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

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

doi:10.1097/SLA.0b013e31826b4dcc

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

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

Research output: Contribution to journal › Article › peer-review

63 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	642-650
Number of pages	9
Journal	Annals of surgery
Volume	256
Issue number	4
DOIs	https://doi.org/10.1097/SLA.0b013e31826b4dcc
State	Published - Oct 2012

Keywords

colorectal cancer
metachronous colorectal liver metastases
somatic gene mutations

ASJC Scopus subject areas

Surgery

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10.1097/SLA.0b013e31826b4dcc

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Andreou, A., Kopetz, S., Maru, D. M., Chen, S. S., Zimmitti, G., Brouquet, A., Shindoh, J., Curley, S. A., Garrett, C., Overman, M. J., Aloia, T. A., & Vauthey, J. N. (2012). 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. Annals of surgery, 256(4), 642-650. https://doi.org/10.1097/SLA.0b013e31826b4dcc

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; Kopetz, Scott ; Maru, Dipen M. et al.
In: Annals of surgery, Vol. 256, No. 4, 10.2012, p. 642-650.

Research output: Contribution to journal › Article › peer-review

Andreou, A, Kopetz, S , Maru, DM, Chen, SS, Zimmitti, G, Brouquet, A, Shindoh, J, Curley, SA, Garrett, C, Overman, MJ, Aloia, TA & Vauthey, JN 2012, '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', Annals of surgery, vol. 256, no. 4, pp. 642-650. https://doi.org/10.1097/SLA.0b013e31826b4dcc

@article{686efb6ec0d44f0387f72b89633f3ba3,

title = "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",

abstract = "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.",

keywords = "colorectal cancer, metachronous colorectal liver metastases, somatic gene mutations",

author = "Andreas Andreou and Scott Kopetz and Maru, {Dipen M.} and Chen, {Su S.} and Giuseppe Zimmitti and Antoine Brouquet and Junichi Shindoh and Curley, {Steven A.} and Christopher Garrett and Overman, {Michael J.} and Aloia, {Thomas A.} and Vauthey, {Jean Nicolas}",

year = "2012",

month = oct,

doi = "10.1097/SLA.0b013e31826b4dcc",

language = "English (US)",

volume = "256",

pages = "642--650",

journal = "Annals of surgery",

issn = "0003-4932",

publisher = "Lippincott Williams and Wilkins",

number = "4",

}

TY - JOUR

T1 - 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

AU - Andreou, Andreas

AU - Kopetz, Scott

AU - Maru, Dipen M.

AU - Chen, Su S.

AU - Zimmitti, Giuseppe

AU - Brouquet, Antoine

AU - Shindoh, Junichi

AU - Curley, Steven A.

AU - Garrett, Christopher

AU - Overman, Michael J.

AU - Aloia, Thomas A.

AU - Vauthey, Jean Nicolas

PY - 2012/10

Y1 - 2012/10

N2 - 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.

AB - 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.

KW - colorectal cancer

KW - metachronous colorectal liver metastases

KW - somatic gene mutations

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DO - 10.1097/SLA.0b013e31826b4dcc

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AN - SCOPUS:84866534339

SN - 0003-4932

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JO - Annals of surgery

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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

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