Seizure prophylaxis in glioma surgery: a synopsis from the SPRING RCT

Area of Science:

• Neurosurgery
• Oncology
• Clinical Trials

Background:

• Glioma patients have a high lifetime risk of seizures, often drug-resistant.
• Seizure risk escalates perioperatively, during tumor progression, and near death.
• Current guidelines do not mandate prophylactic antiseizure medication for seizure-naive glioma patients undergoing surgery.

Purpose of the Study:

• To evaluate if prophylactic levetiracetam (pre-op and 1-year post-op) reduces seizure risk by over 50% in seizure-naive glioma patients undergoing surgery.
• To assess the cost-effectiveness of prophylactic levetiracetam compared to standard care (no prophylaxis).
• To investigate the impact of prophylactic levetiracetam on survival, tumor recurrence, and quality of life.

Main Methods:

• A two-arm, multicenter phase III randomized trial involving 14 neurosurgery units.
• Comparison of 12 months of prophylactic levetiracetam versus no antiseizure medication in suspected cerebral glioma patients.
• Intention-to-treat analysis of primary outcomes (12-month seizure occurrence) and secondary outcomes (time to seizure, survival, progression-free survival).

Main Results:

• The trial closed early with 94 participants due to slow recruitment, significantly underpowering the study.
• No significant difference in 12-month seizure risk was observed: 47% in the levetiracetam group vs. 41% in the no prophylaxis group.
• Median time to first seizure was shorter in the no prophylaxis group (2.5 months) compared to the levetiracetam group (5.0 months).

Conclusions:

• The underpowered trial provides no definitive evidence for the efficacy or cost-effectiveness of prophylactic levetiracetam in this patient population.
• The role of prophylactic antiseizure medication in glioma surgery remains unclear.
• Further definitive trials are necessary to address this clinical question.