Overview of Light-Ion Beam Therapy (2006)

In 1930, Ernest Orlando Lawrence at the University of California at Berkeley invented the cyclotron. One of his students, M. Stanley Livingston, constructed a 13-cm diameter model that had all the features of early cyclotrons, accelerating protons to 80 keV using less than 1 kV on a semi-circular accelerating electrode, now called the ''dee''. Soon after, Lawrence constructed the first two-dee 27-Inch (69-cm) Cyclotron, which produced protons and deuterons of 4.8 MeV. In 1939, Lawrence constructed the 60-Inch (150-cm) Cyclotron, which accelerated deuterons to 19 MeV. Just before WWII, Lawrence designed a 184-inch cyclotron, but the war prevented the building of this machine. Immediately after the war ended, the Veksler-McMillan principle of phase stability was put forward, which enabled the transformation of conventional cyclotrons to successful synchrocyclotrons. When completed, the 184-Inch Synchrocyclotron produced 340-MeV protons. Following it, more modern synchrocyclotrons were built around the globe, and the synchrocyclotrons in Berkeley and Uppsala, together with the Harvard cyclotron, would perform pioneering work in treatment of human cancer using accelerated hadrons (protons and light ions). When the 184-Inch Synchrocyclotron was built, Lawrence asked Robert Wilson, one of his former graduate students, to look into the shielding requirements for of the new accelerator. Wilson soon realized that the 184-Inch would produce a copious number of protons and other light ions that had enough energy to penetrate human body, and could be used for treatment of deep-seated diseases. Realizing the advantages of delivering a larger dose in the Bragg peak when placed inside deep-seated tumors, he published in a medical journal a seminal paper on the rationale to use accelerated protons and light ions for treatment of human cancer. The precise dose localization provided by protons and light ions means lower doses to normal tissues adjacent to the treatment volume compared to those in conventional (photon) treatments. Wilson wrote his personal account of this pioneering work in 1997. In 1954 Cornelius Tobias and John Lawrence at the Radiation Laboratory (former E.O. Lawrence Berkeley National Laboratory) of the University of California, Berkeley performed the first therapeutic exposure of human patients to hadron (deuteron and helium ion) beams at the 184-Inch Synchrocyclotron. By 1984, or 30 years after the first proton treatment at Berkeley, programs of proton radiation treatments had opened at: University of Uppsala, Sweden, 1957; the Massachusetts General Hospital-Harvard Cyclotron Laboratory (MGH/HCL), USA, 1961; Dubna (1967), Moscow (1969) and St Petersburg (1975) in Russia; Chiba (1979) and Tsukuba (1983) in Japan; and Villigen, Switzerland, 1984. These centers used the accelerators originally constructed for nuclear physics research. The experience at these centers has confirmed the efficacy of protons and light ions in increasing the tumor dose relative to normal tissue dose, with significant improvements in local control and patient survival for several tumor sites. M.R. Raju reviewed the early clinical studies. In 1990, the Loma Linda University Medical Center in California heralded in the age of dedicated medical accelerators when it commissioned its proton therapy facility with a 250-MeV synchrotron. Since then there has been a relatively rapid increase in the number of hospital-based proton treatment centers around the world, and by 2006 there are more than a dozen commercially-built facilities in use, five new facilities under construction, and more in planning stages. In the 1950s larger synchrotrons were built in the GeV region at Brookhaven (3-GeV Cosmotron) and at Berkeley (6-GeV Bevatron), and today most of the world's largest accelerators are synchrotrons. With advances in accelerator design in the early 1970s, synchrotrons at Berkeley and Princeton accelerated ions with atomic numbers between 6 and 18, at energies that permitted the initiation of several biological studies. It is worth noting that when the Bevatron was converted to accelerate light ions, the main push came from biomedical users who wanted to use high-LET radiation for treating human cancer.