Toward unraveling the correlates of fatigue in glioma

Abstract Background Even though fatigue is one of the most prevalent and burdensome symptoms in patients with glioma, its etiology and determinants are still poorly understood. We aimed to identify which demographic, tumor- and treatment-related characteristics and patient-reported outcome measures (PROMs) are associated with or are predictors of fatigue in glioma. Methods In this retrospective observational study, we included glioma patients with preoperative and postoperative assessments including PROMs on fatigue, depression, cognitive functioning, and health-related quality of life (HRQoL). Linear mixed models were used to identify which clinical factors and PROMs were associated with fatigue and linear multiple regression was used to detect predictors of postoperative fatigue. Results In this study, 222 patients were included (78% grade II-III glioma, 22% grade IV). These patients had performed 333 assessments (193 preoperative and 116 one year postoperatively). Of all assessments, 39% was indicative of severe fatigue. Several HRQoL domains, depression, and right-sided tumors were significantly associated with fatigue (marginal R 2 = 0.63). Contrary to common expectations, tumor type, treatment-related factors and timing of the assessment, were not associated with fatigue. In a subgroup of seventy patients with follow-up assessments, preoperative fatigue and physical functioning were predictors of postoperative fatigue (adjusted R 2 = 0.31). Conclusion Fatigue is a complex symptom, which should not solely be attributed to the tumor or its treatment, but is instead related to different aspects of mood and HRQoL. These insights are of importance in understanding fatigue and could guide symptom management, especially in patients with lower grade tumors. Key points Up to 40% of patients are severely fatigued, regardless of tumor type or timing of assessment HRQoL, depression, and right-sided tumor explain 63% of variance in fatigue severity Demographics, tumor type and treatment are not associated with fatigue severity Importance of the Study Despite fatigue being one of the most frequent and burdensome symptoms in patients with glioma, its etiology remains poorly understood. We aimed to unravel the impact of demographic, tumor- and treatment-related factors, symptoms, and HRQoL to grasp the complexity of fatigue in 222 glioma patients. Our findings demonstrate that fatigue is associated with several domains of HRQoL and depression, as well as having a tumor in the right hemisphere. What stands out is that fatigue is not associated with tumor type, treatment-related characteristics or phase of the disease. These findings could be important in symptom management since tumor- and treatment-related factors are non-modifiable, whilst depressive symptoms and social and physical functioning could be more suitable treatment targets. These results underscore the need for timely screening and symptom management focusing not only on fatigue but also on mood and diminished HRQoL.