Hyperthermia as an adjuvant to radiation therapy of recurrent or metastatic malignant melanoma. A multicentre randomized trial by the European Society for Hyperthermic Oncology

Abstract

The ESHO protocol 3-85 is a multicentre randomized trial investigating the value of hyperthermia as an adjuvant to radiotherapy in treatment of malignant melanoma. A total of 134 metastatic of recurrent malignant melanoma lesions in 70 patients were randomized to receive radiotherapy alone (3 fractions in 8 days) or each fraction followed by hyperthermia (aimed for 43 C for 60 min). Radiation was given with high voltage photons or electrons. Tumours were stratified according to institution and size (above or below 4 cm) and randomly assigned to a total radiation dose of either 24 or 27 Gy to be given with or without hyperthermia. The endpoint was persistent complete response in the treated area. A number of 128 tumours in 68 patients were evaluable, with an observation time between 3 and 72 months. Sixty-five tumours were randomized to radiation alone and 63 to radiation þ heat. Sixty received 24 Gy and 68 tumours received 27 Gy, respectively. Size was 4 cm in 81 and 44 cm in 47 tumours. Overall the 2-year actuarial local tumour control was 37%. Univariate analysis showed prognostic influence of hyperthermia (rad alone 28% vs. rad þ heat 46%, p ¼ 0.008) and radiation dose (24 Gy 25% vs. 27 Gy 56%, p ¼ 0.02), but not of tumour size (small 42% vs. large 29%, p ¼ 0.21). A Cox multivariate regression analysis showed the most important prognostic parameters to be: hyperthermia (odds ratio: 1.73 (1.07-2.78), p ¼ 0.02), tumour size (odds ratio: 0.91 (0.85-0.99), p ¼ 0.05) and radiation dose (odds ratio: 1.17 (1.01-1.36), p ¼ 0.05). Analysis of the heating quality showed a significant relationship between the extent of heating and local tumour response. Addition of heat did not significantly increase the acute or late radiation reactions. The overall 5-year survival rate of the patients was 19%, but 38% in patients if all known disease was controlled, compared to 8% in the patients with persistent active disease.

The effects of 41°C hyperthermia on the DNA repair protein, MRE11, correlate with radiosensitization in four human tumor cell lines

“…However, recent and ongoing clinical trails continue to support the conclusion that the radiosensitizing effects of hyperthermia can enhance the effectiveness of radiation therapy [2][3][4][5][6][7][8][9].…”

Conformal radiotherapy plus local hyperthermia in patients affected by locally advanced high risk prostate cancer: Preliminary results of a prospective phase II study

“…Randomized clinical trials have demonstrated the efficacy of CRT and LHT in many tumours [8][9][10]. In the Duke University experience, high risk patients with stage T3 or T4 prostate cancer were treated in a non-randomized study with CRT and LHT to a maximum dose of 70 Gy.…”

Glass-Ceramics: Fundamental Aspects Regarding the Interaction with Proteins

“…By adding radioactivable isotopes like yttrium, dysprosium, samarium, or rhenium, these materials can be used for in situ radiotherapy, while the addition of iron oxide makes them suitable for hyperthermia applications [11]. The simultaneous application of both radiotherapy and hyperthermia considerably enhances the therapeutic effects of these cancer treatment methods [12,13]. In both therapy cases, the aluminosilicate particles have to be injected locally or intravenously at the tumor site, and they are rapidly coated by components of circulation, such as blood plasma proteins.…”