The ANDANTE project will integrate the disciplines of radiation physics, molecular biology, systems biology modelling, and epidemiology in order to investigate the relative risk of induction of cancer from exposure to neutrons compared to photons. The project will focus on three specific cancers that may be detected as second malignant neoplasms following paediatric photon radiotherapy: salivary gland, thyroid gland, and breast tissue. Stem cells from each of the types of tissue will be exposed to well characterised beams of neutrons, and biological markers of possible tumorigenesis will be used to develop RBE models. In parallel a track structure model will be developed to simulate the exact experimental conditions and to explore the relationships between exposure parameters and response. The combination of radiobiology and biophysics/systems biology will generate a strongly directed epidemiological investigation to validate the RBE model using clinical data from paediatric proton therapy patients compared to existing cohorts of paediatric photon radiotherapy patients. The limitations of the epidemiological approach alluded to above will be addressed on the one hand by using the discipline for model validation rather than model generation, and on the other hand a prospective study will be designed in order to accumulate sufficient statistical power. To establish a multi-centre cohort of paediatric patients is a decisive task at the current phase where proton therapy is on the advance world-wide. The overarching objective of the project is to determine values of RBE for neutrons, for specific tissues and neutron energies, which can then be validated using paediatric proton therapy data.
Each task in the project forms an essential component part of this objective. The individual task objectives can be split up as follows:
(i) Physical characterisation, using measurements and modelling, of the neutron fields of various energy spectra used for experimental irradiation of cells, and generated during paediatric proton radiotherapy for the purpose of accurate dosimetry and track structure simulation and model development of the damage response;
(ii) Investigation of the damage induction in stem cells as an indicator of the relative carcinogenic effectiveness of low and intermediate doses from neutrons compared to photons; use of the results to generate provisional values for RBE and explore the dependence on neutron energy and dose;
(iii) Integration of functional relationships from biophysical simulations and radiobiological stem cell experiments to develop predictive neutron risk models for second primary malignancies following paediatric proton therapy that can be validated using clinical treatment and follow-up data: proof-of-principle pilot study leading to design of a multi-centre prospective study.
The ANDANTE project is expected to produce results that will have an impact on any facet of radiation protection where neutrons are a significant factor. The re-evaluation of RBE for neutrons will provide information of fundamental importance to the ICRP formalism of radiation protection. This will have direct implications for any industry where neutrons are produced as a by-product.