No excess fatigue in young adult survivors of childhood cancer

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Abstract

Clinical reports suggest that many survivors of childhood cancer experience fatigue as a long-term effect of their treatment. To investigate this issue further, we assessed the level of fatigue in young adult survivors of childhood cancer. We compared the results with a group of young adults with no history of cancer. The impact of demographic, medical and treatment factors and depressive symptoms on survivors' fatigue was studied. Participants were 416 long-term survivors of childhood cancer (age range 16–49 years, 48% of whom were female) who had completed treatment an average of 15 years previously and 1026 persons (age range 16–53 years, 55% female) with no history of cancer. All participants completed the Multidimensional Fatigue Inventory (MFI-20), a self-report instrument consisting of five scales (general fatigue, physical fatigue, mental fatigue, reduced activity, reduced motivation) and the Center for Epidemiologic Studies Depression Scale (CES-D). Small differences were found in the mean scores for the different dimensions of fatigue between the long-term survivors and controls (range effect sizes −0.34 to 0.34). Women experienced more fatigue than men. Logistic regression revealed that being female and unemployed were the only demographic characteristics explaining the various dimensions of fatigue. With regard to medical and treatment factors, diagnosis and severe late effects/health problems were associated with fatigue. Finally, depression was significantly associated with fatigue on all subscales. Our clinical practice suggests a difference in fatigue in young adult childhood cancer survivors and their peers. This could not be confirmed in this study using the MFI-20. The well known correlation between fatigue and depression was confirmed in our study. Further research is needed to clarify the undoubtedly complex somatic and psychological mechanisms responsible for the development, maintenance and treatment of fatigue in childhood cancer survivors.

Introduction

Since the 1970s, the results from the treatment of children with cancer have significantly improved. Nowadays, the cure rate is approximately 70% and in countries with advanced medical care, 1 in every 1000 young adults are cured [1]. It is well recognised that treatment can be associated with significant adverse late effects, including second malignancies, endocrine abnormalities, cardiac dysfunction, pulmonary disease, hepatic, renal, and gastrointestinal dysfunction, neurocognitive dysfunction and psychological sequelae 2, 3, 4. While these long-term effects are discussed extensively in the literature, there is limited discussion of fatigue as a symptom experienced by survivors of childhood cancer.

Among cancer patients fatigue is a common, debilitating and distressing symptom, due to their illness and/or their treatment 5, 6, 7, 8. While different definitions of cancer-related fatigue have been suggested, most include references to tiredness [9] or weariness, weakness, exhaustion and lack of energy 8, 10. Recent multidimensional conceptualisations of fatigue in adult cancer patients suggest that fatigue is a subjective experience with significant physical (e.g. weakness), behavioural (e.g. alterations in sleep patterns and activity level), cognitive, and affective (e.g. mood disturbance) components 7, 8, 9, 11. Fatigue can have serious adverse effects on quality of life 12, 13, as well as a considerable impact on self-care activities [14].

It has also been reported that some patients experience significant degrees of fatigue long after the conclusion of cancer treatment, even if all known causes have been resolved and the patients are in remission 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31. These studies investigated patients treated for breast cancer, Hodgkin's disease, lymphoma patients and various types of cancer. The mean time elapsed since treatment varied from 9 months to 12 years and percentages of fatigue from 17 to 30% [32].

To our knowledge, no studies in the literature have specifically focused on fatigue in childhood cancer survivors. Wasserman and colleagues [33] reported “easy fatigability” in 5% of 40 survivors of childhood and adolescent Hodgkin's disease. In the study by Kanabar and colleagues [34], four out of 50 survivors who had completed treatment with chemotherapy and/or radiation therapy followed by autologous bone marrow rescue had problems related to a lack of energy. Moe and colleagues [35] found that the somatization score on the General Health Questionnaire with items closely related to fatigue demonstrated a significantly higher score for survivors of acute lymphoblastic leukaemia (ALL) than for the controls. Finally, Zeltzer and colleagues [36] reported no difference between the Profile of Moods State Fatigue subscale score of 552 survivors of childhood ALL and 394 sibling controls. Because no difference in fatigue was found in this population, a further evaluation of risk factors for fatigue was not performed. The above findings contrast to clinical observation and reports of former childhood cancer patients. Results from a former qualitative study performed by us, indicate that fatigue is a serious problem in a subgroup of young adult survivors of childhood cancer and that fatigue affects many aspects of quality of life [37].

However, the symptom of fatigue is not specific for cancer. Fatigue and lack of energy is a prevalent symptom in the general population, and prevalence estimates range from 11 to 45% 38, 39. Fatigue is also a major complaint among attenders of general practices 40, 41, and it is a central symptom in many other diseases, for example, ischaemic heart disease [42] and depression [41]. To interpret the significance of results obtained in follow-up studies involving childhood cancer patients, a comparison should therefore be made with persons without a history of cancer. Some studies indicate that disease-free cancer patients report more fatigue than controls do 15, 18, 19, 21, 22. However, in other studies no differences in fatigue scores were found between cancer patients, following treatment 22 and 9 months before, respectively, and healthy comparisons 17, 20.

Little is known about the role of demographic, medical and former treatment modalities in predicting posttreatment fatigue. Some studies have found higher prevalences or higher mean scores in women 17, 38, 39, 41, 43, 44, whereas others did not find such differences 45, 46. Servaes and colleagues [32] evaluated 16 studies in which the focus was on “off-treatment fatigue”. Most studies found no relationships between present fatigue and former disease- and treatment variables. In two studies, the severity of posttreatment fatigue was related to the extent of treatment. In these studies, former chemotherapy patients (sometimes in combination with radiation therapy and/or hormonal therapy) reported higher levels of fatigue compared with those treated with radiation therapy alone 16, 17, 19, 20, 24.

The relationship between depression and fatigue experienced by cancer survivors has not been systematically studied per se; however, most of the data suggests a positive relationship between depressive symptoms and fatigue 15, 17, 18, 19, 20, 31. The relationship between these two constructs is clearly complex. Fatigue may be the result of a depressed mood [47]. However, the person who continuously perceives his or her energy as insufficient may become depressed. To complicate matters, in cancer, depression and fatigue may co-occur without having a causal relationship, because they can both originate from the same pathology [48].

The aim of the present study was to assess the level of fatigue in young adult survivors of childhood cancer. The severity was compared with that observed in a group of young adults with no history of cancer. Furthermore, the impact of demographic, medical and treatment factors and depressive symptoms on the survivor's fatigue was studied.

Section snippets

Study group

Data were collected from two samples: young adult survivors of childhood cancer (hereafter referred to as the ‘survivors’ group) and a reference group of persons with no history of cancer (hereafter referred to as the ‘comparison’ group).

Characteristics of survivors and comparison group

Information about the demographic and medical characteristics of the survivor group and the comparison group is listed in Table 1. The survivors' age at diagnosis ranged from 0 to 18 years (median 8), the range of the time since completion of therapy was 5 to 33 years (median 15). The median duration of treatment was 16 months (range 0–170 months). The survivors were treated for a variety of cancers. The most frequent diagnoses were leukaemia, non-Hodgkin's lymphoma, Hodgkin's disease and

Discussion

In this study, the level of fatigue among young adult survivors of childhood cancer was compared with a sample of young adults with no history of cancer. In addition, the relationship between the demographic, medical and treatment factors and depression on the survivor's fatigue were examined. The following discussion summarises the main findings, considers the clinical implications, and identifies several directions for future research.

The survivors and the comparison group differed in some

Acknowledgements

The authors would like to thank the survivors and the persons of the comparison group who generously contributed to this study. This work was supported by a grant from the Dutch Cancer Society.

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