Authors :
Presenting Author: Hyo Jin Park, MD, PhD – Seoul National University Bundang Hospital
Kihwan Hwang, MD, PhD – Seoul National University Bundang Hospital
Chae-Yong Kim, MD, PhD – Seoul National University Bundang Hospital
Ho Kang, MD, PhD – Seoul National University Bundang Hospital
Jae Rim Kim, MD, PhD – Chungnam National University Sejong Hospital
Sun-Ku Han, MD – Seoul National University Bundang Hospital
Chang-Ho Yun, MD, PhD – Seoul National University Bundang Hospital
Woo-Jin Lee, MD, PhD – Seoul National University Bundang Hospital
Rationale:
Bevacizumab (BVCZ) is commonly used in patients with high-grade glioma (HGG) when tumor progression (PD) is suspected. While seizure exacerbation or clinical deterioration is occasionally observed during the early phases of BVCZ treatment, its prevalence, prognostic value, and associated factors remain undemonstrated. This study aimed to evaluate the temporal pattern of symptomatic seizure and clinical aggravation following BVCZ initiation and their associations with clinical outcome in HGG patients.
Methods:
Based on the brain tumor database from a tertiary hospital, we retrospectively analyzed 175 patients with HGG who received at least one dose of BVCZ between 2016 and 2024. Data on demographics, tumor characteristics, clinical features, and treatments were collected. Seizure exacerbation, clinical deterioration, and radiological findings were assessed at BVCZ initiation (timepoint 1, TP1), and subsequently at 4 weeks (TP2), 2-3 months (TP3), and 4-5 months (TP4) after initiation. At TP1, patients were classified as definite/probable or possible PD based on the level of clinical and radiological certainty regarding disease progression. Survival outcomes, including progression-free survival (PFS) and overall survival (OS), were analyzed using Kaplan-Meier estimates and Cox proportional hazards models, adjusted for sex, age, extent of resection, tumor type, IDH mutation, MGMT methylation, baseline Karnofsky Performance Status at BVCZ start, and time from diagnosis to BVCZ initiation.
Results:
Among 175 patients (mean age: 56.3±13.8 years; 53% male), 152 (87%) had glioblastoma. Seizure aggravation during BVCZ treatment occurred in 20 patients (11%), and clinical deterioration in 73%. No significant baseline differences were found between definite/probable PD (n=132) and possible PD (n=21) groups. Median OS was slightly shorter in the definite/probable PD group than in the possible PD group (log-rank p = 0.056). On multivariate analysis, definite/probable PD at TP1 was independently associated with worse OS (HR 0.566, 95% CI 0.34 - 0.95, p = 0.030). In the definite/probable PD subgroup, clinical deterioration between TP2 - TP4 was significantly associated with shorter PFS (HR 2.39 95% CI 1.60-3.56, p < 0.001). In contrast, seizure aggravation during the same period was not predictive of PFS (HR 1.51, 95% CI 0.90-2.52, p = 0.115) or OS (HR 1.17, 95% CI 0.70-1.93, p = 0.550).
Conclusions:
Seizure and clinical deterioration after BVCZ treatment exhibit distinct prognostic implications, possibly influenced by the certainty of PD at treatment start. The mechanism of BVCZ—reducing abnormal vessel growth and leakiness while briefly normalizing blood flow (and thus lowering the seizure threshold)—may explain why seizure worsening and clinical decline carry different prognoses. This study provides valuable insight into seizure dynamics in the context of antiangiogenic therapy in HGG.
Funding: No funding was received.