title: Phase II multicenter clinical trial of pulmonary metastasectomy and isolated lung perfusion with melphalan in patients with resectable lung metastases.
abstract: BACKGROUND
  The 5-year overall survival rate of patients undergoing complete surgical resection of pulmonary metastases (PM) from colorectal cancer (CRC) and sarcoma remains low (20-50%). Local recurrence rate is high (48-66%). Isolated lung perfusion (ILuP) allows the delivery of high-dose locoregional chemotherapy with minimal systemic leakage to improve local control.
  
  
  METHODS
  From 2006 to 2011, 50 patients, 28 male, median age 57 years (15-76), with PM from CRC (n = 30) or sarcoma (n = 20) were included in a phase II clinical trial conducted in four cardiothoracic surgical centers. In total, 62 ILuP procedures were performed, 12 bilaterally, with 45 mg of melphalan at 37°C, followed by resection of all palpable PM. Survival was calculated according to the Kaplan-Meier method.
  
  
  RESULTS
  Operative mortality was 0%, and 90-day morbidity was mainly respiratory (grade 3: 42%, grade 4: 2%). After a median follow-up of 24 months (3-63 mo), 18 patients died, two without recurrence. Thirty patients had recurrent disease. Median time to local pulmonary progression was not reached. The 3-year overall survival and disease-free survival were 57% ± 9% and 36% ± 8%, respectively. Lung function data showed a decrease in forced expiratory volume in 1 second and diffusing capacity of the alveolocapillary membrane of 21.6% and 25.8% after 1 month, and 10.4% and 11.3% after 12 months, compared with preoperative values.
  
  
  CONCLUSIONS
  Compared with historical series of PM resection without ILuP, favorable results are obtained in terms of local control without long-term adverse effects. These data support the further investigation of ILuP as additional treatment in patients with resectable PM from CRC or sarcoma.
authors.affiliation: *Department of Thoracic and Vascular Surgery, Antwerp University Hospital, Edegem, Belgium; †Department of Cardiac Surgery, Antwerp University Hospital, Edegem, Belgium; ‡Department of Medical Oncology, Antwerp University Hospital, Edegem, Belgium; §Center for Oncological Research, University of Antwerp, Wilrijk, Belgium; ‖Department of Thoracic Surgery, Leiden University Medical Center, Leiden, the Netherlands; ¶Department of Clinical Oncology, Leiden University Medical Center, Leiden, the Netherlands; #Department of Pulmonary Medicine, St. Antonius Hospital, Nieuwegein, the Netherlands; **Department of Thoracic Surgery, Amsterdam Medical Center, Amsterdam, the Netherlands; ††Department of Thoracic Surgery, St. Antonius Hospital, Nieuwegein, the Netherlands; and ‡‡Department of Thoracic Surgery, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Willem A
authors.initials: WA
authors.lastname: den Hengst
authors.forename: Jeroen M H
authors.initials: JM
authors.lastname: Hendriks
authors.forename: Bram
authors.initials: B
authors.lastname: Balduyck
authors.forename: Inez
authors.initials: I
authors.lastname: Rodrigus
authors.forename: Jan B
authors.initials: JB
authors.lastname: Vermorken
authors.forename: Filip
authors.initials: F
authors.lastname: Lardon
authors.forename: Michel I M
authors.initials: MI
authors.lastname: Versteegh
authors.forename: Jerry
authors.initials: J
authors.lastname: Braun
authors.forename: Hans
authors.initials: H
authors.lastname: Gelderblom
authors.forename: Franz M N H
authors.initials: FM
authors.lastname: Schramel
authors.forename: Wim-Jan
authors.initials: WJ
authors.lastname: Van Boven
authors.forename: Bart P
authors.initials: BP
authors.lastname: Van Putte
authors.forename: Özcan
authors.initials: Ö
authors.lastname: Birim
authors.forename: Alexander P W M
authors.initials: AP
authors.lastname: Maat
authors.forename: Paul E Y
authors.initials: PE
authors.lastname: Van Schil
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D001859:Bone Neoplasms / Q000473:pathology; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods; D015179:Colorectal Neoplasms / Q000473:pathology; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary* / Q000601:surgery / Q000628:therapy*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage*; D059146:Metastasectomy / Q000379:methods; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D012516:Osteosarcoma / Q000473:pathology; D015996:Survival Rate; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan