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Biomedical subjects

W Sauerwein

Publications and source records attributed to W Sauerwein.

At least 37 records · Page 2Linked to original sources
PubMed2001

Endoluminal beta-radiation therapy for the prevention of coronary restenosis after balloon angioplasty. The Dose-Finding Study Group.

BACKGROUND: Beta radiation is effective in reducing vascular neointimal proliferation in animals after injury caused by balloon angioplasty. However, the lowest dose that can prevent restenosis after coronary angioplasty has yet to be determined. METHODS: After successful balloon angioplasty of a previously untreated coronary stenosis, 181 patients were randomly assigned to receive 9, 12, 15, or 18 Gy of radiation delivered by a centered yttrium-90 source. Adjunctive stenting was required in 28 percent of the patients. The primary end point was the minimal luminal diameter six months after treatment, as a function of the delivered dose of radiation. RESULTS: At the time of follow-up coronary angiography, the mean minimal luminal diameter was 1.67 mm in the 9-Gy group, 1.76 mm in the 12-Gy group, 1.83 mm in the 15-Gy group, and 1.97 mm in the 18-Gy group (P=0.06 for the comparison of 9 Gy with 18 Gy), resulting in restenosis rates of 29 percent, 21 percent, 16 percent, and 15 percent, respectively (P=0.14 for the comparison of 9 Gy with 18 Gy). At that time, 86 percent of the patients had had no serious cardiac events. In 130 patients treated with balloon angioplasty alone, restenosis rates were 28 percent, 17 percent, 16 percent, and 4 percent, respectively (P=0.02 for the comparison of 9 Gy with 18 Gy). Among these patients, there was a dose-dependent enlargement of the lumen in 28 percent, 50 percent, 45 percent, and 74 percent of patients, respectively (P<0.001 for the comparison of 9 Gy with 18 Gy). The rate of repeated revascularization was 18 percent with 9 Gy and 6 percent with 18 Gy (P=0.26). CONCLUSIONS: Intracoronary beta radiation therapy produces a significant dose-dependent decrease in the rate of restenosis after angioplasty. An 18-Gy dose not only prevents the renarrowing of the lumen typically observed after successful balloon angioplasty, but actually induces luminal enlargement.

Aged↗
PubMed2001

Comparison of quality assurance for performance and safety characteristics of the facility for Boron Neutron Capture therapy in Petten/NL with medical electron accelerators.

BACKGROUND AND PURPOSE: The European Council Directive on health protection 97/43/EURATOM requires radiotherapy quality assurance programmes for performance and safety characteristics including acceptance and repeated tests. For Boron Neutron Capture therapy (BNCT) at the High Flux Reactor (HFR) in Petten/NL such a programme has been developed on the basis of IEC publications for medical electron accelerators. RESULTS: The fundamental differences of clinical dosimetry for medical electron accelerators and BNCT are presented and the order of magnitude of dose components and their stability and that of the main other influencing parameter 10B concentration for BNCT patient treatments. A comparison is given for requirements for accelerators and BNCT units indicating items which are not transferable, equal or additional. Preliminary results of in vivo measurements done with a set of 55Mn, 63Cu and 197Au activation foils for all single fields for the four fractions at all 15 treated patients show with < +/- 4% up to now a worse reproducibility than the used dose monitoring systems (+/- 1.5%) caused by influence of hair position on the foil-skull distance. CONCLUSIONS: Despite the more complex clinical dosimetry (because of four relevant dose components, partly of different linear energy transfer (LET)) BNCT can be regulated following the principles of quality assurance procedures for therapy with medical electron accelerators. The reproducibility of applied neutron fluence (proportional to absorbed doses) and the main safety aspects are equal for all teletherapy methods including BNCT.

Acceleration↗
PubMed2001

Transplantation of CD34-enriched peripheral stem cells from an HLA-haplotype mismatched donor to a patient with severe aplastic anemia.

A 14-year-old girl developed very severe aplastic anemia unresponsive to steroids, cyclosporine, ATG and filgrastim. She experienced repeated bacterial infections, hypermenorrhagia and epistaxis and received numerous transfusions. Lacking a matched family or unrelated donor, she was transplanted 6 months after diagnosis with CD34+ cell-enriched peripheral stem cells from her HLA-haploidentical uncle. Conditioning included fludarabine, cyclophosphamide, 800 cGy TLI and OKT3. Prompt and sustained trilineage engraftment occurred. Acute GVHD grade 1 and herpes esophagitis were successfully treated. Eight months after grafting she was well with stable hematopoiesis. She then succumbed to fulminant hepatic failure due to adenovirus infection.

Adenoviridae Infections↗
PubMed2001

Optimal detection of the neutron capture therapy agent borocaptate sodium (BSH): a comparison between 1H and 10B NMR.

Boron Neutron Capture Therapy (BNCT), an experimental binary cancer treatment modality, requires selective targeting of 10B containing compounds to tumors. One of the compounds under evaluation in an EORTC phase I trial, and used in Japan for patient treatments for many years, is borocaptate sodium (BSH, also known as sulfhydril boron hydride). To optimize the clinical applications, a noninvasive method is needed to monitor the distribution of the boron compound, and NMR may offer such a possibility. A comparison between the relative sensitivities for detecting BSH by 10B or 1H NMR was conducted at two magnetic field strengths: 2 and 4.7 T. At each field strength, similar-sized radio frequency (rf) coils were used for both nuclei. Theoretical predictions for the intrinsic signal to noise (S/N) advantage of 1H over 10B detection vary between a factor of 5.4 and a factor of 28.9, depending on whether the effective resistance is dominated by coil losses or sample losses. Our tests, conducted on relatively small aqueous samples, which loaded the coils less than expected for animal or human subjects, resulted nevertheless in advantage factors close to the lower limit of this range. The measured S/N detection advantage factors for 1H were about 5.2 at 4.7 T, using a dedicated 1H coil, and 7.7 at 2 T, where the measurements were conducted with a double-tuned coil. However, when predicting the expected performance for in vivo MRS or MRI, one should bear in mind that proton detection has to be conducted by spectral-editing pulse sequences with an inherent S/N loss by at least a factor of 2, and that the T1 relaxation time for 10B in BSH is about 30 times shorter than the 1HT1 value. In view of these considerations, direct 10B detection could well be the preferred strategy for MRI/MRS of BSH in vivo.

Biophysical Phenomena↗
PubMed1999

Organisation and management of the first clinical trial of BNCT in Europe (EORTC protocol 11961).EORTC BNCT study group.

Boron Neutron Capture Therapy is based on the ability of the isotope 10B to capture thermal neutrons and to disintegrate instantaneously producing high LET particles. The only neutron beam available in Europe for such a treatment is based at the European High Flux Reactor HFR at Petten (The Netherlands). The European Commission, owners of the reactor, decided that the potential benefit of the facility should be opened to all European citizens and therefore insisted on a multinational approach to perform the first clinical trial in Europe on BNCT. This precondition had to be respected as well as the national laws and regulations. Together with the Dutch authorities actions were undertaken to overcome the obvious legal problems. Furthermore, the clinical trial at Petten takes place in a nuclear research reactor, which apart from being conducted in a non-hospital environment, is per se known to be dangerous. It was therefore of the utmost importance that special attention is given to safety, beyond normal rules, and to the training of staff. In itself, the trial is an unusual Phase I study, introducing a new drug with a new irradiation modality, with really an unknown dose-effect relationship. This trial must follow optimal procedures, which underscore the quality and qualified manner of performance.

Boron Neutron Capture Therapy↗
PubMed1999

Postoperative treatment of glioblastoma with BNCT at the petten irradiation facility (EORTC protocol 11,961).

The boron neutron capture therapy is based on the reaction occurring between the isotope 10B and thermal neutrons. A low energy neutron is captured by the nucleus and it disintegrates into two densely ionising particles, Li nucleus and He nucleus (alpha particle), with high biological effectiveness. On the basis of comprehensive preclinical investigations in the frame of the European Collaboration with Na2B12H11SH (BSH), as boron delivery agent, the first European phase I, clinical trial was designed at the only available epithermal beam in Europe, at the High Flux Reactor, Petten, in the Netherlands. The goal of this study is to establish the safe BNCT dose for cranial tumors under defined conditions. BNCT is applied as postoperative radiotherapy in 4 fractions, after removal of the tumor for a group of patients suffering from glioblastoma, who would have no benefit from conventional treatment, but have sufficient life expectancy to detect late radiation morbidity due to BNCT. The starting dose is set at 80% of the dose where neurological effects occurred in preclinical large animal experiments following a single fraction. The radiation dose will be escalated, by constant boron concentration in blood, in 4 steps for cohorts of ten patients, after an observation period of at least 6 months after the end of BNCT of the last patient of a cohort. The adverse events on healthy tissues due to BSH and due to the radiotherapy will be analysed in order to establish the maximal tolerated dose and dose limiting toxicity. Besides of the primary aim of this study the survival will be recorded. The first patient was treated in October 1997, and further four patients have been irradiated to-date. The protocol design proved to be well applicable, establishing the basis for scientific evaluation, for performance of safe patient treatment in a very complex situation and for opening the possibility to perform further clinical research work on BNCT.

Brain Neoplasms↗
PubMed1998

Boron neutron capture therapy: principles and potential.

This book on the therapeutic applications of neutrons and high-LET radiations in cancer therapy would not have been complete without a review of the present situation of boron neutron capture therapy (BNCT) and a discussion of its future perspectives. BNCT is a special type of high-LET radiation therapy that attempts to achieve a selectivity at the cellular level. The rationale is to incorporate boron atoms selectively in the cancer cells and then bombard those atoms with thermal neutrons to produce a neutron capture reaction and subsequent decay that emits alpha and lithium particles. The efficiency of the technique depends upon achieving selective incorporation of the boron atoms in the cancer cells and not (or to a lesser extent) in the normal cells. The present status and future directions are described, with emphasis on boron carriers (drugs) and their delivery, as well as physical and treatment planning aspects.

Boron Neutron Capture Therapy↗
PubMed1998

[Workshop "Radio-oncology and the Law"].

From 25 to 27 Sept 1997, a workshop was organized at the Essen Medical School (Universitätsklinikum Essen), at which radiooncologists and jurists from universities and courts as well as lawyers contributed their views on mutual problems. The following topics were discussed by papers and in round table meetings: "Requirements on the patient's information", "definition of therapeutic guidelines-limits of clinical research and standard treatments", "treatment documentation", "liability of the physician for treatment faults" and "technical standard and preserve of quality". The consensual guidelines to the topics "patient's information", "therapeutic guidelines" and "liability" are presented here.

Documentation↗
PubMed1998

Calculation of boron neutron capture cell inactivation in vitro based on particle track structure and x-ray sensitivity.

The Monte-Carlo technique was used to perform quantitative microdosimetric model calculations of cell survival after boron neutron capture irradiations in vitro. The high energy 7Li and alpha-particles resulting from the neutron capture reaction 10B (n,alpha)7Li are of short range and are highly damaging to cells. The biophysical model of the Monte-Carlo calculations is based on the track structure of these a-particles and 7Li-ions and the x-ray sensitivity of the irradiated cells. The biological effect of these particles can be determined if the lethal effect of local doses deposited in very small fractional volumes of the cell nucleus is known. This lethal effect can be deduced from experimental data of cell survival after x-ray irradiation assuming a Poisson distribution for lethal events. The input data used in a PC-based computer program are the radial dose distribution inside the track of the released particles, cell survival after x-ray irradiation, geometry of the tumor cells, subcellular 10B concentration, and thermal neutron fluence. The basic concept of this Monte-Carlo computer model is demonstrated. Validations of computer calculations are presented by comparing them with experimental data on cell survival.

Alpha Particles↗
PubMed1998

Primary conjunctival rhabdomyosarcoma: 2.5 years' follow-up after combined chemotherapy and brachytherapy.

BACKGROUND: The 2.5-year outcome of a 3-year-old girl with a primary intraconjunctival rhabdomyosarcoma treated by biopsy-controlled combined chemo- and brachytherapy is reported. METHODS: The patient presented with a conjunctival dermoid-like lesion which showed modest growth on 1-month follow-up. The first biopsy appointment was missed because of a viral illness. When she showed up 3 months later a further increase in size was obvious and several incisional biopsies were taken immediately. RESULTS: Light microscopy revealed an undifferentiated subepithelial small cell tumour. On immunohistochemistry the tumour reacted with vimentin and desmin antibodies. Thus, the diagnosis of an embryonal rhabdomyosarcoma was made. The patient underwent 9 cycles of polychemotherapy and the tumour mass disappeared macroscopically. However, immunohistochemistry of incisional biopsies showed residual tumour cells. The latter were eradicated by an individually shaped strontium-90 applicator. CONCLUSION: At 2.5 years after biopsy-controlled combined chemotherapy and brachytherapy the patient is free of tumour at a manageable level of complications. This new approach appears to be a good alternative in the treatment of primary conjunctival rhabdomyosarcomas since it takes advantage of the unique location of this rare tumour and avoids hemifacial retardation, known to be induced by external beam radiation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Evaluation of boron neutron capture effects in cell culture using sulforhodamine-B assay and a colony assay.

PURPOSE: The purpose of this study was to find an in vitro method for determining the cytotoxicity of boronated drugs as well as their potential suitability for neutron capture therapy. MATERIALS AND METHODS: The survival of human melanoma cells has been determined by a colony assay and the sulforhodamine-B assay after X-irradiation and irradiation with fast d(14) + Be-neutrons using the boronated compound borocaptate sodium (BSH). The cytotoxic effects of BSH have been studied using both methods. RESULTS: Under well-defined experimental conditions, and after a sufficient amount of time for the expression of radiation damage, the results of the sulforhodamine-B assay are qualitatively comparable with the results of the colony assay. CONCLUSION: The sulforhodamine-B assay is suitable for the screening of compounds for potential use in neutron capture therapy because it is a fast and efficient method that is reproducible and technically advantageous.

Boron Neutron Capture Therapy↗
PubMed1998

Selective delivery of 10B to soft tissue sarcoma using 10B-L-borophenylalanine for boron neutron capture therapy.

Boron neutron capture therapy (BNCT) may improve the locoregional control of radio/chemoresistant tumours like soft tissues sarcomas (STS). This technique uses the 10B(n,alpha)7Li nuclear reaction to destroy tumour cells, provided that a sufficient amount of 10B may be carried selectively into them. In order to evaluate the targeting potential of 10B-L-borophenylalanine (BPA) a 10B biodistribution study was carried out in 24 Wistar rats bearing Yoshida sarcoma. Six animals received increasing intraperitoneal doses of BPA (300, 600 and 1200 mg kg-1), while the remainder received a BPA dose of 600 mg kg-1 but with a sacrifice at six different time points: 1, 2, 4, 6, 9 and 12 h. The 10B concentrations in the tumours, normal tissues and blood were analysed with neutron capture radiography (NCR). The analysis shows that 36 micrograms g-1 (+/- 4 SD) of 10B may be incorporated into the tumour, with a ratio of 13 (+/- 4 SD) versus the muscle and a ratio of 15 (+/- 3 SD) versus the blood, 6 h after an intraperitoneal injection of 600 mg kg-1 of BPA. The BPA appears to be abundantly incorporated in the tumour, and the kidney proximal tubule area. These data suggest that BNCT using BPA may provide an improved therapeutic ratio for the treatment of STS.

Animals↗
PubMed1997

Long-term results after low dose ocular irradiation for choroidal haemangiomas.

AIM/BACKGROUND: The most common choice of treatment for choroidal haemangiomas (CH) in the past has been the employment of scatter photocoagulation of the surface. This management often requires repetitive treatment or additional invasive management due to massive exudative detachment of the retina. The aim of this retrospective study was to investigate the outcome of the alternative application of low dose external beam irradiation with high energetic photons on these tumours. METHODS: A total absorbed dose of 20 Gy was applied to a total of 51 symptomatic eyes: 36 with a circumscribed CH of the posterior pole and 15 with diffuse CH as part of the Sturge-Weber syndrome. The indication for treatment was an exudative retinal detachment including or threatening the fovea. The mean follow up times in each group were 4.5 and 5.3 years, respectively. Out of a group of 33 patients from whom reliable data could be derived, 17 had symptoms lasting longer than 6 months. RESULTS: In 23 cases (63.8%) with circumscribed CH complete resolution of the subretinal fluid was achieved; the remaining 13 cases (36.2%) showed residual serous detachment distant to the fovea. The visual acuity improved by two or more lines in 14 cases (38.9%), remained stable in 14 cases (38.9%), and decreased in eight cases (22.2%). The functional success was dependent on the lag duration between onset of first subjective symptoms and treatment. The morphological results with diffuse CH were similar to those of the group of circumscribed CH. The visual acuity (VA) at last examination was improved in seven cases (46.6%); in the remaining eight cases, VA was unchanged or had deteriorated. The poor functional outcome in the latter was mainly attributable to secondary glaucoma. CONCLUSION: External beam irradiation is a useful and a low invasive therapeutic option for CH. A successful functional outcome is dependent on the time delay between first onset of symptoms and the beginning of therapy, the formation of subretinal fibrosis, and also on secondary glaucoma in the case of Sturge-Weber syndrome.

Adolescent↗