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Abstract
Purpose: This study aimed to identify a specific subgroup of patients among elderly glioblastoma patients aged 70 years or older with unmethylated O6-methylguanine-DNA methyltransferase promoters (eGBM-unmethylated) who would significantly benefit from the addition of temozolomide (TMZ) to radiotherapy (RT).

Materials and methods: Newly diagnosed patients with Isocitrate dehydrogenase wild-type eGBM-unmethylated treated with RT were included in this multicenter analysis (n=182). RT dose was 45 Gy in 15 fractions (62.3%), 60 Gy in 30 fractions, or 61.2 Gy in 34 fractions. For patients treated with RT plus TMZ (60.4%), TMZ was administered concurrently with RT, followed by six adjuvant cycles. The primary endpoint was overall survival.

Results: During a median follow-up of 11.3 months for survivors, the median survival was 12.2 months. The median survival duration significantly improved with the addition of TMZ to RT compared with that with RT alone (13.6 months vs. 10.5 months, p=0.028). In the multivariable analysis adjusted for clinical, radiological, and genetic biomarkers, the addition of TMZ significantly improved overall survival (hazard ratio, 0.459; p=0.006). In subgroup analysis, median survival was especially improved by 4-5 months in patients with residual disease (p < 0.001), Karnofsky performance status ≥ 60 (p=0.033), and age ≤ 75 years (p=0.090). A significant benefit of TMZ was noted only in patients with two or three of the above factors (median survival, 14.1 months vs. 10.5 months; p=0.014).

Conclusion: The addition of TMZ significantly improved the survival of patients with eGBM-unmethylated treated with RT. The suggested criteria for the specific subgroup in these patients warrant external validation for clinical application.

Affiliations

Chan Woo Wee 1 2, Joo Ho Lee 3 4, Hye In Lee 5, Jina Kim 6, Jong Hee Chang 7, Seok-Gu Kang 7, Eui Hyun Kim 7, Ju Hyung Moon 7, Jaeho Cho 1, Chul-Kee Park 8, Chae-Yong Kim 9, Kihwan Hwang 9, Hong In Yoon 1 2, In Ah Kim 3
1Department of Radiation Oncology, Yonsei Cancer Center, Heavy Ion Therapy Research Institute, Yonsei University College of Medicine, Seoul, Korea.
2Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea.
3Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul.
4Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
5Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
6Department of Radiation Oncology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
7Department of Neurosurgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
8Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul.
9Department of Neurosurgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam.