Research addressing specific symptoms that affect QOL has focused on fatigue, sleep, pain, seizures, mood disturbance, and cognitive function. This research has been mostly descriptive, and most studies examine a heterogeneous group of patients receiving different therapies at different stages of their illness.
Fatigue appears to be the most significant symptom facing patients with high-grade gliomas3,6
and may be more significant a problem compared to patients with low-grade tumors.18
In patients with recurrent malignant gliomas, the incidence of fatigue may approach 89%–94%.3
In a study evaluating patients with high-grade gliomas enrolled in three phase II protocols, significant fatigue was found in one-third of patients and independently predicted poorer overall survival.6
In that study, Eastern Cooperative Oncology Group performance status was correlated with overall QOL, excessive daytime somnolence, and increased fatigue. For low-grade glioma patients, one small study showed that of all QOL variables tested, fatigue had the strongest relationship with overall QOL.12
Sleep disturbance is also a common problem in primary brain tumor patients.12,19
For example, one study evaluating the incidence of major depressive disorder in a neurooncology clinic showed some type of sleep disturbance in 31.6%–52% of the patients evaluated.19
Other patient series suggest that high-grade glioma patients may have an even higher prevalence of sleep disturbance.3,20
Pain is another symptom that glioma patients often face.21
Headache is the most common type of pain, which more than 50% of patients with high-grade gliomas experience.3
Unfortunately, studies to date have not examined the type, location, or intensity of headache pain, the distress it caused, or its overall relationship to QOL in brain tumor patients.
Seizures in glioma patients are associated with deterioration in multiple cognitive domains.13
Low-grade glioma patients may have a higher incidence of epileptic seizures than do high-grade glioma patients, and in one study, antiepileptic therapy was able to control seizures only in approximately 50% of patients.13
The presence of seizures has not been shown to be a prognostic factor in some studies17
and was a positive prognostic factor in other studies when no other symptoms were present.16,22,23
Studies on mood disturbance in brain tumor patients have reported varying results, noting depression in anywhere between 7.9% and 90% of cases8,19,24–26
and significant anxiety in 29%–60% of cases.8,25,27
The use of formal criteria from the Diagnostic and Statistical Manual of Mental Disorders
, 4th edition, was employed in only a few studies to study depression.19,26
Of note, in some cohorts of primary brain tumor patients, depression was the most important independent predictor of QOL28,29
and has been shown to have an adverse impact on survival.26,30,31
Depression may also be under-treated. For example, in one study, only 60% of patients reported by their physicians to be depressed received antidepressants.26
Depression and anxiety may both have biologic foundations in brain tumor patients. In particular, measurable serotonin binding sites and strong peripheral benzo-diazepine receptor expression were present in the tumors of rats implanted with gliomas.32
Expression of certain serotonin receptors has also been found in human fetal astrocytes and glioma cell lines.33
The biologic connections between tumor and symptoms could suggest that symptoms in some cases may not only be prognostic, but may be a surrogate marker for disease.
Cognitive functioning has also been studied in brain tumor patients and has been recently reviewed.34
Malignant glioma patients, in particular, deal with a significant burden in terms of cognitive dysfunction, with as many as 49% experiencing cognitive impairment.5
In smaller trials, there is evidence that cognitive dysfunction is present even prior to treatment.35
There is an unmet need for early neurocognitive evaluation and intervention. In addition, the prevalence of neurocognitive dysfunction has implications for decision making and informed consent.
Evaluation of cognitive function also has prognostic value.9,36,37
For example, one study of recurrent malignant gliomas showed that cognitive deterioration may precede radiographic evidence of progression by almost 6 weeks.36
A simple screening examination such as the Mini Mental Status Examination (MMSE) can have prognostic significance in glioma patients.38–40
However, while the MMSE is feasible and convenient to use in brain tumor patients, it has not consistently been shown to detect cognitive decline in brain tumor patients.6
Moreover, the test has been validated for dementia screening but does not have a high degree of sensitivity for other cognitive domains.41
New neuropsychologic tests need to be validated in this population, because many of the standard tests lack sensitivity, especially at the lower end of the impaired range.42
In fact, attempts are being made in large cooperative trials to standardize the measurement of cognitive status. Numerous brain studies being conducted by cooperatives such as the Radiation Therapy Oncology Group are using well-known tests of neurocognitive function, such as the Hopkins Verbal Learning Test, the Trail Making Test, and the Controlled Word Association Test.
In summary, brain tumor patients deal with a significant symptom burden. The main areas of concern are in fatigue, sleep, pain, seizures, mood, and cognitive function. Malignant glioma patients are particularly affected by fatigue, whereas low-grade glioma patients have a large symptom burden from seizures. Further research is necessary not only to better define this symptom burden, but also to examine individual symptoms within specific populations.