Using the photon isoeffective dose formalism to compare and combine BNCT and carbon-ion radiotherapy: an example of head and neck tumour
Authors: Postuma Ian , Magni Chiara , Marcaccio Barbara , Fatemi Setareh , Vercesi Valerio , Ciocca Mario , Magro Giuseppe , Orlandi Ester , Vischioni Barbara , Ronchi Sara , Liu Yuan-Hao , Geng Changran , Gonzalez Sara Josefina , Bortolussi Silva , Han Yang 
Published: October 2023

Abstract
Boron Neutron Capture Therapy (BNCT) is a radiotherapy technique based on the enrichment of tumour cells with suitable10-boron concentration and on subsequent neutron irradiation. Low-energy neutron irradiation produces a localized depositionof radiation dose caused by boron neutron capture reactions. Boron is vehiculated into tumour cells via proper boratedformulations, able to accumulate in the malignancy more than in normal tissues. The neutron capture releases two high-LETcharged particles, losing their energy in a distance comparable to the average dimension of one cell. Thus BNCT is selective atthe cell level and characterized by high biological effectiveness. As the radiation field is due to the interaction of neutrons withthe components of biological tissues and with boron, the dosimetry requires a formalism to express the absorbed dose intophoton-equivalent units. This work analyzes a clinical case of an adenoid cystic carcinoma treated with carbon-ion radiotherapy(CIRT), located close to optic nerve and deep-seated as a practical example of how to apply the formalism of BNCT photonisoeffective dose and how to evaluate the BNCT dose distribution against CIRT. The example allows presenting differentdosimetrical and radiobiological quantities and drawing conclusions on the potential of BNCT stemming on the clinical result ofthe CIRT. The patient received CIRT with a dose constraint on the optic nerve, affecting the peripheral part of the PlanningTarget Volume (PTV). After the treatment, the tumour recurred in this low-dose region. BNCT was simulated for the primarytumour, with the goal to calculate the dose distribution in isoeffective units and a Tumour Control Probability (TCP) to becompared with the one of the original treatment. BNCT was then evaluated for the recurrence in the underdosed regionwhich was not optimally covered by charged particles due to the proximity of the optic nerve. Finally, a combined treatmentconsisting in BNCT and carbon ion therapy was considered to show the consistency and the potential of the model. For theprimary tumour, the photon isoeffective dose distribution due to BNCT was evaluated and the resulted TCP was higher thanthat obtained for the CIRT. The formalism produced values that are consistent with those of carbon-ion. For the recurrence,BNCT dosimetry produces a similar TCP than that of primary tumour. A combined treatment was finally simulated, showing aTCP comparable to the BNCT-alone with overall dosimetric advantage in the most peripheral parts of the treatment volume.Isoeffective dose formalism is a robust tool to analyze BNCT dosimetry and to compare it with the photon-equivalent dosecalculated for carbon-ion treatment. This study introduces for the first time the possibility to combine the dosimetry obtained bytwo different treatment modalities, showing the potential of exploiting the cellular targeting of BNCT combined with the precisionof charged particles in delivering an homogeneous dose distribution in deep-seated tumours.