Nuclear fusion enhances cancer cell killing efficacy in a protontherapy model

Protontherapy is hadrontherapy fastest-growing modality and a pillar in the battle against cancer. Hadrontherapy 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) $^{12}$C 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 $^{12}$C-ion clinical amenability. Thus, enhancing proton RBE is desirable. To this end, we exploited the p + $^{11}$B $\rightarrow$3$\alpha$ 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 $^{10}$B-enriched BSH for neutron irradiation-triggered alpha-particles. We recorded significantly increased cellular lethality and chromosome aberration complexity. A strategy combining protontherapy ballistic precision with the higher RBE promised by BNCT and $^{12}$C-ion therapy is thus demonstrated.