Clinical Evaluation of Absolute Biological Effectiveness Dose In Boron Neutron Capture Therapy
Abstract
Purpose
Clinical boron neutron capture therapy (BNCT) dose calculations commonly rely on fixed compound biological effectiveness (CBE) factors, which may fail to capture inter-patient biological heterogeneity relevant to treatment response. This study investigates whether the Absolute Biological Effectiveness (ABE) dose, derived from tumor-specific nucleocytoplasmic (N/C) ratios, provides improved discrimination in patients with malignant brain tumors undergoing BNCT.
Methods
Seventeen patients with malignant brain tumors treated with BNCT were retrospectively analyzed. Tumor N/C ratios were quantitatively determined from histopathological images using a standardized image analysis protocol. Patient-specific biological sensitivity was modeled using Ono’s formulation, where D0=0.341(N/C)-1.586, which links cellular morphology to radiation response, and the ABE factor was defined as D0-1 accordingly. The ABE dose was calculated by weighting the physical boron dose with the corresponding ABE factor. Treatment response was classified as progressive disease (PD) or non-progressive disease (non-PD) based on RANO criteria. Only cases with more than 1500 quantified nuclei were included to ensure statistical robustness.
Results
Conventional physical equivalent dose metrics, including mean equivalent dose (ED), did not show significant differentiation between PD and non-PD groups (Ρ= 0.878). In contrast, ABE-based metrics, including mean ABE dose and ABE D50%, demonstrated superior separation between response groups. In glioblastoma (GBM) cases, ABE dose metrics consistently distinguished PD from non-PD outcomes, indicating that tumor biological sensitivity characterized by the N/C ratio plays a critical role in BNCT treatment response. Higher N/C ratios were associated with enhanced tumor control.
Conclusion
The ABE dose integrates patient-specific cellular characteristics into BNCT dosimetry and provides a biologically informed metric for treatment evaluation. Compared with fixed-weight physical dose assessment, ABE-based dosimetry demonstrates improved discrimination of clinical response and supports the feasibility of incorporating biology-informed dose metrics into personalized BNCT treatment planning for malignant brain tumor patients.