Accelerator-based BNCT for Patients with Recurrent Glioblastoma: a Multicenter Phase II Study

Overview

Journal Neurooncol Adv

Publisher Oxford University Press

Date 2021 Jun 21

PMID 34151269

Citations 35

Authors

Shinji Kawabata

Minoru Suzuki

Katsumi Hirose

Hiroki Tanaka

Takahiro Kato

Hiromi Goto

Yoshitaka Narita

Shin-Ichi Miyatake

Affiliations

Soon will be listed here.

Abstract

Background: Boron neutron capture therapy (BNCT) utilizes tumor-selective particle radiation. This study aimed to assess the safety and efficacy of accelerator-based BNCT (AB-BNCT) using a cyclotron-based neutron generator (BNCT 30) and B-boronophenylalanine (SPM-011) in patients with recurrent malignant glioma (MG) (primarily glioblastoma [GB]).

Methods: This multi-institutional, open-label, phase II clinical trial involved 27 recurrent MG cases, including 24 GB cases, who were enrolled from February 2016 to June 2018. The study was conducted using the abovementioned AB-BNCT system, with 500 mg/kg SPM-011 (study code: JG002). The patients were bevacizumab-naïve and had recurrent MG after standard treatment. The primary endpoint was the 1-year survival rate, and the secondary endpoints were overall survival (OS) and progression-free survival (PFS). Results were compared to those of a previous Japanese domestic bevacizumab trial for recurrent GB (JO22506).

Results: The 1-year survival rate and median OS of the recurrent GB cases in this trial were 79.2% (95% CI: 57.0-90.8) and 18.9 months (95% CI: 12.9-not estimable), respectively, whereas those of JO22506 were 34.5% (90% CI: 20.0-49.0) and 10.5 months (95% CI: 8.2-12.4), respectively. The median PFS was 0.9 months (95% CI: 0.8-1.0) by the RANO criteria. The most prominent adverse event was brain edema. Twenty-one of 27 cases were treated with bevacizumab following progressive disease.

Conclusions: AB-BNCT demonstrated acceptable safety and prolonged survival for recurrent MG. AB-BNCT may increase the risk of brain edema due to re-irradiation for recurrent MG; however, this appears to be controlled well with bevacizumab.

Citing Articles

Acute Kidney Injury Due to Ureteral Damage by Needle-Shaped Crystals Associated With Boron Neutron Capture Therapy.

Mima A, Matsuki T, Nakamoto T, Saito Y, Morikawa T, Kure S Cureus. 2025; 16(12):e76094.

PMID: 39834996 PMC: 11743920. DOI: 10.7759/cureus.76094.

A national survey of medical staffs' required capability and workload for accelerator-based boron neutron capture therapy.

Nakamura S, Tanaka H, Kato T, Akita K, Takemori M, Kasai Y J Radiat Res. 2024; 65(5):712-724.

PMID: 39167773 PMC: 11420840. DOI: 10.1093/jrr/rrae058.

Evaluation of sodium borocaptate (BSH) and boronophenylalanine (BPA) as boron delivery agents for neutron capture therapy (NCT) of cancer: an update and a guide for the future clinical evaluation of new boron delivery agents for NCT.

Barth R, Gupta N, Kawabata S Cancer Commun (Lond). 2024; 44(8):893-909.

PMID: 38973634 PMC: 11337926. DOI: 10.1002/cac2.12582.

Boron neutron capture therapy delays the decline in neurological function in a mouse model of metastatic spinal tumors.

Fujikawa Y, Kawabata S, Tsujino K, Yamada H, Kashiwagi H, Yagi R Cancer Sci. 2024; 115(8):2774-2785.

PMID: 38860412 PMC: 11309935. DOI: 10.1111/cas.16245.

Nonclinical pharmacodynamics of boron neutron capture therapy using direct intratumoral administration of a folate receptor targeting novel boron carrier.

Tsujino K, Kashiwagi H, Nishimura K, Fujikawa Y, Kayama R, Fukuo Y Neurooncol Adv. 2024; 6(1):vdae062.

PMID: 38770220 PMC: 11102930. DOI: 10.1093/noajnl/vdae062.

References

Nonoguchi N, Miyatake S, Fukumoto M, Furuse M, Hiramatsu R, Kawabata S . The distribution of vascular endothelial growth factor-producing cells in clinical radiation necrosis of the brain: pathological consideration of their potential roles. J Neurooncol. 2011; 105(2):423-31. DOI: 10.1007/s11060-011-0610-9. View

Miyatake S, Kawabata S, Yokoyama K, Kuroiwa T, Michiue H, Sakurai Y . Survival benefit of Boron neutron capture therapy for recurrent malignant gliomas. J Neurooncol. 2008; 91(2):199-206. DOI: 10.1007/s11060-008-9699-x. View

Kazmi F, Soon Y, Leong Y, Koh W, Vellayappan B . Re-irradiation for recurrent glioblastoma (GBM): a systematic review and meta-analysis. J Neurooncol. 2018; 142(1):79-90. DOI: 10.1007/s11060-018-03064-0. View

Tanaka H, Sakurai Y, Suzuki M, Masunaga S, Mitsumoto T, Fujita K . Experimental verification of beam characteristics for cyclotron-based epithermal neutron source (C-BENS). Appl Radiat Isot. 2011; 69(12):1642-5. DOI: 10.1016/j.apradiso.2011.03.020. View

Chadha M, Capala J, Coderre J, Elowitz E, Iwai J, JOEL D . Boron neutron-capture therapy (BNCT) for glioblastoma multiforme (GBM) using the epithermal neutron beam at the Brookhaven National Laboratory. Int J Radiat Oncol Biol Phys. 1998; 40(4):829-34. DOI: 10.1016/s0360-3016(97)00891-2. View

Kawabata S, Miyatake S, Kajimoto Y, Kuroda Y, Kuroiwa T, Imahori Y . The early successful treatment of glioblastoma patients with modified boron neutron capture therapy. Report of two cases. J Neurooncol. 2003; 65(2):159-65. DOI: 10.1023/b:neon.0000003751.67562.8e. View

Hundsberger T, Brugge D, Putora P, Weder P, Weber J, Plasswilm L . Re-irradiation with and without bevacizumab as salvage therapy for recurrent or progressive high-grade gliomas. J Neurooncol. 2013; 112(1):133-9. DOI: 10.1007/s11060-013-1044-3. View

Galanis E, Jaeckle K, Maurer M, Reid J, Ames M, Hardwick J . Phase II trial of vorinostat in recurrent glioblastoma multiforme: a north central cancer treatment group study. J Clin Oncol. 2009; 27(12):2052-8. PMC: 2669764. DOI: 10.1200/JCO.2008.19.0694. View

Kankaanranta L, Seppala T, Koivunoro H, Valimaki P, Beule A, Collan J . L-boronophenylalanine-mediated boron neutron capture therapy for malignant glioma progressing after external beam radiation therapy: a Phase I study. Int J Radiat Oncol Biol Phys. 2011; 80(2):369-76. DOI: 10.1016/j.ijrobp.2010.02.031. View

10.

Cloughesy T, Wen P, Robins H, Chang S, Groves M, Fink K . Phase II trial of tipifarnib in patients with recurrent malignant glioma either receiving or not receiving enzyme-inducing antiepileptic drugs: a North American Brain Tumor Consortium Study. J Clin Oncol. 2006; 24(22):3651-6. DOI: 10.1200/JCO.2006.06.2323. View

11.

Gilbert M, Pugh S, Aldape K, Sorensen A, Mikkelsen T, Penas-Prado M . NRG oncology RTOG 0625: a randomized phase II trial of bevacizumab with either irinotecan or dose-dense temozolomide in recurrent glioblastoma. J Neurooncol. 2016; 131(1):193-199. PMC: 5263144. DOI: 10.1007/s11060-016-2288-5. View

12.

See S, Levin V, Yung W, Hess K, Groves M . 13-cis-retinoic acid in the treatment of recurrent glioblastoma multiforme. Neuro Oncol. 2004; 6(3):253-8. PMC: 1871997. DOI: 10.1215/S1152851703000607. View

13.

Nagane M, Nishikawa R, Narita Y, Kobayashi H, Takano S, Shinoura N . Phase II study of single-agent bevacizumab in Japanese patients with recurrent malignant glioma. Jpn J Clin Oncol. 2012; 42(10):887-95. PMC: 3448378. DOI: 10.1093/jjco/hys121. View

14.

Kong D, Lee J, Park K, Kim J, Lim D, Nam D . Efficacy of stereotactic radiosurgery as a salvage treatment for recurrent malignant gliomas. Cancer. 2008; 112(9):2046-51. DOI: 10.1002/cncr.23402. View

15.

Niyazi M, Ganswindt U, Schwarz S, Kreth F, Tonn J, Geisler J . Irradiation and bevacizumab in high-grade glioma retreatment settings. Int J Radiat Oncol Biol Phys. 2010; 82(1):67-76. DOI: 10.1016/j.ijrobp.2010.09.002. View

16.

Miyatake S, Kawabata S, Nonoguchi N, Yokoyama K, Kuroiwa T, Matsui H . Pseudoprogression in boron neutron capture therapy for malignant gliomas and meningiomas. Neuro Oncol. 2009; 11(4):430-6. PMC: 2743223. DOI: 10.1215/15228517-2008-107. View

17.

Morris S, Zhu P, Rao M, Martir M, Zhu J, Hsu S . Gamma Knife Stereotactic Radiosurgery in Combination with Bevacizumab for Recurrent Glioblastoma. World Neurosurg. 2019; 127:e523-e533. DOI: 10.1016/j.wneu.2019.03.193. View

18.

Rosenthal M, Gruber M, Glass J, Nirenberg A, Finlay J, Hochster H . Phase II study of combination taxol and estramustine phosphate in the treatment of recurrent glioblastoma multiforme. J Neurooncol. 2000; 47(1):59-63. DOI: 10.1023/a:1006426215005. View

19.

Flieger M, Ganswindt U, Schwarz S, Kreth F, Tonn J, Fougere C . Re-irradiation and bevacizumab in recurrent high-grade glioma: an effective treatment option. J Neurooncol. 2014; 117(2):337-45. DOI: 10.1007/s11060-014-1394-5. View

20.

Chanana , Capala , Chadha , Coderre , DIAZ , Elowitz . Boron neutron capture therapy for glioblastoma multiforme: interim results from the phase I/II dose-escalation studies. Neurosurgery. 1999; 44(6):1182-92; discussion 1192-3. DOI: 10.1097/00006123-199906000-00013. View