About 20-40% of patients with brain tumor have seizures; all of whom must be treated with antiepileptic drugs (AEDs) that can cause side effects which may influence quality of life (QoL). However, little data are available regarding the weight of epilepsy on QoL in brain tumor (BT) patients, despite the fact that epilepsy is considered the most important risk factor for long-term disability in this patient population. Aim of this study is to explore the weight of epilepsy in BT patients, and to identify which factors might contribute to their epilepsy burden, as expressed by them only at their first visit in a specialized epilepsy center, in order to have a snapshot for that moment in their care cycle. We reviewed medical charts and results from a battery of tests (routinely given at our outpatient center), administered to 100 consecutive BTRE patients at their first visit, followed from 2007 to 2010. Our results reveal: (1) neurological performances and global neurocognitive status were not influenced by factors related to neoplastic disease or to epilepsy (2) side effects, cognitive deficits, and QoL concerns, as well as patients' perception of these, were significantly related to polytherapy, especially in patients who had been taking AEDs for a period longer that 6 months (3) the seizure number did not influence patients' QoL. We found that the weight of epilepsy in BTRE patients was related to AED therapy. Our study highlights the fact that epilepsy in our patients adds a significant burden, and suggests the need to give the proper attention to patients' concerns regarding the challenges that this pathology might present. Nevertheless, future studies could be designed with a follow-up period and with a patient stratification in order to better understand the weight of epilepsy for these patients.
To date, no data have been published in literature regarding either a "model" or systematic approach to caring for patients with brain tumor-related epilepsy (BTRE). In Italy, there are numerous dedicated centers for epilepsy. Study aims: to investigate how many BTRE patients were followed by these specialized centers, independent of histological grade; to have a national snapshot of the range of care issues concerning these patients, with surveys completed by Italian centers adhering to the Italian League Against Epilepsy (LICE) study group for BTRE. Each participating Italian center received a survey requesting: description of organizational structure/service model for diagnosis and treatment of epilepsy; number of patients followed (from 1/2010 to 12/2011); services offered, within the same institution or in close proximity; degree of access to colleagues from other disciplines for discussion of cases, with indication of departments/areas of specialization were sought. Thirty out of the 35 centers adhering to LICE study group completed the survey indicating total of 2,528 patients with BTRE had been treated with 940 new patients/year. Data regarding the care model, service offerings, referral sources were collected. This study is a first collaborative project of epilepsy centers throughout Italy, aimed at collecting data on a national scale. Results indicate: (1) 2,528 patients had been followed by participating centers and account for 21 % of estimated patients with BTRE in Italy (2) difficulties in organizing meetings with other specialists (e.g. for discussion of cases/patient briefings); (3) need for multidisciplinary integration with other specialists as a priority area for intervention.
In patients with brain tumor, seizures are the onset symptom in 20-40% of the patients, while a further 20-45% of the patients will present them during the course of the disease. These data are important when considering the choice of antiepileptic drugs for this particular patient population, because brain tumor-related epilepsy (BTRE) is often drug resistant, has a strong impact on the quality of life and weighs heavily on public health expenditures. In brain tumor patients, the presence of epilepsy is considered as the most important risk factor for long-term disability. For this reason, the problem of the proper administration of medications and their potential side effects is of great importance, because good seizure control can significantly improve the patients psychological and relational sphere. In these patients, new generation drugs such as gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, topiramate, and zonisamide are preferred, because they have fewer drug interactions and cause fewer side effects. Among the recently marketed drugs, lacosamide has demonstrated promising results and should be considered as a possible treatment option. Therefore, it is necessary to develop a customized treatment plan for each patient with BTRE, whose goals are complete seizure control, minimal or no side effects, and elimination of cognitive impairment and/or psychosocial problems.
To evaluate the therapeutic strategies commonly employed in the clinic for the management of brain metastases (BMs) and to correlate disease outcome with type of treatment and therapeutic resources available at the treating center.
We performed a case series analysis to evaluate the effects of levetiracetam (LEV) monotherapy on seizures, adverse events, cognitive functioning and quality of life (QoL) in patients with brain tumor-related epilepsy (BTRE). We also explored the possible effects of systemic therapies on the efficacy of LEV. Twenty-nine patients were followed (13 female, 16 male; age 24-75 years) with 12 months of follow-up. Patients were evaluated by QoL and neuropsychological tests. At final follow-up, mean LEV dosage was 1991.4 mg/day. Among patients who reached the final follow-up of 12 months (n = 15), 1 patient had ?50% reduction of seizure frequency (SF), and 14/15 were seizure free. The difference in presence/absence of seizures between baseline and final follow-up was significant (p < 0.001). Responder rate was 100%. We observed five side-effects: four mild (reversible) and one severe. Logistic regression revealed that chemotherapy and radiotherapy did not affect the efficacy of LEV in seizure outcome (p = 0.999). The following statistically significant observations emerged by tests evaluation: less worry about seizures, effects of antiepileptic, and ability to maintain social functions. Our data suggest that seizure occurrence can be an important warning sign that the clinician should heed throughout the duration of the illness. Patients with BTRE represent a unique patient population that presents difficulties regarding management of two very different pathologies: epilepsy on the one hand, and brain tumor on the other. Our data indicate that LEV, in patients with BTRE, is safe and efficacious, with positive impact on QoL.
Fotemustine at the conventional dose of 100 mg/m(2) is an active treatment for recurrent malignant gliomas (RMGs). However, it is associated with a relevant incidence of severe myelotoxicity, which is not justified in the palliative setting of this disease. This study was conducted to address whether administration of fotemustine at 60 mg/m(2) (induction) followed by 75 mg/m(2) (maintenance) would preserve clinical activity with the advantage of improved tolerance. Forty patients with RMGs pretreated with ?2 lines of chemotherapy were enrolled. Median age was 57 years (26-80) and median Karnofsky performance status was 80 (60-100). Thirty-one patients (77.5%) had tissue available for analysis of the O(6)-methylguanine methyltransferase (MGMT) gene promoter which was found to be methylated in 14 cases (45%). Overall, 8 partial responses (20%) and 13 disease stabilizations (32.5%) were observed for a disease-control rate of 52.5%. At 6 months, 21% of patients were free from progression. Grades 3 and 4 platelet and white blood cell toxicity occurred in ?10% of patients, and no patients discontinued treatment because of toxicity. No significant difference was observed for disease control rate between methylated and unmethylated patients, although a trend toward improved progression-free survival was reported for methylated patients. Low-dose fotemustine has activity comparable with that of the full-dose regimen, therefore it should be preferred for its greater tolerability. The role of MGMT gene promoter methylation status in relation to sensitivity to fotemustine is still unclear and needs further evaluation in future clinical trials.
The aim of this pilot study was to investigate the effects of levetiracetam monotherapy on seizure control, quality of life and neurocognitive performance in patients with brain tumor-related epilepsy. We present here preliminary data from 18 patients with follow-up of 6 months. We evaluated seizure frequency at baseline. We used administered Mini Mental State Examination (MMSE), Karnofsky Performance Status (KPS), Barthel index (BI), QOLIE 31P (V2), EORTC QLQ-C30 and Adverse Events Profile. After 6 months, 16 patients were seizure free (88.9%), 2 (11.1%) had reduction in seizure frequency >50%. Compared to baseline, we observed a worsening of performance (KPS p = 0.011; BI = 0.008) and global lower cognitive performance (MMSE p = 0.011); distress related to seizure frequency (p = 0.003) and medication effects (p = 0.046) were significantly lower. Levetiracetam caused mild and reversible side effects. These preliminary data on LEV monotherapy in patients with brain tumor-related epilepsy show that this antiepileptic drug is efficacious and well tolerated.
In recurrent malignant gliomas (MGs), a high rate of haematological toxicity is observed with the use of fotemustine at the conventional schedule (100 mg/m(2) weekly for 3 consecutive weeks followed by triweekly administration after a 5-week rest period). Also, the impact of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status on fotemustine activity has never been explored in the clinical setting.
In patients with brain tumor (BT), seizures are the onset symptom in 20-40% of patients, while a further 20-45% of patients will present them during the course of the disease. These patients present a complex therapeutic profile and require a unique and multidisciplinary approach. The choice of antiepileptic drugs is challenging for this particular patient population because brain tumor-related epilepsy (BTRE) is often drug-resistant, has a strong impact on the quality of life and weighs heavily on public health expenditures.In BT patients, the presence of epilepsy is considered the most important risk factor for long-term disability. For this reason, the problem of the proper administration of medications and their potential side effects is of great importance, because good seizure control can significantly improve the patients psychological and relational sphere. In these patients, new generation drugs such as gabapentin, lacosamide, levetiracetam, oxcarbazepine, pregabalin, topiramate, zonisamide are preferred because they have fewer drug interactions and cause fewer side effects. Among the recently marketed drugs, lacosamide has demonstrated promising results and should be considered a possible treatment option. Therefore, it is necessary to develop a customized treatment plan for each individual patient with BTRE. This requires a vision of patient management concerned not only with medical therapies (pharmacological, surgical, radiological, etc.) but also with emotional and psychological support for the individual as well as his or her family throughout all stages of the illness.
Epilepsy is common in patients with brain tumors. Patients presenting seizures as the first sign of a malignant glioma are at increased risk of recurrent seizures despite treatment with antiepileptic drugs. However, little is known about the incidence of epilepsy in the last stage of disease and in the end-of-life phase of brain tumor patients. We retrospectively analyzed the incidence of seizures in the last months of life in a series of patients affected by high-grade gliomas who were assisted at home during the whole course of the disease until death. A total of 157 patients were available for analysis. Of these patients, 58 (36.9 %) presented seizures in the last month before death. The risk of seizures in the end-of-life phase is higher in patients presenting previous history of epilepsy, particularly in patients with late-onset epilepsy. Out of the 58 patients presenting seizures in the last month of life, 86.2 % had previously had seizures and 13.8 % were seizure free. Most patients may encounter swallowing difficulties in taking anticonvulsants orally due to dysphagia and disturbances of consciousness, thus anticonvulsant treatment needs to be modified in advance. Loss of seizure control in the end-of-life phase may influence the quality of life of patients and their caregivers.
Epilepsy occurs in glioma, especially in low-grade glioma (LGG), but also in glioblastoma (GBM). In about 20 % of patients pharmacological treatment with anti-epileptic drugs (AEDs) fails. Refractory epilepsy is a multifactorial phenomenon not yet completely understood. The multidrug resistance phenotype was initially associated to P-glycoprotein (Pgp), an ATP-dependent transporter belonging to the same superfamily of multidrug resistance-associated proteins (MRPs). Glutathione-S-transferase-? (GST-?) is also involved in refractory epilepsy. In the present work we investigated the expression of Pgp, MRP1, MRP3 and GST-? in surgical specimens obtained from 35 patients with glioma and epilepsy. We observed MRP1 expression in tumor and endothelial cells (EC), MRP3 and Pgp expression mainly in ECs and GST-? predominantly in tumor cells (TC). MRP1 and MRP3 were more expressed in high grade glioma (HGG) than in LGG. In 6 cases we could compare tumor and periphery detecting the same MRP1 and Pgp expression, while MRP3 was mainly expressed in the tumor. We observed a trend of a better outcome in seizure control associated with a lower expression of MRP1 and MRP3. MRP3 was statistically more expressed in TCs of HGG than LGG (p = 0.0401) and more expressed in tumor than in periphery, in agreement with recent works that identify MRP3 as a potential target in GBM. Moreover, MRP3 was investigated in association with refractory epilepsy for the first time in our study and it was less expressed in patients with complete response to AEDs (p = 0.0550). Our preliminary data show an association between multidrug resistance transporters and refractory epilepsy in glioma.
Patients with brain tumor-related epilepsy (BTRE) present a complex therapeutic profile and require a unique and multidisciplinary approach. They, in fact, must face two different pathologies at the same time, brain tumor and epilepsy. Therefore, it is necessary to develop a customized treatment plan for each individual with BTRE. This requires a vision of patient management concerned not only with medical therapies related to the oncological disease and to the correct choice of antiepileptic therapies but also with emotional and psychological support for the individual and his/her family. The choice of antiepileptic drugs is challenging for these patients because BTRE is often drug-resistant, has a strong impact on the quality of life, and weighs heavily on public health expenditures. In brain tumor patients, the presence of epilepsy is considered the most important risk factor for long-term disability. The problem of the proper administration of medications and their potential side effects is of great importance, because good seizure control also has a significant impact on the patients psychological and relational sphere.
To determine whether early monitoring of the effects of bevacizumab in patients with recurrent high-grade gliomas, by a Perfusion Computed Tomography (PCT), may be a predictor of the response to treatment assessed through conventional MRI follow-up.
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