EGFR mutant locally advanced non-small cell lung cancer is at increased risk of brain metastasis.
Brain metastasis
EGFR
Lung cancer
Journal
Clinical and translational radiation oncology
ISSN: 2405-6308
Titre abrégé: Clin Transl Radiat Oncol
Pays: Ireland
ID NLM: 101713416
Informations de publication
Date de publication:
Sep 2019
Sep 2019
Historique:
received:
13
06
2019
accepted:
24
06
2019
entrez:
26
7
2019
pubmed:
26
7
2019
medline:
26
7
2019
Statut:
epublish
Résumé
Small studies of primarily metastatic non-small cell lung cancer (NSCLC) have suggested an association between EGFR mutation (EGFR+) and likelihood of brain metastasis. However, these studies are confounded by follow-up time bias. We performed a competing risk analysis of brain metastasis in a more uniform locally advanced NSCLC (LA-NSCLC) cohort with known tumor genotype. Between 2002 and 2014, 255 patients with LA-NSCLC underwent tumor genotyping for EGFR, ALK and/or KRAS (180 patients had follow-up brain imaging). Cumulative incidence and Fine-Gray regression were performed on clinical variables including genotype and risk of brain metastasis, with death as a competing event. The proportion of tumors with aberrations in EGFR, ALK and KRAS were 17%, 4% and 28%, respectively. The median follow-up was 68 months. On multivariate analysis, EGFR+ was significantly associated with risk of brain metastasis in the full patient cohort (HR 2.04, 95% CI 1.22-3.39, p = 0.006) as well as in the subset of patients with brain follow-up imaging (HR 1.91. 95% CI 1.17-3.13, p = 0.01). This translated to a higher cumulative incidence of brain metastasis in EGFR+ patients at 3 and 5 years (33.3% vs. 23.2 and 43.8% vs. 24.2%, p = 0.006). Patients with EGFR+ LA-NSCLC have a significantly higher likelihood of developing brain metastasis after standard combined modality therapy, independent of their longer overall survival. This high-risk genotypic subgroup may benefit from routine surveillance with brain MRI to allow early salvage with targeted systemic- and/or radiation-therapies.
Sections du résumé
BACKGROUND AND PURPOSE
OBJECTIVE
Small studies of primarily metastatic non-small cell lung cancer (NSCLC) have suggested an association between EGFR mutation (EGFR+) and likelihood of brain metastasis. However, these studies are confounded by follow-up time bias. We performed a competing risk analysis of brain metastasis in a more uniform locally advanced NSCLC (LA-NSCLC) cohort with known tumor genotype.
MATERIALS AND METHODS
METHODS
Between 2002 and 2014, 255 patients with LA-NSCLC underwent tumor genotyping for EGFR, ALK and/or KRAS (180 patients had follow-up brain imaging). Cumulative incidence and Fine-Gray regression were performed on clinical variables including genotype and risk of brain metastasis, with death as a competing event.
RESULTS
RESULTS
The proportion of tumors with aberrations in EGFR, ALK and KRAS were 17%, 4% and 28%, respectively. The median follow-up was 68 months. On multivariate analysis, EGFR+ was significantly associated with risk of brain metastasis in the full patient cohort (HR 2.04, 95% CI 1.22-3.39, p = 0.006) as well as in the subset of patients with brain follow-up imaging (HR 1.91. 95% CI 1.17-3.13, p = 0.01). This translated to a higher cumulative incidence of brain metastasis in EGFR+ patients at 3 and 5 years (33.3% vs. 23.2 and 43.8% vs. 24.2%, p = 0.006).
CONCLUSION
CONCLUSIONS
Patients with EGFR+ LA-NSCLC have a significantly higher likelihood of developing brain metastasis after standard combined modality therapy, independent of their longer overall survival. This high-risk genotypic subgroup may benefit from routine surveillance with brain MRI to allow early salvage with targeted systemic- and/or radiation-therapies.
Identifiants
pubmed: 31341973
doi: 10.1016/j.ctro.2019.06.008
pii: S2405-6308(19)30083-7
pmc: PMC6612652
doi:
Types de publication
Journal Article
Langues
eng
Pagination
32-38Déclaration de conflit d'intérêts
RM – Astra Zeneca – Scientific Advisory Board; Varian – Consulting. All other authors declare they have no conflicts of interest.
Références
Cancer. 2002 May 15;94(10):2698-705
pubmed: 12173339
J Clin Oncol. 2004 Jul 15;22(14):2865-72
pubmed: 15254054
J Clin Oncol. 2005 Mar 1;23(7):1530-7
pubmed: 15735128
J Clin Oncol. 2005 Sep 1;23(25):5900-9
pubmed: 16043828
Clin Neurol Neurosurg. 2010 Nov;112(9):770-4
pubmed: 20621414
Mol Cancer. 2010 Jul 13;9:188
pubmed: 20624322
J Clin Oncol. 2011 Jan 20;29(3):279-86
pubmed: 21135267
J Clin Oncol. 2011 Jan 20;29(3):272-8
pubmed: 21135270
Int J Radiat Oncol Biol Phys. 2013 Jul 15;86(4):656-64
pubmed: 23597420
Clin Cancer Res. 2013 Aug 1;19(15):4273-81
pubmed: 23729361
Clin Cancer Res. 2013 Oct 1;19(19):5523-32
pubmed: 23897899
BMC Res Notes. 2013 Nov 26;6:489
pubmed: 24279718
J Thorac Oncol. 2013 Dec;8(12):1570-3
pubmed: 24389440
J Thorac Oncol. 2014 Feb;9(2):195-9
pubmed: 24419416
Neuro Oncol. 2015 Feb;17(2):296-302
pubmed: 25053852
Lung Cancer. 2014 Nov;86(2):255-61
pubmed: 25224251
Ann Oncol. 2015 Mar;26(3):504-9
pubmed: 25515658
Lung Cancer. 2015 Apr;88(1):108-11
pubmed: 25682925
Lung Cancer. 2016 Jun;96:101-7
pubmed: 27133758
Br J Cancer. 2016 Jul 26;115(3):346-53
pubmed: 27336603
J Radiat Res. 2016 Sep;57(5):449-459
pubmed: 27534790
Oncotarget. 2016 Dec 20;7(51):84666-84674
pubmed: 27835868
JCI Insight. 2016 Nov 17;1(19):e87062
pubmed: 27882345
Sci Rep. 2017 Jan 04;7:39721
pubmed: 28051122
Oncotarget. 2017 Jan 31;8(5):8717-8725
pubmed: 28060728
J Clin Oncol. 2017 Apr 1;35(10):1070-1077
pubmed: 28113019
Oncotarget. 2017 Apr 11;8(15):25046-25054
pubmed: 28212572
Pract Radiat Oncol. 2017 Jul - Aug;7(4):e263-e273
pubmed: 28254368
Lancet Oncol. 2017 May;18(5):663-671
pubmed: 28343976
J Thorac Dis. 2017 Aug;9(8):2510-2520
pubmed: 28932557
Radiother Oncol. 2018 Feb;126(2):368-374
pubmed: 29111173
J Thorac Oncol. 2018 May;13(5):715-720
pubmed: 29269007
Lung Cancer. 2018 May;119:120-126
pubmed: 29656746
Front Oncol. 2018 Apr 20;8:115
pubmed: 29732317
J Clin Oncol. 2018 Aug 10;36(23):2366-2377
pubmed: 29787357
JAMA Oncol. 2018 Jul 1;4(7):1001-1003
pubmed: 29799956
Clin Lung Cancer. 2019 May;20(3):e256-e264
pubmed: 30926356