Strong synergy of heat and modulated electromagnetic field in tumor cell killing.

BACKGROUND AND PURPOSE: Hyperthermia is an emerging complementary method in radiooncology. Despite many positive studies and comprehensive reviews, the method is not widely accepted as a combination to radiotherapy. Modulated electrohyperthermia (mEHT; capacitive, electric field modulated, 13.56 MHz) has been used in clinical practice for almost 2 decades in Germany, Austria and Hungary. This in vivo study in nude mice xenograft tumors compares mEHT with "classic" radiative hyperthermia (radHT). MATERIAL AND METHODS: Nude mice were xenografted with HT29 human colorectal carcinoma cells. 28 mice in four groups with seven animals each and two tumors per animal (totally 56 tumors) were included in the present study: group 1 as untreated control; group 2 treated with radHT at 42 degrees C; group 3 treated with mEHT at identical 42 degrees C; group 4 treated with mEHT at 38 degrees C (by intensively cooling down the tumor). 24 h after treatment, animals were sacrificed and the tumor cross sections studied by precise morphological methods for the respective relative amount of "dead" tumor cells. RESULTS: The effect of mEHT established a double effect as a synergy between the purely thermal (temperature-dependent) and nonthermal (not directly temperature-dependent) effects. The solely thermal enhancement ratio (TER) of cell killing was shown to be 2.9. The field enhancement ratio (FER) at a constant temperature of 42 degrees C was measured as 3.2. Their complex application significantly increased the therapeutic enhancement to 9.4. CONCLUSION: mEHT had a remarkable cancer cell-killing effect in a nude mice xenograft model.

Involved-field radiotherapy is equally effective and less toxic compared with extended-field radiotherapy after four cycles of chemotherapy in patients with early-stage unfavorable Hodgkin's lymphoma: results of the HD8 trial of the German Hodgkin's Lymphoma Study Group.

PURPOSE: To investigate whether radiotherapy can be reduced without loss of efficacy from extended field (EF) to involved field (IF) after four cycles of chemotherapy. PATIENTS AND METHODS: Between 1993 and 1998, patients with newly diagnosed early-stage unfavorable HD were enrolled onto this multicenter study. Patients were randomly assigned to receive cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) + doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for two cycles followed by radiotherapy of 30 Gy EF + 10 Gy to bulky disease (arm A) or 30 Gy IF + 10 Gy to bulky disease (arm B). RESULTS: Of 1,204 patients randomly assigned to treatment, 1,064 patients were informative and eligible for the arm comparison (532 patients in arm A; 532 patients in arm B). The median observation time was 54 months. Five years after random assignment, the overall survival (OSran) for all eligible patients was 91% and freedom from treatment failure (FFTFran) was 83%. Survival rates at 5 years after start of radiotherapy revealed no differences for arms A and B, respectively, in terms of FFTF (85.8% and 84.2%) and OS at 5 years (90.8% and 92.4%). There also were no differences between arms A and B, respectively, in terms of complete remission (98.5% and 97.2%), progressive disease (0.8% and 1.9%), relapse (6.4% and 7.7%), death (8.1% and 6.4%), and secondary neoplasia (4.5% and 2.8%). In contrast, acute side effects including leukopenia, thrombocytopenia, nausea, gastrointestinal toxicity, and pharyngeal toxicity were more frequent in the EF arm. CONCLUSION: Radiotherapy volume size reduction from EF to IF after COPP + ABVD chemotherapy for two cycles produces similar results and less toxicity in patients with early-stage unfavorable HD.

Treatment of locoregional metastases of malignant melanomas with radiotherapy and intralesional beta-interferon injection.

Intralesional injection of beta-interferon can lead to remission of metastatic melanomas. Simultaneous radiotherapy may augment the effect of these injections. The effect of intralesional beta-interferon injections combined with radiotherapy was examined in patients with metastatic malignant melanoma. A total of 20 patients with inoperable, incapacitating and disfiguring malignant melanoma metastases were treated with simultaneous external beam radiotherapy (electrons and/or photons) and intralesional injection of beta-interferon. The total radiation dosage ranged from 40-50 Gy, fractionated as 1.8 Gy five times per week. beta-Interferon (Fiblaferon) 3-5 million units per injection was administered three times weekly until symptoms disappeared or until termination of therapy. One patient was treated with beta-interferon alone; the area harbouring the tumour had been previously irradiated. Five patients treated in this way showed partial remission after combined therapy and 12 showed complete remission, with permanent regression of metastases. The latter group included five patients with lengthy survival times, including one patient who has been free of symptoms for 7 years following treatment. Injected metastases showed complete regression in the patient who was treated exclusively with beta-interferon post-irradiation. In conclusion, combined treatment with radiotherapy and intratumoral injection of beta-interferon controlled local tumour growth in inoperable metastatic malignant melanomas.