E. Antonio Chiocca
Jill S. Barnholtz-Sloan, Vonetta L. Williams, John L. Maldonado, Dilip Shahani, Heather G. Stockwell, Marc Chamberlain and Andrew E. Sloan
This study was undertaken to evaluate the association between age at diagnosis, patterns of care, and outcome among elderly individuals with anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM).
Using the Surveillance, Epidemiology and End Results database, the authors identified 1753 individuals with primary GBM and 205 individuals with primary AA (diagnosed between June 1991 and December 1999) who were 66 years and older and whose records were linked to Medicare information. To facilitate gathering of prediagnosis comorbidity and postdiagnosis treatment information, only those individuals were included who had the same Medicare coverage for 6 months before and 12 months after diagnosis. The odds of undergoing various combinations of treatments and the associations with outcome were calculated by tumor type and age and adjusted by various predictors.
Age was not associated with treatment differences in individuals with AA. Very elderly individuals (≥ 75 years old) with GBM were more likely to have biopsy only (odds ratio [OR] 2.53, 95% confidence interval [CI] 1.78–3.59), surgery only (OR 1.47, 95% CI 1.15–1.87), or biopsy and radiation (OR 1.39, 95% CI 1.07–1.82) and were less likely to receive multimodal therapy. Regardless of patient age or lesion histological characteristics, survival was decreased in patients treated with biopsy only. Individuals with GBM who had surgery only or biopsy and radiation had worse outcomes than individuals treated with surgery and radiation. There were no differences in survival by lesion histological characteristics. Very elderly individuals with malignant astrocytomas were more likely to receive limited treatment (most pronounced in individuals with GBM). Survival variation correlated with treatment combinations.
These findings suggest that in clinical neurooncology patient age is associated with not receiving effective therapies and hence worse prognosis.
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
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.
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.
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.
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.
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
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.
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.
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).
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.