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Original Article
Choosing Wisely Between Radiotherapy Dose-Fractionation Schedules: The Molecular Graded Prognostic Assessment for Elderly Glioblastoma Patients
Hye In Lee1,2orcid , Jina Kim3, In Ah Kim4, Joo Ho Lee1, Jaeho Cho3, Rifaquat Rahman5, Geoffrey Fell6, Chan Woo Wee3,7orcid , Hong In Yoon3orcid

DOI: https://doi.org/10.4143/crt.2024.680 [Accepted]
Published online: September 11, 2024
1Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
2Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
3Department of Radiation Oncology, Yonsei Cancer Center, Heavy Ion Therapy Research Institute, Yonsei University College of Medicine, Seoul, Korea
4Department of Radiation Oncology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
5Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, USA
6Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, USA
7Department of Radiation Oncology, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
Corresponding author:  Chan Woo Wee
Tel: 82-2-2228-8121 Fax: 82-2-2227-7823 Email: wcw0108@hanmail.net
Hong In Yoon
Tel: 82-2-2228-8110 Fax: 82-2-2227-7823 Email: YHI0225@yuhs.ac
Hye In Lee and Jina Kim contributed equally to this study as co-first authors.
Received: 22 July 2024   • Accepted: 10 September 2024
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Purpose
This study aimed to develop a graded prognostic assessment (GPA) model integrating genomic characteristics for elderly patients with glioblastoma (eGBM), and to compare the efficacy of different radiotherapy schedules.
Materials and Methods
This multi-institutional retrospective study included patients aged ≥65 years who underwent surgical resection followed by radiotherapy with or without temozolomide (TMZ) for newly diagnosed eGBM. Based on the significant factors identified in the multivariate analysis for overall survival (OS), the molecular GPA for eGBM (eGBM-molGPA) was established.
Results
A total of 334 and 239 patients who underwent conventionally fractionated radiotherapy (CFRT) and hypofractionated radiotherapy (HFRT) were included, respectively, with 86% of patients receiving TMZ-based chemoradiation. With a median follow-up of 17.4 months (range, 3.3–149.9), the median OS was 18.7 months for CFRT+TMZ group, 15.1 months for HFRT+TMZ group, and 10.4 months for radiotherapy alone group (CFRT+TMZ vs. HFRT+TMZ: HR 1.52, p<0.001; CFRT+TMZ vs. radiotherapy alone: HR 2.52, p<0.001). In a combined analysis with the NOA-08 and NORDIC trials, CFRT+TMZ group exhibited the highest survival rates among all treatment groups. The eGBM-molGPA, which integrated four clinical and three molecular parameters, stratified patients into low-, intermediate-, and high-risk groups. CFRT+TMZ significantly improved OS compared to HFRT+TMZ or radiotherapy alone in the low-risk (p=0.023) and intermediate-risk groups (p<0.001). However, in the high-risk group, there was no significant difference in OS between treatment options (p=0.770).
Conclusion
CFRT+TMZ may be more effective than HFRT+TMZ or radiotherapy alone for selected eGBM patients. The novel eGBM-molGPA model can guide treatment selection for this patient population.


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