Radiobiology of Particle Therapy: Revisiting the Preclinical Knowledge Base on Helium Ion Therapy

Modern photon-based, intensity-modulated radiation therapy (IMRT) kills tumors but may also excessively damage normal tissues; the resultant morbidity can prompt treatment interruptions, worsen tumor control, and degrade quality of life. Charged particles (eg, protons, carbon ions) may be less toxic and more effective than IMRT because particles irradiate less surrounding normal tissues and are more biologically effective than IMRT. However, protons/carbon ions have physical drawbacks that can affect dose precision. Helium ions are being explored as an alternative type of charged-particle therapy because their biophysical characteristics are intermediate between those of protons and carbon ions, potentially improving treatment precision. However, systematic studies of helium ion radiotherapy (HeRT) are scarce. We review current knowledge of the biophysical effects of HeRT: its relative biological effectiveness (RBE) versus photons; its effects on gene mutation, DNA damage and repair, cell cycling, cell death, and radiosensitization; and early explorations of ultra-high dose rate HeRT.