title: Limb salvage by neoadjuvant isolated perfusion with TNFalpha and melphalan for non-resectable soft tissue sarcoma of the extremities.
abstract: OBJECTIVE
  Patients with non-resectable soft tissue sarcomas of the extremities do not live longer if they are treated by amputation or disarticulation. In order to avoid major amputations, we tested isolated limb perfusion (ILP) with tumour necrosis factor alpha (TNF)+melphalan+/-interferon-gamma (IFN) as a pre-operative, neoadjuvant limb salvage treatment.
  
  
  METHODS
  Twenty-two patients were included (six men and 16 women; three upper limb and 19 lower limb tumours). The AJCC stage was IIA in four patients, III in seven and IV in 11. Thirteen cases were recurrent or progressive after previous therapy; five tumours had a diameter >/=20 cm, and four were multiple or regionally metastatic. There were six malignant fibrous histiocytomas, five liposarcomas, four malignant peripheral nerve sheath tumours, three rhabdomyosarcomas, two leiomyosarcomas, one recurrent extraskeletal osteosarcoma and one angiosarcoma.
  
  
  RESULTS
  Twenty-four ILPs were performed in the 22 patients, and 18 (82%) experienced an objective response: this was complete in four (18%) and partial in 14 (64%). Three patients had a minimal or no response and the tumour progressed in one case. All patients had fever for 24 hours but only one developed a reversible grade 3 distributive shock syndrome with no sequelae. There was no grade 4 toxicity. Seventeen patients (77%) underwent limb-sparing resection of the tumour remnants after a median time of 3.4 months: 10 resections were intracompartmental and seven extracompartmental. Surgery included flaps or skin grafts in five patients, arterial replacement in two and knee arthrodesis in one. Adjuvant chemotherapy was given to eight patients and radiotherapy to six. In one patient amputation was necessary after a second ILP. Secondary amputations were performed for recurrence in two patients, resulting in an overall limb salvage rate of 19/22 (86%). After a median follow-up of 18.7 months, 10 recurrences were recorded: seven were both local and systemic and three were only local. The median disease free and overall survival times have been >12.5 and 18.7 months respectively: this is similar to the outcome after primary amputations for similar cases.
  
  
  CONCLUSIONS
  ILP with TNF and chemotherapy is an efficient limb sparing neoadjuvant therapy for a priori non-resectable limb soft tissue sarcomas.
authors.affiliation: Multidisciplinary Oncology Centre, and Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. Ferdy.Lejeune@chuv.hospvd.ch
authors.forename: F J
authors.initials: FJ
authors.lastname: Lejeune
authors.forename: N
authors.initials: N
authors.lastname: Pujol
authors.forename: D
authors.initials: D
authors.lastname: Liénard
authors.forename: F
authors.initials: F
authors.lastname: Mosimann
authors.forename: W
authors.initials: W
authors.lastname: Raffoul
authors.forename: A
authors.initials: A
authors.lastname: Genton
authors.forename: L
authors.initials: L
authors.lastname: Guillou
authors.forename: M
authors.initials: M
authors.lastname: Landry
authors.forename: P G
authors.initials: PG
authors.lastname: Chassot
authors.forename: R
authors.initials: R
authors.lastname: Chiolero
authors.forename: A
authors.initials: A
authors.lastname: Bischof-Delaloye
authors.forename: S
authors.initials: S
authors.lastname: Leyvraz
authors.forename: R O
authors.initials: RO
authors.lastname: Mirimanoff
authors.forename: D
authors.initials: D
authors.lastname: Bejkos
authors.forename: P F
authors.initials: PF
authors.lastname: Leyvraz
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant; D010478:Chemotherapy, Cancer, Regional Perfusion; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007371:Interferon-gamma / Q000008:administration & dosage / Q000009:adverse effects; D007866:Leg / Q000601:surgery*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000601:surgery; D018714:Radiotherapy, Adjuvant; D016879:Salvage Therapy; D012509:Sarcoma / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery*; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D014409:Tumor Necrosis Factor-alpha; D004317:Doxorubicin; D007371:Interferon-gamma; D008558:Melphalan; D007069:Ifosfamide