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Modern Applied Statistics With S

Approximately 5% of patients with malignant gliomas have a family history of gliomas. Some of these familial cases are associated with rare genetic syndromes, such as neurofibromatosis types 1 and 2, the Li−Fraumeni syndrome (germ-line p53 mutations associated with an increased risk of several cancers), and Turcot’s syndrome (intestinal polyposis and brain tumors). 10 However, most familial cases have

Malignant Gliomas in Adults

Infectious Diseases Society of America.

Prevention of infective endocarditis

A previous placebo-controlled trial has shown that biodegradable 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers (Gliadel wafers) prolong survival in patients with recurrent glioblastoma multiforme. A previously completed phase 3 trial, also placebo controlled, in 32 patients with newly diagnosed malignant glioma also demonstrated a survival benefit in those patients treated with BCNU wafers. Because of the small number of patients in that trial, a larger phase 3 trial was performed to confirm these results. Two hundred forty patients were randomized to receive either BCNU or placebo wafers at the time of primary surgical resection; both groups were treated with external beam radiation postoperatively. The two groups were similar for age, sex, Karnofsky performance status (KPS), and tumor histology. Median survival in the intent-to-treat group was 13.9 months for the BCNU wafer-treated group and 11.6 months for the placebo-treated group (log-rank P -value stratified by country = 0.03), with a 29% reduction in the risk of death in the treatment group. When adjusted for factors affecting survival, the treatment effect remained positive with a risk reduction of 28% ( P = 0.03). Time to decline in KPS and in 10/11 neuroperformance measures was statistically significantly prolonged in the BCNU wafer-treated group ( P </= 0.05). Adverse events were comparable for the 2 groups, except for CSF leak (5% in the BCNU wafer-treated group vs. 0.8% in the placebo-treated group) and intracranial hypertension (9.1% in the BCNU wafer-treated group vs. 1.7% in the placebo group). This study confirms that local chemotherapy with BCNU wafers is well tolerated and offers a survival benefit to patients with newly diagnosed malignant glioma.

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A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma.

In the light of advances in computerized tomography (CT), we have retrospectively evaluated the assumptions that underlie the radiation therapy of glioblastoma: (1) No neuroradiologic technique provides an accurate delineation of tumor bulk and location, (2) glioblastoma is commonly multicentric, and (3) a major source of therapeutic failure is recurrence beyond radiotherapy fields. 1. CT scans, performed on glioblastoma patients within 2 months of postmortem examination, defined both gross and microscopic tumor extent (within a 2-cm margin) in all but 6 of 35 patients evaluated. The major source of error was subependymal spread (four patients). 2. Multicentricity occurred in only 4% of untreated and 6% of treated (radiotherapy with or without chemotherapy) patients. All multicentric lesions were identified on CT scans. 3. Serial CT scans on 42 patients revealed that glioblastoma recurred within a 2-cm margin of the primary site in 90%. Occurrences outside this margin were accurately delineated by CT in all instances. Because most patients show recurrence within or in close proximity to the original site, current radiation doses would appear to be inadequate for therapy of the primary tumor. CT scan accuracy may permit smaller-field and higher-dose irradiation therapy for glioblastoma.

Assumptions in the radiotherapy of glioblastoma

The Spinal Cord: A Review of Functional Neuroanatomy

Background Adult brainstem gliomas (BSG) are uncommon and poorly understood with respect to prognostic factors. We retrospectively evaluated the clinical, radiographic, histologic, and treatment features from 101 adults with presumed or biopsy proven BSG to determine prognostic factors. Patients and Methods We reviewed the records of patients diagnosed from 1987–2005. We used Cox proportional hazard models to determine prognostic factors. Results These 50 male and 51 female patients ranged in age from 18 to 79 years at diagnosis (median 36 years) with follow-ups from 1 to 261 months (median 47 months). The overall survival for all patients at 5 and 10 years was 58% and 41%, respectively, with a median survival of 85 months (range 1–228). Out of 24 candidate prognosis factors, we selected seven covariates for proportional hazards model by Lasso procedure: age of diagnosis, ethnicity, need for corticosteroids, tumor grade, dysphagia, tumor location, and karnofsky performance status (KPS). Univariate analysis showed that these seven factors are significantly associated with survival. Multivariate analysis showed that four covariates significantly increased hazard for survival: ethnicity, tumor location, age of diagnosis, and tumor grade. Conclusions In this study, we identified four prognostic factors that were significantly associated with survival in adults with BSGs. Overall, these patients have a better prognosis than children with BSGs reported in the literature. These results call for larger prospective studies to fully assess the importance of these factors in the clinical setting and to help stratify patients in future clinical studies.

Prognostic factors in adult brainstem gliomas: a multicenter, retrospective analysis of 101 cases

Hematopoietic cell transplantation (HCT) is the preferred treatment for an expanding range of neoplastic and nonmalignant conditions. Increasing numbers of solid organ transplantations (SOTs) add an additional population of immunosuppressed patients with multiple potential neurological problems. While the spectrum of neurological complications varies with conditioning procedure and hematopoietic cell or solid organ source, major neurological complications occur with all transplantation procedures. This 2 part review emphasizes a practical consultative approach to central and peripheral nervous system problems related to HCT or SOT with clinical and neuroimaging examples from the authors’ institutional experience with the following conditions: the diversity of manifestations of common infections such as varicella zoster virus, Aspergillus, and progressive multifocal leukoencephalopathy (PML), drug therapy-related complications, stroke mechanisms, the spectrum of graft versus host disease (GVHD), and neurologically important syndromes of immune reconstitution inflammatory syndrome (IRIS), posterior reversible encephalopathy syndrome (PRES), and posttransplantation lymphoproliferative disorder (PTLD). These complications preferentially occur at specific intervals after HCT and SOT, and neurological consultants must recognize an extensive spectrum of syndromes in order to effect timely diagnosis and expedite appropriate treatment.

Amy A. Pruitt

Papers

Assumptions in the radiotherapy of glioblastoma

The Spinal Cord: A Review of Functional Neuroanatomy

Prognostic factors in adult brainstem gliomas: a multicenter, retrospective analysis of 101 cases

Neurological complications of transplantation: part I: hematopoietic cell transplantation.

Analysis of the treatment of neuromyelitis optica.