Dear Editor, We read with interest the review “Side effects of boron neutron capture therapy.”1 While informative, several statements rely primarily on reactor-era cohorts and legacy infusion and dosing paradigms, resulting in an adverse-event (AE) profile that does not reflect current accelerator-based BNCT (AB-BNCT) practice. We recognize the review was submitted in 2023; since then, accelerator-era evidence and labeling have expanded, and several conclusions merit updating to align with today’s protocols and real-world safety data. Drug administration and current labeling. Much of the severe neurologic or hematologic toxicity historically reported traces to high-load BPA regimens and prolonged infusions that are no longer representative. In contrast, the PMDA-approved borofalan (¹°B) regimen specifies a single 500 mg/kg dose infused over 3 h (200 mg/kg/h for 2 h, then 100 mg/kg/h during irradiation)—a key anchor for AE expectations today. Incorporating this labeling would prevent overestimation of risk when counseling patients and designing supportive care pathways.2 Head and neck cancer: accelerator-era benchmarks. The cyclotron-based JHN002 trial using borofalan (¹°B) reported an AE spectrum dominated by mucocutaneous toxicity (oral mucositis, dermatitis) and transient laboratory abnormalities (e.g., hyperamylasemia), with serious vascular events uncommon under modern selection and prophylaxis. These data, rather than reactor-era series, better represent contemporary safety.3 Moreover, nationwide post-marketing surveillance in Japan corroborates that the AB-BNCT AE profile in routine care is broadly manageable and consistent with trial experience, reinforcing the need to privilege accelerator-era evidence.4 Brain tumors and modern mitigation. For glioma, current programs standardize edema prophylaxis/management (e.g., timely corticosteroids; selective bevacizumab) and employ rigorous imaging adjudication to distinguish treatment-related changes from progression—considerations that differ materially from earlier dosing/workflows and should temper statements on radiation necrosis risk. Prospective evidence in newly diagnosed glioblastoma. Importantly, a prospective phase I protocol for newly diagnosed glioblastoma (GBM) at the University of Tsukuba integrates single-fraction AB-BNCT with subsequent external-beam radiotherapy and temozolomide, with prespecified dose constraints (e.g., normal-brain D2cc caps) and DLT adjudication. Although outcomes are pending, the protocol delineates a forward-looking safety framework distinct from reactor-era practice and should be acknowledged when summarizing present-day risks.5 Recommendations. We respectfully suggest: (i) separating reactor-era and accelerator-era evidence in AE tables/figures, (ii) aligning toxicity statements with current infusion regimens and device-specific dose constraints, and (iii) prioritizing accelerator-era datasets (JHN002 and post-marketing surveillance for head and neck; ongoing prospective protocols for GBM) when formulating clinically actionable risk statements. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Nakai et al. (Thu,) studied this question.