Protons for radiotherapy: a 1946 proposal.

The current enthusiasm for the medical application of charged particles has peaked at a time when nuclear physics research has lost some of its glamour, but nevertheless particles for radiotherapy are a spin-off from the halcyon days of nuclear physics. In the early years of the 20th century, beams of charged particles were used in nuclear disintegration experiments to produce artifi cial radioactive materials. This was the precursor of the nuclear age. Higher and higher energies were called for and made possible, largely by the invention of the cyclotron in 1931. These accelerators, invented and built for the research of nuclear physics, were later adapted for cancer treatment. Robert Wilson was born in Wyoming, USA, and went to graduate school at the University of California Berkeley, USA, with Ernest Lawrence, the inventor of the cyclotron. In 1943, he was recruited to lead the cyclotron group at Los Alamos National Laboratory (NM, USA), working on the Manhattan project, but they had no cyclotron, so the US government bought the one from Harvard University (Cambridge, MA, USA; built in 1937) for US$1 with the promise to replace it after the war. Wilson wrote his seminal paper proposing protons for radiotherapy in 1946, after leaving Los Alamos and moving to Harvard to design and build their new replacement accelerator. He came from a strong Quaker background, and it is said that he was motivated to give some time to this medical application as “atonement for involvement in the development of the bomb at Los Alamos”. Wilson pointed out that protons have advantages over X-rays for the treatment of cancer, because of their physical dose distribution. The dose deposited by a beam of mono-energetic protons increases slowly with depth, but reaches a sharp maximum near the end of the particles range, in the so-called Bragg peak. The beam has sharp edges, with little side-scatter, and the dose falls to zero at the end of the particle’s range. The possibility of precisely confi ning the high-dose region to the tumour volume while minimising the dose to the surrounding normal tissue is the attractive feature of charged particle beams. Unfortunately, the paper had little immediate eff ect in the radiotherapy community at the time. Patients were fi rst treated with protons at accelerators built initially for physics research, but which had become obsolete as bigger and better accelerators were built elsewhere. The earliest eff orts were at the LawrenceBerkeley National Laboratory (CA, USA) in 1954 and in Uppsala, Sweden, in 1962; only a small number of patients were treated at these facilities. In the 1960s, a collaboration was formed between the Harvard cyclotron and physicians from the Massachusetts General Hospital (MA, USA), led by Herman Suit, with the fi rst patient treated in 1973. By the time that the cyclotron was closed in 2002, over 9000 patients had received proton treatment. Currently, several dozen purpose-built hospital-based facilities are in operation, or under construction, in the USA, Europe, and Japan. Most involve protons, but some use heavier ions such as carbon. Proton facilities typically cost about $125 million, with heavier ions involving much higher costs. Such facilities might well revolutionise radiation oncology, mainly because of the decrease in healthy tissue morbidity associated with the improved dose distribution.