title: Hyperthermic isolated limb perfusion in locally advanced limb soft tissue sarcoma: A 24-year single-centre experience.
abstract: BACKGROUND
  Hyperthermic isolated limb perfusion (HILP) is a locoregional treatment aimed at avoiding amputation in patients with advanced extremity soft tissue sarcomas (STS). Over the last 25 years, HILP procedure has been implemented to maximise its therapeutic ratio.
  
  
  METHODS
  A retrospective analysis including 117 patients who underwent HILP from 1989 to 2013 was performed. Three different drug schedules were applied: 1) doxorubicin (n = 47), 2) high dose (3-4 mg) tumour necrosis factor-alpha (TNF-α) plus doxorubicin (n = 30), 3) low dose (1 mg) TNF-α plus melphalan (L-PAM) (n = 40). Tumour response was evaluated by MRI or CT and surgical specimens. Toxicity and local progression-free survival (LPFS) were also evaluated.
  
  
  RESULTS
  In total 92 (78.6%) patients had primary, 25 (21.4%) had recurrent and 17 (14.5%) had metastatic disease. The subjects in the three groups were homogeneous for clinical-pathological features. Pathological response was complete in 55 patients (47%), partial in 35 (29.9%), regardless of drug schedule (p = 0.501) and tumour presentation (p = 0.094). Wieberdink III-V toxicity was registered in 19.1%, 20% and 2.5% of patients, respectively (p < 0.051). Twenty-eight patients (23.9%) received adjuvant radiotherapy with no relevant toxicity. Five-year LPFS was 81.6% and 74.2% in patients with primary or recurrent disease, respectively (p = 0.652). After a median follow-up of 36.5 months, the limb sparing rate was 77.8%.
  
  
  CONCLUSIONS
  HILP performed with different drugs was equally active, either in primary, recurrent or metastatic STS, providing effective limb sparing and durable local control. Low dose TNF-α plus L-PAM had the most favourable toxicity profile. Adjuvant radiotherapy was not associated with relevant toxicity.
authors.affiliation: a Melanoma and Sarcoma Unit, Veneto Institute of Oncology , Padua .
authors.forename: Marco
authors.initials: M
authors.lastname: Rastrelli
authors.affiliation: a Melanoma and Sarcoma Unit, Veneto Institute of Oncology , Padua .
authors.forename: Luca Giovanni
authors.initials: LG
authors.lastname: Campana
authors.affiliation: b Melanoma and Oesophageal Cancer Unit, Veneto Institute of Oncology , Padua , and.
authors.forename: Sara
authors.initials: S
authors.lastname: Valpione
authors.affiliation: c Department of Surgery , Oncology, and Gastroenterology, University of Padua , Padua , Italy.
authors.forename: Saveria
authors.initials: S
authors.lastname: Tropea
authors.affiliation: c Department of Surgery , Oncology, and Gastroenterology, University of Padua , Padua , Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Zanon
authors.affiliation: a Melanoma and Sarcoma Unit, Veneto Institute of Oncology , Padua .|c Department of Surgery , Oncology, and Gastroenterology, University of Padua , Padua , Italy.
authors.forename: Carlo Riccardo
authors.initials: CR
authors.lastname: Rossi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D010478:Chemotherapy, Cancer, Regional Perfusion; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D005121:Extremities; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D008297:Male; D008558:Melphalan / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D012509:Sarcoma / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D047368:Tumor Burden / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D014409:Tumor Necrosis Factor-alpha; D004317:Doxorubicin; D008558:Melphalan
keywords: Hyperthermia; melphalan; perfusion; sarcoma; tumour necrosis factor