT. Patients were recruited from outpatient oncology clinics.⁶ Similar to the CCS, all participants were screened by the referring physician for medical conditions that could explain fatigue, before the start of therapy. Inclusion criteria were age at onset of cancer was 18 years or older, younger than 65 years at the start of the study, severely fatigued, no current psychological or psychiatric treatment, and no evidence of disease recurrence. Furthermore, patients completed cancer treatment at least 1 year before inclusion.

Study methods

The assessment procedure for both ACS and CCS included the completion of multiple scales and questionnaires to assess the six cognitive-behavioral factors as well as depressive symptoms, self-esteem, and optimism. CFS patients filled in the same assessment battery with the exception of the questionnaires related to cancer-specific factors, self-esteem, and optimism. Measures were not adapted for participants under the age of 18 years. Information about demographics (age at intake, gender, and educational level) and cancer and treatment-related characteristics (including cancer diagnosis, treatment, and age at cancer diagnosis) was retrieved from medical records.

Measures

Assessment of cognitive-behavioral maintaining factors for fatigue

Coping with the experience of cancer was measured with the Dutch version of the impact of event scale, consisting of two subscales avoidance and intrusion.²¹ Higher scores indicate more post-traumatic stress symptoms in relation to the cancer diagnosis and treatment.

Fear of cancer recurrence was measured using two items of the cancer acceptance scale.¹³ One item asks directly about fear of cancer recurrence (“I am worried about a cancer recurrence”). The other item focuses on overall health (“I am anxious about my health”). Both items are scored on a 4-point scale, ranging from “not at all applicable” to “very applicable.”

Fatigue-related beliefs were measured with the fatigue self-efficacy scale (SES) and the causal attribution list (CAL). The SES assesses self-efficacy with respect to fatigue. A higher score reflects a higher self-efficacy.⁹ The CAL measures attributions of fatigue and has two subscales assessing physical and psychological attributions, respectively.²² A higher score reflects stronger attributions.

Sleep disturbances were measured with the sickness impact profile (SIP) sleep/rest subscale and the Symptom CheckList-90 (SCL-90) sleep subscale. The SCL-90 sleep subscale measures sleep quality and a higher score indicates lower quality of sleep.^23,24 The SIP sleep/rest subscale measures problems with sleep and rest during the day and night, with a higher score indicating a more impaired sleep.²⁵

Physical activity was measured with an actometer, as described in detail by van der Werf et al.²⁶ An actometer is a motion-sensing device, worn around the ankle, which registers and quantifies physical activity. The device is worn for 14 consecutive days and registers the number of accelerations every 5 minutes. From the data that were collected, an average daily physical activity score can be calculated. A higher score represents a higher level of physical activity. For reference purposes, the average daily physical activity score of healthy Dutch individuals (mean age 40.1 years, range 19–63) is 91 (SD 25).²⁶

Social support was measured with a shortened version of the van Sonderen social support inventory (SSI).²⁷ This questionnaire measures perceived social support (SSI-I), negative interactions (SSI-N), and discrepancy between perceived and desired social support (SSI-D). A higher score on the SSI-I reflects more support, a higher score on the SSI-N reflects more negative interactions, and a higher score on the SSI-D reflects a higher perceived lack of support.

Assessment of other psychosocial outcomes

Self-esteem was measured using the Rosenberg self-esteem scale, higher scores represent higher self-esteem.²⁸ Optimism was measured using the life orientation test, with a higher score reflecting more optimism.²⁹ Depressive symptoms were measured using the Beck depression inventory–primary care. A cutoff score of 4 or higher is indicative of a clinically significant level of depressive symptoms.³⁰

Statistical analysis

Scores obtained of the factors under study at intake were compared. Descriptive statistics were used to present demographic characteristics per group. To compare the factors of interest between groups, an unadjusted regression analysis was performed with the factor under study as dependent variable and the factor group (CCS vs. ACS or CCS vs. CFS patients) as independent variable. Subsequently, an adjusted regression analysis was performed to correct for differences in demographic and cancer treatment-related variables between ACS and CCS. The variables gender, time since diagnosis, and treatment with chemotherapy only (yes/no) were included as covariates in adjusted analysis. The analysis for the comparison between CCS and CFS patients was not adjusted, because these groups were already matched on age and gender. When appropriate, an additional analysis was performed to further explore differences that were found. If <5% of all the data were missing, missing data were not imputed and statistical analyses were performed based on available case analysis. Otherwise, missing data were imputed. To investigate the influence of time since diagnosis, which was different for CCS and ACS, a sensitivity analysis was performed including only survivors who were at least 5 years from diagnosis. All statistical analyses were performed using SPSS version 22.0.³¹

Results

Demographic and medical characteristics

In total, 34 CCS, 102 CFS patients, and 95 ACS were included in this study. Four CCS were under the age of 18 years at the time of intake (ages 11, 15, 16, and 17 years). Demographic and medical characteristics of the groups are given in Table 1. Female survivors were overrepresented in the CCS group and, as a consequence of matching, also in the CFS group. Compared with ACS, a larger number of CCS were treated with chemotherapy only. Mean fatigue severity score was similar in all groups (45.97 vs. 49.94 vs. 47.41 [range 35–56]).

Table 1.

Demographics and Cancer- and Treatment-Related Characteristics of Study Population

	CCS (n = 34)	CFS patients (n = 102)	ACS (n = 95)^a
Mean age at intake (years)	23.27 (SD 6.97; range 11–42)	24.19 (SD 6.27; range 12–42)	45.60 (SD 9.46; range 21–61)
Mean CIS fatigue score at intake	45.97 (SD 4.68; range 36–52)	49.94 (SD 5.92; range 35–56)	47.41 (SD 6.59; range 35–56)
Gender
Female	25 (73.5%)	75 (73.5%)	48 (50.5%)
Male	9 (26.5%)	27 (26.5%)	47 (49.5%)
Mean Educational level (1 = low to 7 = high)	3.97 (SD 1.78)	4.21 (SD 1.70)	4.33 (SD 1.67)
Mean age at cancer diagnosis (years)	9.73 (SD 4.36; range 0–17)	NA	39.36 (SD 10.23; range 18–59)
Mean time between cancer diagnosis and intake treatment center (years)	13.13 (SD 7.27; range 5–34)	NA	6.24 (SD 5.06; range 1–29)
Diagnosis		NA
Bone tumor	6 (17.6%)		3 (3.2%)
Leukemia	13 (38.2%)		3 (3.2%)
Brain tumor	3 (8.8%)		—^b
Lymphoma	7 (20.6%)		14 (14.7%)
Solid tumor	4 (11.8%)		15 (15.8%)
Testis cancer	—^b		23 (24.2%)
Breast cancer	—^b		30 (31.6%
Other	1 (2.9%)		7 (7.4%)
Treatment		NA
Chemotherapy^c	21 (61.8%)		31 (32.6%)
Radiotherapy^c	1 (2.9%)		11 (11.6%)
Chemotherapy and radiotherapy^c	9 (26.5%)		38 (40%)
Surgery only	3 (8.8%)		15 (15.8%)
Stem cell transplantation	4 (11.8%)		—^b
Disease recurrence	5 (14.7%)	NA	—^d
Second primary tumor	1 (2.9%)	NA	—^b

One patient, in the original study identified as ACS, was transferred to the CCS group, because of age at diagnosis (age 10.8 years).

Not present in study population.

Independent of surgery.

Disease recurrence is exclusion criteria in ACS study.

ACS, survivors of adult-onset cancer; CCS, survivors of childhood cancer; CFS, chronic fatigue syndrome; CIS, checklist individual strength; NA, not applicable; SD, standard deviation.

Comparison between CCS and CFS patients

The results of the comparisons between CCS and CFS patients are given in Table 2. CCS reported significantly less problems on the SIP sleep/rest subscale (107.33 vs. 157.37, p = 0.004). Results from the CAL showed that, compared with patients with CFS, CCS attributed their fatigue more often to psychosocial causes (17.67 vs. 9.57, p ≤ 0.001) and less often to physical causes (8.37 vs. 12.35, p ≤ 0.001). No significant differences were found between CCS and CFS patients on the factors physical activity, social support, and depressive symptoms.

Table 2.

Comparison of Factors of Interest Between CCS and CFS Patients

	CCS (n = 34)	CFS patients (n = 102)	Unadjusted
	Mean score	Mean score	Beta coefficient^a	p
Fatigue-related beliefs
Self-efficacy scale	17.82 (SD 2.79)	17.10 (SD 3.41)	−0.76	0.264
Physical attributions	8.37 (SD 1.74)	12.35 (SD 2.91)	3.98	<0.001
Psychosocial attributions	17.67 (SD 3.60)	9.57 (SD 2.52)	−8.09	<0.001
Sleep disturbances
SIP sleep/rest subscale	107.33 (SD 75.24)	157.37 (SD 86.29)	50.03	0.004
SCL-90 sleep scale	6.00 (SD 3.10)	6.92 (SD 3.45)	0.92	0.185
Physical activity
Average daily physical activity score	71.42 (SD 18.58)	71.77 (SD 18.21)	0.35	0.926
Social support
Perceived social support	21.97 (SD 3.77)	21.41 (SD 4.09)	−0.56	0.498
Negative interactions	11.27 (SD 2.73)	11.81 (SD 3.29)	0.54	0.403
Discrepancies	10.21 (SD 2.04)	10.80 (SD 2.94)	0.59	0.294
	N (%)	N (%)	OR (95% CI)	p
Depressive symptoms	14 (41.2)	46 (45.1)	0.87 (0.39–1.96)	0.735

Bold values denote statistical significance at the p < 0.05 level.

The beta coefficient is for the factor group (CCS vs. CFS patients).

CI, confidence interval; OR, odds ratio; SCL-90, Symptom CheckList-90; SIP, sickness impact profile.

Comparison between CCS and ACS

The results of the comparisons between CCS and ACS are given in Table 3. CCS reported receiving significantly more social support (SSL-I: 21.97 vs. 18.69, p = 0.001), and reported more depressive symptoms (odds ratio = 5.00 [95% confidence interval 1.53–16.38], p = 0.008). CCS also reported more sleep problems on the SIP sleep/rest subscale than ACS (107.33 vs. 66.71, p = 0.005). There were no differences between ACS and CCS in mean scores on the factors coping with the experience of cancer, fear of cancer recurrence, fatigue-related beliefs, physical activity, self-esteem, and optimism. The pattern of results was similar in the sensitivity analysis (Supplementary Table S1).

Table 3.

Comparison of Factors of Interest Between CCS and ACS

			Unadjusted		Adjusted^a
	CCS (n = 34) Mean score^b	ACS (n = 95) Mean score^b	Beta coefficient^c	p	Beta coefficient^c	p
Coping with the experience of cancer
Impact of event scale	8.26 (SD 10.73)	11.24 (SD 11.57)	2.98	0.234	1.16	0.708
Fear of cancer recurrence
CAS: recurrence	1.67 (SD 1.04)	2.22 (SD 0.82)	0.55	0.005	0.40	0.091
CAS: anxious about health	2.37 (SD 0.88)	2.54 (SD 0.76)	0.17	0.334	−0.07	0.758
Fatigue-related beliefs
Self-efficacy scale	17.82 (SD 2.79)	18.26 (SD 2.98)	0.44	0.461	0.86	0.247
Physical attributions	8.37 (SD 1.74)	8.55 (SD 1.87)	0.18	0.659	0.15	0.766
Psychosocial attributions	17.67 (SD 3.60)	16.32 (SD 4.63)	−1.34	0.167	−1.51	0.224
Sleep disturbances
SIP sleep/rest subscale	107.33 (SD 75.24)	66.71 (SD 60.63)	−40.62	0.002	−47.55	0.005
SCL-90 sleep scale	6.00 (SD 3.10)	5.87 (SD 2.88)	−0.13	0.831	−0.84	0.257
Physical activity
Average daily physical activity score	71.42 (SD 18.58)	68.63 (SD 21.28)	−2.79	0.515	−3.77	0.480
Social support
Perceived social support	21.97 (SD 3.77)	18.69 (SD 3.12)	−3.28	<0.001	−2.75	0.001
Negative interactions	11.27 (SD 2.73)	10.26 (SD 2.97)	−1.02	0.088	−1.31	0.078
Discrepancies	10.21 (SD 2.04)	10.94 (SD 3.23)	0.72	0.231	0.89	0.242
Comparison of self-esteem, optimism, and depressive symptoms
Self-esteem	36.55 (SD 7. 25)	39.98 (SD 6.26)	3.43	0.012	2.60	0.128
Optimism	19.03 (SD 4.33)	21.30 (SD 4.92)	2.29	0.024	1.38	0.258
	N (%)	N (%)	OR (95% CI)	p	OR (95% CI)	p
Depressive symptoms	14 (41.2)	15 (15.8)	3.83 (1.58–9.28)	0.003	5.00 (1.53–16.38)	0.008

Bold values denote statistical significance at the p < 0.05 level.

Analyses are adjusted for time since diagnosis, gender, and chemotherapy treatment only.

Mean scores represent unadjusted means.

The beta coefficient is for the factor group (CCS vs. ACS).

CAS, cancer acceptance scale.

Comparison of sleep disturbances between CCS and the other groups

Comparison of CCS with CFS patients as well as ACS, showed a difference on the SIP sleep/rest subscale. As there was no difference on the SCL-90 sleep subscale between groups, an additional comparison was made on individual items of the SIP sleep/rest subscale (Table 4). CCS significantly less often reported the item “I lie down more often during the day in order to rest” compared with CFS patients. Compared with ACS, CCS significantly more often reported the items “I spend much of the day lying down in order to rest” and “I sit during much of the day.” The scores on the other items of the SIP sleep/rest subscale were not significantly different.

Table 4.

Comparison of Individual Items of the SIP Sleep/Rest Subscale Between CCS and CFS Patients and CCS and ACS

	CCS (n = 33)	CFS patients (n = 90)^a	ACS (n = 93)	p-value CCS vs. CFS patients	p-value CCS vs. ACS
I spend much of the day lying down to rest	6 (18.2%)	15 (16.7%)	3 (3.2%)	0.843	0.004
I sit during much of the day	20 (60.6%)	47 (52.2%)	33 (34.7%)	0.408	0.012
I am sleeping or dozing most of the time	1 (3.0%)	11 (12.2%)	2 (2.1%)	0.128	0.776
I lie down more often during the day to rest	10 (30.3%)	51 (56.7%)	26 (27.4%)	0.010	0.798
I sit around half-asleep	2 (6.1%)	14 (15.6%)	1 (1.1%)	0.165	0.107
I sleep less at night, for example, wake up to early, don't fall asleep for a long time, awaken frequently	12 (36.4%)	47 (52.2%)	24 (25.3%)	0.119	0.249
I sleep or nap more during the day	8 (24.2%)	38 (42.2%)	18 (18.9%)	0.068	0.551

Bold values denote statistical significance at the p < 0.05 level.

Numbers indicate how many participants indicated this statement is applicable to me. p-Value of Pearson chi-square analysis.

Only CFS patients aged 18 years and older (n = 90/102) completed SIP sleep/rest questionnaire. Comparison with only CCS (n = 30) and CFS patients (n = 90) aged 18 years and older did not change interpretation of result (i.e., same item was significantly different).

Discussion

CBT for the treatment of fatigue has been proven to be effective in fatigued ACS and in patients with CFS.^6,11 A pilot study by our research group showed a positive effect of CBT for fatigue in CCS, with 70% of the participants reporting clinically significant improvement of fatigue at the end of therapy.¹⁰ CBT comprises six modules and has the advantage that it can be tailored to the specific needs of a patient.⁶ CCS differ from ACS, as they were young and in a different stage of development when they were diagnosed with cancer. CCS differ from patients with CFS in that they have experienced a life-threatening disease. In the presented study, we determined the similarities and differences in cognitive-behavioral factors known to be involved in the maintenance of fatigue and are addressed during CBT between CCS and patients with CFS and ACS. The three study populations were all referred for CBT to a tertiary treatment center with similar criteria for referral, namely being severely fatigued, duration of fatigue of at least 6 months, and no medical explanation for fatigue.

Similarities were found between CCS and ACS in the cognitive-behavioral factors that are specific for cancer survivors (i.e., coping with the experience of having had cancer and fear of cancer recurrence), and between CCS and patient with CFS and ACS in the level of physical activity. In addition, similar levels of self-esteem and optimism were found. This substantial overlap suggests that the same cognitive-behavioral factors that are addressed during CBT in ACS and in patients with CFS are also relevant for therapy in CCS.

There were some differences identified between CCS and the other two groups, that is, in fatigue-related beliefs, sleep disturbances, perceived social support, and level of depressive symptoms.

With regard to fatigue-related beliefs, CCS attributed their fatigue significantly more often to psychosocial factors than patients with CFS who attributed their fatigue more often to physical factors. No differences were found between CCS and ACS. This difference in attributions between cancer survivors and patients with CFS has also been found in previous studies.^22,32,33 Overall, this might suggest that cancer survivors are potentially more positive about referrals for psychosocial interventions for fatigue, like CBT, as it corresponds to their beliefs that psychosocial factors are relevant in the maintenance of fatigue.

CCS reported fewer sleep problems than patients with CFS, but more compared with ACS. More specifically, CCS are less often inclined to lay down during the day to rest compared than patients with CFS, but are more inclined to remain inactive compared with ACS. Sleep disturbances and resting during the day can negatively influence the sleep–wake pattern. Factors related to sleep quality are often found to be associated with fatigue.^2,22,34,35 Regulation of the sleep–wake pattern is an important intervention in CBT for fatigue in both CFS patients and ACS.^2,11 Our results demonstrate that regulation of the sleep–wake pattern is a relevant target for CCS perhaps even more than in ACS.

More perceived social support was reported by CCS than by ACS and no differences in social support were shown between CCS and patients with CFS. In general, perceived lack of social support has been associated with higher fatigue levels. Social support is important in reducing stress and enhance coping in cancer survivors.^22,36,37 Although the results indicate that a lack of social support is less an issue in CCS, it is still important to discuss the content of received social support. Verspaandonk et al. identified that solicitous response of partners or relatives during CBT for fatigue can unintentionally enhance inactivity and result in less improvement in fatigue.³⁸ Solicitous responses of relatives could also exist in CCS and are, therefore, important to address during treatment for fatigue.

A subgroup of participants in all three study populations reported clinically relevant levels of depressive symptoms. However, CCS were significantly more likely to report elevated levels of depressive symptoms than ACS, but not more than CFS patients. Fatigue is associated with depression and depressive symptoms, also in long-term cancer survivors.^3,39–41 Our results suggest that screening for depressive symptoms at intake is relevant to determine whether depression could be the primary diagnosis, or whether the depressive symptoms are a reaction of the patients to their persistent and debilitating fatigue. In the case of the latter, it is to be expected that when fatigue levels are reduced after CBT, depressive symptoms will decrease as well, as were found in several previously published studies.^{6–8,10,11,42} Therefore, it is unlikely that adjustment of the existing CBT protocol for fatigue for CCS with regard to depressive symptoms is needed. However, it might be important to assess levels of depressive symptoms at the end of therapy to investigate whether they did actually diminish in CCS after CBT.

A limitation of this study is that CCS and ACS were recruited differently and with different inclusion criteria. ACS were selected from a randomized controlled trial and completed cancer treatment at least 1 year before inclusion, whereas CCS were consecutively referred patients who were at least 5 years postdiagnosis. No difference in fatigue levels was found between ACS and CCS. Furthermore, the pattern of results in the sensitivity analysis including only survivors who were at least 5 years from diagnosis was the same as in the total sample. Although it is plausible, it is not certain that the cognitive-behavioral factors measured in this study are in fact maintaining factors of fatigue in CCS. Evidence showing these factors as maintaining factors of fatigue originates from research in patients with CFS and ACS.^6,11 Future longitudinal studies have to show whether the factors described in this study are indeed fatigue maintaining factors in CCS.

A strength of this study is the inclusion of two control groups: a noncancer age- and gender-matched comparison group of CFS patients and a comparison group of ACS. In both control groups, CBT is already shown to be an effective therapy to reduce fatigue severity.^6,11

In conclusion, the results of this study suggest that the same cognitive-behavioral factors that are addressed during CBT for fatigue in CFS patients and ACS are also relevant for fatigued CCS. Some differences were found that may have clinical implications when CBT for fatigue is provided in CCS.

Footnotes

Ethical Statement

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

Supplementary Material

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