Neuro-oncology
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Vandetanib is a once-daily multitargeted tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2, epidermal growth factor receptor, and the rearranged-during-transfection oncogene. A phase I trial was conducted to describe the pharmacokinetics of vandetanib in patients with recurrent glioma on enzyme-inducing anti-epileptic drugs (EIAEDs) and to identify the maximum tolerated dose (MTD) in this population. A phase II trial evaluated the efficacy of vandetanib in patients with recurrent malignant glioma not on EIAEDs as measured by 6-month progression-free survival (PFS6). ⋯ Median overall survival was 6.3 months in the GBM arm and 7.6 months in the AG arm. Seizures were an unexpected toxicity of therapy. Vandetanib did not have significant activity in unselected patients with recurrent malignant glioma.
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Randomized Controlled Trial
Surgery for primary CNS lymphoma? Challenging a paradigm.
The standard of care for primary central nervous system lymphoma (PCNSL) is systemic chemotherapy with or without whole brain radiotherapy or intrathecal chemotherapy. In contrast to treatment for other brain tumors, efforts at resection are discouraged. This is a secondary analysis of the German PCNSL Study Group-1 trial, a large randomized phase III study comprising 526 patients with PCNSL. ⋯ When controlled for the number of lesions, the HR of biopsy versus subtotal or gross total resection remained unchanged for progression-free survival (HR = 1.37; P = .009) but was smaller for overall survival (HR = 1.27; P = .085). This analysis of the largest PCNSL trial ever performed challenges the traditional view that the extent of resection has no prognostic impact on this disease. Therefore, we propose to reconsider the statement that efforts at resection should be discouraged, at least if resection seems safe, as is often the case in treatment of single PCNSL lesions.
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Histological subtyping and grading by malignancy are the cornerstones of the World Health Organization (WHO) classification of tumors of the central nervous system. They shall provide clinicians with guidance as to the course of disease to be expected and the choices of treatment to be made. Nonetheless, patients with histologically identical tumors may have very different outcomes, notably in patients with astrocytic and oligodendroglial gliomas of WHO grades II and III. ⋯ In 2012, this situation has changed: long-term follow-up of the Radiation Therapy Oncology Group 9402 and European Organisation for Research and Treatment of Cancer 26951 trials demonstrated an overall survival benefit from the addition to RT of chemotherapy with procarbazine/CCNU/vincristine confined to patients with anaplastic oligodendroglial tumors with (vs without) 1p/19q codeletion. Furthermore, in elderly glioblastoma patients, the NOA-08 and the Nordic trial of RT alone versus temozolomide alone demonstrated a profound impact of MGMT promoter methylation on outcome by therapy and thus established MGMT as a predictive biomarker in this patient population. These recent results call for the routine implementation of 1p/19q and MGMT testing at least in subpopulations of malignant glioma patients and represent an encouraging step toward the development of personalized therapeutic approaches in neuro-oncology.
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In the treatment of patients with low-grade glioma, there still is controversy on how surgical intervention, radiation therapy, and chemotherapy contribute to an ameliorated progression-free survival, overall survival, and treatment-related neurotoxicity. With the ongoing changes in treatment options for these patients, neurocognitive functioning is an increasingly important outcome measure, because neurocognitive impairments can have a large impact on self-care, social and professional functioning, and consequently, health-related quality of life. ⋯ This holds for both resective surgery, in which the use of intraoperative stimulation mapping has a high potential benefit concerning survival and patient functioning, and the use of chemotherapy that might have some interesting new applications, such as the facilitation of total resection for initially primary or recurrent diffuse low-grade glioma tumors. This article will discuss these treatment options in patients with low-grade glioma and their potential effects on neurocognitive functioning.
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Peripheral neuropathies induced by chemotherapy (CIPN) are an increasingly frequent problem. Contrary to hematologic adverse effects, which can be treated with hematopoetic growth factors, neither prophylaxis nor specific treatment is available, and only symptomatic treatment can be offered. Neurotoxic drugs are becoming a major dose-limiting factor. ⋯ The most frequent substances causing CIPN are platin compounds, vinka alkaloids, taxanes, and bortezomib and thalidomide. The role of synergistic neurotoxicity caused by previously given chemo-therapies and concomitant chemotherapies and the role pre-existent neuropathy on the development of a CIPN is not clear. As the number of long-term cancer survivors increases and a new focus on long-term effects of chemotherapy-induced neuropathies emerge, concepts of rehabilitation need to be implemented to improve the patients' functions and quality of life.