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PubMed2006

Glioblastoma multiforme of the pineal region.

Glioblastoma multiforme (GBMs) tumors are exceedingly rare tumors in the pineal region. We present three cases in which patients presented with a pineal/posterior third ventricular region mass and review all the previously reported cases in the literature. Pineal region GBM seems to be a very aggressive tumor with a high rate of leptomeningeal and ependymal metastatic disease. Patients usually present with signs and symptoms of hydrocephalus and Parinaud's syndrome. The clinical and radiological characteristics of pineal GBM do not differentiate it from other malignancies of this region, thus surgical biopsy is generally required for definitive diagnosis. Glioblastoma should be considered in the differential diagnosis of the pineal region tumors, especially when evidence of leptomeningeal or ependymal metastatic disease is present.

Adult↗

PubMed2003

Cell type selective accumulation of mercaptoundecahydro- closo-dodecaborate (BSH) in glioblastoma multiforme.

BACKGROUND: Boron uptake in glioblastoma tissue for boron neutron capture therapy is of great importance for the clinical outcome of the treatment. METHODS: The cell type specific distribution of mercaptoundecahydro-closo-dodecaborate (BSH) in glioblastoma multiforme tissue sections of seven patients having received BSH prior to surgery was investigated by light and fluorescence microscopy. FINDINGS: With use of specific antibodies against different tumour specific epitopes and BSH, BSH was found predominantly (approx. 90%) in the cytoplasm of GFAP-positive cells of all but two patients. The latter were younger (33 and 38 years versus 46-71 (mean 60) years). There was no correlation between BSH uptake and expression of EGFR, p53, CD44 and Ki-67. INTERPRETATION: GFAP-positive cells appear to be the primary cell type for BSH uptake in primary glioblastoma, and an important cell type for localisation of BSH in secondary glioblastoma. The molecular basis and the selective uptake mechanism require further work. If a correlation between histologically distinct patterns and clinical outcome for patients undergoing boron neutron capture therapy could be derived, prognostic factors for the treatment could be developed.

Adult↗

PubMed1977

Soluble membrane antigens of brain tumors. I. Controlled testing for cell-mediated immune responses in a long surviving glioblastoma multiforme patient.

A patient with glioblastoma multiforme survived 18 years after diagnosis and underwent 20 operations for extracranial metastasis. An immunologic survey of the patient was made over a 1-year-period using in vitro tests of lymphocyte responsiveness and skin tests with control and tumor antigens isolated from autologous and allogenic brain cell membranes. Two tissue-associated soluble cell membrane antigens also present in normal white matter, and two tumor-associated antigens (TAA) produce cell-mediated immune responses in patients with brain tumors. One of these tumor-associated antigens predominates in meningioma cells. In addition some low molecular weight components appeared, which seemed to be unique for the glioblastoma cells from the long-surviving patient.

Antigens↗

PubMed2006

Cerebellar glioblastoma multiforme in an adult.

Cerebellar glioblastoma multiforme (GBM) is a rare tumor. This is the third case published in Brazilian literature and, the last one has been described more than 15 years ago. The aggressive behavior of GBM prompts for fast treatment, which can be hampered by the fact that the diagnosis of GBM requires a high degree of suspicion. We describe a case of GBM in a 46 years old man. In conjunction, we present a literature review including particular issues, clinical data, advances in imaging studies, pathological characteristics, treatment options and the behavior of such malignant tumor.

Biopsy↗

PubMed2006

Response to chemotherapy of a radiation-induced glioblastoma multiforme.

BACKGROUND: Radiation-induced glioblastoma multiforme (GBM) is particularly resistant to treatment and therapeutic options are limited. We report a patient with a radiation-induced GBM who had a complete response to carmustine and survived for 44 months. PATIENTS AND METHODS: Case report of a 38-year-old man with a radiation-induced GBM that responded to carmustine. RESULTS: Our patient developed a left occipital GBM 35 years after a left cerebellar astrocytoma was treated with surgery and radiation therapy (4500 rad). The GBM was treated with subtotal resection followed by four cycles of carmustine; a complete response was achieved. He relapsed 34 months after diagnosis and with further surgery survived 44 months from his diagnosis of GBM. CONCLUSION: GBMs may be a late complication of radiation treatment for pediatric brain tumors. If further radiotherapy is not a therapeutic option, chemotherapy may result in prolonged survival.

Adult↗

PubMedDate not supplied

Correlation of proliferating cell nuclear antigen assessment, histologic parameters and age with survival in patients with glioblastoma multiforme.

A series of 27 glioblastomas multiforme were studied to compare the prognostic value of age and histologic parameters known to influence survival with that of proliferating cell nuclear antigen (PCNA). The labelling index (LI) of PCNA has been found in previous studies to correlate well with flow cytometry, tritiated thymidine, bromodeoxyuridine incorporation and Ki 67. The histologic parameters estimated were endothelial proliferation, number of mitoses per high power field, cellularity and a grading of necroses. The correlation coefficients between survival and each of the histologic parameters as well as with age were found to be negative but statistically insignificant. The values of these correlations in descending order were survival/age (r = -0.22), survival/endothelial proliferation (r = -0.20), survival/mitoses (r = -0.16), survival/cellularity (r = -0.07) and survival/necroses (r = -0.04). The correlation coefficient between survival and PCNA LI was also found to be negative, higher than those between survival and other estimated parameters (r = -0.37) but in a wide variation and still statistically insignificant. Despite this variation, our finding that for PCNA LI > 35% no patient survived more than 6 months may be of clinical importance.

Adult↗

PubMed2003

Feasibility and toxicity of CCNU therapy in elderly patients with glioblastoma multiforme.

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.

Aged↗

PubMed2001

Treatment costs for glioblastoma multiforme in Nova Scotia.

BACKGROUND: Glioblastoma Multiforme (GBM) is the most common and malignant brain tumor in adults. The median survival in patients harboring this neoplasm is 12 months irrespective of any form of therapy. Health care costs of illnesses with high mortality rates, such as GBM, are of particular interest in times of constrained health care resources. No information regarding costs for the treatment of patients with GBM is available in Canada. The aim of this study was to conduct an analysis of the costs of treatment of GBM in Nova Scotia. METHODS: Patients with histologically proven GBM during a three year period (1996-1998) in Nova Scotia were included in the study. Analysis was based on hospital costs supplemented by data on additional medical services received following discharge for the primary intervention. RESULTS: The mean cost of medical care per patient from the time of diagnosis to death was $17,149. The highest costs were related to hospitalization with ward costs alone accounting for 48% of all costs. Radiotherapy costs were 25%, surgery costs were 16% and chemotherapy costs were 7% of all costs. Costs for diagnostic procedures were 6% of the total costs. CONCLUSION: Our data reflect the costs and practice pattern in the treatment of GBM in Nova Scotia and may be of value as an initial attempt to analyze costs of treatment of GBM in Canada.

Adult↗

PubMed2005

Glioblastoma multiforme with long term survival.

Glioblastoma multiforme (GBM) Patients generally have a dismal prognosis, with median survival of 10-12 months. GBM with long-term survival (LTS) of (3) > or = 5 years is rare, and no definite markers indicating better prognosis have been identified till date. The present study was undertaken to evaluate GBMs with LTS in order to identify additional correlates associated with favourable outcome. The cases were evaluated for relevant clinicopathological data, proliferation index and expression of tumortumour suppressor gene (p53 ), cyclin-dependant kinase-inhibitors (p27 and p16 ) and epidermal growth factor receptor (EGFR) proteins. Six cases of GBM with LTS with an average survival of 9 years (range 5-15 years) were identified. All were young patients with mean age of 27 years (range 8-45 years). Histology of three cases was consistent with conventional GBM, while two showed prominent oligodendroglial component admixed with GBM areas. One was a giant cell GBM, which progressed to gliosarcoma on recurrence. The mean MIB-1LI was 12% (range 6-20%). p53 was immunopositive in 4 out of 5 cases. EGFR and p27 were immunonegative in all, whereas p16 was immunonegative in 3 out of 5 cases. Currently, in the absence of specific molecular and genetic markers, GBM in young patients should be meticulously evaluated for foci of oligodendroglial component and/or giant cell elements, in addition to proliferative index and p53 expression, since these probably have prognostic connotations, as evident in this study. The role of p16 and p27 however needs better definition with study of more number of cases.

Adolescent↗

PubMed2000

The prognostic significance of midline shift at presentation on survival in patients with glioblastoma multiforme.

PURPOSE: While patients with glioblastoma multiforme (GBM) who present with midline shift have a presumably worse prognosis, there is little literature evaluating the prognostic significance of this presentation in multivariate analysis in the context of other known prognostic factors. METHODS AND MATERIALS: From March 1981 to September 1993, 219 patients underwent irradiation for intracranial glioma at our institution. One hundred fourteen patients with a diagnosis of a primary GBM were analyzed for the influence of the presence of midline shift at diagnosis on survival with respect to other known prognostic factors, including age, Karnofsky performance status (KPS), and extent of surgery. Eighty-five patients (74%) presented with midline shift. Surgical treatment consisted of subtotal/total resection in 86 patients (75%). Among patients presenting with midline shift, 68 (80%) underwent subtotal/total resection before irradiation. RESULTS: Multivariate analysis of the entire cohort of patients found none of the potential prognostic factors analyzed to significantly influence survival. The overall median survival was 6 months. However, when multivariate analysis was limited to patients with a KPS of > or = 70, only the presence of midline shift and age were found to significantly influence survival. Patients with a KPS > or = 70 and with midline shift present at diagnosis had a median survival of 8 months, as compared to 14 months for those not having midline shift at presentation (p = 0.04). Patients with a KPS > or = 70 and age > 50 years had a median survival of 5 months as compared to 11 months for those < or = 50 (p = 0.02). CONCLUSION: In this series, where 80% of patients who presented with a midline shift underwent decompressive resection of GBM before irradiation, the presence of midline shift at diagnosis remained an independent prognostic factor influencing survival among good performance status patients. While the role of decompressive surgery in this setting is likely of some benefit, the extent of this benefit remains to be defined.

Adult↗

PubMed1999

Glioblastoma multiforme in a mature ovarian teratoma with recurring brain tumours.

AIMS: We report a case study to highlight the occurrence of glioblastoma multiforme in an ovarian teratoma. METHODS AND RESULTS: A 10-year-old girl presented with a left frontal lobe primitive neuroectodermal tumour which was successfully treated. After 6 uneventful years, she developed glioblastoma multiforme located posterior to the site of the initial tumour. Six years later, she presented with a mature cystic teratoma containing glioblastoma multiforme. CONCLUSIONS: Glioblastoma in an ovarian teratoma is an exceptional event, which might have an initial clinical presentation as a metastatic brain tumour. Alternatively, recurring glial tumours may occur in a genetically predisposed person; the role of radiation and chemotherapy in this context remains to be elucidated.

Biomarkers, Tumor↗

PubMed1981

Primary glioblastoma multiforme of the pineal region with leptomeningeal metastases: a case report.

The incidence of primary intracranial glioblastoma multiforme originating in the pineal region is exceedingly rare. Diffuse leptomeningeal involvement, including spinal subarachnoid metastases, by a primary glioblastoma multiforme of the pineal region has not been reported. A report of a case of primary glioblastoma multiforme of the pineal region accompanied by diffuse leptomeningeal and nodular spinal subarachnoid metastases is presented. Extensive evaluation of the complete neuraxis, including histologic examination, in all cases of primary pineal neoplasm appears to be of both diagnostic and therapeutic value.

Adult↗

PubMed1998

The hydroxyurea-induced loss of double-minute chromosomes containing amplified epidermal growth factor receptor genes reduces the tumorigenicity and growth of human glioblastoma multiforme.

OBJECTIVE: We investigated whether the hydroxyurea-induced loss of double-minute chromosomes containing amplified epidermal growth factor receptor (EGFR) genes would lead to a loss of tumorigenicity of a glioblastoma multiforme cell line. METHODS: Glioblastoma multiforme cells were treated in vitro with 0 (HU0) or 100 micromol/L (HU100) hydroxyurea and then injected into the flanks of nude mice. Survival and tumor volumes were evaluated. Pulsed-field gel electrophoresis, Southern blot hybridization, and slot-blot analysis were used to determine EGFR amplification levels. Flow cytometry and immunofluorescent staining were used for cell-cycle analysis and EGFR protein expression. RESULTS: Prior to injection, HU100 cells lost 95% of their amplified EGFR genes and developed into tumors 6 weeks after injection versus 3 weeks for HU0 cells. Mice with HU100 tumors had a median survival of 62 days versus 43 days for control mice with HU0 tumors. Pulse-field gel electrophoresis analysis showed that HU100 tumors had reamplified the EGFR gene as double-minute chromosomes of the same size as those originally present before hydroxyurea treatment. When HU100 cells were cultured in the absence of hydroxyurea, the EGFR gene also reamplified. HU100 cells grew at less than half the rate of untreated HU0 control cells in culture and showed a decreased number of cells entering the cell cycle. Immunofluorescent staining of HU150 (150 micromol/L) cells showed decreased EGFR protein expression. CONCLUSION: The EGFR gene is important for tumorigenicity in mice and growth in culture. Hydroxyurea induces the loss of double-minute chromosome-amplified EGFR genes against a selection gradient and significantly delays the onset of tumors. These results support the potential use of low-dose hydroxyurea for the treatment of human glioblastoma multiforme.

Animals↗

PubMedDate not supplied

Treatment of glioblastoma multiforme in elderly patients. Clinico-therapeutic remarks in 22 patients older than 80 years.

We report our remarks on 22 patients, 80 years of age and older, who were treated for glioblastoma multiforme. The 16 patients who underwent a multimodality treatment (surgery + radiotherapy + chemotherapy) had an average survival of 16.7 months versus the 5.8 months of the 8 patients treated with biopsy followed by radiotherapy and/or chemotherapy (log-rank test, P < 0.001). Moreover, we point out the importance of MGMT hypermethylation as a significant prognostic factor: the 9 patients with nonmethylated MGMT had a mean survival of 7.7 months vs. 17.9 months of the 13 patients with the MGMT promoter methylated (log-rank test, P = 0.0006). Several studies have pointed out age as an important negative factor for the outcome of elderly patients affected by glioblastoma multiforme. Elderly patients with a diagnosis of glioblastoma multiforme are thus generally excluded from clinical trials of treatment for the neoplasm, because it is a common opinion that the prognosis for such patients is particularly poor. On the contrary, according to our clinical and surgical experience, we firmly believe that patients older than 80 years with a histologically proven diagnosis of glioblastoma multiforme and in good health conditions (Karnofsky performance status >60) should be treated in the same way as younger patients.

Age Factors↗

PubMedDate not supplied

Metastatic glioblastoma multiforme in cervical lymph nodes. Report of a case with diagnosis by fine needle aspiration.

Metastatic glioblastoma multiforme is a rare event usually seen in patients with previous and repeated surgery. Fine needle aspiration from enlarged lymph nodes in a patient with cerebral glioblastoma multiforme showed a highly cellular smear with dispersed single cells and cell clusters. The cells had marked pleomorphism, hyperchromasia, coarse chromatin, prominent nucleoli and occasional intranuclear cytoplasmic inclusions. Multinucleate giant cells and marked endothelial proliferation were also seen. The diagnosis of metastatic glioblastoma multiforme was supported by immunohistochemistry, which showed many cells with thick and large cytoplasmic processes with intense immunoreactivity to glial fibrillary acid protein. The differential diagnosis with other metastatic small cell tumors is discussed.

Biopsy, Needle↗

PubMed1975

Treatment of glioblastoma multiforme. A review.

Experience in irradiating 114 patients with glioblastoma multiforme is reviewed. The split-course therapy utilized in this series, even to high doses (approximately 5 600 rad in 20 fractions over 45 to 50 days), was not associated with an improved survival and does not seem of benefit over conventional fractionation. Adding BCNU (or perhaps tri-iodothyronine) to medium field (less than 135 mc) and moderate dose irradiation (5 000 rad in 25 treatments in 33 days) may improve the outlook for patients with glioblastoma multiforme. An expanded controlled clinical trial to assess this promise of improved treatment results seems indicated.

Adolescent↗

PubMed1995

[Glioblastoma multiforme with liver metastasis--case report].

Extracranial metastasis of glioblastoma is rare. This is an autopsy case report of a patient with glioblastoma multiforme found to have metastasized to the liver. A 42-year-old woman was admitted with a chief complaint of headache. Physical and neurological examinations on admission showed no abnormalities. CT and MRI demonstrated a tumor in the left parietooccipital region with invasion into the subependymal area of the left lateral ventricular trig-one. A cerebral angiogram showed tumor staining in the same area. Subtotal tumor resection was performed uneventfully. The microscopic diagnosis was glioblastoma multiforme. Postoperatively, the patient underwent whole brain and local irradiation, and intra-arterial ACNU infusion therapy. One month later, she developed low back pain, probably due to spinal dissemination. Postmortem examination showed local recurrence of the tumor and subarachnoidal dissemination not only in the base of the skull but in the lower spinal cord. Tumor was also observed in the liver, but no lung or lymph node metastasis was detected. Metastasis to the liver in this patient is believed to have occurred via the anastomosis between the vertebral and portal venous system.

Adult↗

PubMed2006

HDJ-2 as a target for radiosensitization of glioblastoma multiforme cells by the farnesyltransferase inhibitor R115777 and the role of the p53/p21 pathway.

Resistance of glioblastoma multiforme to radiotherapy poses a major clinical challenge. Farnesyltransferase inhibitors (FTI), such as R115777, have potential to increase radiotherapeutic benefit in this disease, although their mechanism of action is unclear. In our study with eight glioblastoma multiforme cell lines, the most sensitive ones underwent cell cycle arrest in response to FTI treatment. Radiosensitization by FTIs, however, seemed to involve other pathways. If R115777 treatment was initiated < 6 hours before irradiation, all eight glioblastoma multiforme lines were radiosensitized. However, if the time between drug and radiation was extended to 24 hours, cells harboring wild type but not mutated p53 were able to counteract drug-induced radiosensitization. The involvement of the p53/p21 pathway in the development of resistance was confirmed by showing that U87 cells transfected with human papillomavirus E6 to block p53 or interfering RNA to inhibit p21 stayed radiosensitive for 24 hours after drug treatment. The time dependency of R115777-induced radiosensitization suggested that the initial FTI target for early radiosensitization was short-lived, and that a p21-directed pathway restored resistance. Consideration of prenylated molecules that could potentially be involved led us to consider HDJ-2, a co-chaperone of heat shock protein 70. This hypothesis was strengthened by finding that cellular radiosensitivity was increased by genetic inhibition of HDJ-2, whereas overexpression conferred radioresistance. Importantly, irradiation of cells caused HDJ-2 to migrate from the cytoplasm to the nucleus, and this migration was inhibited by prior FTI treatment. These results have clinical relevance in that they help explain the variability in responses to FTIs that occurs following radiotherapy and elucidate some of the reasons for the complexity underlying FTI-induced radiosensitization.

Cell Cycle↗