Accelerator-based boron neutron capture therapy, a randomized controlled trial for refractory recurrent high-grade meningiomas.

2083 Background: High-grade meningiomas (HGMs) recurred after X-ray treatment showed pessimistic prognosis. We conducted “A phase II investigator-lead RCT using accelerator-based BNCT system for refractory recurrent high-grade meningioma”. Methods: We prepared 2 study arms, BNCT test treatment arm (12 subjects) and control best supportive care arm (6 subjects) in RCT fashion. PFS judged by the third-party committee was primary endpoint and PFS judged by investigators themselves and OS of BNCT arm and so on were secondary endpoints. Rescue BNCT was permitted for control group patients, if they were judged as PD by investigators. First patient-in and last patient-in were August 2019 and August 2021, respectively. Last patient visit was February 2024 and final OS survey and final observation for effectiveness and safety in BNCT arm were performed in July 2024. These results were compared to EORTC’s RCT of trabectedin. Results: Three and 2 grade 3 subjects were included in BNCT and control arm, respectively. Others were grade 2 subjects. All cases were confirmed relapse after some radiotherapy in follow-up images. One subject allocated in BNCT arms was excluded after enrollment due to protocol violation. At the end of the observation, as primary endpoint, PFS of each arm judged by committees showed statistical significance (p=0.0157, Log-rank). As one of the secondary endpoints, PFS of each arm judged by investigators also showed statistical significance (p=0.0002). Median PFS judged by committees were 14.4 (95% CI:7.9-26.4) and 1.4 (1.0-9.0) months for BNCT and control arm, respectively. Median PFS judged by investigators showed 14.7 (7.6-22.8) and 1.5 (1.0-9.0) months, respectively. Five out of 6 cases in control arm received rescue BNCT after PD assessments. Other endpoints are listed in the table. Conclusions: As primary endpoint, PFS judged by committee showed statistical significance between treatment and control arms. Recently, the results of RCT of “Trabectedin” for recurrent HGMs, organized by EORTC, (EORTC-1320-BTG) was reported. Unfortunately, there was no effect of Trabectedin not only in PFS but in OS. Therefore, EORTC’s report seems to be natural course of recurrent refractory HGMs. Our current BNCT shows extremely excellent results in comparison with EORTC’s RCT in mPFS, PFS-6 months, mOS, OS-1 year and ORR (Table). Clinical trial information: 2051190044 . Comparison of both RCT (current study and EORTC trabectedin). Current study (n=18) EORTC trabectedin (n=90) BNCT Control Trabectedin Control mPFS (months) 14.4 1.4 2.43 4.17 PFS-6 months (%) 100 44.4 21.1 29.1 mOS (months) 46.9 - 11.4 10.6 OS-1 year (%) 100.0 - 48.1 43.0 OS-2 year (%) 90.9 - - - ORR (CR+PR) (%) 27.3 0 1.6 0