title: Complications of combined radiotherapy and isolated limb perfusion with tumor necrosis factor alpha +/- interferon gamma and melphalan in patients with irresectable soft tissue tumors.
abstract: BACKGROUND
  Isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF alpha) +/-interferon gamma (IFN gamma) and melphalan in patients with primarily irresectable soft tissue sarcoma is promising in terms of tumor regression and limb salvage. However, the feasibility of radiotherapy in combination with this treatment modality has not been established.
  
  
  METHODS
  Fifteen patients with irresectable soft tissue tumors of the limb underwent ILP with TNF alpha, +/-IFN gamma, and melphalan. Three groups could be distinguished with respect to the role of radiotherapy. In nine patients, the residual tumor could be resected after ILP, and this was followed by radiotherapy with a total dose of 50-70 Gy (2 Gy/day). In one patient with aggressive fibromatosis, ILP was followed by radiotherapy without tumor resection (Group I). In two patients who underwent ILP for recurrent sarcoma, the primary tumor had been treated before by resection and radiotherapy (60 Gy) (Group II). In three patients whose tumors remained irresectable after ILP, radiotherapy was applied later in the course of disease for local palliation (Group III).
  
  
  RESULTS
  In Group I, healing of the resection wound was markedly delayed in four patients, with soft tissue necrosis and infection necessitating amputation in two of them. Following completion of radiotherapy, persistent lymphoceles were encountered in two patients. Radiotherapy-induced fibrosis was encountered in five patients, resulting in a mild limb malfunction in two. Three-patients developed mild edema during radiotherapy. Tumor-associated neuropathy was aggravated by ILP in three patients causing severely disabling motor deficits and limb contractures in two of them. In Group II, ILP did not cause any local problem in the heavily irradiated areas. In Group III, pre-existing limb edema was increased after a total palliative dose of 20 Gy in one patient. Another patient, who had been re-operated for arterial thrombosis immediately after ILP, developed occlusion of the brachial artery 4 months after completion of palliative radiotherapy (36 Gy in 6 Gy fractions).
  
  
  CONCLUSIONS
  In patients with irresectable soft tissue tumors, multimodality treatment using ILP with TNF alpha +/- IFN gamma and melphalan, tumor resection, and postoperative high-dose radiotherapy is associated with a considerable risk of tissue necrosis and impaired healing. This risk should be weighed against a possible benefit from radiotherapy in local tumor control.
authors.affiliation: Department of Surgery, The Netherlands Cancer Institute (Antoni van Leeuwenhoek ziekenhuis), Amsterdam, The Netherlands.
authors.forename: B C
authors.initials: BC
authors.lastname: Vrouenraets
authors.forename: R B
authors.initials: RB
authors.lastname: Keus
authors.forename: O E
authors.initials: OE
authors.lastname: Nieweg
authors.forename: B B
authors.initials: BB
authors.lastname: Kroon
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001132:Arm; D010478:Chemotherapy, Cancer, Regional Perfusion; D003131:Combined Modality Therapy / Q000009:adverse effects; D004487:Edema / Q000209:etiology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage*; D007866:Leg; D008080:Liposarcoma / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy; D008297:Male; D008558:Melphalan / Q000008:administration & dosage*; D008875:Middle Aged; D009336:Necrosis; D011832:Radiation Injuries / Q000209:etiology; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D012306:Risk; D012509:Sarcoma / Q000532:radiotherapy* / Q000601:surgery / Q000628:therapy*; D012867:Skin / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000532:radiotherapy* / Q000601:surgery / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D008558:Melphalan