Demographic variation in incidence of adult glioma by subtype, United States, 1992-2007

<p>Abstract</p> <p>Background</p> <p>We hypothesized that race/ethnic group, sex, age, and/or calendar period variation in adult glioma incidence differs between the two broad subtypes of glioblastoma (GBM) and non-GBM. Primary GBM, which constitute 90-95% of GBM, differ from non-GBM with respect to a number of molecular characteristics, providing a molecular rationale for these two broad glioma subtypes.</p> <p>Methods</p> <p>We utilized data from the Surveillance, Epidemiology, and End Results Program for 1992-2007, ages 30-69 years. We compared 15,088 GBM cases with 9,252 non-GBM cases. We used Poisson regression to calculate adjusted rate ratios and 95% confidence intervals.</p> <p>Results</p> <p>The GBM incidence rate increased proportionally with the 4^thpower of age, whereas the non-GBM rate increased proportionally with the square root of age. For each subtype, compared to non-Hispanic Whites, the incidence rate among Blacks, Asians/Pacific Islanders, and American Indians/Alaskan Natives was substantially lower (one-fourth to one-half for GBM; about two-fifths for non-GBM). Secondary to this primary effect, race/ethnic group variation in incidence was significantly less for non-GBM than for GBM. For each subtype, the incidence rate was higher for males than for females, with the male/female rate ratio being significantly higher for GBM (1.6) than for non-GBM (1.4). We observed significant calendar period trends of increasing incidence for GBM and decreasing incidence for non-GBM. For the two subtypes combined, we observed a 3% decrease in incidence between 1992-1995 and 2004-2007.</p> <p>Conclusions</p> <p>The substantial difference in age effect between GBM and non-GBM suggests a fundamental difference in the genesis of primary GBM (the driver of GBM incidence) versus non-GBM. However, the commonalities between GBM and non-GBM with respect to race/ethnic group and sex variation, more notable than the somewhat subtle, albeit statistically significant, differences, suggest that within the context of a fundamental difference, some aspects of the complex process of gliomagenesis are shared by these subtypes as well. The increasing calendar period trend of GBM incidence coupled with the decreasing trend of non-GBM incidence may at least partly be due to a secular trend in diagnostic fashion, as opposed to real changes in incidence of these subtypes.</p

MAPK pathway activation in pilocytic astrocytoma

Pilocytic astrocytoma (PA) is the most common tumor of the pediatric central nervous system (CNS). A body of research over recent years has demonstrated a key role for mitogen-activated protein kinase (MAPK) pathway signaling in the development and behavior of PAs. Several mechanisms lead to activation of this pathway in PA, mostly in a mutually exclusive manner, with constitutive BRAF kinase activation subsequent to gene fusion being the most frequent. The high specificity of this fusion to PA when compared with other CNS tumors has diagnostic utility. In addition, the frequency of alteration of this key pathway provides an opportunity for molecularly targeted therapy in this tumor. Here, we review the current knowledge on mechanisms of MAPK activation in PA and some of the downstream consequences of this activation, which are now starting to be elucidated both in vitro and in vivo, as well as clinical considerations and possible future directions

Primary CNS Lymphoma

Primary CNS Lymphoma (PCNSL) accounts for 3% of all primary brain tumors with a median age at onset of about 62 years. In the vast majority of cases, PCNSL presents as unifocal or multifocal enhancing lesions on MRI, frequently adjacent to the ventricles. Stereotactic biopsy is the diagnostic procedure of choice revealing high-grade malignant non-Hodgkin's B-cell lymphoma in more than 90% of cases. Therapy is not evidence based. When eligible, patients should be included in clinical trials. In patients younger than 60 years cure is the aim. Polychemotherapy based on high-dose methotrexate (MTX) or alternatively high-dose chemotherapy with autologous stem cell rescue should be offered to patients eligible for this regimens. For patients over 60 years of age no curative regimen with acceptable toxicity has yet been established. An MTX-based chemotherapy, for example, in combination with temozolomide, is recommended. The role of radiotherapy as part of the initial treatment is not established; however, the combination of radiotherapy with MTX-based chemotherapy potentially leads to severe long-term neurotoxic sequelae. Therefore, radiotherapy as part of the initial therapy is not recommended by the author outside clinical trials. At relapse or in cases of refractory disease, patients will frequently benefit of salvage therapy, which depends on the initial treatment