Protontherapy is hadrontherapy's fastest-growing modality and a pillar in the battle against cancer. Hadrontherapy's superiority lies in its inverted depth-dose profile, hence tumour-confined irradiation. Protons, however, lack distinct radiobiological advantages over photons or electrons. Higher LET (Linear Energy Transfer) 12C-ions can overcome cancer radioresistance: DNA lesion complexity increases with LET, resulting in efficient cell killing, i.e. higher Relative Biological Effectiveness (RBE). However, economic and radiobiological issues hamper 12C-ion clinical amenability. Thus, enhancing proton RBE is desirable. To this end, we exploited the p + 11B → 3α reaction to generate high-LET alpha particles with a clinical proton beam. To maximize the reaction rate, we used sodium borocaptate (BSH) with natural boron content. Boron-Neutron Capture Therapy (BNCT) uses 10B-enriched BSH for neutron irradiation-triggered alpha particles. We recorded significantly increased cellular lethality and chromosome aberration complexity. A strategy combining protontherapy's ballistic precision with the higher RBE promised by BNCT and 12C-ion therapy is thus demonstrated.

Fondazione Bruno Kessler Micro Nano Facility Via Sommarive 18 38123 Povo Trento Italy

INFN Naples Section Complesso Universitario di Monte S Angelo Via Cintia Naples Italy

Institute of Molecular Bioimaging and Physiology National Research Council Italy

Institute of Physics ASCR v v i ELI Beamlines Project Na Slovance 2 Prague 18221 Czech Republic

Istituto Nazionale di Fisica Nucleare Laboratori Nazionali dei Sud via S Sofia 62 Catania Italy

National Physical Laboratory Acoustic and Ionizing Radiation Division Teddington TW11 0LW Middlesex United Kingdom

Physics Department University of Catania via S Sofia 64 Catania Italy

Physics Department University of Naples Federico 2 Naples Italy

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First independent validation of the proton-boron capture therapy concept

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