Health-related Quality of Life and Neurocognitive Functioning After Glioblastoma Treatment

Impact of Disease and Treatment on Health-related Quality of Life

Both the disease and its treatment can affect HRQOL. Common disease-specific symptoms that may negatively influence HRQOL include paresis, sensory loss, visual-perceptual deficits, cognitive deficits, and symptoms associated with increased intracranial pressure, such as nausea and headache. Moreover, fatigue and mood issues can contribute to poorer HRQOL. Patients with newly diagnosed GBM experience significantly lower levels of HRQOL than healthy controls, shortly after surgery. Compared with other neurologic patient groups, HRQOL among patients with stable high-grade glioma is similar, but patients with GBM report less positive affect, more depression, and more illness intrusiveness than other patients with cancer.

The impact of antitumor treatment (surgery followed by radiotherapy and/or chemotherapy) on HRQOL can be both negative and positive. Surgery can either improve HRQOL by reducing tumor mass and the disease-specific symptoms associated with increased intracranial pressure, or it can decrease HRQOL by damaging functional tissue. In patients with low-grade glioma, treatment with radiotherapy has generally been associated with a negative impact on HRQOL, because increased fatigue and cognitive deficits can hinder everyday functioning. These late toxic effects of treatment play a less prominent role in patients with high-grade glioma, who have a poorer prognosis. On the group level, the HRQOL of patients with high-grade glioma does not seem to be negatively influenced by a treatment regimen consisting of radiotherapy and chemotherapy. However, specific aspects of HRQOL, such as social and cognitive functioning, may be affected temporarily. In long-term survivors (>2.5 years) of anaplastic glioma treated with radiotherapy and chemotherapy, lower levels of motor functioning and social, cognitive, and emotional aspects of HRQOL have been reported. The side effects that occur with chemotherapy, such as nausea or vomiting, appetite loss, and drowsiness, can also negatively influence patients’ functioning and HRQOL.

Adding bevacizumab, an antiangiogenic agent that may benefit progression-free survival in a subgroup of patients with recurrent GBM, does not seem to affect HRQOL, although one study reports a decrease in HRQOL. Other medications commonly administered to manage symptoms, such as antiepileptic drugs (AEDs) and corticosteroids, can influence HRQOL. Decreasing seizure frequency may improve HRQOL, but side effects or drug-drug interactions may decrease HRQOL. However, second-generation AEDs such as levetiracetam and oxcarbazepine cause fewer side effects and do not seem to significantly influence HRQOL in the longer term. Similarly, corticosteroids may improve HRQOL by relieving symptoms of increased intracranial pressure but can also cause adverse effects that may harm HRQOL. Therefore, it is advised to administer corticosteroids in the lowest effective dose to minimize side effects.

Of note, the HRQOL results of studies including patients with GBM are often biased, because those patients participating in trials are often young and have a good performance status. In addition, patients who show clinical deterioration are more frequently lost to follow-up. Thus, HRQOL could be overestimated, especially in studies with long follow-up. As GBM recurs or the disease progresses, HRQOL seems to become worse. However, in long-term survivors of GBM (ie, survival ≥16 months) HRQOL can return to a level comparable with normal controls. Despite the poor prognosis, patients often long to return to a normal everyday life, including return to work and social activities after primary treatment. It is especially during this phase of life that HRQOL may be correlated with cognitive functioning, because even subtle cognitive deficits might hamper patients’ autonomy and professional life ( Fig. 21.1 ).