Favorable benefit-risk ratio with teriflunomide treatment in relapsing-remitting multiple sclerosis: Results of the 2-year, multicenter, prospective, noninterventional TAURUS MS study in Austria.

Objectives: A prospective, multicenter, open-label, noninterventional study assessed the efficacy, safety, tolerability, and patient satisfaction with teriflunomide therapy over a 24-month follow-up period under real-world conditions in Austria. Methods: An all-comer population aged ≥18 years was followed in clinic and office-based settings. The primary objective of the study was the annualized relapse rate after 12 and 24 months of teriflunomide treatment. Patient-reported outcomes included treatment satisfaction, health-related quality of life, and fatigue, and were assessed based on the Short Form Health-36, Fatigue Severity Scale, and Treatment Satisfaction Questionnaire for Medication (TSQM)-9 questionnaires. Results: Thirty-one patients were included in the analysis, 23 of whom were still on treatment after 24 months. At 12 months (n = 24), the annualized relapse rate was 0.3 (SD, 0.8), which indicated a significant decrease compared to the annualized relapse rate of 1.0 (SD, 0.9) observed during the 12-month reference period prior to treatment initiation (p = 0.009). Similarly, after 24 months of follow-up (n = 23), the annualized relapse rate of 0.2 (SD, 0.8) was significantly lower than that during the last 24 months reference period prior to treatment initiation of 0.7 (SD, 0.8) (p = 0.0003). The Expanded Disability Status Scale score remained stable over 12 and 24 months. This also applied to patient-reported fatigue of the Fatigue Severity Scale, with a mean change of 0.1 (SD, 1.0). Patient treatment satisfaction as assessed by the TSQM-9 increased for all three domains (i.e., effectiveness, convenience, global satisfaction). This was confirmed by the physician and multiple sclerosis nurse ratings of patient treatment satisfaction and ease of use. Adverse events occurred in 38.7%, with hair thinning and diarrhea as the most common. Conclusions: This noninterventional study showed a sustained favorable benefit-risk ratio for this disease-modifying treatment with teriflunomide over 24 months in patients with relapsing-remitting multiple sclerosis. Patient-reported outcomes and ratings performed by physicians and nurses showed overall trends to improvement for patient treatment satisfaction with teriflunomide treatment and its ease of administration.

Thalidomide as palliative treatment in patients with advanced secondary glioblastoma.

BACKGROUND: For its numerous abilities including sedation, we have been using thalidomide (TH) as the 'last therapeutic option' in patients with advanced gliomas. We noticed that a small subgroup, i.e. patients with secondary glioblastoma (GBM, whose GBM has evolved over several months or years from a less malignant glioma), survived for prolonged periods. Therefore, we retrospectively evaluated the outcomes of patients with secondary GBM treated with TH at our centre. PATIENTS AND METHODS: Starting in the year 2000, we have studied 23 patients (13 females, 10 males, with a median age of 31.5 years) with secondary GBM who have received palliative treatment with TH 100 mg at bedtime. All patients had previously undergone radiotherapy and received at least 1 and up to 5 regimens of chemotherapy. RESULTS: The median duration of TH administration was 4.0 months (range 0.8-32). The median duration of overall survival after the start of TH therapy was 18.3 months (range 0.8-57). Eleven patients with secondary GBM survived longer than 1 year. Symptomatic improvement was most prominent in the restoration of a normal sleep pattern. CONCLUSION: The palliative effects of TH, especially the normalization of a sleep pattern, were highly valued by patients and families. The prolongation of survival of patients with secondary GBM has not been reported previously.

Outcome evaluation in glioblastoma patients older than 65 years: Importance of individual assessment of treatment tolerance.

BACKGROUND: In this retrospective study, we evaluated the outcome of patients with primary glioblastoma multiforme (GBM), aged >= 65 years, treated in our institution from 2003 to 2009, and compared the outcome of patients admitted into the Nordic Glioma Study (NGS group) to the outcomes of elderly patients treated during the same time period outside of studies. The primary endpoint was overall survival (OS). PATIENTS AND METHODS: The study population of 70 patients (32 females) aged 65 - 83, median 71 years, was divided into three groups: the NGS group consisted of 35 patients, 1 group of 12 patients estimated as frail was treated with back then standard radiotherapy of 60 Gy (RT arm), and 23 "fit elderly" were treated with standard radio-chemotherapy (RCT arm). 31 of the 70 patients underwent gross total resection (44%), 21 patients had subtotal resection (30%), and 18 patients underwent biopsy (26%). RESULTS: Survival in the three study arms of the NGS group was very similar to the outcomes in the whole cohort of the Nordic Glioma Study (6 - 10 months). Median OS in the RCT arm was 21.0 (6 - 47) months vs. 3.0 (0.3 - 21) months in the RT arm of the NGS group. In the temozolomide (TMZ) arm, 2 of 10 patients (20%) suffered from grade 3 - 4 thrombocytopenia. In the RCT arm, grade 3 hematologic toxicity occurred in 2 of 23 patients (8.7%) and in 1 patient of the RT arm (8.3%). This retrospective single center experience shows the wide variety of outcomes in elderly patients with GBM and underlines their need for individualized, geriatric assessment-based therapy planning.

Sorafenib for patients with pretreated recurrent or progressive high-grade glioma: a retrospective, single-institution study.

Therapeutic options for patients with pretreated advanced high-grade glioma (HGG) are limited. Sorafenib, a small molecule with multiple potential beneficial actions, appears particularly promising. We reviewed the outcomes of 30 patients with recurrent or progressive HGG treated with sorafenib within a named patient program. Overall, 16 patients suffered from recurrent or progressive glioblastoma multiforme and 14 patients had grade 3 gliomas. All but four patients had previously undergone surgical debulking; all but one patient had received previous standard multimodal treatment; and 18 patients (60%) had received more than one line of chemotherapy, in median three. Progression-free survival (PFS), defined as the time from initiation of sorafenib to treatment discontinuation because of tumor progression or death, was selected as the endpoint. The use of sorafenib resulted in a median PFS of 3 months [95% confidence interval (CI) 1.9-4.1 months] in patients with glioblastoma and of 3.1 months (95% CI 1.4-4.8 months) in patients with other HGG. The PFS-6 for the whole cohort was 23%. Sixteen patients reported adverse events, mostly moderate, with hypertension as the most frequently reported toxicity (seven patients). One patient died of cerebral bleeding (grade 5 toxicity). The overall survival after initiation of sorafenib was 6 months (95% CI 3.9-8.0 months) for patients with glioblastoma multiforme and 10 months (95% CI 3.1-16.9 months) for patients with HGG. In this retrospective analysis of heavily pretreated patients with HGG, sorafenib monotherapy was associated with tumor stabilization in a small subset of patients. The risk-benefit ratio was acceptable in the context of an apparent clinical benefit in patients with a fatal disease.

The caregivers' perspective on the end-of-life phase of glioblastoma patients.

Glioblastoma multiforme (GBM) still harbors a fatal prognosis. The involvement of the neurocognition and psyche poses unique challenges for care provision by relatives. We lack data about the caregivers' perspective on the end-of-life (EOL) phase of GBM patients to improve counseling and support. In this study we investigated the experiences of 52 caregivers of deceased GBM patients treated in Austria. We used a questionnaire developed by the University Medical Centre of Amsterdam for exploration of the EOL-phase in glioma patients. The caregivers (17 men, 34 women) completed the questionnaire in median three years after the patients' death. 29 % of caregivers reported that they felt incompletely prepared for their tasks, however, those with higher education levels felt significantly better informed. 29 % suffered from financial difficulties, which was associated with burnout (60 %) and reduced quality of life (QOL). The patients' most common symptoms reported by caregivers were fatigue (87 %), reduced consciousness (81 %) and aphasia (77 %). 22 % of patients were bedbound during their last three months increasing to 80 % in the last week of life. The reported QOL of caregivers was very low and did not differ between caregivers of patients, who died at home (40 %) and caregivers of patients, who died in hospital (46 %). The caregiver reported that their QOL was only slightly better than the QOL they attributed to the patients. Furthermore, the high frequency of financial difficulties, burnout symptoms and feelings of insufficient information emphasize the urgent need for support and training dedicated to caregivers.

Outcome and molecular characteristics of adolescent and young adult patients with newly diagnosed primary glioblastoma: a study of the Society of Austrian Neurooncology (SANO).

BACKGROUND: Young age is a favorable prognostic factor for patients with glioblastoma multiforme (GBM). We reviewed the outcomes and molecular tumor characteristics of adolescent and young adult patients with GBM treated in 2 Austrian centers. PATIENTS AND METHODS: Data on patients with histologically proven primary GBM diagnosed from 18 through 40 years of age were retrospectively analyzed. All patients were treated with standard first-line therapy. The primary end points were overall survival (OS) and time to progression (TTP). IDH1-R132H mutation status was analyzed using immunohistochemistry, and MGMT promoter methylation was assessed using methylation-specific polymerase chain reaction. RESULTS: We included 70 patients (36 men and 34 women) with a median age of 33 years. IDH1-R132H mutations were detected in 22 (39.3%) of 56 cases and MGMT promoter methylation in 33 (61.1%) of 54 cases with available tissue samples. In patients with wild-type IDH, median TTP was 8.2 months and median OS was 24 months, compared with 18 months and 44 months, respectively, observed in patients with mutated IDH. Neither IDH1 nor MGMT status showed a statistically significant association with TTP or OS. Of note, the social and economical situation of the young patients with GBM was alarming, because only 17% succeeded in staying employed after receiving the diagnosis. CONCLUSIONS: We found a high frequency of IDH1 mutations and MGMT promoter methylation among young adult patients with primary GBM that may contribute to the generally favorable outcome associated with young age. The social and economic coverage of patients with glioma remains an unsolved socio-ethical problem.

Neurocognitive and sociodemographic functioning of glioblastoma long-term survivors.

An increasing number of patients with glioblastoma multiforme live longer than 3 years after diagnosis (long-term survivors). Even so, little is known about their everyday performance and quality of life. We studied 17 glioblastoma patients surviving for longer than 3 years. We assessed all patients using the computerized neurocognitive assessment instrument NeuroCog FX test, the EORTC QLQ-C30, the EORTC QLQ-BN20, the Hospital Anxiety and Depression Scale, the Ten-Meter Walking Test, the Nine Hole Peg Test, the Boston Aphasia Severity Scale, and the Activities of Daily Living and Instrumental Activities of Daily Living forms. We included 9 female and 8 male glioblastoma long-term survivors with a median age of 51 years (24-71). The majority of the patients (10/17) scored normal in the NeuroCog FX test. However, financial difficulties, reduced social and cognitive functioning, and future uncertainty were frequently reported. Three patients showed conspicuous depression scores, two had noticeable anxiety results. Drowsiness and fatigue were the most often reported physical complaints. There were 12/17 patients who were fully independent concerning activities of daily living and 14 patients (82%) showed ≥90 points in the Barthel Index, but 6 patients (35%) were impaired in their manual dexterity, and 1 patient in mobility. Glioblastoma long-term survivors show moderate impairment in their cognitive functions and more often neurological symptoms. However, the majority of these patients are able to manage their daily routine independently. Nevertheless, future prospects remain poor and patients suffer from financial difficulties.