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Adjuvant Chemotherapy With FOLFOX for Primary Colorectal Cancer Is Associated With Increased Somatic Gene Mutations and Inferior Survival in Patients Undergoing Hepatectomy for Metachronous Liver Metastases

Andreou, Andreas MD*; Kopetz, Scott MD; Maru, Dipen M. MD; Chen, Su S. MD§; Zimmitti, Giuseppe MD*; Brouquet, Antoine MD*; Shindoh, Junichi MD*; Curley, Steven A. MD*; Garrett, Christopher MD; Overman, Michael J. MD; Aloia, Thomas A. MD*; Vauthey, Jean-Nicolas MD*

doi: 10.1097/SLA.0b013e31826b4dcc
Papers of the 132nd ASA Annual Meeting

Objective: We hypothesized that metachronous colorectal liver metastases (CLM) have different biology after failure of oxaliplatin (FOLFOX) compared to 5-fluorouracil (5-FU) or no chemotherapy for adjuvant treatment of colorectal cancer (CRC).

Background: It is unclear whether patients treated with liver resection for metachronous CLM after adjuvant FOLFOX for CRC have worse outcomes than those who received 5-FU or no chemotherapy.

Methods: We identified 341 patients who underwent hepatectomy for metachronous CLM (disease-free interval ≥12 months, 1993–2010). Mass-spectroscopy genotyping for somatic gene mutations in CLM was performed in a subset of 129 patients.

Results: Adjuvant treatment for primary CRC was FOLFOX in 77 patients, 5-FU in 169 patients, and no chemotherapy in 95 patients. Node-positive primary was comparable between FOLFOX and 5-FU but lower in the no-chemotherapy group (P < 0.0001). Median metastasis size was smaller in the FOLFOX group (2.5 cm) than in the 5-FU (3.0 cm) or no-chemotherapy (3.5 cm) groups, (P = 0.008) although prehepatectomy chemotherapy utilization, metastases number, and carcinoembryonic antigen levels were similar. Disease-free survival (DFS) and overall survival (OS) rates after hepatectomy were worse in patients treated with adjuvant FOLFOX [DFS at 3 years: 14% vs 38% (5-FU) vs 45% (no-chemo), OS at 3 years: 58% vs 70% (5-FU) vs 84% (no-chemo)]. On multivariate analysis, adjuvant FOLFOX was associated with worse DFS (P < 0.0001) and OS (P < 0.0001). Mutation analysis revealed ≥1 mutations in 57% of patients (27/47) after FOLFOX, 29% (12/41) after 5-FU, and 32% (13/41) after no chemotherapy (P = 0.011).

Conclusions: Adjuvant FOLFOX for primary CRC is associated with a high rate of somatic mutations in liver metastases and inferior outcomes after hepatectomy for metachronous CLM.

Outcomes and frequency of somatic gene mutations were analyzed by the adjuvant chemotherapy type for colorectal cancer (CRC) in patients treated with hepatectomy for metachronous colorectal liver metastases (CLM). Adjuvant FOLFOX for CRC is associated with a high rate of somatic mutations in metachronous CLM and inferior outcomes after hepatectomy.

*Departments of Surgical Oncology

Gastrointestinal Medical Oncology

Pathology

§Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX.

Reprints: Jean-Nicolas Vauthey, MD, Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX 77030. E-mail: jvauthey@mdanderson.org.

Disclosure: This research was supported in part by the National Institutes of Health through MD Anderson's Cancer Center Support Grant (CA016672). The authors declare no conflicts of interest.

© 2012 Lippincott Williams & Wilkins, Inc.