An investigation of boron neutron capture therapy for recurrent glioblastoma multiforme

Pellettieri, Luigi; H-Stenstam, B.; Rezaei, Arash; Giusti, Valerio; Sköld, K.

doi:10.1111/j.1600-0404.2007.00924.x

Cited by 35 publications

(22 citation statements)

References 15 publications

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“…The low radiation doses used in recent BNCT treatments of recurrent GBM at Studsvik [11] were not associated with any treatment-related side effects. There was also no clear evidence of radiation damage detected in the postmortem examination of seven patients offered BNCT as primary radiotherapy [12].…”

Section: General Considerationsmentioning

confidence: 90%

Boron neutron capture therapy for newly diagnosed glioblastoma multiforme: an assessment of clinical potential

Sköld¹,

Gorlia²,

Pellettieri³

et al. 2010

BJR

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ABSTRACT. The purpose of this study was to assess the potential of boron neutron capture therapy (BNCT), with a 6-h infusion of the boron carrier L-boronophenylalanine as a fructose preparation (BPA-f), as first-line radiotherapy for newly diagnosed glioblastoma multiforme (GBM). Patient survival data from a Phase II study using BNCT were compared with retrospective data from the two arms of a Phase III study using conventional radiotherapy (RT) in the reference arm and using RT plus concomitant and adjuvant medication with temozolomide (TMZ) in the experimental arm, and were also compared with small subgroups of these patients for whom the methylation status of the MGMT (O 6 -methylguanine-DNA methyltransferase) DNA repair gene was known. Differences in the baseline characteristics, salvage therapy after recurrence and levels of severe adverse events were also considered. The results indicate that BNCT offers a treatment that is at least as effective as conventional RT alone. For patients with an unmethylated MGMT DNA repair gene, a possible clinical advantage of BNCT over RT/ TMZ was suggested. BNCT is a single-day treatment, which is of convenience to patients, with mild side effects, which would offer an initial 6 weeks of good-quality life during the time when patients would otherwise be undergoing daily treatments with RT and TMZ. It is suggested that the use of BNCT with a 6-h infusion of BPA-f should be explored in a stratified randomised Phase II trial in which patients with the unmethylated MGMT DNA repair gene are offered BNCT in the experimental arm and RT plus TMZ in the reference arm. Boron neutron capture therapy (BNCT) is an experimental radiotherapy that, to date, has mostly been applied to treating patients with newly diagnosed glioblastoma multiforme (GBM). Several hundred GBM patients have been treated in Phase I and Phase II studies in Europe, the USA and Japan, and survival times similar to those obtained with standard radiotherapy (RT) have been reported from several of these studies [1]. No randomised trial in which BNCT is compared with standard therapies has yet been undertaken.Proper assessment of the results from these Phase II trials has been hampered by the lack of information on baseline characteristics of the patient populations, both in reports of the BNCT studies and in reports on other therapies, notably standard fractionated photon therapy (RT), to which the results from BNCT should ultimately be compared. The recursive partitioning analysis (RPA) of prognostic factors by Curran et al [2] established a method to characterise patient status prior to treatment, useful both for the planning of clinical studies and for the assessment of the significance of the results from clinical studies. The reliability and usefulness of the RPA method has been verified by Mirimanoff et al [3] by applying it to data obtained from a randomised Phase III study [4], in which RT with concomitant and adjuvant temozolomide (RT/TMZ) was offered to 287 patients with newly diagnosed GBM in the experimen...

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Section: General Considerationsmentioning

confidence: 90%

Boron neutron capture therapy for newly diagnosed glioblastoma multiforme: an assessment of clinical potential

Sköld¹,

Gorlia²,

Pellettieri³

et al. 2010

BJR

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“…The biodistribution of BPA in GBM, melanoma, and head and neck cancer patients achieved T/B ratios ranging from 1.1 to 3.6 [12][13][14][15], T/N ratios of 1.1-2.9 [12,15,36], and tumor boron levels in the range of 1.8-34.8 ppm [12,13,15,17,36]. This data illustrates that more selective and targeted agents are urgently needed.…”

Section: Boronophenylalaninementioning

confidence: 76%

“…To put the severity of these diagnoses into perspective, consider the 2-and 5-year survival rates of newly diagnosed GBM are 10 and 1%, respectively [37]. High grade glioma patients enrolled in BNCT clinical trials have affirmed that BNCT is tolerated well, has comparable (or fewer) side effects than conventional radiation therapy, typically requires only 1-2 treatment sessions, and the median survival times are comparable to standard of care (radiation and temozolomide treatment) [15,38]. Clinical findings such as this encourage further investigation of Tumor Pre-treated with 10 BNCT as a therapeutic option.…”

Section: Introductionmentioning

confidence: 98%

“…Despite the potential of BNCT becoming an alternative (or adjunct) treatment modality for glioblastoma multiforme (GBM) [12][13][14][15][16][17][18][19][20][21][22][23], melanoma brain metastases [12,24], adenocarcinoma liver metastases [25][26][27][28][29][30], hepatocellular carcinoma [31] and recurrent head and neck cancer patients [32][33][34][35][36], only two drugs have been investigated in these BNCT clinical trials: L-boronophenylalanine (BPA) and sodium borocaptate (BSH) [10]. The vast majority of patients diagnosed with the aforementioned malignancies undergo palliative care options.…”

Section: Introductionmentioning

confidence: 99%

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Advancements in Tumor Targeting Strategies for Boron Neutron Capture Therapy

2015

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Boron neutron capture therapy (BNCT) is a promising cancer therapy modality that utilizes the nuclear capture reaction of epithermal neutrons by boron-10 resulting in a localized nuclear fission reaction and subsequent cell death. Since cellular destruction is limited to approximately the diameter of a single cell, primarily only cells in the neutron field with significant boron accumulation will be damaged. However, the emergence of BNCT as a prominent therapy has in large part been hindered by a paucity of tumor selective boron containing agents. While L-boronophenylalanine and sodium borocaptate are the most commonly investigated clinical agents, new agents are desperately needed due to their suboptimal tumor selectivity. This review will highlight the various strategies to improve tumor boron delivery including: nucleoside and carbohydrate analogs, unnatural amino acids, porphyrins, antibody-dendrimer conjugates, cationic polymers, cell-membrane penetrating peptides, liposomes and nanoparticles.

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“…In that trial the MST was 10.4-13.2 months for newly diagnosed GBM patients. In a Swedish clinical trial 29 newly diagnosed GBM patients received an infusion of 900 mg/kg BPA in the course of 6 hours (22)(23)(24)(25). The MST was 17.7 months compared to 15.5 months in patients who received standard therapy comprised of surgery followed by RT and TMZ.…”

Section: Discussionmentioning

confidence: 99%

Boron neutron capture therapy (BNCT) for newly-diagnosed glioblastoma: Comparison of clinical results obtained with BNCT and conventional treatment

et al. 2014

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: The purpose of this study was to evaluate the clinical outcome of boron neutron capture therapy (BNCT) and conventional treatment in patients with newly diagnosed glioblastoma. Since 1998 we treated 23 newly-diagosed GBM patients with BNCT without any additional chemotherapy. Their median survival time was 19.5 months ; the 2-, 3-, and 5-year survival rates were 31.8% %, 22.7% %, and 9.1% %, respectively. The clinical results of BNCT in patients with GBM are similar to those of recent conventional treatments based on radiotherapy with concomitant and adjuvant temozolomide.

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An investigation of boron neutron capture therapy for recurrent glioblastoma multiforme

Cited by 35 publications

References 15 publications

Boron neutron capture therapy for newly diagnosed glioblastoma multiforme: an assessment of clinical potential

Boron neutron capture therapy for newly diagnosed glioblastoma multiforme: an assessment of clinical potential

Advancements in Tumor Targeting Strategies for Boron Neutron Capture Therapy

Boron neutron capture therapy (BNCT) for newly-diagnosed glioblastoma: Comparison of clinical results obtained with BNCT and conventional treatment

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