title: Pathologic response to preoperative chemotherapy in colorectal liver metastases: fibrosis, not necrosis, predicts outcome.
abstract: BACKGROUND
  Pathologic response to preoperative chemotherapy for colorectal liver metastases (CLM) is associated with survival after hepatectomy. Histologically, dominant response patterns include fibrosis, necrosis and/or acellular mucin, but some of these changes can appear without previous chemotherapy and their individual correlation with outcome is unknown.
  
  
  METHODS
  Pathology slides from patients who underwent CLM resection (irrespective of preoperative chemotherapy status) were rereviewed by a blinded pathologist. Pathologic response was recorded as the summation of percentage necrosis, fibrosis and acellular mucin. Associations between pathologic response, its components, preoperative chemotherapy, and survival were analyzed.
  
  
  RESULTS
  Pathology slides were rereviewed in 366 patients undergoing CLM resection from 2003 to 2007. Preoperative chemotherapy was administered in 249 (68 %) patients, who, when compared to no preoperative chemotherapy patients, had higher rates of overall pathologic response (57 vs. 46 %, P < .01), fibrosis (21 vs. 12 %, P < .01) and acellular mucin (6 vs. 3 %, P = .05) but similar rates of necrosis (30 vs. 31 %, P = .30). In patients receiving preoperative chemotherapy, overall pathologic response ≥ 75 % (5 year, 83 vs. 47 %, P < .01) and fibrosis ≥ 40 % (5 year, 87 vs. 51 %, P < .01) independently correlated with disease-specific survival after hepatectomy. Preoperative hepatic artery infusion chemotherapy (P = .04) and bevacizumab (P = .05) were marginally associated with overall pathologic response and fibrosis, respectively.
  
  
  CONCLUSIONS
  Fibrosis is the predominant chemotherapy-related pathologic alteration driving the association of treatment response with survival after CLM resection. Necrosis in CLM is not related to chemotherapy or outcome.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: George A
authors.initials: GA
authors.lastname: Poultsides
authors.forename: Fei
authors.initials: F
authors.lastname: Bao
authors.forename: Elliot L
authors.initials: EL
authors.lastname: Servais
authors.forename: Tina
authors.initials: T
authors.lastname: Hernandez-Boussard
authors.forename: Ronald P
authors.initials: RP
authors.lastname: DeMatteo
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Allen
authors.forename: Yuman
authors.initials: Y
authors.lastname: Fong
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Kemeny
authors.forename: Leonard B
authors.initials: LB
authors.lastname: Saltz
authors.forename: David S
authors.initials: DS
authors.lastname: Klimstra
authors.forename: William R
authors.initials: WR
authors.lastname: Jarnagin
authors.forename: Jinru
authors.initials: J
authors.lastname: Shia
authors.forename: Michael I
authors.initials: MI
authors.lastname: D'Angelica
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D005355:Fibrosis; D006498:Hepatectomy; D006801:Humans; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000556:secondary / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009077:Mucins; D015999:Multivariate Analysis; D009336:Necrosis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011300:Preoperative Care; D011379:Prognosis; D012189:Retrospective Studies; D016037:Single-Blind Method
chemical_list: D009077:Mucins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D002166:Camptothecin