title: Timing of multimodality therapy for resectable synchronous colorectal liver metastases: a retrospective multi-institutional analysis.
abstract: The optimal timing of chemotherapy relative to resection of synchronous colorectal liver metastases (SCRLM) is not known. The objective of this retrospective multi-institutional study was to assess the influence of chemotherapy administered before and after hepatic resection on long-term outcomes among patients with initially resectable SCRLM treated from 1995 to 2005. Clinicopathologic data, treatments, and long-term outcomes from patients with initially resectable SCRLM who underwent partial hepatectomy at three hepatobiliary centers were reviewed. Four hundred ninety-nine consecutive patients underwent resection; 297 (59.5%) and 264 (52.9%) were treated with chemotherapy before and after resection. Chemotherapy strategies included pre-hepatectomy alone (n = 148, 24.7%), post-hepatectomy alone (n = 115, 23.0%), perioperative (n = 149, 29.0%), and no chemotherapy (n = 87, 17.4%). Male gender (p = 0.0029, HR = 1.41 [1.12-1.77]), node-positive primary tumor (p = 0.0046, HR = 1.40 [1.11-1.77]), four or more SCRLM (p = 0.0005, HR = 1.65 [1.24-2.18]), and post-hepatectomy chemotherapy treatment for 6 months or longer (p = 0.039, HR = 0.75 [0.57-0.99]) were associated with recurrence-free survival after discovery of SCRLM. Carcinoembryonic antigen >200 ng/ml (p = 0.0003, HR = 2.33 [1.48-3.69]), extrahepatic metastatic disease (p = 0.0025, HR = 2.34 [1.35-4.05]), four or more SCRLM (p = 0.033, HR = 1.43 [1.03-2.00]), and post-hepatectomy chemotherapy treatment for 2 months or longer (p < 0.0001, HR = 0.59 [0.45-0.76]) were associated with overall survival. Pre-hepatectomy chemotherapy was not associated with recurrence-free or overall survival. Patients treated with perioperative chemotherapy had similar outcomes as patients treated with post-hepatectomy chemotherapy only. We conclude that chemotherapy administered after but not before resection of SCRLM was associated with improved recurrence-free and overall survival. However, prospective randomized trials are needed to determine the optimal timing of chemotherapy.
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA. reddy005@mc.duke.edu
authors.forename: Srinevas K
authors.initials: SK
authors.lastname: Reddy
authors.forename: Daria
authors.initials: D
authors.lastname: Zorzi
authors.forename: Ying Wei
authors.initials: YW
authors.lastname: Lum
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Barbas
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Pawlik
authors.forename: Dario
authors.initials: D
authors.lastname: Ribero
authors.forename: Eddie K
authors.initials: EK
authors.lastname: Abdalla
authors.forename: Michael A
authors.initials: MA
authors.lastname: Choti
authors.forename: Clinton
authors.initials: C
authors.lastname: Kemp
authors.forename: Jean-Nicolas
authors.initials: JN
authors.lastname: Vauthey
authors.forename: Michael A
authors.initials: MA
authors.lastname: Morse
authors.forename: Rebekah R
authors.initials: RR
authors.lastname: White
authors.forename: Bryan M
authors.initials: BM
authors.lastname: Clary
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000473:pathology*; D003131:Combined Modality Therapy; D005260:Female; D006498:Hepatectomy / Q000401:mortality*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D012189:Retrospective Studies; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents