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.
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.
Authors: N Wolmark; H Rockette; E Mamounas; J Jones; S Wieand; D L Wickerham; H D Bear; J N Atkins; N V Dimitrov; A G Glass; E R Fisher; B Fisher Journal: J Clin Oncol Date: 1999-11 Impact factor: 44.544
Authors: Greg Yothers; Michael J O'Connell; Carmen J Allegra; J Philip Kuebler; Linda H Colangelo; Nicholas J Petrelli; Norman Wolmark Journal: J Clin Oncol Date: 2011-08-22 Impact factor: 44.544
Authors: C G Moertel; T R Fleming; J S Macdonald; D G Haller; J A Laurie; P J Goodman; J S Ungerleider; W A Emerson; D C Tormey; J H Glick Journal: N Engl J Med Date: 1990-02-08 Impact factor: 91.245
Authors: Eddie K Abdalla; Jean-Nicolas Vauthey; Lee M Ellis; Vickie Ellis; Raphael Pollock; Kristine R Broglio; Kenneth Hess; Steven A Curley Journal: Ann Surg Date: 2004-06 Impact factor: 12.969
Authors: Raja R Narayan; Jennifer W Harris; Joanne F Chou; Mithat Gönen; Fei Bao; Jinru Shia; Peter J Allen; Vinod P Balachandran; Jeffrey A Drebin; William R Jarnagin; Nancy E Kemeny; T Peter Kingham; Michael I D'Angelica Journal: Ann Surg Oncol Date: 2019-10-15 Impact factor: 5.344
Authors: Jean-Nicolas Vauthey; Giuseppe Zimmitti; Scott E Kopetz; Junichi Shindoh; Su S Chen; Andreas Andreou; Steven A Curley; Thomas A Aloia; Dipen M Maru Journal: Ann Surg Date: 2013-10 Impact factor: 12.969
Authors: Amber L Simpson; David A Geller; Alan W Hemming; William R Jarnagin; Logan W Clements; Michael I D'Angelica; Prashanth Dumpuri; Mithat Gönen; Ivan Zendejas; Michael I Miga; James D Stefansic Journal: J Am Coll Surg Date: 2014-03-27 Impact factor: 6.113
Authors: Georgios Karagkounis; Michael S Torbenson; Hubert D Daniel; Nilofer S Azad; Luis A Diaz; Ross C Donehower; Kenzo Hirose; Nita Ahuja; Timothy M Pawlik; Michael A Choti Journal: Cancer Date: 2013-09-19 Impact factor: 6.860
Authors: Maximilian Jara; Jan Bednarsch; Maciej Malinowski; Johann Pratschke; Martin Stockmann Journal: Langenbecks Arch Surg Date: 2015-10-27 Impact factor: 3.445
Authors: Thomas Boerner; Constantinos Zambirinis; Johan Gagnière; Joanne F Chou; Mithat Gonen; Nancy E Kemeny; Andrea Cercek; Louise C Connell; Thomas P Kingham; Peter J Allen; Vinod P Balachandran; Jeffrey Drebin; William R Jarnagin; Michael I D'Angelica Journal: HPB (Oxford) Date: 2020-09-14 Impact factor: 3.647