Females have the survival advantage in glioblastoma

QT Ostrom, JB Rubin, JD Lathia, ME Berens…�- Neuro�…, 2018 - academic.oup.com
Neuro-oncology, 2018academic.oup.com
Glioblastoma is the most common type of malignant brain tumor in the United States, with an
average annual ageadjusted incidence rate (AAAIR) of 3.20/100 000. 1 These tumors are
60% more incident in males (AAAIR= 3.99/100 000) than females (AAAIR= 2.52/100 000). 1
Previous analyses have demonstrated a significant association between female sex and
improved survival, 2 but this has not been systematically assessed within population-based
datasets. This study was approved by the institutional review board at University Hospitals�…
Glioblastoma is the most common type of malignant brain tumor in the United States, with an average annual ageadjusted incidence rate (AAAIR) of 3.20/100 000. 1 These tumors are 60% more incident in males (AAAIR= 3.99/100 000) than females (AAAIR= 2.52/100 000). 1 Previous analyses have demonstrated a significant association between female sex and improved survival, 2 but this has not been systematically assessed within population-based datasets. This study was approved by the institutional review board at University Hospitals Cleveland Medical Center. Data were obtained from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program 3 and from a multicenter study in Ohio (the Ohio Brain Tumor Study [OBTS]) 4 for glioblastoma cases in patients≥ 18 years old and diagnosed in 2007 or later that received standard of care treatment (eg, surgery followed by concurrent chemoradiation). The SEER 18 includes 18 central cancer registries and represents~ 28% of the US population. Ohio is not included within the SEER program. Thus, it is unlikely that individuals from Ohio would be included in both datasets. There were 5372 SEER cases and 228 OBTS cases. Analysis was performed using sex-specific Cox proportional hazards models adjusted for extent of resection (subtotal vs gross total), age at diagnosis, and Karnofsky performance status (KPS)(OBTS only). Postsurgical KPS was available for only 117 of 228 and was imputed using multivariate imputation by chained equations from the R package ‘mice.’Overall median survival was 16 months (95% CI= 16–17) in SEER and 16.9 months (95% CI= 15.1–19.9) in OBTS. Sex was significantly associated with survival in both datasets. In SEER, median survival was 17 months (95% CI= 16–17) in females and 16 months (95% CI= 15–17, P= 0.0034) in males (Fig. 1A), and in OBTS median survival was 22.6 months (95% CI= 19.7–26.0) in females and 15.9 months in males (95% CI= 14.0–19.4, P= 0.0006)(Fig. 1B). The vast majority of glioblastomas are isocitrate dehydrogenase 1/2 (IDH1/2) wildtype (IDHwt,> 95%), but IDH1/2 mutation is significantly associated with improved survival. 5, 6 Potential confounding between sex and molecular classification was assessed in OBTS IDHwt cases (these data were not available in SEER). Among IDHwt cases (N= 102, IDH1/2 status not available on all cases), a female survival advantage remained, with median survival of 25.5 months (95% CI= 18.1–43.2) in females and 15.0 months (95% CI= 13.6–21.4, P= 0.0082) in males (Fig. 1C).
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