[en] Monte Carlo modelling of an irradiation facility, for boron neutron capture therapy (BNCT) application, using a set of advanced type, accelerator based, ³H(d,n)⁴He (D-T) fusion neutron source device is presented. Some general issues concerning the design of a proper irradiation beam shaping assembly, based on very hard energy neutron source spectrum, are reviewed. The facility here proposed, which represents an interesting solution compared to the much more investigated Li or Be based accelerator driven neutron source could fulfil all the medical and safety requirements to be used by an hospital environment

[en] The idea to couple the treatment planning system (TPS) to the information on the real boron distribution in the patient acquired by positron emission tomography (PET) is the main added value of the new methodology set-up at DIMNP (Dipartimento di Ingegneria Meccanica, Nucleare e della Produzione) of University of Pisa, in collaboration with the JRC (Joint Research Centre) at Petten (NL). This methodology has been implemented in a new TPS, called Boron Distribution Treatment Planning System (BDTPS), which takes into account the actual boron distribution in the patient's organ, as opposed to other TPSs used in BNCT that assume an ideal uniform boron distribution. BDTPS is based on the Monte Carlo technique and has been experimentally validated comparing the computed main parameters (thermal neutron flux, boron dose, etc.) to those measured during the irradiation of an ad hoc designed phantom (HEterogeneous BOron phantoM, HEBOM). The results are also in good agreement with those obtained by the standard TPS SERA and by reference calculations carried out using an analytical model with the MCNP code. In this paper, the methodology followed for both the experimental and the computational validation of BDTPS is described

[en] Present standard treatment planning (TP) for glioblastoma multiforme (GBM - a kind of brain tumor), used in all boron neutron capture therapy (BNCT) trials, requires the construction (based on CT and/or MRI images) of a 3D model of the patient head, in which several regions, corresponding to different anatomical structures, are identified. The model is then employed by a computer code to simulate radiation transport in human tissues. The assumption is always made that considering a single value of boron concentration for each specific region will not lead to significant errors in dose computation. The concentration values are estimated 'indirectly', on the basis of previous experience and blood sample analysis. This paper describes an original approach, with the introduction of data on the in vivo boron distribution, acquired by a positron emission tomography (PET) scan after labeling the BPA (borono-phenylalanine) with the positron emitter ¹⁸F. The feasibility of this approach was first tested with good results using the code CARONTE. Now a complete TPS is under development. The main features of the first version of this code are described and the results of a preliminary study are presented. Significant differences in dose computation arise when the two different approaches ('standard' and 'PET-based') are applied to the TP of the same GBM case

[en] Liver metastases are the most frequent kind of malignancy in Western countries (Europe and North America) and represent the most diffused site of recurrence of any primary tumour. Survival of patients with liver metastases depends primarily from the stage of the primary tumour. Nevertheless, untreated patients invariably have a poor prognosis. In particular, as regards liver metastases from colorectal cancer, all the series reported in the last 30 years show that the median survival time of untreated patients is 6 to 12 months. The optimisation of surgical techniques has yielded a remarkable improvement in the results of hepatic resection, which is still to be considered the elective treatment of hepatic metastases from colorectal cancer. In particular, the 5-year survival of patients with radically resected tumour, that underwent adjuvant systemic and/or loco-regional chemotherapy, is about 25-40%. However, for deep, multiple, huge lesions, which cannot be resected, the prognosis remains extremely poor. Taking this into account, the BNCT group in Pavia (Italy) pioneered the extra-corporal treatment of the liver metastases by BNCT, whereby the liver is removed in the operating theatre, taken to the reactor for BNCT, and then returned to the hospital for implantation back into the patient. On the basis of 2 patients that underwent this treatment, BNCT combined with adjuvant chemotherapy is efficient in the treatment of hepatic metastases from colorectal cancer with an important impact on live expectation Consequently, extra-corporal liver treatment is now being planned at the BNCT facility in the High Flux Reactor located in Petten (The Netherlands) in collaboration with the University Hospital of Essen (Germany). A special irradiation facility has been designed and dosimetry measurements, as reported here, using gel dosimetry have been performed, as part of the validation exercise. The preparation of the human liver treatment starts from the evaluation of the dosimetry of the problem. Several calculations have been performed using Monte Carlo simulations of the liver irradiation, in order to design a facility optimised to provide as much as possible a homogeneous thermal neutron fluence in the liver. The simulations are based on a simplified model of the human liver, contained in an ellipsoid, and on the usage of the neutron beam normally used for BNCT clinical trials in Petten. This neutron beam has a spectrum peaked in the epithermal energy region, which varies considerably from the irradiation field used at Pavia. This implies the necessity of a special liver facility, made of PMMA and surrounded by graphite, which thermalizes the incident neutrons. Furthermore, rotation of the holder then produces a homogeneous thermal neutron field inside the liver. Due to the relatively low neutron fluence (∼10⁸ n/cm²s) of incident neutron beam, an irradiation time of 3 hours will be necessary, which is within the constraints imposed by the medical requirements. In order to validate the design calculations, which were performed using the Monte Carlo code MCNP, both activation foils and gel dosimeters have been used. The gel dosimeter is a technique to obtain continuous images of absorbed dose. By properly designing the gel isotopic composition, it is possible to separate the gamma dose and the dose due to charged particles, such as those produced in ¹⁰B reactions, and consequently the thermal neutron flux can be deduced. Therefore, this method gives an indication of the thermal neutron flux and the doses along pre-defined axes and in particular along the axis of the holder, if this axis is in the plane of the gel dosimeter. The gel dosimeters are generally positioned in the liver holder and surrounded with a non-dosimetric gel, whose hydrogen composition is low enough as not to create a problem in the final dosimetry. The main drawback of these dosimeters is their relatively poor sensitivity to low doses. As a rule of thumb, a total dose of about 20 Gy can be enough for attaining a sufficient resolution for evaluating the neutron flux and the gamma dose. The calculated thermal neutron flux appears to be consistent with that obtained in strategic places of the liver holder, making use of the activation foils. The neutron fluence mappings obtained by the gel dosimeters confirm that the BNCT liver facility in Petten is able to provide a proper homogeneous thermal neutron distribution in the liver, as required for the successful treatment of the liver metastases

[en] Since October 1997, a clinical trial of Boron Neutron Capture Therapy (BNCT) for glioblastoma patients has been in progress at the High Flux Reactor, Petten, the Netherlands. The trial is a European Organisation for Research and Treatment of Cancer (EORTC) protocol (no. 11 961) and, as such, must be conducted following the highest quality management and procedures, according to good clinical practice and also other internationally accepted codes. The complexity of BNCT involves not only strict international procedures, but also a variety of techniques to measure the different aspects of the irradiation involved when treating the patient. Applications include: free beam measurements using packets of activation foils; in-phantom measurements for beam calibration using ionisation chambers, pn-diodes and activation foils; monitoring of the irradiation beam during patient treatment using fission chambers and GM-counters; boron in blood measurements using prompt gamma ray spectroscopy; radiation protection of the patient and staff using portable radiation dosimeters and personal dosimeters; and in vivo measurements of the boron in the patient using a prompt gamma ray telescope. The procedures and applications of such techniques are presented here, with particular emphasis on the importance of the quality assurance/quality control procedures and its reporting

[en] An epithermal neutron beam from the High Flux Reactor is used for clinical BNCT at Petten. For the validation of the treatment planning simulations an accurate experimental determination of the different dose components in the mixed beam of neutrons and photons is important. Dosimetry is performed with paired ionisation chambers, among other techniques. Experiments have been made using Mg/Ar and TE/TE ionisation chambers. Calibration factors for both chambers have been obtained from measurements in a ⁶⁰Co gamma-ray beam. Ionisation chambers are sensitive to neutron capture reactions in the structure of the chambers. This paper describes a novel approach to the correction for the parasitic sensitivity to neutron capture. The k' values for ionisation chambers in epithermal neutron beams have been determined previously using thermal neutron flux values. This procedure neglects the contribution of the epithermal neutrons which are present in the low energy part of the intermediate-energy neutron spectrum. In this work k' factors have been determined using reaction rate relations of neutron activation reactions. (author)

[en] The dosimetry method based on Fricke-Xylenol-Orange-infused gels in form of layers has shown noticeable potentiality for in-phantom or in-free-beam dose and thermal flux profiling and imaging in the high fluxes of thermal or epithermal neutrons utilised for boron neutron capture therapy (BNCT). Gel-dosimeters in form of layers give the possibility not only of obtaining spatial dose distributions but also of achieving measurements of each dose contribution in neutron fields. The discrimination of the various dose components is achieved by means of pixel-to-pixel manipulations of pairs of images obtained with gel-dosimeters having different isotopic composition. It is possible to place large dosimeters, detecting in such a way large dose images, because the layer geometry of dosimeters avoids sensitive variation of neutron transport due to the gel isotopic composition. Some results obtained after the last improvements of the method are reported. (Author)