Skip to main content
SpringerLink
Log in

Leptomeningeal Disease in Solid Cancers

  • Reference work entry
  • First Online:
Oncologic Critical Care

  • 129 Accesses

Abstract

Leptomeningeal disease (LMD) is one of the most dreaded complications of solid and hematological malignancies and confers a poor prognosis. LMD occurs in about 5% of patients with solid cancers, most commonly in patients with breast cancer, lung cancer, and melanoma. Diagnosis of leptomeningeal disease is challenging and is dependent on the correlation of typical symptoms and signs, characteristic imaging findings, and evaluation of spinal fluid for malignant cells. The incidence of solid cancer LMD is rising due to improved survival of cancer patients and more frequent imaging. Treatment is dependent on patients’ functional status, extent of systemic cancer, and availability of systemic treatment options. The landscape of treatment for solid cancer LMD is changing with the advent of novel blood-brain penetrant molecular targeted therapies and immunotherapy. More clinical trials are expected to include patients with solid tumors and LMD as novel treatment options have been developed. This chapter aims at reviewing the recent literature on LMD from solid cancers (focusing on breast cancer, lung cancer, and melanoma) and providing an algorithm that can be used to standardize our approach to management of this disease.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 949.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 1,299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Chamberlain M, Soffietti R, Raizer J, Ruda R, Brandsma D, Boogerd W, Taillibert S, Groves MD, Le Rhun E, Junck L, van den Bent M, Wen PY, Jaeckle KA. Leptomeningeal metastasis: a Response Assessment in Neuro-Oncology critical review of endpoints and response criteria of published randomized clinical trials. Neuro-Oncology. 2014;16:1176–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Beauchesne P. Intrathecal chemotherapy for treatment of leptomeningeal dissemination of metastatic tumours. Lancet Oncol. 2010;11:871–9.

    Article  CAS  PubMed  Google Scholar 

  3. Le Rhun E, Weller M, Brandsma D, van den Bent M, de Azambuja E, Henriksson R, Boulanger T, Peters S, Watts C, Wick W, Wesseling P, Ruda R, Preusser M, EANO Executive Board and ESMO Guidelines Committee. EANO-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with leptomeningeal metastasis from solid tumours. Ann Oncol. 2017;28:iv84–99.

    Article  PubMed  Google Scholar 

  4. Armstrong TS, Gilbert MR. The treatment of neoplastic meningitis. Expert Opin Pharmacother. 2004;5:1929–35.

    Article  CAS  PubMed  Google Scholar 

  5. Leal T, Chang JE, Mehta M, Robins HI. Leptomeningeal metastasis: challenges in diagnosis and treatment. Curr Cancer Ther Rev. 2011;7:319–27.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Le Rhun E, Taillibert S, Chamberlain MC. Carcinomatous meningitis: leptomeningeal metastases in solid tumors. Surg Neurol Int. 2013;4:S265–88.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Roth P, Weller M. Management of neoplastic meningitis. Chin Clin Oncol. 2015;4:26.

    PubMed  Google Scholar 

  8. Clatot F, Philippin-Lauridant G, Ouvrier MJ, Nakry T, Laberge-LE-Couteulx S, Guillemet C, Veyret C, Blot E. Clinical improvement and survival in breast cancer leptomeningeal metastasis correlate with the cytologic response to intrathecal chemotherapy. J Neuro-Oncol. 2009;95:421–6.

    Article  CAS  Google Scholar 

  9. Rudnicka H, Niwinska A, Murawska M. Breast cancer leptomeningeal metastasis – the role of multimodality treatment. J Neuro-Oncol. 2007;84:57–62.

    Article  Google Scholar 

  10. Chamberlain MC. Neoplastic meningitis. J Clin Oncol. 2005;23:3605–13.

    Article  PubMed  Google Scholar 

  11. Nayar G, Ejikeme T, Chongsathidkiet P, Elsamadicy AA, Blackwell KL, Clarke JM, Lad SP, Fecci PE. Leptomeningeal disease: current diagnostic and therapeutic strategies. Oncotarget. 2017;8:73312–28.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Erlich SS, Davis RL. Spinal subarachnoid metastasis from primary intracranial glioblastoma multiforme. Cancer. 1978;42:2854–64.

    Article  CAS  PubMed  Google Scholar 

  13. Yung WA, Horten BC, Shapiro WR. Meningeal gliomatosis: a review of 12 cases. Ann Neurol. 1980;8:605–8.

    Article  CAS  PubMed  Google Scholar 

  14. Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131:803–20.

    Article  PubMed  Google Scholar 

  15. Mack F, Baumert BG, Schafer N, Hattingen E, Scheffler B, Herrlinger U, Glas M. Therapy of leptomeningeal metastasis in solid tumors. Cancer Treat Rev. 2016;43:83–91.

    Article  CAS  PubMed  Google Scholar 

  16. Posner JB, Chernik NL. Intracranial metastases from systemic cancer. Adv Neurol. 1978;19:579–92.

    CAS  PubMed  Google Scholar 

  17. Chamberlain MC. Comprehensive neuraxis imaging in leptomeningeal metastasis: a retrospective case series. CNS Oncol. 2013;2:121–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Pauls S, Fischer AC, Brambs HJ, Fetscher S, Hoche W, Bommer M. Use of magnetic resonance imaging to detect neoplastic meningitis: limited use in leukemia and lymphoma but convincing results in solid tumors. Eur J Radiol. 2012;81:974–8.

    Article  PubMed  Google Scholar 

  19. Nayak L, Lee EQ, Wen PY. Epidemiology of brain metastases. Curr Oncol Rep. 2012;14:48–54.

    Article  PubMed  Google Scholar 

  20. Ahn JH, Lee SH, Kim S, Joo J, Yoo H, Lee SH, Shin SH, Gwak HS. Risk for leptomeningeal seeding after resection for brain metastases: implication of tumor location with mode of resection. J Neurosurg. 2012;116:984–93.

    Article  PubMed  Google Scholar 

  21. Ma R, Levy M, Gui B, Lu SE, Narra V, Goyal S, Danish S, Hanft S, Khan AJ, Malhotra J, Motwani S, Jabbour SK. Risk of leptomeningeal carcinomatosis in patients with brain metastases treated with stereotactic radiosurgery. J Neuro-Oncol. 2018;136:395–401.

    Article  Google Scholar 

  22. Suki D, Hatiboglu MA, Patel AJ, Weinberg JS, Groves MD, Mahajan A, Sawaya R. Comparative risk of leptomeningeal dissemination of cancer after surgery or stereotactic radiosurgery for a single supratentorial solid tumor metastasis. Neurosurgery. 2009;64:664–74; discussion 674–6

    Article  PubMed  Google Scholar 

  23. Atalar B, Modlin LA, Choi CY, Adler JR, Gibbs IC, Chang SD, Harsh GRT, Li G, Nagpal S, Hanlon A, Soltys SG. Risk of leptomeningeal disease in patients treated with stereotactic radiosurgery targeting the postoperative resection cavity for brain metastases. Int J Radiat Oncol Biol Phys. 2013;87:713–8.

    Article  PubMed  Google Scholar 

  24. Ojerholm E, Lee JY, Kolker J, Lustig R, Dorsey JF, Alonso-Basanta M. Gamma Knife radiosurgery to four or more brain metastases in patients without prior intracranial radiation or surgery. Cancer Med. 2014;3:565–71.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Yust-Katz S, Garciarena P, Liu D, Yuan Y, Ibrahim N, Yerushalmi R, Penas-Prado M, Groves MD. Breast cancer and leptomeningeal disease (LMD): hormone receptor status influences time to development of LMD and survival from LMD diagnosis. J Neuro-Oncol. 2013;114:229–35.

    Article  CAS  Google Scholar 

  26. Lee S, Ahn HK, Park YH, Nam DH, Lee JI, Park W, Choi DH, Huh SJ, Park KT, Ahn JS, Im YH. Leptomeningeal metastases from breast cancer: intrinsic subtypes may affect unique clinical manifestations. Breast Cancer Res Treat. 2011;129:809–17.

    Article  PubMed  Google Scholar 

  27. Yufen X, Binbin S, Wenyu C, Jialiang L, Xinmei Y. The role of EGFR-TKI for leptomeningeal metastases from non-small cell lung cancer. Springerplus. 2016;5:1244.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Cheng H, Perez-Soler R. Leptomeningeal metastases in non-small-cell lung cancer. Lancet Oncol. 2018;19:e43–55.

    Article  PubMed  Google Scholar 

  29. Pellerino A, Bertero L, Ruda R, Soffietti R. Neoplastic meningitis in solid tumors: from diagnosis to personalized treatments. Ther Adv Neurol Disord. 2018;11:1756286418759618.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Kaplan JG, Desouza TG, Farkash A, Shafran B, Pack D, Rehman F, Fuks J, Portenoy R. Leptomeningeal metastases: comparison of clinical features and laboratory data of solid tumors, lymphomas and leukemias. J Neuro-Oncol. 1990;9:225–9.

    Article  CAS  Google Scholar 

  31. Prommel P, Pilgram-Pastor S, Sitter H, Buhk JH, Strik H. Neoplastic meningitis: how MRI and CSF cytology are influenced by CSF cell count and tumor type. ScientificWorldJournal. 2013;2013:248072.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Herrlinger U, Forschler H, Kuker W, Meyermann R, Bamberg M, Dichgans J, Weller M. Leptomeningeal metastasis: survival and prognostic factors in 155 patients. J Neurol Sci. 2004;223:167–78.

    Article  PubMed  Google Scholar 

  33. Chamberlain M, Junck L, Brandsma D, Soffietti R, Ruda R, Raizer J, Boogerd W, Taillibert S, Groves MD, Le Rhun E, Walker J, van den Bent M, Wen PY, Jaeckle KA. Leptomeningeal metastases: a RANO proposal for response criteria. Neuro-Oncology. 2017;19:484–92.

    Article  PubMed  CAS  Google Scholar 

  34. Glass JP, Melamed M, Chernik NL, Posner JB. Malignant cells in cerebrospinal fluid (CSF): the meaning of a positive CSF cytology. Neurology. 1979;29:1369–75.

    Article  CAS  PubMed  Google Scholar 

  35. Glantz MJ, Cole BF, Glantz LK, Cobb J, Mills P, Lekos A, Walters BC, Recht LD. Cerebrospinal fluid cytology in patients with cancer: minimizing false-negative results. Cancer. 1998;82:733–9.

    Article  CAS  PubMed  Google Scholar 

  36. Jung H, Sinnarajah A, Enns B, Voroney JP, Murray A, Pelletier G, Wu JS. Managing brain metastases patients with and without radiotherapy: initial lessonsfrom a team-based consult service through a multidisciplinary integrated palliative oncology clinic. Support Care Cancer. 2013;21:3379–86.

    Article  PubMed  Google Scholar 

  37. Kak M, Nanda R, Ramsdale EE, Lukas RV. Treatment of leptomeningeal carcinomatosis: current challenges and future opportunities. J Clin Neurosci. 2015;22:632–7.

    Article  PubMed  Google Scholar 

  38. Ahluwalia SC, Chuang FL, Antonio AL, Malin JL, Lorenz KA, Walling AM. Documentation and discussion of preferences for care among patients with advanced cancer. J Oncol Pract. 2011;7:361–6.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Subira D, Serrano C, Castanon S, Gonzalo R, Illan J, Pardo J, Martinez-Garcia M, Millastre E, Aparisi F, Navarro M, Domine M, Gil-Bazo I, Perez Segura P, Gil M, Bruna J. Role of flow cytometry immunophenotyping in the diagnosis of leptomeningeal carcinomatosis. Neuro-Oncology. 2012;14:43–52.

    Article  PubMed  Google Scholar 

  40. Nabors LB, Pornow J, Baehring J, Brem H, Butowski N. Central Nervous System Cancers. NCCN Clinical Practice Guidelines in Oncology Version 1.2018. 2018.

    Google Scholar 

  41. Chamberlain MC. Radioisotope CSF flow studies in leptomeningeal metastases. J Neuro-Oncol. 1998b;38:135–40.

    Article  CAS  Google Scholar 

  42. Grossman SA, Trump DL, Chen DC, Thompson G, Camargo EE. Cerebrospinal fluid flow abnormalities in patients with neoplastic meningitis. An evaluation using 111indium-DTPA ventriculography. Am J Med. 1982;73:641–7.

    Article  CAS  PubMed  Google Scholar 

  43. Glantz MJ, Hall WA, Cole BF, Chozick BS, Shannon CM, Wahlberg L, Akerley W, Marin L, Choy H. Diagnosis, management, and survival of patients with leptomeningeal cancer based on cerebrospinal fluid-flow status. Cancer. 1995;75:2919–31.

    Article  CAS  PubMed  Google Scholar 

  44. Glantz MJ, van Horn A, Fisher R, Chamberlain MC. Route of intracerebrospinal fluid chemotherapy administration and efficacy of therapy in neoplastic meningitis. Cancer. 2010;116:1947–52.

    Article  PubMed  Google Scholar 

  45. Lin N, Dunn IF, Glantz M, Allison DL, Jensen R, Johnson MD, Friedlander RM, Kesari S. Benefit of ventriculoperitoneal cerebrospinal fluid shunting and intrathecal chemotherapy in neoplastic meningitis: a retrospective, case-controlled study. J Neurosurg. 2011;115:730–6.

    Article  PubMed  Google Scholar 

  46. Boogerd W, van den Bent MJ, Koehler PJ, Heimans JJ, van der Sande JJ, Aaronson NK, Hart AA, Benraadt J, CHJ V. The relevance of intraventricular chemotherapy for leptomeningeal metastasis in breast cancer: a randomised study. Eur J Cancer. 2004;40:2726–33.

    Article  CAS  PubMed  Google Scholar 

  47. Glantz MJ, Jaeckle KA, Chamberlain MC, Phuphanich S, Recht L, Swinnen LJ, Maria B, Lafollette S, Schumann GB, Cole BF, Howell SB. A randomized controlled trial comparing intrathecal sustained-release cytarabine (DepoCyt) to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors. Clin Cancer Res. 1999;5:3394–402.

    CAS  PubMed  Google Scholar 

  48. Grossman SA, Finkelstein DM, Ruckdeschel JC, Trump DL, Moynihan T, Ettinger DS. Randomized prospective comparison of intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis. Eastern Cooperative Oncology Group. J Clin Oncol. 1993;11:561–9.

    Article  CAS  PubMed  Google Scholar 

  49. Hitchins RN, Bell DR, Woods RL, Levi JA. A prospective randomized trial of single-agent versus combination chemotherapy in meningeal carcinomatosis. J Clin Oncol. 1987;5:1655–62.

    Article  CAS  PubMed  Google Scholar 

  50. Bendell JC, Domchek SM, Burstein HJ, Harris L, Younger J, Kuter I, Bunnell C, Rue M, Gelman R, Winer E. Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer. 2003;97:2972–7.

    Article  PubMed  Google Scholar 

  51. Pestalozzi BC, Brignoli S. Trastuzumab in CSF. J Clin Oncol. 2000;18:2349–51.

    Article  CAS  PubMed  Google Scholar 

  52. Lin NU, Dieras V, Paul D, Lossignol D, Christodoulou C, Stemmler HJ, Roche H, Liu MC, Greil R, Ciruelos E, Loibl S, Gori S, Wardley A, Yardley D, Brufsky A, Blum JL, Rubin SD, Dharan B, Steplewski K, Zembryki D, Oliva C, Roychowdhury D, Paoletti P, Winer EP. Multicenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer. Clin Cancer Res. 2009;15:1452–9.

    Article  CAS  PubMed  Google Scholar 

  53. Bachelot T, Romieu G, Campone M, Dieras V, Cropet C, Dalenc F, Jimenez M, Le Rhun E, Pierga JY, Goncalves A, Leheurteur M, Domont J, Gutierrez M, Cure H, Ferrero JM, Labbe-Devilliers C. 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;14:64–71.

    Article  CAS  PubMed  Google Scholar 

  54. Ekenel M, Hormigo AM, Peak S, Deangelis LM, Abrey LE. Capecitabine therapy of central nervous system metastases from breast cancer. J Neuro-Oncol. 2007;85:223–7.

    Article  CAS  Google Scholar 

  55. Giglio P, Tremont-Lukats IW, Groves MD. Response of neoplastic meningitis from solid tumors to oral capecitabine. J Neuro-Oncol. 2003;65:167–72.

    Article  Google Scholar 

  56. Tham YL, Hinckley L, Teh BS, Elledge R. Long-term clinical response in leptomeningeal metastases from breast cancer treated with capecitabine monotherapy: a case report. Clin Breast Cancer. 2006;7:164–6.

    Article  PubMed  Google Scholar 

  57. Awada A, Colomer R, Inoue K, Bondarenko I, Badwe RA, Demetriou G, Lee SC, Mehta AO, Kim SB, Bachelot T, Goswami C, Deo S, Bose R, Wong A, Xu F, Yao B, Bryce R, Carey LA. Neratinib plus paclitaxel vs trastuzumab plus paclitaxel in previously untreated metastatic ERBB2-positive breast cancer: the NEfERT-T randomized clinical trial. JAMA Oncol. 2016;2:1557–64.

    Article  PubMed  Google Scholar 

  58. Boogerd W, Dorresteijn LD, van der Sande JJ, de Gast GC, Bruning PF. Response of leptomeningeal metastases from breast cancer to hormonal therapy. Neurology. 2000;55:117–9.

    Article  CAS  PubMed  Google Scholar 

  59. Zoghi B, Elledge R. Endocrine therapy for leptomeningeal metastases from ER-positive breast cancer: case report and a review of the literature. Breast J. 2016;22:218–23.

    Article  PubMed  Google Scholar 

  60. Chen IC, Lin CH, Jan IS, Cheng AL, Lu YS. Bevacizumab might potentiate the chemotherapeutic effect in breast cancer patients with leptomeningeal carcinomatosis. J Formos Med Assoc. 2016;115:243–8.

    Article  CAS  PubMed  Google Scholar 

  61. Wu PF, Lin CH, Kuo CH, Chen WW, Yeh DC, Liao HW, Huang SM, Cheng AL, Lu YS. A pilot study of bevacizumab combined with etoposide and cisplatin in breast cancer patients with leptomeningeal carcinomatosis. BMC Cancer. 2015;15:299.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Oechsle K, Lange-Brock V, Kruell A, Bokemeyer C, de Wit M. Prognostic factors and treatment options in patients with leptomeningeal metastases of different primary tumors: a retrospective analysis. J Cancer Res Clin Oncol. 2010;136:1729–35.

    Article  PubMed  Google Scholar 

  63. 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. The effect of gene alterations and tyrosine kinase inhibition on survival and cause of death in patients with adenocarcinoma of the lung and brain metastases. Int J Radiat Oncol Biol Phys. 2016;96:406–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, Ando M, Miyazawa H, Tanaka T, Saijo Y, Hagiwara K, Morita S, Nukiwa T, North-East Japan Study Group. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010;362:2380–8.

    Article  CAS  PubMed  Google Scholar 

  65. Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361:947–57.

    Article  CAS  PubMed  Google Scholar 

  66. Di Lorenzo R, Ahluwalia MS. Targeted therapy of brain metastases: latest evidence and clinical implications. Ther Adv Med Oncol. 2017;9:781–96.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Jackman DM, Cioffredi LA, Jacobs L, Sharmeen F, Morse LK, Lucca J, Plotkin SR, Marcoux PJ, Rabin MS, Lynch TJ, Johnson BE, Kesari S. A phase I trial of high dose gefitinib for patients with leptomeningeal metastases from non-small cell lung cancer. Oncotarget. 2015;6:4527–36.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Lee Y, Han JY, Kim HT, Yun T, Lee GK, Kim HY, Lee JS. Impact of EGFR tyrosine kinase inhibitors versus chemotherapy on the development of leptomeningeal metastasis in never smokers with advanced adenocarcinoma of the lung. J Neuro-Oncol. 2013c;115:95–101.

    Article  CAS  Google Scholar 

  69. Lee E, Keam B, Kim DW, Kim TM, Lee SH, Chung DH, Heo DS. Erlotinib versus gefitinib for control of leptomeningeal carcinomatosis in non-small-cell lung cancer. J Thorac Oncol. 2013a;8:1069–74.

    Article  CAS  PubMed  Google Scholar 

  70. Togashi Y, Masago K, Masuda S, Mizuno T, Fukudo M, Ikemi Y, Sakamori Y, Nagai H, Kim YH, Katsura T, Mishima M. Cerebrospinal fluid concentration of gefitinib and erlotinib in patients with non-small cell lung cancer. Cancer Chemother Pharmacol. 2012;70:399–405.

    Article  CAS  PubMed  Google Scholar 

  71. Kanemaru R, Morio Y, Takekawa H, Jo H, Kasuga F, Koyama R, Shiota S, Nagaoka T, Takahashi K. Successful treatment with weekly high-dose erlotinib against meningeal metastases from epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma. Respir Investig. 2016;54:372–5.

    Article  PubMed  Google Scholar 

  72. Kawamura T, Hata A, Takeshita J, Fujita S, Hayashi M, Tomii K, Katakami N. High-dose erlotinib for refractory leptomeningeal metastases after failure of standard-dose EGFR-TKIs. Cancer Chemother Pharmacol. 2015;75:1261–6.

    Article  CAS  PubMed  Google Scholar 

  73. Ballard P, Yates JW, Yang Z, Kim DW, Yang JC, Cantarini M, Pickup K, Jordan A, Hickey M, Grist M, Box M, Johnstrom P, Varnas K, Malmquist J, Thress KS, Janne PA, Cross D. Preclinical comparison of osimertinib with other EGFR-TKIs in EGFR-mutant NSCLC brain metastases models, and early evidence of clinical brain metastases activity. Clin Cancer Res. 2016;22:5130–40.

    Article  CAS  PubMed  Google Scholar 

  74. Mok TS, Wu YL, Ahn MJ, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, HE Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA, AURA3 Investigators. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017;376:629–40.

    Article  CAS  PubMed  Google Scholar 

  75. Remon J, Le Rhun E, Besse B. Leptomeningeal carcinomatosis in non-small cell lung cancer patients: a continuing challenge in the personalized treatment era. Cancer Treat Rev. 2017;53:128–37.

    Article  CAS  PubMed  Google Scholar 

  76. Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, Ou SH, Dezube BJ, Janne PA, Costa DB, Varella-Garcia M, Kim WH, Lynch TJ, Fidias P, Stubbs H, Engelman JA, Sequist LV, Tan W, Gandhi L, Mino-Kenudson M, Wei GC, Shreeve SM, Ratain MJ, Settleman J, Christensen JG, Haber DA, Wilner K, Salgia R, Shapiro GI, Clark JW, Iafrate AJ. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363:1693–703.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Shaw AT, Kim DW, Nakagawa K, Seto T, Crino L, Ahn MJ, de Pas T, Besse B, Solomon BJ, Blackhall F, Wu YL, Thomas M, O’Byrne KJ, Moro-Sibilot D, Camidge DR, Mok T, Hirsh V, Riely GJ, Iyer S, Tassell V, Polli A, Wilner KD, Janne PA. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013;368:2385–94.

    Article  CAS  PubMed  Google Scholar 

  78. Solomon BJ, Mok T, Kim DW, Wu YL, Nakagawa K, Mekhail T, Felip E, Cappuzzo F, Paolini J, Usari T, Iyer S, Reisman A, Wilner KD, Tursi J, Blackhall F, PROFILE 1014 Investigators. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014;371:2167–77.

    Article  PubMed  CAS  Google Scholar 

  79. Ou SH, Janne PA, Bartlett CH, Tang Y, Kim DW, Otterson GA, Crino L, Selaru P, Cohen DP, Clark JW, Riely GJ. Clinical benefit of continuing ALK inhibition with crizotinib beyond initial disease progression in patients with advanced ALK-positive NSCLC. Ann Oncol. 2014;25:415–22.

    Article  PubMed  Google Scholar 

  80. Kim DW, Mehra R, Tan DSW, Felip E, Chow LQM, Camidge DR, Vansteenkiste J, Sharma S, de Pas T, Riely GJ, Solomon BJ, Wolf J, Thomas M, Schuler M, Liu G, Santoro A, Sutradhar S, LI S, Szczudlo T, Yovine A, Shaw AT. Activity and safety of ceritinib in patients with ALK-rearranged non-small-cell lung cancer (ASCEND-1): updated results from the multicentre, open-label, phase 1 trial. Lancet Oncol. 2016;17:452–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Qian M, Zhu B, Wang X, Liebman M. Drug resistance in ALK-positiveNon-small cell lungcancer patients. Semin Cell Dev Biol. 2017;64:150–7.

    Article  CAS  PubMed  Google Scholar 

  82. Gainor JF, Chi AS, Logan J, Hu R, Oh KS, Brastianos PK, Shih HA, Shaw AT. Alectinib dose escalation reinduces central nervous system responses in patients with anaplastic lymphoma kinase-positive non-small cell lung cancer relapsing on standard dose alectinib. J Thorac Oncol. 2016;11:256–60.

    Article  PubMed  Google Scholar 

  83. Gainor JF, Sherman CA, Willoughby K, Logan J, Kennedy E, Brastianos PK, Chi AS, Shaw AT. Alectinib salvages CNS relapses in ALK-positive lung cancer patients previously treated with crizotinib and ceritinib. J Thorac Oncol. 2015;10:232–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Sakata Y, Kawamura K, Shingu N, Ichikado K. Erlotinib plus bevacizumab as an effective treatment for leptomeningeal metastases from EGFR mutation-positive non-small cell lung cancer. Lung Cancer. 2016;99:120–2.

    Article  PubMed  Google Scholar 

  85. Sloot S, Chen YA, Zhao X, Weber JL, Benedict JJ, Mule JJ, Smalley KS, Weber JS, Zager JS, Forsyth PA, Sondak VK, Gibney GT. Improved survival of patients with melanoma brain metastases in the era of targeted BRAF and immune checkpoint therapies. Cancer. 2018;124:297–305.

    Article  CAS  PubMed  Google Scholar 

  86. Bollag G, Hirth P, Tsai J, Zhang J, Ibrahim PN, Cho H, Spevak W, Zhang C, Zhang Y, Habets G, Burton EA, Wong B, Tsang G, West BL, Powell B, Shellooe R, Marimuthu A, Nguyen H, Zhang KY, Artis DR, Schlessinger J, Su F, Higgins B, Iyer R, D’Andrea K, Koehler A, Stumm M, Lin PS, Lee RJ, Grippo J, Puzanov I, Kim KB, Ribas A, Mcarthur GA, Sosman JA, Chapman PB, Flaherty KT, Xu X, Nathanson KL, Nolop K. Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature. 2010;467:596–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Flaherty KT, Puzanov I, Kim KB, Ribas A, Mcarthur GA, Sosman JA, O’Dwyer PJ, Lee RJ, Grippo JF, Nolop K, Chapman PB. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med. 2010;363:809–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. King AJ, Arnone MR, Bleam MR, Moss KG, Yang J, Fedorowicz KE, Smitheman KN, Erhardt JA, Hughes-Earle A, Kane-Carson LS, Sinnamon RH, Qi H, Rheault TR, Uehling DE, Laquerre SG. Dabrafenib; preclinical characterization, increased efficacy when combined with trametinib, while BRAF/MEK tool combination reduced skin lesions. PLoS One. 2013;8:e67583.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Tsai J, Lee JT, Wang W, Zhang J, Cho H, Mamo S, Bremer R, Gillette S, Kong J, Haass NK, Sproesser K, Li L, Smalley KS, Fong D, Zhu YL, Marimuthu A, Nguyen H, Lam B, Liu J, Cheung I, Rice J, Suzuki Y, Luu C, Settachatgul C, Shellooe R, Cantwell J, Kim SH, Schlessinger J, Zhang KY, West BL, Powell B, Habets G, Zhang C, Ibrahim PN, Hirth P, Artis DR, Herlyn M, Bollag G. Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc Natl Acad Sci USA. 2008;105:3041–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Long GV, Trefzer U, Davies MA, Kefford RF, Ascierto PA, Chapman PB, Puzanov I, Hauschild A, Robert C, Algazi A, Mortier L, Tawbi H, Wilhelm T, Zimmer L, Switzky J, Swann S, Martin AM, Guckert M, Goodman V, Streit M, Kirkwood JM, Schadendorf D. 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.

    Article  CAS  PubMed  Google Scholar 

  91. Mcarthur GA, Maio M, Arance A, Nathan P, Blank C, Avril MF, Garbe C, Hauschild A, Schadendorf D, Hamid O, Fluck M, Thebeau M, Schachter J, Kefford R, Chamberlain M, Makrutzki M, Robson S, Gonzalez R, Margolin K. Vemurafenib in metastatic melanoma patients with brain metastases: an open-label, single-arm, phase 2, multicentre study. Ann Oncol. 2017;28:634–41.

    Article  CAS  PubMed  Google Scholar 

  92. Davies MA, Saiag P, Robert C, Grob JJ, Flaherty KT, Arance A, Chiarion-Sileni V, Thomas L, Lesimple T, Mortier L, Moschos SJ, Hogg D, Marquez-Rodas I, Del Vecchio M, Lebbe C, Meyer N, Zhang Y, Huang Y, Mookerjee B, Long GV. Dabrafenib plus trametinib in patients with BRAF(V600)-mutant melanoma brain metastases (COMBI-MB): a multicentre, multicohort, open-label, phase 2 trial. Lancet Oncol. 2017;18:863–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Lee JM, Mehta UN, Dsouza LH, Guadagnolo BA, Sanders DL, Kim KB. Long-term stabilization of leptomeningeal disease with whole-brain radiation therapy in a patient with metastatic melanoma treated with vemurafenib: a case report. Melanoma Res. 2013b;23:175–8.

    Article  PubMed  Google Scholar 

  94. Schafer N, Scheffler B, Stuplich M, Schaub C, Kebir S, Rehkamper C, Mack F, Niehusmann P, Simon M, Greschus S, Kuchelmeister K, Herrlinger U, Glas M. Vemurafenib for leptomeningeal melanomatosis. J Clin Oncol. 2013;31:e173–4.

    Article  PubMed  Google Scholar 

  95. Wilgenhof S, Neyns B. Complete cytologic remission of V600E BRAF-mutant melanoma-associated leptomeningeal carcinomatosis upon treatment with dabrafenib. J Clin Oncol. 2015;33:e109–11.

    Article  PubMed  Google Scholar 

  96. Kim T, Amaria RN, Spencer C, Reuben A, Cooper ZA, Wargo JA. Combining targeted therapy and immune checkpoint inhibitors in the treatment of metastatic melanoma. Cancer Biol Med. 2014;11:237–46.

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Smalley KS, Fedorenko IV, Kenchappa RS, Sahebjam S, Forsyth PA. Managing leptomeningeal melanoma metastases in the era of immune and targeted therapy. Int J Cancer. 2016;139:1195–201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Clemons-Miller AR, Chatta GS, Hutchins L, Angtuaco EJ, Ravaggi A, Santin AD, Cannon MJ. Intrathecal cytotoxic T-cell immunotherapy for metastatic leptomeningeal melanoma. Clin Cancer Res. 2001;7:917s–24s.

    CAS  PubMed  Google Scholar 

  99. Glitza IC, Haymaker C, Bernatchez C, Vence L, Rohlfs M, Richard J, Lacey C, Mansaray R, Fulbright OJ, Ramachandran R, Toth C, Wardell S, Patel SP, Woodman SE, Hwu WJ, Radvanyi LG, Davies MA, Papadopoulos NE, Hwu P. Intrathecal administration of tumor-infiltrating lymphocytes is well tolerated in a patient with leptomeningeal disease from metastatic melanoma: a case report. Cancer Immunol Res. 2015;3:1201–6.

    Article  PubMed  PubMed Central  Google Scholar 

  100. Bot I, Blank CU, Brandsma D. Clinical and radiological response of leptomeningeal melanoma after whole brain radiotherapy and ipilimumab. J Neurol. 2012;259:1976–8.

    Article  CAS  PubMed  Google Scholar 

  101. Orlando L, Curigliano G, Colleoni M, Fazio N, Nole F, Martinelli G, Cinieri S, Graffeo R, Peruzzotti G, Goldhirsch A. Intrathecal chemotherapy in carcinomatous meningitis from breast cancer. Anticancer Res. 2002;22:3057–9.

    PubMed  Google Scholar 

  102. Boogerd W, Hart AA, van der Sande JJ, Engelsman E. Meningeal carcinomatosis in breast cancer. Prognostic factors and influence of treatment. Cancer. 1991;67:1685–95.

    Article  CAS  PubMed  Google Scholar 

  103. Fizazi K, Asselain B, Vincent-Salomon A, Jouve M, Dieras V, Palangie T, Beuzeboc P, Dorval T, Pouillart P. Meningeal carcinomatosis in patients with breast carcinoma. Clinical features, prognostic factors, and results of a high-dose intrathecal methotrexate regimen. Cancer. 1996;77:1315–23.

    Article  CAS  PubMed  Google Scholar 

  104. Gauthier H, Guilhaume MN, Bidard FC, Pierga JY, Girre V, Cottu PH, Laurence V, Livartowski A, Mignot L, Dieras V. Survival of breast cancer patients with meningeal carcinomatosis. Ann Oncol. 2010;21:2183–7.

    Article  CAS  PubMed  Google Scholar 

  105. Lara-Medina F, Crismatt A, Villarreal-Garza C, Alvarado-Miranda A, Flores-Hernandez L, Gonzalez-Pinedo M, Gamboa-Vignolle C, Ruiz-Gonzalez JD, Arrieta O. Clinical features and prognostic factors in patients with carcinomatous meningitis secondary to breast cancer. Breast J. 2012;18:233–41.

    Article  PubMed  Google Scholar 

  106. Mego M, Sycova-Mila Z, Obertova J, Rajec J, Liskova S, Palacka P, Porsok S, Mardiak J. Intrathecal administration of trastuzumab with cytarabine and methotrexate in breast cancer patients with leptomeningeal carcinomatosis. Breast. 2011;20:478–80.

    Article  PubMed  Google Scholar 

  107. Salgia S, Fleming GF, Lukas RV. Leptomeningeal carcinomatosis from breast cancer treated with intrathecal topotecan with concomitant intravenous eribulin. J Clin Neurosci. 2014;21:1250–1.

    Article  PubMed  Google Scholar 

  108. Ferrario C, Davidson A, Bouganim N, Aloyz R, Panasci LC. Intrathecal trastuzumab and thiotepa for leptomeningeal spread of breast cancer. Ann Oncol. 2009;20:792–5.

    Article  CAS  PubMed  Google Scholar 

  109. Groves MD, Glantz MJ, Chamberlain MC, Baumgartner KE, Conrad CA, Hsu S, Wefel JS, Gilbert MR, Ictech S, Hunter KU, Forman AD, Puduvalli VK, Colman H, Hess KR, Yung WK. A multicenter phase II trial of intrathecal topotecan in patients with meningeal malignancies. Neuro-Oncology. 2008;10:208–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Walker J, Schultz D, Grisdale K, Groves M. Intraventricular topotecan for the treatment of neoplastic meningitis: five case studies. J Adv Pract Oncol. 2012;3:237–41.

    PubMed  PubMed Central  Google Scholar 

  111. Mir O, Ropert S, Alexandre J, Lemare F, Goldwasser F. High-dose intrathecal trastuzumab for leptomeningeal metastases secondary to HER-2 overexpressing breast cancer. Ann Oncol. 2008;19:1978–80.

    Article  CAS  PubMed  Google Scholar 

  112. Oliveira M, Braga S, Passos-Coelho JL, Fonseca R, Oliveira J. Complete response in HER2+ leptomeningeal carcinomatosis from breast cancer with intrathecal trastuzumab. Breast Cancer Res Treat. 2011;127:841–4.

    Article  CAS  PubMed  Google Scholar 

  113. Pan Z, Yang G, He H, Zhao G, Yuan T, Li Y, Shi W, Gao P, Dong L, Li Y. Concurrent radiotherapy and intrathecal methotrexate for treating leptomeningeal metastasis from solid tumors with adverse prognostic factors: a prospective and single-arm study. Int J Cancer. 2016;139:1864–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Mix M, Elmarzouky R, O’Connor T, Plunkett R, Prasad D. Clinical outcomes in patients with brain metastases from breast cancer treated with single-session radiosurgery or whole brain radiotherapy. J Neurosurg. 2016;125:26–30.

    Article  PubMed  Google Scholar 

  115. Mulvenna P, Nankivell M, Barton R, Faivre-Finn C, Wilson P, Mccoll E, Moore B, Brisbane I, Ardron D, Holt T, Morgan S, Lee C, Waite K, Bayman N, Pugh C, Sydes B, Stephens R, Parmar MK, Langley RE. Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial. Lancet. 2016;388:2004–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Chamberlain MC. Leptomeningeal metastases: a review of evaluation and treatment. J Neuro-Oncol. 1998a;37:271–84.

    Article  CAS  Google Scholar 

  117. Scott BJ, Oberheim-Bush NA, Kesari S. Leptomeningeal metastasis in breast cancer – a systematic review. Oncotarget. 2016;7:3740–7.

    PubMed  Google Scholar 

  118. Abouharb S, Ensor J, Loghin ME, Katz R, Moulder SL, Esteva FJ, Smith B, Valero V, Hortobagyi GN, Melhem-Bertrandt A. Leptomeningeal disease and breast cancer: the importance of tumor subtype. Breast Cancer Res Treat. 2014;146:477–86.

    Article  CAS  PubMed  Google Scholar 

  119. Goldberg SB, Gettinger SN, Mahajan A, Chiang AC, Herbst RS, Sznol M, Tsiouris AJ, Cohen J, Vortmeyer A, Jilaveanu L, Yu J, Hegde U, Speaker S, Madura M, Ralabate A, Rivera A, Rowen E, Gerrish H, Yao X, Chiang V, Kluger HM. 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;17:976–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Niwinska A, Rudnicka H, Murawska M. Breast cancer leptomeningeal metastasis: propensity of breast cancer subtypes for leptomeninges and the analysis of factors influencing survival. Med Oncol. 2013;30:408.

    Article  PubMed  PubMed Central  Google Scholar 

  121. Niwinska A, Rudnicka H, Murawska M. Breast cancer leptomeningeal metastasis: the results of combined treatment and the comparison of methotrexate and liposomal cytarabine as intra-cerebrospinal fluid chemotherapy. Clin Breast Cancer. 2015;15:66–72.

    Article  CAS  PubMed  Google Scholar 

  122. Olar A, Wani KM, Alfaro-Munoz KD, Heathcock LE, van Thuijl HF, Gilbert MR, Armstrong TS, Sulman EP, Cahill DP, Vera-Bolanos E, Yuan Y, Reijneveld JC, Ylstra B, Wesseling P, Aldape KD. IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas. Acta Neuropathol. 2015;129:585–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Nazanin K. Majd & Monica E. Loghin

Authors
  1. Nazanin K. Majd
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Monica E. Loghin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Monica E. Loghin .

Editor information

Editors and Affiliations

  1. Department of Critical Care and Respiratory Care, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Joseph L. Nates

  2. Division of Anesthesiology, Critical Care and Pain Medicine, Department of Critical Care and Respiratory Care, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Kristen J. Price

Section Editor information

  1. Critical Care Department, Universidad del Rosario Hospital Universitario Fundacion Santa Fe de, Bogota, Colombia, Colombia

    Yenny Cardenas

Rights and permissions

Reprints and permissions

Copyright information

© 2020 This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Majd, N.K., Loghin, M.E. (2020). Leptomeningeal Disease in Solid Cancers. In: Nates, J., Price, K. (eds) Oncologic Critical Care. Springer, Cham. https://doi.org/10.1007/978-3-319-74588-6_38

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-74588-6_38

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-74587-9

  • Online ISBN: 978-3-319-74588-6

  • eBook Packages: MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation