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Background: Withdrawal of antiseizure medication treatment (ASM) can be considered after completion of antitumour treatment in glioma patients who no longer suffer from seizures. We compared the risk for recurrent seizures after ASM withdrawal between patients with short-term, medium-term versus long-term seizure freedom after antitumour treatment. Methods: In this retrospective observational study, the primary outcome was time to recurrent seizure, from the starting date of no ASM treatment up to 36 months follow-up. Cox proportional hazards models were used to study the effect of risk factors on time to recurrent seizure. Stratification was done with information known at baseline. Short-term seizure freedom was defined as ≥ 3 months, but < 12 months; medium-term as 12–24 months; and long-term as ≥ 24 months seizure freedom from the date of last antitumour treatment. Results: This study comprised of 109 patients; 31% (34/109) were in the short-term, 29% (32/109) in the medium-term, and 39% (43/109) in the long-term group. A recurrent seizure was experienced by 47% (16/34) of the patients in the short-term, 31% (10/32) in the medium-term, and 44% (19/43) in the long-term group. Seizure recurrence risk was similar between patients in the short-term group as compared to the medium-term (cause-specific adjusted hazard ratio [aHR] = 0.65 [95%CI = 0.29–1.46]) and long-term group (cause-specific aHR = 1.04 [95%CI = 0.52–2.09]). Conclusions: Seizure recurrence risk is relatively similar between patients with short-term, medium-term, and long-term seizure freedom after completion of antitumour treatment.

Background and ObjectivesApproximately 10% of patients with glioma with epilepsy need antiseizure medication (ASM) triple therapy due to refractory epilepsy. The aim of this study was to evaluate whether levetiracetam combined with valproic acid and clobazam (LEV + VPA + CLB), a frequently prescribed triple therapy, has favorable effectiveness compared with other triple therapy combinations in patients with glioma.MethodsThis was a multicenter retrospective observational cohort study. The primary outcome was the cumulative incidence of time to treatment failure for any reason, from the start of ASM triple therapy treatment. The secondary outcomes included cumulative incidences of the following: (1) time to treatment failure due to uncontrolled seizures; (2) time to treatment failure due to adverse effects; and (3) time to recurrent seizures. Patients were followed up for a maximum duration of 36 months.ResultsOf 1,435 patients in the original cohort, 90 patients received ASM triple therapy after second-line ASM treatment failure due to uncontrolled seizures. LEV + VPA + CLB was prescribed to 48% (43/90) and other ASM triple therapy to 52% (47/90) of patients. The cumulative incidence of treatment failure for any reason of LEV + VPA + CLB did not statistically significantly differ from that of other ASM triple therapy combinations (12 months: 47% [95% CI 31%-62%] vs 42% [95% CI 27%-56%], p = 0.892). No statistically significant differences for treatment failure due to uncontrolled seizures (12 months: 12% [95% CI 4%-25%] vs 18% [95% CI 8%-30%], p = 0.445), adverse effects (12 months: 22% [95% CI 11%-36%] vs 15% [95% CI 7%-27%], p = 0.446), or recurrent seizures (1 month: 65% [95% CI 48%-78%] vs 63% [95% CI 47%-75%], p = 0.911) were found.DiscussionLEV + VPA + CLB might show equivalent effectiveness compared with other ASM triple therapy combinations in patients with glioma.Classification of EvidenceThis study provides Class III evidence that for patients with glio

Background and Objectives About 30% of patients with glioma need an add-on antiseizure medication (ASM) due to uncontrolled seizures on ASM monotherapy. This study aimed to determine whether levetiracetam combined with valproic acid (LEV + VPA), a commonly prescribed duotherapy, is more effective than other duotherapy combinations including either LEV or VPA in patients with glioma. Methods In this multicenter retrospective observational cohort study, treatment failure (i.e., replacement by, addition of, or withdrawal of an ASM) for any reason was the primary outcome. Secondary outcomes included (1) treatment failure due to uncontrolled seizures and (2) treatment failure due to adverse effects. Time to treatment failure was estimated from the moment of ASM duotherapy initiation. Multivariable cause-specific Cox proportional hazard models were estimated to study the association between risk factors and treatment failure. The maximum duration of follow-up was 36 months. Results A total of 1,435 patients were treated with first-line monotherapy LEV or VPA, of which 355 patients received ASM duotherapy after they had treatment failure due to uncontrolled seizures on monotherapy. LEV + VPA was prescribed in 66% (236/355) and other ASM duotherapy combinations including LEV or VPA in 34% (119/355) of patients. Patients using other duotherapy vs LEV + VPA had a higher risk of treatment failure for any reason (cause-specific adjusted hazard ratio [aHR] 1.50 [95% CI 1.07–2.12], p = 0.020), due to uncontrolled seizures (cause-specific aHR 1.73 [95% CI 1.10–2.73], p = 0.018), but not due to adverse effects (causespecific aHR 0.88 [95% CI 0.47–1.67], p = 0.703). Discussion This observational cohort study suggests that LEV + VPA has better efficacy than other ASM combinations. Similar toxicities were experienced in the 2 groups. Classification of Evidence This study provides Class III evidence that

Background and Objectives About 30% of patients with glioma need an add-on antiseizure medication (ASM) due to uncontrolled seizures on ASM monotherapy. This study aimed to determine whether levetiracetam combined with valproic acid (LEV + VPA), a commonly prescribed duotherapy, is more effective than other duotherapy combinations including either LEV or VPA in patients with glioma. Methods In this multicenter retrospective observational cohort study, treatment failure (i.e., replacement by, addition of, or withdrawal of an ASM) for any reason was the primary outcome. Secondary outcomes included (1) treatment failure due to uncontrolled seizures and (2) treatment failure due to adverse effects. Time to treatment failure was estimated from the moment of ASM duotherapy initiation. Multivariable cause-specific Cox proportional hazard models were estimated to study the association between risk factors and treatment failure. The maximum duration of follow-up was 36 months. Results A total of 1,435 patients were treated with first-line monotherapy LEV or VPA, of which 355 patients received ASM duotherapy after they had treatment failure due to uncontrolled seizures on monotherapy. LEV + VPA was prescribed in 66% (236/355) and other ASM duotherapy combinations including LEV or VPA in 34% (119/355) of patients. Patients using other duotherapy vs LEV + VPA had a higher risk of treatment failure for any reason (cause-specific adjusted hazard ratio [aHR] 1.50 [95% CI 1.07-2.12], p = 0.020), due to uncontrolled seizures (cause-specific aHR 1.73 [95% CI 1.10-2.73], p = 0.018), but not due to adverse effects (cause-specific aHR 0.88 [95% CI 0.47-1.67], p = 0.703). Discussion This observational cohort study suggests that LEV + VPA has better efficacy than other ASM combinations. Similar toxicities were experienced in the 2 groups. Classification of Evidence This study provides Class III evidence that for patients with glioma with

Background: Glioblastoma (GBM), the most common glial primary brain tumour, is without exception lethal. Every year approximately 600 patients are diagnosed with this heterogeneous disease in The Netherlands. Despite neurosurgery, chemo -and radiation therapy, these tumours inevitably recur. Currently, there is no gold standard at time of recurrence and treatment options are limited. Unfortunately, the results of dedicated trials with new drugs have been very disappointing. The goal of the project is to obtain the evidence for changing standard of care (SOC) procedures to include whole genome sequencing (WGS) and consequently adapt care guidelines for this specific patient group with very poor prognosis by offering optimal and timely benefit from novel therapies, even in the absence of traditional registration trials for this small volume cancer indication. Methods: The GLOW study is a prospective diagnostic cohort study executed through collaboration of the Hartwig Medical Foundation (Hartwig, a non-profit organisation) and twelve Dutch centers that perform neurosurgery and/or treat GBM patients. A total of 200 patients with a first recurrence of a glioblastoma will be included. Dual primary endpoint is the percentage of patients who receive targeted therapy based on the WGS report and overall survival. Secondary endpoints include WGS report success rate and number of targeted treatments available based on WGS reports and number of patients starting a treatment in presence of an actionable variant. At recurrence, study participants will undergo SOC neurosurgical resection. Tumour material will then, together with a blood sample, be sent to Hartwig where it will be analysed by WGS. A diagnostic report with therapy guidance, including potential matching off-label drugs and available clinical trials will then be sent back to the treating physician for discussing of the results in molecular tumour boards and targeted treatment decision making. Discussion: The GLOW s

Objective: This study aimed at estimating the cumulative incidence of antiepileptic drug (AED) treatment failure of first-line monotherapy levetiracetam vs valproic acid in glioma patients with epilepsy. Methods: In this retrospective observational study, a competing risks model was used to estimate the cumulative incidence of treatment failure, from AED treatment initiation, for the two AEDs with death as a competing event. Patients were matched on baseline covariates potentially related to treatment assignment and outcomes of interest according to the nearest neighbor propensity score matching technique. Maximum duration of follow-up was 36 months. Results: In total, 776 patients using levetiracetam and 659 using valproic acid were identified. Matching resulted in two equal groups of 429 patients, with similar covariate distribution. The cumulative incidence of treatment failure for any reason was significantly lower for levetiracetam compared to valproic acid (12 months: 33% [95% confidence interval (CI) 29%–38%] vs 50% [95% CI 45%–55%]; P <.001). When looking at specific reasons of treatment failure, treatment failure due to uncontrolled seizures was significantly lower for levetiracetam compared to valproic acid (12 months: 16% [95% CI 12%–19%] vs 28% [95% CI 23%–32%]; P < 0.001), but no differences were found for treatment failure due to adverse effects (12 months: 14% [95% CI 11%–18%] vs 15% [95% CI 11%–18%]; P =.636). Significance: Our results suggest that levetiracetam may have favorable efficacy compared to valproic acid, whereas level of toxicity seems similar. Therefore, levetiracetam seems to be the preferred choice for first-line AED treatment in patients with glioma.