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Steven Hsu, Marisa Quattrone, Quinn Ostrom, Timothy C. Ryken, Andrew E. Sloan and Jill S. Barnholtz-Sloan

Object

Primary malignant spinal glioma represents a significant clinical challenge due to the devastating effect on clinical outcomes in the majority of cases. As they are infrequently encountered in any one center, there has been limited population-based data analysis on the incidence patterns of these aggressive tumors. The objective of this study was to use publically available Surveillance, Epidemiology and End Results (SEER) program data to examine the overall incidence and incidence patterns over time with regard to age at diagnosis, sex, race, primary site of tumor, and histological subtype in patients in whom primary malignant spinal cord gliomas were diagnosed between 1973 and 2006.

Methods

The study population of interest was limited to primary, malignant, pathologically confirmed spinal cord gliomas based on data drawn from the SEER 9 standard registries for patients diagnosed between 1973 and 2006. Variables of interest included age at diagnosis, sex, race, primary site of tumor, and histological subtype of tumor. The SEER*Stat 6.5.2 program was used to calculate frequencies, age-adjusted incidence rates with 95% CIs, and annual percentage change (APC) statistics with a 2-sided p value. In addition, linear correlation coefficients (R2) were calculated for the time association stratified by variables of interest.

Results

The overall age-adjusted incidence rate for primary malignant spinal gliomas was 0.12 per 100,000, which increased significantly over the study period (APC = 1.74; p = 0.0004; R2 = 0.36). The incidence was highest in patients diagnosed at ages 35–49 (0.17 per 100,000), males (0.14 per 100,000), whites (0.13 per 100,000), and those with ependymomas (0.07 per 100,000). Over the study period, the incidence of ependymomas increased significantly (APC = 3.17; p < 0.0001; R2 = 0.58) as did the incidence of these tumors in whites (APC = 2.13; p = 0.0001) and for both males (APC = 1.90, p value < 0.0001) and females (APC = 1.60, p < 0.0001). The authors found no significant changes in the incidence over time by age of diagnosis.

Conclusions

This study demonstrates an increasing overall incidence of primary, malignant spinal cord glioma over the past 3 decades. Notably, for ependymoma the incidence has increased, whereas the incidence of most other glioma subtypes remained stable. This may be due to improved diagnostic and surgical techniques, changes in histological classification criteria, and changes in neuropathology diagnostic criteria. Although primary, malignant spinal cord gliomas are rare, an improved understanding of the incidence will assist investigators and clinicians in planning potential studies and preparing for allocation of resources to care for these challenging patients.

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Jaime Vengoechea, Andrew E. Sloan, Yanwen Chen, Xiaowei Guan, Quinn T. Ostrom, Amber Kerstetter, Devan Capella, Mark L. Cohen, Yingli Wolinsky, Karen Devine, Warren Selman, Gene H. Barnett, Ronald E. Warnick, Christopher McPherson, E. Antonio Chiocca, J. Bradley Elder and Jill S. Barnholtz-Sloan

Object

Although most meningiomas are benign, about 20% are atypical (Grade II or III) and have increased mortality and morbidity. Identifying tumors with greater malignant potential can have significant clinical value. This validated genome-wide methylation study comparing Grade I with Grade II and III meningiomas aims to discover genes that are aberrantly methylated in atypical meningiomas.

Methods

Patients with newly diagnosed meningioma were identified as part of the Ohio Brain Tumor Study. The Infinium HumanMethylation27 BeadChip (Illumina, Inc.) was used to interrogate 27,578 CpG sites in 14,000 genes per sample for a discovery set of 33 samples (3 atypical). To verify the results, the Infinium HumanMethylation450 BeadChip (Illumina, Inc.) was used to interrogate 450,000 cytosines at CpG loci throughout the genome for a verification set containing 7 replicates (3 atypical), as well as 12 independent samples (6 atypical). A nonparametric Wilcoxon exact test was used to test for difference in methylation between benign and atypical meningiomas in both sets. Heat maps were generated for each set. Methylation results were validated for the 2 probes with the largest difference in methylation intensity by performing Western blot analysis on a set of 20 (10 atypical) samples, including 11 replicates.

Results

The discovery array identified 95 probes with differential methylation between benign and atypical meningiomas, creating 2 distinguishable groups corresponding to tumor grade when visually examined on a heat map. The validation array evaluated 87 different probes and showed that 9 probes were differentially methylated. On heat map examination the results of this array also suggested the existence of 2 major groups that corresponded to histological grade. IGF2BP1 and PDCD1, 2 proteins that can increase the malignant potential of tumors, were the 2 probes with the largest difference in intensity, and for both of these the atypical meningiomas had a decreased median production of protein, though this was not statistically significant (p = 0.970 for IGF2BP1 and p = 1 for PDCD1).

Conclusions

A genome-wide methylation analysis of benign and atypical meningiomas identified 9 genes that were reliably differentially methylated, with the strongest difference in IGF2BP1 and PDCD1. The mechanism why increased methylation of these sites is associated with an aggressive phenotype is not evident. Future research may investigate this mechanism, as well as the utility of IGF2BP1 as a marker for pathogenicity in otherwise benign-appearing meningiomas.

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Haley Gittleman, Quinn T. Ostrom, Paul D. Farah, Annie Ondracek, Yanwen Chen, Yingli Wolinsky, Carol Kruchko, Justin Singer, Varun R. Kshettry, Edward R. Laws, Andrew E. Sloan, Warren R. Selman and Jill S. Barnholtz-Sloan

Object

Pituitary tumors are abnormal growths that develop in the pituitary gland. The Central Brain Tumor Registry of the United States (CBTRUS) contains the largest aggregation of population-based data on the incidence of primary CNS tumors in the US. These data were used to determine the incidence of tumors of the pituitary and associated trends between 2004 and 2009.

Methods

Using incidence data from 49 population-based state cancer registries, 2004–2009, age-adjusted incidence rates per 100,000 population for pituitary tumors with ICD-O-3 (International Classification of Diseases for Oncology, Third Edition) histology codes 8040, 8140, 8146, 8246, 8260, 8270, 8271, 8272, 8280, 8281, 8290, 8300, 8310, 8323, 9492 (site C75.1 only), and 9582 were calculated overall and by patient sex, race, Hispanic ethnicity, and age at diagnosis. Corresponding annual percent change (APC) scores and 95% confidence intervals were also calculated using Joinpoint to characterize trends in incidence rates over time. Diagnostic confirmation by subregion of the US was also examined.

Results

The overall annual incidence rate increased from 2.52 (95% CI 2.46–2.58) in 2004 to 3.13 (95% CI 3.07–3.20) in 2009. Associated time trend yielded an APC of 4.25% (95% CI 2.91%–5.61%). When stratifying by patient sex, the annual incidence rate increased from 2.42 (95% CI 2.33–2.50) to 2.94 (95% CI 2.85–3.03) in men and 2.70 (95% CI 2.62–2.79) to 3.40 (95% CI 3.31–3.49) in women, with APCs of 4.35% (95% CI 3.21%–5.51%) and 4.34% (95% CI 2.23%–6.49%), respectively. When stratifying by race, the annual incidence rate increased from 2.31 (95% CI 2.25–2.37) to 2.81 (95% CI 2.74–2.88) in whites, 3.99 (95% CI 3.77–4.23) to 5.31 (95% CI 5.06–5.56) in blacks, 1.77 (95% CI 1.26–2.42) to 2.52 (95% CI 1.96–3.19) in American Indians or Alaska Natives, and 1.86 (95% CI 1.62–2.13) to 2.03 (95% CI 1.80–2.28) in Asians or Pacific Islanders, with APCs of 3.91% (95% CI 2.88%–4.95%), 5.25% (95% CI 3.19%–7.36%), 5.31% (95% CI –0.11% to 11.03%), and 2.40% (95% CI –3.20% to 8.31%), respectively. When stratifying by Hispanic ethnicity, the annual incidence rate increased from 2.46 (95% CI 2.40–2.52) to 3.03 (95% CI 2.97–3.10) in non-Hispanics and 3.12 (95% CI 2.91–3.34) to 4.01 (95% CI 3.80–4.24) in Hispanics, with APCs of 4.15% (95% CI 2.67%–5.65%) and 5.01% (95% CI 4.42%–5.60%), respectively. When stratifying by age at diagnosis, the incidence of pituitary tumor was highest for those 65–74 years old and lowest for those 15–24 years old, with corresponding overall age-adjusted incidence rates of 6.39 (95% CI 6.24–6.54) and 1.56 (95% CI 1.51–1.61), respectively.

Conclusions

In this large patient cohort, the incidence of pituitary tumors reported between 2004 and 2009 was found to increase. Possible explanations for this increase include changes in documentation, changes in the diagnosis and registration of these tumors, improved diagnostics, improved data collection, increased awareness of pituitary diseases among physicians and the public, longer life expectancies, and/or an actual increase in the incidence of these tumors in the US population.