The long-term course and relationship with survival of multidimensional fatigue in patients with brain metastases after Gamma Knife radiosurgery

Purpose: The aims of this study were to evaluate long-term multidimensional fatigue in patients with brain metastases (BM) up to 21 months after Gamma Knife radiosurgery (GKRS) and (change in) fatigue as predictor of survival. Methods: Patients with 1 to 10 BM, expected survival > 3 months, and Karnofsky Performance Status ≥ 70, and Dutch non-cancer controls were included. Fatigue was measured with the Multidimensional Fatigue Inventory. Levels of fatigue between patients and controls were compared using independent-samples t-tests. Linear mixed models were used to evaluate fatigue within the patient group up to 21 months after GKRS. Pre-GKRS fatigue and minimal clinically important (MCI) changes in fatigue in the first three months (defined as a 2-point difference) after GKRS were evaluated as predictors of survival time. Results: Prior to GKRS, patients with BM (n = 92) experienced significantly higher fatigue on all subscales than controls (n = 104). Over 21 months, physical fatigue increased, and mental fatigue decreased significantly. More specifically, general, and physical fatigue increased significantly between pre-GKRS and 3 months, followed by stable scores between 3 (n = 67) and 6 (n = 53), 6 and 12 (n = 34) and 12 and 21 (n = 21) months. An MCI increase in general or physical fatigue over the first 3 months after GKRS was a significant predictor of shorter survival time. Conclusion: Except for mental fatigue, all aspects of fatigue remained elevated or further increased up to 21 months after treatment. Furthermore, an increase in general or physical fatigue within three months after GKRS may be a prognostic indicator for poorer survival. ClinicalTrials.gov identifier: NCT02953756, November 3, 2016.