title: Hyperthermic isolated limb perfusion in locally advanced soft tissue sarcoma and progressive desmoid-type fibromatosis with TNF 1 mg and melphalan (T1-M HILP) is safe and efficient.
abstract: BACKGROUND
  In a prior randomized phase II trial comparing hyperthermic isolated limb perfusion (HILP) with four different doses of tumor necrosis factor alpha (TNF-alpha), no dose effect was detected for response, but systemic toxicity was far lower with low-dose TNF-alpha. The objective of the present study was to confirm these data on a larger sample size of locally advanced or recurrent extremity soft tissue sarcomas with low-dose TNF-alpha.
  
  
  METHODS
  We assessed a prospective database comprising 100 HILP (38-40 degrees C) with melphalan (10 mg/L) and TNF-alpha (1 mg). The remnant tumor was resected 2 months later.
  
  
  RESULTS
  Among 52 recurrences, 18 were in a previously irradiated field. Stages according to the American Joint Committee on Cancer classification were II (19 patients), III (78 patients), and IV (3 patients). The site/size were: 30 patients/57 mm and 70 patients/86 mm for the upper and lower limbs, respectively. Tumor grades (FNCLCC) were 1 (23 patients), 2 (34 patients), and 3 (43 patients). Fifty-one patients had received systemic chemotherapy before HILP. Responses on magnetic resonance imaging were 30% complete, 49% partial, 9% no change, and 12% progression. No mortality or systemic toxicity occurred. Local toxicity (Wieberdink) attained grade 2 (16 patients), 3 (5 patients), and 4 (1 patient). Limbs were able to be saved in 87% patients. Three-year overall survival and the local recurrence rate were 89% and 18%, respectively. Age, sex, tumor size, recurrence, uni- or multifocality, grade, preoperative chemotherapy, and a previously irradiated field were not predictive of response or local toxicity.
  
  
  CONCLUSIONS
  We confirm that 1 mg of TNF-alpha is as effective as the standard dose and results in no systemic toxicity.
authors.affiliation: Department of Surgery, Institut Gustave Roussy, Villejuif Cedex, France. sylvie.bonvalot@igr.fr
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bonvalot
authors.forename: Françoise
authors.initials: F
authors.lastname: Rimareix
authors.forename: Sylvain
authors.initials: S
authors.lastname: Causeret
authors.forename: Cécile
authors.initials: C
authors.lastname: Le Péchoux
authors.forename: Bérénice
authors.initials: B
authors.lastname: Boulet
authors.forename: Philippe
authors.initials: P
authors.lastname: Terrier
authors.forename: Axel
authors.initials: A
authors.lastname: Le Cesne
authors.forename: Jane
authors.initials: J
authors.lastname: Muret
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D010478:Chemotherapy, Cancer, Regional Perfusion; D004359:Drug Therapy, Combination; D005121:Extremities / Q000473:pathology*; D005260:Female; D018222:Desmoid Tumors / Q000473:pathology / Q000628:therapy*; D005500:Follow-Up Studies; D006801:Humans; D006979:Hyperthermia, Induced; D008297:Male; D008558:Melphalan / Q000008:administration & dosage*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012509:Sarcoma / Q000473:pathology / Q000628:therapy*; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D014409:Tumor Necrosis Factor-alpha; D008558:Melphalan