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Ep09.06 First-in-human Use of Accelerator-based Bnct With Concurrent P-boronophenylalanine (nbb-001) and Single-dose Bevacizumab for Recurrent Glioblastoma

Year: 2025
Type: conference-abstract
Abstract: BACKGROUND Recurrent glioblastoma remains one of the most therapeutically challenging malignancies, with rapid progression and limited salvage options. BNCT (Boron Neutron Capture Therapy) offers biologically targeted irradiation by delivering high-LET alpha particles selectively to tumor cells containing boron-10. This case represents the first-in-human clinical use of the NeuPex Block-I (Neuboron) system—a compact, hospital-integrated tandem accelerator delivering epithermal neutrons via a lithium target. MATERIAL AND METHODS A 52-year-old male patient with right frontal glioblastoma WHO grade 4 (IDH1/2 wild-type, 1p/19q non-codeleted, MGMT promoter methylated) underwent surgery on 20.12.2023. This was followed by standard radiochemotherapy per Stupp protocol (60 Gy with concurrent temozolomide), and adjuvant temozolomide. Multiparametric MRI and FET-PET uptake in dual acquisition confirmed recurrence showing rapid clinical deterioration shortly after radiological recurrence. The patient was treated with a single session of accelerator-based BNCT using p-boronophenylalanine (NBB-001) followed by a single infusion of Bevacizumab post-treatment. Neutron irradiation was performed using the NeuPex Block-I (Neuboron) system. Clinical monitoring, imaging, hematology, and quality-of-life evaluations were conducted at baseline and at regular intervals post-treatment. RESULTS BNCT dosimetry showed selective tumor targeting with favorable distribution of boron concentrations and corresponding compound biological effectiveness (CBE). The highest boron concentration was observed in the tumor (GTV: 66 µg/ml, CBE 3.8), while normal brain tissue showed significantly lower values (26.25 µg/ml, CBE 1.3). DVH analysis confirmed adequate dose coverage, with Dmax and Dmean for the GTV reaching 43.045 Gy-Eq and 22.276 Gy-Eq, respectively. In contrast, healthy brain tissue received substantially lower doses (Dmax 6.757 Gy-Eq, Dmean 1.121 Gy-Eq), indicating good sparing of surrounding structures. Post-BNCT imaging demonstrated early radiologic changes consistent with therapeutic effect. The patient experienced a resolution of neurological symptoms and maintained an excellent quality of life, with no alopecia, no skin reactions, and no hematologic toxicity. For four months post-treatment, the patient remained fully independent and functionally intact. At six months, MRI findings raised suspicion of radiation necrosis, prompting reintroduction of Bevacizumab. CONCLUSION This case illustrates the first clinical use of NeuPex Block-I (Neuboron) BNCT system, combined with BPA and adjunctive Bevacizumab. The treatment was well-tolerated, preserved quality of life, and showed promising early therapeutic effect. These data show the potential of accelerator-based BNCT for recurrent brain tumors and support further clinical studies.
DOI: 10.1093/neuonc/noaf193.602
Language: English
Field: Medicine
Open Access status: bronze
OpenAlex ID: W4414800072
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