Journal of neuro-oncology
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Journal of neuro-oncology · Mar 2009
Evaluation of MGMT promoter methylation status and correlation with temozolomide response in orthotopic glioblastoma xenograft model.
CpG methylation within the O6-methylguanine-DNA-methyltransferase (MGMT) promoter is associated with enhanced survival of glioblastoma multiforme (GBM) patients treated with temozolomide (TMZ). Although MGMT promoter is methylated in approximately 50% of GBM, several studies have reported a lack of correlation between MGMT methylation and protein expression levels and consequently inaccurate discrimination of TMZ sensitive and resistant patients. To understand the limitations of currently used assays, TMZ responsiveness of 13 GBM xenograft lines was correlated with MGMT protein expression and MGMT promoter methylation determined by (1) standard methylation-specific polymerase chain reaction (MS-PCR), (2) quantitative MS-PCR (qMS-PCR), and (3) bisulfite sequencing. ⋯ However, bisulfite sequencing revealed heterogeneity in the extent of CpG methylation in those tumors with a robust qMS-PCR signal. Three of the 4 GBM lines with a qMS-PCR signal greater than 10% had at least 1 unmethylated CpG site, while only one line was fully methylated at all 12 CpG sites. These data highlight one potential limitation of the evaluation of MGMT methylation by MS-PCR assay and suggest that more detailed evaluation of methylation at individual CpG sites relative to TMZ response may be worth pursuing.
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Journal of neuro-oncology · Feb 2009
Relationship of pre-surgery metabolic and physiological MR imaging parameters to survival for patients with untreated GBM.
Glioblastoma Multiforme (GBM) are heterogeneous lesions, both in terms of their appearance on anatomic images and their response to therapy. The goal of this study was to evaluate the prognostic value of parameters derived from physiological and metabolic images of these lesions. Fifty-six patients with GBM were scanned immediately before surgical resection using conventional anatomical MR imaging and, where possible, perfusion-weighted imaging, diffusion-weighted imaging, and proton MR spectroscopic imaging. ⋯ Intensity parameters associated with survival were the maximum and the sum of levels of lactate and of lipid within the CNI lesion, as well as the magnitude of the 10th percentile of the normalized ADC within the contrast-enhancing lesion. Patients whose imaging parameters indicating that lesions with a relatively large percentage with breakdown of the blood brain barrier or necrosis, large regions with abnormal metabolism or areas with restricted diffusion have relatively poor survival. These parameters may provide useful information for predicting outcome and for the stratification of patients into high or low risk groups for clinical trials.
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Journal of neuro-oncology · Jan 2009
Clinical TrialHypofractionated radiotherapy followed by adjuvant chemotherapy with temozolomide in elderly patients with glioblastoma.
The optimal treatment for elderly patients (age >70 years) with glioblastoma (GBM) remains controversial. We conducted a prospective trial in 43 consecutive elderly patients with GBM treated with hypofractionated radiotherapy (RT) followed by adjuvant temozolomide. ⋯ Hypofractionated RT followed by temozolomide may provide survival benefit maintaining a good quality of life in elderly patients with GBM. It may represent a reasonable therapeutic approach especially in patients with less favourably prognostic factors.
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Journal of neuro-oncology · Jan 2009
Surgical resection and permanent iodine-125 brachytherapy for brain metastases.
To evaluate the efficacy and toxicity of surgical resection and permanent iodine-125 brachytherapy without adjuvant whole brain radiation therapy (WBRT) for brain metastases. ⋯ Excellent local control was achieved using permanent iodine-125 brachytherapy for brain metastasis resection cavities, although there is a high risk of radiation necrosis over time. These data support consideration of permanent brachytherapy without adjuvant WBRT as a treatment option in patients with symptomatic or large newly diagnosed or recurrent brain metastases.
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Journal of neuro-oncology · Nov 2008
Blood loss and short-term outcome of infants undergoing brain tumour removal.
To evaluate perioperative management, early outcomes and hemocoagulative disorders in infants up to 1 year old, undergoing neurosurgery for brain tumors removal. ⋯ We illustrated the relationships between intraoperative blood loss, transfusions and haemostatic impairment in babies following brain tumor removal. Youngest infants had the higher risk to experience hemocoagulative disorders. These infants showed significantly higher impact on the global PICU burden of care, as represented by the need of mechanical ventilation, cardiovascular support and PICU length of stay.