Tumor stabilization after hyperthermia: an important criterion of response to thermal therapy

Several investigators have indicated that changes in tumor size may not occur after hyperthermia therapy even with substantial tumor cell kill, because of early edema and subsequent fibrosis of background stroma, suggesting that "tumor stabilization" might be an important benefit of thermal therapy. Recently, 9 institutions completed a national cooperative study of localized hyperthermia for patients with advanced, recurrent, or metastatic solid cancer that evaluated the potential significance of this response variable in a standardized clinical trial. Of 960 evaluable patients who completed at least one course of hyperthermia, thermoradiotherapy, or thermochemotherapy, 85 (9%) had complete responses for 1-34 months, 173 (18%) had partial responses for 1-39 months, 95 (10%) had minimal responses for 1-15 months, and 313 (33%) had disease stabilization for 1-32 months. Of 313 patients who had no change (i.e., +/- 25%) in the size of their tumors after hyperthermia, the response lasted only 1-3 months in 170 (54%) patients, a finding of questionable clinical significance. However, disease stabilization was observed for more than 3 months in 143 (46%), for more than 6 months in 67 (21%), more than 9 months in 33 (10%), and more than 12 months in 16 (5%). Disease stabilization was also associated with improved activity for 1-22 months in 79 (25%) of these patients, and improved pain for 1-22 months in 100 (32%). Disease stabilization appeared to be independent of tumor histology, location, or depth within the body, size, or minimum treatment temperature, but was somewhat more frequent after hyperthermia combination therapy. There is sufficient accumulative data to suggest that tumor stabilization after hyperthermia should not be dismissed as a placebo effect. This response variable well may be a unique and potentially important criterion of response to localized hyperthermia therapy.