This is the first cross-sectional study to explore predictors of fatigue and their impact on quality of life in patients with newly diagnosed meningiomas before surgery in China. Our findings indicate that fatigue is a prominent pretreatment symptom in meningioma patients, and the prevalence of severe total fatigue is 23.3%, based on a MFI-20 total score > 60. Furthermore, fatigue among meningioma patients is significantly associated with clinical characteristics (comorbidity, KPS score, headache), psychological problems (anxiety and depression), and sleep quality (sleep disturbance and ESS score).
Studies on fatigue in patients with brain tumors were more focused on gliomas with more aggressive and worse clinical prognosis[8,34-36]. However, as in gliomas, fatigue was frequently reported as a common and troublesome symptom before and after treatment for meningioma patients[9,18,37]. In our study, we conducted a more in-depth research of multidimensional fatigue in patients with newly diagnosed meningiomas. Indeed, among patients with newly diagnosed meningiomas, the prevalence of severe fatigue varied between 11.7% for mental fatigue and 33.3% for general fatigue. In a prior study by van der Linden et al with preoperative data that could be compared with ours the fatigue rate of each dimension was higher than that of our corresponding dimensions. Differences in study design, patient selection, evaluation time point, and definition of severe fatigue may explain the differences in prevalence and hinder meaningful comparison between studies.
Only a limited number of studies have focused on the relationship between comorbidity and fatigue in brain tumor patients. In a prior study, the univariate analysis showed that comorbidity was significantly associated with fatigue in patients with brain tumors undergoing proton beam therapy, but the multivariate analysis did not further prove this relationship. In this study, we found a significant association between comorbidity and total fatigue in meningioma patients. The majority of participants (age > 60 years) have other comorbid conditions that may affect the symptom of fatigue, such as cardiovascular disease and diabetes. It is unclear how comorbidities influence fatigue as these coexisting conditions may share a common pathophysiological pathway or share symptoms resulting in a synergistic symptom experience. Further studies with larger samples are needed to examine the summative and potentiating effects of comorbid conditions on fatigue symptom. Furthermore, our study did not examine which comorbid condition contributed to fatigue. Therefore, further research is needed to examine the contribution of specific comorbid conditions on fatigue.
Poor functional status is a well-known negative factor affecting the quality of life of meningioma patients. Our study shows high correlations between KPS score and fatigue, and low KPS score is an independent factor for total fatigue, reduced activity, and mental fatigue. In accordance with our findings, a previous prospective study of fatigue in glioma patients indicated a significant relationship between low KPS and high fatigue before surgery, which also existed after surgery, while another study on gliomas found no relationship between KPS and fatigue after surgery. It is necessary to explore in depth fatigue in meningioma patients at various stages in the disease trajectory.
Headache was another independent factor for total fatigue and general fatigue. Headache is the most frequent symptom and occurs in about two thirds of meningioma patients. The headache of meningiomas may depend on compression of specific structures or an increase in intracranial pressure. Compared with other headaches, those associated with increased intracranial pressure are more likely to be severe, continuous, associated with nausea and vomiting, and refractory to analgesics. Patients may experience more negative emotions (e.g., anxiety, depression, fatigue) due to frequent and intense headache. A cross-sectional study conducted by Spierings et al. has shown higher levels of fatigue in patients with chronic headache. Conversely, another cross-sectional study found that fatigue was a risk factor for headache. Hence, the nature of the causal relationship between fatigue and headache is unclear and longitudinal data involving a larger sample are required.
The results of the current study also revealed that anxiety and depression were significantly associated with fatigue in meningioma patients. Similarly, other researchers have established an association between fatigue, depression, and anxiety in studies of other primary brain tumors[8,45]. Moreover, one study argued that meningioma, over other types of tumors, can lead to greater levels of anxiety and depression, resulting in the aggravation of health-related complications. Therefore, we recommend the routine screening of patients for psychological disorders in order to determine targeted interventions to help meningioma patients to get rid of fatigue.
Moreover, we also found that sleep quality was strongly correlated with fatigue, consistent with previous studies on primary brain tumors[14,15]. Sleep-wake disturbances, which include both alterations in sleep (insomnia) and daytime sleepiness, are frequently reported as the most severely rated symptoms within health-related quality of life across the disease course or treatments, along with fatigue, and in turn can contribute to other symptoms and psychopathology[47,48]. In our analysis, reduced motivation was more likely to occur in patients with more severe daytime sleepiness. In a previous study, primary brain-tumor patients with sleepiness also had lower quality of life, poor performance status and shorter survival. In addition, although fatigue and sleepiness are considered as two distinct symptoms, they also show a great overlap and presumably, at least to some extent, similar pathophysiology. Thus, sleepiness is undoubtedly associated with fatigue, which is confirmed by our findings. Clinically, our results suggest that interventions to improve sleep may be effective for meningioma patients with reduced motivation. Unfortunately, no study has examined an intervention specifically aimed at improving the sleep of brain tumor patients. The interventions to alleviate fatigue and sleepiness need further research in the further.
Considering the importance of HRQoL in clinical neuro-oncology, our study also explored the impact of fatigue on HRQoL of meningioma patients. A largest prospective, longitudinal cross-sectional cohort study of HRQoL in postoperative meningiomas to date, indicated that fatigue was significantly associated with HRQoL. In our analysis, we found a significant relation between all dimensions of fatigue (expressed by MFI-20) and all dimensions of HRQoL (expressed by SF-36) in meningioma patients newly diagnosed. It follows then that eliminating fatigue is very important to improve HRQoL. In clinical settings, early identification of patients at high risk for fatigue facilitates timely provision of information and intervention. At present, although only a few intervention studies have been conducted on fatigue in patients with brain tumors, we can take lessons from the cancer literature to apply to meningiomas. Psychotherapy such as cognitive–behavioral therapy to alter the way people behave has been shown to be successful in cope with fatigue and functional impairment in cancer survivors. Psychological educational and lifestyle management interventions, such as energy conservation and activity management (ECAM), have been studied in multiple randomized controlled trials to demonstrate a positive impact on fatigue outcomes. Support complementary therapies (e.g., qigong, yoga, hypnosis, and music therapy) may also offer some benefits to cancer patients. Exercise and physical activity have demonstrated to improve cancer-related fatigue and overall quality of life. However, for meningioma patients, these interventions and their effectiveness need to be further investigated.
To our knowledge, this is the first study to explore the multidimensional fatigue and its effects on HRQoL of meningioma patients newly diagnosed and ready for surgery in China. The fatigue assessment with the MFI-20 is beneficial because it includes multiple fatigue subtypes, allowing for stratification of these subtypes and identification of key issues. However, acknowledged limitations of this study should be considered that participants were recruited from a single neurosurgery clinic and sample size needed to be expanded. And, because of the cross-sectional in design, the current study only demonstrates associations but not causation. Therefore, further systematic studies from multiple centers and neurophysiological researches should be conducted to clarify effective interventions to reduce or treat fatigue, potentially resulting in improvement of HRQoL in meningioma patients.