Combined treatment of inoperable carcinomas of the uterine cervix with radiotherapy and regional hyperthermia. Results of a phase II trial

Abstract

Aim: The disappointing results for inoperable, advanced tumors of the uterine cervix after conventional radiotherapy alone necessitates improving of radiation therapy. Simultaneous chemotherapy or altered radiation fractionation, such as accelerated regimen, increase acute toxicity and treatment is often difficult to deliver in the planned manner. The purpose of this phase II study was to investigate the toxicity and effectiveness of a combined approach with radiotherapy and regional hyperthermia.

Patients and methods: From January 1994 to October 1995 18 patients with advanced carcinomas of the uterine cervix were treated in combination with radiotherapy and hyperthermia. The patients were treated with 6 to 20 MV photons delivered by a linear accelerator in a 4-field-box technique to a total dose of 50.4 Gy in 28 fractions. In the first and fourth week 2 regional hyperthermia treatments were each applied with the Sigma-60 applicator from a BSD-2000 unit. After this a boost to the primary tumor was given with high-dose-rate iridium-192 brachytherapy by an afterloading technique with 4 x 5 Gy at point A to a total of 20 Gy and for the involved parametrium anterioposterior-posterioanterior to 9 Gy in 5 fractions.

Results: The acute toxicity was low and similar to an external radiotherapy alone treatment. No Grade III/IV acute toxicity was found. The median age was 47 years (range 34 to 67 years). In 16 of 18 patients a rapid tumor regression was observed during combined thermo-radiotherapy, which allowed the use of intracavitary high-dose-rate brachytherapy in these cases. Complete and partial remission were observed in 13 and 4 cases, respectively. One patient did not respond to the treatment. The median follow-up was 24 months (range 17 to 36 months). The local tumor control rate was 48% at 2 years. Median T20, T50 and T90 values were 41.7 degrees C (range 40.3 to 43.2 degrees C), 41.1 degrees C (range 39.2 to 42.5 degrees C) and 39.9 degrees C (range 37.7 to 41.9 degrees C), respectively. Cumulative minutes of T90 > 40 degrees C (Cum40T90) and cumulative minutes, which were isoeffective to 43 degrees C, were calculated (CEM43T90, CEM43T50, CEM43T20). CEM43T90 was found to be a significant parameter in terms of local tumor control for the 4 hyperthermia treatments (p = 0.019).

Conclusions: This treatment modality has proved to be feasible and well tolerable. The rapid tumor shrinkage in the combined approach of radiotherapy with hyperthermia before beginning brachytherapy seems to be a good prerequisite for improving of the disappointing results in cure of advanced cancer of the uterine cervix.