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BMC Cancer
Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

Systematic review: brain metastases from colorectal cancer—Incidence and patient characteristics

Authors: Troels Dreier Christensen, Karen-Lise Garm Spindler, Jesper Andreas Palshof, Dorte Lisbet Nielsen

Published in: BMC Cancer | Issue 1/2016

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Abstract

Background

Brain metastases (BM) from colorectal cancer (CRC) are a rare event. However, the implications for affected patients are severe, and the incidence has been reported to be increasing. For clinicians, knowledge about the characteristics associated with BM is important and could lead to earlier diagnosis and improved survival.

Method

In this paper, we describe the incidence as well as characteristics associated with BM based on a systematic review of the current literature, following the PRISMA guidelines.

Results

We show that the incidence of BM in CRC patients ranges from 0.6 to 3.2 %. BM are a late stage phenomenon, and young age, rectal primary and lung metastases are associated with increased risk of developing BM. Molecular markers such as KRAS, BRAF, NRAS mutation as well as an increase in CEA and CA19.9 levels are suggested predictors of brain involvement. However, only KRAS mutations are reasonably well investigated and associated with an increased risk of BM.

Conclusion

The incidence of BM from CRC is 0.6 to 3.2 % and did not seem to increase over time. Development of BM is associated with young age, lung metastases, rectal primary and KRAS mutation. Increased awareness of brain involvement in patients with these characteristics is necessary.
Literature
1.
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–386.CrossRefPubMed
2.
Go PH, Klaassen Z, Meadows MC, Chamberlain RS. Gastrointestinal cancer and brain metastasis: a rare and ominous sign. Cancer. 2011;117(16):3630–40.CrossRefPubMed
3.
4.
Damiens K, Ayoub JP, Lemieux B, Aubin F, Saliba W, Campeau MP, Tehfe M. Clinical features and course of brain metastases in colorectal cancer: an experience from a single institution. Curr Oncol. 2012;19(5):254–8.CrossRefPubMedPubMedCentral
5.
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151(4):264–9. W264.CrossRefPubMed
6.
Aprile G, Zanon E, Tuniz F, Iaiza E, De Pauli F, Pella N, Pizzolitto S, Buffoli A, Piga A, Skrap M. Neurosurgical management and postoperative whole-brain radiotherapy for colorectal cancer patients with symptomatic brain metastases. J Cancer Res Clin Oncol. 2009;135(3):451–7.CrossRefPubMed
7.
Noura S, Ohue M, Shingai T, Fujiwara A, Imada S, Sueda T, Yamada T, Fujiwara Y, Ohigashi H, Yano M. Brain metastasis from colorectal cancer: prognostic factors and survival. J Surg Oncol. 2012;106(2):144–8.CrossRefPubMed
8.
Suzuki Y, Yamaguchi T, Matsumoto H, Nakano D, Honda G, Shinoura N, Karasawa K, Takahashi K. Prognostic factors and treatment effects in patients with curatively resected brain metastasis from colorectal cancer. Dis Colon Rectum. 2014;57(1):56–63.CrossRefPubMed
9.
Hugen N, van de Velde CJ, de Wilt JH, Nagtegaal ID. Metastatic pattern in colorectal cancer is strongly influenced by histological subtype. Ann Oncol. 2014;25(3):651–7.CrossRefPubMedPubMedCentral
10.
11.
Mongan JP, Fadul CE, Cole BF, Zaki BI, Suriawinata AA, Ripple GH, Tosteson TD, Pipas JM. Brain metastases from colorectal cancer: risk factors, incidence, and the possible role of chemokines. Clin Colorectal Cancer. 2009;8(2):100–5.CrossRefPubMedCentral
12.
Jung M, Ahn JB, Chang JH, Suh CO, Hong S, Roh JK, Shin SJ, Rha SY. Brain metastases from colorectal carcinoma: prognostic factors and outcome. J Neurooncol. 2011;101(1):49–55.CrossRefPubMed
13.
Pramateftakis MG, Hatzigianni P, Kanellos D, Vrakas G, Kanellos I, Agelopoulos S, Ouzounidis N, Lazaridis C. Brain metastases in colorectal cancer. Tech Coloproctol. 2010;14 Suppl 1:S67–68.CrossRefPubMed
14.
Jiang XB, Yang QY, Sai K, Zhang XH, Chen ZP, Mou YG. Brain metastases from colorectal carcinoma: a description of 60 cases in a single Chinese cancer center. Tumour Biol. 2011;32(6):1249–56.CrossRefPubMed
15.
Tevlin R, Larkin JO, Hyland JM, O’Connell PR, Winter DC. Brain metastasis from colorectal carcinoma: a single cancer centre experience. Ir J Med Sci. 2015;184(3):673–5.CrossRefPubMed
16.
Tanriverdi O, Kaytan-Saglam E, Ulger S, Bayoglu IV, Turker I, Ozturk-Topcu T, Cokmert S, Turhal S, Oktay E, Karabulut B. The clinical and pathological features of 133 colorectal cancer patients with brain metastasis: a multicenter retrospective analysis of the gastrointestinal tumors working committee of the turkish oncology group (TOG). Med Oncol. 2014;31(9):152.CrossRefPubMed
17.
Temple DF, Ledesma EJ, Mittelman A. Cerebral metastases. From adenocarcinoma of the colon and rectum. N Y State J Med. 1982;82(13):1812–4.PubMed
18.
Naito H, Sasaki M, Kondo K, Gotoda A, Kawamura K, Asama T, Osawa H, Ohara K, Takamatsu H, Fukuoka S. Radical treatment of brain metastasis of colorectal-cancer. Oncol Rep. 1994;1(6):1203–5.PubMed
19.
Hammoud MA, McCutcheon IE, Elsouki R, Schoppa D, Patt YZ. Colorectal carcinoma and brain metastasis: distribution, treatment, and survival. Ann Surg Oncol. 1996;3(5):453–63.CrossRefPubMed
20.
Ko FC, Liu JM, Chen WS, Chiang JK, Lin TC, Lin JK. Risk and patterns of brain metastases in colorectal cancer: 27-year experience. Dis Colon Rectum. 1999;42(11):1467–71.CrossRefPubMed
21.
Zorrilla M, Alonso V, Herrero A, Corral M, Puertolas T, Trufero JM, Artal A, Anton A. Brain metastases from colorectal carcinoma. Tumori. 2001;87(5):332–4.PubMed
22.
Schouten LJ, Rutten J, Huveneers HA, Twijnstra A. Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer. 2002;94(10):2698–705.CrossRefPubMed
23.
Barnholtz-Sloan JS, Sloan AE, Davis FG, Vigneau FD, Lai P, Sawaya RE. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the metropolitan detroit cancer surveillance system. J Clin Oncol. 2004;22(14):2865–72.CrossRefPubMed
24.
Kim HJ, Huh JW, Jung TY, Kim IY, Kim HR, Jung S, Kim YJ. Clinical outcome with gamma-knife surgery or surgery for brain metastases from colorectal cancer. J Clin Neurosci. 2013;20(10):1417–21.CrossRefPubMed
25.
Sundermeyer ML, Meropol NJ, Rogatko A, Wang H, Cohen SJ. Changing patterns of bone and brain metastases in patients with colorectal cancer. Clin Colorectal Cancer. 2005;5(2):108–13.CrossRefPubMed
26.
Yaeger R, Cowell E, Chou JF, Gewirtz AN, Borsu L, Vakiani E, Solit DB, Rosen N, Capanu M, Ladanyi M, et al. RAS mutations affect pattern of metastatic spread and increase propensity for brain metastasis in colorectal cancer. Cancer. 2015;121(8):1195–1203.CrossRefPubMed
27.
Chyun Y, Hayward E, Lokich J. Metastasis to the central nervous system from colorectal cancer. Med Pediatr Oncol. 1980;8(3):305–8.CrossRefPubMed
28.
Patanaphan V, Salazar OM. Colorectal cancer: metastatic patterns and prognosis. South Med J. 1993;86(1):38–41.CrossRefPubMed
29.
Tran B, Kopetz S, Tie J, Gibbs P, Jiang ZQ, Lieu CH, Agarwal A, Maru DM, Sieber O, Desai J. Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer. Cancer. 2011;117(20):4623–32.CrossRefPubMedPubMedCentral
30.
Hess KR, Varadhachary GR, Taylor SH, Wei W, Raber MN, Lenzi R, Abbruzzese JL. Metastatic patterns in adenocarcinoma. Cancer. 2006;106(7):1624–33.CrossRefPubMed
31.
Tie J, Lipton L, Desai J, Gibbs P, Jorissen RN, Christie M, Drummond KJ, Thomson BN, Usatoff V, Evans PM. KRAS mutation is associated with lung metastasis in patients with curatively resected colorectal cancer. Clin Cancer Res. 2011;17(5):1122–30.CrossRefPubMed
32.
Khattak MA, Martin HL, Beeke C, Price T, Carruthers S, Kim S, Padbury R, Karapetis CS. Survival differences in patients with metastatic colorectal cancer and with single site metastatic disease at initial presentation: results from South Australian clinical registry for advanced colorectal cancer. Clin Colorectal Cancer. 2012;11(4):247–54.CrossRefPubMed
33.
Kemeny NE, Chou JF, Capanu M, Gewirtz AN, Cercek A, Kingham TP, Jarnagin WR, Fong YC, DeMatteo RP, Allen PJ. KRAS mutation influences recurrence patterns in patients undergoing hepatic resection of colorectal metastases. Cancer. 2014;120(24):3965–71.CrossRefPubMedPubMedCentral
34.
Yoshidome H, Ito H, Kimura F, Ambiru S, Shimizu H, Togawa A, Ohtsuka M, Kato A, Nukui Y, Miyazaki M. Surgical treatment for extrahepatic recurrence after hepatectomy for colorectal metastases. Hepatogastroenterology. 2004;51(60):1805–9.PubMed
35.
de Jong MC, Pulitano C, Ribero D, Strub J, Mentha G, Schulick RD, Choti MA, Aldrighetti L, Capussotti L, Pawlik TM. Rates and patterns of recurrence following curative intent surgery for colorectal liver metastasis: an international multi-institutional analysis of 1669 patients. Ann Surg. 2009;250(3):440–8.PubMed
36.
Byrne BE, Geddes T, Welsh FK, John TG, Chandrakumaran K, Rees M. The incidence and outcome of brain metastases after liver resection for colorectal cancer metastases. Colorectal Dis. 2012;14(6):721–6.CrossRefPubMed
37.
Higashiyama M, Kodama K, Higaki N, Takami K, Murata K, Kameyama M, Yokouchi H. Surgery for pulmonary metastases from colorectal cancer: the importance of prethoracotomy serum carcinoembryonic antigen as an indicator of prognosis. Jpn J Thorac Cardiovasc Surg. 2003;51(7):289–96.CrossRefPubMed
38.
Chiang JM, Hsieh PS, Chen JS, Tang R, You JF, Yeh CY. Rectal cancer level significantly affects rates and patterns of distant metastases among rectal cancer patients post curative-intent surgery without neoadjuvant therapy. World J Surg Oncol. 2014;12:197.CrossRefPubMedPubMedCentral
39.
Weiss L, Grundmann E, Torhorst J, Hartveit F, Moberg I, Eder M, Fenoglio-Preiser CM, Napier J, Horne CH, Lopez MJ. Haematogenous metastatic patterns in colonic carcinoma: an analysis of 1541 necropsies. J Pathol. 1986;150(3):195–203.CrossRefPubMed
40.
Cascino TL, Leavengood JM, Kemeny N, Posner JB. Brain metastases from colon cancer. J Neurooncol. 1983;1(3):203–9.CrossRefPubMed
41.
Takagawa R, Fujii S, Ohta M, Nagano Y, Kunisaki C, Yamagishi S, Osada S, Ichikawa Y, Shimada H. Preoperative serum carcinoembryonic antigen level as a predictive factor of recurrence after curative resection of colorectal cancer. Ann Surg Oncol. 2008;15(12):3433–9.CrossRefPubMed
42.
van Gestel YR, de Hingh IH, van Herk-Sukel MP, van Erning FN, Beerepoot LV, Wijsman JH, Slooter GD, Rutten HJ, Creemers GJ, Lemmens VE. Patterns of metachronous metastases after curative treatment of colorectal cancer. Cancer Epidemiol. 2014;38(4):448–54.CrossRefPubMed
43.
Tokoro T, Okuno K, Hida JC, Ueda K, Yoshifuji T, Daito K, Sugiura F. Prognostic factors for patients with advanced colorectal cancer and symptomatic brain metastases. Clin Colorectal Cancer. 2014;13(4):226–31.CrossRefPubMed
44.
Scartozzi M, Bearzi I, Berardi R, Mandolesi A, Fabris G, Cascinu S. Epidermal growth factor receptor (EGFR) status in primary colorectal tumors does not correlate with EGFR expression in related metastatic sites: implications for treatment with EGFR-targeted monoclonal antibodies. J Clin Oncol. 2004;22(23):4772–8.CrossRefPubMed
45.
Kruser TJ, Chao ST, Elson P, Barnett GH, Vogelbaum MA, Angelov L, Weil RJ, Pelley R, Suh JH. Multidisciplinary management of colorectal brain metastases: a retrospective study. Cancer. 2008;113(1):158–65.CrossRefPubMed
46.
47.
Fokas E, Henzel M, Hamm K, Surber G, Kleinert G, Engenhart-Cabillic R. Multidisciplinary treatment of brain metastases derived from colorectal cancer incorporating stereotactic radiosurgery: analysis of 78 patients. Clin Colorectal Cancer. 2011;10(2):121–5.CrossRefPubMed
48.
Magni E, Santoro L, Ravenda PS, Leonardi MC, Bonomo G, Monfardini L, Nole F, Zampino MG. Brain metastases from colorectal cancer: main clinical factors conditioning outcome. Int J Colorectal Dis. 2014;29(2):201–8.CrossRefPubMed
49.
Farnell GF, Buckner JC, Cascino TL, O’Connell MJ, Schomberg PJ, Suman V. Brain metastases from colorectal carcinoma. The long term survivors. Cancer. 1996;78(4):711–6.CrossRefPubMed
50.
Kye BH, Kim HJ, Kang WK, Cho HM, Hong YK, Oh ST. Brain metastases from colorectal cancer: the role of surgical resection in selected patients. Colorectal Dis. 2012;14(7):e378–385.CrossRefPubMed
51.
Baek JY, Kang MH, Hong YS, Kim TW, Kim DY, Oh JH, Lee SH, Park JH, Kim JH, Kim SY. Characteristics and prognosis of patients with colorectal cancer-associated brain metastases in the era of modern systemic chemotherapy. J Neurooncol. 2011;104(3):745–53.CrossRefPubMed
52.
Nieder C, Pawinski A, Balteskard L. Colorectal cancer metastatic to the brain: time trends in presentation and outcome. Oncology. 2009;76(5):369–74.CrossRefPubMed
53.
Bartelt S, Momm F, Weissenberger C, Lutterbach J. Patients with brain metastases from gastrointestinal tract cancer treated with whole brain radiation therapy: prognostic factors and survival. World J Gastroenterol. 2004;10(22):3345–8.CrossRefPubMedPubMedCentral
54.
Heisterkamp C, Haatanen T, Schild SE, Rades D. Dose escalation in patients receiving whole-brain radiotherapy for brain metastases from colorectal cancer. Strahlenther Onkol. 2010;186(2):70–5.CrossRefPubMed
55.
Matsunaga S, Shuto T, Kawahara N, Suenaga J, Inomori S, Fujino H. Gamma Knife surgery for brain metastases from colorectal cancer. Clinical article J Neurosurg. 2011;114(3):782–9.CrossRefPubMed
56.
Schoeggl A, Kitz K, Reddy M, Zauner C. Stereotactic radiosurgery for brain metastases from colorectal cancer. Int J Colorectal Dis. 2002;17(3):150–5.CrossRefPubMed
57.
Wronski M, Arbit E. Resection of brain metastases from colorectal carcinoma in 73 patients. Cancer. 1999;85(8):1677–85.CrossRefPubMed
58.
Fowler A, Cook R, Biggs M, Little N, Assaad N, McDonald K. Survival of patients following neurosurgical treatment of colorectal adenocarcinoma metastasis in the Northern Sydney-Central Coast area. J Clin Neurosci. 2008;15(9):998–1004.CrossRefPubMed
59.
Maglio GD, Casagrande M, Guardascione M, Fontanella C, Lutrino SE, Rihawi K, Pisa FE, Tuniz F, Fasola G, Pizzolitto S. MGMT promoter methylation status in brain metastases from colorectal cancer and corresponding primary tumors. Future Oncol. 2015;11(8):1201–9.CrossRefPubMed
60.
Mege D, Ouaissi M, Fuks D, Metellus P, Peltier J, Dufour H, Regimbeau JM, Dahan L, Sielezneff I, Sastre B. Patients with brain metastases from colorectal cancer are not condemned. Anticancer Res. 2013;33(12):5645–8.PubMed
61.
Taher C, Frisk G, Fuentes S, Religa P, Costa H, Assinger A, Vetvik KK, Bukholm IR, Yaiw KC, Smedby KE. High prevalence of human cytomegalovirus in brain metastases of patients with primary breast and colorectal cancers. Transl Oncol. 2014;7(6):732–40.CrossRefPubMedPubMedCentral
62.
D’Andrea G, Isidori A, Caroli E, Orlando ER, Salvati M. Single cerebral metastasis from colorectal adenocarcinoma. Neurosurg Rev. 2004;27(1):55–7.CrossRefPubMed
63.
Simonova G, Liscak R, Novotny Jr J, Novotny J. Solitary brain metastases treated with the Leksell gamma knife: prognostic factors for patients. Radiother Oncol. 2000;57(2):207–13.CrossRefPubMed
64.
Onodera H, Nagayama S, Tachibana T, Fujimoto A, Imamura M. Brain metastasis from colorectal cancer. Int J Colorectal Dis. 2005;20(1):57–61.CrossRefPubMed
65.
Howlader NNA, Krapcho M, et al. SEER cancer statistics review, 1975–2010. Bethesda: National Cancer Institute; 2013.
66.
Duffy MJ, Lamerz R, Haglund C, Nicolini A, Kalousova M, Holubec L, Sturgeon C. Tumor markers in colorectal cancer, gastric cancer and gastrointestinal stromal cancers: European group on tumor markers 2014 guidelines update. Int J Cancer. 2014;134(11):2513–22.CrossRefPubMedPubMedCentral
67.
Tampellini M, Ottone A, Alabiso I, Baratelli C, Forti L, Berruti A, Aroasio E, Scagliotti GV. The prognostic role of baseline CEA and CA 19-9 values and their time-dependent variations in advanced colorectal cancer patients submitted to first-line therapy. Tumour Biol. 2015;36(3):1519–27.CrossRefPubMed
68.
Zang YW, Gu XD, Xiang JB, Chen ZY. Brain metastases from colorectal cancer: microenvironment and molecular mechanisms. Int J Mol Sci. 2012;13(12):15784–800.CrossRefPubMedPubMedCentral
Metadata
Title
Systematic review: brain metastases from colorectal cancer—Incidence and patient characteristics
Authors
Troels Dreier Christensen
Karen-Lise Garm Spindler
Jesper Andreas Palshof
Dorte Lisbet Nielsen
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2290-5

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