The 20th Gray lecture 2019: health and heavy ions.

OBJECTIVE: Particle radiobiology has contributed new understanding of radiation safety and underlying mechanisms of action to radiation oncology for the treatment of cancer, and to planning of radiation protection for space travel. This manuscript will highlight the significance of precise physical and biologically effective dosimetry to this translational research for the benefit of human health.This review provides a brief snapshot of the evolving scientific basis for, and the complex current global status, and remaining challenges of hadron therapy for the treatment of cancer. The need for particle radiobiology for risk planning in return missions to the Moon, and exploratory deep-space missions to Mars and beyond are also discussed. METHODS: Key lessons learned are summarized from an impressive collective literature published by an international cadre of multidisciplinary experts in particle physics, radiation chemistry, medical physics of imaging and treatment planning, molecular, cellular, tissue radiobiology, biology of microgravity and other stressors, theoretical modeling of biophysical data, and clinical results with accelerator-produced particle beams. RESULTS: Research pioneers, many of whom were Nobel laureates, led the world in the discovery of ionizing radiations originating from the Earth and the Cosmos. Six radiation pioneers led the way to hadron therapy and the study of charged particles encountered in outer space travel. Worldwide about 250,000 patients have been treated for cancer, or other lesions such as arteriovenous malformations in the brain between 1954 and 2019 with charged particle radiotherapy, also known as hadron therapy. The majority of these patients (213,000) were treated with proton beams, but approximately 32,000 were treated with carbon ion radiotherapy. There are 3500 patients who have been treated with helium, pions, neon or other ions. There are currently 82 facilities operating to provide ion beam clinical treatments. Of these, only 13 facilities located in Asia and Europe are providing carbon ion beams for preclinical, clinical, and space research. There are also numerous particle physics accelerators worldwide capable of producing ion beams for research, but not currently focused on treating patients with ion beam therapy but are potentially available for preclinical and space research. Approximately, more than 550 individuals have traveled into Lower Earth Orbit (LEO) and beyond and returned to Earth. CONCLUSION: Charged particle therapy with controlled beams of protons and carbon ions have significantly impacted targeted cancer therapy, eradicated tumors while sparing normal tissue toxicities, and reduced human suffering. These modalities still require further optimization and technical refinements to reduce cost but should be made available to everyone in need worldwide. The exploration of our Universe in space travel poses the potential risk of exposure to uncontrolled charged particles. However, approaches to shield and provide countermeasures to these potential radiation hazards in LEO have allowed an amazing number of discoveries currently without significant life-threatening medical consequences. More basic research with components of the Galactic Cosmic Radiation field are still required to assure safety involving space radiations and combined stressors with microgravity for exploratory deep space travel. ADVANCES IN KNOWLEDGE: The collective knowledge garnered from the wealth of available published evidence obtained prior to particle radiation therapy, or to space flight, and the additional data gleaned from implementing both endeavors has provided many opportunities for heavy ions to promote human health.

The Denekamp diadems--a review of Julie's achievements.

Dr Julie Denekamp, DSc, PhD, BSc was present at a symposium held in her honour in Uppsala in February 2001. This article presents some biographical details and summarizes the main features of the scientific work for which she is known in radiobiology applied to cancer treatment, now called Translational Research. Topics include fractionation, proliferation in normal tissues as well as tumours, early versus late reactions, radiosensitizers, vascular attack in tumours, neutrons (and pions), radiosensitizers, radioprotectors, hyperthermia, research methodology, and theoretical modelling.

Neutron therapy--the historical background.

Neutron therapy was first introduced by Stone et al. in 1938, i.e. more than 10 years earlier than electron beam therapy and only 6 years after the discovery of neutrons. In spite of the impressive accomplishment in generating an adequate therapy beam, time was also found for careful radiobiological studies of neutron beams. However, it was not considered that for a certain early reaction the late effects were much greater with neutrons than with x-rays. The severe late sequelae in proportion to the few good results motivated the closure of this therapy. Neutron therapy was again introduced in Hammersmith hospital at the end of the 1960's. The major reason seems to have been to overcome the oxygen effect. Encouraging results were reported. It was argued that the very favourable statistics on local tumour control were obtained at the expense of more frequent and more severe complications. A clinical trial in Edinburgh seemed to indicate this, but it was not proved in the end as the two trials differed regarding fractionation. Today about 16,000 patients have been treated with neutrons. The neutron beams now used differ significantly, both regarding dose distributions and microdosimetrical properties, from those utilized earlier. The advantage of neutrons is still, however, controversial. There are indications that neutron treatment may be favourable for some tumours. A careful cost-benefit study ought to be performed before the creation of a neutron therapy centre in Sweden as the group of patients suitable for neutrons is limited, and there may be new possibilities for improvement of photon and electron treatment with much smaller resources.