HIGH-ENERGY SHOCK-WAVES ENHANCE HYPERTHERMIC RESPONSE OF TUMORS - EFFECTS ON BLOOD-FLOW, ENERGY-METABOLISM, AND TUMOR-GROWTH

Background: The ability to kill cancerous tissue by heating is often l imited 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 hypoth esized that impairment of tumor blood flow by HESWs might result in in creased effectiveness of hyperthermia treatment. Purpose: The purpose of our work was to determine whether HESWs enhance the response of tum ors to hyperthermia. Methods: Seventy A-Mel-3 amelanotic hamster melan omas were exposed to either 700 HESWs (20 kV, 80 nanofarads), local hy perthermia (43.3-degrees-C for 30 minutes), or a combination of both. Three, 12, or 24 hours later, tumor blood flow and adenosine triphosph ate (ATP) concentrations were measured by [4-N-methyl-C-14]iodoantipyr ine autoradiography and quantative ATP imaging bioluminescence, respec tively. In separate experiments, the effects of the separate and combi ned treatments on tumor growth were studied in 52 animals. Results: Co mbining HESWs and hyperthermia produced a significantly longer and mor e pronounced reduction of tumor and adjacent tissue perfusion than eit her HESWs or hyperthermia alone (P<.05). ATP concentrations were marke dly reduced following HESW treatment alone and following the combined therapy compared with untreated controls (P<.05). Three hours after co mbined therapy, ATP concentrations were significantly below values mea sured 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 rec eiving combined treatment showed complete local tumor cure over 52 day s of observation, and 46% showed partial remission. Conclusion: The co mbination of HESWs and hyperthermia might be an effective new way of t reating cancer, especially in patients who are not candidates for surg ery. Implications: These results must be viewed cautiously, as the vas culature of human tumors seems to be less sensitive to hyperthermia th an has been observed in experimental tumors.