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Feasibility and efficacy of external beam radiotherapy after hyperthermic isolated limb perfusion with TNF-alpha and melphalan for limb-saving treatment in locally advanced extremity soft-tissue sarcoma. 1998

A F Olieman, and E Pras, and R J van Ginkel, and W M Molenaar, and H Schraffordt Koops, and H J Hoekstra
Department of Surgical Oncology, Groningen University Hospital, The Netherlands.

OBJECTIVE Hyperthermic isolated limb perfusion (HILP) with tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and melphalan is associated with a dramatic antitumor effect in locally advanced extremity soft-tissue sarcomas (STS). The aim of this study was to demonstrate the feasibility and efficacy of adjuvant radiotherapy after HILP with TNF-alpha, IFN-gamma, and melphalan and delayed surgical resection. METHODS Between 1991 and 1995, 34 patients--16 males and 18 females, median age 50 (range 18-80) years--underwent HILP for locally advanced extremity STS. Resection of the residual tumor mass was performed in most patients after 6-8 weeks. Fifteen patients with histopathological viable tumor after resection received adjuvant 60-70 Gy external beam radiotherapy (EBRT) (44%, HILP + EBRT group). Nineteen patients received HILP without adjuvant EBRT (56%, HILP-only group). Five patients in the HILP-only group had also distant metastases (15%) and received HILP as a palliative treatment. Treatment morbidity, local recurrences, and regional and distant metastases were scored. RESULTS During a median follow-up of 34 months (range 8-54), limb salvage was achieved in 29 patients (85%): 14 patients after HILP + EBRT and 15 patients after HILP only. None of the patients from the HILP + EBRT group developed local recurrences; however, five patients from the HILP-only did (26%) (p < 0.05). Regional metastases were observed in one patient from the HILP + EBRT group (7%) and in two patients from the HILP-only group who were treated with curative intent (14%). Distant metastases occurred in four patients after HILP + EBRT (27%) and in four patients after HILP only with curative intent (29%). The mean morbidity (subjective, objective, medical management, and analytical evaluation) score in both groups was, respectively, 0.33 for skin and subcutaneous tissue and for muscle and soft tissue, 0.34 (HILP + EBRT group) and 0.33 (HILP-only group). CONCLUSIONS Adjuvant EBRT after HILP with TNF-alpha, IFN-gamma, and melphalan and delayed tumor resection of locally advanced extremity STS is feasible and may increase local tumor control without increasing treatment morbidity.

UI MeSH Term Description Entries
D006979 Hyperthermia, Induced Abnormally high temperature intentionally induced in living things regionally or whole body. It is most often induced by radiation (heat waves, infra-red), ultrasound, or drugs. Fever Therapy,Hyperthermia, Local,Hyperthermia, Therapeutic,Thermotherapy,Induced Hyperthermia,Therapeutic Hyperthermia,Therapy, Fever,Local Hyperthermia
D007371 Interferon-gamma The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES. Interferon Type II,Interferon, Immune,gamma-Interferon,Interferon, gamma,Type II Interferon,Immune Interferon,Interferon, Type II
D008297 Male Males
D008558 Melphalan An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - MELPHALAN, the racemic mixture - MERPHALAN, and the dextro isomer - MEDPHALAN; toxic to bone marrow, but little vesicant action; potential carcinogen. Medphalan,Merphalan,Phenylalanine Mustard,Sarcolysine,Sarkolysin,4-(Bis(2-chloroethyl)amino)phenylalanine,Alkeran,L-PAM,Mustard, Phenylalanine
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009364 Neoplasm Recurrence, Local The local recurrence of a neoplasm following treatment. It arises from microscopic cells of the original neoplasm that have escaped therapeutic intervention and later become clinically visible at the original site. Local Neoplasm Recurrence,Local Neoplasm Recurrences,Locoregional Neoplasm Recurrence,Neoplasm Recurrence, Locoregional,Neoplasm Recurrences, Local,Recurrence, Local Neoplasm,Recurrence, Locoregional Neoplasm,Recurrences, Local Neoplasm,Locoregional Neoplasm Recurrences,Neoplasm Recurrences, Locoregional,Recurrences, Locoregional Neoplasm
D010478 Chemotherapy, Cancer, Regional Perfusion Neoplasm drug therapy involving an extracorporeal circuit with temporary exclusion of the tumor-bearing area from the general circulation during which high concentrations of the drug are perfused to the isolated part. Cancer Chemotherapy, Regional Perfusion,Perfusion Cancer Chemotherapy, Regional,Regional Perfusion Antineoplastic Chemotherapy,Isolation Perfusion Cancer Chemotherapy,Regional Perfusion Cancer Chemotherapy
D003131 Combined Modality Therapy The treatment of a disease or condition by several different means simultaneously or sequentially. Chemoimmunotherapy, RADIOIMMUNOTHERAPY, chemoradiotherapy, cryochemotherapy, and SALVAGE THERAPY are seen most frequently, but their combinations with each other and surgery are also used. Multimodal Treatment,Therapy, Combined Modality,Combined Modality Therapies,Modality Therapies, Combined,Modality Therapy, Combined,Multimodal Treatments,Therapies, Combined Modality,Treatment, Multimodal,Treatments, Multimodal
D005121 Extremities The farthest or outermost projections of the body, such as the HAND and FOOT. Limbs,Extremity,Limb
D005240 Feasibility Studies Studies to determine the advantages or disadvantages, practicability, or capability of accomplishing a projected plan, study, or project. Feasibility Study,Studies, Feasibility,Study, Feasibility

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