21 augustus 2013: In feite is Boron Neutron Capture Therapy vergelijkbaar met CIRT - Carbon Ion Radiotherapy. Zie gerelateerde artikelen of zoek via CIRT in zoekmachine rechts bovenaan dit artikel.
Onderaan heb ik abstract van deze studie: Current status of boron neutron capture therapy of high grade gliomas and recurrent head and neck cancer welke volledig gratis is in te zien toegevoegd. Onderaan artikel ook plaatjes van statistieken enz. toegevoegd.
9 april 2013: Een abstract van een reviewstudie van Boron Neutron Capture Therapy bij glioblastomen toegevoegd. Deze reviewstudie is in 2008 gepubliceerd.
26 januari 2005: Bron: J Neurooncol. 1997 May;33(1-2):105-15.
De techniek van BCNT = Boron neutron capture therapy - behandelen van hersentumoren met neutronen en borium wordt steeds beter sinds studies vanaf eind jaren '90. Deze onderstaande studie geeft wel een goed beeld van de effecten van BNCT bij verschillende vormen van hersentumoren, uitgevoerd in japan over een periode van 30 jaar.
Boron neutron capture therapy. Clinical brain tumor studies. Nakagawa Y, Hatanaka H. Department of Neurosurgery, National Kagawa Children's Hospital, Japan.
Since 1968, we have treated 149 patients and performed boron-neutron capture therapy (BNCT) on 164 occasions using 5 reactors in Japan. There were 64 patients with glioblastoma, 39 patients with anaplastic astrocytoma and 17 patients with low grade astrocytoma (grade 1 or 2). There were 30 patients with other types of tumor. The overall response rate in the glioma patients was 64%. Seven patients (12%) of glioblastoma, 22 patients (56%) of anaplastic astrocytoma and 8 patients (62%) of low grade astrocytoma lived more than 2 years. Median survival time of glioblastoma was 640 days. Median survival times of patients with anaplastic astrocytoma was 1811 days, and 1669 days in low grade astrocytoma. Six patients (5 glioblastoma and one anaplastic astrocytoma) died within 90 days after BNCT. Six patients (two glioblastoma and four anaplastic astrocytomas) lived more than 10 years. Histological grading, age of the patients, neutron fluence at the target point and target depth or size of the tumor were proved to be important factors. BNCT is an effective treatment for malignant brain tumors. We are now able to radiate the tumor more correctly with a high enough dose of neutron beam, even if we use thermal neutron beam.
PMID: 9151228 [PubMed - indexed for MEDLINE]
Boron neutron capture therapy for glioblastoma.
Department of Neurosurgery, Institute of Clinical Medicine, University of Tsukuba, Tenno-dai 1-1-1, Tsukuba City, Ibaraki 305-8575, Japan. firstname.lastname@example.org
Boron neutron capture therapy (BNCT) theoretically allows the preferential destruction of tumor cells while sparing the normal tissue, even if the cells have microscopically spread to the surrounding normal brain. The tumor cell-selective irradiation used in this method is dependent on the nuclear reaction between the stable isotope of boron ((10)B) and thermal neutrons, which release alpha and (7)Li particles within a limited path length (-9 microm) through the boron neutron capture reaction, (10)B(n,alpha)(7)Li. Recent clinical studies of BNCT have focused on high-grade glioma and cutaneous melanoma; however, cerebral metastasis of melanoma, anaplastic meningioma, head and neck tumor, and lung and liver metastasis have been investigated as potential candidates for BNCT. To date, more than 350 high-grade gliomas have been treated in BNCT facilities worldwide. Current clinical BNCT trials for glioblastoma (GBM) have used the epithermal beam at a medically optimized research reactor, and p-dihydroxyboryl-phenylalanine (BPA) and/or sulfhydryl borane Na(2)B(12)H(11)SH (BSH) as the boron delivery agent(s). The results from these rather small phase I/II trials for GBM appear to be encouraging, but prospective randomized clinical trials will be needed to confirm the efficacy of this theoretically promising modality. Improved tumor-targeting boron compounds and optimized administration methods, improved boron drug delivery systems, development of a hospital-based neutron source, and/or other combination modalities will enhance the therapeutic effectiveness of BNCT in the future.
- [PubMed - indexed for MEDLINE]
Current status of boron neutron capture therapy of high grade gliomas and recurrent head and neck cancer.
Current status of boron neutron capture therapy of high grade gliomas and recurrent head and neck cancer.
Department of Pathology, The Ohio State University, 165 Hamilton Hall, 1645 Neil Avenue, Columbus, OH, 43210, USA. email@example.com
Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Clinical interest in BNCT has focused primarily on the treatment of high grade gliomas, recurrent cancers of the head and neck region and either primary or metastatic melanoma. Neutron sources for BNCT currently have been limited to specially modified nuclear reactors, which are or until the recent Japanese natural disaster, were available in Japan, United States, Finland and several other European countries, Argentina and Taiwan. Accelerators producing epithermal neutron beams also could be used for BNCT and these are being developed in several countries. It is anticipated that the first Japanese accelerator will be available for therapeutic use in 2013. The major hurdle for the design and synthesis of boron delivery agents has been the requirement for selective tumor targeting to achieve boron concentrations in the range of 20 μg/g. This would be sufficient to deliver therapeutic doses of radiation with minimal normal tissue toxicity. Two boron drugs have been used clinically, a dihydroxyboryl derivative of phenylalanine, referred to as boronophenylalanine or "BPA", and sodium borocaptate or "BSH" (Na2B12H11SH). In this report we will provide an overview of other boron delivery agents that currently are under evaluation, neutron sources in use or under development for BNCT, clinical dosimetry, treatment planning, and finally a summary of previous and on-going clinical studies for high grade gliomas and recurrent tumors of the head and neck region. Promising results have been obtained with both groups of patients but these outcomes must be more rigorously evaluated in larger, possibly randomized clinical trials. Finally, we will summarize the critical issues that must be addressed if BNCT is to become a more widely established clinical modality for the treatment of those malignancies for which there currently are no good treatment options.
- [PubMed - indexed for MEDLINE]
Results: 111.Radiographic changes following BNCT in two representative patients with GBM. In both, there was a reduction in both mass and peritumoral edema without the administration of corticosteroids or mannitol within a few days. This is also shown in the FLAIR image of Case #12.Rolf F Barth, et al. Radiat Oncol. 2012;7:146-146.2.Graphical representation of a parameterized model converting the maximum weighted dose, calculated Treatment Planning System (TPSs) from each center to an MIT calibrated dose as a function of boron uptake in tissue . The plotted curves afford an easy and direct comparison of dose specification between participants of the International Dosimetry Exchange.Rolf F Barth, et al. Radiat Oncol. 2012;7:146-146.3.A three-field treatment plan for a brain tumor (GBM) patient calculated using the MiMMC treatment planning system. The prescription is a mean brain dose of 7.7 Gyw. Isodose contours calculated for tumor and normal brain are shown on axial and sagittal slices through the target volumes. The integral dose volume histograms (DVHs) summarize dosimetry for structures of interest including target volumes and organs at risk.Rolf F Barth, et al. Radiat Oncol. 2012;7:146-146.4.Kaplan-Meier survival plots of patients with either newly diagnosed or recurrent tumors of the head and neck region, treated by Suzuki et al. with BNCT. A total of 68 patients were treated. One and 2 year OS rates were 43.1% and 24.2% respectively. Thirty-three patients had squamous cell carcinomas (53%), 20 had adenocarcinomas (32%) and 11 (18%) had malignant melanomas.Rolf F Barth, et al. Radiat Oncol. 2012;7:146-146.5.18FDG-PET study prior and 6 months after BNCT of a 56 year-old male patient with recurrent squamous cell carcinoma of the maxilla.A: FDG accumulated in the left orbital region (arrows) and frontal lobe of brain (arrow heads). B: No accumulation of FDG-PET was detected 6 months after BNCT and the patient was disease free for 61 months at the time of the original report. Photographs are from Applied Radiation and Isotopes, 67:S37-S42, 2009.Rolf F Barth, et al. Radiat Oncol. 2012;7:146-146.6.Before BNCT (left) and 22 months after the first BNCT (right) of a patient with a recurrent mucoepidermoid carcinoma of the parotid gland. Three treatments with BNCT produced a remarkable reduction in tumor size, but also resolution of a cutaneous ulcer and re-epithelization by normal skin. These results clearly demonstrate that BNCT is a highly tumor-selective treatment modality. She lived for 7 years following treatment (Applied Radiation and Isotopes, 61:1069–1073, 2004).Rolf F Barth, et al. Radiat Oncol. 2012;7:146-146.7.A. Kaplan-Meier estimates of overall survival for all newly diagnosed glioblastoma (WHO grade 4, n = 21). The median survival time of boron neutron capture therapy (BNCT) group (blue line) is 15.6 months. There is statistical significance between both group Log-rank test (p = 0.0035). B. Kaplan-Meier estimates of overall survival for all newly diagnosed glioblastoma (protocol 1 and 2). External beam X-ray irradiation (XRT) boost after boron neutron capture therapy (BNCT) was carried for the latter 11 cases. This improved the median survival time to 23.5 months (from 14.1 months for BNCT only, protocol 1, dotted line in blue).Rolf F Barth, et al. Radiat Oncol. 2012;7:146-146.8.Contrast-enhanced T1-weighted MRI of representative glioblastoma patient and18 F-labeled BPA-PET image after initial debulking surgery. The patients received 18 F-BPA-PET to assess the distribution of BPA and to estimate the boron concentration in tumors before BNCT without direct determination of boron concentration in the tumor. The lesion to normal brain (L/N) ratio of the enhanced tumor was 7.8 in this case. Note that even the periphery of the main mass, i.e., the infiltrative portion of the tumor, showed BPA uptake. The L/N ratio of BPA uptake can be estimated from this study and dose planning was done according to this L/N ratio, and if the L/N ratio was more than 2.5, then BNCT was initiated. 18 F-BPA-PET accurate BPA provided an accurate estimate of the accumulation and distribution of BPA as previously reported [64,65].Rolf F Barth, et al. Radiat Oncol. 2012;7:146-146.9.18FBPA-PET study prior to and 7 months following the first BNCT treatment.A. A 61 year-old female with residual maxillary adenoid cystic carcinoma (arrows) infiltrating into pterygopalatine fossa (T4N1M0) after maxillectomy, who was treated twice with BNCT using BPA followed by chemotherapy. B. Residual maxillary cancer and a regional lymph node metastasis were no longer evident at 42 months although bilateral multiple pulmonary metastases were detected at 18 months after the first BNCT treatment. The patient lived for 59 months following BNCT (Applied Radiation and Isotopes, 67:S37-S42, 2009).Rolf F Barth, et al. Radiat Oncol. 2012;7:146-146.10.Kaplan-Meier survival plots of patients with recurrent HNC treated by Kato et al. (6) with BNCT (26 cases, red line) and those who treated with other than BNCT (16 cases, blue line). The outcomes for the 26 patients: Mean survival time: 33.6 months, 4-year Overall survival (OS): 37.0%, 6-year OS: 31.7%. Most of the 26 patients had either recurrent or far advanced cancers of the head and neck region and 15 (58%) had regional lymph node metastases and 6 had developed distant metastases. Nineteen of the patients had squamous cell carcinomas, 4 salivary gland carcinomas and 3 had sarcomas. All but one had received standard therapy and developed recurrent tumors for which there were no other treatment options.Rolf F Barth, et al. Radiat Oncol. 2012;7:146-146.11.Schematic diagram of the Massachusetts Institute of Technology Reactor (MITR). The fission converter based epithermal neutron irradiation (FCB) facility is housed in the experimental hall of the MITR and operates in parallel with other user applications. The FCB contains an array of 11 MITR-II fuel elements cooled by forced convection of heavy water coolant. The converter power is 120 kW at 6 MW reactor power. A shielded horizontal beam line contains an aluminum and Teflon® filter-moderator to tailor the neutron energy spectrum into the desired epithermal energy range. A patient collimator defines the beam aperture and extends into the shielded medical room to provide circular apertures ranging from 16 to 8 cm in diameter. The in-air epithermal flux is 6.2 × 109 n/cm2s at the patient position with the 12 cm collimator. The measured specific absorbed doses are constant for all field sizes and are well below the inherent background of 2.8 × 10-12 Gywcm2/n produced by epithermal neutrons in tissue. The dose distributions achieved with the FCB approach the theoretical optimum for BNCT. This facility is useful for clinical studies of superficial cancers and small animal studies.Rolf F Barth, et al. Radiat Oncol. 2012;7:146-146.
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