title: Adjuvant chemotherapy for resected colorectal cancer metastases: Literature review and meta-analysis.
abstract: Surgical resection is the only option of cure for patients with metastatic colorectal cancer (CRC). However, the risk of recurrence within 18 mo after metastasectomy is around 75% and the liver is the most frequent site of relapse. The current international guidelines recommend an adjuvant therapy after surgical resection of CRC metastases despite the lower level of evidence (based on the quality of studies in this setting). However, there is still no standard treatment and the effective role of an adjuvant therapy remains controversial. The aim of this review is to report the state-of-art of systemic chemotherapy and regional chemotherapy with hepatic arterial infusion in the management of patients after resection of metastases from CRC, with a literature review and meta-analysis of the relevant randomized controlled trials.
authors.affiliation: Giovanni Brandi, Maria Abbondanza Pantaleo, Guido Biasco, Department of Experimental, Diagnostic and Specialty Medicine, Sant'Orsola-Malpighi Hospital and "G. Prodi" Interdepartmental Center for Cancer Research, Bologna University, 40138 Bologna, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Brandi
authors.affiliation: Giovanni Brandi, Maria Abbondanza Pantaleo, Guido Biasco, Department of Experimental, Diagnostic and Specialty Medicine, Sant'Orsola-Malpighi Hospital and "G. Prodi" Interdepartmental Center for Cancer Research, Bologna University, 40138 Bologna, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: De Lorenzo
authors.affiliation: Giovanni Brandi, Maria Abbondanza Pantaleo, Guido Biasco, Department of Experimental, Diagnostic and Specialty Medicine, Sant'Orsola-Malpighi Hospital and "G. Prodi" Interdepartmental Center for Cancer Research, Bologna University, 40138 Bologna, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Nannini
authors.affiliation: Giovanni Brandi, Maria Abbondanza Pantaleo, Guido Biasco, Department of Experimental, Diagnostic and Specialty Medicine, Sant'Orsola-Malpighi Hospital and "G. Prodi" Interdepartmental Center for Cancer Research, Bologna University, 40138 Bologna, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Curti
authors.affiliation: Giovanni Brandi, Maria Abbondanza Pantaleo, Guido Biasco, Department of Experimental, Diagnostic and Specialty Medicine, Sant'Orsola-Malpighi Hospital and "G. Prodi" Interdepartmental Center for Cancer Research, Bologna University, 40138 Bologna, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Ottone
authors.affiliation: Giovanni Brandi, Maria Abbondanza Pantaleo, Guido Biasco, Department of Experimental, Diagnostic and Specialty Medicine, Sant'Orsola-Malpighi Hospital and "G. Prodi" Interdepartmental Center for Cancer Research, Bologna University, 40138 Bologna, Italy.
authors.forename: Filippo Gustavo
authors.initials: FG
authors.lastname: Dall'Olio
authors.affiliation: Giovanni Brandi, Maria Abbondanza Pantaleo, Guido Biasco, Department of Experimental, Diagnostic and Specialty Medicine, Sant'Orsola-Malpighi Hospital and "G. Prodi" Interdepartmental Center for Cancer Research, Bologna University, 40138 Bologna, Italy.
authors.forename: Maria Aurelia
authors.initials: MA
authors.lastname: Barbera
authors.affiliation: Giovanni Brandi, Maria Abbondanza Pantaleo, Guido Biasco, Department of Experimental, Diagnostic and Specialty Medicine, Sant'Orsola-Malpighi Hospital and "G. Prodi" Interdepartmental Center for Cancer Research, Bologna University, 40138 Bologna, Italy.
authors.forename: Maria Abbondanza
authors.initials: MA
authors.lastname: Pantaleo
authors.affiliation: Giovanni Brandi, Maria Abbondanza Pantaleo, Guido Biasco, Department of Experimental, Diagnostic and Specialty Medicine, Sant'Orsola-Malpighi Hospital and "G. Prodi" Interdepartmental Center for Cancer Research, Bologna University, 40138 Bologna, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Biasco
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology*; D006498:Hepatectomy / Q000009:adverse effects / Q000401:mortality; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000401:mortality / Q000556:secondary* / Q000628:therapy*; D059146:Metastasectomy / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents
keywords: Adjuvant chemotherapy; Adjuvant hepatic artery infusion; Colorectal cancer; Liver metastases; Metastasectomy
references.citation: J Clin Oncol. 1997 Mar;15(3):938-46
references.pmid: 9060531
references.citation: Oncologist. 2013;18(9):1004-12
references.pmid: 23881988
references.citation: Ann Surg. 2015 Sep;262(3):476-85; discussion 483-5
references.pmid: 26258316
references.citation: Br J Surg. 1990 Nov;77(11):1241-6
references.pmid: 2253003
references.citation: J Clin Oncol. 2009 Jul 1;27(19):3117-25
references.pmid: 19451425
references.citation: Lancet Oncol. 2013 Nov;14(12):1208-15
references.pmid: 24120480
references.citation: J Clin Oncol. 2007 Oct 10;25(29):4575-80
references.pmid: 17925551
references.citation: J Clin Oncol. 2007 Sep 20;25(27):4224-30
references.pmid: 17548839
references.citation: Ann Surg. 2012 Mar;255(3):405-14
references.pmid: 22330038
references.citation: J Surg Oncol. 2008 May 1;97(6):503-7
references.pmid: 18425789
references.citation: J Surg Oncol. 2014 Aug;110(2):182-96
references.pmid: 24760444
references.citation: Ann Surg. 1997 Jan;225(1):51-60; discussion 60-2
references.pmid: 8998120
references.citation: Hepatogastroenterology. 2015 Mar-Apr;62(138):303-8
references.pmid: 25916054
references.citation: Cancer Chemother Pharmacol. 2015 Jun;75(6):1281-8
references.pmid: 25929347
references.citation: Ann Surg. 2008 Jan;247(1):125-35
references.pmid: 18156932
references.citation: Lancet Oncol. 2012 Dec;13(12):1225-33
references.pmid: 23168362
references.citation: J Clin Oncol. 2005 Dec 20;23(36):9441-2
references.pmid: 16361649
references.citation: Ann Surg. 2005 May;241(5):715-22, discussion 722-4
references.pmid: 15849507
references.citation: J Hepatobiliary Pancreat Surg. 2004;11(2):79-83
references.pmid: 15127268
references.citation: J Gastrointest Surg. 2006 Jan;10(1):6-11
references.pmid: 16368485
references.citation: Langenbecks Arch Surg. 2012 Oct;397(7):1069-77
references.pmid: 22711237
references.citation: Ann Surg. 2013 Jun;257(6):1079-88
references.pmid: 23426338
references.citation: Oncology. 2013;84(1):14-21
references.pmid: 23076023
references.citation: Int J Colorectal Dis. 2010 Oct;25(10):1243-9
references.pmid: 20574727
references.citation: Lancet Oncol. 2014 Sep;15(10):1065-75
references.pmid: 25088940
references.citation: J Clin Oncol. 2010 Feb 10;28(5):853-8
references.pmid: 20048179
references.citation: Br J Surg. 2003 Nov;90(11):1436-40
references.pmid: 14598428
references.citation: Ann Surg. 2002 Jun;235(6):863-71
references.pmid: 12035044
references.citation: Liver Int. 2009 Jan;29(1):89-102
references.pmid: 18673436
references.citation: Ann Oncol. 2014 Sep;25 Suppl 3:iii1-9
references.pmid: 25190710
references.citation: J Clin Oncol. 2011 Mar 1;29(7):884-9
references.pmid: 21189384
references.citation: N Engl J Med. 2005 Feb 17;352(7):734-5
references.pmid: 15716576
references.citation: J Am Coll Surg. 1999 Sep;189(3):291-9
references.pmid: 10472930
references.citation: Ann Surg Oncol. 2015;22(6):1933-42
references.pmid: 25564160
references.citation: J Clin Oncol. 2009 Feb 10;27(5):663-71
references.pmid: 19114683
references.citation: Ann Surg. 2002 Jun;235(6):759-66
references.pmid: 12035031
references.citation: J Clin Oncol. 2009 Jul 1;27(19):3109-16
references.pmid: 19451431
references.citation: J Clin Oncol. 2007 May 1;25(13):1670-6
references.pmid: 17470860
references.citation: Clin Colorectal Cancer. 2013 Sep;12(3):188-94
references.pmid: 23773458
references.citation: Cochrane Database Syst Rev. 2012;6:CD006317
references.pmid: 22696357
references.citation: J Clin Oncol. 2008 Apr 20;26(12):2006-12
references.pmid: 18421053
references.citation: Ann Oncol. 2008 Apr;19(4):734-8
references.pmid: 18272912
references.citation: World J Gastroenterol. 2014 May 28;20(20):6133-45
references.pmid: 24876735
references.citation: Lancet. 2008 Mar 22;371(9617):1007-16
references.pmid: 18358928
references.citation: J Gastrointest Surg. 2007 Jul;11(7):860-8
references.pmid: 17492335
references.citation: N Engl J Med. 2015 Jan 15;372(3):291-2
references.pmid: 25587960
references.citation: Arch Surg. 2008 Dec;143(12):1204-12
references.pmid: 19075173
references.citation: BMJ. 2003 Sep 6;327(7414):557-60
references.pmid: 12958120
references.citation: Nature. 2013 Sep 19;501(7467):338-45
references.pmid: 24048066
references.citation: N Engl J Med. 2005 Jun 30;352(26):2696-704
references.pmid: 15987918
references.citation: J Surg Oncol. 2014 Nov;110(6):734-8
references.pmid: 24965163
references.citation: Cancer Treat Rev. 2006 May;32(3):214-28
references.pmid: 16546323
references.citation: Ann Oncol. 2009 Dec;20(12):1964-70
references.pmid: 19567451
references.citation: J Clin Oncol. 2007 Jun 1;25(16):2198-204
references.pmid: 17470851
references.citation: Ann Oncol. 2014 Sep;25(9):1743-9
references.pmid: 24942277
references.citation: J Clin Oncol. 1991 Jul;9(7):1105-12
references.pmid: 2045852
references.citation: Oncology. 2011;81(3-4):175-83
references.pmid: 22057187
references.citation: Nature. 2013 Sep 19;501(7467):355-64
references.pmid: 24048068
references.citation: J Clin Oncol. 2011 Apr 10;29(11):1465-71
references.pmid: 21383294
references.citation: Arch Surg. 2005 Feb;140(2):183-9
references.pmid: 15724001
references.citation: J Clin Oncol. 2006 May 1;24(13):2065-72
references.pmid: 16648507
references.citation: Ann Oncol. 2013 Oct;24 Suppl 6:vi64-72
references.pmid: 24078664
references.citation: Ann Surg Oncol. 2012 Mar;19(3):834-41
references.pmid: 21879262
references.citation: Gan To Kagaku Ryoho. 1999 Oct;26(12):1698-701
references.pmid: 10560374
references.citation: J Clin Oncol. 2009 Feb 10;27(5):672-80
references.pmid: 19114685
references.citation: J Clin Oncol. 2006 Nov 1;24(31):4976-82
references.pmid: 17075115
references.citation: Surg Clin North Am. 2002 Oct;82(5):1075-90, x-xi
references.pmid: 12507210
references.citation: J Surg Oncol. 2009 Dec 15;100(8):713-8
references.pmid: 19771561
references.citation: Ann Surg. 2013 Jan;257(1):114-20
references.pmid: 23235397
references.citation: N Engl J Med. 2013 Sep 12;369(11):1023-34
references.pmid: 24024839
references.citation: Surg Today. 2015 Dec;45(12):1527-34
references.pmid: 25563588
references.citation: CA Cancer J Clin. 2015 Jan-Feb;65(1):5-29
references.pmid: 25559415
references.citation: Ann Surg Oncol. 2003 Nov;10(9):1059-69
references.pmid: 14597445
references.citation: J Gastrointest Surg. 2006 Jan;10(1):86-94
references.pmid: 16368496
references.citation: Cancer. 1996 Apr 1;77(7):1254-62
references.pmid: 8608500
references.citation: J Clin Oncol. 2008 Oct 20;26(30):4906-11
references.pmid: 18794541
references.citation: BMC Cancer. 2010;10:545
references.pmid: 20937118
references.citation: J Clin Oncol. 2007 Aug 10;25(23):3456-61
references.pmid: 17687149
references.citation: Cancer Chemother Pharmacol. 2015 Jul;76(1):133-9
references.pmid: 25994854
references.citation: Surg Oncol Clin N Am. 2007 Jul;16(3):525-36, viii
references.pmid: 17606192
references.citation: J Surg Oncol. 2010 Dec 15;102(8):988-95
references.pmid: 21166003
references.citation: Lancet Oncol. 2014 May;15(6):601-11
references.pmid: 24717919
references.citation: N Engl J Med. 1999 Dec 30;341(27):2039-48
references.pmid: 10615075
references.citation: World J Surg Oncol. 2014;12:127
references.pmid: 24767422
references.citation: HPB (Oxford). 2010 May;12(4):227-38
references.pmid: 20590892
references.citation: Lancet. 2000 Mar 25;355(9209):1041-7
references.pmid: 10744089
references.citation: Ann Surg. 2011 Dec;254(6):851-6
references.pmid: 21975318
references.citation: Ann Thorac Surg. 2005 Jan;79(1):278-82; discussion 283
references.pmid: 15620957
references.citation: J Clin Oncol. 2004 Apr 1;22(7):1209-14
references.pmid: 15051767
references.citation: Ann Surg. 2007 Oct;246(4):559-65; discussion 565-7
references.pmid: 17893492
references.citation: Cancer Treat Rev. 2004 Dec;30(8):711-3
references.pmid: 15541581
references.citation: Ann Thorac Surg. 2007 Jul;84(1):324-38
references.pmid: 17588454
references.citation: J Clin Oncol. 2009 Feb 20;27(6):872-7
references.pmid: 19124803
references.citation: JAMA. 2012 Apr 4;307(13):1383-93
references.pmid: 22474202
references.citation: Br J Cancer. 2004 Mar 22;90(6):1190-7
references.pmid: 15026800
references.citation: N Engl J Med. 2009 Apr 2;360(14):1408-17
references.pmid: 19339720
references.citation: Ann Surg. 2004 Dec;240(6):1037-49; discussion 1049-51
references.pmid: 15570209
references.citation: Ann Surg. 2003 Dec;238(6):871-83; discussion 883-4
references.pmid: 14631224
references.citation: Br J Surg. 2004 Aug;91(8):1066-71
references.pmid: 15286972
references.citation: J Clin Oncol. 2007 Oct 20;25(30):4779-86
references.pmid: 17947725
references.citation: Ann Surg Oncol. 2011 Oct;18(10):2757-63
references.pmid: 21638093
references.citation: J Am Coll Surg. 1997 Dec;185(6):554-9
references.pmid: 9404879
references.citation: J Clin Oncol. 2014 Jul 20;32(21):2240-7
references.pmid: 24687833
references.citation: J Clin Oncol. 2000 Aug;18(16):2938-47
references.pmid: 10944126
references.citation: Eur J Cancer. 2014 Sep;50(13):2231-40
references.pmid: 24958736
references.citation: HPB (Oxford). 2015 Feb;17(2):176-84
references.pmid: 25041611
references.citation: Ann Surg. 1999 Sep;230(3):309-18; discussion 318-21
references.pmid: 10493478
references.citation: Jpn J Clin Oncol. 2009 Jun;39(6):406-9
references.pmid: 19389795
references.citation: Nat Rev Genet. 2012 Nov;13(11):795-806
references.pmid: 23044827
references.citation: J Clin Oncol. 2011 Jan 1;29(1):11-6
references.pmid: 20940184