title: Local Treatment of Unresectable Colorectal Liver Metastases: Results of a Randomized Phase II Trial.
abstract: Tumor ablation is often employed for unresectable colorectal liver metastases. However, no survival benefit has ever been demonstrated in prospective randomized studies. Here, we investigate the long-term benefits of such an aggressive approach.
  
  
  
  In this randomized phase II trial, 119 patients with unresectable colorectal liver metastases (n < 10 and no extrahepatic disease) received systemic treatment alone or systemic treatment plus aggressive local treatment by radiofrequency ablation ± resection. Previously, we reported that the primary end point (30-month overall survival [OS] > 38%) was met. We now report on long-term OS results. All statistical tests were two-sided. The analyses were according to intention to treat.
  
  
  
  At a median follow up of 9.7 years, 92 of 119 (77.3%) patients had died: 39 of 60 (65.0%) in the combined modality arm and 53 of 59 (89.8%) in the systemic treatment arm. Almost all patients died of progressive disease (35 patients in the combined modality arm, 49 patients in the systemic treatment arm). There was a statistically significant difference in OS in favor of the combined modality arm (hazard ratio [HR] = 0.58, 95% confidence interval [CI] = 0.38 to 0.88, P = .01). Three-, five-, and eight-year OS were 56.9% (95% CI = 43.3% to 68.5%), 43.1% (95% CI = 30.3% to 55.3%), 35.9% (95% CI = 23.8% to 48.2%), respectively, in the combined modality arm and 55.2% (95% CI = 41.6% to 66.9%), 30.3% (95% CI = 19.0% to 42.4%), 8.9% (95% CI = 3.3% to 18.1%), respectively, in the systemic treatment arm. Median OS was 45.6 months (95% CI = 30.3 to 67.8 months) in the combined modality arm vs 40.5 months (95% CI = 27.5 to 47.7 months) in the systemic treatment arm.
  
  
  
  This phase II trial is the first randomized study demonstrating that aggressive local treatment can prolong OS in patients with unresectable colorectal liver metastases.
authors.affiliation: Netherlands Cancer Institute, Antoni Van Leeuwenhoek Ziekenhuis, Amsterdam, The Netherlands.
authors.forename: Theo
authors.initials: T
authors.lastname: Ruers
authors.affiliation: Netherlands Cancer Institute, Antoni Van Leeuwenhoek Ziekenhuis, Amsterdam, The Netherlands.
authors.forename: Frits
authors.initials: F
authors.lastname: Van Coevorden
authors.affiliation: Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Cornelis J A
authors.initials: CJ
authors.lastname: Punt
authors.affiliation: Leeuwarden Medical Center, Leeuwarden, The Netherlands.
authors.forename: Jean-Pierre E N
authors.initials: JE
authors.lastname: Pierie
authors.affiliation: Universitair Medisch Centrum, Academisch Ziekenhuis, Utrecht, The Netherlands.
authors.forename: Inne
authors.initials: I
authors.lastname: Borel-Rinkes
authors.affiliation: Cancer Research UK and UCL Cancer Trials Centre and UCL Hospitals, London, United Kingdom.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Ledermann
authors.affiliation: Aintree University Hospital, Liverpool, United Kingdom.
authors.forename: Graeme
authors.initials: G
authors.lastname: Poston
authors.affiliation: Frankfurt University Hospital and Clinics, Frankfurt, Germany.
authors.forename: Wolf
authors.initials: W
authors.lastname: Bechstein
authors.affiliation: EORTC Headquarters, Data Management Unit, Brussels, Belgium.
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Lentz
authors.affiliation: EORTC Headquarters, Statistics Department, Brussels, Belgium.
authors.forename: Murielle
authors.initials: M
authors.lastname: Mauer
authors.affiliation: University Cancer Center, University Hospital Carl Gustav Carus, Dresden, Germany.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Folprecht
authors.affiliation: Digestive Oncology, University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: Van Cutsem
authors.affiliation: Institut Gustave Roussy, Villejuif, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Ducreux
authors.affiliation: Assistance Publique Hôpitaux de Paris, Boulogne-Billancourt, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Nordlinger
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D017115:Catheter Ablation / Q000379:methods; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery / Q000628:therapy*; D018572:Disease-Free Survival; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary* / Q000601:surgery / Q000628:therapy*; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil