Considerations in identifying optimal particles for radiation medicine.

Of the many ionizing particles discovered so far, only a few are reasonable to consider for radiation therapy. These include photons, protons, neutrons, electrons, mesons, antiprotons, and ions heavier than hydrogen. Most of these particles are used therapeutically to destroy or inactivate malignant and sometimes benign cells. Since the late 1930s, accelerators have been developed that have expanded radiation oncologists' abilities to produce various ionizing particle beams. Over the past decade, radiation oncologists have become increasingly interested in pursuing particles other than the conventional photons that have been used almost exclusively since X-rays were discovered in 1895. Physicians recognize that normal-tissue morbidity from all forms of anti-cancer treatment is the primary factor limiting the success of those treatments. In radiation therapy, all particles mentioned above can destroy any cancer cell; controlling the beam in three dimensions, thus providing the physician with the capability of avoiding normal-tissue injury, is the fundamental deficiency in the use of X-rays (photons). Heavy charged particles possess near-ideal characteristics for exercising control in three dimensions; their primary differences are due to the number of protons contained within their nuclei. As their number of protons increase (atomic number) their ionization density (LET) increases. In selecting the optimal particle for therapy from among the heavy charged particles, one must carefully consider the ionization density created by each specific particle. Ionization density creates both advantages and disadvantages for patient treatment; these factors must be matched with the patients' precise clinical needs. The current state of the art involves studying the clinical advantages and disadvantages of the lightest ion, the proton, as compared to other particles used or contemplated for use. Full analysis must await adequate data developed from long-term studies to determine the precise role of each potential particle for human use. It is expected that one particle beam will emerge as the mainstream for treating human disease, and a small number of particles may emerge in an adjunctive role.