Neon ion radiotherapy: physics and biology

Neon ion (²⁰Ne) beam radiotherapy was one of the primary particle therapy candidates investigated during the clinical trials beginning in the 1970s at the Lawrence Berkely National Laboratory (LBNL), which shut down in the early 1990s. Currently, therapeutic neon ion beams are available at only one clinical facility worldwide, the National Institutes for Quantum Science and Technology (QST) in Chiba, Japan. Recently, neon ion beams were commissioned at QST Hospital as part of the first clinical multi-ion therapy (MIT) program, which aims to improve clinical outcomes by escalating higher linear energy transfer (LET) radiation in the tumor for treating therapy-resistant disease. With the advancement of high-precision scanning delivery techniques, neon ion treatments in the present day could be delivered more safely and with greater precision compared to the first and only clinical application decades prior at LBNL using passive scattering technology. Despite their promising results, preclinical investigations of neon ions are scarce outside of Japan and further independent studies are needed. Clinically, neon ion therapy may offer benefits in treating certain malignancies by escalating LET in the tumor, but its limited availability and high costs restrict its current use and adoption. Studies have shown that²⁰Ne or multi-ion mixtures (⁴He,¹²C,¹⁶O and/or²⁰Ne) can provide larger degrees of freedom in optimization of dose, LET and relative biological effectiveness, otherwise unattainable with other single ion techniques. Neon ion beams are under investigation in the ongoing MIT clinical trials which will establish their broader applicability. In this review, the technology, physics, radiobiology, and potential clinical applications of neon ion beams are outlined. The status of therapeutic neon ion beams is provided while discussing future research and clinical directions, including technological development of novel particle therapy delivery techniques, such as multi-ion, mini-beam, arc, and ultra-high dose rate.