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PubMedDate not supplied

A case of cervical lymph node metastasis resulting from glioblastoma multiforme.

This article presents a rare case of metastatic glioblastoma multiforme (GM) to the cervical lymph node. In spite of very aggressive tumor behavior, extracranial metastasis from intra-cerebral GM is rare. Only a few cases are reported in the world literature. This infrequent extracranial metastasis may be due to the fact that patients do not live long enough to manifest metastases or result from the fact that brain tissue has some structural differences from other tissues in the body. This tumor can be easily mistaken for other anaplastic tumors like malignant melanoma, malignant lymphoma, or anaplastic carcinoma. Positive glial fibrillary acidic (GFA) protein stain (an immunoperoxidase stain) of this metastatic tumor can eliminate all other time consuming, expensive, and exhausting procedures for the patient.

Adult↗
PubMed2006

Recurrent glioblastoma multiforme: a review of natural history and management options.

Glioblastoma multiforme (GBM) is one of the most aggressive primary brain tumors, with a grim prognosis despite maximal treatment. Advancements in the past decades have not significantly increased the overall survival of patients with this disease. The recurrence of GBM is inevitable, its management often unclear and case dependent. In this report, the authors summarize the current literature regarding the natural history, surveillance algorithms, and treatment options of recurrent GBM. Furthermore, they provide brief discussions regarding current novel efforts in basic and clinical research. They conclude that although recurrent GBM remains a fatal disease, the literature suggests that a subset of patients may benefit from maximal treatment efforts. Nevertheless, further research effort in all aspects of GBM diagnosis and treatment remains essential to improve the overall prognosis of this disease.

Antineoplastic Protocols↗
PubMed1996

Prognostic factors for glioblastoma multiforme--development of a prognostic index.

The prognosis for glioblastoma multiforme is generally poor. However, it can be useful to identify groups of patients with varying prognosis. Based on data from 495 consecutive patients admitted to the Norwegian Radium Hospital during 1980-1994, multivariable methods were used to identify prognostic factors independently associated with length of survival. A prognostic index was derived in 384 randomly selected patients, and tested in 111 other patients. Performance status, dexamethasone dependency, age group, surgery and behavioural changes were prognostic discriminators. On this basis a prognostic index was made and three separate subsets with different survival prognoses could be identified. The prognostic index was then tested among 20% of the patients and shown to predict reliable survival curves. In the subset with the highest index (high risk subset) almost all patients in the main group as well as in the the test group were dead within 18 months.

Age Factors↗
PubMed1999

Primary cerebellar glioblastomas multiforme in children. Report of four cases.

Primary cerebellar glioblastomas multiforme are exceedingly rare in children. The authors therefore retrospectively characterized the clinical behavior and pathological features of these tumors. A review of the database at the Hospital for Sick Children, Toronto, Canada revealed four patients with cerebellar tumors that displayed significant pleomorphism, hypercellularity, mitoses, and necrosis with pseudopalisading. The authors performed a detailed clinical, radiological, histological, and immunohistochemical analysis of the tumors in these four children (three boys and one girl; average age at presentation 7 years; range 21 months-15 years). Magnetic resonance imaging and computerized tomography most commonly revealed a large lesion with minimal edema, inhomogeneous contrast enhancement, and a discrete border. Tumor resection was subtotal in one patient and gross total in three patients. Immunostaining of the tumor cells with antisera to glial fibrillary acidic protein and vimentin was positive in varying degrees. Initial adjuvant therapy consisted of local radiation only (one patient), chemotherapy only (one patient), and radiation and chemotherapy (one patient). One patient received no adjuvant therapy. Tumor recurrence was documented in all patients: two local recurrences (at 3.5 and 7 months), one spinal recurrence (at 14 months), and one local recurrence with ventricular and spinal spread (at 8 months). Ultimately, three of the four patients developed leptomeningeal tumor spread. Patient follow up ranged from 8 to 17 months (mean 12.5 months). Three patients were dead at last follow up with a mean survival of 15 months. The prognosis for patients with cerebellar glioblastomas is extremely poor, and the tumor has a tendency for cerebrospinal fluid dissemination. The optimal management of patients harboring of these difficult-to-treat tumors, including the role of craniospinal radiation and chemotherapy, has not yet been achieved.

Adolescent↗
PubMed1996

Diffuse bone marrow metastases from glioblastoma multiforme: the role of dural invasion.

Two cases of glioblastoma multiforme (GBM) diffusely metastatic to bone marrow are presented; both patients developed back pain, thrombocytopenia, and hemorrhagic diatheses from their diffuse bony disease. In one patient the intracranial and extracranial symptoms were synchronous in their presentation. Both patients had known dural involvement by GBM at the time of craniotomy and dural venous invasion microscopically. Tumor infiltration of dura and dural vessels is a significant mechanism for extracranial spread and should be noted by surgical pathologists in their reports if it is found. Although cases of metastatic GBM have been uncommon in the past, especially without antecedent surgery or ventriculoperitoneal shunt placement, better control of local disease may enhance the possibility of extracranial spread in the future from GBM. The finding of dural invasion by GBM either at surgery or microscopically should prompt oncologists to initiate at least a limited metastatic work-up for this subset of GBM patients.

Bone Marrow Neoplasms↗
PubMedDate not supplied

Immunotreatment in patients with glioblastoma multiforme--a histopathological evaluation of reactive and inflammatory changes.

Glioblastoma multiforme (GBM) is the most common highly malignant brain tumor and is also one among the most therapy-resistant human neoplasias. At the University Hospital in Lund, a group of patients with GBM were treated with a new therapy form attempting immunization by glioma cells transfected to produce interferon-gamma. The purpose of this report was to evaluate tumor material from the first nine patients treated with this therapy, assessing the levels of inflammatory/reactive cells (lymphocytes and macrophages). Tumor biopsies from surgery performed at different time points during treatment were analyzed with conventional histotechnical methods and immunohistochemistry. A post-mortem neuropathological investigation with a whole brain assessment was achieved in 5 immunized patients. The results show that cytotoxic T lymphocytes exhibited a mild increase during immunotreatment. This increase indicates an invoked stimulation of a cytotoxic T cell reaction, which may prove beneficial when immunization is adequately manipulated in dosage and timing.

Aged↗
PubMed2001

EGFR overexpression and radiation response in glioblastoma multiforme.

PURPOSE: Recent studies have suggested relative radioresistance in glioblastoma multiforme (GM) tumors in older patients, consistent with their shorter survival. Two common molecular genetic abnormalities in GM are age related: epidermal growth factor receptor (EGFR) overexpression in older patients and p53 mutations in younger patients. We tested whether these abnormalities correlated with clinical heterogeneity in GM response to radiation treatment. METHODS AND MATERIALS: Radiographically assessed radiation response (5-level scale) was correlated with EGFR immunoreactivity, p53 immunoreactivity, and p53 exon 5-8 mutation status in 170 GM patients treated using 2 prospective clinical protocols. Spearman rank correlation and proportional-odds ordinal regression were used for univariate and multivariate analysis. RESULTS: Positive EGFR immunoreactivity predicted poor radiographically assessed radiation response (p = 0.046). Thirty-three percent of tumors with no EGFR immunoreactivity had good radiation responses (>50% reduction in tumor size by CT or MRI), compared to 18% of tumors with intermediate EGFR staining and 9% of tumors with strong staining. There was no significant relationship between p53 immunoreactivity or mutation status and radiation response. Significant relationships were noted between EGFR score and older age and between p53 score or mutation status and younger age. CONCLUSION: The observed relative radioresistance of some GMs is associated with overexpression of EGFR.

Adolescent↗
PubMed2003

Survival with dacarbazine and fotemustine in newly diagnosed glioblastoma multiforme.

A total of 55 patients with histologically proven glioblastoma multiforme (total gross resection: n=24, subtotal resection: n=20, stereotactic biopsy: n=11) were treated with the combination of dacarbazine (D) (200 mg m(-2)) and fotemustine (F) (100 mg m(-2)) and concomitant radiotherapy (2 Gy day(-1), 5 days per week using limited fields up to 60 Gy) to assess efficacy and toxicity of this regimen. Survival (median survival, 12-, 18- and 24-month survival rates) and time to progression (median time to progression (TTP), 6-month progression-free survival) were analysed by Kaplan-Meier's method. A total of 268 (range 1-8, median: 5) cycles were administered. Median survival is 14.5+ (range: 0.5-40+) months, and the 12-, 18- and 24-month survival rates are 58, 29 and 23%, respectively. Median TTP from the start of D/F therapy is 9.5+ (range: 0.5-33+) months. The 6-month progression-free survival is 54%. Partial remissions were observed in 3.6%. Main toxicity was thrombocytopenia. Five patients were excluded from further D/F application, four patients because of prolonged thrombocytopenia NCI-CTC grades 3 and 4 and one patient because of whole body erythrodermia. One patient died because of septic fever during thrombocytopenia and leukopenia NCI-CTC grade 4 after the first cycle. No other toxicities of NCI-CTC grade 3 or 4 occurred. The treatment is feasible in a complete outpatient setting and the results of the D/F regimen justify further investigations with these compounds.

Adolescent↗
PubMed2005

Phase II study of CCI-779 in patients with recurrent glioblastoma multiforme.

PURPOSE: Loss of PTEN, which is common in glioblastoma multiforme (GBM), results in activation of the mammalian target of rapapmycin (mTOR), thereby increasing mRNA translation of a number of key proteins required for cell-cycle progression. CCI-779 is an inhibitor of mTOR. The primary objectives of this study were to determine the efficacy of CCI-779 in patients with recurrent GBM and to further assess the toxicity of the drug. EXPERIMENTAL DESIGN: CCI-779 was administered weekly at a dose of 250 mg intravenously for patients on enzyme-inducing anti-epileptic drugs (EIAEDs). Patients not on EIAEDs were initially treated at 250 mg; however, the dose was reduced to 170 mg because of intolerable side effects. Treatment was continued until unacceptable toxicity, tumor progression, or patient withdrawal. The primary endpoint was 6-month progression-free survival. RESULTS: Forty-three patients were enrolled; 29 were not on EIAEDs. The expected toxicity profile of increased lipids, lymphopenia, and stomatitis was seen. There were no grade IV hematological toxicities and no toxic deaths. One patient was progression free at 6 months. Of the patients assessable for response, there were 2 partial responses and 20 with stabilization of disease. The median time to progression was 9 weeks. CONCLUSIONS: CCI-779 was well tolerated at this dose schedule; however, there was no evidence of efficacy in patients with recurrent GBM. Despite initial disease stabilization in approximately 50% of patients, the durability of response was short. Because of the low toxicity profile, CCI-779 may merit exploration in combination with other modalities.

Adult↗
PubMed1999

Reactivation of insulin-like growth factor binding protein 2 expression in glioblastoma multiforme: a revelation by parallel gene expression profiling.

We carried out a gene expression profiling study using cDNA array technology with 24 primary glioma tissues of low-grade (oligodendroglioma), intermediate-grade (anaplastic oligodendroglioma and anaplastic astrocytoma), and high-grade (glioblastomas multiforme) tumors and found that insulin-like growth factor binding protein 2 (IGFBP2) was consistently overexpressed only in glioblastoma multiforme. The cDNA array results were confirmed by Northern and Western blotting. The fact that the IGFBP2 gene, which is normally expressed in fetal cells and turned off in adult cells, becomes reactivated in the most advanced stage of glioma suggests that glioma progression is a result of dedifferentiation or results from a block of differentiation. Identification of IGFBP2 as a gene associated with glioma progression demonstrates the power and utility of high-throughput gene expression profiling in cancer gene discovery.

Gene Expression Regulation, Enzymologic↗
PubMed2004

A feasibility study of interstitial hyperthermia plus external beam radiotherapy in glioblastoma multiforme using the Multi ELectrode Current Source (MECS) system.

PURPOSE: Thermoradiotherapy has been shown in several randomized trials to increase local control compared to radiotherapy alone. The first randomized study of interstitial hyperthermia in glioblastoma multiforme showed a survival benefit for hyperthermia, though small. Improvement of the heating technique could lead to improved results. The purpose of this feasibility study is to present the clinical and thermal data of application of an improved interstitial hyperthermia system. METHODS AND MATERIALS: Six patients with a glioblastoma multiforme were treated with interstitial hyperthermia using the Multi Electrode Current Source Interstitial Hyperthermia (MECS-IHT) system. The MECS-IHT system has the capability of spatial monitoring of temperature and individually steering of heating electrodes. Three sessions were given aiming at a steady state temperature of 42 degrees C for 1 h, with an interval of 3-4 days, during an external irradiation scheme of 60 Gy in 6 weeks. Hyperthermia was delivered with a mean of 10 catheters, 18 heating electrodes and 38 thermal probes per patient. RESULTS: Sub-optimal temperatures were encountered in the first two patients leading to adjustments in technique thereafter with subsequent improvement of thermal data. With a catheter spacing of 11-12 mm, measurements yielded a mean T(90), T(50) and T(10) of 39.9, 43.7 and 45.2 degrees C, respectively, over three sessions in the last patient. The power per electrode to reach this temperature distribution varied from 25-100% of full power in each of the last four patients. Thermal data were reproducible over the three sessions. Acute toxicity was minimal. CONCLUSIONS: Despite the spatial steering capabilities of the MECS-IHT system, a large temperature heterogeneity was encountered. The heterogeneity was the reason to limit the catheter spacing to 11-12 mm, thus making only small tumour volumes feasible for interstitial heating.

Aged↗
PubMed1980

Histologic factors of prognostic significance in the glioblastoma multiforme.

The pretreatment biopsy specimens from 184 cases of malignant gliomas from The National Brain Tumor Study Group were reviewed in order to determine which, if any, of nine histologic factors were useful in subdividing the glioblastoma multiforme. In the smaller group of cases treated with surgery and supportive care only, there was a strong negative correlation between cellularity and survival. For those cases treated with surgery and radiation only, and for the study as a whole, there was a positive relationship between survival and the presence of a giant cell neoplasm. We have concluded, on the basis of this limited sample of this select group of patients, that this latter features offers a potential basis of subclassification of the glioblastoma multiforme.

Adult↗
PubMed1987

Cerebral gliomas with palisading necrosis: glioblastoma multiforme or high grade cerebral neuroblastoma? A light and electron microscopical study of three cases.

Three adult patients had cerebral malignant gliomas composed predominantly of small cells and displaying many areas of palisading necrosis, which are usually characteristic of glioblastoma multiforme. Light and electron microscopy, however, revealed tumour cells with neuritic processes, while astrocytic differentiation was convincingly excluded. It is suggested that palisading necrosis is not pathognomonic of glioblastoma multiforme and that high grade cerebral neuroblastoma should be considered in the differential diagnosis. The need for comprehensive light and electron microscopic studies for the accurate classification of gliomas is stressed.

Aged↗
PubMed2005

[F-18]-fluorodeoxyglucose positron emission tomography for targeting radiation dose escalation for patients with glioblastoma multiforme: clinical outcomes and patterns of failure.

PURPOSE: [F-18]-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging for brain tumors has been shown to identify areas of active disease. Radiation dose escalation in the treatment of glioblastoma multiforme may lead to improved disease control. Based on these premises, we initiated a prospective study of FDG-PET for the treatment planning of radiation dose escalation for the treatment of glioblastoma multiforme. METHODS AND MATERIALS: Forty patients were enrolled. Patients were treated with standard conformal fractionated radiotherapy with volumes defined by MRI imaging. When patients reached a dose of 45-50.4 Gy, they underwent FDG-PET imaging for boost target delineation, for an additional 20 Gy (2 Gy per fraction) to a total dose of 79.4 Gy (n = 30). RESULTS: The estimated 1-year and 2-year overall survival (OS) for the entire group was 70% and 17%, respectively, with a median overall survival of 70 weeks. The estimated 1-year and 2-year progression-free survival (PFS) was 18% and 3%, respectively, with a median of 24 weeks. No significant improvements in OS or PFS were observed for the study group in comparison to institutional historical controls. CONCLUSIONS: Radiation dose escalation to 79.4 Gy based on FDG-PET imaging demonstrated no improvement in OS or PFS. This study establishes the feasibility of integrating PET metabolic imaging into radiotherapy treatment planning.

Brain Neoplasms↗
PubMed1995

Phase II study of accelerated fractionation radiation therapy with carboplatin followed by vincristine chemotherapy for the treatment of glioblastoma multiforme.

PURPOSE: To conduct a Phase II one-arm study to evaluate the long-term efficacy and safety of accelerated fractionated radiotherapy combined with intravenous carboplatin for patients with previously untreated glioblastoma multiforme tumors. METHODS AND MATERIALS: Between 1988 and 1992, 83 patients received 1.9-2.0 Gy radiation three times a day with 2-h infusions of 33 mg/m2 carboplatin for two 5-day cycles separated by 2 weeks; following radiotherapy, patients received procarbazine, lomustine (CCNU), and vincristine (PCV) for 1 year or until tumor progressed. RESULTS: Eighty-three patients were evaluable for analysis. Seventy-four of the 83 patients (89%) received one or more courses of PCV; their median survival was 55 weeks. Total resection was performed in 20% (15 of 74), subtotal resection in 69% (51 of 74), and biopsy in 11% (8 of 74); reoperation (total or subtotal resection) was performed in 28 patients (37%). Survival was worst for those > or = 61 year old (median 35 weeks). Fits of the Cox proportional hazards regression model showed covariates individually predictive of improved survival were younger age (p < 0.01), smaller log of radiation volume (p = 0.008), total or subtotal resection vs. biopsy (p = 0.056), and higher Karnofsky performance status (p = 0.055). A multivariate analysis showed that age (p = 0.013) and extent of initial surgery (p = 0.003) together were predictive of a better survival with no other variables providing additional significance. Only 8.4% (7 of 83) of patients had clinically documented therapy-associated neurotoxicity ("radiation necrosis"). CONCLUSION: When comparable selection criteria were applied, the survival in this study is similar to the results currently attainable with other chemoradiation approaches. The relative safety of accelerated fractionated radiotherapy, as used in this study with carboplatin, enables concomitant full-dose administration of chemotherapy or radiosensitizing agents in glioblastoma multiforme patients.

Adult↗
PubMed2006

Dynamic susceptibility contrast-enhanced perfusion magnetic resonance (MR) imaging combined with contrast-enhanced MR imaging in the follow-up of immunogene-treated glioblastoma multiforme.

PURPOSE: To assess the value of the combined use of dynamic susceptibility contrast-enhanced perfusion magnetic resonance imaging (MRI) and conventional contrast-enhanced MRI for the follow-up of treatment of glioblastoma multiforme (GBM). MATERIAL AND METHODS: 79 examinations were performed in six surgically and immunogene-treated patients and two surgically treated patients. Ratios of the relative cerebral blood volume (rCBV) in lesions and in the contralateral normal-appearing white matter were calculated. The regions with elevated rCBV were compared with those with contrast enhancement. Tissue specimens from surgical biopsies and autopsies were studied histopathologically. RESULTS: The lesion-to-normal rCBV ratios were high in the tumors prior to operation (7.3 to 18.2) as well as in the recurrent tumors (1.6 to 13.2). The volumes of the regions with elevated rCBV were similar to those with contrast enhancement in 63 of the 79 examinations. However, in 11 of 79 examinations, the regions with high rCBV were smaller than the regions with contrast enhancement ("mismatch"). In two samples from the immunogene-treated patients this was correlated with the histopathological finding of malignant tumor with numerous proliferating GBM vessels with multiple minimal lumina, sometimes thrombotized or ruptured. These vessels may have increased permeability with contrast enhancement not accompanied by increased microvascular volume. CONCLUSION: 1) Elevated rCBV on perfusion MRI corresponding to the contrast-enhancing lesion supports the diagnosis of recurrent malignant tumor. 2) A mismatch showing a volume of rCBV elevation smaller than that of contrast enhancement can be seen in particularly aggressive tumor growth and is thus not always a sign of reactive non-tumor changes. 3) The combination of perfusion MRI and conventional contrast MRI provides useful information in the follow-up of glioblastoma multiforme treatment.

Aged↗
PubMed1989

Loss of heterozygosity on chromosome 10 in human glioblastoma multiforme.

Recessive mutations, revealed by loss of the wild-type allele, have been associated with the development of a variety of cancers in children and adults. Polymorphic chromosome 10 markers were used to screen paired tumor and lymphocyte DNA samples in 13 patients with glioblastoma multiforme. Ten patients showed loss of constitutional heterozygosity in the tumor samples. This finding suggests that a recessive gene involved in the development of glioblastoma multiforme is present on chromosome 10.

Alleles↗