Salvage Boron Neutron Capture Therapy for Malignant Brain Tumor Patients in Compliance with Emergency and Compassionate Use: Evaluation of 34 Cases in Taiwan

Abstract

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.

Keywords: BNCT; T/B ratio; T/N ratio; glioblastoma; radioresistance.

Figure 1

Kaplan–Meier curves for different tumor types. Kaplan–Meier survival curves for overall survival (OS) and cancer-specific survival (CSS) of patients with astrocytoma and glioblastoma. BNCT treatment showed a better OS in patients with astrocytoma than in those with glioblastoma.

Figure 2

Kaplan–Meier survival curve of tumors with MIB-1 ≤ 40 and MIB-1 > 40. A MIB-1 labelling index higher than 40% predicted poor cancer-specific survival (CSS) and poor relapse-free survival (RFS).

Figure 3

Kaplan–Meier survival curve of tumors from RPA classes I–III and RPA classes IV–VII. A higher RPA class predicted poor overall survival (OS), cancer-specific survival (CSS), and relapse-free survival (RFS).

Figure 4

Kaplan–Meier cancer-specific survival curves of patients treated with BNCT according to the T/N ratio, tumor volume, and tumor size. (A) The T/N ratio denotes the tumor-to-normal tissue uptake ratio of 18F-L-BPA. Patients with a T/N ratio ≥ 4 had better CSS values than patients with a T/N ratio < 4. (B) Patients with a tumor volume < 20 mL or (C) a receiving mean tumor dose ≥ 25 Gy-E had better CSS values after BNCT treatment. p values are marked in the upper right corner, and p values of less than 0.05 were regarded as statistically significant. CSS denotes cancer specific survival.

Figure 5

Representative images of tumor shrinkage after BNCT treatment. (A) Before BNCT treatment, ¹⁸F-BPA-PET revealed the location of strong tumor activity in the right fronto-temporal lobe. (B) MRI imaging of the patient before BNCT treatment. An anaplastic astrocytoma was observed in the right temporal lobe (white dashed circles). (C) Three months after BNCT treatment, a follow-up MRI image of the patient showed a significant reduction in tumor volume (white dashed circles).

Figure 6

Invisible tumor activity revealed by 18F-BPA-PET. (A) MRI of patient after surgical resection of brain tumors. Postoperative MRI did not identify overt lesions after surgery. (B) Postoperative 18F-BPA-PET revealed strong tumor activity in the surgical margin. The white arrows indicate the infiltrative tumor lesions.