Survival after hypofractionated radiation versus standard radiation in glioblastoma by MGMT promoter methylation status and age: an analysis of the national cancer database

Megan Parker; Austin Carmichael; Calixto-Hope G Lucas Jr; Karisa C Schreck; Kristin J Redmond; Lawrence R Kleinberg; Jordina Rincon-Torroella

doi:10.1007/s11060-026-05612-5

Survival after hypofractionated radiation versus standard radiation in glioblastoma by MGMT promoter methylation status and age: an analysis of the national cancer database

J Neurooncol. 2026 Jun 9;178(2):55. doi: 10.1007/s11060-026-05612-5.

Authors

Megan Parker¹, Austin Carmichael¹, Calixto-Hope G Lucas Jr², Karisa C Schreck³, Kristin J Redmond⁴, Lawrence R Kleinberg⁴, Jordina Rincon-Torroella⁵

Affiliations

¹ Department of Neurosurgery, Johns Hopkins University School of Medicine, 600 N. Wolfe Street Phipps Building, Suite 123, Baltimore, MD, 21287, USA.
² Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Departments of Neurology and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, MD, USA.
⁵ Department of Neurosurgery, Johns Hopkins University School of Medicine, 600 N. Wolfe Street Phipps Building, Suite 123, Baltimore, MD, 21287, USA. jrincon2@jhmi.edu.

PMID: 42265433
DOI: 10.1007/s11060-026-05612-5

Abstract

Purpose: Hypofractionated radiotherapy (HFRT) is recommended by NCCN and EANO guidelines for elderly patients with glioblastoma, but large real-world comparisons with standard fractionated radiotherapy (SFRT) are limited. We evaluated the association between HFRT and survival among patients with glioblastoma, stratified by elderly status and MGMT promoter (MGMTp) methylation, in a national cancer registry.

Methods: In this retrospective cohort study of the 2022 National Cancer Database, we identified 2,401 elderly (≥ 70 years) and 4,944 non-elderly (< 70 years) patients with histologically confirmed glioblastoma. Overall survival was compared between HFRT (40 Gy/15 fractions) and SFRT (60 Gy/30 fractions) with Kaplan-Meier and multivariable Cox proportional hazards analyses stratified by age, MGMTp methylation, and chemotherapy status. Covariables included demographic variables, Charlson-Deyo score, extent of resection, and tumor size.

Results: Among elderly patients, 1,432 received HFRT and 969 received SFRT. Kaplan-Meier analysis indicated a survival advantage for elderly individuals who received SFRT plus chemotherapy compared to those who received HFRT plus chemotherapy (15.01 versus 10.71 months, p < 0.001), regardless of MGMTp methylation. However, multivariable analyses revealed no survival difference between HFRT and SFRT in elderly individuals across all chemotherapy and MGMTp subgroupings. Among non-elderly patients (557 HFRT; 4,387 SFRT), both Kaplan-Meier and multivariable analyses demonstrated shorter survival with HFRT across chemotherapy and MGMTp subgroups.

Conclusion: SFRT was associated with longer survival in non-elderly patients, possibly reflecting selection of poorer-risk patients for HFRT. In elderly patients, HFRT was noninferior regardless of MGMTp status, supporting its use as a less intensive approach with comparable survival and reduced treatment burden.

Keywords: Chemoradiation; Elderly; Glioblastoma; Hypofractionated radiotherapy; MGMT; NCDB; Survival.

Publication types

Comparative Study

MeSH terms

Adult
Age Factors
Aged
Aged, 80 and over
Brain Neoplasms* / genetics
Brain Neoplasms* / mortality
Brain Neoplasms* / pathology
Brain Neoplasms* / radiotherapy
DNA Methylation*
DNA Modification Methylases* / genetics
DNA Repair Enzymes* / genetics
Databases, Factual
Female
Follow-Up Studies
Glioblastoma* / genetics
Glioblastoma* / mortality
Glioblastoma* / pathology
Glioblastoma* / radiotherapy
Humans
Male
Middle Aged
Prognosis
Promoter Regions, Genetic
Radiation Dose Hypofractionation*
Retrospective Studies
Survival Rate
Tumor Suppressor Proteins* / genetics

Substances

DNA Modification Methylases
Tumor Suppressor Proteins
DNA Repair Enzymes
MGMT protein, human