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Background: To analyse the prevalence of seizures and use of antiepileptic drugs (AEDs) in the end-of-life (EOL) phase of patients with high-grade glioma (HGG) and to identify patient characteristics associated with the occurrence of seizures in the last week of life., Methods: Patients were recruited from a cohort of adults with HGG diagnosed in 2005 and 2006 in three tertiary referral centres for patients with brain tumour. Physicians involved in the EOL care of patients who had HGG and had died were asked to fill in a questionnaire regarding seizures and antiepileptic treatment in the last 3 months and in the last week of life. Data on seizures and use of AEDs before the EOL phase were obtained from medical correspondence and hospital medical charts., Results: Out of 155 patients who had died, data for 92 patients were eligible for analysis. Twenty-nine percent of these 92 patients had seizures during the last week of life; 33% of patients had a history of seizures and 22% did not. Besides a history of status epilepticus (p=0.047), we identified no other significant risk factors for developing seizures in the last week of life. Seventy percent of all patients used AEDs before the last week of life. In 35% of patients in whom AEDs were tapered, seizures occurred in the last week of life., Conclusions: Our results demonstrate that seizures are a common symptom in patients with HGG during the last week of life and emphasise the importance of adequate AED treatment throughout the EOL phase.

Background: During the disease course of high-grade glioma (HGG) patients, the goal of therapy eventually shifts from primarily life-prolongation to primarily sustaining the quality of life as good as possible. End-of-life care is aimed at prolongation of life with good quality, but inevitably also may require medical decisions for prevention and relief of suffering with a potential life shortening effect. Few data are available on this end-of-life decision (ELD) making process in HGG patients, with decreased consciousness, confusion or cognitive deficits preventing them to participate. In this study the ELD-making process in HGG patients is described., Methods: Physicians and relatives of a cohort of 155 deceased HGG patients were identified to fill in a questionnaire regarding the end-of-life conditions (patients' ELD preferences, patients' competence) and ELD-making (forgoing treatment and the administration of drugs with a potential life-shortening effect) for their patient or relative. Data were analysed with descriptive statistics., Findings: Of 101 patients, physicians completed surveys including questions about ELDs (62% response rate). More than half of the patients relatively early became incompetent to make decisions due to delirium, cognitive deficits and/or decreasing consciousness. In 40% of patients the physician did not discuss ELD preferences with his/her patient. At least one ELD was made in 72% of patients, most often this comprised the withdrawal of dexamethasone. Palliative sedation was performed in 30% of patients and physician assisted death in 7%., Interpretation: ELDs are common practises amongst HGG patients, although their preferences towards ELDs are frequently unknown to the physician. Because the majority of patients become incompetent towards death, participation in ELD-making is only possible with advanced care planning. Hence, timely discussion of ELD preferences is encouraged., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Despite multimodal treatment, it is not possible to cure high-grade glioma (HGG) patients. Therefore, the aim of treatment is not only to prolong life, but also to prevent deterioration of health-related quality of life as much as possible. When the patient's condition declines and no further tumor treatment seems realistic, patients in the Netherlands are often referred to a primary care physician for end-of-life care. This end-of-life phase has not been studied adequately yet. The purpose of this study was to explore specific problems and needs experienced in the end-of-life phase of patients with HGG. We retrospectively examined the files of 55 patients who received treatment in our outpatient clinic and died between January 2005 and August 2008. The clinical nurse specialist in neuro-oncology maintained contact on a regular basis with (relatives of) HGG patients once tumor treatment for recurrence was no longer given. She systematically asked for signs and symptoms. The majority of the patients experienced loss of consciousness and difficulty with swallowing, often arising in the week before death. Seizures occurred in nearly half of the patients in the end-of-life phase and more specifically in one-third of the patients in the week before dying. Other common symptoms reported in the end-of-life phase are progressive neurological deficits, incontinence, progressive cognitive deficits, and headache. Our study demonstrates that HGG patients, unlike the general cancer population, have specific symptoms in the end-of-life phase. Further research is needed in order to develop specific palliative care guidelines for these patients.

Background: Because survival benefits of treatment with radiotherapy are questionable and such treatment can cause substantial damage to the brain over time, the optimum management strategy for low-grade gliomas remains controversial. We aimed to identify the specific effects of radiotherapy on objective and self-reported cognitive function, and on cognitive deterioration over time, in patients with low-grade gliomas treated with early radiotherapy., Methods: 195 patients with low-grade glioma (of whom 104 had received radiotherapy 1-22 years previously) were compared with 100 low-grade haematological patients and 195 healthy controls. Our analyses aimed to differentiate between the effects of the tumour (eg, disease duration, lateralisation) and treatment effects (neurosurgery, radiotherapy, antiepileptic drugs) on cognitive function and on relative risk of cognitive disability., Findings: Low-grade glioma patients had lower ability in all cognitive domains than did low-grade haematological patients, and did even less well by comparison with healthy controls. Use of radiotherapy was associated with poorer cognitive function; however, cognitive disability in the memory domain was found only in radiotherapy patients who received fraction doses exceeding 2 Gy. Antiepileptic drug use was strongly associated with disability in attentional and executive function., Interpretation: Our findings suggest that the tumour itself has the most deleterious effect on cognitive function and that radiotherapy mainly results in additional long-term cognitive disability when high fraction doses are used. Additionally, the effects of other medical factors, especially antiepileptic drug use, on cognitive function in glioma patients deserve attention.

To investigate the extent and nature of the objective and subjective cognitive deficits and health-related quality of life (HRQOL) in adult outpatients with relatively well-controlled partial epilepsy without symptomatic aetiology, who were on carbamazepine (CBZ) monotherapy. Furthermore, we studied the influence of the epilepsy history and medication on various cognitive functions and the HRQOL. 56 outpatients (29 male, 27 female, mean age 41.3 years) with partial epilepsy were compared with 56 age-, gender-, and education-matched healthy controls. Patients were tested on attention, memory, speed of information processing, and executive functioning. Questionnaires aimed at measuring self-perceived cognitive functioning (CFQ) and HRQOL (SF-36) were administered. Mann Whitney-U tests were used to compare the two groups. Linear regression analysis was performed to identify the epilepsy and medication-related factors that are associated with cognitive functioning and HRQOL. Patients scored lower on measures of attention (P = 0.03), learning (P = 0.02) and speed of information processing (P = 0.00). Mental aspects of HRQOL such as fatigue were lower (P = 0.00), whereas physical functioning was unaffected. These patients also expressed reductions in mental functioning as indicated by a low self-perceived cognitive functioning (P = 0.01). Age at onset, duration of epilepsy, seizure type, seizure frequency, localisation, years on CBZ, and CBZ dosage were not related to cognitive functioning or HRQOL. Patients with partial epilepsy, even when able to maintain regular jobs, have impaired cognition and HRQOL that cannot be attributed to their epilepsy history or CBZ dosage or years of CBZ intake. Therefore, physicians should be more aware of their cognition and HRQOL, in addition to the antiepileptic drug regime.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is a novel cytostatic agent that has shown interesting antitumor activity in patients with advanced breast cancer. Depending on variable patient characteristics and amount and type of prior therapy, as well as the applied dose and schedule of paclitaxel, response rates have varied from 13% to 62%. However, optimal dose and schedule are still unknown. We studied a high-dose (250 to 300 mg/m2) 3-hour paclitaxel infusion schedule in a poor prognostic group of breast cancer patients who progressed or relapsed while taking anthracyclines. This regimen was given every 3 weeks. Twenty-one of the 36 patients studied had increased liver enzymes and 18 had documented liver metastases. The objective response rate was only 6%, but response rate by disease site indicated that soft tissue lesions responded in 30% of cases. For a better comparison with other reported data a uniform definition of "anthracycline refractory" is needed. Neuropathy, which was found to be dose limiting, and arthralgia/myalgia syndrome were the most frequently occurring toxicities. Both severe myelosuppression (and infections) and severe diarrhea and mucositis were reported more frequently in patients with liver dysfunction. As higher peak levels, increased areas under the concentration time curves, and longer times during which plasma concentrations were above the threshold level of 0.1 mumol/L were found in patients with elevated liver enzymes, a correlation with the observed toxicities is assumed. Further pharmacodynamic studies in such patients receiving a 3-hour infusion seem warranted.