Abstract
Despite the recent improvements in multimodal therapies that include surgery, radiotherapy, and chemotherapy, glioblastoma multiforme (GBM) easily recurs and continues to have a median overall survival time of less than 1.5 year.
Eight nonrandomized prospective external beam BNCT trials have been performed over 15 years. The p-dihydroxyboryl-phenylalanine (BPA)-mediated BNCT was performed in the Brookhaven National Laboratory (BNL) trial, the trial of Harvard/MIT, the trial of University of Helsinki and VTT (Technical Research Centre of Finland), and the trial of Studsvik. The sulfhydryl borane Na2B12H11SH (BSH)-mediated BNCT was performed in the European Organisation for Research and Treatment of Cancer (EORTC) 11961 trial and the trial of Nuclear Research Institute (NRI) in Rez. The combination of BPA and BSH was used in the trial of Osaka Medical College and the trial of University of Tsukuba and JAEA. In the trial of Studsvik and Osaka Medical College, the long-term infusion of BPA was employed. Additional photon irradiation was performed in the trial of Osaka Medical College and the trial of University of Tsukuba and Japan Atomic Energy Agency (JAEA). Four of eight studies, even in subgroups of the patient population, suggest that external beam BNCT may improve survival in newly diagnosed GBM. Of these eight studies, four primarily phase I trials demonstrated only modest toxicity. The median time to progression and the median survival time vary from 6 to 12 months and 12 to 27 months, respectively.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Stummer W, Pichlmeier U, Meinel T et al (2006) Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomized controlled multicentre phase III trial. Lancet Oncol 7:392–401
Nimsky C, Ganslandt O, von Keller B, Fahlbusch R (2006) Intraoperative visualization for resection of gliomas: the role of functional neuronavigation and intraoperative 1.5 T MRI. Neurol Res 28:482–487
Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996
Vinjamuri M, Adumala RR, Altaha R et al (2009) Comparative analysis of temozolomide (TMZ) versus 1,3-bis (2-chloroethyl)-1 nitrosourea (BCNU) in newly diagnosed glioblastoma multiforme (GBM) patients. J Neurooncol 91:221–225
Ali SA, McHayleh WM, Ahmad A et al (2008) Bevacizumab and irinotecan therapy in glioblastoma multiforme: a series of 13 cases. J Neurosurg 109:268–272
Vredenburgh JJ, Desjardins A, Herndon JE 2nd et al (2007) Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol 25:4722–4729
Walker MD, Alexander E Jr, Hunt WE et al (1978) Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas: cooperative clinical trial. J Neurosurg 49:333–343
Walker MD, Green SB, Byar DP et al (1980) Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. N Engl J Med 303:1323–1329
Kristiansen K, Hagen S, Kollevold T et al (1981) Combined modality therapy of operated astrocytomas grade III and IV: confirmation of the value of postoperative irradiation and lack of potentiation of bleomycin on survival time: a prospective multicenter trial of the Scandinavian Glioblastoma Study Group. Cancer 47:649–652
Sandberg-Wollheim M, Malmstrom P, Stromblad LG et al (1991) A randomized study of chemotherapy with procarbazine, vincristine, and the lomustine with and without radiation therapy for astrocytoma grade 3 and/or 4. Cancer 68:22–29
Anderson AP (1978) Postoperative irradiation of glioblastomas. Results in a randomized series. Acta Radiol Oncol Radiat Phys Biol 17:475–484
Bleehen NM, Stennning SP (1991) A Medical Research Council trial of two radiotherapy doses in the treatment of grades 3 and 4 astrocytoma. Br J Cancer 64:769–774
Gasper LE, Fisher BJ, Macdonald DR et al (1992) Supratentorial malignant glioma: patterns of recurrence and implications for external beam local treatment. Int J Radiat Oncol Biol Phys 24:55–57
Oppitz U, Maessen D, Zunterer H et al (1999) 3D-recurrence-patterns of glioblastomas after CT-planned postoperative irradiation. Radiother Oncol 53:53–57
Tanaka M, Ino Y, Nakagawa K et al (2005) High-dose conformal radiotherapy for supratentorial malignant glioma: a historical comparison. Lancet Oncol 6:953–960
Nwokedi EC, DiBase SJ, Jabbour S, Herman J, Amin P, Chin LS et al (2002) Gamma knife stereotactic radiosurgery for patients with glioblastoma multiforme. Neurosurgery 50:41–47
Baumert BG, Lutterbach J, Bernays R et al (2003) Fractionated stereotactic radiotherapy boost after post-operative radiotherapy in patients with high-grade gliomas. Radiother Oncol 67:183–190
Souhami L, Seiferheld W, Brachman D et al (2004) Randomized comparison of stereotactic radiosurgery followed by conventional radiotherapy with carmustine to conventional radiotherapy with carmustine for patients with glioblastoma multiforme: report of Radiation Therapy Oncology Group 93–05 protocol. Int J Radiat Oncol Biol Phys 60:853–860
Fitzek MM, Thornton AF, Rabinov JD et al (1990) Accelerated fractionated proton/photon irradiation to 90 cobalt gray equivalent for glioblastoma multiforme: results of a phase II prospective trial. J Neurosurg 91:251–260
Halperin EC, Burger PC, Bullard DE (1988) The fallacy of the localized supratentorial malignant glioma. Int J Radiat Oncol Biol Phys 15:505–509
Sullivani FJ, Herscher LL, Cook JA et al (1994) National Cancer Institute (phase II) study of high-grade glioma treated with accelerated hyperfractionated radiation and iododeoxyuridine: results in anaplastic astrocytomas. Int J Radiat Oncol Biol Phys 30:583–590
Hideghety K, Sauerwein W, Wittig A et al (2003) Tissue uptake of BSH in patients with glioblastoma in the EORTC 11961 phase I BNCT trial. J Neurooncol 62:145–156
Wittig A, Hideghety K, Paquis P et al (2002) Current clinical results of the EORTC-study 11961. In: Sauerwein W, Moss R, Wittig A (eds) Research and development in neutron capture therapy. Monduzzi Editore, Bologna, pp 1117–1122
Diaz AZ (2003) Assessment of the results from the phase I/II boron neutron capture therapy trials at the Brookhaven National Laboratory from a clinician’s point of view. J Neurooncol 62:101–109
Chanana AD, Capala J, Chadha M et al (1999) Boron neutron capture therapy for glioblastoma multiforme: interim results from the phase I/II dose-escalation studies. Neurosurgery 44:1182–1193
Busse PM, Harling OK, Palmer MR et al (2003) A critical examination of the results from the Harvard-MIT NCT program phase I clinical trial of neutron capture therapy for intracranial disease. J Neurooncol 62:111–121
Palmer MR, Goorley JT, Kiger WS III et al (2002) Treatment planning and dosimetry for the Harvard-MIT phase I clinical trial of cranial neutron capture therapy. Int J Radiat Oncol Biol Phys 53:1361–1379
Joensuu H, Kankaanranta L, Seppälä T et al (2003) Boron neutron capture therapy of brain tumors: clinical trials at the Finnish facility using boronophenylalanine. J Neurooncol 62:123–134
Kankaanranta L, Koivunoro H, Kortesniemi M et al (2008) BPA-based BNCT in the treatment of glioblastoma multiforme: a dose escalation study. In: Zonta A, Altieri S, Roveda L, Barth R (eds) Proceedings of the 13th International Congress on Neutron Capture Therapy “A new option against cancer”. ENEA, Italian National Agency for New Technologies, Energy and the Environment. ISBN: 88-8286-167-8, Florenz, pp. 30–32
Henriksson R, Capala J, Michanek A et al (2008) Boron neutron capture therapy (BNCT) for glioblastoma multiforme: a phase II study evaluating a prolonged high-dose of boronophenylalanine (BPA). Radiother Oncol 88:183–191
Burian J, Marek M, Rataj J et al (2002) Report on the first patient group of the phase I BNCT trial at the LVR-15 reactor. In: Sauerwein W, Moss R, Wittig A (eds) Research and development in neutron capture therapy. Monduzzi Editore, Bologna, pp 1107–1112
Kawabata S, Miyatake S, Kuroiwa T et al (2008) Boron neutron capture therapy for newly diagnosed glioblastoma. J Radiat Res (Tokyo) 50:51–60
Yamamoto T, Nakai K, Kageji T et al (2009) Boron neutron capture therapy for newly diagnosed glioblastoma. Radiother Oncol 91:80–84
Ono K, Masunaga SI, Suzuki M et al (1999) The combined effect of boronophenylalanine and borocaptate in boron neutron capture therapy for SCCVII tumors in mice. Int J Radiat Oncol Biol Phys 43:431–436
Yoshida F, Matsumura A, Shibata Y et al (2002) Cell cycle dependence of boron uptake from two boron compounds used for clinical neutron capture therapy. Cancer Lett 87:135–141
Soloway AH, Hatanaka H, Davis MA (1967) Penetration of brain and brain tumor. VII. Tumor-binding sulfhydryl boron compounds. J Med Chem 10:714–747
Coderre JA, Turcotte JC, Riley KJ et al (2003) Boron neutron capture therapy: cellular targeting of high linear energy transfer radiation. Technol Cancer Res Treat 2:1–21
Joel DD, Coderre JA, Micca PL, Nawrocky MM (1999) Effect of dose and infusion time on the delivery of p-boronophenylalanine for neutron capture therapy. J Neurooncol 41:213–221
Smith D, Chandra S, Barth R et al (2001) Quantitative imaging and microlocalization of boron-10 in brain tumors and infiltrating tumor cells by SIMS ion microscopy: relevance to neutron capture therapy. Cancer Res 61:8179–8187
Morris GM, Coderre JA, Hopewell JW et al (1997) Response of the central nervous system to fractionated boron neutron capture irradiation: studies with borocaptate sodium. Int J Radiat Biol 71:185–192
Coderre JA, Morris GM, Micca PL et al (1995) Comparative assessment of single-dose and fractionated boron neutron capture therapy. Radiat Res 144:310–317
Miyatake S, Kajimoto Y, Kawabata S et al (2005) Modified boron neutron capture therapy for malignant gliomas performed using epithermal neutron and two boron compounds with different accumulation mechanisms: an efficacy study based on findings on neuroimages. J Neurosurg 103:1000–1009
Barth RF, Grecula JC, Yang W et al (2004) Combination of boron neutron capture therapy and external beam radiotherapy for brain tumors. Int J Radiat Oncol Biol Phys 58:267–277
Sweet WH, Soloway AH, Brownell GL (1963) Boron-slow neutron capture therapy of gliomas. Acta Radiol 1:114–121
Yamamoto T, Matsumura A, Yamamoto K et al (2002) In-phantom two-dimensional thermal neutron distribution for intraoperative boron neutron capture therapy of brain tumours. Phys Med Biol 47:2387–2396
Imahori Y, Ueda S, Ohmori Y et al (1998) Positron emission tomography-based boron neutron capture therapy using boronophenylalanine for high-grade gliomas: part II. Clin Cancer Res 4:1833–1841
Nariai T, Ishiwata K, Kimura Y et al (2008) PET pharmacokinetic analysis to estimate boron concentration in tumor and brain as a guide to plan BNCT for malignant cerebral glioma. In: Zonta A, Altieri S, Roveda L, Barth R (eds) Proceedings of the 13th international congress of neutron capture therapy. A new opinion against cancer. ENEA, Roma, pp 244–247
Coderre JA, Hopewell JW, Turcottea JC et al (2004) Tolerance of normal human brain to boron neutron capture therapy. Appl Radiat Isot 61:1083–1087
Vos MJ, Turowski B, Zanella FE et al (2005) Radiologic findings in patients treated with boron neutron capture therapy for glioblastoma multiforme within EORTC trial 11961. Int J Radiat Oncol Biol Phys 61:392–399
Honová H, Safanda M, Petruzelka L et al (2004) Neutron capture therapy in the treatment of glioblastoma multiforme. Initial experience in the Czech Republic. Cas Lec Cesk 143:44–47
Capala J, Stenstam BH, Sköld K et al (2003) Boron neutron capture therapy for glioblastoma multiforme: clinical studies in Sweden. J Neurooncol 62:135–144
Shrieve DC, Eben A, Black PM et al (1999) Treatment of patients with primary glioblastoma multiforme with standard postoperative radiotherapy and radiosurgical boost: prognostic factors and long-term outcome. J Neurosurg 90:72–77
Gannett D, Stea B, Lulu B et al (1995) Stereotactic radiosurgery as an adjunct to surgery and external beam radiotherapy in the treatment of patients with malignant gliomas. Int J Radiat Oncol Biol Phys 33:461–468
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Yamamoto, T., Matsumura, A. (2012). External Beam BNCT for Glioblastoma Multiforme. In: Sauerwein, W., Wittig, A., Moss, R., Nakagawa, Y. (eds) Neutron Capture Therapy. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-31334-9_20
Download citation
DOI: https://doi.org/10.1007/978-3-642-31334-9_20
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-31333-2
Online ISBN: 978-3-642-31334-9
eBook Packages: MedicineMedicine (R0)