Glioblastoma survival in rural America: a 10-year experience from a quaternary care center

Abstract

Background: Glioblastoma (GBM) is the most aggressive primary brain tumor with dismal prognosis. Patients residing in rural and Appalachian regions encounter multiple barriers to timely diagnosis and access to multidisciplinary neuro-oncology care, but whether these barriers translate into worse survival remains uncertain. West Virginia (WV), a predominantly rural Appalachian state, is served by a primary academic medical center (WV University Ruby Memorial Hospital) with a dedicated neuro-oncology program. We performed a retrospective analysis of the electronic health record to characterize overall survival and prognostic factors among WV residents diagnosed with GBM.

Methods: Retrospective cohort of 380 adults (≥ 18 years) with pathologically confirmed Isocitrate Dehydrogenase-wildtype (IDH-WT) GBM (2015-2025). Rurality defined by ZIP-code RUCA. Cox proportional hazards models were used to assess the association between overall survival (OS) and age, sex, treatment, rurality, and O⁶-methylguanine-DNA methyltransferase (MGMT) promoter methylation status.

Results: Median OS was 12.7 months. Age ≥ 65 was associated with worse survival (15.9 vs. 9.1 months; p < 0.001). Rural and non-rural survival was equivalent (12.5 vs. 12.7 months; p = 0.87). Temozolomide (TMZ) use significantly improved OS (14.0 vs. 6.2 months; p < 0.001). Gross total resection and MGMT promoter methylation were both associated with significantly improved overall survival (p < 0.001 and p = 0.0005, respectively).

Conclusions: In a predominantly rural state served by a primary academic neuro-oncology program, median overall survival for GBM was 12.7 months indicating centralized care eliminates rural-urban survival gaps in GBM.

Keywords: Centralized care; Glioblastoma; Real-world evidence; Rural health disparities; Survival analysis; Temozolomide.

Fig. 1

Flow diagram of patient selection for the study cohort of IDH-wildtype glioblastoma. Patients were initially identified from institutional records using ICD-10 code C71 (malignant neoplasm of brain) between the study period, yielding a total of 1015 cases. All cases were then assessed for confirmation of IDH-wildtype glioblastoma (WHO grade 4) based on integrated histopathologic, molecular, and clinical criteria (including IDH1/IDH2 sequencing or immunohistochemistry demonstrating wild-type status). A total of 380 patients met the inclusion criteria for confirmed newly diagnosed IDH-wildtype glioblastoma and were included in the final study population. The remaining 635 cases were excluded as they represented non-glioblastoma entities (e.g., other gliomas, metastases, non-malignant tumors, or IDH-mutant gliomas). This selection process ensured a homogeneous cohort focused exclusively on IDH-wildtype glioblastoma for subsequent survival and prognostic analyses. Numbers at each step indicate the sample size retained or excluded

Fig. 2

Overall survival in 380 adults with newly diagnosed, pathologically confirmed glioblastoma treated at WVU Ruby Memorial Hospital, 2015–2025. Kaplan–Meier estimate of overall survival from date of histologic diagnosis. mOS was 12.69 months (95% CI: 11.61–14.00). One-year survival probability was 53% (95% CI: 47–59%) and two-year survival probability was 25% (95% CI: 20–32%). Tick marks indicate censored observations. Number at risk is shown below the x-axis at 6-month intervals

Fig. 3

Kaplan–Meier estimates of overall survival stratified by age at diagnosis (≤ 65 years, n = 197 vs. >65 years, n = 183) in 380 patients with newly diagnosed, pathologically confirmed glioblastoma. mOS was 15.9 months (95% CI: 13.57–19.57) for patients ≤ 65 years and 7.67 months (95% CI: 5.38–10.39) for those > 65 years (log-rank p < 0.0001). Shaded regions represent 95% confidence intervals. Tick marks indicate censored observations. The number at risk is displayed below the x-axis at 6-month intervals

Fig. 4

Kaplan–Meier estimates of overall survival stratified by TMZ receipt (yes, n = 254 vs. no, n = 126) in 380 patients with newly diagnosed, pathologically confirmed glioblastoma. MOS was 14.0 months (95% CI: 12.72–16.89) for patients who received TMZ and 6.66 months (95% CI: 3.61–12.20) for those who did not (log-rank p < 0.0001). Tick marks indicate censored observations. The number at risk is displayed below the x-axis at 6-month intervals

Fig. 5

Kaplan–Meier estimates of overall survival stratified by sex (female, n = 159 vs. male, n = 221) in 380 patients with newly diagnosed, pathologically confirmed glioblastoma. MOS was 13.57 months (95% CI: 11.38–18.00) for females and 12.13 months (95% CI: 10.92–14.00) for males (log-rank p = 0.61). Tick marks indicate censored observations. The number at risk is displayed below the x-axis at 6-month intervals

Fig. 6

Kaplan–Meier estimates of overall survival stratified by rural residence (non-rural, n = 204 vs. rural, n = 176) in 380 patients with newly diagnosed, histologically confirmed glioblastoma. Median overall survival was 12.69 months (95% CI: 11.51–16.03) for non-rural patients and 12.52 months (95% CI: 10.20–16.36) for rural patients (log-rank p = 0.87). Tick marks indicate censored observations. The number at risk is displayed below the x-axis at 6-month intervals

Fig. 7

Kaplan–Meier estimates of overall survival stratified by extent of resection (GTR = Yes vs. GTR = No) in patients with IDH-wildtype glioblastoma. The red curve represents patients who achieved gross total resection (GTR = Yes), while the black curve represents those with subtotal resection or biopsy (GTR = No). Overall survival probability is plotted against time in months. Median overall survival was 20.1 months (95% CI: 17.5–24.0) for the GTR group versus 12.3 months (95% CI: 10.5–14.8) for the non-GTR group (log-rank p < 0.0001). Tick marks indicate censored observations. The number at risk is displayed below the x-axis at selected intervals (e.g., every 10–20 months). Error bars represent 95% confidence intervals at key time points

Fig. 8

Kaplan–Meier estimates of overall survival stratified by MGMT promoter methylation status (methylated vs. unmethylated) in patients with IDH-wildtype glioblastoma. The red curve represents patients with MGMT promoter methylated tumors, while the black curve represents those with MGMT promoter unmethylated tumors. Overall survival probability is plotted against time in months. Median overall survival was 16.8 months (95% CI: 14.5–19.5) for the methylated group versus 11.9 months (95% CI: 10.2–13.8) for the unmethylated group (log-rank p = 0.0005). Tick marks indicate censored observations. The number at risk is displayed below the x-axis at selected intervals (e.g., every 10–20 months). Error bars represent 95% confidence intervals at key time points

Fig. 9

Choropleth map of glioblastoma patient density by ZCTA in West Virginia. Heatmap shows case density (380 incident IDH-wildtype GBM cases diagnosed at WVU Ruby Memorial Hospital, 2015–2025; 2023 Census ZCTA estimates), with color gradient from sparse (blue) to dense (red/yellow). Cancer centers overlaid: green dots = WVU-affiliated, blue dots = non-affiliated, yellow star = Mary Babb Randolph Cancer Center at J.W. Ruby Memorial Hospital (Morgantown). WV border outlined in black. Highest densities cluster in central/northern counties near the WVU hub

Fig. 10

Choropleth map of RUCA rural-urban classification by ZCTA in West Virginia with cancer center overlay. Rural areas (RUCA-based) shaded blue; non-rural shaded light blue. Cancer centers geocoded by ZIP centroid: green dots = WVU-affiliated, blue dots = non-affiliated, yellow star = Mary Babb Randolph Cancer Center at J.W. Ruby Memorial Hospital. WV border outlined in black. Map illustrates predominant rural classification statewide, with WVU-affiliated centers distributed across rural and non-rural zones