Cases reported "Glioblastoma"

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1/31. Reduction of end-stage malignant glioma by injection with autologous cytotoxic T lymphocytes.

    Autologous cytotoxic T lymphocytes (CTL) against primary-cultured malignant gliomas were generated from peripheral blood mononuclear cells in vitro in 4 patients. Activities of the CTL were highly specific to the corresponding autologous glioma and were inhibited, in one patient, with antibodies against CD3, CD8 and MHC-class I molecules. When the CTL were injected 3 times into the primary-tumor-resected cavity via an Ommaya tube, reduction of the recurrent tumors with magnetic resonance imaging (MRI)-measured volumes exceeding 45 cm3 was observed in 3 patients. In a patient with glioblastoma multiforme (GBM), the tumor volume (estimated, 130 cm3) was rapidly reduced to 1/3, although re-recurrence of the tumor followed 40 days later. A slight but distinct rapid reduction of the tumor volume was observed in another GBM patient and in an anaplastic astrocytoma patient; essentially no change was observed in a further GBM patient. These results suggest that adoptive immunotherapy with autologous CTL will be clinically effective against end-stage malignant gliomas.
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2/31. Simultaneous quantitative cerebral perfusion and Gd-DTPA extravasation measurement with dual-echo dynamic susceptibility contrast MRI.

    Quantification of cerebral perfusion using dynamic susceptibility contrast MRI generally relies on the assumption of an intact blood-brain barrier. The present study proposes a method to correct the tissue response function that does not require this assumption, thus, allowing perfusion studies in, for example, high-grade brain tumors. The correction for contrast extravasation in the tissue during the bolus passage is based on a two-compartment kinetic model. The method separates the intravascular hemodynamic response and the extravascular component and returns the corrected tissue response function for perfusion quantification as well as the extravasation rate constant of the vasculature. Results of simulation experiments with different degrees of contrast extravasation are presented. The clinical potential is illustrated by determination of the perfusion and extravasation of a glioblastoma multiforme. The correction scheme proves to be fast and reliable even in cases of low signal-to-noise ratio. It is applicable whether extravasation occurs or not. When extravasation is present, application of the proposed method is mandatory for accurate cerebral blood volume measurements. Magn Reson Med 43:820-827, 2000.
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3/31. Registration of functional and anatomical MRI: accuracy assessment and application in navigated neurosurgery.

    OBJECTIVE: A procedure for acquisition, automated registration, and fusion of functional and anatomical magnetic resonance images is presented. Its accuracy is quantitatively assessed using a publicly available gold standard. A patient case is used to illustrate the technique's clinical usefulness in image-guided neurosurgery. MATERIALS AND methods: Before and after functional MRI (fMRI) acquisition, additional anatomical images were acquired at spatial locations identical to those of the functional images (5-10 slices) for the purpose of voxel-based image registration. Registration accuracy of the anatomical volumes and high-resolution 3D MRI volumes (MP-rage imaging) was quantified using adapted data (8 patients) originating from the Vanderbilt Retrospective Registration Evaluation Project (NIH project 1 R01 NS33926-02). Selecting three subsets of slices from that data (5 slices/6 mm slice distance, 10 slices/3 mm distance, and 10 slices/6 mm distance), the small number of images available from fMRI acquisition was taken into account. Accuracies in registering these sparse data sets were then compared to the accuracy achieved using complete data. For clinical patient data (16 patients), fMRI images were fused with MP-rage images, thereby integrating anatomical images with information about the locations of functional areas. The resulting images were used for planning and navigation during tumor resections using an operating microscope (MKM, Zeiss). RESULTS: Quantitative analysis showed no loss of registration accuracy due to a reduced number of slices, regardless of whether 5 or 10 slices were used. For small-volume coverage in the anatomical images (thickness 24 mm), registration of one patient failed, and this could easily be identified by visual inspection. No failures were experienced when 54 mm was covered. In the clinical environment, all 16 interventions using fused fMRI and MRI data were successful. CONCLUSIONS: Automatic registration of functional and high-resolution anatomical MRI was found to be sufficiently accurate and reliable for use in stereotactic neurosurgery.
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4/31. Mapping therapeutic response in a patient with malignant glioma.

    Short-interval scanning of patients offers a detailed understanding of the natural progression of tumor tissue, as revealed through imaging markers such as contrast enhancement and edema, prior to therapy. Following treatment, short-interval scanning can also provide evidence of attenuation of growth rates. We present a longitudinal imaging study of a patient with glioblastoma multiforme (GBM) scanned 15 times in 104 days on a 3 T MR scanner. Images were analyzed independently by two automated algorithms capable of creating detailed maps of tumor changes as well as volumetric analysis. The algorithms, a nearest-neighbor-based tissue segmentation and a surface-modeling algorithm, tracked the patient's response to temozolomide, showing an attenuation of growth. The need for surrogate imaging end-points, of which growth rates are an example, is discussed. Further, the strengths of these algorithms, the insight gained by short-interval scanning, and the need for a better understanding of imaging markers are also described.
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5/31. Impact of brain shift on intraoperative neurophysiological monitoring with cortical strip electrodes.

    BACKGROUND: intraoperative neurophysiological monitoring has become the standard procedure for locating eloquent regions of the brain. Such continuous electrical stimulation of motor pathways is usually applied by means of flat silicon-embedded electrodes placed directly on the motor cortex. However, shifting of the silicon strip on the cortical surface as well as electrode displacement due to brain shift underneath the electrode can lead to inaccurate recordings not directly caused by intraoperative impairment of the motor cortex or the motor pathways. METHOD: This prospective study was conducted to quantify cortical brain shift during open cranial surgery and to assess its impact on electrode positioning in 31 procedures near the precentral gyrus. Three groups of different lesion volumes were distinguished. movement of the cortex between opening of the dura and completion of tumor removal as well as cortical electrode shifting were digitally measured and analyzed. FINDINGS: Cortical surface structures evidenced a significantly larger shift (up to 23.4 mm) in comparison to the electrode strips (up to 4.2 mm) in lesions with a volume of over 20 ml. Cortex shifting highly correlated with lesion volume, whereas strip electrode movement was almost unidirectional and did not differ significantly among the three groups. However, the way they were placed (completely on the cortex vs. partly underlying or overlapping the craniotomy borders) affected the magnitude of their intraoperative displacement. As a consequence, 3 of the 31 cases (9.3%) showed a significant change in the recorded motor responses due to intraoperative dislocation of the stimulating electrode. INTERPRETATION: Changes in the location of cerebral structures due to intraoperative brain shift may exert a marked influence on intraoperative neurophysiological monitoring if cortical strip electrodes are used. Therefore, long-term monitoring of the central region requires continuous checking of the position of stimulating electrodes and, if necessary, correction of their location.
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6/31. Comparative treatment planning: proton vs. x-ray beams against glioblastoma multiforme.

    The survival of patients with glioblastoma multiforme is extremely poor, the 5-year survival rate being almost zero. The cause of failure is almost exclusively local progression of tumor, the remainder is due to complications of treatment. Although this tumor is clearly radiation resistant, there is evidence of a dose response relationship. Using a thin slice CT scan of the entire head of a patient with glioblastoma multiforme, 3-dimensional radiation treatment plans were developed for treatment to a dose of 90 cobalt-Gray-equivalent (CGE). Dose distributions using protons were compared to those using x-rays. The results showed advantages for the proton beam technique. Namely the proton plan irradiated less non-target brain than the x-ray plan; this was especially so in the decrease of coverage of deep-seated structures. The volume of non-target brain that received more than 70 CGE was 175 ml for the x-ray plan and 94 ml for the proton plan. This study indicates that for a subpopulation of patients with glioblastoma multiforme, at least 90 CGE could be delivered with proton beam techniques to the target with only small volumes of normal brain structures receiving more than 70 CGE.
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7/31. Quantitation of treatment volumes from CT and MRI in high-grade gliomas: implications for radiotherapy.

    Long-term survival of patients with high-grade gliomas remains extremely poor. The main reason for such an outcome is local failure, or recurrence, after surgery and/or radiotherapy. Higher doses of radiation may result in decreased local failure rates provided that the location (and extent) of gross tumor and microscopic disease can be defined accurately. The abnormalities appearing in images from diagnostic modalities, such as CT and MRI, are being used as a starting point and as a guide for the clinical definition of tumor and its extensions. However, some recent studies on two-dimensional specimens, correlating histopathological findings to CT and MRI images, showed that the resulting definition of tumor cell extensions was unsatisfactory, different, and in need of ample margins. We carried out a retrospective analysis to compare the target volumes that would have been defined by CT, T2-weighted MRI, and T1-weighted postgadolinium MRI images of the same individual and to explore the implications of the resulting volume definitions for radiotherapy. The results of our limited study, based on the margins used, indicate that the CT-defined target volume is consistently larger than that from either of the two MRI modalities and suggest that noncoplanar approaches for its treatment and other local approaches for tumor boost should be considered. We conclude that until more definitive histopathological guidelines correlated to image features have been formulated and agreed upon, one should try to make full use of all available diagnostic information in order to minimize the possibility of geographical miss of target extensions.
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8/31. The early successful treatment of glioblastoma patients with modified boron neutron capture therapy. Report of two cases.

    We very effectively treated two patients with recurrent glioblastoma with modified boron neutron capture therapy (BNCT). In this paper, we describe the effectiveness of this treatment, and discuss the ways in which we modified the treatment. A 61-year-old man had a first operation for a right temporal glioblastoma, followed by full-dose chemo-radiotherapy. One year after the operation a partial removal was performed for the recurrent tumor at the same site. Fifty days after the second surgery, the patient received BNCT. We used an epithermal neutron beam as the neutron source, and used both sodium borocapate and boronophenylalanine as boron compounds with the craniotomy. Forty-eight hours after the BNCT, the follow-up MRI was applied to estimate the early effect of this treatment, which showed a 70% reduction in the contrast enhanced lesion, compared with the pretreatment MRI. In addition, the lesion/normal brain ratio of thallium-SPECT had improved markedly. No serial sequelae appeared after this treatment, and the patient remains healthy 6 months after the treatment. A 29-year-old young lady had a right temporal brain tumor, which was partially resected and followed by stereotactic radiosurgery for the residual mass. Seven months after the radiosurgery, a second operation was performed, which revealed the glioblastoma as diagnosis. We applied BNCT uneventfully for this patient with epithermal beam and two kinds of boron compounds as described above. For the treatment of the patient irradiation was applied without craniotomy with marked reduction of tumor volume immediately after the treatment.
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9/31. radiation necrosis and brain edema association with CyberKnife treatment.

    The CyberKnife (CK) is a frameless and image guided robotic controlled instrument for stereotactic irradiation. The authors studied CK treatment of glioma and glioblastoma, and analyzed frequency and risk factors of radiation necrosis. Of 61 patients with glioma and glioblastoma treated with CyberKnife, four patients showed symptomatic radiation necrosis. All of these patients were treated with stereotactic radiotherapy, varying from 3 to 6 fractions without previous radiation therapy. Two patients required necrotomy through craniotomy. Two patients were treated conservatively. Our four patients with radiation necrosis were not specific in terms of tumor volume and dose delivery. glioma cells invade the normal brain tissue and over-radiation to this intermingling area is one of the risk factors for injury to normal endothelial cells. The homogeneity of the maximum dose area is an important factor to reduce over radiation to the normal brain parenchyma. The dose volume effect has been discussed in terms of risk factor; however, the number of fractions and dose per fraction should be considered to avoid radiation necrosis. We consider that conformal treatment with inverse algorism, fractionated stereotactic radiotherapy and precise anatomic targeting reduce the risk of radiation necrosis.
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10/31. Sustained radiographic and clinical response in patient with bifrontal recurrent glioblastoma multiforme with intracerebral infusion of the recombinant targeted toxin TP-38: case study.

    glioblastoma multiforme remains refractory to conventional therapy, and novel therapeutic modalities are desperately needed. TP-38 is a recombinant chimeric protein containing a genetically engineered form of the cytotoxic pseudomonas exotoxin fused to transforming growth factor (TGF)-alpha. TGF-alpha binds with high affinity to the epidermal growth factor receptor, which is uniformly overexpressed in malignant gliomas, often because of gene amplification. Prior to therapy with TP-38, the patient described here was completely refractory to multiple other therapies, with radiographic and pathologic evidence of tumor progression. After therapy, she improved clinically, was weaned off steroids and anti-convulsants, and experienced a progressive decrease in enhancing tumor volume. Despite multiple prior recurrences, she has not progressed for >43 months after TP-38 therapy. Small remaining areas of enhancement demonstrate no evidence of tumor histologically and are hypometabolic on positron emission tomography. This report describes a dramatic and sustained clinical and radiographic response in a patient with a bifrontal glioblastoma multiforme treated with intratumoral infusion of a novel targeted toxin, TP-38.
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