title: Progression while receiving preoperative chemotherapy should not be an absolute contraindication to liver resection for colorectal metastases.
abstract: OBJECTIVE
  Tumor progression while receiving neoadjuvant chemotherapy (PD) has been associated with poor outcome and is commonly considered a contraindication to liver resection (LR). This study aims to clarify in a large multicenter setting whether PD is always a contraindication to LR.
  
  
  METHODS
  Data from the LiverMetSurvey international registry were analyzed. Patients undergoing LR for colorectal metastases without extrahepatic disease after neoadjuvant chemotherapy between 1990 and 2009 were reviewed.
  
  
  RESULTS
  Among 2143 patients, PD occurred in 176 (8.2 %). Risk of progression was increased after 5-FU or irinotecan (22.7 % vs. 6.8 % after other regimens, p < 0.0001; 14.9 % vs. 7.2 %, p < 0.0001), while it was reduced after oxaliplatin (5.6 % vs. 12.0 %, p < 0.0001) and still diminished among patients receiving targeted therapies (2.6 %). PD was an independent prognostic factor of survival at multivariate analysis (35 % vs. 49 %, p = 0.0006). In the PD group, 3 independent prognostic factors were identified: carcinoembryonic antigen (CEA) ≥ 200 ng/mL (p = 0.003), >3 metastases (p = 0.028), and tumor diameter ≥ 5 0 mm (p = 0.002). A survival predictive model showed that patients without any risk factors had 5-year survival rates of 53.3 %; good survival results were still observed if metastases were >3 or ≥ 50 mm (29.9 and 19.1 %, respectively). On the contrary, survival was less than 10 % at 3 years in the presence of >1 prognostic factor or CEA of ≥ 200 ng/mL.
  
  
  CONCLUSIONS
  PD is a negative prognostic factor, but it is not an absolute contraindication to LR. Patients with PD could be scheduled for LR except for those with >3 metastases and ≥ 50 mm, or CEA ≥ 200 ng/mL in whom further chemotherapy is recommended.
authors.affiliation: Department of HPB and Digestive Surgery, Ospedale Mauriziano Umberto I, Turin, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Viganò
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Capussotti
authors.forename: Eduardo
authors.initials: E
authors.lastname: Barroso
authors.forename: Gennaro
authors.initials: G
authors.lastname: Nuzzo
authors.forename: Christophe
authors.initials: C
authors.lastname: Laurent
authors.forename: Jan N M
authors.initials: JN
authors.lastname: Ijzermans
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Gigot
authors.forename: Joan
authors.initials: J
authors.lastname: Figueras
authors.forename: Thomas
authors.initials: T
authors.lastname: Gruenberger
authors.forename: Darius F
authors.initials: DF
authors.lastname: Mirza
authors.forename: Dominique
authors.initials: D
authors.lastname: Elias
authors.forename: Graeme
authors.initials: G
authors.lastname: Poston
authors.forename: Christian
authors.initials: C
authors.lastname: Letoublon
authors.forename: Helena
authors.initials: H
authors.lastname: Isoniemi
authors.forename: Javier
authors.initials: J
authors.lastname: Herrera
authors.forename: Francisco Castro
authors.initials: FC
authors.lastname: Sousa
authors.forename: Fernando
authors.initials: F
authors.lastname: Pardo
authors.forename: Valerio
authors.initials: V
authors.lastname: Lucidi
authors.forename: Irinel
authors.initials: I
authors.lastname: Popescu
authors.forename: René
authors.initials: R
authors.lastname: Adam
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002272:Carcinoembryonic Antigen / Q000097:blood; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000097:blood / Q000473:pathology*; D000075202:Contraindications; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006498:Hepatectomy; D006801:Humans; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000556:secondary* / Q000601:surgery*; D008297:Male; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D047368:Tumor Burden
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D002272:Carcinoembryonic Antigen; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000077146:Irinotecan; D000068818:Cetuximab; D005472:Fluorouracil; D002166:Camptothecin