Incidence of clinically relevant psychiatric symptoms during glioblastoma treatment: an exploratory study.

PURPOSE: In addition to neurological symptoms glioblastoma (GBM) patients can experience psychiatric complaints, which are often hard to recognize and difficult to treat. Research on psychiatric symptoms during glioblastoma treatment is limited, but can have significant impact on quality of life, treatment processes and even survival. The aim of this study is to explore the incidence of clinically relevant psychiatric symptoms, during glioblastoma treatment and active surveillance. METHODS: Medical records of 302 GBM patients were reviewed from diagnostic surgery until discontinuation of treatment or active surveillance. Clinical relevance was defined as psychiatric symptoms that interfered with the oncological treatment and required referral to a psychiatrist. "Referred" versus "non-referred" GBM patients were compared using the Pearson Chi-Square test, Fisher's Exact Test or Mann Whitney-U test. RESULTS: Psychiatric symptoms occurred in 11.5% of patients during glioblastoma treatment or active surveillance, most often mood or behavioral symptoms, followed by psychotic symptoms. Referral occurred mainly during concomitant chemoradiation or adjuvant chemotherapy (64.3%). In 28.6% of patients psychiatric symptoms were thought to be attributive to medication. Treatment was discontinued in 17.9% of patients and temporarily interrupted in 3.6%. Possible risk factors included male gender, history of psychiatric disorder, postoperative delirium, non-frontal tumor location, anti-epileptic drug use at baseline and corticosteroid initiation during treatment. CONCLUSION: The found incidence of 11.5% and the high number of patients discontinuing treatment due to psychiatric symptoms justify more research in this, to date, understudied topic in scientific literature. Further prospective studies are needed to identify risk factors and unravel possible effects on survival.

Clinical implementation of standardized neurocognitive assessment before and after radiation to the brain.

Background: Radiotherapy induced impairment of cognitive function can lead to a reduced quality of life. The aim of this study was to describe the implementation and compliance of standardized neurocognitive assessment. In addition, the first results of cognitive changes for patients receiving a radiation dose to the brain are described. Materials and methods: Patients that received radiation dose to the brain (neuro, head and neck and prophylactic cranial irradiation between April-2019 and Dec-2021 were included. Three neuro cognitive tests were performed a verbal learning and memory test, the Hopkins Verbal Learning Test; a verbal fluency test, the Controlled Oral Word Association Test and a speed and cognitive flexibility test, the Trail Making Test A&B. Tests were performed before the start of radiation, 6 months (6 m) and 1 year (1y) after irradiation. The Reliable Change Index (RCI) between baseline and follow-up was calculated using reference data from literature. Results: 644 patients performed the neurocognitive tests at baseline, 346 at 6 months and 205 at 1y after RT, with compliance rates of 90.4%, 85.6%, and 75.3%, respectively. Reasons for non-compliance were: 1. Patient did not attend appointment (49%), 2. Patient was unable to perform the test due to illness (12%), 3. Patient refused the test (8 %), 4. Various causes, (31%). A semi-automated analysis was developed to evaluate the test results. In total, 26% of patients showed a significant decline in at least one of variables at 1y and 11% on at least 2 variables at 1y. However, an increase in cognitive performance was observed in 49% (≥1 variable) and 22% (≥2 variables). Conclusion: Standardized neurocognitive testing within the radiotherapy clinic was successfully implemented, with a high patient compliance. A semi-automatic method to evaluate cognitive changes after treatment was defined. Data collection is ongoing, long term follow-up (up to 5 years after treatment) and dose-effect analysis will be performed.

Radiation-enhanced vascular endothelial growth factor (VEGF) secretion in glioblastoma multiforme cell lines--a clue to radioresistance?

OBJECTIVE: Postoperative radiotherapy is standard treatment for patients with a glioblastoma multiforme (GBM). However, a GBM is radioresistant and almost always recurs, even after a high dose of radiation. A GBM is characterized by its extensive neo-angiogenesis, which can be attributed to the high levels of vascular endothelial growth factor (VEGF). The scope of this study is to investigate the VEGF secretion by GBM cells with different radiosensitivity after irradiation. METHODS: Three human GBM cell lines (U251, U251-NG2 and U87) were irradiated with single doses of 0, 5, 10 and 20 Gy of gamma-rays from a (137)Cs source. VEGF levels in medium were measured by ELISA at 24, 48 and 72 h after radiation. Cell survival was measured by the XTT assay 7 days after irradiation. RESULTS: Following single dose radiation, the VEGF levels showed a dose dependent increase in U251, U251-NG2 and U87 glioma cells. Both base-line and radiation-enhanced VEGF levels were about 10-fold higher in U87 compared to U251 and U251-NG2 cells. In addition, in the XTT assay, the U87 was more radioresistant than both U251 and U251-NG2 cell lines (dose modifying factor (DMF) = 1.6 and 1.7 resp). CONCLUSION: Irradiation enhanced VEGF secretion in all three tested glioma cell lines (up to eight times basal levels). It is tempting to associate the radiation-enhanced VEGF secretion with an increased angiogenic potential of the tumor, which may be a factor in radioresistance.