Prevalence and predictors of fatigue in glioblastoma: a prospective study

Glioblastoma is the most common primary brain tumor in adults, with an estimated incidence of about 3 per 100 000 inhabitants per year in Europe and North America.1 The standard of care for newly diagnosed glioblastoma, subsequent to surgery, comprises radiotherapy with concomitant temozolomide followed by adjuvant temozolomide. In the study defining this treatment regimen, median survival was limited to 15 months,2 and median survival was reported to be only 12 months in a population-based analysis of more than 10 000 glioblastoma patients.3 Independent of any treatment, fatigue is a common symptom in cancer patients in general as well as in primary brain tumor patients, with an estimated prevalence of 50%–90% and 40%–70%, respectively.4,5 Cancer-related fatigue is defined by the National Comprehensive Cancer Network (NCCN) as a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning.6 The patients themselves indicate fatigue as one of the most distressing symptom related to cancer and its treatment.7 It is a strong predictor of decreased patient satisfaction and health-related quality of life (QoL) and may represent one of the key reasons for discontinuing treatment.8–10 Nevertheless, fatigue is believed to be underdiagnosed and underestimated in cancer patients despite its possible impact on treatment compliance.4,11 As a consequence, some groups have questioned whether the standard treatment for glioblastoma is justified in view of the limited benefit on survival and the severity of associated symptoms.12 Compared with other tumor types, namely breast and lung cancer, few studies have addressed the problem of fatigue in glioblastoma patients in depth, and several limitations have to be mentioned. First, many groups have included patients with all sorts of primary brain tumors despite large differences in underlying neurobiology, treatment procedures, and prognosis.5,13 Second, baseline data are often missing, particularly in studies using a cross-sectional design.5 As a consequence, fatigue was mainly assessed as a treatment complication, thereby failing to acknowledge the primary impact of the tumor itself and other treatment-independent factors.14 Third, the results of many older series cannot be directly compared with the current situation because of advances in radiation techniques. Finally, while many validated fatigue questionnaires are available,9,15 the large majority of neuro-oncological studies identified and quantified fatigue in a very rudimental way, using the Visual Analogue Scale (VAS) or one single fatigue item appearing in tools such as the European Organisation for Research and Treatment of Cancer (EORTC) QoL questionnaire, the M D Anderson Symptom Inventory–Brain Tumor Module, or the Symptom Distress Scale.9,12,16–18 Thus, in this prospective study, we aimed at examining frequency and predictors of fatigue severity in a homogeneous cohort of glioblastoma patients at baseline prior to combined radio-chemotherapy. For this goal, we used the Fatigue Severity Scale (FSS), which has been identified as the most widely adopted fatigue questionnaire in clinical practice and has been validated for a variety of neurological diseases.15,19,20 In addition, we explored the evolution of fatigue, sleepiness, and mood disorders during and after combined radio-chemotherapy.