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OBJECTIVE An autologous formalin-fixed tumor vaccine (AFTV) derived from resected glioblastoma (GBM) tissue can be used against unidentified tumor antigens. Thus, the authors conducted a multicenter double-blind phase IIb trial to investigate the efficacy of an AFTV. METHODS Eligible patients were adults with supratentorial GBMs, 16–75 years of age, with Karnofsky Performance Scale (KPS) scores ≥ 60%, and no long-term steroid administration. An AFTV comprising fixed paraffin-embedded tumor tissue with immune adjuvants or an identical placebo without fixed tumor tissue was injected intradermally over three courses before and after chemoradiotherapy. The primary and secondary end points were overall survival (OS), progression-free survival (PFS), and 3-year survival rate. RESULTS Sixty-three patients were enrolled. The average patient age was 61 years. The median KPS score was 80%, and the median resection rate was 95%. The full analysis set of 57 patients indicated no significant difference in OS (p = 0.64) for the AFTV group (median OS 25.6 months, 3-year OS rate 38%) compared with the placebo group (31.5 months and 41%, respectively) and no difference in PFS (median PFS 13.3 months in both groups, p = 0.98). For patients with imaging-based total tumor removal, the 3-year PFS rate was 81% in the AFTV group versus 46% in the placebo group (p = 0.067), whereas the 3-year OS rate was 80% versus 54% (p = 0.16), respectively. Similar results were obtained in the p53-negative subgroups. Severe adverse effects were not observed. CONCLUSIONS The AFTV may have potential effects in certain patient subgroups. A phase III study for patients with total tumor removal remains warranted to confirm these findings. Clinical trial registration no.: UMIN000010602 (UMIN Clinical Trials Registry)

Improvement of visual field defects after surgical treatment for occipital lobe epilepsy is rare. Here, the authors report on a 24-year-old man with a 15-year history of refractory epilepsy that developed after he had undergone an occipital craniotomy to remove a cerebellar astrocytoma at the age of 4. His seizures started with an elementary visual aura, followed by secondary generalized tonic-clonic convulsion. Perimetry revealed left-sided incomplete hemianopia, and MRI showed an old contusion in the right occipital lobe. After evaluation with ictal video-electroencephalography, electrocorticography, and mapping of the visual cortex with subdural electrodes, the patient underwent resection of the scarred tissue, including the epileptic focus at the occipital lobe. After surgery, he became seizure free and his visual field defect improved gradually. In addition, postoperative 123I-iomazenil (IMZ) SPECT showed partly normalized IMZ uptake in the visual cortex. This case is a practical example suggesting that neurological deficits attributable to the functional deficit zone can be remedied by successful focal resection.

Object Interleukin-6 (IL-6) is a pleiotropic cytokine that regulates diverse physiological functions, including cell proliferation and survival. Recent studies have shown that IL-6 expression is often elevated in response to several types of glioma. Although IL-6 is said to play an important role in glioma, the involvement of IL-6 signaling has been quite controversial. The aim of this study was to evaluate the involvement of IL-6 signaling in glioma and the inhibitory effect of IL-6 signaling on glioma tumor proliferation. Methods The expression of IL-6 receptors (IL-6Rs) was evaluated in glioma tissues by means of immunohistochemical analysis, and the involvement of IL-6 signaling in glioblastoma multiforme (GBM) U87MG cell proliferation was also determined. In addition, to examine the inhibitory effect of IL-6 signaling on glioma cell proliferation, the authors investigated the effects of tocilizumab, the humanized anti–human IL-6R antibody in U87MG cells. Results Increased immunoreactivity for IL-6R was predominantly found in the cytoplasm of endothelial cells in all GBM samples. Inhibition of IL-6 signaling by both IL-6– and IL-6R–specific small interfering RNA and AG490, a specific inhibitor of JAK2 phosphorylation, suppressed glioma cell proliferation. Furthermore, tocilizumab, a clinically developed humanized anti–human IL-6R antibody, exerted an antiproliferative effect on cells from the GBM cell line U87MG via the IL-6R–dependent JAK-STAT3 pathway. Conclusions The IL-6 signaling pathway plays an important role in glioma cell proliferation, and tocilizumab exerts an antitumor effect in U87MG glioma cells. These results may bring new insight into the molecular pathogenesis of glioma and may lead to a new therapeutic intervention.

Object. The most frequent genetic abnormality in human malignant gliomas is loss of heterozygosity (LOH) on chromosome 10. Candidate genes on chromosome 10 that are associated with the prognosis of patients with anaplastic astrocytoma (AA) and glioblastoma (GBM) were evaluated. Methods. The authors used 12 fluorescent microsatellite markers on both arms of chromosome 10 to study LOH in 108 primary astrocytic tumors. The LOH on chromosome 10 was observed in 11 (32%) of 34 AAs and 34 (56%) of 61 GBMs. No LOH was detected in 13 low-grade gliomas. Loss of heterozygosity was not detected in any AA in the seven patients younger than 35 years, but it was discovered in 41% of the patients older than 35 years. The prognostic significance of LOH at each locus was evaluated in 89 patients older than 15 years; 33 (37%) had supratentorial AAs and 56 (63%) had supratentorial GBMs. The Cox proportional hazards model, adjusted for patient age at surgery, the preoperative Karnofsky Performance Scale score, and the extent of surgical resection revealed that LOH on marker D10S209 near the FGFR2 and DMBT1 genes was significantly associated with shorter survival in patients with AA. The LOH on markers D10S215 and D10S541, which contain the PTEN/MMAC1 gene between them, was significantly associated with shorter survival in patients with GBM. Conclusions. In the present study it is found that LOH on chromosome 10 is an age-dependent event for patients with AAs and that LOH on marker D10S209 near the FGFR2 and DMBT1 loci is a significantly unfavorable prognostic factor. It is also reported that LOH on the PTEN/MMAC1 gene is a significantly unfavorable prognostic factor in patients with GBM.

Object. Glioblastoma multiforme (GBM) remains incurable by conventional treatments, although some patients experience long-term survival. A younger age, a higher Karnofsky Performance Scale (KPS) score, more aggressive treatment, and long progression-free intervals have been reported to be positively associated with long-term postoperative patient survival. The aim of this retrospective study was the identification of additional favorable prognostic factors affecting long-term survival in surgically treated adult patients with supratentorial GBM. Methods. Of 113 adult patients newly diagnosed with histologically verified supratentorial GBM who were enrolled in Phase III trials during the period between 1987 and 1998, six (5.3%) who survived for longer than 5 years were defined as long-term survivors, whereas the remaining 107 patients served as controls. All six were women and were compared with the controls; they were younger (mean age 44.2 years, range 31–60 years), and their preoperative KPS scores were higher (mean 85, range 60–100). Four of the six patients underwent gross-total resection. In five patients (83.3%) the progression-free interval was longer than 5 years and in three a histopathological diagnosis of giant cell GBM was made. This diagnosis was not made in the other 107 patients. Conclusions. Among adult patients with supratentorial GBM, female sex and histopathological characteristics consistent with giant cell GBM may be predictive of a better survival rate, as may traditional factors (that is, younger age, good KPS score, more aggressive resection, and a long progression-free interval).

✓ Myofibroblastoma is a rare type of benign mesenchymal tumor; only two cases of intracranial myofibroblastoma have been reported in the literature. The authors report on the case of a 34-year-old woman with a myofibroblastoma in the suprasellar region who presented with the complaint of sudden onset of headache followed within 2 weeks by progressively worsening visual disturbance. Computerized tomography scanning demonstrated a mixed low- and high-density mass in the suprasellar region and contrast-enhanced magnetic resonance imaging revealed the mass to be of mixed intensity with heterogeneous enhancement. The tumor was subtotally removed via a right frontobasal translamina—terminalis approach and her vision improved immediately. Histologically, the tumor was characterized by alternating areas of spindle-shaped and round cells that were separated by collagen fibers. The diagnosis of myofibroblastoma was based on the tumor's intense immunoreactivity for α—smooth-muscle actin and the ultrastructural identification of myofibroblasts. The tumor was thought to have originated from the meninges in the suprasellar region.

Object. One of the most frequent genetic abnormalities found in patients with glioblastoma multiforme (GBM) is homozygous deletion of the p16 tumor suppressor gene. The authors investigated whether this deletion is associated with prognosis in patients with GBM. Methods. In 46 adult patients with supratentorial GBM, homozygous deletion of the p16 gene in tumor DNA was examined using the multiplex polymerase chain reaction assay. The deletion was confirmed in 14 (30.4%) of 46 patients, eight (30.8%) of 26 men and six (30.0%) of 20 women. Cox proportional hazard regression analysis, adjusted for age at surgery, the Karnofsky Performance Scale score, extent of resection, and the MIB-1 labeling index, revealed that homozygous deletion of the p16 gene was significantly associated with overall survival and progression-free survival in men, but not in women. Conclusions. The results of this study suggest that p16 homozygous deletion is a significant unfavorable prognostic factor in male patients with GBM.