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 journey from proton to gamma knife.

It was generally accepted by the early 1960s that proton beam radiosurgery was too complex and impractical. The need was seen for a new machine. The beam design had to be as good as a proton beam. It was also decided that a static design was preferable even if the evolution of that notion is no longer clear. Complex collimators were designed that using sources of cobalt-60 could produce beams with characteristics adequately close to those of proton beams. The geometry of the machine was determined including the distance of the sources from the patient the optimal distance between the sources. The first gamma unit was built with private money with no contribution from the Swedish state, which nonetheless required detailed design information in order to ensure radiation safety. This original machine was built with rectangular collimators to produce lesions for thalamotomy for functional work. However, with the introduction of dopamine analogs, this indication virtually disappeared overnight.

Proton: the particle.

The purpose of this article is to review briefly the nature of protons: creation at the Big Bang, abundance, physical characteristics, internal components, and life span. Several particle discoveries by proton as the experimental tool are considered. Protons play important roles in science, medicine, and industry. This article was prompted by my experience in the curative treatment of cancer patients by protons and my interest in the nature of protons as particles. The latter has been stimulated by many discussions with particle physicists and reading related books and journals. Protons in our universe number ≈10(80). Protons were created at 10(-6) -1 second after the Big Bang at ≈1.37 × 10(10) years beforethe present. Proton life span has been experimentally determined to be ≥10(34) years; that is, the age of the universe is 10(-24)th of the minimum life span of a proton. The abundance of the elements is hydrogen, ≈74%; helium, ≈24%; and heavier atoms, ≈2%. Accordingly, protons are the dominant baryonic subatomic particle in the universe because ≈87% are protons. They are in each atom in our universe and thus involved in virtually every activity of matter in the visible universe, including life on our planet. Protons were discovered in 1919. In 1968, they were determined to be composed of even smaller particles, principally quarks and gluons. Protons have been the experimental tool in the discoveries of quarks (charm, bottom, and top), bosons (W(+), W(-), Z(0), and Higgs), antiprotons, and antineutrons. Industrial applications of protons are numerous and important. Additionally, protons are well appreciated in medicine for their role in radiation oncology and in magnetic resonance imaging. Protons are the dominant baryonic subatomic particle in the visible universe, comprising ≈87% of the particle mass. They are present in each atom of our universe and thus a participant in every activity involving matter.

Photons or protons for non-central nervous system solid malignancies in children: a historical perspective and important highlights.

Over the years, major advances have occurred in radiotherapy techniques, delivery, and treatment planning. Although radiotherapy is an integral treatment component of pediatric solid tumors, it is associated with potential acute and long-term untoward effects and risk of secondary malignancy particularly in growing children. Two major advances in external beam radiotherapy are intensity-modulated radiotherapy (IMRT) and proton beam radiotherapy. Their use in the treatment of children with cancer has been steadily increasing. IMRT uses multiple modulated radiation fields that enhance the conformality of the dose distribution to the target volume and avoid high doses to normal tissues. However, IMRT may be associated with increased volume of normal tissue that receives low doses and potential risk of secondary malignancy. Contrary to IMRT, proton beam radiotherapy uses a few beams and a fast dose fall-off distal to the target volume. Although both modalities require substantial personnel time and effort, the very high cost and limited availability of proton radiotherapy have constrained its widespread use. It is anticipated that both modalities may markedly improve tumor control and quality of life for long-term cancer survivors. Clinical trials with long-term follow-up are needed to confirm the premise that proton beam therapy will decrease late effects and secondary malignancies without compromising local control in pediatric patients with cancer.

A review of proton beam radiation therapy.

Beams of protons have been used for radiation treatment for approximately 40 years. This paper provides a short summary of activities from institutions that have contributed to the field over this period. The paper reviews some of the basic interactions of protons with matter that are relevant to radiation treatment and summarizes current knowledge pertaining to the response of biological systems to proton beam radiation. The technical means of producing and delivering proton treatment beams are discussed along with examples of the implementation of these methods at treatment facilities around the world. Finally, the clinical dosimetry of proton beams is summarized and sample data are presented.