A PHASE-I II STUDY TO EVALUATE RADIATION-THERAPY AND HYPERTHERMIA FORDEEP-SEATED TUMORS - A REPORT OF RTOG-89-08/

The purpose of this paper is to evaluate the safety and efficacy of de ep hyperthermia in conjunction with radiation therapy. This study empl oyed 'second generation' electromagnetic devices which were fell to be better able to confine heating and spare normal tissue than the devic es evaluated in a previous study (RTOG 84-01). Sixty six patients at s ix institutions were enrolled on a prospective Phase I/II study. Eligi ble deep seated tumours were treated with a combination of external hy perthermia and radiation therapy. Radiation consisted of 1.7-2 Gy per fraction, 4-5 fractions per week, to > 20 Gy (previously irradiated le sions) or > 50 Gy (no previous radiation). Deep hyperthermia was deliv ered with electromagnetic devices: BSD 2000 for 92% of cases, Thermotr on for 5% of cases, other low frequency electromagnetic for 4% of case s. Hyperthermia was delivered less than or equal to twice weekly. Over all complete and partial response rates were 34% and 16% respectively. Response was not correlated with maximum tumour temperature or diseas e site. There was, however, a strong association with radiation dose: 54% CR with greater than or equal to 45 Gy versus 7% with < 45 Gy (p < 0.0001). The achieved temperatures were less than ideal. Although the average maximum tumor temperature was 41.8 degrees C (range 35.7 degr ees C-46.7 degrees C), the minimum tumour temperatures were low. The a verage minimum tumour temperature was 38.5 degrees C and was never > 4 1.8 degrees C. Treatment was well tolerated with no fatalities. There were four acute grade 3 or 4 toxicities (6% of patients). Patient disc omfort resulted in interruption or discontinuation of sessions in 30% of the sessions. In 12 cases (18% of patients) the planned course of h yperthermia was discontinued due to acute discomfort. The devices used in this study were better tolerated than the devices used in the prev ious Phase I/II deep hyperthermia trial (RTOG 84-01) with less patient discomfort and no problems with severe systemic cardiovascular stress . In the previous study 68% of the hyperthermia courses were premature ly terminated primarily due to patient discomfort and toxicity; in the present study 18% were prematurely terminated. However, as indicated by the low minimum tumour temperature, fundamental problems with achie ving acceptable temperature distributions remain.