title: Prognostic factors after resection of colorectal liver metastases following preoperative second-line chemotherapy: Impact of RAS mutations.
abstract: BACKGROUND
  After resection of colorectal liver metastases (CLM), RAS mutations are associated with modest survival benefit and second-line chemotherapy confers limited hope for cure.
  
  
  OBJECTIVE
  To evaluate the impact of RAS mutation after second-line chemotherapy for patients undergoing potentially curative liver resection for CLM.
  
  
  METHODS
  Among 1357 patients operated for CLM between January 2005 and November 2014, patients with known RAS mutational status were identified. Outcomes after second-line chemotherapy were analyzed by RAS status.
  
  
  RESULTS
  Among 635 patients undergoing resection of CLM, 46 received second-line chemotherapy before resection, including 14 patients (30%) with RAS mutations. Patients who received second-line chemotherapy had significantly larger and greater number of liver metastases and were more likely to undergo major hepatectomy. Median overall (OS) and recurrence free survival (RFS) were significantly worse among patients requiring second-line chemotherapy (OS: 44.4 vs. 61.1 months, p = 0.021; RFS: 7.3 vs. 12.0 months, p = 0.001). Among patients undergoing liver resection after second-line chemotherapy, RAS mutations were associated with worse median OS and RFS (OS: 35.2 vs. 60.7 months, p = 0.038; RFS: 3.6 vs. 8.3 months, p = 0.015). RAS mutation was the only independent factor associated with OS and RFS. All patients with RAS mutations recurred within 18 months. Among patients with RAS wild-type tumors, the receipt of second-line chemotherapy did not affect OS (p = 0.493).
  
  
  CONCLUSIONS
  Among patients undergoing resection of CLM after second-line chemotherapy, RAS mutational status is an independent predictor of survival and outweighs other factors to select patients for liver resection.
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, USA.
authors.forename: G
authors.initials: G
authors.lastname: Passot
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, USA.
authors.forename: Y S
authors.initials: YS
authors.lastname: Chun
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Kopetz
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Overman
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, USA.
authors.forename: C
authors.initials: C
authors.lastname: Conrad
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Aloia
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, USA. Electronic address: jvauthey@mdanderson.org.
authors.forename: J-N
authors.initials: JN
authors.lastname: Vauthey
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006498:Hepatectomy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics* / Q000556:secondary / Q000628:therapy; D008297:Male; D059146:Metastasectomy; D008875:Middle Aged; D009154:Mutation; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology*; D011300:Preoperative Care; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D018631:ras Proteins
keywords: Chemotherapy; Colorectal; Liver; Metastases; RAS