title: 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 degrees 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 + heat. Sixty received 24 Gy and 68 tumours received 27 Gy, respectively. Size was < or = 4 cm in 81 and > 4 cm in 47 tumours. Overall the 2-year actuarial local tumour control was 37%. Univariate analysis showed prognostic influence of hyperthermia (rad alone 28% versus rad + heat 46%, p = 0.008) and radiation dose (24 Gy 25% versus 27 Gy 56%, p = 0.02), but not of tumour size (small 42% versus large 29%, p = 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 = 0.02), tumour size (odds ratio: 0.91 (0.85-0.99), p = 0.05) and radiation dose (odds ratio: 1.17 (1.01-1.36), p = 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.
authors.affiliation: Danish Cancer Society, Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Overgaard
authors.forename: D
authors.initials: D
authors.lastname: Gonzalez Gonzalez
authors.forename: M C
authors.initials: MC
authors.lastname: Hulshof
authors.forename: G
authors.initials: G
authors.lastname: Arcangeli
authors.forename: O
authors.initials: O
authors.lastname: Dahl
authors.forename: O
authors.initials: O
authors.lastname: Mella
authors.forename: S M
authors.initials: SM
authors.lastname: Bentzen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced / Q000009:adverse effects / Q000379:methods; D008297:Male; D008545:Melanoma / Q000532:radiotherapy* / Q000556:secondary / Q000628:therapy*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy; D011879:Radiotherapy Dosage; D011882:Radiotherapy, High-Energy; D012878:Skin Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000628:therapy*; D015996:Survival Rate; D013997:Time Factors