Clinical thermoradiotherapy: the influence of some prognostic parameters on recurrence-free survival

Thirty-one patients with loco-regional advanced tumors accessible for local thermoradiotherapy were treated at the Institute of Oncology in Ljubljana, between 1989-1993. There were six primary inoperable and 25 recurrent or residual tumors after previous radiotherapy. In 13 patients treatment consisted of combined interstitial water hyperthermia and brachyradiotherapy, in 5 patients combination of interstitial hyperthermia and percutaneous radiotherapy was used, and percutaneous microwave hyperthermia with percutaneous irradiation was employed in remaining 13 patients. Complete response (CR) was achieved in 17/31 (55%) of all treated patients. Among various tumoral and therapeutic parameters tested significant influence on complete response rate was found for tumor volume (p = 0.047), minimum intratumoral temperature (p = 0.004), time interval between hyperthermia and radiotherapy (p = 0.02), and fraction-size of immediate radiotherapy (p = 0.002). More than one hyperthermia treatment and total tumor dose of irradiation > 45 Gy did not significantly improve local control rate in our patients. For all 31 patients treated with thermoradiotherapy 3-year recurrence-free survival (RFS) of 41% was achieved. For the group of 9 patients in whom the interval between hyperthermia and irradiation exceeded 1 hour, RFS of 18% compared to 53% for 22 patients treated with "synchronous" thermoradiotherapy was achieved, however the difference between the groups was not significant (log rank p = 0.17). In 25 patients in whom minimum intratumoral temperature (Tmin50) exceeded 42.5 degrees C significant difference in RFS between the subgroups of 19 patients treated synchronously and 6 patients in whom time interval between the two modalities was longer than 1 hour, i.e. 65% vs. 25% respectively, was found (log rank p = 0.048). However, most favorable RFS of 81% was achieved in the subgroup of 15 patients in whom good hyperthermia treatment (Tmin50 > or = 42.5 degrees C) was followed by an immediate irradiation using fraction size > or = 3 Gy (p = 0.015). Treatment related toxicity was acceptable and did not correlate with response rate. Our conclusion is that thermoradiotherapy is more effective when somewhat larger fraction-size of radiotherapy than conventional, i.e. 3-5 Gy, are employed in synchronous combination of both treatment modalities.