Potential Applications of the Compact Fast-neutron Generator for the Adjuvant Treatment of Solid Tumours with the Intra-operative Radiotherapy (nIORT®) Technique: Simulation and Dosimetry Analyses with the MCNP Code

Abstract

The potentiality of the intraoperative radiotherapy (IORT) with fast neutrons as an adjuvant treatment for severe solid cancers has been investigated in a 5-year research program. The therapeutic dose is administered by a single irradiation directly within the surgical cavity after surgical resection by means of a compact neutron generator (CNG) with the so-called neutron-IORT technique patented as nIORT®. Two CNG prototypes – exploiting the deuterium–deuterium fusion reaction to produce neutrons of 2.45 MeV energy - are currently undergoing experimental characterisation with the main objectives of demonstrating: - the therapeutic effectiveness of fast neutrons, having a relative biological effectiveness (RBE) ≈ 3÷4 times greater than that of standard RT treatments with X-rays and electrons, and low sensitivity to hypoxia; - the feasibility of installing the CNG - surrounded by ~1 m cube shield - in a hospital operating room dedicated to nIORT® treatments, without posing safety and environmental concerns. In parallel, several dosimetry analyses have been conducted using the MCNP Monte Carlo code by a detailed modelling of the CNG equipped with cylindrical and hemispherical nIORT® applicators positioned within brain and breast surgical cavities, respectively. Thanks to the high neutron flux (~10⁸ cm⁻² s⁻¹) and leveraging on the high RBE of fast neutrons, the MCNP simulations indicate that dose targets of ~10 Gy(RBE) could be administered in ~10÷20 minutes only. Moreover, the diffuse neutron beam may enable: the treatment of large and topographically irregular tumour beds, which remain challenging targets for the focused beams employed in standard RT and IORT techniques; the irradiation of the tumour bed margins - typically infiltrated by quiescent cancer cells and locale recurrences - thereby potentially enhancing the local tumour control; a limited damage and adverse effects to the nearest organs at risk, due to the limited penetration of neutrons over few centimetres in the biological tissues; to integrate the nIORT® adjuvant treatment for radioresistant tumours with local recurrences in a multimodal approach integrating surgery, chemotherapy and/or immunotherapy. In memory of Marina Gherardi, Marika de Feo and Gianluca Costamagna