Abstract

Few population-based analyses have investigated survival change in glioblastoma multiforme (GBM) patients treated with concomitant radiotherapy-temozolomide (RT-TMZ) and adjuvant temozolomide (TMZ) and then bevacizumab (BEV) after Food and Drug Administration (FDA) approval, respectively. We aimed to explore the effects on survival with RT-TMZ, adjuvant TMZ and BEV in general GBM population based on the Surveillance, Epidemiology, and End Results (SEER) and Texas Cancer Registry (TCR) databases. A total of 28933 GBM patients from SEER (N = 24578) and TCR (N = 4355) between January 2000 and December 2013 were included. Patients were grouped into three calendar periods based on date of diagnosis: pre-RT-TMZ and pre-BEV (1/2000–2/2005, P1), post-RT-TMZ and pre-BEV (3/2005–4/2009, P2), and post-RT-TMZ and post-BEV (5/2009–12/2013, P3). The association between calendar period of diagnosis and survival was analyzed in SEER and TCR, separately, by the Kaplan-Meier method and Cox proportional hazards model. We found a significant increase in median overall survival (OS) across the three periods in both populations. In multivariate models, the risk of death was significantly reduced during P2 and further decreased in P3, which remained unchanged after stratification. Comparison and validation analysis were performed in the combined dataset, and consistent results were observed. We conclude that the OS of GBM patients in a “real-world” setting has been steadily improved from January 2000 to December 2013, which likely resulted from the administrations of TMZ concomitant with RT and adjuvant TMZ for newly diagnosed GBM and then BEV for recurrent GBM after respective FDA approval.

Highlights

  • Glioblastoma multiforme (GBM) comprises approximately 46.1% of primary malignant brain tumors, and only about 5.1% of patients survive five years after diagnosis [1]

  • We aimed to explore the effects on survival with RT-TMZ, adjuvant TMZ and BEV in general glioblastoma multiforme (GBM) population based on the Surveillance, Epidemiology, and End Results (SEER) and Texas Cancer Registry (TCR) databases

  • We conclude that the overall survival (OS) of GBM patients in a “real-world” setting has been steadily improved from January 2000 to December 2013, which likely resulted from the administrations of TMZ concomitant with RT and adjuvant TMZ for newly diagnosed GBM and BEV for recurrent GBM after respective Food and Drug Administration (FDA) approval

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Summary

Introduction

Glioblastoma multiforme (GBM) comprises approximately 46.1% of primary malignant brain tumors, and only about 5.1% of patients survive five years after diagnosis [1]. Favorable clinical prognostic factors include maximum safe resection, good performance status, young age at diagnosis, completion of radiation and chemotherapies [1], [2], [3], [4]. Molecular prognostic factors include the presence of the O6-methylguanine-. DNA methyltransferase (MGMT) promoter methylation [5], [6], the isocitrate dehydrogenase 1 and 2 (IDH1/2) mutations [7]. Besides the known hyper-methylation of the MGMT gene, Noushmehr et al [8] revealed that glioma cytosine–phosphate–guanine islands methylator phenotype (G-CIMP) is a positive prognostic marker.

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