Boron neutron capture therapy for glioblastoma multiforme using p-boronophenylalanine and epithermal neutrons: Trial design and early clinical results

@article{Coderre2004BoronNC,
  title={Boron neutron capture therapy for glioblastoma multiforme using p-boronophenylalanine and epithermal neutrons: Trial design and early clinical results},
  author={J. Coderre and E. Elowitz and M. Chadha and R. Bergland and J. Capala and D. Joel and Hungyuan B. Liu and D. Slatkin and A. Chanana},
  journal={Journal of Neuro-Oncology},
  year={2004},
  volume={33},
  pages={141-152}
}
A Phase I/II clinical trial of boron neutroncapture therapy (BNCT) for glioblastoma multiforme is underwayusing the amino acid analog p-boronophenylalanine (BPA) andthe epithermal neutron beam at the Brookhaven MedicalResearch Reactor. Biodistribution studies were carried out in18 patients at the time of craniotomy usingan i.v. infusion of BPA, solubilized as afructose complex (BPA-F). There were no toxic effectsrelated to the BPA-F administration at doses of130, 170, 210, or 250 mg BPA/kg… Expand
Effect of Dose and Infusion Time on the Delivery of p-boronophenylalanine for Neutron Capture Therapy
TLDR
Effect of total dose, infusion time, and route of administration of BPA on tumor and blood boron concentrations were studied in rats bearing the 9L gliosarcoma and the effects on the therapeutic gain potentially achievable with BNCT are discussed. Expand
Boron concentrations in brain during boron neutron capture therapy: in vivo measurements from the phase I trial EORTC 11961 using a gamma-ray telescope.
TLDR
Gamma-ray telescope measurements seem to be a promising method to provide information on the biodistribution of boron during therapy, and opens the possibility of in vivo dosimetry. Expand
Treatment planning and dosimetry for the Harvard-MIT Phase I clinical trial of cranial neutron capture therapy.
TLDR
It is demonstrated that BPA-f-mediated NCT can be precisely planned and delivered in a carefully controlled manner and will be initiated with a new high-intensity, high-quality epithermal neutron beam. Expand
Uptake of two 10B‐compounds in liver metastases of colorectal adenocarcinoma for extracorporeal irradiation with boron neutron capture therapy (EORTC Trial 11001)
TLDR
In conclusion, BSH is not suitable as 10B‐carrier in liver metastases as the10B‐concentration in liver was higher compared to metastasis, and BPA accumulates in hepatic metastases to an extent that allows for extracorporeal irradiation of the liver with BNCT. Expand
Boron Neutron Capture Therapy of Brain Tumors
TLDR
Clinical interest in BNCT has focused primarily on the treatment of high-grade gliomas, and either cutaneous primaries or cerebral metastases of melanoma, and two boron drugs have been used clinically, sodium borocaptate (BSH) (Na2B12H11SH), and a dihydroxyboryl derivative of phenylalanine, referred to as BoronophenylAlanine (BPA). Expand
Tissue uptake of BSH in patients with glioblastoma in the EORTC 11961 phase I BNCT trial
SummaryPurpose: The uptake of the boron compound Na2B12H10-SH (BSH) in tumor and normal tissues was investigated in the frame of the EORTC phase I trial ‘Postoperative treatment of glioblastoma withExpand
Tissue Uptake of BSH in Patients with Glioblastoma in the EORTC 11961 Phase I BNCT Trial
TLDR
The study underlines the importance of a further investigation of BSH uptake in order to obtain enough data for significant statistical analysis, and concludes that the boron concentration in blood seems to be a quite reliable parameter to predict the boregon concentration in other tissues. Expand
Long-Term Infusions of p-Boronophenylalanine for Boron Neutron Capture Therapy: Evaluation Using Rat Brain Tumor and Spinal Cord Models
TLDR
The long-term survival was approximately 50% and was not significantly different between the 2-h and the 6-h infusion groups, which underline the need for clinical biodistribution studies to be carried out to establish 10B partition ratios as a key component in the evaluation of modified administration protocols involving BPA. Expand
Clinical review of the japanese experience with boron neutron capture therapy and a proposed strategy using epithermal neutron beams
TLDR
The relationship between the radiation dose, histological tumor grade, and clinical outcome was examined, and the outcomes for 10 patients who were treated by the new protocol using a new mode composed of thermal and epithermal neutrons are reported. Expand
Boron Neutron Capture Therapy
Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when boron-10, is irradiated with low energy-thermal neutrons to yield high linear energy transfer alpha particlesExpand
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References

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Boron neutron capture therapy of malignant melanoma using 10B-paraboronophenylalanine with special reference to evaluation of radiation dose and damage to the normal skin.
TLDR
A treatment regimen for boron neutron capture therapy of malignant melanomas is described using 10B-paraboronophenylalanine as the tumor-targeting compound and the results indicate that application of the logical approach will be useful for subsequent cases and further development of this therapy. Expand
A history of boron neutron capture therapy of brain tumours. Postulation of a brain radiation dose tolerance limit.
  • D. Slatkin
  • Materials Science, Medicine
  • Brain : a journal of neurology
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TLDR
A new dosimetric analysis of the 1959-1961 clinical trials of BNCT at Brookhaven National Laboratory yields an acute radiation dose tolerance limit estimate of approximately 10 Gy-Eq to the capillary endothelium of human basal ganglia from BnCT. Expand
Control of intracerebral gliosarcomas in rats by boron neutron capture therapy with p-boronophenylalanine.
Boron neutron capture therapy (BNCT) of transplanted intracerebral GS-9L rat gliosarcomas was effected by irradiation at a nuclear reactor, primarily with thermal neutrons, after two intragastricExpand
Boron neutron capture therapy for cancer. Realities and prospects
TLDR
The development of tumor‐localizing boron compounds was discussed, including the sulfhydryl‐containing polyhedral borane, sodium borocaptate, and borono‐phenylalanine, which are currently being used clinically in Japan as capture agents for malignant brain tumors and melanomas, respectively. Expand
Brain Tolerance in Dogs to Boron Neutron Capture Therapy with Borocaptate Sodium (BSH) or Boronophenylalanine (BPA)
Research programs investigating the potential use of BNCT for brain tumors have been initiated in Europe and in the U.S. using epithermal neutron beams and either borocaptate sodium (BSH) orExpand
Neutron capture therapy of the 9L rat gliosarcoma using the p-boronophenylalanine-fructose complex.
TLDR
The high percentage of long-term tumor control in the intracerebral rat 9L gliosarcoma brain tumor model, together with little or no damage to the surrounding normal brain in the majority of surviving animals, demonstrate the substantial therapeutic gain produced by boron neutron capture therapy. Expand
Derivations of relative biological effectiveness for the high-let radiations produced during boron neutron capture irradiations of the 9L rat gliosarcoma in vitro and in vivo.
TLDR
The apparent RBEs calculated for the 10B(n,alpha)7Li reaction were compound-dependent and consistent with differences in the distribution of 10B relative to glioma cell nuclei, similar to other boron neutron capture therapy studies. Expand
Teatment planning figures of merit in thermal and epithermal boron neutron capture therapy of brain tumours.
The boron neutron capture therapy (BNCT) figures of merit of advantage depth, therapeutic depth, modified advantage depth and maximum therapeutic depth have been studied as functions of 10B tumour toExpand
The therapeutic ratio in BNCT: Assessment using the Rat 9L gliosarcoma brain tumor and spinal cord models
During any radiation therapy, the therapeutic tumor dose is limited by the tolerance of the surrounding normal tissue within the treatment volume. The short ranges of the products of the {supExpand
Boron neutron capture therapy: a mechanism for achieving a concomitant tumor boost in fast neutron radiotherapy.
TLDR
BNCT may provide a means of enhancing the therapeutic effectiveness of fast neutron radiotherapy in a wide variety of clinical situations and is an area of research that should be aggressively pursued. Expand
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