Mismatch Repair-Deficient Rectal Cancer and Resistance to Neoadjuvant Chemotherapy.

Adult Aged Aged, 80 and over Antineoplastic Agents / pharmacology Chemotherapy, Adjuvant Colorectal Neoplasms, Hereditary Nonpolyposis / genetics Combined Modality Therapy DNA Mismatch Repair Drug Resistance, Neoplasm / genetics Female Germ-Line Mutation Humans Male Middle Aged Neoplasm Staging Rectal Neoplasms / drug therapy Treatment Outcome Young Adult

Journal

Clinical cancer research : an official journal of the American Association for Cancer Research

ISSN: 1557-3265

Titre abrégé: Clin Cancer Res

Pays: United States

ID NLM: 9502500

Informations de publication

Date de publication:
01 07 2020

Historique:

received: 14 11 2019

revised: 31 01 2020

accepted: 02 03 2020

pubmed: 8 3 2020

medline: 15 9 2021

entrez: 8 3 2020

Statut: ppublish

Résumé

Evaluate response of mismatch repair-deficient (dMMR) rectal cancer to neoadjuvant chemotherapy. dMMR rectal tumors at Memorial Sloan Kettering Cancer Center (New York, NY) were retrospectively reviewed for characteristics, treatment, and outcomes. Fifty patients with dMMR rectal cancer were identified by IHC and/or microsatellite instability analysis, with initial treatment response compared with a matched MMR-proficient (pMMR) rectal cancer cohort. Germline and somatic mutation analyses were evaluated. Patient-derived dMMR rectal tumoroids were assessed for chemotherapy sensitivity. Of 21 patients receiving neoadjuvant chemotherapy (fluorouracil/oxaliplatin), six (29%) had progression of disease. In comparison, no progression was noted in 63 pMMR rectal tumors Over one-fourth of dMMR rectal tumors treated with neoadjuvant chemotherapy exhibited disease progression. Conversely, dMMR rectal tumors were sensitive to chemoradiation. MMR status should be performed upfront in all locally advanced rectal tumors with careful monitoring for response on neoadjuvant chemotherapy and genetic testing for Lynch syndrome in patients with dMMR rectal cancer.

Identifiants

DOI: 10.1158/1078-0432.CCR-19-3728 PMID: 32144135 PMC: PMC7348681

pubmed: 32144135

pii: 1078-0432.CCR-19-3728

doi: 10.1158/1078-0432.CCR-19-3728

pmc: PMC7348681

mid: NIHMS1574186

doi:

Substances chimiques

Antineoplastic Agents 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

3271-3279

Subventions

Organisme : NCI NIH HHS

ID : K08 CA230213

Pays : United States

Organisme : NCI NIH HHS

ID : P30 CA008748

Pays : United States

Organisme : Chief Scientist Office

ID : SCAF/19/01

Pays : United Kingdom

Informations de copyright

Références

N Engl J Med. 2004 Oct 21;351(17):1731-40

pubmed: 15496622

JAMA Oncol. 2018 Jun 14;4(6):e180070

pubmed: 29566113

J Natl Cancer Inst. 2016 Feb 01;108(7):

pubmed: 26839356

Cell Stem Cell. 2020 Jan 2;26(1):17-26.e6

pubmed: 31761724

J Clin Oncol. 2010 Feb 10;28(5):859-65

pubmed: 20065174

Am J Surg Pathol. 2011 Mar;35(3):447-54

pubmed: 21297438

Clin Colorectal Cancer. 2017 Sep;16(3):228-239

pubmed: 28063788

J Clin Oncol. 2008 Dec 10;26(35):5783-8

pubmed: 18809606

Dis Colon Rectum. 2013 Oct;56(10):1109-17

pubmed: 24022527

Dis Colon Rectum. 2000 Apr;43(4):451-9

pubmed: 10789738

J Clin Oncol. 2011 Apr 10;29(11):1465-71

pubmed: 21383294

Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6870-5

pubmed: 9618505

Hum Pathol. 2014 Oct;45(10):2029-36

pubmed: 25150747

Br J Cancer. 2009 Jan 27;100(2):266-73

pubmed: 19165197

Nat Med. 2015 Nov;21(11):1350-6

pubmed: 26457759

J Clin Oncol. 2010 Jul 10;28(20):3219-26

pubmed: 20498393

JAMA Oncol. 2018 Jun 14;4(6):e180071

pubmed: 29566109

J Natl Compr Canc Netw. 2017 Mar;15(3):370-398

pubmed: 28275037

Lancet. 1986 Jun 28;1(8496):1479-82

pubmed: 2425199

Science. 1993 May 7;260(5109):816-9

pubmed: 8484122

Anticancer Res. 2003 Mar-Apr;23(2C):1773-7

pubmed: 12820457

J Clin Oncol. 2011 Aug 10;29(23):3153-62

pubmed: 21747089

Sci Rep. 2016 Jul 15;6:29765

pubmed: 27416752

Stat Med. 2009 Jan 30;28(2):205-20

pubmed: 18991332

N Engl J Med. 2015 Jun 25;372(26):2509-20

pubmed: 26028255

Gastroenterology. 2011 Nov;141(5):1762-72

pubmed: 21889923

J Clin Oncol. 2014 Feb 20;32(6):513-8

pubmed: 24419115

Cancer. 2011 Oct 15;117(20):4623-32

pubmed: 21456008

J Natl Compr Canc Netw. 2014 Apr;12(4):513-9

pubmed: 24717570

Cancer Res. 1997 Mar 1;57(5):808-11

pubmed: 9041175

Ann Surg. 2004 Oct;240(4):711-7; discussion 717-8

pubmed: 15383798

Sci Transl Med. 2019 Oct 9;11(513):

pubmed: 31597751

Lancet Oncol. 2010 Mar;11(3):241-8

pubmed: 20106720

JCO Precis Oncol. 2017;2017:

pubmed: 30211344

J Clin Oncol. 2016 Sep 1;34(25):3039-46

pubmed: 27432916

Colorectal Dis. 2016 Aug;18(8):763-72

pubmed: 27169752

Eur J Cancer. 2012 May;48(8):1235-43

pubmed: 22071131

Lancet Oncol. 2017 Sep;18(9):1182-1191

pubmed: 28734759

J Natl Cancer Inst. 2014 Sep 22;106(10):

pubmed: 25249540

Ann Oncol. 2013 May;24(5):1274-82

pubmed: 23235802

Nat Med. 2019 Oct;25(10):1607-1614

pubmed: 31591597

Lancet Oncol. 2014 Dec;15(13):1481-1492

pubmed: 25456367

Clin Cancer Res. 2012 Dec 1;18(23):6531-41

pubmed: 23045248

Korean J Pathol. 2013 Feb;47(1):1-8

pubmed: 23482947

Anticancer Res. 2004 Sep-Oct;24(5B):3161-7

pubmed: 15510606

Cancer Causes Control. 2009 Nov;20(9):1763-8

pubmed: 19669908

Cancer Res. 1993 Dec 15;53(24):5849-52

pubmed: 8261392