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Background The importance of QoL and neurocognitive functions in patients with glioblastoma (GB) is above controversy by now. We followed newly diagnosed GB patients treated with radio-chemotherapy during their course of disease by continuously evaluating their quality of life (QoL) and cognitive functions. Methods We included consecutive patients with newly diagnosed GB from 2010 to 2013 at the Medical University of Vienna. To assess QoL the EORTC QLQ C30 and BN20 questionnaire were used. Neurocognition was measured with the NeuroCog FX. The evaluations were done 6 times every three months, beginning at the beginning of radio-chemotherapy. Results 42 patients participated in this study. We also recorded QoL and neurocognition in 23 patients after the first disease progression. Patients maintained their cognitive summary score until relapse. Patients with left-sided tumors showed significant lower scores in the subscale verbal fluency than patients with right-sided tumors. The global health score of QoL decreased after the fifth evaluation (13 months after diagnosis) whereas a peak of fatigue symptoms was obtained at the third evaluation. Furthermore, fatigue symptoms increased strongly 7 months after diagnosis and patients’ financial difficulties were mentioned more frequently by younger patients and in patients with lower education levels. Conclusions QoL and cognitive long-term assessments are feasible also in some patients with GB after a symptomatic progression. Our study demonstrates maintenance of QoL and cognitive summary scales before tumor progression. Moreover, it highlights subgroups according to tumor location and socioeconomic factors.

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.

Patients with glioblastoma multiforme (GBM) and symptomatic seizures are in need of a sufficient antiepileptic treatment. Haematological toxicity is a limiting side effect of both, first line radio-chemotherapy with temozolomide (TMZ) and co-medication with antiepileptic drugs. Valproic acid (VPA) and levetiracetam (LEV) are considered favourable agents in brain tumor patients with seizures, but are commonly reported to induce haematological side effects on their own. We hypothesized, that antiepileptic treatment with these agents has no increased impact on haematological side effects during radio-chemotherapy in the first line setting. We included 104 patients from two neuro-oncologic centres with GBM and standard radio-chemotherapy in a retrospective cohort study. Patients were divided according to their antiepileptic treatment with either VPA, LEV or without antiepileptic drug therapy (control group). Declines in haemoglobin levels and absolute blood cell counts for neutrophil granulocytes, lymphocytes and thrombocytes were analyzed twice during concomitant and once during adjuvant phase. A comparison between the examined groups was performed, using a linear mixed model. Neutrophil granulocytes, lymphocytes and thrombocytes significantly decreased over time in all three groups (all p < 0.012), but there was no significant difference between the compared groups. A significant decline in haemoglobin was observed in the LEV treated group (p = 0.044), but did not differ between the compared groups. As a novel finding, this study demonstrates that co-medication either with VPA or LEV in GBM patients undergoing first line radio-chemotherapy with TMZ has no additional impact on medium-term haematological toxicity.

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.

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.

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults. Compared with other malignancies, remote metastases in GBM are rare. However, multicentric spreading within the central nervous system is common and also metastases to the spinal cord have been reported. Some of these drop metastases may also lead to malignant spinal cord compression (MSCC). We retrospectively identified nine patients from 2001 to 2010 and performed data analysis according to a standardized clinical protocol. We also provide a review of the literature on this rare condition. MSCC from cerebral GBM is rare and is found in approximately 1 % of GBM patients. Median age of 54 years in this case series is comparable with that of GBM patients without MSCC. Treatment regimens for cerebral GBM and overall survival was similar to those for patients without MSCC. Spinal metastasis seems to occur in the advanced state of the disease, and the outcome subsequently is extremely poor. All patients presented with multicentric radiological features of GBM on cerebral MRI when MSCC was diagnosed. Subependymal enhancement is another common radiological finding in GBM patients with spinal drop metastases. Steroids and focal radiotherapy were used to treat all patients, with little clinical benefit. This study is the largest case series of MSCC from cerebral GBM. Multicentric cerebral distribution and subependymal enhancement of GBM are observed on cerebral MRI at the time of MSCC. On the basis of our results, no specific treatment recommendations for MSCC in GBM patients can be given. However, accurate diagnosis of MSCC in GBM patients with spinal signs and symptoms can lead to adequate management of symptoms and improvement of quality of life in terms of best palliative care.

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.

Purpose: Epithelial ovarian cancer is the most common cause of mortality from gynecologic malignancies. Due to advanced stage at diagnosis, most patients need systemic treatment in addition to surgery. Tumor necrosis factor (TNF)–related apoptosis-inducing ligand (TRAIL) is a member of the TNF family with a promising toxicity profile and synergistic activity with chemotherapeutic agents.Experimental Design: We used an arrayed panel of epithelial ovarian cancer tissue to assess the protein expression of TRAIL and the clinically most relevant members of its pathway death receptors 4 and 5 (DR4 and DR5) and the long form of FLICE inhibitory protein (FLIPL).Results: We could show that a majority (66.2%) of the tumor tissues displayed either reduced DR4/DR5 expression (20.6%), increased FLIPL expression (39.7%), or both (5.9%) as determined by immunohistochemistry. Furthermore, higher TRAIL expression in the surrounding connective tissue but not in the tumor cells is significantly (P < 0.05) linked with favorable overall survival in advanced-stage patients.Conclusions: Mechanisms to escape the immune surveillance mediated by TRAIL are developed by ovarian cancer cells in a high percentage. TRAIL expression in the ovarian cancer microenvironment has an effect on overall survival. These findings enhance our understanding of ovarian cancer pathology and might be helpful in guiding TRAIL-based therapy in future.

BACKGROUND: The importance of QOL and neurocognitive functions in patients with GBM is meanwhile beyond controversy. We followed newly diagnosed patients with GBM treated according to actual standard therapy during their course of disease by additionally evaluating their QOL and cognitive functions. METHODS: We included 42 consecutive patients with newly diagnosed GBM. To assess QOL we used the EORTC QLQ C30 and BN20 questionnaire. Neurocognition was measured with the NeuroCog FX. The evaluations were done 6 times every three months, beginning at the initiation of radiotherapy. RESULTS: 21/42 patients were able to do three assessments within 7 months. Afterwards, condition deterioration led to drop outs. The cognitive summary scale showed moderate impairment but remained stable. Patients with left-sided tumors showed significant lower scores in the subscale verbal fluency than patients with right-sided tumors during 4 months. The global health score of QOL decreased 20 points after the fifth evaluation whereas perceived fatigue symptoms were already increased one assessment before. Furthermore the patientś financial difficulties due to the disease increased strongly 7 months after diagnosis and were mentioned more frequently in younger patients and in patients with lower education levels. CONCLUSION: QOL and cognitive long-term assessments are feasible in patients with GBM before symptomatic progression occurs. Our study shows maintenance of QOL and cognitive summary scales before tumor progression and highlights subgroups according to tumor location and socioeconomic factors.

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. © 2014 S. Karger AG, Basel

Background: Brain metastases (BM) are an increasing challenge in modern oncology, as treatment options especially after exhaustion of local treatment approaches are very limited. Patient and Methods: A long-term surviving patient with brain-only metastatic breast cancer, who presented at our department with massive corticosteroid-refractory brain edema with serious neurological symptoms after exhaustion of all local therapy options, was started on bevacizumab. Results: Initiation of bevacizumab monotherapy led to rapid decrease of contrast-enhancing lesions and alleviation of brain edema, and allowed tapering and termination of corticosteroid administration. Neurological and neurocognitive function was restored and marked improvement in quality of life was observed. Conclusion: Our case highlights that bevacizumab may represent a feasible and effective salvage treatment option in selected patients with BM.

Background Autoantigens have been reported in a variety of tumors, providing insight into the interplay between malignancies and the immune response, and also giving rise to novel diagnostic and therapeutic concepts. Why certain tumor-associated proteins induce an immune response remains largely elusive. Results This paper analyzes the proposed link between increased abundance of a protein in cancerous tissue and the increased potential of the protein for induction of a humoral immune response, using ovarian cancer as an example. Public domain data sources on differential gene expression and on autoantigens associated with this malignancy were extracted and compared, using bioinformatics analysis, on the levels of individual genes and proteins, transcriptional coregulation, joint functional pathways, and shared protein-protein interaction networks. Finally, a selected list of ovarian cancer-associated, differentially regulated proteins was tested experimentally for reactivity with antibodies prevalent in sera of ovarian cancer patients. Genes reported as showing differential expression in ovarian cancer exhibited only minor overlap with the public domain list of ovarian cancer autoantigens. However, experimental screening for antibodies directed against antigenic determinants from ovarian cancer-associated proteins yielded clear reactions with sera. Conclusion A link between tumor protein abundance and the likelihood of induction of a humoral immune response in ovarian cancer appears evident.

2062 Background: The importance of QOL and neurocognitive functions in patients with GBM is meanwhile beyond controversy. We followed newly diagnosed patients with GBM during first and second line therapy by evaluating their QOL and cognitive functions Methods: Consecutive newly diagnosed patients with GBM were included in this study. To assess QOL we used the EORTC QLQ C30 and BN20 questionnaire and the computer based NeuroCog FX for neurocognitive assessments. The first assessment was done at the beginning of radiotherapy and was followed by further 5 evaluations every three months Results: 42 patients underwent radiation therapy with concomitant and adjuvant temozolomide. Non enzyme enhancing antiepileptic drugs (NEIAED) was prescribed for the majority of the patients (71%). Median progression free survival was 9.6 months (2.5-30.9 months). Second line therapies applied were bevacizumab in 11 patients (26%), dose-dense temozolomide in 10 patients (24%) and imatinib in 8 patients. (19%). Neither QOL nor...

2071 Background: Glioblastoma multiforme (GBM) still harbours an inevitably fatal prognosis. The specially course of this disease poses unique challenges in care provision to the relatives. We still lack data about the end-of-life phase of GBM patients to improve counseling and supporting GBM patients and their proxies. Methods: In this retrospecitve study we included 52 caregivers of deceased GBM patients treated in two hospitals in Vienna, Austria. We used a specially developed questionnaire by the Medical University of Amsterdam to explore and document the last three months of living of GBM patients. Results: Most of the included caregivers were the partners of the patients (88%) and two thirds were female. The most common symptom in GBM patients was fatigue (87%), followed by reduced consciousness (81%) and aphasia (77%). 22% of the patients were bedbound during their last three months increasing to 80% in the last week of life. 30% of the caregivers told that they felt incompletely informed for their task and about the illness of their loved one. They stated the quality of life (QOL) of the patients with 2.2 and their own with 2.8 on a scale of 1 to 7 whereas 7 displays the best possible answer. The majority of the patients (46%) died in hospitals and 38% at home, which was the most often expressed wish for place of death (45%)by patients. Regarding the caregivers’ symptoms, sadness (90%), fear (69%), burnout (60%), less interest in others (54%) and irritation (42%) were the leading ones and did not differ significantly in-between the places of death. Conclusions: The end-of-life phase of GBM patients is different from that of patients dying from other cancers. Most alarmingly, one thirds of their caregivers feels poorly informed. About two thirds of the caregivers fell overstrained and stresses thereby the urgent need for support and dedicated educational programs.

Objective Glioblastoma multiforme (GBM) still harbours an inevitably fatal prognosis. The specially course of this disease poses unique challenges in care provision to the relatives. We lack data about the caregiverś perspective on the end-of-life (EOL) phase of GBM patients to improve counseling and support. Methods In this retrospective study we included 52 caregivers of deceased GBM patients treated in two hospitals in Vienna, Austria. We used a specially developed questionnaire by the Medical University of Amsterdam to explore and document the last three months of living of GBM patients. Results Most of the included caregivers were the partners of the patients (88%) and two thirds were female. The most common symptom in GBM patients was fatigue (87%), followed by reduced consciousness (81%) and aphasia (77%). 22% of the patients were bedbound during their last three months increasing to 80% in the last week of life. 30% of the caregivers told that they felt incompletely informed for their task and about the illness of their loved one. They stated the quality of life (QOL) of the patients with 2.2 and their own with 2.8 on a scale of 1 to 7 whereas 7 displays the best possible answer. The majority of the patients (46%) died in hospitals and 38% at home, which was the most often expressed wish for place of death (45%) by patients. Regarding the caregiverś symptoms, sadness (90%), fear (69%), burnout (60%), less interest in others (54%) and irritation (42%) were the leading ones and did not differ significantly in-between the places of death. Conclusion The caregivers reported that their quality of life (QOL) was only slightly better than the QOL they attributed to the patients. About two thirds of the caregivers felt overstrained and stress thereby the urgent need for support and dedicated educational programs. Disclosure All authors have declared no conflicts of interest.

Background Young age is well-known as favorable prognostic factor for patients with glioblastoma multiforme (GBM). We reviewed the outcome and molecular tumor characteristics of “young” adult patients with newly diagnosed GBM treated in two Austrian Neurooncology centers. Patients and methods Data of patients with histologically proven GBM diagnosed between age 18 and 40 were retrospectively analysed. All cases presented as newly diagnosed GBM without previous history of neurological disease. All were treated with standard first line therapy. IDH1-R132H mutation status was analyzed by immunohistochemistry. Moreover, tumour samples were tested for MGMT promoter methylation using methylation-specific polymerase chain reaction (MS-PCR). The primary endpoint was overall survival (OS) and time to tumour progression (TTP). Results We included 70 patients (36 men and 34 women; 47 from Vienna, 23 from Linz) with a median age of 33 (range 18 to 40 years) in our study. IDH1-R132H mutations were detected in 22/56 (39.3%) cases and MGMT promoter methylation in 33/54 (61.1%) cases with available tissue samples. IDH1 mutation was highly significantly associated with MGMT promoter methylation (p 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 favourable outcome associated with young age in glioblastoma patients. The social and economic coverage of glioma patients remains an unsolved socio-ethical problem. Disclosure All authors have declared no conflicts of interest.

e12507 Background: An increasing number of patients with Glioblastoma mulitforme (GBM) are alive up to three years after diagnosis (long-term survivors). Hence there is an urgent need for data abou...