Proton radiobiology, radiosurgery and radiotherapy.

This review briefly traces the historical developments of proton radiobiology, radiosurgery and radiotherapy for the benefit of young researchers and clinicians entering into this field. In preparing to use protons in radiosurgery and radiotherapy, radiobiological effects of protons were studied extensively by various groups, including the University of California at Berkeley, the University of Uppsala, Massachusetts General Hospital, and the Harvard Cyclotron Laboratory. Considerable work on proton radiobiology was also done because protons are a major component of the radiation environment in space. The biological effects of proton beams were found to be quantitatively and qualitatively similar to conventional radiations used in radiotherapy. The relative biological effectiveness (RBE) of protons suitable for large-field radiotherapy, compared with 60Co gamma-rays, is generally in the range 1.0-1.25, and remains the same with depth of penetration, except for the descending portion of the depth-dose curve. Also, unlike other heavier charged particles and neutrons, the RBE of high-energy protons, which are suitable for large-field radiotherapy, compared with 60Co gamma-rays, is generally found to be independent of the fraction size in in vivo experiments. The oxygen enhancement ratio for high-energy protons is not significantly different from that of X-rays. An RBE = 1.1, compared with 60Co gamma-rays, is generally used in the clinical application of protons; however, the radiobiological data on mouse, rat, rabbit and primate suggest that the gastrointestinal tissues may be relatively more sensitive to protons. About 13,000 patients have been treated with protons at about 15 facilities around the world. Nearly half of these patients were neurosurgical patients treated with stereotactic radiosurgery. The pioneering efforts at the Harvard Cyclotron in collaboration with the Massachusetts General Hospital and the Massachusetts Eye and Ear Infirmary were responsible for the development of proton treatment for choroidal melanoma and for the tumours of the skull base and spine. There has been extensive confirmation of these results by other groups, especially the groups at Lawrence Berkeley Laboratory and Paul Scherrer Institute. The first medically dedicated proton facility is in operation at Loma Linda University in California. The construction in the USA of another proton treatment facility at Massachusetts General Hospital has been decided upon, and there are plans for many more worldwide.