Back with Weight: Revisiting Very Heavy Ions for Precision Radiotherapy

Accelerated charged particles offer significant physical advantages over X-rays in radiotherapy. In addition to their superior depth-dose distribution, heavy ions provide notable biological benefits compared to protons. Specifically, at therapeutic energies, very heavy ions are expected to exhibit high relative biological effectiveness and a low oxygen enhancement ratio, making them potentially ideal for treating radioresistant tumors. Over fifty years ago, the Lawrence Berkeley Laboratory started a clinical trial to treat cancer patients with particles ranging from helium to argon. However, treatments with ions of atomic number greater than 10 proved highly toxic to normal tissue. Most patients were ultimately treated with helium ions, whose biological effects closely resemble those of protons. In recent years, novel strategies have emerged that can reduce normal tissue toxicity in radiotherapy while preserving tumor control. These advancements open the possibility of revisiting the clinical use of heavier ions. In this paper, we propose that neon ions may serve as an effective modality for treating resistant, hypoxic tumors. Their associated toxicity may be mitigated by employing approaches such as ultra-high dose rate (FLASH) or spatially fractionated radiotherapy. Current plans and prospects for the clinical application of neon ions will be discussed.