{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T23:12:00Z","timestamp":1787872320717,"version":"build-2784847793"},"reference-count":112,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T00:00:00Z","timestamp":1651104000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T00:00:00Z","timestamp":1651104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Curr. Treat. Options in Oncol."],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Opinion statement<\/jats:title><jats:p>Compared to liver and lung metastases, brain metastases (BMs) from colorectal cancer (CRC) are rare and remain poorly investigated despite the anticipated rise in their incidence. CRC patients bearing BM have a dismal prognosis with a median survival of 3\u20136 months, significantly lower than that of patients with BM from other primary tumors, and of those with metastatic CRC manifesting extracranially. While liver and lung metastases from CRC have more codified treatment strategies, there is no consensus regarding the treatment of BM in CRC, and their management follows the approaches of BM from other solid tumors. Therapeutic strategies are driven by the number and localisation of the lesion, consisting in local treatments such as surgery, stereotactic radiosurgery, or whole-brain radiotherapy. Novel treatment modalities are slowly finding their way into this shy unconsented armatorium including immunotherapy, monoclonal antibodies, tyrosine kinase inhibitors, or a combination of those, among others.<\/jats:p><jats:p>This article reviews the pioneering strategies aiming at understanding, diagnosing, and managing this disease, and discusses future directions, challenges, and potential innovations in each of these domains.<\/jats:p>\n                <jats:p><jats:bold>Highlights<\/jats:bold><\/jats:p>\n                <jats:p>\u2022 With the increasing survival in CRC, brain and other rare\/late-onset metastases are rising.<\/jats:p>\n                <jats:p>\u2022 Distal colon\/rectal primary location, long-standing progressive lung metastases, and longer survival are risk factors for BM development in CRC.<\/jats:p>\n                <jats:p>\u2022 Late diagnosis and lack of consensus treatment strategies make BM-CRC diagnosis very dismal.<\/jats:p>\n                <jats:p>\u2022 Liquid biopsies using circulating tumor cells might offer excellent opportunities in the early diagnosis of BM-CRC and the search for therapeutic options.<\/jats:p>\n                <jats:p>\u2022 Multi-modality treatment including surgical metastatic resection, postoperative SRS with\/without WBRT, and chemotherapy is the best current treatment option.<\/jats:p>\n                <jats:p>\u2022 Recent mid-sized clinical trials, case reports, and preclinical models show the potential of unconventional therapeutic approaches as monoclonal antibodies, targeted therapies, and immunotherapy.<\/jats:p>","DOI":"10.1007\/s11864-022-00982-0","type":"journal-article","created":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T08:03:14Z","timestamp":1651132994000},"page":"980-1000","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Where Are We Now and Where Might We Be Headed in Understanding and Managing Brain Metastases in Colorectal Cancer Patients?"],"prefix":"10.1007","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4419-2705","authenticated-orcid":false,"given":"Ribal Bou","family":"Mjahed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoforos","family":"Astaras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Roth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibaud","family":"Koessler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,4,28]]},"reference":[{"key":"982_CR1","doi-asserted-by":"publisher","first-page":"E359","DOI":"10.1002\/ijc.29210","volume":"136","author":"J Ferlay","year":"2015","unstructured":"Ferlay J, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359\u201386. https:\/\/doi.org\/10.1002\/ijc.29210.","journal-title":"Int J Cancer"},{"key":"982_CR2","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1186\/s12885-016-2290-5","volume":"16","author":"TD Christensen","year":"2016","unstructured":"Christensen TD, Spindler KL, Palshof JA, Nielsen DL. Systematic review: brain metastases from colorectal cancer--incidence and patient characteristics. BMC Cancer. 2016;16:260. https:\/\/doi.org\/10.1186\/s12885-016-2290-5.","journal-title":"BMC Cancer"},{"key":"982_CR3","doi-asserted-by":"publisher","first-page":"108","DOI":"10.3816\/ccc.2005.n.022","volume":"5","author":"ML Sundermeyer","year":"2005","unstructured":"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;5:108\u201313. https:\/\/doi.org\/10.3816\/ccc.2005.n.022.","journal-title":"Clin Colorectal Cancer"},{"key":"982_CR4","doi-asserted-by":"publisher","unstructured":"Palmer, J. D. et al. Multidisciplinary patient-centered management of brain metastases and future directions. Neurooncol Adv 2, vdaa034, https:\/\/doi.org\/10.1093\/noajnl\/vdaa034 (2020).","DOI":"10.1093\/noajnl\/vdaa034"},{"key":"982_CR5","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1007\/s11912-011-0203-y","volume":"14","author":"L Nayak","year":"2012","unstructured":"Nayak L, Lee EQ, Wen PY. Epidemiology of brain metastases. Curr Oncol Rep. 2012;14:48\u201354. https:\/\/doi.org\/10.1007\/s11912-011-0203-y.","journal-title":"Curr Oncol Rep"},{"key":"982_CR6","doi-asserted-by":"publisher","first-page":"3345","DOI":"10.3748\/wjg.v10.i22.3345","volume":"10","author":"S Bartelt","year":"2004","unstructured":"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;10:3345\u20138. https:\/\/doi.org\/10.3748\/wjg.v10.i22.3345.","journal-title":"World J Gastroenterol"},{"key":"982_CR7","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1007\/BF02235049","volume":"42","author":"FC Ko","year":"1999","unstructured":"Ko FC, et al. Risk and patterns of brain metastases in colorectal cancer: 27-year experience. Dis Colon Rectum. 1999;42:1467\u201371. https:\/\/doi.org\/10.1007\/BF02235049.","journal-title":"Dis Colon Rectum"},{"key":"982_CR8","doi-asserted-by":"publisher","first-page":"2698","DOI":"10.1002\/cncr.10541","volume":"94","author":"LJ Schouten","year":"2002","unstructured":"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;94:2698\u2013705. https:\/\/doi.org\/10.1002\/cncr.10541.","journal-title":"Cancer"},{"key":"982_CR9","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.1093\/neuonc\/nox077","volume":"19","author":"DN Cagney","year":"2017","unstructured":"Cagney DN, et al. Incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy: a population-based study. Neuro-Oncology. 2017;19:1511\u201321. https:\/\/doi.org\/10.1093\/neuonc\/nox077.","journal-title":"Neuro-Oncology"},{"key":"982_CR10","doi-asserted-by":"publisher","first-page":"100","DOI":"10.3816\/CCC.2009.n.016","volume":"8","author":"JP Mongan","year":"2009","unstructured":"Mongan JP, et al. Brain metastases from colorectal cancer: risk factors, incidence, and the possible role of chemokines. Clin Colorectal Cancer. 2009;8:100\u20135.","journal-title":"Clin Colorectal Cancer"},{"key":"982_CR11","doi-asserted-by":"publisher","unstructured":"Jin, Z., Breen, W., Jin, R., Brown, P. D. & Hubbard, J. M. Multimodality management of brain metastasis from colorectal cancer. J Clin Oncol 38, 204-204, https:\/\/doi.org\/10.1200\/JCO.2020.38.4\\_suppl.204 (2020).","DOI":"10.1200\/JCO.2020.38.4\\_suppl.204"},{"key":"982_CR12","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1007\/BF02305763","volume":"3","author":"MA Hammoud","year":"1996","unstructured":"Hammoud MA, McCutcheon IE, Elsouki R, Schoppa D, Patt YZ. Colorectal carcinoma and brain metastasis: distribution, treatment, and survival. Ann Surg Oncol. 1996;3:453\u201363. https:\/\/doi.org\/10.1007\/BF02305763.","journal-title":"Ann Surg Oncol"},{"key":"982_CR13","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.clcc.2014.09.008","volume":"13","author":"T Tokoro","year":"2014","unstructured":"Tokoro T, et al. Prognostic factors for patients with advanced colorectal cancer and symptomatic brain metastases. Clin Colorectal Cancer. 2014;13:226\u201331. https:\/\/doi.org\/10.1016\/j.clcc.2014.09.008.","journal-title":"Clin Colorectal Cancer"},{"key":"982_CR14","doi-asserted-by":"publisher","unstructured":"Roussille P, et al. Pathological and molecular characteristics of colorectal cancer with brain metastases. Cancers (Basel). 2018;10 https:\/\/doi.org\/10.3390\/cancers10120504.","DOI":"10.3390\/cancers10120504"},{"key":"982_CR15","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1007\/s00384-013-1781-y","volume":"29","author":"E Magni","year":"2014","unstructured":"Magni E, et al. Brain metastases from colorectal cancer: main clinical factors conditioning outcome. Int J Color Dis. 2014;29:201\u20138. https:\/\/doi.org\/10.1007\/s00384-013-1781-y.","journal-title":"Int J Color Dis"},{"key":"982_CR16","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1080\/0284186X.2017.1290272","volume":"56","author":"TD Christensen","year":"2017","unstructured":"Christensen TD, et al. Risk factors for brain metastases in patients with metastatic colorectal cancer. Acta Oncol. 2017;56:639\u201345. https:\/\/doi.org\/10.1080\/0284186X.2017.1290272.","journal-title":"Acta Oncol"},{"key":"982_CR17","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1002\/cncr.29196","volume":"121","author":"R Yaeger","year":"2015","unstructured":"Yaeger R, et al. RAS mutations affect pattern of metastatic spread and increase propensity for brain metastasis in colorectal cancer. Cancer. 2015;121:1195\u2013203. https:\/\/doi.org\/10.1002\/cncr.29196.","journal-title":"Cancer"},{"key":"982_CR18","doi-asserted-by":"publisher","first-page":"4623","DOI":"10.1002\/cncr.26086","volume":"117","author":"B Tran","year":"2011","unstructured":"Tran B, et al. Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer. Cancer. 2011;117:4623\u201332. https:\/\/doi.org\/10.1002\/cncr.26086.","journal-title":"Cancer"},{"key":"982_CR19","doi-asserted-by":"publisher","first-page":"4772","DOI":"10.1200\/JCO.2004.00.117","volume":"22","author":"M Scartozzi","year":"2004","unstructured":"Scartozzi M, et al. 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;22:4772\u20138. https:\/\/doi.org\/10.1200\/JCO.2004.00.117.","journal-title":"J Clin Oncol"},{"key":"982_CR20","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.2217\/fon.15.2","volume":"11","author":"G De Maglio","year":"2015","unstructured":"De Maglio G, et al. MGMT promoter methylation status in brain metastases from colorectal cancer and corresponding primary tumors. Future Oncol. 2015;11:1201\u20139. https:\/\/doi.org\/10.2217\/fon.15.2.","journal-title":"Future Oncol"},{"key":"982_CR21","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1007\/s12032-014-0152-z","volume":"31","author":"O Tanriverdi","year":"2014","unstructured":"Tanriverdi O, et al. 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;31:152. https:\/\/doi.org\/10.1007\/s12032-014-0152-z.","journal-title":"Med Oncol"},{"key":"982_CR22","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1007\/BF02719380","volume":"51","author":"M Higashiyama","year":"2003","unstructured":"Higashiyama M, et al. 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;51:289\u201396. https:\/\/doi.org\/10.1007\/BF02719380.","journal-title":"Jpn J Thorac Cardiovasc Surg"},{"key":"982_CR23","doi-asserted-by":"publisher","first-page":"1677","DOI":"10.1002\/(sici)1097-0142(19990415)85:8<1677::aid-cncr6>3.0.co;2-c","volume":"85","author":"M Wronski","year":"1999","unstructured":"Wronski M, Arbit E. Resection of brain metastases from colorectal carcinoma in 73 patients. Cancer. 1999;85:1677\u201385. https:\/\/doi.org\/10.1002\/(sici)1097-0142(19990415)85:8<1677::aid-cncr6>3.0.co;2-c.","journal-title":"Cancer"},{"key":"982_CR24","doi-asserted-by":"publisher","first-page":"254","DOI":"10.3747\/co.19.1048","volume":"19","author":"K Damiens","year":"2012","unstructured":"Damiens K, et al. Clinical features and course of brain metastases in colorectal cancer: an experience from a single institution. Curr Oncol. 2012;19:254\u20138. https:\/\/doi.org\/10.3747\/co.19.1048.","journal-title":"Curr Oncol"},{"key":"982_CR25","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1007\/BF02058708","volume":"39","author":"TD Alden","year":"1996","unstructured":"Alden TD, Gianino JW, Saclarides TJ. Brain metastases from colorectal cancer. Dis Colon Rectum. 1996;39:541\u20135. https:\/\/doi.org\/10.1007\/BF02058708.","journal-title":"Dis Colon Rectum"},{"key":"982_CR26","doi-asserted-by":"publisher","first-page":"e378","DOI":"10.1111\/j.1463-1318.2012.02962.x","volume":"14","author":"BH Kye","year":"2012","unstructured":"Kye BH, et al. Brain metastases from colorectal cancer: the role of surgical resection in selected patients. Color Dis. 2012;14:e378\u201385. https:\/\/doi.org\/10.1111\/j.1463-1318.2012.02962.x.","journal-title":"Color Dis"},{"key":"982_CR27","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1186\/1477-7819-12-197","volume":"12","author":"JM Chiang","year":"2014","unstructured":"Chiang JM, et al. 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. https:\/\/doi.org\/10.1186\/1477-7819-12-197.","journal-title":"World J Surg Oncol"},{"key":"982_CR28","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1093\/annonc\/mdt591","volume":"25","author":"N Hugen","year":"2014","unstructured":"Hugen N, van de Velde CJH, de Wilt JHW, Nagtegaal ID. Metastatic pattern in colorectal cancer is strongly influenced by histological subtype. Ann Oncol. 2014;25:651\u20137. https:\/\/doi.org\/10.1093\/annonc\/mdt591.","journal-title":"Ann Oncol"},{"key":"982_CR29","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1159\/000210026","volume":"76","author":"C Nieder","year":"2009","unstructured":"Nieder C, Pawinski A, Balteskard L. Colorectal cancer metastatic to the brain: time trends in presentation and outcome. Oncology. 2009;76:369\u201374. https:\/\/doi.org\/10.1159\/000210026.","journal-title":"Oncology"},{"key":"982_CR30","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1007\/s10151-017-1707-8","volume":"21","author":"IL Silva","year":"2017","unstructured":"Silva IL, et al. A systematic review to assess the management of patients with cerebral metastases secondary to colorectal cancer. Tech Coloproctol. 2017;21:847\u201352. https:\/\/doi.org\/10.1007\/s10151-017-1707-8.","journal-title":"Tech Coloproctol"},{"key":"982_CR31","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/1756-9966-30-10","volume":"30","author":"A Fabi","year":"2011","unstructured":"Fabi A, et al. Brain metastases from solid tumors: disease outcome according to type of treatment and therapeutic resources of the treating center. J Exp Clin Cancer Res. 2011;30:10. https:\/\/doi.org\/10.1186\/1756-9966-30-10.","journal-title":"J Exp Clin Cancer Res"},{"key":"982_CR32","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.radonc.2015.08.023","volume":"117","author":"F Pietrantonio","year":"2015","unstructured":"Pietrantonio F, et al. A new nomogram for estimating survival in patients with brain metastases secondary to colorectal cancer. Radiother Oncol. 2015;117:315\u201321. https:\/\/doi.org\/10.1016\/j.radonc.2015.08.023.","journal-title":"Radiother Oncol"},{"key":"982_CR33","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1016\/s0360-3016(96)00619-0","volume":"37","author":"L Gaspar","year":"1997","unstructured":"Gaspar L, et al. Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys. 1997;37:745\u201351. https:\/\/doi.org\/10.1016\/s0360-3016(96)00619-0.","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"982_CR34","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s11060-004-8093-6","volume":"75","author":"IT Gavrilovic","year":"2005","unstructured":"Gavrilovic IT, Posner JB. Brain metastases: epidemiology and pathophysiology. J Neuro-Oncol. 2005;75:5\u201314. https:\/\/doi.org\/10.1007\/s11060-004-8093-6.","journal-title":"J Neuro-Oncol"},{"key":"982_CR35","doi-asserted-by":"publisher","first-page":"2316","DOI":"10.1002\/cncr.28729","volume":"120","author":"R Yaeger","year":"2014","unstructured":"Yaeger R, et al. BRAF mutation predicts for poor outcomes after metastasectomy in patients with metastatic colorectal cancer. Cancer. 2014;120:2316\u201324. https:\/\/doi.org\/10.1002\/cncr.28729.","journal-title":"Cancer"},{"key":"982_CR36","doi-asserted-by":"publisher","first-page":"2030","DOI":"10.1172\/JCI42002","volume":"120","author":"J Eyles","year":"2010","unstructured":"Eyles J, et al. Tumor cells disseminate early, but immunosurveillance limits metastatic outgrowth, in a mouse model of melanoma. J Clin Invest. 2010;120:2030\u20139. https:\/\/doi.org\/10.1172\/JCI42002.","journal-title":"J Clin Invest"},{"key":"982_CR37","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1038\/nature06309","volume":"450","author":"CM Koebel","year":"2007","unstructured":"Koebel CM, et al. Adaptive immunity maintains occult cancer in an equilibrium state. Nature. 2007;450:903\u20137. https:\/\/doi.org\/10.1038\/nature06309.","journal-title":"Nature"},{"key":"982_CR38","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1038\/ng.3214","volume":"47","author":"A Sottoriva","year":"2015","unstructured":"Sottoriva A, et al. A Big Bang model of human colorectal tumor growth. Nat Genet. 2015;47:209\u201316. https:\/\/doi.org\/10.1038\/ng.3214.","journal-title":"Nat Genet"},{"key":"982_CR39","doi-asserted-by":"publisher","first-page":"5774","DOI":"10.1073\/pnas.1716552115","volume":"115","author":"MD Ryser","year":"2018","unstructured":"Ryser MD, Min BH, Siegmund KD, Shibata D. Spatial mutation patterns as markers of early colorectal tumor cell mobility. Proc Natl Acad Sci U S A. 2018;115:5774\u20139. https:\/\/doi.org\/10.1073\/pnas.1716552115.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"982_CR40","doi-asserted-by":"publisher","unstructured":"Hu, Z. et al. Quantitative evidence for early metastatic seeding in colorectal cancer. Nat Genet 51, 1113-1122, https:\/\/doi.org\/10.1038\/s41588-019-0423-x (2019). A pioneering conceptual and analytical work providing in vivo evidence of the early metastatic spred in colorectal cancer, paving the road for innovative more accurate strategies for patient stratification and therapeutic targeting of the canonical drivers of tumorigenesis.","DOI":"10.1038\/s41588-019-0423-x"},{"key":"982_CR41","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1126\/science.aai8515","volume":"357","author":"K Naxerova","year":"2017","unstructured":"Naxerova K, et al. Origins of lymphatic and distant metastases in human colorectal cancer. Science. 2017;357:55\u201360. https:\/\/doi.org\/10.1126\/science.aai8515.","journal-title":"Science"},{"key":"982_CR42","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1158\/2159-8290.CD-15-0369","volume":"5","author":"PK Brastianos","year":"2015","unstructured":"Brastianos PK, et al. Genomic characterization of brain metastases reveals branched evolution and potential therapeutic targets. Cancer Discov. 2015;5:1164\u201377. https:\/\/doi.org\/10.1158\/2159-8290.CD-15-0369.","journal-title":"Cancer Discov"},{"key":"982_CR43","doi-asserted-by":"publisher","first-page":"1726","DOI":"10.1080\/15384047.2015.1113356","volume":"16","author":"WS El-Deiry","year":"2015","unstructured":"El-Deiry WS, et al. Molecular profiling of 6,892 colorectal cancer samples suggests different possible treatment options specific to metastatic sites. Cancer Biol Ther. 2015;16:1726\u201337. https:\/\/doi.org\/10.1080\/15384047.2015.1113356.","journal-title":"Cancer Biol Ther"},{"key":"982_CR44","doi-asserted-by":"publisher","first-page":"135","DOI":"10.2217\/fon-2016-0196","volume":"13","author":"G Aprile","year":"2017","unstructured":"Aprile G, et al. Comparison of the molecular profile of brain metastases from colorectal cancer and corresponding primary tumors. Future Oncol. 2017;13:135\u201344. https:\/\/doi.org\/10.2217\/fon-2016-0196.","journal-title":"Future Oncol"},{"key":"982_CR45","doi-asserted-by":"crossref","unstructured":"Harter, P. N. et al. Distribution and prognostic relevance of tumor-infiltrating lymphocytes (TILs) and PD-1\/PD-L1 immune checkpoints in human brain metastases. Oncotarget 6, 40836-40849, 10.18632\/oncotarget.5696 (2015).","DOI":"10.18632\/oncotarget.5696"},{"key":"982_CR46","doi-asserted-by":"publisher","first-page":"1953","DOI":"10.1093\/annonc\/mdw289","volume":"27","author":"AS Mansfield","year":"2016","unstructured":"Mansfield AS, et al. Temporal and spatial discordance of programmed cell death-ligand 1 expression and lymphocyte tumor infiltration between paired primary lesions and brain metastases in lung cancer. Ann Oncol. 2016;27:1953\u20138. https:\/\/doi.org\/10.1093\/annonc\/mdw289.","journal-title":"Ann Oncol"},{"key":"982_CR47","doi-asserted-by":"publisher","unstructured":"Sun, J. et al. Genomic signatures reveal DNA damage response deficiency in colorectal cancer brain metastases. Nat Commun 10, 3190, https:\/\/doi.org\/10.1038\/s41467-019-10987-3 (2019). A key study suggesting the need of biomarker-based therapy in CRC BM patients. This study reveals that brain metastases exhibit a significantly diverse mutational pattern than that of their primary colorectal origin and postulates that treatment options should be decided according to the genomic characteristics of metastatic biopsies rather than those of the primary tumor.","DOI":"10.1038\/s41467-019-10987-3"},{"key":"982_CR48","doi-asserted-by":"publisher","unstructured":"Terstappen, L. W. et al. Flow cytometry--principles and feasibility in transfusion medicine. Enumeration of epithelial derived tumor cells in peripheral blood. Vox Sang 74 Suppl 2, 269-274, https:\/\/doi.org\/10.1111\/j.1423-0410.1998.tb05431.x (1998).","DOI":"10.1111\/j.1423-0410.1998.tb05431.x"},{"key":"982_CR49","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.molonc.2016.01.007","volume":"10","author":"MM Ferreira","year":"2016","unstructured":"Ferreira MM, Ramani VC, Jeffrey SS. Circulating tumor cell technologies. Mol Oncol. 2016;10:374\u201394. https:\/\/doi.org\/10.1016\/j.molonc.2016.01.007.","journal-title":"Mol Oncol"},{"key":"982_CR50","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.mam.2019.06.002","volume":"69","author":"M Marcuello","year":"2019","unstructured":"Marcuello M, et al. Circulating biomarkers for early detection and clinical management of colorectal cancer. Mol Asp Med. 2019;69:107\u201322. https:\/\/doi.org\/10.1016\/j.mam.2019.06.002.","journal-title":"Mol Asp Med"},{"key":"982_CR51","doi-asserted-by":"publisher","unstructured":"Hardingham, J. E. et al. Detection and Clinical significance of circulating tumor cells in colorectal cancer--20 years of progress. Mol Med 21 Suppl 1, S25-S31, https:\/\/doi.org\/10.2119\/molmed.2015.00149 (2015).","DOI":"10.2119\/molmed.2015.00149"},{"key":"982_CR52","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1007\/978-3-642-28160-0_6","volume":"195","author":"C Alix-Panabieres","year":"2012","unstructured":"Alix-Panabieres C. EPISPOT assay: detection of viable DTCs\/CTCs in solid tumor patients. Recent Results Cancer Res. 2012;195:69\u201376. https:\/\/doi.org\/10.1007\/978-3-642-28160-0_6.","journal-title":"Recent Results Cancer Res"},{"key":"982_CR53","doi-asserted-by":"crossref","unstructured":"Tsai, W.-S. et al. Prospective clinical study of circulating tumor cells for colorectal cancer screening. J Clin Oncol 36, 556-556, 10.1200\/JCO.2018.36.4\\_suppl.556 (2018).","DOI":"10.1200\/JCO.2018.36.4_suppl.556"},{"key":"982_CR54","doi-asserted-by":"publisher","first-page":"8152","DOI":"10.1158\/1078-0432.CCR-04-1110","volume":"10","author":"S Meng","year":"2004","unstructured":"Meng S, et al. Circulating tumor cells in patients with breast cancer dormancy. Clin Cancer Res. 2004;10:8152\u201362. https:\/\/doi.org\/10.1158\/1078-0432.CCR-04-1110.","journal-title":"Clin Cancer Res"},{"key":"982_CR55","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1038\/nature06385","volume":"450","author":"S Nagrath","year":"2007","unstructured":"Nagrath S, et al. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature. 2007;450:1235\u20139. https:\/\/doi.org\/10.1038\/nature06385.","journal-title":"Nature"},{"key":"982_CR56","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1136\/jclinpath-2014-202499","volume":"67","author":"SH Lim","year":"2014","unstructured":"Lim SH, et al. Circulating tumour cells and the epithelial mesenchymal transition in colorectal cancer. J Clin Pathol. 2014;67:848\u201353. https:\/\/doi.org\/10.1136\/jclinpath-2014-202499.","journal-title":"J Clin Pathol"},{"key":"982_CR57","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1186\/1471-2407-12-178","volume":"12","author":"TM Gorges","year":"2012","unstructured":"Gorges TM, et al. Circulating tumour cells escape from EpCAM-based detection due to epithelial-to-mesenchymal transition. BMC Cancer. 2012;12:178. https:\/\/doi.org\/10.1186\/1471-2407-12-178.","journal-title":"BMC Cancer"},{"key":"982_CR58","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.3892\/ijo.2015.2824","volume":"46","author":"G van Dalum","year":"2015","unstructured":"van Dalum G, et al. Importance of circulating tumor cells in newly diagnosed colorectal cancer. Int J Oncol. 2015;46:1361\u20138. https:\/\/doi.org\/10.3892\/ijo.2015.2824.","journal-title":"Int J Oncol"},{"key":"982_CR59","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1038\/s41467-019-10122-2","volume":"10","author":"YH Cheng","year":"2019","unstructured":"Cheng YH, et al. Hydro-Seq enables contamination-free high-throughput single-cell RNA-sequencing for circulating tumor cells. Nat Commun. 2019;10:2163. https:\/\/doi.org\/10.1038\/s41467-019-10122-2.","journal-title":"Nat Commun"},{"key":"982_CR60","doi-asserted-by":"publisher","first-page":"2195","DOI":"10.1245\/s10434-011-2178-1","volume":"19","author":"NN Rahbari","year":"2012","unstructured":"Rahbari NN, et al. Compartmental differences of circulating tumor cells in colorectal cancer. Ann Surg Oncol. 2012;19:2195\u2013202. https:\/\/doi.org\/10.1245\/s10434-011-2178-1.","journal-title":"Ann Surg Oncol"},{"key":"982_CR61","doi-asserted-by":"publisher","first-page":"1384","DOI":"10.1373\/clinchem.2013.202846","volume":"59","author":"E Deneve","year":"2013","unstructured":"Deneve E, et al. Capture of viable circulating tumor cells in the liver of colorectal cancer patients. Clin Chem. 2013;59:1384\u201392. https:\/\/doi.org\/10.1373\/clinchem.2013.202846.","journal-title":"Clin Chem"},{"key":"982_CR62","doi-asserted-by":"publisher","first-page":"1714","DOI":"10.1053\/j.gastro.2010.01.008","volume":"138","author":"NN Rahbari","year":"2010","unstructured":"Rahbari NN, et al. Meta-analysis shows that detection of circulating tumor cells indicates poor prognosis in patients with colorectal cancer. Gastroenterology. 2010;138:1714\u201326. https:\/\/doi.org\/10.1053\/j.gastro.2010.01.008.","journal-title":"Gastroenterology"},{"key":"982_CR63","doi-asserted-by":"publisher","unstructured":"Gorges, T. M. et al. Improved Detection of circulating tumor cells in metastatic colorectal cancer by the combination of the CellSearch(R) System and the AdnaTest(R). PLoS One 11, e0155126, https:\/\/doi.org\/10.1371\/journal.pone.0155126 (2016).","DOI":"10.1371\/journal.pone.0155126"},{"key":"982_CR64","doi-asserted-by":"publisher","first-page":"2584","DOI":"10.1002\/ijc.31752","volume":"143","author":"KC Andree","year":"2018","unstructured":"Andree KC, et al. Toward a real liquid biopsy in metastatic breast and prostate cancer: diagnostic LeukApheresis increases CTC yields in a European prospective multicenter study (CTCTrap). Int J Cancer. 2018;143:2584\u201391. https:\/\/doi.org\/10.1002\/ijc.31752.","journal-title":"Int J Cancer"},{"key":"982_CR65","doi-asserted-by":"publisher","first-page":"16580","DOI":"10.1073\/pnas.1313594110","volume":"110","author":"JC Fischer","year":"2013","unstructured":"Fischer JC, et al. Diagnostic leukapheresis enables reliable detection of circulating tumor cells of nonmetastatic cancer patients. Proc Natl Acad Sci U S A. 2013;110:16580\u20135. https:\/\/doi.org\/10.1073\/pnas.1313594110.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"982_CR66","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1038\/s41551-018-0257-3","volume":"2","author":"O Vermesh","year":"2018","unstructured":"Vermesh O, et al. An intravascular magnetic wire for the high-throughput retrieval of circulating tumour cells in vivo. Nat Biomed Eng. 2018;2:696\u2013705. https:\/\/doi.org\/10.1038\/s41551-018-0257-3.","journal-title":"Nat Biomed Eng"},{"key":"982_CR67","doi-asserted-by":"publisher","first-page":"345ra389","DOI":"10.1126\/scitranslmed.aad7369","volume":"8","author":"I Cima","year":"2016","unstructured":"Cima I, et al. Tumor-derived circulating endothelial cell clusters in colorectal cancer. Sci Transl Med. 2016;8:345ra389. https:\/\/doi.org\/10.1126\/scitranslmed.aad7369.","journal-title":"Sci Transl Med"},{"key":"982_CR68","doi-asserted-by":"publisher","first-page":"2241","DOI":"10.1002\/1873-3468.12662","volume":"591","author":"C Alix-Panabieres","year":"2017","unstructured":"Alix-Panabieres C, Pantel K. Characterization of single circulating tumor cells. FEBS Lett. 2017;591:2241\u201350. https:\/\/doi.org\/10.1002\/1873-3468.12662.","journal-title":"FEBS Lett"},{"key":"982_CR69","doi-asserted-by":"publisher","first-page":"2965","DOI":"10.1158\/0008-5472.CAN-12-4140","volume":"73","author":"E Heitzer","year":"2013","unstructured":"Heitzer E, et al. Complex tumor genomes inferred from single circulating tumor cells by array-CGH and next-generation sequencing. Cancer Res. 2013;73:2965\u201375. https:\/\/doi.org\/10.1158\/0008-5472.CAN-12-4140.","journal-title":"Cancer Res"},{"key":"982_CR70","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1016\/j.molonc.2014.12.011","volume":"9","author":"NA Mohamed Suhaimi","year":"2015","unstructured":"Mohamed Suhaimi NA, et al. Non-invasive sensitive detection of KRAS and BRAF mutation in circulating tumor cells of colorectal cancer patients. Mol Oncol. 2015;9:850\u201360. https:\/\/doi.org\/10.1016\/j.molonc.2014.12.011.","journal-title":"Mol Oncol"},{"key":"982_CR71","first-page":"241","volume":"142","author":"P Mandel","year":"1948","unstructured":"Mandel P, Metais P. Nuclear acids in human blood plasma. C R Seances Soc Biol Fil. 1948;142:241\u20133.","journal-title":"C R Seances Soc Biol Fil"},{"key":"982_CR72","first-page":"139","volume":"4","author":"SA Leon","year":"1977","unstructured":"Leon SA, Ehrlich GE, Shapiro B, Labbate VA. Free DNA in the serum of rheumatoid arthritis patients. J Rheumatol. 1977;4:139\u201343.","journal-title":"J Rheumatol"},{"key":"982_CR73","doi-asserted-by":"publisher","first-page":"224ra224","DOI":"10.1126\/scitranslmed.3007094","volume":"6","author":"C Bettegowda","year":"2014","unstructured":"Bettegowda C, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014;6:224ra224. https:\/\/doi.org\/10.1126\/scitranslmed.3007094.","journal-title":"Sci Transl Med"},{"key":"982_CR74","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1038\/nrc.2017.7","volume":"17","author":"JCM Wan","year":"2017","unstructured":"Wan JCM, et al. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat Rev Cancer. 2017;17:223\u201338. https:\/\/doi.org\/10.1038\/nrc.2017.7.","journal-title":"Nat Rev Cancer"},{"key":"982_CR75","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1158\/2159-8290.CD-17-1009","volume":"8","author":"JH Strickler","year":"2018","unstructured":"Strickler JH, et al. Genomic landscape of cell-free DNA in Patients with colorectal cancer. Cancer Discov. 2018;8:164\u201373. https:\/\/doi.org\/10.1158\/2159-8290.CD-17-1009.","journal-title":"Cancer Discov"},{"key":"982_CR76","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1136\/gutjnl-2014-308859","volume":"65","author":"T Reinert","year":"2016","unstructured":"Reinert T, et al. Analysis of circulating tumour DNA to monitor disease burden following colorectal cancer surgery. Gut. 2016;65:625\u201334. https:\/\/doi.org\/10.1136\/gutjnl-2014-308859.","journal-title":"Gut"},{"key":"982_CR77","doi-asserted-by":"publisher","first-page":"346ra392","DOI":"10.1126\/scitranslmed.aaf6219","volume":"8","author":"J Tie","year":"2016","unstructured":"Tie J, et al. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med. 2016;8:346ra392. https:\/\/doi.org\/10.1126\/scitranslmed.aaf6219.","journal-title":"Sci Transl Med"},{"key":"982_CR78","doi-asserted-by":"publisher","first-page":"5416","DOI":"10.1158\/1078-0432.CCR-16-3155","volume":"23","author":"F Garlan","year":"2017","unstructured":"Garlan F, et al. Early evaluation of circulating tumor DNA as marker of therapeutic efficacy in metastatic colorectal cancer patients (PLACOL Study). Clin Cancer Res. 2017;23:5416\u201325. https:\/\/doi.org\/10.1158\/1078-0432.CCR-16-3155.","journal-title":"Clin Cancer Res"},{"key":"982_CR79","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.1158\/1078-0432.CCR-19-3467","volume":"26","author":"AR Parikh","year":"2020","unstructured":"Parikh AR, et al. Serial ctDNA monitoring to predict response to systemic therapy in metastatic gastrointestinal cancers. Clin Cancer Res. 2020;26:1877\u201385. https:\/\/doi.org\/10.1158\/1078-0432.CCR-19-3467.","journal-title":"Clin Cancer Res"},{"key":"982_CR80","doi-asserted-by":"publisher","unstructured":"Naidoo M, Gibbs P, Tie J. ctDNA and Adjuvant therapy for colorectal cancer: time to re-invent our treatment paradigm. Cancers (Basel). 2021;13 https:\/\/doi.org\/10.3390\/cancers13020346.","DOI":"10.3390\/cancers13020346"},{"key":"982_CR81","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/s41576-018-0071-5","volume":"20","author":"E Heitzer","year":"2019","unstructured":"Heitzer E, Haque IS, Roberts CES, Speicher MR. Current and future perspectives of liquid biopsies in genomics-driven oncology. Nat Rev Genet. 2019;20:71\u201388. https:\/\/doi.org\/10.1038\/s41576-018-0071-5.","journal-title":"Nat Rev Genet"},{"key":"982_CR82","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1016\/S1470-2045(18)30904-5","volume":"20","author":"F Meric-Bernstam","year":"2019","unstructured":"Meric-Bernstam F, et al. Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway): an updated report from a multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol. 2019;20:518\u201330. https:\/\/doi.org\/10.1016\/S1470-2045(18)30904-5.","journal-title":"Lancet Oncol"},{"key":"982_CR83","doi-asserted-by":"publisher","first-page":"3046","DOI":"10.1158\/1078-0432.CCR-18-3389","volume":"25","author":"G Siravegna","year":"2019","unstructured":"Siravegna G, et al. Plasma HER2 (ERBB2) copy number predicts response to HER2-targeted therapy in metastatic colorectal cancer. Clin Cancer Res. 2019;25:3046\u201353. https:\/\/doi.org\/10.1158\/1078-0432.CCR-18-3389.","journal-title":"Clin Cancer Res"},{"key":"982_CR84","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1038\/bjc.2011.26","volume":"104","author":"N Knijn","year":"2011","unstructured":"Knijn N, et al. KRAS mutation analysis: a comparison between primary tumours and matched liver metastases in 305 colorectal cancer patients. Br J Cancer. 2011;104:1020\u20136. https:\/\/doi.org\/10.1038\/bjc.2011.26.","journal-title":"Br J Cancer"},{"key":"982_CR85","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1001\/jamaoncol.2018.5080","volume":"5","author":"C Cremolini","year":"2019","unstructured":"Cremolini C, et al. Rechallenge for patients with RAS and BRAF wild-type metastatic colorectal cancer with acquired resistance to first-line cetuximab and irinotecan: a phase 2 single-arm clinical trial. JAMA Oncol. 2019;5:343\u201350. https:\/\/doi.org\/10.1001\/jamaoncol.2018.5080.","journal-title":"JAMA Oncol"},{"key":"982_CR86","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1056\/NEJMoa1213261","volume":"368","author":"SJ Dawson","year":"2013","unstructured":"Dawson SJ, et al. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med. 2013;368:1199\u2013209. https:\/\/doi.org\/10.1056\/NEJMoa1213261.","journal-title":"N Engl J Med"},{"key":"982_CR87","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1373\/clinchem.2014.222679","volume":"61","author":"E Heitzer","year":"2015","unstructured":"Heitzer E, Ulz P, Geigl JB. Circulating tumor DNA as a liquid biopsy for cancer. Clin Chem. 2015;61:112\u201323. https:\/\/doi.org\/10.1373\/clinchem.2014.222679.","journal-title":"Clin Chem"},{"key":"982_CR88","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1373\/clinchem.2015.253476","volume":"62","author":"J Tie","year":"2016","unstructured":"Tie J, Gibbs P. Sequencing circulating cell-free DNA: the potential to refine precision cancer medicine. Clin Chem. 2016;62:796\u20138. https:\/\/doi.org\/10.1373\/clinchem.2015.253476.","journal-title":"Clin Chem"},{"key":"982_CR89","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1200\/JCO.2005.04.6235","volume":"24","author":"MA Vogelbaum","year":"2006","unstructured":"Vogelbaum MA, Suh JH. Resectable brain metastases. J Clin Oncol. 2006;24:1289\u201394. https:\/\/doi.org\/10.1200\/JCO.2005.04.6235.","journal-title":"J Clin Oncol"},{"key":"982_CR90","doi-asserted-by":"publisher","first-page":"i1","DOI":"10.1093\/neuonc\/now197","volume":"19","author":"MC Chamberlain","year":"2017","unstructured":"Chamberlain MC, Baik CS, Gadi VK, Bhatia S, Chow LQ. Systemic therapy of brain metastases: non-small cell lung cancer, breast cancer, and melanoma. Neuro-Oncology. 2017;19:i1\u2013i24. https:\/\/doi.org\/10.1093\/neuonc\/now197.","journal-title":"Neuro-Oncology"},{"key":"982_CR91","doi-asserted-by":"crossref","unstructured":"De Falco, V. et al. - How we treat metastatic colorectal cancer. - ESMO Open2020 Aug 01; 4, - e000813.","DOI":"10.1136\/esmoopen-2020-000813"},{"key":"982_CR92","doi-asserted-by":"publisher","first-page":"5255","DOI":"10.1200\/JCO.2009.22.0616","volume":"27","author":"MA Socinski","year":"2009","unstructured":"Socinski MA, et al. Safety of bevacizumab in patients with non-small-cell lung cancer and brain metastases. J Clin Oncol. 2009;27:5255\u201361. https:\/\/doi.org\/10.1200\/JCO.2009.22.0616.","journal-title":"J Clin Oncol"},{"key":"982_CR93","doi-asserted-by":"publisher","unstructured":"The advantage of bevacizumab in treating colorectal brain metastasis. Journal of Cancer Research and Practice. 2014;1:146\u201351. https:\/\/doi.org\/10.6323\/JCRP.2014.1.2.08.","DOI":"10.6323\/JCRP.2014.1.2.08"},{"key":"982_CR94","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1159\/000360132","volume":"7","author":"Y Yoshida","year":"2014","unstructured":"Yoshida Y, et al. Efficacy of XELOX plus bevacizumab in brain metastasis from rectal cancer. Case Rep Oncol. 2014;7:117\u201321. https:\/\/doi.org\/10.1159\/000360132.","journal-title":"Case Rep Oncol"},{"key":"982_CR95","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1097\/01.cad.0000236313.50833.ee","volume":"18","author":"HJ Stemmler","year":"2007","unstructured":"Stemmler HJ, et al. Ratio of trastuzumab levels in serum and cerebrospinal fluid is altered in HER2-positive breast cancer patients with brain metastases and impairment of blood-brain barrier. Anti-Cancer Drugs. 2007;18:23\u20138. https:\/\/doi.org\/10.1097\/01.cad.0000236313.50833.ee.","journal-title":"Anti-Cancer Drugs"},{"key":"982_CR96","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.ctrv.2018.05.004","volume":"67","author":"R Duchnowska","year":"2018","unstructured":"Duchnowska R, Loibl S, Jassem J. Tyrosine kinase inhibitors for brain metastases in HER2-positive breast cancer. Cancer Treat Rev. 2018;67:71\u20137. https:\/\/doi.org\/10.1016\/j.ctrv.2018.05.004.","journal-title":"Cancer Treat Rev"},{"key":"982_CR97","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1016\/j.phrs.2017.11.006","volume":"129","author":"J Wang","year":"2018","unstructured":"Wang J, et al. P-glycoprotein (MDR1\/ABCB1) and breast cancer resistance protein (BCRP\/ABCG2) affect brain accumulation and intestinal disposition of encorafenib in mice. Pharmacol Res. 2018;129:414\u201323. https:\/\/doi.org\/10.1016\/j.phrs.2017.11.006.","journal-title":"Pharmacol Res"},{"key":"982_CR98","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1002\/cncr.32547","volume":"126","author":"K Holbrook","year":"2020","unstructured":"Holbrook K, et al. Intracranial antitumor activity with encorafenib plus binimetinib in patients with melanoma brain metastases: a case series. Cancer. 2020;126:523\u201330. https:\/\/doi.org\/10.1002\/cncr.32547.","journal-title":"Cancer"},{"key":"982_CR99","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1038\/nm.4292","volume":"23","author":"H Davies","year":"2017","unstructured":"Davies H, et al. HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures. Nat Med. 2017;23:517\u201325. https:\/\/doi.org\/10.1038\/nm.4292.","journal-title":"Nat Med"},{"key":"982_CR100","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/s11095-014-1442-z","volume":"32","author":"S Durmus","year":"2015","unstructured":"Durmus S, et al. Breast cancer resistance protein (BCRP\/ABCG2) and P-glycoprotein (P-GP\/ABCB1) restrict oral availability and brain accumulation of the PARP inhibitor rucaparib (AG-014699). Pharm Res. 2015;32:37\u201346. https:\/\/doi.org\/10.1007\/s11095-014-1442-z.","journal-title":"Pharm Res"},{"key":"982_CR101","doi-asserted-by":"publisher","first-page":"5236","DOI":"10.1021\/acs.molpharmaceut.8b00742","volume":"15","author":"MC de Gooijer","year":"2018","unstructured":"de Gooijer MC, et al. ABCB1 attenuates the brain penetration of the PARP inhibitor AZD2461. Mol Pharm. 2018;15:5236\u201343. https:\/\/doi.org\/10.1021\/acs.molpharmaceut.8b00742.","journal-title":"Mol Pharm"},{"key":"982_CR102","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/j.neo.2020.06.009","volume":"22","author":"Y Xiong","year":"2020","unstructured":"Xiong Y, et al. Pamiparib is a potent and selective PARP inhibitor with unique potential for the treatment of brain tumor. Neoplasia. 2020;22:431\u201340. https:\/\/doi.org\/10.1016\/j.neo.2020.06.009.","journal-title":"Neoplasia"},{"key":"982_CR103","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.ccell.2017.02.009","volume":"31","author":"DF Quail","year":"2017","unstructured":"Quail DF, Joyce JA. The microenvironmental landscape of brain tumors. Cancer Cell. 2017;31:326\u201341. https:\/\/doi.org\/10.1016\/j.ccell.2017.02.009.","journal-title":"Cancer Cell"},{"key":"982_CR104","doi-asserted-by":"publisher","unstructured":"Di Giacomo, A. M. et al. Immunotherapy of brain metastases: breaking a \"dogma\". J Exp Clin Cancer Res 38, 419, https:\/\/doi.org\/10.1186\/s13046-019-1426-2 (2019). A \"dogma\"-breaking work gathering conceptual as well as clinical proof of the potential of immunotherapy to control brain metastases from different primary diseases.","DOI":"10.1186\/s13046-019-1426-2"},{"key":"982_CR105","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1016\/S1470-2045(16)30053-5","volume":"17","author":"SB Goldberg","year":"2016","unstructured":"Goldberg SB, et al. Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. Lancet Oncol. 2016;17:976\u201383. https:\/\/doi.org\/10.1016\/S1470-2045(16)30053-5.","journal-title":"Lancet Oncol"},{"key":"982_CR106","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.3389\/fonc.2020.01443","volume":"10","author":"R Huang","year":"2020","unstructured":"Huang R, Boltze J, Li S. Strategies for improved intra-arterial treatments targeting brain tumors: a systematic review. Front Oncol. 2020;10:1443. https:\/\/doi.org\/10.3389\/fonc.2020.01443.","journal-title":"Front Oncol"},{"key":"982_CR107","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1007\/s11060-016-2099-8","volume":"128","author":"S Chakraborty","year":"2016","unstructured":"Chakraborty S, et al. Superselective intraarterial cerebral infusion of cetuximab after osmotic blood\/brain barrier disruption for recurrent malignant glioma: phase I study. J Neuro-Oncol. 2016;128:405\u201315. https:\/\/doi.org\/10.1007\/s11060-016-2099-8.","journal-title":"J Neuro-Oncol"},{"key":"982_CR108","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.wneu.2011.05.056","volume":"77","author":"JK Burkhardt","year":"2012","unstructured":"Burkhardt JK, et al. Intra-arterial delivery of bevacizumab after blood-brain barrier disruption for the treatment of recurrent glioblastoma: progression-free survival and overall survival. World Neurosurg. 2012;77:130\u20134. https:\/\/doi.org\/10.1016\/j.wneu.2011.05.056.","journal-title":"World Neurosurg"},{"key":"982_CR109","doi-asserted-by":"publisher","first-page":"3503","DOI":"10.1200\/JCO.2008.19.3789","volume":"27","author":"L Angelov","year":"2009","unstructured":"Angelov L, et al. Blood-brain barrier disruption and intra-arterial methotrexate-based therapy for newly diagnosed primary CNS lymphoma: a multi-institutional experience. J Clin Oncol. 2009;27:3503\u20139. https:\/\/doi.org\/10.1200\/JCO.2008.19.3789.","journal-title":"J Clin Oncol"},{"key":"982_CR110","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1002\/cncr.22450","volume":"109","author":"D Fortin","year":"2007","unstructured":"Fortin D, Gendron C, Boudrias M, Garant MP. Enhanced chemotherapy delivery by intraarterial infusion and blood-brain barrier disruption in the treatment of cerebral metastasis. Cancer. 2007;109:751\u201360. https:\/\/doi.org\/10.1002\/cncr.22450.","journal-title":"Cancer"},{"key":"982_CR111","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1002\/(SICI)1097-0142(19960815)78:4<711::AID-CNCR3>3.0.CO;2-H","volume":"78","author":"GF Farnell","year":"1996","unstructured":"Farnell GF, et al. Brain metastases from colorectal carcinoma. The long term survivors Cancer. 1996;78:711\u20136. https:\/\/doi.org\/10.1002\/(SICI)1097-0142(19960815)78:4<711::AID-CNCR3>3.0.CO;2-H.","journal-title":"The long term survivors Cancer"},{"key":"982_CR112","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.clcc.2020.09.002","volume":"19","author":"ML Shindorf","year":"2020","unstructured":"Shindorf ML, Jafferji MS, Goff SL. Incidence of asymptomatic brain metastases in metastatic colorectal cancer. Clin Colorectal Cancer. 2020;19:263\u20139. https:\/\/doi.org\/10.1016\/j.clcc.2020.09.002.","journal-title":"Clin Colorectal Cancer"}],"container-title":["Current Treatment Options in Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11864-022-00982-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11864-022-00982-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11864-022-00982-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T16:22:48Z","timestamp":1654618968000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11864-022-00982-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,28]]},"references-count":112,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["982"],"URL":"https:\/\/doi.org\/10.1007\/s11864-022-00982-0","relation":{},"ISSN":["1527-2729","1534-6277"],"issn-type":[{"value":"1527-2729","type":"print"},{"value":"1534-6277","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,28]]},"assertion":[{"value":"21 March 2022","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 April 2022","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Thibaud Koessler discloses consulting and advisory role for Merck Sharp@Dohme (MSD), BMS, Lilly, Roche, Boehringer Ingelheim, and Servie. He has also benefited from Travel grants by Lilly, Ipsen, and Sanofi. The remaining authors have declared no conflicts of interest in connection with this article.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}}]}}