Yukihiko Sonoda1, Yuta Sekino2, Junki Mizusawa2, Ichiyo Shibahara3, Keita Sasaki2, Tetsuya Sekita2, Mayumi Ichikawa4, Hiroshi Igaki5, Manabu Kinoshita6, Junji Shibahara7, Koichi Ichimura7, Yoshiki Arakawa8, Haruhiko Fukuda2, Yoshitaka Narita9
1Department of Neurosurgery, Faculty of Medicine, Yamagata University, Yamagata, Japan;
2Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital, Chuo, Japan;
3Department of Neurosurgery, Kitasato University School of Medicine, Kanagawa, Japan;
4Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Yamagata University, Yamagata, Japan;
5Department of Radiation Oncology, National Cancer Center Hospital, Chuo, Japan;
6Department of Neurosurgery, Asahikawa Medical University, Asahikawa, Japan;
7Department of Pathology, Kyorin University Faculty of Medicine, Mitaka, Japan;
8Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan;
9Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Chuo, Japan
Correspondence to: Yukihiko Sonoda, MD, PhD. Department of Neurosurgery, Faculty of Medicine, Yamagata University, 2-2-2, Iida-Nishi, Yamagata-city, Yamagata 9909585, Japan. Email: yukihikosonoda@gmail.com.
Background: Complete resection of contrast-enhanced lesions [gross total resection (GTR)] without severe neurological deficits has been generally accepted as the goal of surgery. However, it remains unclear if additional resection of surrounding fluid-attenuated inversion recovery (FLAIR) hyper-intense lesions combined with GTR (FLAIRectomy) has survival advantage of primary glioblastoma patients. Multicenter, open-label, randomized phase III trial was commenced to confirm the superiority of FLAIRectomy to GTR alone followed by radiotherapy with concomitant and adjuvant temozolomide in terms of overall survival (OS) for primary glioblastoma IDH-wildtype patients. This trial investigates not only survival but also postoperative neurological and neurocognitive deficits in detail.
Methods: We assumed a 2-year OS of 50% in the GTR arm and expected a 15% improvement in the FLAIRectomy arm. A total of 130 patients is required with a one-sided alpha of 5%, power of 70%, and will be accrued from 49 Japanese institutions in 4 years and follow-up will last 2.5 years. Patients aged 18–75 years will be registered and randomly assigned to each arm with 1:1 allocation. The primary endpoint is OS, and the secondary endpoints are progression-free survival, frequency of adverse events, proportion of Karnofsky performance status preservation, proportion of National Institutes of Health stroke scale preservation, proportion of mini-mental state examination preservation and proportion of health-related quality of life preservation. The Japan Clinical Oncology Group Protocol Review Committee approved this study protocol in May 2023. Ethics approval was granted by the National Cancer Center Hospital Certified Review Board. Patient enrollment began in July 2023.
Results: If FLAIRectomy is superior to GTR alone, aggressive surgery will become a standard surgical treatment for glioblastoma with resectable contrast-enhanced lesion.
Conclusions: Registry number: jRCT1031230245. Date of registration: 19/July/2023. Date of first participant enrollment: 28/July/2023.
Keywords: Glioblastoma; fluid-attenuated inversion recovery hyper-intense lesions combined with gross total resection (FLAIRectomy); gross total resection (GTR)
