Adaptive functioning in pediatric brain tumor survivors: An examination of ethnicity and socioeconomic status.

BACKGROUND: Survivors of pediatric brain tumor are at risk for adaptive difficulties. The present study examined adaptive functioning in a multiethnic sample of survivors accounting for socioeconomic status, and whether demographic, diagnostic, and/or treatment-related variables predict adaptive outcomes. METHOD: Participants included a multiethnic sample of survivors (58 Caucasian, 34 Hispanic, and 22 other non-Caucasian; M age = 14.05 years, SD = 4.33) who were approximately seven years post-treatment. Parents rated adaptive functioning and provided demographic information. Diagnostic and treatment-related information was abstracted from the electronic medical record. RESULTS: Parent ratings of adaptive functioning were similar across Caucasian, Hispanic, and other non-Caucasian survivors covarying for family income and primary caregiver education, both of which served as proxies for socioeconomic status. All ethnic groups were rated lower than the normative mean in overall adaptive functioning as well as the specific domains of conceptual, social, and practical skills. Demographic, diagnostic, and treatment-related variables were differentially associated with adaptive functioning in survivors of pediatric brain tumor, though socioeconomic status emerged as a strong significant predictor of adaptive functioning domains. CONCLUSIONS: Adaptive outcomes do not differ as a function of ethnicity after accounting for primary caregiver education and family income. Racial and ethnic minorities may be at increased risk for poorer outcomes given their overrepresentation at lower income levels. Assessing demographic and treatment-related variables early on may be helpful in identifying children likely to develop adaptive difficulties.

Adult Glioma Incidence and Survival by Race or Ethnicity in the United States From 2000 to 2014.

Importance: Glioma is the most commonly occurring malignant brain tumor in the United States, and its incidence varies by age, sex, and race or ethnicity. Survival after brain tumor diagnosis has been shown to vary by these factors. Objective: To quantify the differences in incidence and survival rates of glioma in adults by race or ethnicity. Design, Setting, and Participants: This population-based study obtained incidence data from the Central Brain Tumor Registry of the United States and survival data from Surveillance, Epidemiology, and End Results registries, covering the period January 1, 2000, to December 31, 2014. Average annual age-adjusted incidence rates with 95% CIs were generated by glioma histologic groups, race, Hispanic ethnicity, sex, and age groups. One-year and 5-year relative survival rates were generated by glioma histologic groups, race, Hispanic ethnicity, and insurance status. The analysis included 244 808 patients with glioma diagnosed in adults aged 18 years or older. Data were collected from January 1, 2000, to December 31, 2014. Data analysis took place from December 11, 2017, to January 31, 2018. Results: Overall, 244 808 patients with glioma were analyzed. Of these, 150 631 (61.5%) were glioblastomas, 46 002 (18.8%) were non-glioblastoma astrocytomas, 26 068 (10.7%) were oligodendroglial tumors, 8816 (3.6%) were ependymomas, and 13 291 (5.4%) were other glioma diagnoses in adults. The data set included 137 733 males (56.3%) and 107 075 (43.7%) females. There were 204 580 non-Hispanic whites (83.6%), 17 321 Hispanic whites (7.08%), 14 566 blacks (6.0%), 1070 American Indians or Alaska Natives (0.4%), and 5947 Asians or Pacific Islanders (2.4%). Incidences of glioblastoma, non-glioblastoma astrocytoma, and oligodendroglial tumors were higher among non-Hispanic whites than among Hispanic whites (30% lower overall), blacks (52% lower overall), American Indians or Alaska Natives (58% lower overall), or Asians or Pacific Islanders (52% lower overall). Most tumors were more common in males than in females across all race or ethnicity groups, with the great difference in glioblastoma where the incidence was 60% higher overall in males. Most tumors (193 329 [79.9%]) occurred in those aged 45 years or older, with differences in incidence by race or ethnicity appearing in all age groups. Survival after diagnosis of glioma of different subtypes was generally comparable among Hispanic whites, blacks, and Asians or Pacific Islanders but was lower among non-Hispanic whites for many tumor types, including glioblastoma, irrespective of treatment type. Conclusions and Relevance: Incidence of glioma and 1-year and 5-year survival rates after diagnosis vary significantly by race or ethnicity, with non-Hispanic whites having higher incidence and lower survival rates compared with individuals of other racial or ethnic groups. These findings can inform future discovery of risk factors and reveal unaddressed health disparities.

Unequal Cumulative Incidence and Mortality Outcome in Childhood Brain and Central Nervous System Malignancy in the USA.

BACKGROUND: While survival in overall pediatric malignancy has improved during recent decades, brain/central nervous system (CNS) tumors has not demonstrated comparable survival advantage. Incidence and mortality data in this malignancy continue to illustrate race and sex differences; however, there are few data in the pediatric setting. This study sought to characterize brain/CNS tumors by socio-demographic and assess racial and sex variances in both cumulative incidence and mortality. METHODS: A retrospective cohort design with Surveillance, Epidemiology and End Results (SEER) 1973-2014 was used for the assessment of children aged < 1-19 years diagnosed with brain/CNS tumors. The age-adjusted incidence rates were used for temporal trends, percent change, and annual percent change. We utilized binomial regression model to determine the exposure effect of race and sex on cancer mortality, adjusting for potential confounders. RESULTS: Childhood brain/CNS tumor cumulative incidence (CmI) continues to rise in annual percent change, and mortality varied by race, sex, and year of diagnosis. The CmI was highest among whites, intermediate among blacks, and lowest among Asians, as well as lower in females relative to that in males. Compared to whites, blacks were 21% more likely to die from brain/CNS tumors [risk ratio (RR) 1.21, 95% confidence interval (C.I.) 1.13-1.28], while males were 4% more likely to die relative to females (RR 1.04, 95% C.I. 1.00-1.08). After controlling for age, sex, and tumor grade, racial disparities persisted, with 16% increased risk of dying among blacks relative to whites [adjusted risk ratio 1.16, (99% C.I.) 1.08-1.25, p < 0.001]. CONCLUSION: The cumulative incidence of brain/CNS malignancy is higher among whites relative to that in blacks; however, blacks experienced survival disadvantage even after adjustment for potential tumor prognostic and predisposing factors.

Assessment of the Association between Isocitrate Dehydrogenase 1 Mutation and Mortality Risk of Glioblastoma Patients.

Previous studies showed that isocitrate dehydrogenase 1 (IDH1) mutation might be a prognostic biomarker of prognosis in glioblastoma (GBM) patients, but the outcomes were various. A meta-analysis of published studies was carried out to reach a reliable assessment of the association between IDH1 mutation and mortality of GBM patients. Relative risks (RRs) with 95% confidence intervals (95%CIs) were pooled using meta-analysis to assess risk of mortality in patients with IDH1 mutation. A total of 20 studies (3 prospective cohort and 17 retrospective cohort studies) were finally included into the meta-analysis. Meta-analysis of total included studies suggested that GBM patients with IDH1 mutation had decreased risk of mortality compared those patients without IDH1 mutation (RR = 0.43, 95%CI 0.35-0.54, P < 0.001). GBM patients with IDH1 mutation from European countries had also decreased mortality risk compared with those patients without IDH1 mutation (RR = 0.35, 95%CI 0.25-0.49, P < 0.001), but GBM patients with IDH1 mutation from Asians only dad 32% decrease of mortality risk compared with those patients without IDH1 mutation (RR = 0.68, 95%CI 0.49-0.94, P = 0.018). The findings from the meta-analysis provide strong evidence for the association between IDH1 mutation and decreased mortality risk of GBM patients. In addition, there is an obvious difference in the mortality risk of GBM patients with IDH1 mutation between western and eastern countries.

Quantitative assessment of the association between TP53 Arg72Pro polymorphism and risk of glioma.

Many studies have investigated on the association between TP53 Arg72Pro polymorphism and risk of glioma, but the impact of TP53 Arg72Pro polymorphism on glioma risk is unclear owing to the obvious inconsistence among those studies. To shed light on these inconclusive findings and get a quantitative assessment of the association between the TP53 Arg72Pro polymorphism and risk of glioma, we conducted a meta-analysis of eligible studies. We searched PubMed and Embase databases for studies investigating on the association between the TP53 Arg72Pro polymorphism and risk of glioma. The pooled odds ratios (OR) with their 95% confidence intervals (95% CI) was calculated to assess the association between the TP53 Arg72Pro polymorphism and risk of glioma. A total of 12 studies were finally included into the meta-analysis. Meta-analysis of the 12 studies showed that TP53 Arg72Pro polymorphism was not associated with the risk of glioma (OR(Pro vs. Arg) = 1.07, 95% CI 0.93∼1.22; OR(ProPro vs. ArgArg) = 1.02, 95% CI 0.85∼1.22; OR(ProPro/ArgPro vs. ArgArg )= 1.06, 95% CI 0.85∼1.34; and OR(ProPro vs. ArgArg/ArgPro) = 1.07, 95% CI 0.91∼1.27). Subgroup analyses by ethnicity further identified that TP53 Arg72Pro polymorphism was not associated with the risk of glioma in Caucasians. However, there was a mild association between the TP53 Arg72Pro polymorphism and risk of glioma in Asians (OR(ProPro vs. ArgArg/ArgPro) = 1.42, 95% CI 1.00∼2.02). Thus, there is limited evidence for the association between the TP53 Arg72Pro polymorphism and risk of glioma, and more studies are needed to provide a more comprehensive assessment of the association in Asians.

Quantitative assessment of the association between +61A>G polymorphism of epidermal growth factor gene and susceptibility to glioma.

Numerous studies have investigated the risk of cancer associated with the polymorphism of epidermal growth factor (EGF) 61A>G, but results have been inconsistent. We performed this meta-analysis to drive a more precise estimation of the association between this polymorphism and risk of glioma. A comprehensive search was conducted to identify all case-control studies on the EGF +61A>G polymorphism and glioma risk. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to assess the strength of the association. Statistical analysis was performed with the software program Stata (version 12.0). A total of ten eligible studies, including 1,888 cases and 2,836 controls were included in this work. Overall, there was a significant association between EGF +61A>G polymorphism and glioma risk in the allele model (OR = 1.419, 95% CI = 1.144-1.759, P = 0.001). In the subgroup analysis by ethnicity, significant associations were also found in Asian populations under all different genetic models (homozygote model: OR = 1.727, 95% CI = 1.310-2.275, P = 0.000; heterozygote model: OR = 1.202, 95% CI = 1.023-1.413, P = 0.025; dominant model: OR = 1.279, 95% CI = 1.096-1.491, P = 0.002; recessive model: OR = 1.590, 95% CI = 1.221-2.070, P = 0.001; and A-allele versus G-allele OR = 1.600, 95% CI = 1.145-2.236, P = 0.006). However, no significant associations were found among Caucasians in all comparison models. In conclusion, the results suggest that there is a significant association between EGF +61A>G polymorphism and glioma risk among Asians.

Immunohistochemical assessment of MGMT expression and p53 mutation in glioblastoma multiforme.

AIMS AND BACKGROUND: The prognosis of glioblastoma multiforme (GBM) remains poor despite advances in surgery and adjuvant therapies. TP53 and O6-methylguanine-DNA methyltransferase (MGM) are tumor suppressor genes that are implicated in GBM resistance to radiation and chemotherapy. In order to assess the expression of the protein products of these two genes, 50 GBM samples were analyzed in this study. METHODS: Demographic and clinical data along with postsurgery tumor samples from 50 GBM patients were collected from the pathology archive. MGMT and p53 protein expression was evaluated by immunohistochemistry. RESULTS: 52% of cases had mutated p53, predominantly expressed in the nuclei of tumor cells. MGMT immunohistochemistry was negative in 35 (70%) patients and positive in 15 (30%) others. Immunohistochemistry-negative specimens for MGMT expression showed a significantly higher expression of mutant p53 (P = 0.03). CONCLUSION: MGMT expression was significantly lower in cells bearing p53 mutation. This indicates that there is a tendency for p53 activity to decline with MGMT inactivation. However, this study could not deduce which protein was the regulator of the other.

Incidence and management of high grade glioma in Maori and non-Maori patients.

A retrospective analysis of 301 patients was undertaken between 1993 and 2003 to evaluate the relationship of ethnicity with incidence, treatment and survival in patients undergoing surgery for high grade glioma (HGG) in New Zealand. There was no difference in age standardised incidence of HGG in Maori compared to non-Maori patients; 4.2/100,000 person years (95% confidence interval [CI] 2.6-6.9) versus 4.1 (95% CI 3.6-4.6). Maori were more likely to have complete tumour resection (odds ratio 3.59 (95% CI 1.01-12.76)) but waited 1.32 (95% CI 0.98-1.79) times longer for radiotherapy. Median survival was 29 weeks with poorer survival in Maori compared to non-Maori (hazard ratio 1.55 [95% CI 0.95-2.55]). We concluded that the incidence of HGG in Maori is similar to non-Maori. However, Maori with HGG have higher rates of complete resection but wait longer for radiotherapy and may have poorer overall survival than non-Maori.

Variations in referral patterns for hypophysectomies among pediatric patients with sellar and parasellar tumors.

PURPOSE: It has been shown that patients admitted to high-volume hospitals for resection of sellar and parasellar lesions experience reduced mortality and morbidity. It remains unknown what preoperative factors influence admission to high-volume centers. We report a nationwide analysis of patients <18 years of age undergoing neurosurgical intervention for these lesions. METHODS: A retrospective analysis of the Nationwide Inpatient Sample was performed with additional factors from the Area Resource File. International Classification of Diseases, 9th Revision diagnosis/procedural codes were used to identify patients undergoing resection of tumors from the pituitary gland or related structures. Patients >or=18 years old were excluded. Covariates included age, gender, race, and insurance status. Multivariate analysis was performed using multiple logistic regression models. A p value <0.05 was considered statistically significant. RESULTS: In total, 1,063 patients were identified. Most (69.8%) were seen at low-volume centers. Mean (median) patient age was 13.7 (15) years. The majority of patients were female (54.8%), white (61.9%), and insured (90.3%). Hispanics were 44% less likely (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.34-0.92, p < 0.05) to be seen at high-volume centers than their Caucasian counterparts. Each increase in 2-year patient age category was associated with greater access to high-volume centers (OR 1.12, 95% CI 1.03-1.23, p < 0.05), relative to 0-2 years old. Female gender, insurance status, county poverty, neurosurgeon density, and calendar year were not significantly associated with admission to high-volume centers. CONCLUSIONS: Age and racial disparities play a significant role in access neurosurgical care, affecting admission of pediatric patients to high-volume neurosurgical centers across the USA.

Disparities in access to pediatric neurooncological surgery in the United States.

OBJECTIVE: The objective of this study was to investigate whether disparities in access to high-volume centers for neurooncological care existed in the United States in 1988-2005. METHODS: A retrospective analysis of the Nationwide Inpatient Sample (1988-2005) was performed, with additional factors incorporated from the Area Resource File (2006). International Classification of Diseases, Ninth Revision, diagnosis/procedure coding was used to identify patients. High-volume centers were defined as those with > or =50 neurosurgical cases per year. Patients >18 years of age were excluded. Covariates included age, gender, race, Charlson Index score, insurance, and county-level characteristics (including median home value, proportion of foreign born residents, and county neurosurgeon density). Multivariate analysis was performed by using multiple logistic regression models. P values of <.05 were considered statistically significant. RESULTS: A total of 4421 patients were identified; 1651 (37.34%) were admitted to high-volume centers. Overall access to high-volume centers improved slightly over the 18-year period (odds ratio [OR]: 1.04). Factors associated with greater access to high-volume centers included greater county neurosurgeon density (OR: 1.72) and greater county home value (OR: 1.66). Factors associated with worse access included Hispanic ethnicity (OR: 0.68) and each 1% increase in foreign residents per county (OR: 0.59). All reported P values were <.05. CONCLUSION: This study demonstrates that racial and socioeconomic disparities in access to high-volume neurooncological care exist for the pediatric population. We also identify numerous prehospital factors that potentially contribute to persistent disparities and may be amenable to change through national health policy interventions.

Racial disparities in the development of breast cancer metastases among older women: a multilevel study.

BACKGROUND: Distant metastases are the most common and lethal type of breast cancer relapse. The authors examined whether older African American breast cancer survivors were more likely to develop metastases compared with older white women. They also examined the extent to which 6 pathways explained racial disparities in the development of metastases. METHODS: The authors used 1992-1999 Surveillance, Epidemiology, and End Results (SEER) data with 1991-1999 Medicare data. They used Medicare's International Classification of Diseases, Ninth Revision, Clinical Modification codes to identify metastases of respiratory and digestive systems, brain, bone, or other unspecified sites. The 6 pathways consisted of patient characteristics, tumor characteristics, type of treatment received, access to medical care, surveillance mammography use, and area-level characteristics (poverty rate and percentage African American) and were obtained from the SEER or Medicare data. RESULTS: Of the 35,937 women, 10.5% developed metastases. In univariate analysis, African American women were 1.61 times (95% confidence interval [CI], 1.54-1.83) more likely to develop metastasis than white women. In multivariate analysis, tumor grade, stage at diagnosis, and census-tract percentage African American explained why African American women were more likely to develop metastases than white women (hazard ratio, 0.84; 95% CI, 0.68-1.03). CONCLUSIONS: Interventions to reduce late-stage breast cancer among African Americans also may reduce racial disparities in subsequent increased risk of developing metastasis. African Americans diagnosed with high-grade breast cancer could be targeted to reduce their risk of metastasis. Future studies should identify specific reasons why the racial distribution in census tracts was associated with racial disparities in the risk of breast cancer metastases.

Racial/ethnic differences in survival among elderly patients with a primary glioblastoma.

BACKGROUND: Few studies have assessed racial/ethnic differences in survival after primary glioblastoma diagnosis. We investigate these differences, incorporating information on White, Hispanics and Asians, as well as White, non-Hispanics and Blacks, among elderly individuals with a primary glioblastoma utilizing the population-based Surveillance, Epidemiology and End Results (SEER) Program-Medicare linked database. METHODS: A total of 1,530 individuals diagnosed > = 66 years of age from 6/1/91 to 12/31/99 in the SEER data were linked with Medicare information from 1/1/91 to 12/31/01. All individuals had Medicare Parts A and B and were non-HMO for 6 months before and 12 months after diagnosis to gather pre-diagnosis co-morbidities and post-diagnosis first course of treatment. Survival differences by race/ethnicity and by race/ethnicity stratified by treatment type and/or median household income were examined using Kaplan-Meier and multivariable Cox proportional hazards models. RESULTS: Significant racial/ethnic differences existed between White, non-Hispanics and Blacks in marital status, income and SEER registry region for the entire US. In analysis limited to the West region, significant racial/ethnic differences existed for income only. Overall there were no differences in survival between White, non-Hispanics and Blacks, however, in analysis limited to the West region, Asians had a lower risk of death compared to White, non-Hispanics [HR = 0.67, 95% CI (0.43, 1.03)]. Asians who had multiple treatments also had a lower risk of death compared to White, non-Hispanics [HR = 0.65, 95% CI (0.41, 1.01)]. CONCLUSIONS: Racial/ethnic differences in survival after primary glioblastoma diagnosis exist and may be partially explained by racial/ethnic differences in treatment and income.