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Jill S. Barnholtz-Sloan and Carol Kruchko

✓ Meningiomas are among the most common primary intracranial tumors. Although the vast majority of these tumors are considered histologically benign, the incidence of complications can be high. Few studies have investigated the causes and risk factors for meningioma; this review highlights the current state of knowledge. Gaining a better understanding of the origin of this disease is essential so that treatments and outcomes can be improved and prevention strategies can be developed.

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Jill S. Barnholtz-Sloan, Andrew E. Sloan, and Ann G. Schwartz

Object. The purpose of this study was to examine patterns of diagnosis and relative survival rates in individuals in whom a primary malignant brain tumor was diagnosed between 1973 and 1997; follow-up review of these patients continued through the end of 1999.

Methods. The study population was composed of 21,493 patients with primary malignant brain tumors that were diagnosed between 1973 and 1997. Data on these patients were obtained from the population-based Surveillance, Epidemiology, and End Results Program. The study population was divided into three cohorts based on the year of diagnosis, and these groups were compared with respect to variables of interest by performing chi-square tests and relative survival analysis with the life table method.

Over time, there were consistently more men, more Caucasians, more patients undergoing surgery, and more individuals 70 years and older who received the diagnosis of primary malignant brain tumor. An examination of proportions of individuals with astrocytoma, other; oligodendroglioma, other; and oligodendroglioma Grade III showed significant temporal changes with frontal and temporal lobe tumors occurring most often. The diagnosis was obtained at an earlier age in African-American than in Caucasian patients. Caucasians had higher proportions of glioblastoma multiforme (GBM), which was associated with decreased survival times, and of oligodendroglioma, other, whereas African Americans had higher proportions of astrocytoma, other; ependymoma Grade II or III; and medulloblastoma, all of which were associated with increased survival times. The relative survival case demonstrated a continuous improvement over time, although older patients, those who underwent biopsy only, and those with GBMs continue to have the poorest survival times. The relative survival rates of African Americans consistently were similar or worse than those of Caucasians when the groups were stratified by prognostic factors.

Conclusions. Over time, the relative survival rate of individuals with primary malignant brain tumor has improved and differences in survival are seen by examining the race of the patients.

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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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Jill S. Barnholtz-Sloan, Vonetta L. Williams, John L. Maldonado, Dilip Shahani, Heather G. Stockwell, Marc Chamberlain, and Andrew E. Sloan

Object

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).

Methods

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.

Results

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.

Conclusions

These findings suggest that in clinical neurooncology patient age is associated with not receiving effective therapies and hence worse prognosis.

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Christina Huang Wright, James Wright, Gino Cioffi, Alia Hdeib, Manish K. Kasliwal, Carol Kruchko, Jill S. Barnholtz-Sloan, and Andrew E. Sloan

OBJECTIVE

Chordomas of the spine and sacrum are a rare but debilitating cancer and require complex multidisciplinary care. Studies of other such rare cancers have demonstrated an association of high-volume and/or multidisciplinary centers with improved outcomes and survival. Such an association has been proposed for chordomas, but evidence to support this claim is lacking. The authors performed a study to investigate if treatment facility type is associated with patterns of care and survival for patients with spinal and sacral chordomas by assessing records from a US-based cancer database.

METHODS

In this observational retrospective cohort study, the authors identified 1266 patients from the National Cancer Database with vertebral column or sacral chordomas diagnosed between 2004 and 2015. The primary study outcome was overall survival, and secondary outcomes included odds of receiving treatment and time to treatment, defined as radiation therapy, surgery, and/or any treatment, including surgery, radiation therapy, chemotherapy, or participation in clinical trials. The results were adjusted for age, sex, race/ethnicity, level of education, income, and Charlson/Deyo score.

RESULTS

Of the 1266 patients identified, the mean age at diagnosis was 59.70 years (SD 16.2 years), and the patients were predominantly male (n = 791 [62.50%]). Patients treated at community cancer programs demonstrated an increased risk of death (HR 1.98, 95% CI 1.13–3.47, p = 0.018) when compared to patients treated at academic/research programs (ARPs). The median survival was longest for those treated at ARPs (131.45 months) compared to community cancer programs (79.34 months, 95% CI 48.99–123.17) and comprehensive community cancer programs (CCCPs) (109.34 months, 95% CI 84.76–131.45); 5-year survival rates were 76.08%, 52.71%, and 61.57%, respectively. Patients treated at community cancer programs and CCCPs were less likely to receive any treatment compared to those treated at ARPs (OR 6.05, 95% CI 2.62–13.95, p < 0.0001; OR 3.74, 95% CI 2.23–6.28, p < 0.0001, respectively). Patients treated at CCCPs and community cancer programs were less likely to receive surgery than those treated at ARPs (OR 2.69, 95% CI 1.82–3.97, p = 0.010; OR = 2.64, 95% CI 1.22–5.71, p = 0.014, respectively). Patients were more likely to receive any treatment (OR 0.59, 95% CI 0.40–0.87, p = 0.007) and surgery (OR 0.58, 95% CI 0.38–0.88, p < 0.0001) within 30 days at a CCCP compared to an ARP. There were no differences in odds of receiving radiation therapy or time to radiation by facility type.

CONCLUSIONS

Clinical care at an ARP is associated with increased odds of receiving treatment that is associated with improved overall survival for patients with spinal and sacral chordomas, suggesting that ARPs provide the most comprehensive specialized care for patients with this rare and devastating oncological disease.

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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.

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Jianning Shao, Jaes Jones, Patrick Ellsworth, Ghaith Habboub, Gino Cioffi, Nirav Patil, Quinn T. Ostrom, Carol Kruchko, Jill S. Barnholtz-Sloan, Varun R. Kshettry, and Pablo F. Recinos

OBJECTIVE

Spinal cord astrocytoma (SCA) is a rare tumor whose epidemiology has not been well defined. The authors utilized the Central Brain Tumor Registry of the United States (CBTRUS) to provide comprehensive up-to-date epidemiological data for this disease.

METHODS

The CBTRUS was queried for SCAs on ICD-O-3 (International Classification of Diseases for Oncology, 3rd edition) histological and topographical codes. The age-adjusted incidence (AAI) per 100,000 persons was calculated and stratified by race, sex, age, and ethnicity. Joinpoint was used to calculate the annual percentage change (APC) in incidence.

RESULTS

Two thousand nine hundred sixty-nine SCAs were diagnosed in the US between 1995 and 2016, resulting in an average of approximately 136 SCAs annually. The overall AAI was 0.047 (95% CI 0.045–0.049), and there was a statistically significant increase from 0.051 in 1995 to 0.043 in 2016. The peak incidence of 0.064 (95% CI 0.060–0.067) was found in the 0- to 19-year age group. The incidence in males was 0.053 (95% CI 0.050–0.055), which was significantly greater than the incidence in females (0.041, 95% CI 0.039–0.044). SCA incidence was significantly lower both in patients of Asian/Pacific Islander race (AAI = 0.034, 95% CI 0.028–0.042, p = 0.00015) and in patients of Hispanic ethnicity (AAI = 0.035, 95% CI 0.031–0.039, p < 0.001). The incidence of WHO grade I SCAs was significantly higher than those of WHO grade II, III, or IV SCAs (p < 0.001).

CONCLUSIONS

The overall AAI of SCA from 1995 to 2016 was 0.047 per 100,000. The incidence peaked early in life for both sexes, reached a nadir between 20 and 34 years of age for males and between 35 and 44 years of age for females, and then slowly increased throughout adulthood, with a greater incidence in males. Pilocytic astrocytomas were the most common SCA in the study cohort. This study presents the most comprehensive epidemiological study of SCA incidence in the US to date.

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Shahed Tish, Ghaith Habboub, Min Lang, Quinn T. Ostrom, Carol Kruchko, Jill S. Barnholtz-Sloan, Pablo F. Recinos, and Varun R. Kshettry

OBJECTIVE

Spinal schwannoma remains the third most common intradural spinal tumor following spinal meningioma and ependymoma. The available literature is generally limited to single-institution reports rather than epidemiological investigations. As of 1/1/2004, registration of all benign central nervous system tumors in the United States became mandatory after the Benign Brain Tumor Cancer Registries Amendment Act took action, which provided massive resources for United States population-based epidemiological studies. This article describes the epidemiology of spinal schwannoma in the United States from January 1, 2006, through December 31, 2014.

METHODS

In this study, the authors utilized the Central Brain Tumor Registry of the United States, which corresponds to 100% of the American population. The Centers for Disease Control and Prevention’s National Program of Cancer Registries and the National Cancer Institute’s Surveillance Epidemiology and End Results program provide the resource for this data registry. The authors included diagnosis years 2006 to 2014. They used the codes per the International Coding of Diseases for Oncology, 3rd Edition: histology code 9560/0 and site codes C72.0 (spinal cord), C70.1 (spinal meninges), and C72.1 (cauda equina). Rates are per 100,000 persons and are age-adjusted to the 2000 United States standard population. The age-adjusted incidence rates and 95% confidence intervals are calculated by age, sex, race, and ethnicity.

RESULTS

There were 6989 spinal schwannoma cases between the years 2006 and 2014. The yearly incidence eminently increased between 2010 and 2014. Total incidence rate was 0.24 (95% CI 0.23–0.24) per 100,000 persons. The peak adjusted incidence rate was seen in patients who ranged in age from 65 to 74 years. Spinal schwannomas were less common in females than they were in males (incidence rate ratio = 0.85; p < 0.001), and they were less common in blacks than they were in whites (IRR = 0.52; p < 0.001) and American Indians/Alaska Natives (IRR = 0.50; p < 0.001) compared to whites. There was no statistically significant difference in incidence rate between whites and Asian or Pacific Islanders (IRR = 0.92; p = 0.16).

CONCLUSIONS

The authors’ study results demonstrated a steady increase in the incidence of spinal schwannomas between 2010 and 2014. Male sex and the age range 65–74 years were associated with higher incidence rates of spinal schwannomas, whereas black and American Indian/Alaska Native races were associated with lower incidence rates. The present study represents the most thorough assessment of spinal schwannoma epidemiology in the American population.

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Mir Amaan Ali, Kate T. Carroll, Robert C. Rennert, Thomas Hamelin, Leon Chang, Brian P. Lemkuil, Mayur Sharma, Jill S. Barnholtz-Sloan, Charlotte Myers, Gene H. Barnett, Kris Smith, Alireza M. Mohammadi, Andrew E. Sloan, and Clark C. Chen

OBJECTIVE

Therapeutic options for brain metastases (BMs) that recur after stereotactic radiosurgery (SRS) remain limited.

METHODS

The authors provide the collective experience of 4 institutions where treatment of BMs that recurred after SRS was performed with stereotactic laser ablation (SLA).

RESULTS

Twenty-six BMs (in 23 patients) that recurred after SRS were treated with SLA (2 patients each underwent 2 SLAs for separate lesions, and a third underwent 2 serial SLAs for discrete BMs). Histological findings in the BMs treated included the following: breast (n = 6); lung (n = 6); melanoma (n = 5); colon (n = 2); ovarian (n = 1); bladder (n = 1); esophageal (n = 1); and sarcoma (n = 1). With a median follow-up duration of 141 days (range 64–794 days), 9 of the SLA-treated BMs progressed despite treatment (35%). All cases of progression occurred in BMs in which < 80% ablation was achieved, whereas no disease progression was observed in BMs in which ≥ 80% ablation was achieved. Five BMs were treated with SLA, followed 1 month later by adjuvant SRS (5 Gy daily × 5 days). No disease progression was observed in these patients despite ablation efficiency of < 80%, suggesting that adjuvant hypofractionated SRS enhances the efficacy of SLA. Of the 23 SLA-treated patients, 3 suffered transient hemiparesis (13%), 1 developed hydrocephalus requiring temporary ventricular drainage (4%), and 1 patient who underwent SLA of a 28.9-cm3 lesion suffered a neurological deficit requiring an emergency hemicraniectomy (4%). Although there is significant heterogeneity in corticosteroid treatment post-SLA, most patients underwent a 2-week taper.

CONCLUSIONS

Stereotactic laser ablation is an effective treatment option for BMs in which SRS fails. Ablation of ≥ 80% of BMs is associated with decreased risk of disease progression. The efficacy of SLA in this setting may be augmented by adjuvant hypofractionated SRS.