Background Gliomas are associated with significant healthcare burden, yet reports of costs are scarce. While many costs are unavoidable there may be treatable symptoms contributing to higher costs. We describe healthcare and societal costs in glioma patients at high risk for depression and their family caregivers, and explore relationships between costs and treatable symptoms. Methods Data from a multicenter randomized trial on effects of internet-based therapy for depressive symptoms were used (NTR3223). Costs of self-reported healthcare utilization, medication use, and productivity loss were calculated for patients and caregivers separately. We used generalized linear regression models to predict costs with depressive symptoms, fatigue, cognitive complaints, tumor grade (low-/high-grade), disease status (stable or active/progression), and intervention (use/non-use) as predictors. Results Multiple assessments from baseline through 12 months from 91 glioma patients and 46 caregivers were used. Mean overall costs per year were M = €20,587.53 ( sd = €30,910.53) for patients and M = €5,581.49 ( sd = €13,102.82) for caregivers. In patients , higher healthcare utilization costs were associated with more depressive symptoms; higher medication costs were associated with active/progressive disease. In caregivers , higher overall costs were linked with increased caregiver fatigue, cognitive complaints, and lower patient tumor grade. Higher healthcare utilization costs were related to more cognitive complaints and lower tumor grade. More productivity loss costs were associated with increased fatigue (all P < 0.05). Conclusions There are substantial healthcare and societal costs for glioma patients and caregivers. Associations between costs and treatable psychological symptoms indicate that possibly, adequate support could decrease costs. Trial registration Netherlands Trial Register NTR3223.

Abstract Background Surgical resection and irradiation of diffuse glioma are guided by standard MRI: T2/fluid attenuated inversion recovery (FLAIR)–weighted MRI for non-enhancing and T1-weighted gadolinium-enhanced (T1G) MRI for enhancing gliomas. Amino acid PET has been suggested as the new standard. Imaging combinations may improve standard MRI and amino acid PET. The aim of the study was to determine the accuracy of imaging combinations to detect glioma infiltration. Methods We included 20 consecutive adults with newly diagnosed non-enhancing glioma (7 diffuse astrocytomas, isocitrate dehydrogenase [IDH] mutant; 1 oligodendroglioma, IDH mutant and 1p/19q codeleted; 1 glioblastoma IDH wildtype) or enhancing glioma (glioblastoma, 9 IDH wildtype and 2 IDH mutant). Standardized preoperative imaging (T1-, T2-, FLAIR-weighted, and T1G MRI, perfusion and diffusion MRI, MR spectroscopy and O-(2-[18F]-fluoroethyl)-L-tyrosine ([18F]FET) PET) was co-localized with multiregion stereotactic biopsies preceding resection. Tumor presence in the biopsies was assessed by 2 neuropathologists. Diagnostic accuracy was determined using receiver operating characteristic analysis. Results A total of 174 biopsies were obtained (63 from 9 non-enhancing and 111 from 11 enhancing gliomas), of which 129 contained tumor (50 from non-enhancing and 79 from enhancing gliomas). In enhancing gliomas, the combination of apparent diffusion coefficient (ADC) with [18F]FET PET (area under the curve [AUC], 95% CI: 0.89, 0.79‒0.99) detected tumor better than T1G MRI (0.56, 0.39‒0.72; P < 0.001) and [18F]FET PET (0.76, 0.66‒0.86; P = 0.001). In non-enhancing gliomas, no imaging combination detected tumor significantly better than standard MRI. FLAIR-weighted MRI had an AUC of 0.81 (0.65–0.98) compared with 0.69 (0.56–0.81; P = 0.019) for [18F]FET PET. Conclusion Combining ADC and [18F]FET PET detects glioma infiltration better than standard MRI and [18F]FET PET in enhancing gliomas, potentially enabling better guidance of local therapy.

BackgroundStudies on the associations between preoperative cerebral edema, cognitive functioning, and health-related quality of life (HRQOL) in WHO grade I meningioma patients are virtually lacking. We studied the association between preoperative cerebral edema on postoperative cognitive functioning and HRQOL 6months postoperatively in WHO grade I meningioma patients.MethodsTwenty-one consecutive WHO grade I meningioma patients, who underwent surgery, were matched individually for age, gender, and educational level to healthy controls. Tumor and edema volume were assessed on preoperative T1- and T2-weighted MRI images, respectively. At least 5months postoperatively, functional status, cognitive functioning, and HRQOL, using a cognitive test battery and the Short-Form Health Survey (SF-36), were determined. The correlation between preoperative tumor and cerebral edema volume with postoperative cognitive functioning and HRQOL was investigated using Kendall's tau coefficients.ResultsCompared to healthy controls, patients had lower verbal memory capacity (p=.012), whereas HRQOL was similar to matched healthy controls. In all cognitive domains, postoperative functioning was much lower in patients with preoperative cerebral edema than in those without. There were significant correlations between preoperative cerebral edema and tumor volume and postoperative cognitive functioning. Preoperative cerebral edema and/or tumor volume were not associated with HRQOL.ConclusionsOur results suggest that WHO grade I meningioma patients with larger volumes of preoperative cerebral edema are more at risk of experiencing limitations in longer-term cognitive functioning than patients with no or less edema preoperatively. This is an important knowledge for neurologists and neurosurgeons treating patients with a meningioma. More studies regarding the effect of peritumoral edema on cognitive functioning in meningioma patients are necessary.

Positron emission tomography (PET) is increasingly used to guide local treatment in glioma. The purpose of this study was a direct comparison of two potential tracers for detecting glioma infiltration, O-(2-[18F]-fluoroethyl)-l-tyrosine ([18F] FET) and [11C] choline. Eight consecutive patients with newly diagnosed diffuse glioma underwent dynamic [11C] choline and [18F] FET PET scans. Preceding craniotomy, multiple stereotactic biopsies were obtained from regions inside and outside PET abnormalities. Biopsies were assessed independently for tumour presence by two neuropathologists. Imaging measurements were derived at the biopsy locations from 10 to 40 min [11C] choline and 20–40, 40–60 and 60–90 min [18F] FET intervals, as standardized uptake value (SUV) and tumour-to-brain ratio (TBR). Diagnostic accuracies of both tracers were compared using receiver operating characteristic analysis and generalized linear mixed modelling with consensus histopathological assessment as reference. Of the 74 biopsies, 54 (73%) contained tumour. [11C] choline SUV and [18F] FET SUV and TBR at all intervals were higher in tumour than in normal samples. For [18F] FET, the diagnostic accuracy of TBR was higher than that of SUV for intervals 40–60 min (area under the curve: 0.88 versus 0.81, p = 0.026) and 60–90 min (0.90 versus 0.81, p = 0.047). The diagnostic accuracy of [18F] FET TBR 60–90 min was higher than that of [11C] choline SUV 20–40 min (0.87 versus 0.67, p = 0.005). [18F] FET was more accurate than [11C] choline for detecting glioma infiltration. Highest accuracy was found for [18F] FET TBR for the interval 60–90 min post-injection.

Introduction Meningioma patients often have subtle cognitive deficits that might be attributed to the tumor itself, to surgical treatment, or to the occurrence of seizures and their treatment. Magnetoencephalography (MEG) analysis of resting-state functional networks (RSNs) could help to understand the neurophysiological basis of cognitive impairment in these patients. We explored the correlation between RSN functional connectivity and topology of functional networks on the one hand, and cognition on the other hand in WHO grade I meningioma patients. Methods Twenty adult WHO grade I meningioma patients who had undergone tumor resection, as well as 20 healthy matched controls, were included. Neuropsychological assessment was done through a standardized test battery. MEG data were recorded, and projected to the anatomical space of the Automated Anatomical Labeling atlas. Functional connectivity (PLI), within the default mode network (DMN) and the bilateral frontoparietal networks were correlated to cognitive performance. Minimum spanning tree (MST) characteristics were correlated with cognitive functioning. Results Compared to healthy controls, meningioma patients had lower working memory capacity ( p = 0.037). Within the patient group, lower working memory performance was associated with lower DMN connectivity and a lower maximum MST degree in the theta band (resp. p = 0.044 and p = 0.003). Conclusions This study shows that cognitive functioning is correlated with functional connectivity in the default mode network and hub-pathology in WHO grade I meningioma patients. Future longitudinal studies are needed to corroborate these findings and to further investigate the pathophysiology of cognitive deficits and possible changes in functional brain networks in meningioma patients.

Depressive symptoms are common in glioma patients, and can negatively affect health-related quality of life (HRQOL). We performed a nation-wide randomized controlled trial to evaluate the effects of an online guided self-help intervention for depressive symptoms in adult glioma patients. Glioma patients with depressive symptoms were randomized to a 5-week online course based on problem-solving therapy, or a waiting list control group. After having received the intervention, the glioma patient groups combined were compared with patients with cancer outside the central nervous system (non-CNS cancer controls), who also received the intervention. Sample size calculations yielded 63 participants to be recruited per arm. The primary outcome [depressive symptoms (CES-D)] and secondary outcomes [fatigue (Checklist Individual Strength (CIS)) and HRQOL (Short Form-36)], were assessed online at baseline, post-intervention, and 3 and 12 months follow-up. In total, 89 glioma patients (intervention N = 45; waiting list N = 44) and 26 non-CNS cancer controls were included, of whom 35 and 54% completed the intervention, respectively. Recruitment could not be extended beyond 3.5 years due to funding. On depression, no statistically significant differences between the groups were found. Fatigue decreased post-treatment in the glioma intervention group compared with the waiting list group (p = 0.054, d = 0.306). At 12 months, the physical component summary (HRQOL) remained stable in glioma patients, while scores improved in non-CNS cancer controls (p = 0.035, d = 0.883). In this underpowered study, no evidence for the effectiveness of online guided self-help for depression or HRQOL in glioma patients was found, but it may improve fatigue. Trial registration Netherlands Trial Register NTR3223.

Clinical trials in glioma patients with neurocognitive deficits face challenges due to lacking or unreliable patient self-reports on their health-related quality of life (HRQOL). Patient–proxy data could help solve this issue. We determined whether patient–proxy concordance levels were affected by patients’ neurocognitive functioning.

Purpose To investigate the scale structure and psychometrics of the EORTC chemotherapy-induced peripheral neuropathy module (QLQ-CIPN20). Methods Using confirmatory factor analyses (CFA), we tested two hypothesized scale structure models of the QLQ-CIPN20 in 473 patients with non-small cell lung cancer, 281 patients with heterogeneous cancer diagnoses, and 500 patients with colorectal cancer. We also modeled the two hypothesized models as bi-factor models. These included a general factor, in addition to the specific domain factors. Additional models were investigated with exploratory factor analysis (EFA). Known groups validity was evaluated where justified. Results CFA could not confirm the two hypothesized models (Model 1: CFI < 0.926; TLI < 0.914; RMSEA > 0.077 and Model 2: CFI < 0.906; TLI < 0.887; RMSEA > 0.105) in any of the three samples. Including a general factor to these two hypothesized models to produce a bi-factor model also did not yield satisfactory results. Using EFA, we identified four different factor structures in the three samples that were unstable due to cross loadings of the items. When scoring the QLQ-CIPN20 as a simple, additive checklist evidence was found for known groups validity in the first two samples based on Common Toxicity Criteria (CTC-AE), and in the third sample based on exposure to CIPN-inducing chemotherapy. Conclusions Neither CFA nor EFA yielded support for a stable subscale structure for the QLQ-CIPN20. Scoring the questionnaire as a simple additive checklist results in acceptable validity.

BACKGROUND: Brain imaging in diffuse glioma is used for diagnosis, treatment planning, and follow-up. PURPOSE: In this meta-analysis, we address the diagnostic accuracy of imaging to delineate diffuse glioma. DATA SOURCES: We systematically searched studies of adults with diffuse gliomas and correlation of imaging with histopathology. STUDY SELECTION: Study inclusion was based on quality criteria. Individual patient data were used, if available. DATA ANALYSIS: A hierarchic summary receiver operating characteristic method was applied. Low- and high-grade gliomas were analyzed in subgroups. DATA SYNTHESIS: Sixty-one studies described 3532 samples in 1309 patients. The mean Standard for Reporting of Diagnostic Accuracy score (13/25) indicated suboptimal reporting quality. For diffuse gliomas as a whole, the diagnostic accuracy was best with T2-weighted imaging, measured as area under the curve, false-positive rate, true-positive rate, and diagnostic odds ratio of 95.6%, 3.3%, 82%, and 152. For low-grade gliomas, the diagnostic accuracy of T2-weighted imaging as a reference was 89.0%, 0.4%, 44.7%, and 205; and for high-grade gliomas, with T1-weighted gadolinium-enhanced MR imaging as a reference, it was 80.7%, 16.8%, 73.3%, and 14.8. In high-grade gliomas, MR spectroscopy (85.7%, 35.0%, 85.7%, and 12.4) and 11C methionine–PET (85.1%, 38.7%, 93.7%, and 26.6) performed better than the reference imaging. LIMITATIONS: True-negative samples were underrepresented in these data, so false-positive rates are probably less reliable than true-positive rates. Multimodality imaging data were unavailable. CONCLUSIONS: The diagnostic accuracy of commonly used imaging is better for delineation of low-grade gliomas than high-grade gliomas on the basis of limited evidence. Improvement is indicated from advanced techniques, such as MR spectroscopy and PET.

We aimed to analyze the value of seizure reduction and radiological response as prognostic markers of survival in patients with low-grade glioma (LGG) treated with temozolomide (TMZ) chemotherapy. We retrospectively reviewed adult patients with a progressive LGG and uncontrolled epilepsy in two hospitals (VUmc Amsterdam; MCH The Hague), who received chemotherapy with TMZ between 2002 and 2014. End points were a ≥50 % seizure reduction and MRI response 6, 12 and 18 months (mo) after the start of TMZ, and their relation with progression-free survival (PFS) and overall survival (OS). We identified 53 patients who met the inclusion criteria. Seizure reduction was an independent prognostic factor for both PFS (HR 0.38; 95 % CI 0.19–0.73; p = 0.004) and OS (HR 0.39; 95 % CI 0.18–0.85; p = 0.018) after 6mo, adjusting for age and histopathological diagnosis, as well as after 12 and 18mo. Patients with an objective radiological response showed a better OS (median 87.5mo; 95 % CI 62.0–112.9) than patients without a response (median 34.4mo; 95 % CI 26.1–42.6; p = 0.046) after 12mo. However, after 6 and 18mo OS was similar in patients with and without a response on MRI. Seizure reduction is an early and consistent prognostic marker for survival after treatment with TMZ, that seems to precede the radiological response. Therefore, seizure reduction may serve as a surrogate marker for tumor response.

Background During the end-of-life (EOL) phase of glioma patients, a rapid deterioration in neurological functioning may interfere with the oral intake of antiepileptic drugs (AEDs). We aimed to assess the feasibility of non-oral AED treatment in an out-of-hospital setting according to an expert-based guideline. Methods Glioma patients with a history of epilepsy, in whom further antitumor therapy was considered to be no longer meaningful, were recruited at two Dutch hospitals. As soon as swallowing difficulties developed, the patient’s caregiver administered prophylactic treatment with buccal clonazepam. Acute seizures were treated with intranasal midazolam. We evaluated the adherence to the study medication, seizure prevalence, and caregiver’s satisfaction. Results Of the 34 patients who were approached, 25 gave consent to participate and 23 had died at the end of the study. Thirteen of 19 patients (68.4 %) who had developed swallowing difficulties showed adherence to the study protocol. Thirteen patients used prophylactic buccal clonazepam, of which eight patients remained seizure-free until death. Six patients received treatment with intranasal midazolam at least once. In all patients, seizure control was reached. None of the patients needed to be transferred to the hospital due to recurrent seizures. All caregivers were to some degree satisfied with the use of the study medication. Conclusions Our results demonstrate that it is feasible to treat seizures with a combination of non-oral benzodiazepines in the EOL phase of glioma patients, as it seems to provide an important level of comfort among caregivers to be able to manage seizures at home.

Studies in rodents suggest that flumazenil is a P-glycoprotein substrate at the blood-brain barrier. This study aimed to assess whether [11C]flumazenil is a P-glycoprotein substrate in humans and to what extent increased P-glycoprotein function in epilepsy may confound interpretation of clinical [11C]flumazenil studies used to assess gamma-aminobutyric acid A receptors. Nine drug-resistant patients with epilepsy and mesial temporal sclerosis were scanned twice using [11C]flumazenil before and after partial P-glycoprotein blockade with tariquidar. Volume of distribution, nondisplaceable binding potential, and the ratio of rate constants of [11C]flumazenil transport across the blood-brain barrier (K1/k2) were derived for whole brain and several regions. All parameters were compared between pre- and post-tariquidar scans. Regional results were compared between mesial temporal sclerosis and contralateral sides. Tariquidar significantly increased global K1/k2 (+23%) and volume of distribution (+10%), but not nondisplaceable binding potential. At the mesial temporal sclerosis side volume of distribution and nondisplaceable binding potential were lower in hippocampus (both ∼-19%) and amygdala (both ∼-16%), but K1/k2 did not differ, suggesting that only regional gamma-aminobutyric acid A receptor density is altered in epilepsy. In conclusion, although [11C]flumazenil appears to be a (weak) P-glycoprotein substrate in humans, this does not seem to affect its role as a tracer for assessing gamma-aminobutyric acid A receptor density.

Studies in rodents suggest that flumazenil is a P-glycoprotein substrate at the blood–brain barrier. This study aimed to assess whether [ 11 C]flumazenil is a P-glycoprotein substrate in humans and to what extent increased P-glycoprotein function in epilepsy may confound interpretation of clinical [ 11 C]flumazenil studies used to assess gamma-aminobutyric acid A receptors. Nine drug-resistant patients with epilepsy and mesial temporal sclerosis were scanned twice using [ 11 C]flumazenil before and after partial P-glycoprotein blockade with tariquidar. Volume of distribution, nondisplaceable binding potential, and the ratio of rate constants of [ 11 C]flumazenil transport across the blood–brain barrier (K1/k2) were derived for whole brain and several regions. All parameters were compared between pre- and post-tariquidar scans. Regional results were compared between mesial temporal sclerosis and contralateral sides. Tariquidar significantly increased global K1/k2 (þ23%) and volume of distribution (þ10%), but not nondisplaceable binding potential. At the mesial temporal sclerosis side volume of distribution and nondisplaceable binding potential were lower in hippocampus (both 19%) and amygdala (both 16%), but K1/k2 did not differ, suggesting that only regional gamma-aminobutyric acid A receptor density is altered in epilepsy. In conclusion, although [ 11 C]flumazenil appears to be a (weak) P-glycoprotein substrate in humans, this does not seem to affect its role as a tracer for assessing gamma-aminobutyric acid A receptor density.

PURPOSE:Patients with low-grade glioma (LGG) often experience long periods of stable disease, emphasizing the importance of maintaining good health-related quality of life (HRQOL). We assessed the changes in HRQOL in long-term survivors of WHO grade I or II astrocytoma, oligodendroglioma, or oligoastrocytoma with clinically and radiologically stable disease.PATIENTS AND METHODS:Patients completed self-report measures of generic HRQOL (Short Form-36 [SF-36]) and disease-specific HRQOL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Brain Cancer Module). Assessments took place at midterm and long-term follow-up, on average 6 and 12 years after histologic diagnosis and initial treatment, respectively. Comparisons between patients with LGG and individually matched healthy controls were made, and change within the patients with LGG was calculated, as was minimal detectable change.RESULTS:Although no statistically significant differences between patients with LGG and healthy matched controls were found at midterm follow-up, patients with LGG had worse physical role functioning (P = .004) and general health perceptions (P = .004) than controls at long-term follow-up. Within patients with stable LGG (n = 65), physical HRQOL (the SF-36 physical component summary and the physical functioning subscale) was significantly worse at long-term than at midterm follow-up (both P < .001). Although 48% of patients improved or remained stable on all HRQOL scales, 38.5% of patients experienced detectable decline on one or more scales.CONCLUSION:Although HRQOL remains mostly preserved in the majority of patients with LGG, a subset of patients experience detectable decline on one or more HRQOL scales despite long-term stable disease. For this subgroup, further research is recommended to better aid patients in dealing with the consequences of LGG.

BACKGROUND: A rapid deterioration in neurological functioning may hamper the oral administration of antiepileptic drugs (AEDs) in the end of life (EOL) phase of glioma patients. We aimed to assess the feasibility of treatment with non-oral AEDs in an out-of-hospital setting. METHODS: We included patients with a histopathological diagnosis of World Health Organization (WHO) grade II-IV glioma and a history of epilepsy, in whom further antitumor treatment was considered to be no longer meaningful. When swallowing difficulties developed, the patient's caregiver started to administer prophylactic AED treatment with buccal clonazepam. Acute seizures were treated with intranasal midazolam. We evaluated the adherence to the study medication, seizure prevalence as well as caregiver's satisfaction. RESULTS: Thirty-four patients were approached, of which 25 gave consent to participate and 23 had died at the end of the study. Fourteen of 19 patients (73.7%) who had developed swallowing difficulties used the study medication. Prophylactic buccal clonazepam was used by 13 patients, of which 8 patients remained seizure free until death. Six patients received treatment with intranasal midazolam at least once. In all patients seizure control could be reached. None of the patients had to be transferred to the hospital because of recurrent seizures. All caregivers reported satisfaction with the use of the study medication. CONCLUSIONS: It is feasible to treat glioma patients with seizures in the EOL phase with a combination of buccal clonazepam and intranasal midazolam. Additionally, it seems to provide an important level of comfort among caregivers to be able to manage seizures at home.

Temozolomide (TMZ) increases the overall survival of patients with glioblastoma (GBM), but its role in the clinical management of diffuse low-grade gliomas (LGG) is still being defined. DNA hypermethylation of the O 6 -methylguanine-DNA methyltransferase (MGMT) promoter is associated with an improved response to TMZ treatment, while inactivation of the DNA mismatch repair (MMR) pathway is associated with therapeutic resistance and TMZ-induced mutagenesis. We previously demonstrated that TMZ treatment of LGG induces driver mutations in the RB and AKT–mTOR pathways, which may drive malignant progression to secondary GBM. To better understand the mechanisms underlying TMZ-induced mutagenesis and malignant progression, we explored the evolution of MGMT methylation and genetic alterations affecting MMR genes in a cohort of 34 treatment-naïve LGGs and their recurrences. Recurrences with TMZ-associated hypermutation had increased MGMT methylation compared to their untreated initial tumors and higher overall MGMT methylation compared to TMZ-treated non-hypermutated recurrences. A TMZ-associated mutation in one or more MMR genes was observed in five out of six TMZ-treated hypermutated recurrences. In two cases, pre-existing heterozygous deletions encompassing MGMT, or an MMR gene, were followed by TMZ-associated mutations in one of the genes of interest. These results suggest that tumor cells with methylated MGMT may undergo positive selection during TMZ treatment in the context of MMR deficiency.

There is growing evidence that antitumor treatment contributes to better seizure control in low-grade glioma patients. We performed a systematic review of the current literature on seizure outcome after radiotherapy and chemotherapy and evaluated the association between seizure outcome and radiological response. Twenty-four studies were available, of which 10 described seizure outcome after radiotherapy and 14 after chemotherapy. All studies demonstrated improvements in seizure outcome after antitumor treatment. Eight studies reporting on imaging response in relation to seizure outcome showed a seizure reduction in a substantial part of patients with stable disease on MRI. Seizure reduction may therefore be the only noticeable effect of antitumor treatment. Our findings demonstrate the clinical relevance of monitoring seizure outcome after radiotherapy and chemotherapy, as well as the potential role of seizure reduction as a complementary marker of tumor response in low-grade glioma patients.

BACKGROUND Glioma patients are not only confronted with the diagnosis and treatment of a brain tumor, but also with changes in cognitive and neurological functioning that can profoundly affect their daily lives. At present, little is known about the relationship between cognitive functioning and health-related quality of life (HRQOL) during the disease trajectory. We studied this association in low-grade glioma (LGG) patients with stable disease at an average of 6 years after diagnosis. METHODS Patients and healthy controls underwent neuropsychological testing and completed self-report measures of generic (MOS SF36) and disease-specific (EORTC BN20) HRQOL. Associations were determined with Pearson correlations, and corrections for multiple testing were made. RESULTS We analyzed data gathered from 190 LGG patients. Performance in all cognitive domains was positively associated with physical health (SF36 Physical Component Summary). Executive functioning, processing speed, working memory, and information processing were positively associated with mental health (SF36 Mental Component Summary). We found negative associations between a wide range of cognitive domains and disease-specific HRQOL scales. CONCLUSIONS In stable LGG patients, poorer cognitive functioning is related to lower generic and disease-specific HRQOL. This confirms that cognitive assessment of LGG patients should not be done in isolation from assessment of its impact on HRQOL, both in clinical and in research settings.

Background Seizures are a common symptom in patients with low-grade glioma (LGG), negatively influencing quality of life, if uncontrolled. Besides antiepileptic drugs, antitumour treatment might contribute to a reduction in seizure frequency. The aim of this study was to determine the effect of temozolomide (TMZ) chemotherapy on seizure frequency, to identify factors associated with post-treatment seizure reduction and to analyse the prognostic value of seizure reduction for survival.Methods We retrospectively reviewed adult patients with supratentorial LGG and epilepsy who received chemotherapy with TMZ as initial treatment or for progressive disease in two hospitals (VUmc Amsterdam; MCH The Hague) between 2002 and 2012.Results We identified 104 patients with LGG with epilepsy who had received TMZ. Uncontrolled epilepsy in the 3 months preceding chemotherapy was present in 66 of 104 (63.5%) patients. A >= 50% reduction in seizure frequency after 6 months occurred in 29 of 66 (43.9%) patients. Focal symptoms at presentation (OR 6.55; 95% CI 1.45 to 32.77; p=0.015) appeared to be positively associated with seizure reduction. Seizure reduction was an independent prognostic factor for progression-free survival (HR 0.32; 95% CI 0.15 to 0.66; p=0.002) and overall survival (HR 0.33; 95% CI 0.14 to 0.79; p=0.013), along with a histological diagnosis of oligodendroglioma (HR 0.38; 95% CI 0.17 to 0.86; p=0.021). Objective responses on MRI were similar for patients with and without seizure reduction.Conclusions TMZ may contribute to an important reduction in seizure frequency in patients with LGG. Seizure reduction following TMZ treatment has prognostic significance and may serve as an important clinical outcome measure in patients with LGG.