title: Selective pulmonary artery perfusion with melphalan is equal to isolated lung perfusion but superior to intravenous melphalan for the treatment of sarcoma lung metastases in a rodent model.
abstract: OBJECTIVE
  Isolated lung perfusion (ILuP) and selective pulmonary artery perfusion (SPAP) are experimental surgical techniques to deliver high-dose chemotherapy selectively to the lung for the treatment of lung metastases. ILuP with melphalan (MN) has shown to be feasible in clinical studies but can only be used once because it is invasive. SPAP as an endovascular technique can be repeated several times, but no results have been reported so far. Pharmacokinetics and efficacy of SPAP with MN were studied in a rodent lung metastasis model and compared it with ILuP and intravenous (IV) therapy.
  
  
  METHODS
  Pharmacokinetics: forty-five Wag-Rij rats were randomized into three groups: IV 0.5 mg MN, ILuP 0.5 mg MN and SPAP 0.5 mg MN. Every treatment group was again randomized in three groups: 15 min treatment, 30 min treatment and 30 min treatment with 30 min reperfusion. Blood and tissue samples were taken for MN concentrations.
  
  
  RESULTS
  twenty-five Wag-Rij rats were randomized into five groups: control, sham thoracotomy, IV 0.5 mg MN, ILuP 0.5 mg MN and SPAP 0.5 mg MN. At day 0, bilateral lung metastases were induced, and treatment followed at day 7. At day 28, rats were sacrificed and pulmonary metastases counted. Survival: thirty Wag-Rij rats were randomized into five groups: control, sham ILuP, IV 0.5 mg MN, ILuP 0.5 mg MN, SPAP 0.5 mg MN. At day 0, left-sided lungmetastases were induced with treatment at day 7. Endpoints were death due to disease or survival up to 90 days.
  
  
  RESULTS
  Pharmacokinetics: SPAP and ILuP resulted in significantly higher left lung MN concentrations compared with IV (P = 0.05).
  
  
  RESULTS
  SPAP (30 ± 22 nodules) and ILuP (20 ± 9 nodules) resulted in significantly less nodules compared with IV (113 ± 17 nodules; P < 0.01). Survival: median survival of SPAP (74 ± 8 days) was equal to ILuP MN (71 ± 10 days) but significantly longer compared with IV (54 ± 7 days; P < 0.01 both).
  
  
  CONCLUSIONS
  SPAP with MN for the treatment of sarcoma lung metastases in rats is equally effective to ILuP but resulted in a significantly better survival compared with IV MN. As SPAP can be applied as a minimally invasive endovascular procedure, continued research with this technique is warranted.
authors.affiliation: Department of Thoracic and Vascular Surgery,  Antwerp University Hospital, Edegem,  Belgium.
authors.forename: Willem A
authors.initials: WA
authors.lastname: Den Hengst
authors.forename: Jeroen M H
authors.initials: JM
authors.lastname: Hendriks
authors.forename: Tom
authors.initials: T
authors.lastname: Van Hoof
authors.forename: Karel
authors.initials: K
authors.lastname: Heytens
authors.forename: Gunther
authors.initials: G
authors.lastname: Guetens
authors.forename: Gert
authors.initials: G
authors.lastname: de Boeck
authors.forename: Filip
authors.initials: F
authors.lastname: Lardon
authors.forename: Paul E Y
authors.initials: PE
authors.lastname: Van Schil
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods*; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D008558:Melphalan / Q000008:administration & dosage* / Q000493:pharmacokinetics; D009368:Neoplasm Transplantation; D011651:Pulmonary Artery; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D012208:Rhabdomyosarcoma / Q000188:drug therapy* / Q000556:secondary; D016019:Survival Analysis
chemical_list: D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan