title: Adjuvant radioimmunotherapy improves survival of rats after resection of colorectal liver metastases.
abstract: OBJECTIVE
  The aim of this study was to test the hypothesis that adjuvant radioimmunotherapy (RIT) prevents recurrent liver metastases and/or results in improved survival after tumorectomy in an experimental model.
  
  
  BACKGROUND
  Although partial hepatectomy can improve 5-year survival of patients with colorectal liver metastases up to 58%, recurrent tumor growth in the liver occurs frequently. Radioimmunotherapy using radiolabeled monoclonal antibodies directed against tumor-associated antigens is considered most suited for treating minimal residual disease and could therefore serve as an adjuvant after surgery.
  
  
  METHODS
  Liver metastases were induced in male Wag/Rij rats by a mini-laparotomy with intrahepatic injection of 0.3 × 106 CC531 tumor cells. The biodistribution of the radiolabeled monoclonal antibody MG1, directed against a 80-kDa cell surface antigen on CC531 tumors, in this model was determined at 1, 3, and 7 days after intravenous administration. The therapeutic efficacy of 177Lu-MG1 was compared with that of a sham antibody (UPC10), labeled with the same activity dose of Lu-177, and saline only. Radioimmunotherapy was administered either at the day of the tumorectomy (day 14 after tumor cell inoculation) or 7 days later. Primary endpoint was survival.
  
  
  RESULTS
  Radiolabeled MG1 preferentially accumulated in tumor lesions in the liver reaching a maximum 3 days postinjection (8.7 ± 0.6% injected dose per gram). Both the administration of 177Lu-MG1 and 177Lu-UPC10 resulted in a transient decrease in body weight. No other signs of clinical discomfort were registered. The survival curves of the group that received 177Lu-UPC10 and the group that received saline only did not differ (P=0.886). Administration of RIT immediately after surgery improved survival compared to administration of the control antibody (hazard ratio [HR], 1.54; P = 0.051), which was even more pronounced when survival was adjusted for the weight of the resected tumor (HR, 1.71; P = 0.027). A therapeutic efficacy of delayed treatment seemed likely (HR, 2.34; P = 0.055). Survival after early administration did not differ from delayed administration (HR, 1.16; P = 0.763).
  
  
  CONCLUSIONS
  This study provides proof of principle that RIT can be an effective adjuvant treatment modality after surgical treatment of colorectal liver metastases.
authors.affiliation: Division of Abdominal and Oncological Surgery, Department of Surgery, Radboud University Nijmegen Medical Centre, Geert Grooteplein Zuid 10, Nijmegen, the Netherlands. g.dejong@chir.umcn.nl
authors.forename: Gabie M
authors.initials: GM
authors.lastname: de Jong
authors.forename: Thijs
authors.initials: T
authors.lastname: Hendriks
authors.forename: Annemarie
authors.initials: A
authors.lastname: Eek
authors.forename: Wim J G
authors.initials: WJ
authors.lastname: Oyen
authors.forename: Iris D
authors.initials: ID
authors.lastname: Nagtegaal
authors.forename: Robert P
authors.initials: RP
authors.lastname: Bleichrodt
authors.forename: Otto C
authors.initials: OC
authors.lastname: Boerman
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology*; D006498:Hepatectomy; D007205:Indium Radioisotopes / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary* / Q000601:surgery; D008187:Lutetium / Q000627:therapeutic use; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D016499:Radioimmunotherapy; D011868:Radioisotopes / Q000627:therapeutic use; D018714:Radiotherapy, Adjuvant; D051381:Rats; D011919:Rats, Inbred Strains; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D011868:Radioisotopes; D008187:Lutetium