First BNCT treatment of a skin melanoma in Argentina: dosimetric analysis and clinical outcome

González, Sara Josefina; Bonomi, Marcelo; Cruz, Gustavo A. Santa; Blaumann, Herman; Larrieu, O. A. Calzetta; Menéndez, Pablo Federico Bonvicini; Rebagliati, Raúl Jiménez; Longhino, Juan; Feld, D.; Dagrosa, María Alejandra; Argerich, Cosme; Castiglia, S.G. de; Batistoni, Daniel A.; Liberman, S.; Roth, Berta

doi:10.1016/j.apradiso.2004.05.060

Cited by 135 publications

(83 citation statements)

References 4 publications

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“…As demonstrated radiographically, a second patient with a brain metastasis had a partial response. Several other patients with either cutaneous or metastatic melanoma to the brain have been treated at other institutions, including the first in Argentina (184), and the consensus seems to be that these tumors are more responsive to BNCT than glioblastoma multiforme. This is supported by experimental studies carried out by two of us (R.F.B.…”

Section: Clinical Studies Of Boron Neutron Capture Therapy For Othertmentioning

confidence: 99%

Boron Neutron Capture Therapy of Cancer: Current Status and Future Prospects

Barth

Coderre²,

Vicente³

et al. 2005

Clinical Cancer Research

924

666

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Background: 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 A particles and recoiling lithium-7 nuclei. Clinical interest in BNCT has focused primarily on the treatment of high-grade gliomas and either cutaneous primaries or cerebral metastases of melanoma, most recently, head and neck and liver cancer. Neutron sources for BNCT currently are limited to nuclear reactors and these are available in the United States, Japan, several European countries, and Argentina. Accelerators also can be used to produce epithermal neutrons and these are being developed in several countries, but none are currently being used for BNCT. Boron Delivery Agents: Two boron drugs have been used clinically, sodium borocaptate (Na 2 B 12 H 11 SH) and a dihydroxyboryl derivative of phenylalanine called boronophenylalanine. The major challenge in the development of boron delivery agents has been the requirement for selective tumor targeting to achieve boron concentrations (f20 Ag/g tumor) sufficient to deliver therapeutic doses of radiation to the tumor with minimal normal tissue toxicity. Over the past 20 years, other classes of boron-containing compounds have been designed and synthesized that include boroncontaining amino acids, biochemical precursors of nucleic acids, DNA-binding molecules, and porphyrin derivatives. High molecular weight delivery agents include monoclonal antibodies and their fragments, which can recognize a tumor-associated epitope, such as epidermal growth factor, and liposomes. However, it is unlikely that any single agent will target all or even most of the tumor cells, and most likely, combinations of agents will be required and their delivery will have to be optimized. Clinical Trials: Current or recently completed clinical trials have been carried out inJapan, Europe, and the United States. The vast majority of patients have had high-grade gliomas. Treatment has consisted first of ''debulking'' surgery to remove as much of the tumor as possible, followed by BNCTat varying times after surgery. Sodium borocaptate and boronophenylalanine administered i.v have been used as the boron delivery agents. The best survival data from these studies are at least comparable with those obtained by current standard therapy for glioblastoma multiforme, and the safety of the procedure has been established. Conclusions: Critical issues that must be addressed include the need for more selective and effective boron delivery agents, the development of methods to provide semiquantitative estimates of tumor boron content before treatment, improvements in clinical implementation of BNCT, and a need for randomized clinical trials with an unequivocal demonstration of therapeutic efficacy. If these issues are adequately addressed, then BNCTcould move forward as a treatment modality.

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Section: Clinical Studies Of Boron Neutron Capture Therapy For Othertmentioning

confidence: 99%

Boron Neutron Capture Therapy of Cancer: Current Status and Future Prospects

Barth

Coderre²,

Vicente³

et al. 2005

Clinical Cancer Research

924

666

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“…In this framework, a small photo-converter prototype "Phones Bianco" has been designed and manufactured to obtain a mixed thermal and epithermal neutron field. In the following, we will refer to such a field with the name "hyperthermal" as used in (Gonzalez et al, 2004). Several measurements have been carried out in different hospitals and the hyperthermal neutron field has been characterized with bubble neutron detectors, Gd2O3 gadolinium imaging plates (Bevilaqua et al, 2007) and microstrip silicon detectors (Mattera et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Design and simulation of an optimized e-linac based neutron source for BNCT research

Durisi

Alikaniotis

Borla

et al. 2015

Applied Radiation and Isotopes

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The paper is focused on the study of a novel photo-neutron source for BNCT preclinical research based on medical electron Linacs. Previous studies by the authors already demonstrated the possibility to obtain a mixed thermal and epithermal neutron flux of the order of 10 7 cm -2 s -1 . This paper investigates possible Linac's modifications and a new photo-converter design to rise the neutron flux above 5 10 7 cm -2 s -1 , also reducing the gamma contamination.

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“…In addition, because BNCT involves biochemical rather than geometric targeting, it is ideally suited to treat infiltrating tumor cells, undetectable micrometastases (2), and the foci of malignant transformation in field-cancerized tissue (3). Clinical trials of BNCT for the treatment of glioblastoma multiforme and/or melanoma and, more recently, head and neck tumors and liver metastases, using boronophenylalanine (BPA) or sodium mercaptoundecahydrododecaborane as the 10 B carriers, have been performed or are under way in Argentina, Europe, Japan, Taiwan, and the United States (4)(5)(6)(7)(8). These treatments have been marginally more effective than external-beam radiation therapy (9)(10)(11).…”

mentioning

confidence: 99%

Therapeutic efficacy of boron neutron capture therapy mediated by boron-rich liposomes for oral cancer in the hamster cheek pouch model

Heber

Hawthorne

Kueffer

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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The application of boron neutron capture therapy (BNCT) mediated by liposomes containing 10 B-enriched polyhedral borane and carborane derivatives for the treatment of head and neck cancer in the hamster cheek pouch oral cancer model is presented. These liposomes are composed of an equimolar ratio of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine, incorporating K[nido-7-CH 3 (CH 2 ) 15 -7,8-C 2 B 9 H 11 ] (MAC) in the bilayer membrane while encapsulating the hydrophilic species Na 3 [ae-B 20 H 17 NH 3 ] (TAC) in the aqueous core. Unilamellar liposomes with a mean diameter of 83 nm were administered i.v. in hamsters. After 48 h, the boron concentration in tumors was 67 ± 16 ppm whereas the precancerous tissue contained 11 ± 6 ppm, and the tumor/normal pouch tissue boron concentration ratio was 10:1. Neutron irradiation giving a 5-Gy dose to precancerous tissue (corresponding to 21 Gy in tumor) resulted in an overall tumor response (OR) of 70% after a 4-wk posttreatment period. In contrast, the beam-only protocol gave an OR rate of only 28%. Once-repeated BNCT treatment with readministration of liposomes at an interval of 4, 6, or 8 wk resulted in OR rates of 70-88%, of which the complete response ranged from 37% to 52%. Because of the good therapeutic outcome, it was possible to extend the follow-up of BNCT treatment groups to 16 wk after the first treatment. No radiotoxicity to normal tissue was observed. A salient advantage of these liposomes was that only mild mucositis was observed in dose-limiting precancerous tissue with a sustained tumor response of 70-88%.oncology | cancer | boronated liposomes | BNCT | neutron radiation

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First BNCT treatment of a skin melanoma in Argentina: dosimetric analysis and clinical outcome

Cited by 135 publications

References 4 publications

Boron Neutron Capture Therapy of Cancer: Current Status and Future Prospects

Boron Neutron Capture Therapy of Cancer: Current Status and Future Prospects

Design and simulation of an optimized e-linac based neutron source for BNCT research

Therapeutic efficacy of boron neutron capture therapy mediated by boron-rich liposomes for oral cancer in the hamster cheek pouch model

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