First Clinical Application of Repeated Boron Neutron Capture Therapy for Olfactory Neuroblastoma: Achieving Local Control Despite Regional Progression

To evaluate the feasibility and clinical outcomes of two-course boron neutron capture therapy (BNCT) as a salvage treatment for multiply recurrent olfactory neuroblastoma (ONB), and to discuss the implications of intratumoral heterogeneity on treatment planning. A 50-year-old male with recurrent ONB with extensive intracranial invasion underwent BNCT after exhausting surgical and conventional radiotherapy options. Boronophenylalanine (BPA) was administered at 500 mg/kg. The patient received two courses of neutron irradiation at the Tsing Hua Open-Pool Reactor (THOR). Dosimetry was guided by 18F-fluciclovine PET imaging (serving as a surrogate for BPA biodistribution) and calculated using the simulation environment for radiotherapy applications (SERA) treatment planning system. The first BNCT course (April 2024, Tumor Dmax 49.2 Gy-Eq) resulted in significant tumor shrinkage; however, PET imaging revealed residual metabolic activity in centrally necrotic regions. Consequently, a second BNCT course was administered (March 2025, Tumor Dmax 40.73 Gy-Eq). The patient achieved a near-complete response at the primary skull base site with no high-grade adverse effects. Although local control was sustained as of November 2025, a new cervical lymph node metastasis was identified. BNCT serves as a potent and safe salvage modality for recurrent, radio-resistant ONB, allowing for high tumor doses while sparing critical brain structures. The discordant response between the tumor rim and necrotic core highlights the challenge of heterogeneity, supporting the rationale for fractionated BNCT protocols and careful surveillance of regional nodal basins.