title: Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neo-adjuvant chemotherapy followed by liver surgery.
abstract: BACKGROUND
  The purpose of the study was to characterize histological response to chemotherapy of hepatic colorectal metastases (HCRM), evaluate efficacy of different chemotherapies on histological response, and determine whether tumor regression grading (TRG) of HCRM predicts clinical outcome.
  
  
  METHODS
  TRG was evaluated on 525 HCRM surgically resected from 181 patients, 112 pretreated with chemotherapy. Disease-free survival (DFS) and overall survival (OS) were correlated to TRG.
  
  
  RESULTS
  Tumor regression was characterized by fibrosis overgrowing on tumor cells, decreased necrosis, and tumor glands (if present) at the periphery of HCRM. With irinotecan/5-fluorouracil (5-FU), major (MjHR), partial (PHR), and no (NHR) histological tumor regression were observed in 17%, 13%, and 70% of patients, respectively. With oxaliplatin/5-FU, MjHR, PHR, and NHR were observed in 37%, 45%, and 18% of patients, respectively. Five patients, treated with oxaliplatin, had complete response in all their metastases. MjHR was associated with an improved 3-year DFS compared with PHR or NHR. MjHR and PHR were associated with an improved 5-year OS compared with NHR.
  
  
  CONCLUSIONS
  Histological tumor regression of HCRM to chemotherapy corresponds to fibrosis overgrowth and not to increase of necrosis. TRG should be considered when evaluating efficacy of chemotherapy for HCRM. Histological tumor regression was most common among oxaliplatin-treated patients and associated with better clinical outcome.
authors.affiliation: Unit of Gastrointestinal and Liver Pathology, University Hospital, Geneva, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Rubbia-Brandt
authors.forename: E
authors.initials: E
authors.lastname: Giostra
authors.forename: C
authors.initials: C
authors.lastname: Brezault
authors.forename: A D
authors.initials: AD
authors.lastname: Roth
authors.forename: A
authors.initials: A
authors.lastname: Andres
authors.forename: V
authors.initials: V
authors.lastname: Audard
authors.forename: P
authors.initials: P
authors.lastname: Sartoretti
authors.forename: B
authors.initials: B
authors.lastname: Dousset
authors.forename: P E
authors.initials: PE
authors.lastname: Majno
authors.forename: O
authors.initials: O
authors.lastname: Soubrane
authors.forename: S
authors.initials: S
authors.lastname: Chaussade
authors.forename: G
authors.initials: G
authors.lastname: Mentha
authors.forename: B
authors.initials: B
authors.lastname: Terris
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 / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005355:Fibrosis / Q000209:etiology; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin