Wenjun Zhu, Jie Rao, Guangyuan Hu, Runkun Wang, Xiaoxiao Luo, Qianxia Li
In this retrospective cohort of Chinese patients with grade 4 glioma, adding TTFields to maintenance TMZ therapy following standard postoperative radiochemotherapy was associated with improved OS compared with maintenance TMZ alone, whereas the improvement in PFS did not reach statistical significance. The co-occurrence of chromosome 7 gain and chromosome 10 loss was identified as a significant risk factor for shorter PFS and OS. Exploratory subgroup analyses suggested greater potential benefit in patients with MGMT-unmethylated tumors, IDH wild-type tumors, multiple surgical sites, or Ki-67 < 20%. Given the small sample size, retrospective non-randomized design, and wide confidence intervals in some subgroup estimates, these findings should be interpreted cautiously and validated in larger prospective multicenter studies.
OBJECTIVE: The EF-14 trial established the survival benefit of adding Tumor Treating Fields (TTFields) to maintenance temozolomide (TMZ) following standard radiochemotherapy in glioblastoma (GBM). Whether this benefit is reproducible in Chinese grade 4 glioma patients in real-world practice-and what biomarkers predict response-remains unknown. This study evaluates TTFields efficacy in a Chinese cohort and explores predictive biomarkers.
METHODS: We conducted a retrospective analysis of Chinese patients with grade 4 gliomas who underwent surgery and postoperative radiochemotherapy, followed by maintenance TMZ with or without TTFields treatment at Tongji Hospital, Huazhong University of Science and Technology, between November 2019 and November 2024. The Kaplan-Meier method was used to plot survival curves for overall survival (OS) and progression-free survival (PFS), and the log-rank test was applied for group comparisons. Univariate Cox proportional hazards regression analysis was performed to identify factors associated with PFS and OS. Subgroup analyses were conducted, and results were visualized using forest plots.
RESULTS: A comprehensive dataset of 64 postoperative grade 4 glioma patient records was compiled in the study. Among them, 22 patients (34.4%) were administered TTFields treatment. The TTFields-treated group demonstrated a significant improvement in OS compared to the non-TTFields-treated group (median OS: 15 months vs. 11 months, P = .047). Univariate Cox analysis identified the chromosome 7 gain and chromosome 10 loss as a significant risk factor for shortened PFS (HR = 2.294; 95% CI, 1.268-4.150; P = .006) and OS (HR = 2.831; 95% CI, 1.507-5.316; P = .001). Subgroup analysis revealed that TTFields treatment resulted in better PFS for O6-methylguanine DNA methyltranferase (MGMT)-unmethylated patients (HR [95% CI] = 2.269 [1.066-4.83], P = .033) and isocitrate dehydrogenase (IDH) wild-type patients (HR [95% CI] = 2.101 [1.029-4.291], P = .042). In terms of OS, TTFields treatment was associated with improved OS in patients with multiple surgical sites (HR [95% CI] = 4.148 [1.073-16.033], P = .039), MGMT-unmethylated patients (HR [95% CI] = 2.421 [1.113-5.263], P = .026), IDH wild-type patients (HR [95% CI] = 2.169 [1.039-4.526], P = .039), and those with Ki-67 < 20% (HR [95% CI] = 9.398 [1.122-78.75], P = .039).
CONCLUSION: In this retrospective cohort of Chinese patients with grade 4 glioma, adding TTFields to maintenance TMZ therapy following standard postoperative radiochemotherapy was associated with improved OS compared with maintenance TMZ alone, whereas the improvement in PFS did not reach statistical significance. The co-occurrence of chromosome 7 gain and chromosome 10 loss was identified as a significant risk factor for shorter PFS and OS. Exploratory subgroup analyses suggested greater potential benefit in patients with MGMT-unmethylated tumors, IDH wild-type tumors, multiple surgical sites, or Ki-67 < 20%. Given the small sample size, retrospective non-randomized design, and wide confidence intervals in some subgroup estimates, these findings should be interpreted cautiously and validated in larger prospective multicenter studies.