Sites of metastasis and association with clinical outcome in advanced stage cancer patients treated with immunotherapy.
Clinical outcomes
Immune checkpoint blockade
Immunotherapy
Liver metastasis
Phase 1 clinical trials
Sites of metastasis
Tumor immunology
Tumor microenvironment
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
29 Aug 2019
29 Aug 2019
Historique:
received:
22
09
2018
accepted:
22
08
2019
entrez:
30
8
2019
pubmed:
30
8
2019
medline:
21
1
2020
Statut:
epublish
Résumé
Selecting the appropriate patients to receive immunotherapy (IO) remains a challenge due to the lack of optimal biomarkers. The presence of liver metastases has been implicated as a poor prognostic factor in patients with metastatic cancer. We investigated the association between sites of metastatic disease and clinical outcomes in patients receiving IO. We conducted a retrospective review of 90 patients treated on IO-based phase 1 clinical trials at Winship Cancer Institute of Emory University between 2009 and 2017. Overall survival (OS) and progression-free survival (PFS) were measured from the first dose of IO to date of death or hospice referral and clinical or radiographic progression, respectively. Clinical benefit (CB) was defined as a best response of complete response (CR), partial response (PR), or stable disease (SD). Univariate analysis (UVA) and Multivariate analysis (MVA) were carried out using Cox proportional hazard model or logistic regression model. Covariates included age, whether IO is indicated for the patient's histology, ECOG performance status, Royal Marsden Hospital (RMH) risk group, number of metastatic sites, and histology. The median age was 63 years and 53% of patients were men. The most common histologies were melanoma (33%) and gastrointestinal cancers (22%). Most patients (73.3%) had more than one site of distant metastasis. Sites of metastasis collected were lymph node (n = 58), liver (n = 40), lung (n = 37), bone (n = 24), and brain (n = 8). Most patients (80.7%) were RMH good risk. Most patients (n = 62) had received 2+ prior lines of systemic treatment before receiving IO on trial; 27 patients (30.0%) received prior ICB. Liver metastases were associated with significantly shorter OS (HR: 0.38, CI: 0.17-0.84, p = 0.017). Patients with liver metastasis also trended towards having shorter PFS (HR: 0.70, CI: 0.41-1.19, p = 0.188). The median OS was substantially longer for patients without liver metastases (21.9 vs. 8.1 months, p = 0.0048). Liver metastases may be a poor prognostic factor in patients receiving IO on phase 1 clinical trials. The presence of liver metastases may warrant consideration in updated prognostic models if these findings are validated in a larger prospective cohort.
Sections du résumé
BACKGROUND
BACKGROUND
Selecting the appropriate patients to receive immunotherapy (IO) remains a challenge due to the lack of optimal biomarkers. The presence of liver metastases has been implicated as a poor prognostic factor in patients with metastatic cancer. We investigated the association between sites of metastatic disease and clinical outcomes in patients receiving IO.
METHODS
METHODS
We conducted a retrospective review of 90 patients treated on IO-based phase 1 clinical trials at Winship Cancer Institute of Emory University between 2009 and 2017. Overall survival (OS) and progression-free survival (PFS) were measured from the first dose of IO to date of death or hospice referral and clinical or radiographic progression, respectively. Clinical benefit (CB) was defined as a best response of complete response (CR), partial response (PR), or stable disease (SD). Univariate analysis (UVA) and Multivariate analysis (MVA) were carried out using Cox proportional hazard model or logistic regression model. Covariates included age, whether IO is indicated for the patient's histology, ECOG performance status, Royal Marsden Hospital (RMH) risk group, number of metastatic sites, and histology.
RESULTS
RESULTS
The median age was 63 years and 53% of patients were men. The most common histologies were melanoma (33%) and gastrointestinal cancers (22%). Most patients (73.3%) had more than one site of distant metastasis. Sites of metastasis collected were lymph node (n = 58), liver (n = 40), lung (n = 37), bone (n = 24), and brain (n = 8). Most patients (80.7%) were RMH good risk. Most patients (n = 62) had received 2+ prior lines of systemic treatment before receiving IO on trial; 27 patients (30.0%) received prior ICB. Liver metastases were associated with significantly shorter OS (HR: 0.38, CI: 0.17-0.84, p = 0.017). Patients with liver metastasis also trended towards having shorter PFS (HR: 0.70, CI: 0.41-1.19, p = 0.188). The median OS was substantially longer for patients without liver metastases (21.9 vs. 8.1 months, p = 0.0048).
CONCLUSIONS
CONCLUSIONS
Liver metastases may be a poor prognostic factor in patients receiving IO on phase 1 clinical trials. The presence of liver metastases may warrant consideration in updated prognostic models if these findings are validated in a larger prospective cohort.
Identifiants
pubmed: 31464611
doi: 10.1186/s12885-019-6073-7
pii: 10.1186/s12885-019-6073-7
pmc: PMC6716879
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
857Subventions
Organisme : NCI NIH HHS
ID : P30 CA138292
Pays : United States
Organisme : Winship Cancer Institute
ID : P30CA138292
Références
Ann Surg. 1999 Sep;230(3):309-18; discussion 318-21
pubmed: 10493478
Eur J Surg Oncol. 2000 Apr;26(3):209-12
pubmed: 10753531
Br J Cancer. 2003 Jul 21;89(2):284-90
pubmed: 12865918
Br J Radiol. 1953 May;26(305):234-41
pubmed: 13042090
Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17174-9
pubmed: 15569934
Br J Cancer. 2008 Mar 25;98(6):1029-33
pubmed: 18349817
J Clin Oncol. 2009 Jun 1;27(16):2692-6
pubmed: 19332724
Med Oncol. 2011 Sep;28(3):682-8
pubmed: 20373055
Cancer. 2012 Mar 1;118(5):1422-8
pubmed: 21823111
Eur J Surg Oncol. 2012 Oct;38(10):910-7
pubmed: 22682709
Immunotherapy. 2012 Nov;4(11):1081-5
pubmed: 23194355
J Clin Oncol. 2013 Jun 1;31(16):1931-8
pubmed: 23569301
Hepatology. 2014 Apr;59(4):1351-65
pubmed: 24677194
Cancer Treat Rev. 2014 Oct;40(9):1056-64
pubmed: 25060490
Ann Oncol. 2015 Feb;26(2):259-71
pubmed: 25214542
Nature. 2014 Nov 27;515(7528):563-7
pubmed: 25428504
J Immunol. 2015 Feb 1;194(3):950-9
pubmed: 25539810
Am J Clin Pathol. 2015 Apr;143(4):471-8
pubmed: 25779997
Cancer Treat Rev. 2015 Jun;41(6):503-10
pubmed: 25872878
J Transl Med. 2015 Feb 15;13:64
pubmed: 25885919
Oncol Rep. 2015 Jun;33(6):3075-84
pubmed: 25963805
N Engl J Med. 2015 Nov 5;373(19):1803-13
pubmed: 26406148
Pharmacotherapy. 2015 Oct;35(10):963-76
pubmed: 26497482
Eur J Cancer. 2016 Feb;54:139-148
pubmed: 26765102
Curr Opin Obstet Gynecol. 2016 Apr;28(2):142-7
pubmed: 26881392
Lancet. 2016 May 7;387(10031):1909-20
pubmed: 26952546
Ann Oncol. 2016 Aug;27(8):1386-422
pubmed: 27380959
Lancet. 2017 Jan 7;389(10064):67-76
pubmed: 27939400
Cancer Immunol Res. 2017 Jan;5(1):17-28
pubmed: 28003187
Medicine (Baltimore). 2016 Dec;95(52):e5539
pubmed: 28033249
N Engl J Med. 2017 Mar 16;376(11):1015-1026
pubmed: 28212060
Cell Mol Gastroenterol Hepatol. 2017 Jan 20;3(2):163-173
pubmed: 28275683
Adv Anat Pathol. 2017 Nov;24(6):311-335
pubmed: 28777143
J Natl Compr Canc Netw. 2017 Oct;15(10):1277-1284
pubmed: 28982752
Science. 2018 Feb 16;359(6377):801-806
pubmed: 29301960
Cancer Immunol Res. 2018 Apr;6(4):402-408
pubmed: 29437040
N Engl J Med. 2018 May 31;378(22):2093-2104
pubmed: 29658845
J Immunother Cancer. 2018 May 16;6(1):39
pubmed: 29769148
J Immunother Cancer. 2018 Jun 4;6(1):46
pubmed: 29866197
J Clin Med. 2018 Jun 15;7(6):null
pubmed: 29914100
J Thorac Dis. 2018 May;10(Suppl 13):S1494-S1502
pubmed: 29951301
Dis Colon Rectum. 1988 Jan;31(1):1-4
pubmed: 3366020
Br J Cancer. 1972 Dec;26(6):466-72
pubmed: 4647397
Surg Gynecol Obstet. 1968 Jul;127(1):1-11
pubmed: 5657778