Journal of neuro-oncology
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Journal of neuro-oncology · Jul 2012
Results of phase I study of a multi-modality treatment for newly diagnosed glioblastoma multiforme using local implantation of concurrent BCNU wafers and permanent I-125 seeds followed by fractionated radiation and temozolomide chemotherapy.
Previously we demonstrated median survival of 69 weeks after combination therapy of permanent, low-activity I-125 seeds and BCNU wafers for recurrent glioblastoma multiforme (GBM). We designed this prospective phase I trial to assess efficacy of this combination treatment for newly diagnosed GBM. Patients with newly diagnosed GBMs deemed amenable to gross total resection were included. ⋯ The 3 patients who developed radiation toxicity, which was documented on follow-up MRI and confirmed by MRI spectroscopy (median 20 weeks), underwent treatment with steroids and bevacizumab. Our phase I study was closed during enrollment of the first 6-patient cohort because of the high incidence (60 %) of early radiation toxicity. We do not recommend the seed-wafer therapy for newly diagnosed GBM patients but rather reserve this as salvage therapy for select patients with recurrent GBM.
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Journal of neuro-oncology · Jul 2012
Expression of epidermal growth factor variant III (EGFRvIII) in pediatric diffuse intrinsic pontine gliomas.
Despite numerous clinical trials over the past 2 decades, the overall survival for children diagnosed with diffuse intrinsic pontine glioma (DIPG) remains 9-10 months. Radiation therapy is the only treatment with proven effect and novel therapies are needed. Epidermal growth factor receptor variant III (EGFRvIII) is the most common variant of the epidermal growth factor receptor and is expressed in many tumor types but is rarely found in normal tissue. ⋯ In addition, analysis of tumor samples collected immediately post mortem and of DIPG cells in culture by RT-PCR, western blot analysis, and flow cytometry confirmed EGFRvIII expression. We were therefore able to detect EGFRvIII expression in 6 of 11 DIPG cases. These data suggest that EGFRvIII warrants investigation as a target for these deadly pediatric tumors.
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As targeted therapies advance treatment for brain tumors, standard clinical trial endpoints of survival, progression free survival and radiographic response have become insufficient to capture clinical benefit. Brain cancer is a malignancy with neurodegenerative features. In this setting prolongation of life and/or radiographic stability are less clinically meaningful if neurocognitive function substantially declines. Hence evaluation of new therapeutic strategies should routinely include periodic assessment of neurocognitive function.
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Journal of neuro-oncology · Jun 2012
ReviewCognition and resective surgery for diffuse infiltrative glioma: an overview.
Compared to classical oncological outcome measures such as time to progression and survival, the importance of cognitive functioning in patients with diffuse infiltrative brain tumors has only recently been recognized. Apart from the relatively low incidence and the invariably fatal outcome of gliomas, the general assumption that cognitive assessment is time-consuming and burdensome contributes to this notion. ⋯ The impact of other factors affecting cognition in glioma patients such as direct tumor effects, radiotherapy and chemotherapy, and medical treatment, including anti-epileptic drugs and steroids, have been studied more extensively. The purpose of this paper is to provide an overview of cognition in patients with diffuse infiltrative gliomas and the impact of resective surgery as well as other tumor and treatment-related factors.
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Journal of neuro-oncology · Jun 2012
Cognitive outcome as part and parcel of clinical outcome in brain tumor surgery.
Although validated tools (neuropsychological tests, patient reported outcomes, mood and psychological profile) were first introduced many years ago in clinical practice, the impact of the tumor itself on patient cognition has not been extensively studied. Furthermore, while outcome research is evolving in an attempt to adapt the use of different tools to the preoperative and postoperative phases, the standard guidelines for evaluating outcome after brain surgery, by neurological examination and complication assessment, are frequently neglected in the current literature. This article attempts to provide an appraisal of the evidence for the impact of surgical treatment on cognitive function of brain tumor patients within the context of general outcome.