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Radiation therapy with negative pi-mesons (pions) was administered to 36 patients with bladder cancer. According to a Phase 1/11 study, doses varied from 3OOO to 3600 pion rad. Although only two complete responses were achieved among 8 evaluable patients who had predominantly papillary bladder tumors, more promising results were obtained in 22 evduable patients who had sessile, invasive carcinomas: 19 bladders were cystoscopically and cytologically cleared of tumor after 6 months. Although the side effects during the ambulatory treatment were minimal or tolerable, a steep dose-response curve for late side effects was observed with severe complications in 7 of 11 patients who received 3600 or more pion rad. Densely ionizing radiation from heavy charged particles, such as certain ions (carbon, neon, argon) or negative pi-mesons (pions), is theoretically more advantageous because of particular physical properties; the maximum of energy is released only at the end of the particle range (Bragg peak), within a few centimeters (Fig. 1). Furthermore, high linear energy transfer (LET) particles in the stopping region reduce variations in cell-cycle radiosensitivity and enhance damage to hypoxic tumor cells more than low LET (x-ray and gamma ray) radiation.' Compared with uncharged heavy particles (neutrons), pions have (because of their negative electric charge) excellent dosedistribution characteristics. This makes it possible to design a well-defined volume of irradiation around the tumor and to reduce irradiation effects in the surrounding

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