title: 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.
abstract: 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.
authors.affiliation: Department of Surgical Oncology, Groningen University Hospital, The Netherlands.
authors.forename: A F
authors.initials: AF
authors.lastname: Olieman
authors.forename: E
authors.initials: E
authors.lastname: Pras
authors.forename: R J
authors.initials: RJ
authors.lastname: van Ginkel
authors.forename: W M
authors.initials: WM
authors.lastname: Molenaar
authors.forename: H
authors.initials: H
authors.lastname: Schraffordt Koops
authors.forename: H J
authors.initials: HJ
authors.lastname: Hoekstra
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000671:Amputation, Surgical; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D010478:Chemotherapy, Cancer, Regional Perfusion; D003131:Combined Modality Therapy; D005121:Extremities; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D007371:Interferon-gamma / Q000008:administration & dosage; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D018714:Radiotherapy, Adjuvant; D012509:Sarcoma / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage
chemical_list: D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D008558:Melphalan