Clinical and molecular determinants of extrahepatic disease progression in patients with metastatic colorectal cancer with liver-limited metastases deemed initially unresectable.

extrahepatic disease progression liver-limited disease metastatic colorectal cancer

Journal

ESMO open
ISSN: 2059-7029
Titre abrégé: ESMO Open
Pays: England
ID NLM: 101690685

Informations de publication

Date de publication:
2019
Historique:
received: 19 01 2019
revised: 19 02 2019
accepted: 21 02 2019
entrez: 25 6 2019
pubmed: 25 6 2019
medline: 25 6 2019
Statut: epublish

Résumé

No tools to predict the probability of extrahepatic disease progression (ePD) of initially unresectable, liver-limited metastatic colorectal cancer (mCRC) are currently available. To estimate the likelihood to develop ePD and to identify clinical and molecular factors that could predict extrahepatic progression-free survival (ePFS), we conducted an observational, retrospective, multicentre cohort study. We retrospectively identified a cohort of 225 patients with initially unresectable liver-limited disease (LLD), treated from January 2004 to December 2017 with first-line doublets or triplet plus a biological agent at two Italian institutions. 173 (77%) patients experienced ePD which occurred within 1, 2 or 3 years from the diagnosis of mCRC in 15%, 49% and 66% of patients, respectively. Globally, 164 (73%) patients underwent a liver resection at some point of their disease history, and 54 (33%) of them underwent a subsequent locoregional treatment. Age > 70 years, locoregional nodal involvement at diagnosis of colorectal cancer and ≥4 liver metastases were significantly associated with higher risk of ePD while liver resections were associated with reduced risk of ePD. In the multivariable model, number of liver metastases (subdistribution HR, SHR 1.63, 95% CI 1.12 to 2.36; p = 0.01) and liver resections (SHR 0.43, 95% CI 0.29 to 0.63; p = 0.001) were still associated with ePD. Number of liver metastases < 4, no nodal involvement at diagnosis and liver resections were also associated with prolonged ePFS. The identified clinical factors could help physicians in personalising the intensity and aggressiveness of liver-directed treatments in patients with mCRC with initially unresectable LLD.

Sections du résumé

BACKGROUND BACKGROUND
No tools to predict the probability of extrahepatic disease progression (ePD) of initially unresectable, liver-limited metastatic colorectal cancer (mCRC) are currently available. To estimate the likelihood to develop ePD and to identify clinical and molecular factors that could predict extrahepatic progression-free survival (ePFS), we conducted an observational, retrospective, multicentre cohort study.
METHODS METHODS
We retrospectively identified a cohort of 225 patients with initially unresectable liver-limited disease (LLD), treated from January 2004 to December 2017 with first-line doublets or triplet plus a biological agent at two Italian institutions.
RESULTS RESULTS
173 (77%) patients experienced ePD which occurred within 1, 2 or 3 years from the diagnosis of mCRC in 15%, 49% and 66% of patients, respectively. Globally, 164 (73%) patients underwent a liver resection at some point of their disease history, and 54 (33%) of them underwent a subsequent locoregional treatment. Age > 70 years, locoregional nodal involvement at diagnosis of colorectal cancer and ≥4 liver metastases were significantly associated with higher risk of ePD while liver resections were associated with reduced risk of ePD. In the multivariable model, number of liver metastases (subdistribution HR, SHR 1.63, 95% CI 1.12 to 2.36; p = 0.01) and liver resections (SHR 0.43, 95% CI 0.29 to 0.63; p = 0.001) were still associated with ePD. Number of liver metastases < 4, no nodal involvement at diagnosis and liver resections were also associated with prolonged ePFS.
CONCLUSIONS CONCLUSIONS
The identified clinical factors could help physicians in personalising the intensity and aggressiveness of liver-directed treatments in patients with mCRC with initially unresectable LLD.

Identifiants

pubmed: 31231562
doi: 10.1136/esmoopen-2019-000496
pii: S2059-7029(20)30181-2
pmc: PMC6555604
doi:

Types de publication

Journal Article

Langues

eng

Pagination

e000496

Déclaration de conflit d'intérêts

Competing interests: None declared.

Références

J Am Coll Surg. 1999 Sep;189(3):291-9
pubmed: 10472930
Ann Surg. 2000 Jan;231(1):59-66
pubmed: 10636103
World J Surg. 2001 May;25(5):638-44
pubmed: 11369992
J Hepatobiliary Pancreat Surg. 2004;11(2):79-83
pubmed: 15127268
Ann Surg. 2004 Oct;240(4):644-57; discussion 657-8
pubmed: 15383792
Langenbecks Arch Surg. 2004 Oct;389(5):371-9
pubmed: 15605168
Arch Surg. 2005 Feb;140(2):183-9
pubmed: 15724001
Arch Surg. 2006 Oct;141(10):1006-12; discussion 1013
pubmed: 17043279
Ann Surg. 2007 Aug;246(2):183-91
pubmed: 17667495
J Clin Oncol. 2007 Oct 10;25(29):4575-80
pubmed: 17925551
Ann Surg. 2007 Nov;246(5):806-14
pubmed: 17968173
Ann Surg. 2008 Jan;247(1):125-35
pubmed: 18156932
J Am Coll Surg. 2008 May;206(5):857-68; discussion 868-9
pubmed: 18471711
Hepatogastroenterology. 2008 Jan-Feb;55(81):173-8
pubmed: 18507101
Liver Int. 2009 Jan;29(1):89-102
pubmed: 18673436
J Clin Oncol. 1991 Jul;9(7):1105-12
pubmed: 2045852
Ann Surg Oncol. 2012 Sep;19(9):2860-8
pubmed: 22526903
Ann Oncol. 2014 May;25(5):1018-25
pubmed: 24585720
Ann Oncol. 2015 Apr;26(4):702-8
pubmed: 25538173
Br J Cancer. 2015 Jun 9;112(12):1921-8
pubmed: 25942399
J Gastrointest Oncol. 2015 Dec;6(6):645-9
pubmed: 26697197
Ann Oncol. 2016 Aug;27(8):1386-422
pubmed: 27380959
Annu Rev Med. 2017 Jan 14;68:183-196
pubmed: 27686016
Eur J Cancer. 2017 Mar;73:74-84
pubmed: 27986363
Lancet Oncol. 2017 Sep;18(9):1159-1171
pubmed: 28781171
J Natl Compr Canc Netw. 2018 Apr;16(4):359-369
pubmed: 29632055
JAMA Surg. 2018 Jul 18;153(7):e180996
pubmed: 29799910
World J Surg. 1995 Jan-Feb;19(1):59-71
pubmed: 7740812
Cancer. 1996 Apr 1;77(7):1254-62
pubmed: 8608500
J Clin Oncol. 1997 Mar;15(3):938-46
pubmed: 9060531

Auteurs

Elena Ongaro (E)

Unit of Medical Oncology 2, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.
Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy.
Department of Oncology, Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy.

Chiara Cremolini (C)

Unit of Medical Oncology 2, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.
Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy.

Daniele Rossini (D)

Unit of Medical Oncology 2, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.
Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy.

Francesca Corti (F)

Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.

Filippo Pagani (F)

Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.

Luca Morelli (L)

General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.

Lucio Urbani (L)

Department of General Surgery, Liver Metastasis Parenchyma Sparing Surgery Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.

Gianluca Masi (G)

Unit of Medical Oncology 2, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.
Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy.

Carlo Sposito (C)

Department of Gastrointestinal and Hepatobilio-Pancreatic Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.

Beatrice Filippi (B)

Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.

Beatrice Borelli (B)

Unit of Medical Oncology 2, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.
Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy.

Gemma Zucchelli (G)

Unit of Medical Oncology 2, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.
Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy.

Roberto Moretto (R)

Unit of Medical Oncology 2, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.
Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy.

Alessandra Boccaccino (A)

Unit of Medical Oncology 2, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.
Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy.

Leonardo Solaini (L)

Department of Medical and Surgical Sciences, DIMEC, Alma Mater Studiorum, University of Bologna, Bologna, Italy.

Filippo de Braud (F)

Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
Department of Oncology and Hemato-oncology, Universityof Milan, Milan, Italy.

Vincenzo Mazzaferro (V)

Department of Gastrointestinal and Hepatobilio-Pancreatic Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.

Alfredo Falcone (A)

Unit of Medical Oncology 2, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.
Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy.

Alessandro Cucchetti (A)

Department of Medical and Surgical Sciences, DIMEC, Alma Mater Studiorum, University of Bologna, Bologna, Italy.

Filippo Pietrantonio (F)

Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
Department of Oncology and Hemato-oncology, Universityof Milan, Milan, Italy.

Classifications MeSH