PREOPERATIVE RADIO-CHEMO-THERMOTHERAPY IN LOCALLY ADVANCED RECTAL-CANCER - A PHASE-II STUDY

Background: Recent studies show that preoperative radio-chemotherapy c an increase resectability and local control of locally advanced rectal carcinomas. Additional regional hyperthermia might increase remission rates and tumor response. We therefore tested regional hyperthermia t ogether with radio-chemotherapy in a phase-II study on locally advance d rectal carcinomas. Patients and Methods: Thirty-seven patients with primary advanced stage uT3/T4 rectal carcinomas were treated with preo perative radio-chemo-thermo-therapy. The initial tumor depth was deter mined using endosonography, CT, and MRI. Radiotherapy was carried out in prone position (on a belly board) using standard techniques, with 5 x 1.8 Gy per week up to 45 Gy at the reference point. 5-Fluorouracil (300 to 500 mg/m(2)) was administered with low doses of leucovorin (50 mg) on days 1 to 5 and 22 to 28. The patients were treated with regio nal hyperthermia each week prior to radiotherapy and simultaneously wi th chemotherapy, using the Sigma 60 ring from the BSD-2000 system. Tem perature/position curves and temperature/time curves were recorded in endocavitary (endorectal) catheters in tumor contact and as well in bl adder and vagina. Following endosonographic restaging, the operation w as carried out 4 to 6 weeks after the end of preoperative therapy and adjuvant chemotherapy continued in four cycles. In cases where tumors were non-resectable, a boost up to 64 Gy was aimed. Results: Thirty-on e of the 37 patients (84%) with primary carcinoma proved locally RO-re sectable. In addition we had 1 R1-resection (3%) and 5 non-resectable tumors (13%). Among the resected tumors, 53% experienced a reduction o f depth infiltration from the initial endosonographic stage during pre operative therapy. The actuarial survival rate after 4 years is 65% (f ree of progression 57%). The actuarial 4-year survival rate was partic ularly favorable for the group of responders. Overall, the preoperativ e multimodal therapy was well tolerated, and premature termination was only necessary in 1 case (3%). Grade III/IV toxicities in the intesti ne and skin were reduced as far as possible by field blockings and coo ling of the perineal region. They occurred only in 5/37 patients (13%) at the intestine and in 6/37 patients (16%) at the skin. The thermal data were subjected to a statistical analysis. The quality of temperat ure distribution (T-90, cum min T-90 greater than or equal to 40.5 deg rees C) depends on the power level and relative power density. The res ponse (reduction of tumor size or depth infiltration) correlated signi ficantly with quality parameters of the temperature distributions. Thi s dependency is found as a trend for progression-free survival, too. C onclusions: Preoperative radio-chemo-thermo-therapy proved to be pract ical and effective, with encouraging remission rates and excellent loc al control rates. For this reason, a phase-III study to test regional hyperthermia has been initiated. At the same time, certain technical i mprovements are still under development for regional hyperthermia.