Eefje M. Sizoo

Symptoms and problems in the end-of-life phase of high-grade glioma patients.

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 patients 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.

Review on Quality of Life Issues in Patients with Primary Brain Tumors

Health-related quality of life (HRQOL) has become an important outcome measure in clinical trials in primary brain tumor (i.e., glioma) patients, because they have an incurable disease. HRQOL is assessed using self-reported, validated questionnaires, addressing physical, psychological, emotional, and social issues. In addition to generic HRQOL instruments, disease-specific questionnaires have been developed, including for brain tumor patients. For the analysis and interpretation of HRQOL measurements, low compliance and missing data are methodological challenges. HRQOL in glioma patients may be negatively affected by the disease itself as well as by side effects of treatment. But treatment with surgery, radiotherapy, and chemotherapy may improve patient functioning and HRQOL, in addition to extending survival. Although HRQOL has prognostic significance in brain tumor patients, it is not superior to well-known clinical parameters, such as age and performance status. In clinical practice, assessing HRQOL may be helpful in the communication between doctor and patient and may facilitate treatment decisions.

Levetiracetam improves verbal memory in high-grade glioma patients

BACKGROUND Treatment of high-grade glioma (HGG) patients with anti-epileptic drugs (AEDs) has met with various side effects, such as cognitive deterioration. The cognitive effects of both older and newer AEDs in HGG patients are largely unknown. The aim of this study was to determine the effect of older and newer AEDs on cognitive performance in postoperative HGG patients. METHODS We selected HGG patients from 3 separate cohorts for use of older, newer, or no AEDs, as they represented distinct treatment eras and provided the opportunity to compare older and newer AEDs. In all 3 cohorts, patients were included within 6 weeks following neurosurgery before the start of postoperative treatment. Cognitive functioning was evaluated by an extensive neuropsychological assessment, executed in 6 cognitive domains (attention, executive functioning, verbal memory, working memory, psychomotor functioning, and information processing speed). RESULTS One hundred seventeen patients met the inclusion criteria; 44 patients used no AED, 35 were on monotherapy with a newer AED (all levetiracetam), and 38 were on monotherapy with an older AED (valproic acid or phenytoin). Patients on older and newer AEDs performed equally well as patients not on an AED, and patients on levetiracetam performed even better on verbal memory tests than patients not on an AED. Post-hoc analyses revealed that within the group using older AEDs, patients on valproic acid performed better than patients on phenytoin. CONCLUSIONS Neither levetiracetam nor valproic acid was associated with additional cognitive deficits in HGG patients. Both AEDs even appeared to have a beneficial effect on verbal memory in these patients.

The End-of-Life Phase of High-Grade Glioma Patients: Dying With Dignity?

BACKGROUND In the end-of-life (EOL) phase, high-grade glioma (HGG) patients have a high symptom burden and often lose independence because of physical and cognitive dysfunction. This might affect the patients personal dignity. We aimed to (a) assess the proportion of HGG patients dying with dignity as perceived by their relatives and (b) identify disease and care factors correlated with dying with dignity in HGG patients. METHODS We approached relatives of a cohort of 155 deceased HGG patients for the study. Participants completed a questionnaire concerning the EOL phase of the patient, covering several subthemes: (a) symptoms and signs, (b) health-related quality of life, (c) decision making, (d) place and quality of EOL care, and (e) dying with dignity. RESULTS Relatives of 81 patients participated and 75% indicated that the patient died with dignity. These patients had fewer communication deficits, experienced fewer transitions between health care settings in the EOL phase, and more frequently died at their preferred place of death. Relatives were more satisfied with the physician providing EOL care and reported that the physician adequately explained treatment options. Multivariate analysis identified satisfaction with the physician, the ability to communicate, and the absence of transitions between settings as most predictive of a dignified death. CONCLUSIONS Physicians caring for HGG patients in the EOL phase should timely focus on explaining possible treatment options, because patients experience communication deficits toward death. Physicians should strive to allow patients to die at their preferred place and avoid transitions during the last month of life.

The end-of-life phase of high-grade glioma patients: a systematic review

BackgroundHigh-grade gliomas (HGG) are rare and incurable; yet, these neoplasms result in a disproportionate share of cancer morbidity and mortality. Treatment of HGG patients is directed not merely towards prolonging life but also towards quality of life, which becomes the major goal in the end of life (EOL). The latter has received increasing attention over the last decade.MethodsWe reviewed the literature related to the EOL phase of HGG patients from 1966 up to April 2012. Articles were retrieved from PubMed, Embase, Cinahl, PsycINFO and Cochrane database. We then selected papers for analysis using pre-determined inclusion criteria and subtracted information on the topics of interest.ResultsThe search yielded 695 articles, of which 17 were classified eligible for analysis according to pre-defined inclusion criteria. Reviewed topics were symptoms and signs, quality of life and quality of dying, caregiver burden, organization and location of palliative care, supportive treatment, and EOL decision making. Nearly all identified studies were observational, with only two non-randomized intervention studies. Symptom burden is high in the EOL phase and affects the quality of life of both patient and carer. Palliative care services are more intensively used compared to other cancer patients. Cognitive deficits increase as the disease progresses, hampering communication and decision making.ConclusionThe EOL phase of HGG is substantially different from other patient groups, and more clinical studies in HGG on supportive medication, advance care planning and decision making are required. The organization of care, development of guidelines and interventions to decrease caregiver burden in the EOL phase are critical as well.

Seizures in patients with high-grade glioma: a serious challenge in the end-of-life phase

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.

Neurologic aspects of palliative care: the end of life setting.

As there are, to date, few curative treatment options for many neurologic diseases, end of life (EOL) care is an important aspect of the treatment of neurologic patients. In the EOL phase, treatment should be aimed at relieving symptoms, maintaining quality of life, and facilitating a peaceful and dignified way of dying. Common signs and symptoms in the EOL phase of neurologic patients are raised intracranial pressure, seizures, confusion, cognitive deficits, and impaired motor function. Supportive treatment of these symptoms (such as analgesic drugs, dexamethasone, antiepileptic and neuroleptic drugs) is of major importance to maintain quality of life as long as possible. Another key aspect of EOL care is EOL decision making, such as withholding or withdrawing life-sustaining treatment, and palliative sedation. The main goal of EOL decision making is the prevention and relief of suffering, even if this might hasten death. Especially in advanced stages of many neurologic diseases, confusion, cognitive deficits, communication deficits, and decreasing levels of consciousness may impair the competence of patients to participate in EOL decision making. Given that patient autonomy is increasingly essential, advance care planning (ACP) at an early stage of the disease should be considered.

MRI and thallium-201 SPECT in the prediction of survival in glioma.

IntroductionThis paper aims to study the value of MRI and Thallium 201 (201Tl) single-photon emission computed tomography (SPECT) in the prediction of overall survival (OS) in glioma patients treated with temozolomide (TMZ) and to evaluate timing of radiological follow-up.MethodsWe included patients treated with TMZ chemoradiotherapy for newly diagnosed glioblastoma multiforme (GBM) and with TMZ for recurrent glioma. MRIs and 201Tl SPECTs were obtained at regular intervals. The value of both imaging modalities in predicting OS was examined using Cox regression analyses.ResultsAltogether, 138 MRIs and 113 201Tl SPECTs in 46 patients were performed. Both imaging modalities were strongly related to OS (P ≤ 0.02). In newly diagnosed GBM patients, the last follow-up MRI (i.e., after six adjuvant TMZ courses) and SPECT (i.e., after three adjuvant TMZ courses) were the strongest predictors of OS (P = 0.01). In recurrent glioma patients, baseline measurements appeared to be the most predictive of OS (P < 0.01). The addition of one imaging modality to the other did not contribute to the prediction of OS.ConclusionsBoth MRI and 201Tl SPECT are valuable in the prediction of OS. It is adequate to restrict to one of both modalities in the radiological follow-up during treatment. In the primary GBM setting, MRI after six adjuvant TMZ courses contributes significantly to the prediction of survival. In the recurrent glioma setting, baseline MRI appears to be a powerful predictor of survival, whereas follow-up MRIs during TMZ seem to be of little additional value.

Glioma of the Central Nervous System Surveillance Counterpoint: Europe

Astrocytomas are conventionally graded according to WHO criteria. Patients with low-grade astrocytomas have a long survival and many features of chronic disease and will not be considered here. In comparison with other tumors, glioblastoma is rare [1]. Glioblastoma patients typically have a short survival duration.

Health-Related Quality of Life in Patients with High Grade Gliomas

The concept of health-related quality of life (HRQOL) was founded to evaluate the effect of a disease and its treatment on the patients’ subjective functioning and well-being. Because patients with HGG cannot be cured, HRQOL as an outcome measure in clinical trials evaluating new treatment modalities has become increasingly important. Furthermore, assessment of HRQOL in daily clinical practice improves physician-patient communication and could thereby in turn improve the patient’s quality of life. More focussed HRQOL questionnaires are needed for common use in daily practice.