BACKGROUND The prognostic role of racial and socioeconomic factors in patients with glioblastoma is controversially debated. We aimed to evaluate how these factors may affect survival outcomes in an overall and cause-specific manner using large, national cancer registry cohort data in the temozolomide chemoradiation era. METHODS The National Cancer Institute’s Surveillance, Epidemiology, and End Results database was queried for patients diagnosed with glioblastoma between 2005 and 2016. Overall survival was assessed using Cox proportional hazard models using disease intrinsic and extrinsic factors. Cause-specific mortality was assessed using cumulative incidence curves and modeled using multivariate cumulative risk regression. RESULTS A total of 28,954 patients met the prespecified inclusion criteria and were included in this analysis. The following factors were associated with all-cause mortality: age, calendar year of diagnosis, sex, treatment receipt, tumor size, tumor location, extent of resection, median household income, and race. Asian/Pacific Islanders and Hispanic Whites had lower mortality compared to Non-Hispanic Whites. Cause-specific mortality was associated with both racial and socioeconomic groups. After adjusting for treatment and tumor-related factors, Asian/Pacific and black patients had lower glioblastoma-specific mortality. However, lower median household income and black race were associated with significantly higher non-glioblastoma mortality. CONCLUSION Despite the aggressive nature of glioblastoma, racial and socioeconomic factors influence glioblastoma-specific and non-glioblastoma associated mortality. Our study shows that patient race has an impact on glioblastoma-associated mortality independently of tumor and treatment related factors. Importantly, socioeconomic and racial differences largely contribute to non-glioblastoma mortality, including death from other cancers, cardio- and cerebrovascular events.
BACKGROUND RNA expression and DNA methylation studies have identified different subclasses of isocitrate dehydrogenase (IDH)-wildtype (wt) glioblastoma (GBM). However, the prognostic significance of molecular subclasses is unclear. Although hyperglycemia has been previously associated with worse survival, attempts to lower glucose have yielded mixed responses. The role of hyperglycemia may be confounded by molecular heterogeneity and have different impact in molecularly distinct GBM subclasses. METHODS Clinical, laboratory, and molecular data on 89 IDH-wt GBMs profiled by clinical next-generation sequencing and treated with Stupp protocol were reviewed. IDH-wt GBMs were subclassified into RTKI (Proneural), RTKII (Classical) and Mesenchymal subtypes using DNA methylation. Average glucose was calculated by time-weighting plasma glucose measurements between diagnosis and last follow-up. RESULTS Patients were stratified into three groups using average glucose: tertile one (< 100mg/dL), tertile two (100-115mg/dL), and tertile three ( > 115mg/dL). Comparison across glucose tertiles revealed no significant differences in Karfnosky Performance Status (KPS), dexamethasone dose, MGMT methylation, or methylation subclass. Overall survival (OS) was not affected by methylation subclass (log-rank p=0.9) but decreased with higher glucose (log-rank p=0.015). Higher glucose tertiles were associated with poorer OS among RTK I (log-rank p=0.08) and mesenchymal tumors (log-rank p=0.05), but not RTK II (log-rank p=0.99). After controlling for age, KPS, dexamethasone dose, and MGMT status, glucose remained significantly associated with survival (adjusted hazard ratio=5.2, p=0.02). DNA methylation clustering did not identify a unique signature associated with high or low glucose levels. Metabolomic analysis of 23 tumors showed minimal variation across metabolites within the cohort with no differences across molecular subclasses. CONCLUSION Higher average glucose values were associated with poorer OS in RTKI and Mesenchymal IDH-wt GBM, but not RTKII. There were no discernible epigenetic or metabolomic differences between tumors in different glucose environments, suggesting a potential survival benefit with systemic glucose lowering in selected molecular subtype.
1593 Background: Cranial radiation is known to increase the relative risk for developing a second primary neoplasm, but existing analyses do not take into account differential survival or follow-up. The absolute risk, or true incidence, of developing a second primary neoplasm in the central nervous system (CNS) is not well characterized. Methods: Patients diagnosed with cancer from between 1976 and 2016 were sampled using the Surveillance, Epidemiology, and End Results (SEER) Program. Relative risks were estimated using standardized incidence ratios (SIRs) and absolute risks were estimated using cumulative incidence (CI) functions with death as a competing risk. Among CNS primaries, comparison groups were matched by age, sex, year of diagnosis, primary histology, and lesion location. Results: Over 3.8 million patient records, including 13,167 second primary CNS tumors, were extracted from SEER. The relative risk of developing a second primary CNS neoplasm is elevated in all patients diagnosed with a CNS primary cancer (SIR = 9.6), but higher in those who received radiation (SIR = 13.1) or chemotherapy (SIR = 12.6). The absolute risk of developing a second primary CNS neoplasm at 25-years is highest in CNS and endocrine cancers (CI 1.0% and 0.50%, respectively). Among long-term ( > 10-year) survivors of CNS primaries, the 25-year CI of a second primary CNS neoplasm was 4.4%. Cranial radiation increased the incidence of second primary tumors in pediatric patients (25-year CI 4.8% vs 1.2%, p = 0.007), but not adults (25-year CI 5.1% vs 4.9%, p = 0.85). Chemotherapy did not increase CI in either pediatric (25-year CI 7.0% vs 5.4%, p = 0.87) or adult (25-year CI 3.6% vs 5.8%, p = 0.11) populations. Meningiomas (39.3% vs 22.0%, p = 1e-6) and glioblastomas (21.1% vs 14.6%, p = 0.03) represent a greater proportion of the second primary CNS tumors in those who received cranial irradiation. Conclusions: The risk of developing a second primary CNS neoplasm is elevated in patients with a prior CNS cancer. Cranial irradiation increased the CI of second primary tumors in pediatric patients but did not affect adult patients. The association between radiation therapy and risk for subsequent cancers may be limited to the pediatric population.
12023 Background: The burden of prescription drug use is higher in cancer survivors than the general population. We examined the prevalence and temporal trends of prescription drug use among cancer survivors, with an emphasis on central nervous system (CNS) active medications used to manage long-term cancer sequelae. Methods: Adult respondents with (n=3207) and without (n=40,440) a prior cancer diagnosis from 8 cycles (2001-2016) of the National Health and Nutritional Examinational Survey (NHANES) were evaluated for prescription drug usage. Cross-sectional analyses and temporal trends across cycles were evaluated and weighted to represent the US adult population. Results: Cancer survivors report higher rates of prescription drug usage (85.1% vs 54.3%, p<0.001, and 75.8%, p<0.001) and polypharmacy (27.8% vs 10.7%, p<0.001, and 22.7%, p<0.001) than both unadjusted and age-adjusted controls. Younger survivors report greater usage of CNS (36.8% vs 13.1%, p<0.001), psychotherapeutic (18.4% vs 7.7%, p<0.001), hormonal agents (19.1% vs 10.1%, p=0.003), and gastrointestinal (10.7% vs 4.7%, p=0.02) than controls, while differences are attenuated in older cohorts. Among broad drug categories, the usage of cardiovascular (p-trend<0.001), metabolic (p-trend<0.001), and immunologic agents (p-trend=0.01) has increased. Among CNS active subclasses, the usage of anticonvulsants (p-trend<0.001), anxiolytics (p-trend =0.02), narcotics (p-trend=0.02) and GABA analogs (p-trend<0.001) has increased. When comparing respondents with and without a history of cancer, the increased usage of anti-depressant prescription medications (18.3% vs 1.5% p<0.001), including SSRIs (11.2% vs 1.0%, p<0.001), SSNRIs (3.5% vs 0.3%, p<0.001), tricyclics (2.8% vs 0.1%, p<0.001), among cancer survivors was disproportionate compared to the increased proportion of positive depression screens (9.2% vs 7.0%, p=0.006). Conclusions: Cancer survivors report higher prescription drug use for both chronic conditions and late effects of cancer. The usage of CNS active medications, many of which are used on and off label for their pain management properties, has increased. The higher rates of pharmaceutical use may result in unanticipated long-term toxicities and financial burdens.
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