Risk factors for brain metastases in patients with metastatic colorectal cancer

Troels Dreier Christensen; Jesper Andreas Palshof; Finn Ole Larsen; Estrid Høgdall; Tim Svenstrup Poulsen; Per Pfeiffer; Benny Vittrup Jensen; Mette Karen Yilmaz; Ib Jarle Christensen; Dorte Nielsen

doi:10.1080/0284186x.2017.1290272

Risk factors for brain metastases in patients with metastatic colorectal cancer

Troels Dreier Christensen, Jesper Andreas Palshof, Finn Ole Larsen, Estrid Høgdall, Tim Svenstrup Poulsen, Per Pfeiffer, Benny Vittrup Jensen, Mette Karen Yilmaz, Ib Jarle Christensen, Dorte Nielsen

Institut for Klinisk Medicin

16 Citationer (Scopus)

Abstract

BACKGROUND: Brain metastases (BM) from colorectal cancer (CRC) are rare, but the incidence is suspected to rise as treatment of metastatic (m) CRC improves. The aim of this study was to identify possible biological and clinical characteristics at initial presentation of mCRC that could predict later risk of developing BM. Furthermore, we wished to estimate the incidence of BM in long-term surviving patients.

MATERIAL AND METHODS: We conducted a retrospective study on a Danish multicenter cohort of patients with mCRC who received cetuximab and irinotecan (CetIri) as third-line treatment. All patients had previously progression on 5-FU, irinotecan and oxaliplatin containing regimens and received CetIri treatment independent of RAS mutations status. We subsequently performed KRAS, NRAS, BRAF, PIK3CA, PTEN, ERBB2 and EGFR sequencing of DNA extracted from primary tumor tissue.

RESULTS: Totally, 480 patients were included in our study. BM were diagnosed in 42 [8.8%; 95% confidence interval (CI) 6.4-11.6%] patients. Patients with BM had a significantly longer survival from mCRC diagnosis than non-BM patients (median = 32 versus 28 months, p = 0.001). On univariate cox regression analysis, the risk of developing BM was significantly increased in patients with rectal cancer (HR = 3.9; 95% CI = 1.2-13.3), metachronous metastatic disease (HR = 2.3; 95% CI = 1.2-4.4) and lung metastases (HR = 4.2; 95% CI = 2.2-7.9). On multivariate cox regression analysis only lung metastases were significantly associated BM (HR = 3.5; 95% CI = 1.8-6.8). None of the investigated mutations were associated with BM.

CONCLUSION: The incidence of BM was 8.8% in patients with mCRC who received third-line therapy. The most important risk factor for developing BM was lung metastases. Furthermore, rectal cancer, metachronous metastatic disease and long survival were linked to BM development.

Originalsprog	Engelsk
Tidsskrift	Acta Oncologica
Vol/bind	56
Udgave nummer	5
Sider (fra-til)	639-645
ISSN	0284-186X
DOI	https://doi.org/10.1080/0284186x.2017.1290272
Status	Udgivet - 3 jun. 2017

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10.1080/0284186x.2017.1290272

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@article{433f7dddf0a44628af9cc3cad249cae5,

title = "Risk factors for brain metastases in patients with metastatic colorectal cancer",

abstract = "BACKGROUND: Brain metastases (BM) from colorectal cancer (CRC) are rare, but the incidence is suspected to rise as treatment of metastatic (m) CRC improves. The aim of this study was to identify possible biological and clinical characteristics at initial presentation of mCRC that could predict later risk of developing BM. Furthermore, we wished to estimate the incidence of BM in long-term surviving patients.MATERIAL AND METHODS: We conducted a retrospective study on a Danish multicenter cohort of patients with mCRC who received cetuximab and irinotecan (CetIri) as third-line treatment. All patients had previously progression on 5-FU, irinotecan and oxaliplatin containing regimens and received CetIri treatment independent of RAS mutations status. We subsequently performed KRAS, NRAS, BRAF, PIK3CA, PTEN, ERBB2 and EGFR sequencing of DNA extracted from primary tumor tissue.RESULTS: Totally, 480 patients were included in our study. BM were diagnosed in 42 [8.8%; 95% confidence interval (CI) 6.4-11.6%] patients. Patients with BM had a significantly longer survival from mCRC diagnosis than non-BM patients (median = 32 versus 28 months, p = 0.001). On univariate cox regression analysis, the risk of developing BM was significantly increased in patients with rectal cancer (HR = 3.9; 95% CI = 1.2-13.3), metachronous metastatic disease (HR = 2.3; 95% CI = 1.2-4.4) and lung metastases (HR = 4.2; 95% CI = 2.2-7.9). On multivariate cox regression analysis only lung metastases were significantly associated BM (HR = 3.5; 95% CI = 1.8-6.8). None of the investigated mutations were associated with BM.CONCLUSION: The incidence of BM was 8.8% in patients with mCRC who received third-line therapy. The most important risk factor for developing BM was lung metastases. Furthermore, rectal cancer, metachronous metastatic disease and long survival were linked to BM development.",

keywords = "Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Biomarkers, Tumor/genetics, Brain Neoplasms/drug therapy, Colorectal Neoplasms/drug therapy, Female, Follow-Up Studies, Humans, Liver Neoplasms/drug therapy, Lung Neoplasms/drug therapy, Lymphatic Metastasis, Male, Middle Aged, Mutation, Peritoneal Neoplasms/drug therapy, Prognosis, Retrospective Studies, Risk Factors, Survival Rate, Young Adult",

author = "Christensen, {Troels Dreier} and Palshof, {Jesper Andreas} and Larsen, {Finn Ole} and Estrid H{\o}gdall and Poulsen, {Tim Svenstrup} and Per Pfeiffer and Jensen, {Benny Vittrup} and Yilmaz, {Mette Karen} and Christensen, {Ib Jarle} and Dorte Nielsen",

year = "2017",

month = jun,

day = "3",

doi = "10.1080/0284186x.2017.1290272",

language = "English",

volume = "56",

pages = "639--645",

journal = "Acta Oncologica",

issn = "0284-186X",

publisher = "Taylor & Francis",

number = "5",

}

TY - JOUR

T1 - Risk factors for brain metastases in patients with metastatic colorectal cancer

AU - Christensen, Troels Dreier

AU - Palshof, Jesper Andreas

AU - Larsen, Finn Ole

AU - Høgdall, Estrid

AU - Poulsen, Tim Svenstrup

AU - Pfeiffer, Per

AU - Jensen, Benny Vittrup

AU - Yilmaz, Mette Karen

AU - Christensen, Ib Jarle

AU - Nielsen, Dorte

PY - 2017/6/3

Y1 - 2017/6/3

N2 - BACKGROUND: Brain metastases (BM) from colorectal cancer (CRC) are rare, but the incidence is suspected to rise as treatment of metastatic (m) CRC improves. The aim of this study was to identify possible biological and clinical characteristics at initial presentation of mCRC that could predict later risk of developing BM. Furthermore, we wished to estimate the incidence of BM in long-term surviving patients.MATERIAL AND METHODS: We conducted a retrospective study on a Danish multicenter cohort of patients with mCRC who received cetuximab and irinotecan (CetIri) as third-line treatment. All patients had previously progression on 5-FU, irinotecan and oxaliplatin containing regimens and received CetIri treatment independent of RAS mutations status. We subsequently performed KRAS, NRAS, BRAF, PIK3CA, PTEN, ERBB2 and EGFR sequencing of DNA extracted from primary tumor tissue.RESULTS: Totally, 480 patients were included in our study. BM were diagnosed in 42 [8.8%; 95% confidence interval (CI) 6.4-11.6%] patients. Patients with BM had a significantly longer survival from mCRC diagnosis than non-BM patients (median = 32 versus 28 months, p = 0.001). On univariate cox regression analysis, the risk of developing BM was significantly increased in patients with rectal cancer (HR = 3.9; 95% CI = 1.2-13.3), metachronous metastatic disease (HR = 2.3; 95% CI = 1.2-4.4) and lung metastases (HR = 4.2; 95% CI = 2.2-7.9). On multivariate cox regression analysis only lung metastases were significantly associated BM (HR = 3.5; 95% CI = 1.8-6.8). None of the investigated mutations were associated with BM.CONCLUSION: The incidence of BM was 8.8% in patients with mCRC who received third-line therapy. The most important risk factor for developing BM was lung metastases. Furthermore, rectal cancer, metachronous metastatic disease and long survival were linked to BM development.

AB - BACKGROUND: Brain metastases (BM) from colorectal cancer (CRC) are rare, but the incidence is suspected to rise as treatment of metastatic (m) CRC improves. The aim of this study was to identify possible biological and clinical characteristics at initial presentation of mCRC that could predict later risk of developing BM. Furthermore, we wished to estimate the incidence of BM in long-term surviving patients.MATERIAL AND METHODS: We conducted a retrospective study on a Danish multicenter cohort of patients with mCRC who received cetuximab and irinotecan (CetIri) as third-line treatment. All patients had previously progression on 5-FU, irinotecan and oxaliplatin containing regimens and received CetIri treatment independent of RAS mutations status. We subsequently performed KRAS, NRAS, BRAF, PIK3CA, PTEN, ERBB2 and EGFR sequencing of DNA extracted from primary tumor tissue.RESULTS: Totally, 480 patients were included in our study. BM were diagnosed in 42 [8.8%; 95% confidence interval (CI) 6.4-11.6%] patients. Patients with BM had a significantly longer survival from mCRC diagnosis than non-BM patients (median = 32 versus 28 months, p = 0.001). On univariate cox regression analysis, the risk of developing BM was significantly increased in patients with rectal cancer (HR = 3.9; 95% CI = 1.2-13.3), metachronous metastatic disease (HR = 2.3; 95% CI = 1.2-4.4) and lung metastases (HR = 4.2; 95% CI = 2.2-7.9). On multivariate cox regression analysis only lung metastases were significantly associated BM (HR = 3.5; 95% CI = 1.8-6.8). None of the investigated mutations were associated with BM.CONCLUSION: The incidence of BM was 8.8% in patients with mCRC who received third-line therapy. The most important risk factor for developing BM was lung metastases. Furthermore, rectal cancer, metachronous metastatic disease and long survival were linked to BM development.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use

KW - Biomarkers, Tumor/genetics

KW - Brain Neoplasms/drug therapy

KW - Colorectal Neoplasms/drug therapy

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Liver Neoplasms/drug therapy

KW - Lung Neoplasms/drug therapy

KW - Lymphatic Metastasis

KW - Male

KW - Middle Aged

KW - Mutation

KW - Peritoneal Neoplasms/drug therapy

KW - Prognosis

KW - Retrospective Studies

KW - Risk Factors

KW - Survival Rate

KW - Young Adult

U2 - 10.1080/0284186x.2017.1290272

DO - 10.1080/0284186x.2017.1290272

M3 - Journal article

C2 - 28447565

SN - 0284-186X

VL - 56

SP - 639

EP - 645

JO - Acta Oncologica

JF - Acta Oncologica

IS - 5

ER -

Risk factors for brain metastases in patients with metastatic colorectal cancer

Abstract

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