Fatigue in cancer treatment - assessment, course and etiology
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Aims. The major aims of the present work were to increase the understanding of cancer related fatigue with respect to assessment methodology, frequency and possible etiology. The validity of two fatigue instruments was evaluated and compared in order to enable an evaluation of the fatigue assessments in different patient cohorts. Secondly, the frequency and course of fatigue during curative cancer treatment, as well as the frequency of fatigue in cancer survivors were investigated in order to demonstrate the symptom burden during treatment and after ending curative treatment. The tertiary aim was to explore possible etiologic factors that may explain fatigue in cancer survivors. Background: The long term survival of cancer patients has risen dramatically during the last decades. Several follow-up studies have shown that the long term side effects of curative treatment are more pronounced than first expected. During the last years much more attention have been given to the need for systematic follow up and assessment of long term effects on objective and subjective health after curative treatment. Fatigue is reported to be one of the most frequent and disturbing symptom in cancer patients in general, and is experienced by cancer patients at all stages of their disease. Fatigue is also observed as a subjective late effect in cancer survivors. The prevalence of chronic fatigue (elevated fatigue levels > 6 months) is 2-3 times higher in Hodgkin´s Disease Survivors (HDS) than in the general population. Despite the high prevalence of fatigue, the etiology and causes of the symptom is not clear. Most studies of fatigue in cancer patients are cross sectional and of limited value when exploring the frequency and contributing factors to the etiology. Since fatigue is a subjective phenomenon, it is agreed that it should be measured by patients self assessment. Several instruments are developed for fatigue measurement, both uni - and multi -dimensional. As in research in general, the validity of the subjective outcomes are of crucial importance. Methods: Five different studies were conducted in order to meet the major aims. Two aspects of the validity of the fatigue scale in the health related quality of life (HRQoL) questionnaire EORTC QLQ-C30 were addressed, the dimensionality of the fatigue scale (FA) and the sensitivity of the FA. The instruments were evaluated in two different patient cohorts, a palliative patients cohort and a cohort of hematooncological malignancy patients after curative treatment. A longitudinal follow up study of HRQoL and fatigue in lymphoma and leukaemia patient before, during and until three to five years post treatment with high dose chemotherapy and stem cell support was conducted in order to evaluate the trajectory of fatigue and HRQoL during and after treatment, and to compare symptom and function levels between the cohorts. The relationship between fatigue and late effects of pulmonary, cardiac and endocrine function as well as brain MRI abnormalities were investigated in order to explore possible etiologic factors of fatigue in lymphoma survivors after transplant therapy and in HDS after standard treatment. Findings: The EORTC QLQ-C30 fatigue scale is one - dimensional measuring physical fatigue. A floor/ceiling effect illustrated a poor sensitivity of the scale in patients with lowest respectively highest fatigue level. According to the longitudinal study lymphoma patients report more fatigue, poorer functioning and poorer quality of life as compared to leukaemia patients three to five years after post transplant and as compared to the general population. This pattern was also observed at baseline before transplant. Pulmonary dysfunction was associated with fatigue in HDS whereas cardiac and thyroid dysfunction as late effects after curative treatment did not explain high levels of fatigue in HDS. A questionable association between fatigue and thyroid and gonadal dysfunction were observed. Neither cytokines nor brain white matter lesions were associated with fatigue in HDS. Conclusion: The fatigue subscale, FA, of the EORTC QLQ C30 is measuring physical fatigue. The ability of FA to discriminate between patients with different levels of fatigue is poorer as compared to a fatigue specific instrument (Fatigue Questionnaire). The validation of instruments in different cohorts with differences in frequency and intensity of symptoms is important. As illustrated in earlier studies, fatigue is a prevalent symptom in lymphoma patients before and after treatment indicating that fatigue may be related to the lymphoma disease. Pulmonary late effects was predictor of fatigue in HDS, and the explanatory value of cardiac and endocrine late effects need further investigation. Follow-up program that extend 15-20 years post treatment should be considered in order to explore the effect of clinical relevant medical late effects on subjective health including fatigue.
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