Although boron neutron capture therapy (BNCT) is a promising treatment option for malignant brain tumors, the optimal BNCT parameters for patients with immediately life-threatening, end-stage brain tumors remain unclear. We performed BNCT on 34 patients with life-threatening, end-stage brain tumors and analyzed the relationship between survival outcomes and BNCT parameters. Before BNCT, MRI and ¹⁸F-BPA-PET analyses were conducted to identify the tumor location/distribution and the tumor-to-normal tissue uptake ratio (T/N ratio) of ¹⁸F-BPA. No severe adverse events were observed (grade ≥ 3). The objective response rate and disease control rate were 50.0% and 85.3%, respectively. The mean overall survival (OS), cancer-specific survival (CSS), and relapse-free survival (RFS) times were 7.25, 7.80, and 4.18 months, respectively. Remarkably, the mean OS, CSS, and RFS of patients who achieved a complete response were 17.66, 22.5, and 7.50 months, respectively. Kaplan–Meier analysis identified the optimal BNCT parameters and tumor characteristics of these patients, including a T/N ratio ≥ 4, tumor volume < 20 mL, mean tumor dose ≥ 25 Gy-E, MIB-1 ≤ 40, and a lower recursive partitioning analysis (RPA) class. In conclusion, for malignant brain tumor patients who have exhausted all available treatment options and who are in an immediately life-threatening condition, BNCT may be considered as a therapeutic approach to prolong survival.

Brainstem tumors are heterogenous and cancerous glioma tumors arising from the midbrain, pons, and the medulla that are relatively common in children, accounting for 10% to 20% of all pediatric brain tumors. However, the prognosis of aggressive brainstem gliomas remains extremely poor despite aggressive treatment with chemotherapy and radiotherapy. That means there are many life-threatening patients who have exhausted all available treatment options and are beginning to face end-of-life stage. Therefore, the unique properties of highly selective heavy particle irradiation with boron neutron capture therapy (BNCT) may be well suited to prolong the lives of patients with end-stage brainstem gliomas. Herein, we report a case series of life-threatening patients with end-stage brainstem glioma who eligible for Emergency and Compassionate Use, in whom we performed a scheduled two fractions of salvage BNCT strategy with low treatment dosage each time. No patients experienced acute or late adverse events related to BNCT. There were 3 patients who relapsed after two fractionated BNCT treatment, characterized by younger age, lower T/N ratio, and receiving lower treatment dose. Therefore, two fractionated low-dose BNCT may be a promising treatment for end-stage brainstem tumors. For younger patients with low T/N ratios, more fractionated low-dose BNCT should be considered.

Purpose: Boron Neutron Capture Therapy (BNCT) has gained popularity in recent years, with over 500 treatment courses performed in Taiwan since 2017. Traditionally, the tumor-to-normal tissue ratio (T/N ratio) is assessed using SUV measurements from 4-borono-2-(18) F-fluoro-phenylalanine (F-BPA) PET, allowing for precise tumor boron concentration estimation when serum boron levels are measured on the day of treatment. However, limited accessibility to F-BPA PET complicates dose calculations, and in its absence, a fixed T/N ratio of 3 is used in treatment planning. Fluciclovine PET has recently been explored as an alternative, as both fluciclovine and BPA share the L-type amino acid transporter 1 (LAT-1) transporter, although fluciclovine can also be transported via alanine-serine-cysteine transporter 2 (ASCT2). However, its accuracy in reflecting BPA distribution and its correlation with treatment response remain uncertain. Patients and Methods: Since June 2022, fluciclovine PET has been used for brain tumor evaluation in Taiwan. By June 2024, 80 brain tumor patients underwent pre-BNCT assessment with fluciclovine PET. After excluding those who received a second treatment course, 44 patients were analyzed. The average T/N ratio in this cohort was 4.6, higher than reported averages for F-BPA PET (2.5 for head and neck tumors, 3 for brain tumors). The tumor response rate was defined as patients achieving either a complete or partial response, as evaluated by experienced neuroradiologists. Patients were categorized based on response achievement, and potential prognostic factors were compared. Results: The mean T/N ratio of fluciclovine PET was 4.61±1.43 (range: 2.58–8.86). Among 15 patients who underwent follow-up fluciclovine PET 3 months post-BNCT, the mean T/N ratio decreased significantly to 2.85±1.16 (range: 1.00–5.47). Treatment response assessment at 3 months post-BNCT revealed that 4 patients achieved complete response (CR), 26 had partial response (PR), 5 exhibited stable disease (SD), and 9 experienced progressive disease (PD). Responders had significantly smaller tumors compared with nonresponders (35.74 vs. 83.83 cm³, p=0.009) and received higher minimum tumor doses (18.50 vs. 12.13 GyE, p=0.033). In addition, a significant decline in T/N ratio was observed following BNCT, decreasing from 4.602±0.368 pretreatment to 2.847±0.300 at 3 months post-treatment. Conclusions: Our findings suggest that while fluciclovine PET may provide an estimate of BPA uptake, it is not a reliable predictor of treatment response. However, it remains an effective tool for assessing treatment effect following BNCT. Further studies are necessary to identify key prognostic factors for selecting BNCT candidates and to determine whether fluciclovine PET can effectively predict BNCT outcomes.

Tumor-to-normal ratio (T/N) measurement of ¹⁸F-FBPA is crucial for patient eligibility to receive boron neutron capture therapy. This study aims to compare the difference in standard uptake value ratios on brain tumors and normal brains using PET/MR ZTE and atlas-based attenuation correction with the current standard PET/CT attenuation correction. Regarding the normal brain uptake, the difference was not significant between PET/CT and PET/MR attenuation correction methods. The T/N ratio of PET/CT-AC, PET/MR ZTE-AC and PET/MR AB-AC were 2.34 ± 0.95, 2.29 ± 0.88, and 2.19 ± 0.80, respectively. The T/N ratio comparison showed no significance using PET/CT-AC and PET/MR ZTE-AC. As for the PET/MRI AB-AC, significantly lower T/N ratio was observed (− 5.18 ± 9.52%; p < 0.05). The T/N difference between ZTE-AC and AB-AC was also significant (4.71 ± 5.80%; p < 0.01). Our findings suggested PET/MRI imaging using ZTE-AC provided superior quantification on ¹⁸F-FBPA-PET compared to atlas-based AC. Using ZTE-AC on ¹⁸F-FBPA-PET /MRI might be crucial for BNCT pre-treatment planning.