Biopsy with same-session MRI-guided laser interstitial thermal therapy versus biopsy alone in patients with primary unresectable glioblastoma: a multicentre randomised controlled trial.

Background: Glioblastoma (GBM) is an aggressive malignancy with poor outcomes, particularly when resection is infeasible. Laser Interstitial Thermal Therapy (LITT) offers a minimally invasive cytoreductive option, though robust evidence remains limited. The aim of the EMITT trial (NCT05318612) was to evaluate LITT in these patients. However, the study was terminated early following funding retraction due to slow patient inclusion. Despite being underpowered, its findings provide valuable insights into LITT's potential role. Methods: In this non-blinded multicentre randomised controlled trial, adult patients with unresectable GBM were randomised 1:1 to biopsy or biopsy with same-session LITT followed by standard of care. Patients were recruited by seven Dutch neurosurgical hospitals. Primary outcomes were overall survival and health-related quality of life (HR-QoL) at 5 months post-randomization. Minimum follow-up was 18 months or until death. Findings: Patients were included between April 19, 2022, and March 19, 2024. Twenty-nine patients were included; three were excluded post-randomization, leaving twenty-six for intention-to-treat analyses: fourteen in the control group and twelve in the intervention group. Median survival was 4.8 months (95%CI 3.4-not estimable) in controls and 7.8 months (95%CI 2.58-not estimable) in intervention. Mean QLQ-C30 summary scores at 5 months were 77 (SD 11) and 81 (SD 11). Interpretation: Definitive conclusions regarding (cost-)effectiveness are precluded by small sample size and baseline imbalances. This work highlights the need for larger prospective studies to establish LITT's effectiveness in this population and lessons learned may inform the design of future trials. Funding: Funding by the Dutch Healthcare Institute and ZonMw.