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

Chen, Yi Wei; Lee, Yi Yen; Lin, Ching-Fuh; Pan, Po Shen; Chen, Jen Kun; Wang, Chun Wei; Hsu, Shih Ming; Kuo, Yi Chun; Lan, Tien Li; Hsu, Sanford P.C.; Liang, Muh Lii; Chen, Robert Hsin Hung; Chang, Feng Chi; Wu, Chao‐Hsiung; Lin, Shih Chieh; Liang, H.K.; Lee, Jia Cheng; Chen, Shih Kuan; Liu, Hong Ming; Peir, Jinn-Jer; Lin, Kon Ping; Huang, Wen Sheng; Chen, Kuan Hsuan; Kang, Yu‐Mei; Liou, Shueh C.; Wang, Chun Chieh; Pai, Ping‐Ching; Li, Chih Wei; Chiek, Daniel Quah Song; Wong, Tai-Tong; Chiou, Shih Hwa; Chao, Yee; Tanaka, Hiroki; Chou, Fong‐In; Ono, Koji

doi:10.3390/biology10040334

Cited by 39 publications

(32 citation statements)

References 39 publications

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“…The early induction of bevacizumab treatment could suppress radiation toxicity after BNCT, as with other radiation therapies. Recently, a Taiwanese research group reported on BNCT of lower tumor dose (range, 8.51-25.09 Gy-equivalent) than other reports in treatment of recurrent MG with life-threatening, end-stage status [24]. Their median PFS and OS were 4.18 and 7.25 months, respectively.…”

Section: Discussionmentioning

confidence: 99%

Boron neutron capture therapy and add-on bevacizumab in patients with recurrent malignant glioma

Furuse

Kawabata

Wanibuchi

et al. 2022

Japanese Journal of Clinical Oncology

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Background Although boron neutron capture therapy has shown excellent survival data, previous studies have shown an increase in radiation necrosis against recurrent malignant glioma. Herein, we proposed that bevacizumab may reduce radiation injury from boron neutron capture therapy by re-irradiation. We evaluated the efficacy and safety of a boron neutron capture therapy and add-on bevacizumab combination therapy in patients with recurrent malignant glioma. Methods Patients with recurrent malignant glioma were treated with reactor-based boron neutron capture therapy. Treatment with bevacizumab (10 mg/kg) was initiated 1–4 weeks after boron neutron capture therapy and was administered every 2–3 weeks until disease progression. Initially diagnosed glioblastomas were categorized as primary glioblastoma, whereas other forms of malignant glioma were categorized as non-primary glioblastoma. Results Twenty-five patients (14 with primary glioblastoma and 11 with non-primary glioblastoma) were treated with boron neutron capture therapy and add-on bevacizumab. The 1-year survival rate for primary glioblastoma and non-primary glioblastoma was 63.5% (95% confidence interval: 33.1–83.0) and 81.8% (95% confidence interval: 44.7–95.1), respectively. The median overall survival was 21.4 months (95% confidence interval: 7.0–36.7) and 73.6 months (95% confidence interval: 11.4–77.2) for primary glioblastoma and non-primary glioblastoma, respectively. The median progression-free survival was 8.3 months (95% confidence interval: 4.2–12.1) and 15.6 months (95% confidence interval: 3.1–29.8) for primary glioblastoma and non-primary glioblastoma, respectively. Neither pseudoprogression nor radiation necrosis were identified during bevacizumab treatment. Alopecia occurred in all patients. Six patients experienced adverse events ≥grade 3. Conclusions Boron neutron capture therapy and add-on bevacizumab provided a long overall survival and a long progression-free survival in recurrent malignant glioma compared with previous studies on boron neutron capture therapy alone. The add-on bevacizumab may reduce the detrimental effects of boron neutron capture therapy, including pseudoprogression and radiation necrosis. Further studies of the combination therapy with a larger sample size and a randomized controlled design are warranted.

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Section: Discussionmentioning

confidence: 99%

Boron neutron capture therapy and add-on bevacizumab in patients with recurrent malignant glioma

Furuse

Kawabata

Wanibuchi

et al. 2022

Japanese Journal of Clinical Oncology

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“…In a recent study in Taiwan, a total of 34 patients with malignant brain tumors in an immediately life-threatening condition who were treated by BNCT were investigated. The T/N ratio was a significant prognostic factor of cancer-specific survival, such as a 12-month survival rate with a T/N ratio < 3 (42%), 3-4 (22%), > 4 (100%), and the p value when the T/N ratio ≥ 4 and < 4 was 0.035, although the T/B ratio did not show a significant difference in overall, cancer-specific, and relapse-free survivals [27].…”

Section: Clinical Assessment Of 18 Fbpa Petmentioning

confidence: 93%

Development of an Imaging Technique for Boron Neutron Capture Therapy

Fukumitsu¹,

Matsumoto

2021

Cells

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The development of 4-10B-borono-2-18F-fluoro-L-phenylalanine (18FBPA) for use in positron emission tomography (PET) has contributed to the progress of boron neutron capture therapy (BNCT). 18FBPA has shown similar pharmacokinetics and distribution to 4-10B-borono-L-phenylalanine (BPA) under various conditions in many animal studies. 18FBPA PET is useful for treatment indication. A higher 18FBPA accumulation ratio of the tumor to the surrounding normal tissue (T/N ratio) indicates that a superior treatment effect is expected. In clinical settings, a T/N ratio of higher than 2.5 or 3 is often used for patient selection. Moreover, 18FBPA PET is useful for predicting the 10B concentration delivered to the tumor and surrounding normal tissues, enabling high-precision treatment planning. Precise dose prediction using 18FBPA PET data has greatly improved the treatment accuracy of BNCT. However, the methodology used for the data analysis of 18FBPA PET findings varies; thus, data should be evaluated using a consistent methodology so as to be more reliable. In addition to PET applications, the development of 18FBPA as a contrast agent for magnetic resonance imaging that combines gadolinium and 10B is also in progress.

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“…In this model, the maximum tumor RBE dose was determined to be 42.2 Gy-Eq and the mean tumor RBE dose was estimated to be 28.9 Gy-Eq [ 37 ]. Studies in malignant brain tumors and recurrent head and neck cancers treated with BNCT have demonstrated that doses of 18–25 Gy-E delivered to at least 80% of the tumor volume are associated with improved control rates [ 38 , 39 ]. More recently, a newer model of BNCT dose calculation known as the photon isoeffective model was developed and validated in a limited number of studies.…”

Section: Treatment Planning Considerations and Radiobiologic Aspects ...mentioning

confidence: 99%

Exploring the Biological and Physical Basis of Boron Neutron Capture Therapy (BNCT) as a Promising Treatment Frontier in Breast Cancer

Seneviratne

Advani

Trifiletti

et al. 2022

Cancers

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BNCT is a high LET radiation therapy modality that allows for biologically targeted radiation delivery to tumors while reducing normal tissue impacts. Although the clinical use of BNCT has largely been limited to phase I/II trials and has primarily focused on difficult-to-treat malignancies such as recurrent head and neck cancer and recurrent gliomas, recently there has been a renewed interest in expanding the use of BNCT to other disease sites, including breast cancer. Given its high LET characteristics, its biologically targeted and tumor specific nature, as well as its potential for use in complex treatment settings including reirradiation and widespread metastatic disease, BNCT offers several unique advantages over traditional external beam radiation therapy. The two main boron compounds investigated to date in BNCT clinical trials are BSH and BPA. Of these, BPA in particular shows promise in breast cancer given that is taken up by the LAT-1 amino acid transporter that is highly overexpressed in breast cancer cells. As the efficacy of BNCT is directly dependent on the extent of boron accumulation in tumors, extensive preclinical efforts to develop novel boron delivery agents have been undertaken in recent years. Preclinical studies have shown promise in antibody linked boron compounds targeting ER/HER2 receptors, boron encapsulating liposomes, and nanoparticle-based boron delivery systems. This review aims to summarize the physical and biological basis of BNCT, the preclinical and limited clinical data available to date, and discuss its potential to be utilized for the successful treatment of various breast cancer disease states.

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

Cited by 39 publications

References 39 publications

Boron neutron capture therapy and add-on bevacizumab in patients with recurrent malignant glioma

Boron neutron capture therapy and add-on bevacizumab in patients with recurrent malignant glioma

Development of an Imaging Technique for Boron Neutron Capture Therapy

Exploring the Biological and Physical Basis of Boron Neutron Capture Therapy (BNCT) as a Promising Treatment Frontier in Breast Cancer

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