Skip to main content

Advertisement

SpringerLink
Log in

Precision Medical Approaches to the Diagnoses and Management of Brain Metastases

  • Neuro-oncology (GJ Lesser, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Brain metastases represent a common and devastating complication of cancer with survival on the order of a few months in most patients. Melanoma, breast cancer, and lung cancer remain the primary disease histologies with the highest rates of metastatic spread to the brain. The incidence of brain metastases has continued to rise, likely explained by multiple factors. Improvement in progression-free survival in systemic cancer is likely attributable to advances in medical therapy, earlier supportive and symptomatic care, and improved precision around diagnosis and detection. In this context, longer survival and improved extracranial control disease has likely contributed to the increased development of metastatic spread intracranially. The foundation of management remains systemic therapy, as well as a combination of surgery and radiation therapy. In the era of targeted therapies, specific agents have demonstrated improved CNS penetration, however with varying degrees of durable responses. Most patients develop resistance to targeted agents, limiting their duration of use for patients. In this era of personalized medicine, the role of genomic characterization in cancer has been critical in the field of brain metastases, as alterations unique to both the brain metastases and its systemic predecessor have been identified, potentially offering new avenues for therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Brastianos HC, Cahill DP, Brastianos PK. Systemic therapy of brain metastases. Curr Neurol Neurosci Rep. 2015;15(2):518.

    PubMed  Google Scholar 

  2. Leece R, Xu J, Ostrom QT, Chen Y, Kruchko C, Barnholtz-Sloan JS. Global incidence of malignant brain and other central nervous system tumors by histology, 2003-2007. Neuro Oncol. 2017. Oct 19;19(11):1553-1564

    PubMed  PubMed Central  Google Scholar 

  3. Cagney DN, Martin AM, Catalano PJ, Redig AJ, Lin NU, Lee EQ, et al. Incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy: a population-based study. Neuro-Oncology. 2017. Oct 19;19(11):1511-1521

    PubMed  PubMed Central  Google Scholar 

  4. Neagu MR, Gill CM, Batchelor TT, Brastianos PK. Genomic profiling of brain metastases: current knowledge and new frontiers. Chin Clin Oncol. 2015;4(2):22.

    PubMed  Google Scholar 

  5. Fox BD, Cheung VJ, Patel AJ, Suki D, Rao G. Epidemiology of metastatic brain tumors. Neurosurg Clin N Am. 2011;22(1):1–6.

    PubMed  Google Scholar 

  6. Sperduto PW, Chao ST, Sneed PK, Luo X, Suh J, Roberge D, et al. Diagnosis-specific prognostic factors, indexes, and treatment outcomes for patients with newly diagnosed brain metastases: a multi-institutional analysis of 4,259 patients. Int J Radiat Oncol Biol Phys. 2010 Jul 1;77(3):655–61.

    PubMed  Google Scholar 

  7. Kort A, Sparidans RW, Wagenaar E, Beijnen JH, Schinkel AH. Brain accumulation of the EML4-ALK inhibitor ceritinib is restricted by P-glycoprotein (P-GP/ABCB1) and breast cancer resistance protein (BCRP/ABCG2). Pharmacol Res. 2015 Dec;102:200–7.

    CAS  PubMed  Google Scholar 

  8. •• Brastianos PK, Carter SL, Santagata S, Cahill DP, Taylor-Weiner A, Jones RT, et al. Genomic characterization of brain metastases reveals branched evolution and potential therapeutic targets. Cancer Discov. 2015;5(11):1164–77 This paper discusses the genomic divergence of brain metastases from the primary disease site and other sites of disease.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. •• Pentsova EI, Shah RH, Tang J, Boire A, You D, Briggs S, et al. Evaluating cancer of the central nervous system through next-generation sequencing of cerebrospinal fluid. J Clin Oncol. 2016;34(20):2404–15 This is a compelling investigation of non-invasive strategies towards understanding natural history and potentially treatment response using cerebrospinal fluid for CNS tumors.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Villarreal-Garza C, de la Mata D, Zavala DG, Macedo-Perez EO, Arrieta O. Aggressive treatment of primary tumor in patients with non-small-cell lung cancer and exclusively brain metastases. Clin Lung Cancer. 2013;14:6–13.

    CAS  PubMed  Google Scholar 

  11. 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;94:2698–705.

    PubMed  Google Scholar 

  12. Barlesi F, Gervais R. Lena H Pemetrexed and cisplatin as first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) with asymptomatic inoperable brain metastases: a multicenter phase II trial (GFPC 07–01). Ann Oncol. 2011;22(11):2466–70.

    CAS  PubMed  Google Scholar 

  13. Bearz A, Garassino I, Tiseo M. Activity of pemetrexed on brain metastases from non-small cell lung cancer. Lung Cancer. 2010;68(2):264–8.

    PubMed  Google Scholar 

  14. • Sperduto PW, Yang TJ, Beal K, Pan H, Brown PD, Bangdiwala A, Shanley R, Yeh N, Gaspar LE, Braunstein S, Sneed P, Boyle J, Kirkpatrick JP, Mak KS, Shih HA, Engelman A, Roberge D, Arvold ND, Alexander B, Awad MM, Contessa J, Chiang V, Hardie J, Ma D, Lou E, Sperduto W, Mehta MP. Estimating Survival in Patients With Lung Cancer and Brain Metastases: An Update of the Graded Prognostic Assessment for Lung Cancer Using Molecular Markers (Lung-molGPA). JAMA Oncol. 2017 Jun 1;3(6):827-831.This is a follow-up to the 2010 paper, now incorporating genomic signals into collective understanding of survival, in brain metastases from solid tumors.

    PubMed  Google Scholar 

  15. Arteaga CL. Overview of epidermal growth factor receptor biology and its role as a therapeutic target in human neoplasia. Semin Oncol. 2002 Oct;29(5 Suppl 14):3–9.

    CAS  PubMed  Google Scholar 

  16. Kosaka T, Yatabe Y, Endoh H, Kuwano H, Takahashi T, Mitsudomi T. Mutations of the epidermal growth factor receptor gene in lung cancer: biological and clinical implications. Cancer Res. 2004 Dec 15;64(24):8919–23.

    CAS  PubMed  Google Scholar 

  17. Bunn PA Jr, Franklin W. Epidermal growth factor receptor expression, signal pathway, and inhibitors in non-small cell lung cancer. Semin Oncol. 2002 Oct;29(5 Suppl 14):38–44.

    CAS  PubMed  Google Scholar 

  18. Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13(3):239–46.

    CAS  PubMed  Google Scholar 

  19. Bauml J, Mick R, Zhang Y. Frequency of EGFR and KRAS mutations in patients with non-small cell lung cancer by racial background: do disparities exist? Lung Cancer. 2013;81(3):347–53.

    PubMed  PubMed Central  Google Scholar 

  20. Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, et al. Ramalingam SS; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378(2):113–25.

    CAS  PubMed  Google Scholar 

  21. Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361(10):947–57.

    CAS  PubMed  Google Scholar 

  22. Sequist LV, Yang JC, Yamamoto N, O’Byrne K, Hirsh V, Mok T, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013;31(27):3327–34.

    CAS  PubMed  Google Scholar 

  23. Lee CK, Davies L, Wu YL, Mitsudomi T, Inoue A, Rosell R, et al. Gefitinib or erlotinib vs chemotherapy for EGFR mutation-positive lung cancer: individual patient data meta-analysis of overall survival. J Natl Cancer Inst. 2017; Jun 1;109(6).

  24. Porta R, Sánchez-Torres JM, Paz-Ares L, Massutí B, Reguart N, Mayo C, et al. Brain metastases from lung cancer responding to erlotinib: the importance of EGFR mutation. Eur Respir J. 2011;37(3):624–31.

    CAS  PubMed  Google Scholar 

  25. Wu YL, Zhou C, Cheng Y, Lu S, Chen GY, Huang C, et al. Erlotinib as second-line treatment in patients with advanced non-small-cell lung cancer and asymptomatic brain metastases: a phase II study (CTONG-0803). Ann Oncol. 2013;24(4):993–9.

    PubMed  Google Scholar 

  26. Yang JC, Hirsh V, Schuler M, Yamamoto N, O’Byrne KJ, Mok TS, et al. Symptom control and quality of life in LUX-Lung 3: a phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013;31(27):3342–50.

    CAS  PubMed  Google Scholar 

  27. Wu YL, Zhou C, Hu CP, Feng J, Lu S, Huang Y, et al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol. 2014;15(2):213–22.

    CAS  PubMed  Google Scholar 

  28. Cataldo VD, Gibbons DL, Pérez-Soler R, Quintás-Cardama A. Treatment of non-small-cell lung cancer with erlotinib or gefitinib. N Engl J Med. 2011;364(10):947–55.

    CAS  PubMed  Google Scholar 

  29. • Goss G, Tsai C-M, Shepherd F, et al. MA16.11 CNS response to osimertinib in patients with T790M-positive advanced NSCLC: pooled data from two phase II trials. J Thorac Oncol. 2017;12(1):Suppl:S440-S441 Retrospective analysis of CNS response to osimertinib in metastastic NSCLC.

    Google Scholar 

  30. • Mok TS, Wu Y-L, Ahn M-J, Garassino MC, Kim HR, Ramalingam SS, et al. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017;376(7):629–40 In combination with the Goss paper, this highlights the efficacy of osimertinib in EGFR-mutated NSCLC patients with brain metastases.

    CAS  PubMed  Google Scholar 

  31. Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007;448(7153):561–6.

    CAS  PubMed  Google Scholar 

  32. Takahashi T, Sonobe M, Kobayashi M, Yoshizawa A, Menju T, Nakayama E, et al. Clinicopathologic features of non-small-cell lung cancer with EML4-ALK fusion gene. Ann Surg Oncol. 2010;17(3):889–97.

    PubMed  Google Scholar 

  33. Costa DB, Shaw AT, Ou SH. Clinical experience with crizotinib in patients with advanced ALK-rearranged non-small-cell lung cancer and brain metastases. J Clin Oncol. 2015;33(17):1881–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Kim DW, Tiseo M, Ahn MJ, Reckamp KL, Hansen KH, Kim SW, et al. Brigatinib in patients with Crizotinib-refractory anaplastic lymphoma kinase-positive non-small-cell lung cancer: a randomized. Multicenter Phase II Trial J Clin Oncol. 2017;5:JCO2016715904. https://doi.org/10.1200/JCO.2016.71.5904 [Epub ahead of print].

    CAS  PubMed  Google Scholar 

  35. Soria JC, Tan DS, Chiari R, Wu YL, Paz-Ares L, Wolf J, et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet. 2017;389(10072):917–29.

    CAS  PubMed  Google Scholar 

  36. Hida T, Nokihara H, Kondo M, Kim YH, Azuma K, Seto T, et al. Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. Lancet. 2017;390(10089):29–39.

    CAS  PubMed  Google Scholar 

  37. Gainor JF, Shaw AT. J-ALEX: alectinib versus crizotinib in ALK-positive lung cancer. Lancet. 2017;390(10089):3–4.

    PubMed  Google Scholar 

  38. Zhou C, Lu Y, Kim SW, et al. Primary results of ALESIA: a randomised, phase III, open-label study of alectinib vs crizotinib in Asian patients with treatment-naïve ALK+ advanced NSCLC. Eur Soc Med Oncol. 2018:LBA10.

  39. Camidge DR, Kim DW, Tiseo M, Langer CJ, Ahn MJ, Shaw AT, et al. Exploratory analysis of brigatinib activity in patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer and brain metastases in two clinical trials. J Clin Oncol. 2018;36(26):2693–701.

    CAS  PubMed  Google Scholar 

  40. Ilhan-Mutlu A, Siehs C, Berghoff AS, Ricken G, Widhalm G, Wagner L, et al. Expression profiling of angiogenesis-related genes in brain metastases of lung cancer and melanoma. Tumour Biol. 2016;37(1):1173–82.

    CAS  PubMed  Google Scholar 

  41. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30.

    PubMed  Google Scholar 

  42. 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.

    PubMed  Google Scholar 

  43. Evans AJ, James JJ, Cornford EJ, Chan SY, Burrell HC, Pinder SE, et al. Brain metastases from breast cancer: identification of a high-risk group. Clin Oncol (R Coll Radiol). 2004;16(5):345–9.

    CAS  Google Scholar 

  44. Pestalozzi BC, Zahrieh D, Price KN, Holmberg SB, Lindtner J, Collins J, et al. Identifying breast cancer patients at risk for central nervous system (CNS) metastases in trials of the International Breast Cancer Study Group (IBCSG). Ann Oncol. 2006;17(6):935–44.

    CAS  PubMed  Google Scholar 

  45. Lin NU, Amiri-Kordestani L, Palmieri D, Liewehr DJ, Steeg PS. CNS metastases in breast cancer: old challenge, new frontiers. Clin Cancer Res. 2013;19(23):6404–18.

    CAS  PubMed  Google Scholar 

  46. Ross JS, Gay LM. Comprehensive genomic sequencing and the molecular profiles of clinically advanced breast cancer. Pathology. 2017;49(2):120–32.

    CAS  PubMed  Google Scholar 

  47. Tham YL, Sexton K, Kramer R, Hilsenbeck S, Elledge R. Primary breast cancer phenotypes associated with propensity for central nervous system metastases. Cancer. 2006;107(4):696–704.

    PubMed  Google Scholar 

  48. Dawood S, Broglio K, Buzdar AU, Hortobagyi GN, Giordano SH. Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: an institutional-based review. J Clin Oncol. 2010;28:92–8.

    CAS  PubMed  Google Scholar 

  49. Brufsky AM, Mayer M, Rugo HS, Kaufman PA, Tan-Chiu E, Tripathy D, et al. Central nervous system metastases in patients with HER2-positive metastatic breast cancer: incidence, treatment, and survival in patients from registHER. Clin Cancer Res. 2011 Jul 15;17(14):4834–43.

    CAS  PubMed  Google Scholar 

  50. de Azambuja E, Zardavas D, Lemort M, Rossari J, Moulin C, Buttice A, et al. Phase I trial combining temozolomide plus lapatinib for the treatment of brain metastases in patients with HER2-positive metastatic breast cancer: the LAPTEM trial. Ann Oncol. 2013;24(12):2985–9.

    PubMed  Google Scholar 

  51. Rabindran SK, Discafani CM, Rosfjord EC, Baxter M, Floyd MB, Golas J, et al. Antitumor activity of HKI-272, an orally active, irreversibleinhibitor of the HER-2 tyrosine kinase. Cancer Res. 2004;64(11):3958–65.

    CAS  PubMed  Google Scholar 

  52. Bachelot T, Romieu G, Campone M, Diéras V, Cropet C, Dalenc F, et al. Lapatinib plus capecitabine in patients with previously untreated brain metastases from HER2-positive metastatic breast cancer (LANDSCAPE): a single-group phase 2 study. Lancet Oncol. 2013;14(1):64–71.

    CAS  PubMed  Google Scholar 

  53. Freedman RA, Gelman RS, Wefel JS, Melisko ME, Hess KR, Connolly RM, et al. Translational Breast cancer Research Consortium (TBCRC) 022: a phase II trial of neratinib for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases. J Clin Oncol. 2016;34(9):945–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Xu H, Yu S, Liu Q, Yuan X, Mani S, Pestell RG, et al. Recent advances of highly selective CDK4/6 inhibitors in breast cancer. J Hematol Oncol. 2017;10(1):97.

    PubMed  PubMed Central  Google Scholar 

  55. Johnson JD, Young B. Demographics of brain metastasis. Neurosurg Clin N Am. 1996;7(3):337–44.

    CAS  PubMed  Google Scholar 

  56. Davies MA, Liu P, McIntyre S, Kim KB, Papadopoulos N, Hwu WJ, et al. Prognostic factors for survival in melanoma patients with brain metastases. Cancer. 2011;117(8):1687–96.

    PubMed  Google Scholar 

  57. Ramakrishna N, Margolin KA. Multidisciplinary approach to brain metastasis from melanoma; local therapies for central nervous system metastases. Am Soc Clin Oncol Educ Book. 2013;33:399–403.

    Google Scholar 

  58. Glitza IC, Heimberger AB, Sulman EP, Davies MA. Prognostic factors for survival in melanoma patients with brain metastases. In: Hayat M, editor. Brain metastases from primary tumors. Academic Press: New York; 2016. p. 267–92.

    Google Scholar 

  59. Chapman PB, Hauschild A, Robert C. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364:2507–16.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Berghoff AS, Preusser M. Targeted therapies for melanoma brain metastases. Curr Treat Options Neurol. 2017;19(4):13. https://doi.org/10.1007/s11940-017-0449-2 Review. PubMed PMID: 28374234; PubMed Central PMCID: PMC5378732.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Long GV, Trefzer U, Davies MA. Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB), a multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13:1087–95.

    CAS  PubMed  Google Scholar 

  62. Long GV, Menzies AM, Nagrial AM, Haydu LE, Hamilton AL, Mann GJ, et al. Prognostic and clinicopathologic associations of oncogenic BRAF in metastatic melanoma. J Clin Oncol. 2011;29(10):1239–46.

    PubMed  Google Scholar 

  63. Ramanujam S, Schadendorf D, Long GV. Systemic therapies for melanoma brain metastases: which drug for whom and when? Chin Clin Oncol. 2015;4(2):25.

    PubMed  Google Scholar 

  64. •• Long GV, Atkinson V, Lo S, Sandhu S, Guminski AD, Brown MP, et al. Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicenter randomised phase 2 study. Lancet Oncol. 2018;19(5):672–81 This is one of the more recent papers showing improved intracranial responses to dual checkpoint blockade in melanoma brain metastases, when compared to single-agent immunotherapy.

    CAS  PubMed  Google Scholar 

  65. •• Tawbi HA, Forsyth PA, Algazi A, Hamid O, Hodi FS, Moschos SJ, et al. Combined nivolumab and ipilimumab in melanoma metastatic to the brain. N Engl J Med. 2018;379(8):722–30 This paper also demonstrated both improved intracranial responses to dual checkpoint blockade in melanoma brain metastases, as well as a trend towards increased intracranial progression-free survival.

    CAS  Google Scholar 

  66. Dummer R, Ascierto PA, Gogas HJ, Arance A, Mandala M, Liszkay G, et al. Overall survival in patients with BRAF-mutant melanoma receiving encorafenib plus binimetinib versus vemurafenib or encorafenib (COLUMBUS): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2018;19(10):1315–27.

    CAS  PubMed  Google Scholar 

  67. •• Robert C, Karaszewska B, Schachter J. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015;372:30–9 This is one of the earliest papers describing the benefit of BRAF/MEK-directed therapy in BRAF-mutated melanoma.

    PubMed  Google Scholar 

  68. Guirguis LM, Yang JC, White DE. Safety and efficacy of high-dose interleukin-2 therapy in patients with brain metastases. J Immunother. 2002;25(1):82–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Margolin K, Ernstoff MS, Hamid O, Lawrence D, McDermott D, Puzanov I, et al. Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Lancet Oncol. 2012;13(5):459–65.

    CAS  PubMed  Google Scholar 

  70. Aupérin A, Arriagada R, Pignon JP, Le Péchoux C, Gregor A, Stephens RJ, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med. 1999;341(7):476–84.

    PubMed  Google Scholar 

  71. Slotman B, Faivre-Finn C, Kramer G, Rankin E, Snee M, Hatton M, et al. EORTC Radiation Oncology Group and Lung Cancer Group. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med. 2007;357(7):664–72.

    CAS  Google Scholar 

  72. George J, Lim JS, Jang SJ, Cun Y, Ozretić L, Kong G, et al. Comprehensive genomic profiles of small cell lung cancer. Nature. 2015 Aug 6;524(7563):47–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Früh M, De Ruysscher D, Popat S. Small-cell lung cancer (SCLC), ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(Suppl. 6):vi99–vi105.

    PubMed  Google Scholar 

  74. Go PH, Klaassen Z, Meadows MC, Chamberlain RS. Gastrointestinal cancer and brain metastasis: a rare and ominous sign. Cancer. 2011;117:3630–40.

    PubMed  Google Scholar 

  75. Christensen TD, Palshof JA, Larsen FO, Høgdall E, Poulsen TS, Pfeiffer P, et al. Risk factors for brain metastases in patients with metastatic colorectal cancer. Acta Oncol. 2017;56(5):639–45.

    PubMed  Google Scholar 

  76. Tie J, Lipton L, Desai J, Gibbs P, Jorissen RN, Christie M, et al. KRAS mutation is associated with lung metastasis in patients with curatively resected colorectal cancer. Clin Cancer Res. 2011;17:1122–30.

    CAS  PubMed  Google Scholar 

  77. Yaeger R, Cowell E, Chou JF, Gewirtz AN, Borsu L, Vakiani E, et al. RAS mutations affect pattern of metastatic spread and increase propensity for brain metastasis in colorectal cancer. Cancer. 2015;121:1195–203.

    CAS  PubMed  Google Scholar 

  78. Kemeny NE, Chou JF, Capanu M, Gewirtz AN, Cercek A, Kingham TP, et al. KRAS mutation influences recurrence patterns in patients undergoing hepatic resection of colorectal metastases. Cancer. 2014;120:3965–71.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Lan YT, Jen-Kou L, Lin CH. Mutations in the RAS and PI3K pathways are associated with metastatic location in colorectal cancers. J Surg Oncol. 2015;111(7):905–10.

    CAS  PubMed  Google Scholar 

  80. Anupol N, Ghamande S, Odunsi K. Evaluation of prognostic factors and treatment modalities in ovarian cancer with brain metastases. Gynecol Oncol. 2002;85:487–92.

    PubMed  Google Scholar 

  81. Rodriguez GC, Soper JT, Berchuck A. Improved palliation of cerebral metastases in epithelial ovarian cancer using a combined modality approach including radiation therapy, chemotherapy, and surgery. J Clin Oncol. 1992;10:1553Y1560.

    Google Scholar 

  82. McMeekin DS, Kamelle SA, Vasilev SA. Ovarian cancer metastatic to the brain: what is the optimal management? J Surg Oncol. 2001;78:194Y200.

    Google Scholar 

  83. Uccella S, Morris JM, Multinu F, Cliby WA, Podratz KC, Gostout BS, et al. Primary brain metastases of endometrial cancer: a report of 18 cases and review of the literature. Gynecol Oncol. 2016 Jul;142(1):70–5.

    PubMed  Google Scholar 

  84. Frank I, Blute ML, Cheville JC, Lohse CM, Weaver AL, Zincke H. An outcome prediction model for patients with clear cell renal cell carcinoma treated with radical nephrectomy based on tumor stage, size, grade and necrosis: the SSIGN score. J Urol. 2002;168(6):2395–400.

    PubMed  Google Scholar 

  85. N. Howlander, A.M. Noone, M. Krapcho, J. Garshell, D. Miller, S.F. Altekruse, C.L. Kosary, M. Yu, J. Ruhl, Z. Tatalovich, et al. SEER cancer statistics review, 1975–2012.

    Google Scholar 

  86. Du Y, Pahernik S, Hadaschik B, Teber D, Duensing S, Jäger D, et al. Impact of resection and systemic therapy on the survival of patients with brain metastasis of metastatic renal cell carcinoma. J Neuro-Oncol. 2016 Oct;130(1):221–8.

    Google Scholar 

  87. Vickers MM, Al-Harbi H, Choueiri TK, Kollmannsberger C, North S, MacKenzie M, et al. Prognostic factors of survival for patients with metastatic renal cell carcinoma with brain metastases treated with targeted therapy: results from the international metastatic renal cell carcinoma database consortium. Clin Genitourin Cancer. 2013;11(3):311–5.

    PubMed  Google Scholar 

  88. Verma J, Jonasch E, Allen P, Tannir N, Mahajan A. Impact of tyrosine kinase inhibitors on the incidence of brain metastasis in metastatic renal cell carcinoma. Cancer. 2011 Nov 1;117(21):4958–65.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Neuro-Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA

    Ugonma N. Chukwueke MD

  2. Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA

    Ugonma N. Chukwueke MD

  3. Department of Medical Oncology, Division of Neuro-Oncology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA

    Priscilla K. Brastianos MD

  4. Department of Medicine, Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA

    Priscilla K. Brastianos MD

Authors
  1. Ugonma N. Chukwueke MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Priscilla K. Brastianos MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ugonma N. Chukwueke MD.

Ethics declarations

Conflict of Interest

Ugonma N. Chukwueke declares that she has no conflict of interest. Priscilla K. Brastianos has received research funding from Merck, Pfizer, and Bristol-Myers Squibb and has received compensation from Genentech-Roche, Merck, Lilly, TESARO, and AngioChem for service as a consultant.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Neuro-oncology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chukwueke, U.N., Brastianos, P.K. Precision Medical Approaches to the Diagnoses and Management of Brain Metastases. Curr. Treat. Options in Oncol. 20, 49 (2019). https://doi.org/10.1007/s11864-019-0649-y

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11864-019-0649-y

Keywords

Search

Navigation