High-energy shock waves enhance hyperthermic response of tumors: effects on blood flow, energy metabolism, and tumor growth.

Abstract

The ability to kill cancerous tissue by heating is often limited by heat lost to flowing blood. Recent studies demonstrate that high-energy shock waves (HESWs), when applied to solid tumors, destroy the tumor microvasculature and rapidly decrease blood flow. We hypothesized that impairment of tumor blood flow by HESWs might result in increased effectiveness of hyperthermia treatment. The purpose of our work was to determine whether HESWs enhance the response of tumors to hyperthermia. Seventy A-Mel-3 amelanotic hamster melanomas were exposed to either 700 HESWs (20 kV, 80 nanofarads), local hyperthermia (43.3 degrees C for 30 minutes), or a combination of both. Three, 12, or 24 hours later, tumor blood flow and adenosine triphosphate (ATP) concentrations were measured by [4-N-methyl-14C]iodoantipyrine autoradiography and quantitative ATP imaging bioluminescence, respectively. In separate experiments, the effects of the separate and combined treatments on tumor growth were studied in 52 animals. Combining HESWs and hyperthermia produced a significantly longer and more pronounced reduction of tumor and adjacent tissue perfusion than either HESWs or hyperthermia alone (P < .05). ATP concentrations were markedly reduced following HESW treatment alone and following the combined therapy compared with untreated controls (P < .05). Three hours after combined therapy, ATP concentrations were significantly below values measured after hyperthermia alone (P < .01). Tumor growth was delayed much more effectively by the combination of HESWs and hyperthermia than by either treatment alone (P < .001). Fifty-four percent of the animals receiving combined treatment showed complete local tumor cure over 52 days of observation, and 46% showed partial remission. The combination of HESWs and hyperthermia might be an effective new way of treating cancer, especially in patients who are not candidates for surgery. These results must be viewed cautiously, as the vasculature of human tumors seems to be less sensitive to hyperthermia than has been observed in experimental tumors.