Funded by Italian Ministry of Foreign Affairs and International Cooperation in the frame of the Executive Program of Scientific and Technological Cooperation between Italy and China for the years 2016-2018.
Macro area: Biotechnology and Medicine (proteomics and genomics, cancer research, neurodegenerative and cardiovascular pathologies, regenerative medicine)
- Principal Investigator (Italia): Giuseppe Battistoni (INFN)
- Principal Investigator (China): Xiaobin Tang
Boron Neutron Capture Therapy (BNCT) is an experimental radiotherapy based on the irradiation with low energy neutrons of tumours that have been loaded with 10B. Neutron capture in 10B generates two charged particles that cause non-reparable damages to the cell where boron is. BNCT has been applied worldwide where neutron sources with sufficient intensity were available, that is in centers equipped with research nuclear reactors. Today BNCT is at a turning point, because the technology is ready to produce neutron beams suitable for therapy using proton accelerators, easily installable in hospitals. The Italian National Institute of Nuclear Physics (INFN) has designed and manufactured a proton accelerator based on Radiofrequency Quadrupole technology (RFQ), able to deliver a high proton current (30 mA) and consequently a high neutron flux exploiting the (p,n) reaction on beryllium or lithium. In China, the number of cancer patients per year is becoming a societal problem because many of them have no access whatsoever to any treatment. BNCT may represent an answer, especially because usually it requires only one irradiation session (fraction). The collaboration between Italian and Chinese partners is already active in BNCT research and needs now to be strengthened towards an industrial scaling of the technology. The aim of the project NEU BEAT is to optimize the treatment of some tumours using a neutron beam from RFQ accelerator. The design and construction of the Beam Shaping Assembly (BSA: the moderator/collimator to tailor the beam spectrum) and the treatment planning will be addressed. Moreover, radiobiology studies be carried out by irradiation of tumour cell cultures. BNCT requires expertise in medicine, physics, biology and chemistry, and disseminated clinical trials based on accelerators cannot be started without industry. This project encompasses many of these involving Public Research Institutions, SMEs and a Particle Therapy clinical facility.
NEU BEAT aims at consolidating the existing collaboration in the field of accelerator-based BNCT, to develop and test some technological solutions for clinical trials in Italy and in China, in particular:
- BSA prototyping
- Treatment planning assessments
- Positioning and shielding issues
- Mixed field dosimetry computational models
- Combined irradiation modalities
INFN has developed a proton accelerator suitable to be installed in medical centers for BNCT and has expertise in tailoring neutron beams. Chinese partners have developed a dedicated Treatment Planning System and have the experience of clinical trials with neutron beams from reactors. Moreover, the contribution of National Centre for Oncological Particle Therapy (CNAO) is meant to study further possibilities of BNCT application, for example as a boost or complementary treatment for patients who already received carbon ion therapy, or to compare the effectiveness of dose distributions of the two treatment modalities. Finally, industries are involved for the test of innovative materials for the positioning and shielding of patients and to address the possibility to use materials as aluminum fluoride for the BSA. The Chinese company Neuboron and INFN have already established scientific contacts, and NEU BEAT is a first step to extend in the future the BNCT as a disseminated routine clinical application in China with the participation of INFN. The idea is to extend the technical solutions developed and tested together to a wider industrial project. Finally, NEU BEAT foresees a strong exchange of researchers between China and Italy in order to build a homogeneous research group with all the necessary professional skills mentioned above and to train young investigators capable to reproduce the project in the future facilities both in China and in Italy.
WP1. Optimization of the BSA to tailor an epithermal neutron beam for clinical BNCT.
The BSA will be optimized for two RFQ set-ups: protons of 5 MeV with Be target (as the RFQ already available in Italy) or 2.5 MeV with Li target (a solution in the development phase). Italian group will start from the present project of the BSA of the 5 MeV RFQ, able to deliver a neutron beam between 1 and 10 keV to treat deep seated tumours. Chinese partners will design other configurations, testing different materials, for the configuration at 2.5 MeV. With a private firm the possibility to build homogeneous layers of aluminum and magnesium fluoride will be tested. The project of the two BSAs will be obtained by neutron transport Monte Carlo code MCNP. Prototypes will be built at INFN workshop in Pavia. This task is very important in view of an industrialization of BNCT facilities. BSA is responsible of the quality of the neutron beam and thus the possibility to deliver an effective dose to the tumour while sparing the normal tissues. Moreover, the beam characteristics determine the irradiation time, quantified around 30 minutes with RFQ of INFN. The compactness of the machine, the one or two fractions, and the short irradiation times make BNCT with RFQ an appealing solution to treat many patients at relatively low costs.
WP2. Treatment planning simulations on relevant clinical cases.
BNCT can be interpreted as a selective heavy ion therapy, and it could also be applied as a boost or as a complementary therapy for patients who already received proton or carbon irradiation. To study this possibility, radiotherapists working at the National Centre for Oncological Particle Therapy (CNAO) in Pavia will select interesting clinical cases. The CT scans of patients will be used to simulate treatment with the beams of the RFQ, using the Treatment Planning System developed by Chinese group. These simulations are also useful to verify if the spectral characteristics of the beam are suitable for the treatment of the selected tumours and can serve as a feedback to better tailor the beams. These tests will be carried out with the two RFQ configurations by the Chinese and Italian groups together. Patient positioning requires technical facilities and the possibility to immobilize and shield anatomical parts. Innovative materials for protection and devices for positioning will be developed and tested together with some private Italian companies that are already active in this field. Finally, mixed field dosimetry will be studied, applying new models for the expression of BNCT dose in units that can be coherently compared with dose in photon and heavy-ion therapy.
WP3. Radiobiological Studies
In order to compare BNCT dose with Particle Therapy and photon therapy ones it is necessary to obtain the survival curve of the tumour cell lines as a function of the dose. Irradiations of selected cell lines will be carried out at CNAO with protons and carbon ions and survival assessed by means of plating efficiency assay at University of Pavia. In order to study the effects of the administration of two irradiation modalities (BNCT+ carbon ions) cell cultures will be irradiated. For BNCT, the thermal neutron irradiation at the TRIGA reactor will be used, already characterized from the points of view of neutron spectrum and gamma dose. This task will be carried out by the Italian groups with the participation of Chinese colleagues, experts in dose computation.
- Giuseppe Battistoni
- Saverio Altieri
- Silva Bortolussi
- Ian Postuma
- Nicoletta Protti
- Setareh Fatemi
- Cinzia Ferrari
- Umberto Anselmi Tamburini
- Piero Fossati
- Alfredo Mirandola
- Valerio Vercesi
Neutron beam tailoring for BNCT: new materials, evaluation methods, novel approaches
from Thursday, 24 November 2016 at 10:00 to Friday, 25 November 2016 at 15:00 (Europe/Rome) at INFN, Pavia. Via Bassi 6, 27100 Pavia.
1st collaboration meeting in the frame of the Executive Programme of Scientific and Technological Cooperation between Italy and China for the years 2016-2018: project NEU_BEAT. The meeting is focused on the development of new materials to design neutron beams for clinical BNCT, on the techniques to evaluate the beam performances and on the benchmark of simulation tools for treatment planning.
Con il contributo del Ministero degli Affari Esteri e della Cooperazione Internazionale, Direzione Generale per la Promozione del Sistema Paese Progetto NEU_BEAT PGR00710.