Glioblastoma (GBM) pathologically is defined as an infiltrative glioma and salvage therapy with bevacizumab is believed to increase the incidence of diffuse and distant invasion as assessed ...radiographically. Eighty adult patients with glioblastoma were treated with surgery followed by radiotherapy (RT) and concurrent and adjuvant temozolomide (TMZ). At first recurrence, 80 patients were treated with single agent bevacizumab. At time of progression, 57 patients were treated with bevacizumab and a cytotoxic chemotherapy, cytotoxic chemotherapy alone or on an investigational trial. Magnetic resonance imaging (MRI) were analyzed at four time points in each patient; at presentation, at first, second and third recurrence. Four patterns of radiographic disease were assessed, local (unifocal disease), distant (second lesion noncontiguous with primary lesion), multifocal (>2 lesions including leptomeningeal dissemination) and diffuse. At presentation 87.5% of glioblastoma were local, 6.25% distant, 3.75% multifocal and 2.5% diffuse. At first recurrence following progression on RT/TMZ and before initiation of bevacizumab, 80% were local, 7.5% distant, 6.25% multifocal (including 1 with CSF dissemination) and 6.25% diffuse. At second recurrence following progression on bevacizumab, 71.25% were local, 8.75% distant, 8.75% multifocal (2/7 with CSF dissemination) and 11.25% were diffuse. At third recurrence (57 patients evaluable), 71.25% were local, 7.0% distant, 7.0% multifocal and 14.0% were diffuse. Survival following progression on bevacizumab did not differ by pattern of radiographic recurrence. A majority of adult patients with GBM at diagnosis manifest MRI-defined local disease and maintain this pattern notwithstanding multiple recurrences and treatment with bevacizumab.
Pleomorphic xanthoastrocytoma (PXA) is a World Health Organization Grade 2 glioma that is uncommon (<1 % all adult gliomas) and seen primarily in children and young adults. PXA has been demonstrated ...to manifest the V600E BRAF mutation in nearly 70 % of all tumors, a mutation that constitutively activates the BRAF/MEK signaling pathway. Assess response and toxicity of a BRAF inhibitor, vemurafenib, in recurrent PXA manifesting the V600E mutation. Four adults 2 males; 2 female: median age 45 years (range 34–53) with surgery, radiation and alkylator refractory recurrent PXA demonstrating the BRAF mutation (V600E) were treated with vemurafenib. A cycle of vemurafenib was defined as 4 weeks of continuous therapy. All toxicities seen were grade 2 and included arthralgia, photosensitivity, fatigue and nausea (1 patient each). The median number of cycles of therapy was 5 (range 2–10). Radiographic response was progressive disease in 1, stable disease in 2 and partial response in 1. Median progression free survival was 5 months (range 2–10 months). Median overall survival was 8 months (range 4–14 months). In this small retrospective series of select patients with recurrent PXA manifesting the BRAF V600E activating mutation, vemurafenib appears to have single agent activity with manageable toxicity. Confirmation in a larger series of similar patients is required.
Leptomeningeal metastasis Chamberlain, Marc C
Current opinion in oncology,
2010-November, 2010-Nov, 2010-11-00, 20101101, Letnik:
22, Številka:
6
Journal Article
PURPOSE OF REVIEWLeptomeningeal metastasis occurs in approximately 3–5% of all patients with cancer. A contemporary literature review of methods of diagnosis and treatment of leptomeningeal ...metastasis was performed.
RECENT FINDINGSThe single most important aspect to diagnosis of leptomeningeal metastasis is considering and pursuing the diagnosis in a patient with cancer and neurological signs and symptoms. Evaluation of leptomeningeal metastasis includes contrast-enhanced brain and spine magnetic resonance imaging (MRI) and a radionuclide cerebrospinal fluid (CSF) flow study if leptomeningeal metastasis-directed therapy is being considered. Treatment often requires involved-field radiotherapy to bulky or symptomatic disease sites as well as intra-CSF and systemic chemotherapy. The use of high-dose systemic therapy may benefit patients with leptomeningeal metastasis and obviate the need for intra-CSF chemotherapy. Intra-CSF drug therapy primarily utilizes one of three chemotherapeutic agents (i.e. methotrexate, cytosine arabinoside and thio-TEPA) administered by a variety of schedules either by intralumbar or intraventricular drug delivery. Novel and increasingly utilized intra-CSF agents in the treatment of leptomeningeal metastasis are targeted monoclonal antibodies such as rituximab and trastuzumab.
SUMMARYAlthough treatment of leptomeningeal metastasis is palliative with median patient survival of 2–3 months (15% of patients with leptomeningeal metastasis survive 1 year), treatment may afford stabilization and protection from further neurologic deterioration in patients with leptomeningeal metastasis.
Temozolomide-based chemotherapy represents an incremental improvement in the treatment of patients with high-grade gliomas. Notwithstanding a survival benefit in a subset of patients with high-grade ...gliomas, temozolomide (TMZ; Temodar
®
, Schering-Plough Pharmaceuticals, NJ, USA) is the primarily palliative treatment for the vast majority of patients. Indeed, for patients with newly diagnosed glioblastoma, the median increase in survival for treatment with TMZ and radiotherapy is only 2.5 months compared with radiotherapy alone. Additionally, recent studies suggest that 60-75% of patients with glioblastoma derive no benefit from treatment with TMZ. For the treatment of recurrent anaplastic gliomas, more than 50% of patients fail TMZ treatment with cancer progression at 6 months, demonstrating that TMZ is only a modestly effective chemotherapy. In addition, 15-20% of patients treated with TMZ develop clinically significant toxicity, which can leave further treatment unsafe. Despite the availability of TMZ, there is still a substantial need for a chemotherapeutic agent that is more effective and safe. In fact, there still remains a significant unmet need for more effective treatments of high-grade gliomas (improved palliation or cure), whether that treatment be by surgery, radiotherapy, chemotherapy or any yet to be developed type of treatment, such as 'targeted therapies'.
Neoplastic Meningitis Chamberlain, Marc C.
The oncologist (Dayton, Ohio),
September 2008, Letnik:
13, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Learning Objectives
After completing this course, the reader should be able to:
Describe the epidemiology of leptomeningeal metastasis.
Participate in the diagnosis of leptomeningeal metastasis.
...Engage in the treatment of leptomeningeal metastasis.
This article is available for continuing medical education credit at CME.TheOncologist.com
Background.
Neoplastic meningitis (NM) is a common problem in neuro‐oncology, occurring in approximately 5% of all patients with cancer.
Methods.
Notwithstanding frequent focal signs and symptoms, NM is a disease affecting the entire neuraxis, and therefore staging and treatment need encompass all cerebrospinal fluid (CSF) compartments.
Results.
Central nervous system staging of NM includes contrast‐enhanced cranial computerized tomography or magnetic resonance imaging (MR‐Gd), contrast‐enhanced spine magnetic resonance imaging or computerized tomographic myelography and radionuclide CSF flow study. Treatment of NM incorporates involved‐field radiotherapy of bulky or symptomatic disease sites and intra‐CSF drug therapy. The inclusion of concomitant systemic therapy may benefit patients with NM and may obviate the need for intra‐CSF chemotherapy. At present, intra‐CSF drug therapy is confined to three chemotherapeutic agents (i.e., methotrexate, cytosine, arabinoside, and thio‐TEPA) administered by a variety of schedules either by intralumbar or intraventricular drug delivery.
Conclusions.
Although treatment of NM is palliative with an expected median patient survival of 2 to 6 months, it often affords stabilization and protection from further neurologic deterioration in patients with NM.
This review summarizes the epidemiology, diagnosis, and treatment of neoplastic meningitis.
This guideline provides recommendations for the use of PET imaging in gliomas. The review examines established clinical benefit in glioma patients of PET using glucose ((18)F-FDG) and amino acid ...tracers ((11)C-MET, (18)F-FET, and (18)F-FDOPA). An increasing number of studies have been published on PET imaging in the setting of diagnosis, biopsy, and resection as well radiotherapy planning, treatment monitoring, and response assessment. Recommendations are based on evidence generated from studies which validated PET findings by histology or clinical course. This guideline emphasizes the clinical value of PET imaging with superiority of amino acid PET over glucose PET and provides a framework for the use of PET to assist in the management of patients with gliomas.
Treatment of leptomeningeal metastasis (LMD) remains challenging due to advanced systemic disease at presentation and limited treatment options. All patients underwent standard pre-treatment LMD ...evaluation including CSF assessment (cytology or flow cytometry), brain and spine MR imaging, and radioisotope CSF flow study. DepoCyt (liposomal cytarabine) was administered intraventricularly (
n
= 80) or intralumbar (
n
= 40) at 50 mg every 2 weeks ×4 and then every 4 weeks ×6 in responding patients. Dexamethasone (4 mg orally twice per day ×5 days) was co-administered with each DepoCyt treatment. Patients were seen with each DepoCyt treatment and assessed for toxicity. 120 adult patients median age 51 years (range 33–68) with LMD were treated with DepoCyt. DepoCyt Common Toxicity Criteria ≥Grade 3 neurotoxicity was seen in 60 cycles (11.5 %) in 28 patients (23.3 %). Toxicity included bacterial meningitis (3.75 % of ventricular treatments: 0 % of lumbar treatments); chemical meningitis (17.5:15 %); communicating hydrocephalus (3.75:5 %); conus medullaris/cauda equina syndrome (5:5 %); decreased visual acuity (5:2.5 %); encephalopathy (5:5 %); leukoencephalopathy (7.5:2.5 %); myelopathy (2.5:2.5 %); radiculopathy (1.25:5 %); and seizures (1.25:2.5 %). Distribution of toxicity was similar regardless of route of administration (ventricular vs. lumbar). Toxicities were transient in 34 episodes (57 %) and permanent in 26 (43 %). There were no treatment-related deaths however 20 treatment-related toxicities (32.2 %) required hospitalization. In this retrospective case series, DepoCyt is generally well tolerated however a subset of patients (12.5 %) not easily identified pre-treatment, develop serious treatment-related neurological complications that may be persistent and impact quality of life.
Primary spinal cord tumors constitute 2% to 4% of all central nervous system neoplasms and are characterized based on their location as intramedullary, intradural extramedullary, and extradural. A ...contemporary literature review of primary intradural spinal cord tumors was performed. Among intramedullary tumors, ependymomas are more common and often can be surgically resected. However, astrocytomas infiltrate the spinal cord and complete resection is rare. Intradural extramedullary tumors include schwannomas, neurofibromas, and meningiomas and are usually amenable to surgical resection. Radiotherapy is reserved for malignant variants and recurrent gliomas, whereas chemotherapy is administered for recurrent primary spinal cord tumors without surgical or radiotherapy options. Early recognition of the signs and symptoms related to primary spinal cord tumors facilitates timely discovery, treatment, potentially minimizes neurologic morbidity, and may improve outcome. Treatment consists of surgical resection, and predictors of outcome include preoperative functional status, histologic grade of tumor, and extent of surgical resection.
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