Phase III study of interstitial thermoradiotherapy compared with interstitial radiotherapy alone in the treatment of recurrent or persistent human tumors. A prospectively controlled randomized study by the Radiation Therapy Group.

Purpose: The objectives of this randomized trial were to determine if interstitial thermoradiotherapy (ITRT) improves tumor regression/control in accessible lesions in comparison with interstitial radiotherapy (IRT) alone and to assess the skin and soft tissue complications with either modality.

Methods And Materials: From January 1986 to June 1992, 184 patients with persistent or recurrent tumors after previous radiotherapy and/or surgery, which were amenable to interstitial radiotherapy, were accessioned to a protocol developed by the Radiation Therapy Oncology Group (RTOG). One hundred seventy-three cases were analyzed (87 patients in the IRT group and 86 in the ITRT arm). The two arms were well balanced regarding stratification criteria. Most tumors were in the head and neck (40% in the IRT group and 46% in the ITRT group), and pelvis (42% and 43%, respectively). Eighty-four percent of patients in both arms had prior radiation therapy (> or = 40 Gy); 50% and 40%, respectively, had prior surgery, and 34% in each arm had prior chemotherapy. The dose of radiation therapy administered was dependent on the previous radiation dose and did not exceed a total cumulative dose of 100 Gy. Hyperthermia was delivered in one or two sessions, either before or before and after interstitial implant. The intended goal of the hyperthermia was to maintain a minimal tumor temperature of 42.5 degrees C for 30 to 60 min.

Results: There was no difference in any of the study end points between the two arms. Complete response (CR) was 53% and 55% in both arms. Two-year survival was 34% and 35%, respectively. Complete response rate for persistent lesions was 69% and 63% in the two treatment arms as compared with 40% and 48% for recurrent lesions. A set of minimal adequacy criteria for the delivery of hyperthermia was developed. When these criteria were applied, only one patient had an adequate hyperthermia session. Acute Grade 3 and 4 toxicities were 12% for IRT and 22 % for ITRT. Late Grade 3 and 4 toxicities were 15% for IRT and 20% for ITRT. The difference was not significant.

Conclusions: Interstitial hyperthermia, as applied in this randomized study, did not show any additional beneficial effects over interstitial radiotherapy alone. Delivery of hyperthermia remains a major obstacle (since only one patient met the basic minimum adequacy criteria as defined in this study). The benefit of hyperthermia in addition to radiation therapy still remains to be proven in properly randomized prospective clinical trials after substantial technical improvements in heat delivery and dosimetry are achieved.