-
Annette Leibetseder,
Michael Ackerl,
Birgit Flechl,
Adelheid Wöhrer,
Georg Widhalm,
Karin Dieckmann,
Sabine-Spiegl Kreinecker,
Josef Pichler, Johannes Hainfellner,
Matthias Preusser,
Christine Marosi
[show abstract]
[hide abstract]
ABSTRACT: 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.ResultsWe 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.
Neuro-Oncology 12/2012; · 5.72 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Some unresectable and symptomatic meningiomas recur after conventional radiation therapy or stereotactic radiosurgery and are a therapeutic challenge. Evidence-based data from medical therapy for patients with recurrent meningioma can be deemed insufficient. Because of the prevalent expression of PDGF receptors in meningiomas, the tyrosine kinase imatinib mesylate has attracted interest as a treatment option for this patient group. In this retrospective study we analyzed 18 patients with recurrent meningiomas who were treated at our institution between 1996 and 2008. Nine patients with positive immunohistochemical staining of at least one of the PDGF receptors were given a daily oral dose of 400 mg imatinib mesylate as first, second, or third-line systemic therapy. Immunohistochemical staining was performed on formalin-fixed and paraffin-embedded tumor tissue with antibodies against PDGFR-α and β, c-Kit, Arg, and c-Abl. Imatinib mesylate at a dose of 400-800 mg/day was well tolerated. Of nine patients treated with imatinib, seven had stable disease and two had progressed at the first scan after three months. We observed no complete or partial responses, although prolonged disease stabilization with progression-free survival of 66.7 % at six months was observed. Overall median progression-free survival was 16 months. We conclude that single-agent imatinib mesylate might be a well-tolerated therapeutic option with high achievement of disease stabilization for preselected patients with recurrent meningiomas. Because of the small cohort, non-randomized design, and highly diverse patient population, we propose future prospective studies to validate our results.
Journal of Neuro-Oncology 05/2012; 109(2):323-30. · 3.21 Impact Factor
-
Adelheid Wöhrer,
Thomas Waldhör,
Harald Heinzl,
Monika Hackl,
Johann Feichtinger,
Ulrike Gruber-Mösenbacher,
Andreas Kiefer,
Hans Maier,
Reinhard Motz,
Angelika Reiner-Concin,
Bernd Richling,
Carmen Idriceanu,
Michael Scarpatetti,
Roland Sedivy,
Hans-Christian Bankl,
Wolfgang Stiglbauer,
Matthias Preusser,
Karl Rössler, Johannes Andreas Hainfellner
[show abstract]
[hide abstract]
ABSTRACT: In Austria, registration of malignant brain tumours is legally mandatory, whereas benign and borderline tumours are not reported. The Austrian Brain Tumour Registry (ABTR) was initiated under the auspices of the Austrian Society of Neuropathology for the registration of malignant and non-malignant brain tumours. All Austrian neuropathology units involved in brain tumour diagnostics contribute data on primary brain tumours. Non-microscopically verified cases are added by the Austrian National Cancer Registry to ensure a population-based dataset. In 2005, we registered a total of 1,688 newly diagnosed primary brain tumours in a population of 8.2 million inhabitants with an overall age-adjusted incidence rate of 18.1/100,000 person-years. Non-malignant cases constituted 866 cases (51.3%). The incidence rate was higher in females (18.6/100,000) as compared to males (17.8/100,000), while 95/1,688 (5.6%) cases were diagnosed in children (<18 years). The most common histology was meningioma (n = 504, 29.9%) followed by glioblastoma (n = 340, 20.1%) and pituitary adenoma (n = 151, 8.9%). Comparison with the Central Brain Tumor Registry of the United States (CBTRUS) database showed high congruency of findings. The ABTR model led by neuropathologists in collaboration with epidemiologists and the Austrian National Cancer Registry presents a cooperative way to establish a population-based brain tumour registry with high quality data. This setting links cancer registration to the mission of medical practice and research as defined by the World Medical Association in the Declaration of Helsinki. The continued operation of ABTR will aid in monitoring changes in incidence and in identifying regional disease clusters or geographic variations in brain tumour morbidity/mortality.
Journal of Neuro-Oncology 07/2009; 95(3):401-11. · 3.21 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We present a small series of patients with primary glioblastoma multiforme (GBM), and combine individual genetic data with pathohistologic characteristics and clinical outcome. Eighteen patients (12 men, 6 women, median age 51 years) with histologically proven GBM underwent surgical debulking followed by radiotherapy. Fifteen received concomitant chemotherapy. Histologic typing, immunohistochemistry for CD34, karyotypic analysis, and classification of the pattern of neovascularization was done in all patients. In 12/18, we performed methylation-specific polymerase chain reaction of the MGMT gene (O-6-methylguanine-DNA methyltransferase). The survival duration of patients spanned 3-58 months. By classical banding methods, 15/18 patients showed at least one aberration characteristic for primary glioblastoma (+7 in 7/18, deletions of 9p in 10/18 and -10 or deletions from 10q in 8/18 patients). We could not assess whether patients who survived for longer periods showed less complex or fewer aberrations than the patients who survived less than one year. Losses of 6p21(VEGF), 4q27(bFGF), and 12p11 approximately p13 (ING4) were associated with the "bizarre" pattern of neoangiogenesis. Methylation of the MGMT promoter was found in 3/12 patients. Even in this small series, the main characteristic of GBM was its diversity regarding all investigated histologic and genetic characteristics. This extreme diversity should be considered in the design of targeted therapies in GBM.
Cancer Genetics and Cytogenetics 05/2006; 166(1):46-55. · 1.39 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Pleomorphic xanthoastrocytoma (PXA) is an uncommon, usually low-grade, astrocytic tumor. Characteristic histological features include tumor cell pleomorphism and lipidization of tumor cells. Albeit prognosis in PXA is generally good, cases with histological signs of anaplasia have been observed. In these cases, the differential diagnosis needs to exclude other malignancies, for example, glioblastoma or malignant fibrous histiocytoma. Immunocytochemical detection of GFAP may support exclusion of non-glial neoplasms resembling PXA. However, GFAP expression in PXA may be faint or focal, although complete lack of GFAP has not been described. A 43-year-old woman was operated on for a left occipital parasagital tumor attached to the dura. Histopathology showed a pleomorphic tumor with moderate mitotic activity and necrosis, lack of GFAP immunoreactivity and ultrastructural detection of premelanosome-like structures. These features led to the tentative diagnosis of amelanotic melanoma, and the patient was irradiated. Three years later she had local tumor recurrence and underwent another operation. The recurrent tumor showed similar plain histology as the first specimen. In contrast, anti-GFAP immunoreactivity was now detectable in pleomorphic tumor cells. Anti-GFAP staining of the first biopsy was repeated using monoclonal and polyclonal antibodies in combination with prolonged tissue pretreatment. Focal GFAP staining of tumor cells was now achieved. We conclude that non-standard GFAP staining protocols may enhance sensitivity and thus lead to detection of a low level of GFAP expression in tumor specimens, in which PXA is considered in the differential diagnosis. This may avoid misleading diagnostic considerations that impact on postoperative patient management.
Neuropathology 10/2005; 25(3):241-6. · 2.02 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Histopathologic grading of ependymomas is considered unreliable in terms of outcome prediction. Quantification of tumor cell proliferation may be useful for outcome prediction. We analyzed prognostic and predictive values of tumor cell proliferation rates using anti-Ki-67 antigen (MIB-1 antibody) and anti-topoisomerase-IIalpha (Topo-IIalpha) immunolabeling on tumor samples of 103 consecutive ependymoma patients 0.1 to 74.4 years of age. In this patient cohort, the following clinical and histopathologic parameters showed significant correlation with overall survival on univariate analysis: extent of resection, use of an operating microscope, radiologic imaging with computed tomography and/or magnetic resonance imaging, radiotherapy, tumor size (cutoff 3 cm), WHO grade, presence of tumor necrosis, increased cellularity, microvascular proliferation, and low/high Ki-67 and Topo-IIalpha indices (cutoff 20.5% and 9.4%, respectively). On multivariate analysis, incomplete resection and high Ki-67 index remained independent factors of adverse patient outcome. In Kaplan-Meier survival analysis, low (<20.5%) or high (> or = 20.5%) Ki-67 indices predicted favorable (> or = 5 years) or unfavorable (<5 years) patient outcome at 79% and 70%, respectively. We conclude that Ki-67 immunolabeling index is an independent prognostic factor and accurate predictor of outcome in patients with intracranial ependymoma. Thus, assessment of Ki-67 index in intracranial ependymoma is useful for outcome prediction in the routine diagnostic setting.
American Journal of Surgical Pathology 07/2004; 28(7):914-20. · 4.35 Impact Factor
-
Irene Slavc,
Elisabeth Schuller,
Jutta Falger,
Mehmet Günes,
Konrad Pillwein,
Thomas Czech,
Wolfgang Dietrich,
Karl Rössler,
Karin Dieckmann,
Daniela Prayer, Johannes Hainfellner
[show abstract]
[hide abstract]
ABSTRACT: Treatment options for leptomeningeal disseminated brain tumors are limited by the lack of effective drugs for intrathecal therapy of non-hematologic malignancies. We report on our experience with an intraventricular therapy consisting of mafosfamide, a preactivated cyclophosphamide derivative, and etoposide. Between May 1994 and 2002, 26 patients aged 2-19 years with various intensely pretreated disseminated brain tumors received intraventricular mafosfamide via an indwelling subcutaneous reservoir. Twenty-three of them received a dose of 20 mg. Mafosfamide was administered once or twice weekly until remission was achieved and every 2-6 weeks thereafter as maintenance therapy for a total of 736 administrations (2-63/patient). Since March 1998, two patients were switched to receive intraventricular etoposide and nine received etoposide alternating with mafosfamide. Etoposide was given at a dose of 0.5 mg x 5 d every 3-6 weeks for a total of 122 courses (1-29/patient). Immediate toxicities such as transient headaches, nausea, and vomiting occurred with mafosfamide but were manageable with premedication. Etoposide did not cause any discomfort. No long-term toxicities attributable to intrathecal therapy as evidenced by magnetic resonance imaging or neurologic evaluation were observed. Since all patients received some sort of concurrent anti-cancer therapy, the efficacy of intrathecal therapy cannot be assessed independently. However, seven of 13 patients evaluable for response by cerebrospinal fluid (CSF) cytology developed CSF dissemination under systemic chemotherapy and cleared their CSF only after administration of intrathecal mafosfamide. In conclusion, intraventricularly administered mafosfamide at a dose of 20 mg and etoposide at a dose of 0.5 mg x 5 d for patients over 2 years of age are feasible and safe and may produce responses.
Journal of Neuro-Oncology 10/2003; 64(3):239-47. · 3.21 Impact Factor
-
Maria Piribauer,
Barbara Fazeny-Dörner,
Karl Rössler,
Karl Ungersböck,
Thomas Czech,
Monika Killer,
Karin Dieckmann,
Peter Birner,
Daniela Prayer, Johannes Hainfellner,
Manfred Muhm,
Christine Marosi
[show abstract]
[hide abstract]
ABSTRACT: In our institution, 103 glioblastoma multiforme (GBM) patients aged from 55 to 83 years were treated since November 1994 as follows. All patients underwent surgical intervention (gross total resection, n = 35; subtotal resection, n = 38; stereotactic biopsy, n = 30). Subsequently all patients were offered radiotherapy and chemotherapy with CCNU. Results were as follows: 101 patients started radiotherapy, 93 patients completed it (96% of the patients aged < 65 years and 85% of the patients > or =65 years). All patients received at least 1 cycle of chemotherapy (median 3 cycles). Chemotherapy-associated toxicity was generally mild, more pronounced in females and did not increase with age. Median time to progression was 10.5+/-3.2 months for the patients < 65 years and 5.1+/-1 months for patients > or =65 years. median overall survival was 17.5+/-3.8 months in patients < 65 years and 8.6+/-1 months in patients > or =65 years (p < 0.0001). In multivariate analysis, age and female sex remained independent prognostic factors. Our data indicate that a treatment concept including concomitant radio- and chemotherapy is feasible even in elderly patients with GBM.
Anti-Cancer Drugs 02/2003; 14(2):137-43. · 2.41 Impact Factor
-
Piero Parchi,
Shu G Chen,
Paul Brown,
Wenquan Zou,
Sabina Capellari,
Herbert Budka, Johannes Hainfellner,
Patricio F. Reyes,
Gregory T. Golden,
Jean J. Hauw,
D. Carleton Gajdusek,
Pierluigi Gambetti
[show abstract]
[hide abstract]
ABSTRACT: The clinicopathological phenotype of the Gerstmann–Sträussler–Scheinker disease (GSS) variant linked to the codon 102 mutation in the prion protein (PrP) gene (GSS P102L) shows a high heterogeneity. This variability also is observed in subjects with the same prion protein gene PRNP haplotype and is independent from the duration of the disease. Immunoblot analysis of brain homogenates from GSS P102L patients showed two major protease-resistant PrP fragments (PrP-res) with molecular masses of ≈21 and 8 kDa, respectively. The 21-kDa fragment, similar to the PrP-res type 1 described in Creutzfeldt–Jakob disease, was found in five of the seven subjects and correlated with the presence of spongiform degeneration and “synaptic” pattern of PrP deposition whereas the 8-kDa fragment, similar to those described in other variants of GSS, was found in all subjects in brain regions showing PrP-positive multicentric amyloid deposits. These data further indicate that the neuropathology of prion diseases largely depends on the type of PrP-res fragment that forms in vivo. Because the formation of PrP-res fragments of 7–8 kDa with ragged N and C termini is not a feature of Creutzfeldt–Jakob disease or fatal familial insomnia but appears to be shared by most GSS subtypes, it may represent a molecular marker for this disorder.
Proceedings of the National Academy of Sciences 08/1998; · 9.68 Impact Factor
