Palliative Radiation Therapy for Leptomeningeal Disease

  • Alysa M. FairchildEmail author


Approximately 5–10% of all patients with cancer will develop leptomeningeal metastatic disease (LM), often synchronously with parenchymal brain metastases and extracranial disease progression. The vast majority are symptomatic. As much of the literature is comprised of retrospective single-institution reviews of patients with various histologies treated heterogeneously, there is a lack of evidence supportive of a definitive treatment approach. Palliative external beam radiotherapy (RT) is most often delivered for LM disease, and when in the brain, typically the entire brain is treated with whole brain radiotherapy (WBRT); however, in the spine, typically RT is delivered regionally to areas of clinically relevant gross disease. The latter is due to the potential excessive toxicities associated with whole-spine radiation, in particular myelosuppression. The intent of RT is to stabilize or improve symptoms in the short term; it is unlikely that RT improves survival.


Radiotherapy Palliative Involved field Whole brain Spine Local Craniospinal Leukoencephalopathy 


  1. 1.
    National Comprehensive Cancer Network version 1.2016. Central nervous system cancers. Pgs LEPT-1 to LEPT-4, MS-29 to MS-31.Google Scholar
  2. 2.
    Chamberlain M. Combined-modality treatment of leptomeningeal gliomatosis. Neurosurgery. 2003;52(2):324–30.CrossRefPubMedGoogle Scholar
  3. 3.
    Wasserstrom W, Glass J, Posner J. Diagnosis and treatment of leptomeningeal metastases from solid tumours: experience with 90 patients. Cancer. 1982;49:759–72.CrossRefPubMedGoogle Scholar
  4. 4.
    Little J, Dale A, Okazaki H. Meningeal carcinomatosis. Arch Neurol. 1974;30:138–43.CrossRefPubMedGoogle Scholar
  5. 5.
    Mack F, Baumert B, Schafer N, et al. Therapy of leptomeningeal metastasis in solid tumours. Cancer Treat Rev. 2016;43:83–91.CrossRefPubMedGoogle Scholar
  6. 6.
    Clarke J, Perez H, Jacks L, et al. Leptomeningeal metastases in the MRI era. Neurology. 2010;74(18):1449–54.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Caraceni A, Martini C, Simonetti M. Neurological problems in advanced cancer. In: Doyle D, Hanks G, Cherny N, Calman K, editors. Oxford textbook of palliative medicine. 3rd ed. UK: Oxford University Press; 2005.Google Scholar
  8. 8.
    Olson M, Chernik N, Posner J. Infiltration of the leptomeninges by systemic cancer: a clinical and pathologic study. Arch Neurol. 1974;30:122–37.CrossRefPubMedGoogle Scholar
  9. 9.
    Glass J, Melamed M, Chernik N, et al. Malignant cells in the cerebrospinal fluid: the meaning of a positive CSF cytology. Neurology. 1979;29:1369–75.CrossRefPubMedGoogle Scholar
  10. 10.
    Rosen S, Aisner J, Makuch R, et al. Carcinomatous leptomeningitis in small cell lung cancer. Medicine. 1982;61(1):45–53.CrossRefPubMedGoogle Scholar
  11. 11.
    Huang A, Huang K, Page B, et al. Risk factors for leptomeningeal carcinomatosis in patients with brain metastases who have previously undergone stereotactic radiosurgery. J Neurooncol. 2014;120:163–9.CrossRefPubMedGoogle Scholar
  12. 12.
    Bartsch R, Berghoff A, Preusser M. Optimal management of brain metastases from breast cancer. CNS Drugs. 2013;27:121–34.CrossRefPubMedGoogle Scholar
  13. 13.
    Waki F, Ando M, Takashima A, et al. Prognostic factors and clinical outcomes in patients with leptomeningeal metastasis from solid tumours. J Neurooncol. 2009;93:205–12.CrossRefPubMedGoogle Scholar
  14. 14.
    Pavlidis N. The diagnostic and therapeutic management of leptomeningeal carcinomatosis. Ann Oncol. 2004;15(Suppl 4):iv285–91.PubMedGoogle Scholar
  15. 15.
    Ihde D, Glatstein E, Pass H. Small cell lung cancer. In: DeVita V, Hellman S, Rosenberg S, editors. Cancer: principles & practice of oncology. 5th ed. USA: Lippincott-Raven; 1997.Google Scholar
  16. 16.
    Aisner J, Aisner S, Ostrow S, et al. Meningeal carcinomatosis from small cell carcinoma of the lung. Acta Cytol. 1979;23(4):292–6.PubMedGoogle Scholar
  17. 17.
    Gonzalez-Vitale J, Garcia-Bunuel R. Meningeal carcinomatosis. Cancer. 1976;37:2906–11.CrossRefPubMedGoogle Scholar
  18. 18.
    DeAngelis L, Boutros D. Leptomeningeal metastasis. Cancer Investig. 2005;23:145–54.CrossRefGoogle Scholar
  19. 19.
    Lee SJ, Lee JI, Nam DH, et al. Leptomeningeal carcinomatosis in non-small cell lung cancer patients: impact on survival and correlated prognostic factors. J Thorac Oncol. 2013;8(2):185–91.CrossRefPubMedGoogle Scholar
  20. 20.
    Ozdemir Y, Yildirim B, Topkan E. Whole brain radiotherapy in management of non-small cell carcinoma associated leptomeningeal carcinomatosis: evaluation of prognostic factors. J Neurooncol. 2016;129:329–35.CrossRefPubMedGoogle Scholar
  21. 21.
    Morris P, Reiner A, Rosenvald Szenberg O, et al. Leptomeningeal metastasis from non-small cell lung cancer: survival and the impact of whole brain radiotherapy. J Thorac Oncol. 2012;7(2):382–5.CrossRefPubMedGoogle Scholar
  22. 22.
    Nugent J, Bunn P, Matthews M, et al. CNS metastases in small cell bronchogenic carcinoma: increasing frequency and changing pattern with lengthening survival. Cancer. 1979;44:1885–93.CrossRefPubMedGoogle Scholar
  23. 23.
    Clarke J. Leptomeningeal metastasis from systemic cancer. Continuum (Minneap Minn). 2012;18(2):328–42.Google Scholar
  24. 24.
    Griffo Y, Obbens E. Neurological complications. In: Walsh D, Caraceni A, Fainsinger R, Foley K, Glare P, Goh C, Lloyd-Williams M, Nunez Olarte JM, Radbruch L, editors. Palliative medicine. New York: Saunders Elsevier; 2009.Google Scholar
  25. 25.
    Van der Ree T, Dippel D, Avezaat C, et al. Leptomeningeal metastasis after surgical resection of brain metastasis. J Neurol Neurosurg Psychiatry. 1999;66(2):225–7.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Liaw C, Ng K, Huang J, et al. Meningeal carcinomatosis from solid tumours: clinical analysis of 42 cases. J Formos Med Assoc. 1992;91:299–303.PubMedGoogle Scholar
  27. 27.
    Foley KM. Acute and chronic cancer pain syndromes. In: Doyle D, Hanks G, Cherny N, Calman K, editors. Oxford textbook of palliative medicine. 3rd ed. UK: Oxford University Press; 2005.Google Scholar
  28. 28.
    Feyer P, Sautter-Bihl ML, Budach W, et al. DEGRO practical guidelines for palliative radiotherapy of breast cancer patients: brain metastases and leptomeningeal carcinomatosis. Strahlenther Onkol. 2010;186:63–9.CrossRefPubMedGoogle Scholar
  29. 29.
    Mittl R Jr, Yousem D. Frequency of unexplained meningeal enhancement in the brain after lumbar puncture. Am J Neuroradiol. 1994;15(4):633–8.PubMedGoogle Scholar
  30. 30.
    Freilich R, Krol G, DeAngelis L. Neuroimaging and cerebrospinal fluid cytology in the diagnosis of leptomeningeal metastasis. Ann Neurol. 1995;38:51–7.CrossRefPubMedGoogle Scholar
  31. 31.
    Chamberlain M. Comparative spine imaging in leptomeningeal metastases. J Neurooncol. 1995;23:233–8.CrossRefPubMedGoogle Scholar
  32. 32.
    Cheng T, O’Neill B, Scheithauer B, et al. Chronic meningitis: the role of meningeal or cortical biopsy. Neurosurgery. 1994;34:590–5.PubMedGoogle Scholar
  33. 33.
    Chamberlain M. Leptomeningeal metastasis. Curr Opin Neurol. 2009;22:665–74.CrossRefPubMedGoogle Scholar
  34. 34.
    Shapiro W, Johanson C, Boogerd W. Treatment modalities for leptomeningeal metastases. Semin Oncol. 2009;36(4 Suppl 2):S46–54.CrossRefPubMedGoogle Scholar
  35. 35.
    Mason W, DeAngelis L, Yeh S. 111Indium-DPTA cerebrospinal fluid studies in leptomeningeal metastases predict intrathecal methotrexate distribution and outcome in patients with leptomeningeal metastases. Neurology. 1998;50:438–43.CrossRefPubMedGoogle Scholar
  36. 36.
    Kak M, Nanda R, Ramsdale E, et al. Treatment of leptomeningeal carcinomatosis: current challenges and future opportunities. J Clin Neurosci. 2015;22:632–7.CrossRefPubMedGoogle Scholar
  37. 37.
    Chamberlain M, Goulart B. Are prognostic factors for leptomeningeal metastases defined sufficiently to permit tailored treatment? J Thorac Oncol. 2013;8(7):E66–7.CrossRefPubMedGoogle Scholar
  38. 38.
    Chamberlain M, Eaton K. Is there a role for whole brain radiotherapy in the treatment of leptomeningeal metastases? J Thorac Oncol. 2012;7(7):1204.CrossRefPubMedGoogle Scholar
  39. 39.
    Chamberlain M, Soffietti R, Raizer J, et al. Leptomeningeal metastases: a response assessment in neuro-oncology critical review of endpoints and response criteria of published randomized clinical trials. Neuro Oncol. 2014;16:1176–85.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Glantz M, Hall W, Cole B, et al. Diagnosis, management and survival of patients with leptomeningeal cancer based on cerebrospinal fluid-flow status. Cancer. 1995;75:2919–31.CrossRefPubMedGoogle Scholar
  41. 41.
    Elmore S, Balboni T. Symptom control and predictors of survival in leptomeningeal carcinomatosis of the neuraxis treated with radiation therapy. Int J Radiat Oncol Biol Phys. 2015;93(3 Suppl):E478–9. Abstr 3195CrossRefGoogle Scholar
  42. 42.
    Boogerd W, Hart A, van der Sande J, et al. Meningeal carcinomatosis in breast cancer: prognostic factors and influence of treatment. Cancer. 1991;67:1685–95.CrossRefPubMedGoogle Scholar
  43. 43.
    Gani C, Muller A, Eckert F, et al. Outcome after whole brain radiotherapy alone in intracranial leptomeningeal carcinomatosis from solid tumours. Strahlenther Onkol. 2012;188:148–53.CrossRefPubMedGoogle Scholar
  44. 44.
    Omuro A, Lallana E, Bilsky M, et al. Ventriculoperitoneal shunt in patients with leptomeningeal metastasis. Neurology. 2005;64:1625–7.CrossRefPubMedGoogle Scholar
  45. 45.
    Jung T, Chung W, Oh I. The prognostic significance of surgically treated hydrocephalus in leptomeningeal metastases. Clin Neurol Neurosurg. 2014;119:80–3.CrossRefPubMedGoogle Scholar
  46. 46.
    Mackillop WJ. The principles of palliative radiotherapy: a radiation oncologist’s perspective. Can J Oncol. 1996;6(Suppl 1):5–11.PubMedGoogle Scholar
  47. 47.
    Chamberlain M, Kormanik P. Prognostic significance of 111indium-DTPA CSF flow studies in leptomeningeal metastases. Neurology. 1996;46:1674–7.CrossRefPubMedGoogle Scholar
  48. 48.
    Grossman S, Trump C, Chen D, et al. Cerebrospinal fluid abnormalities in patients with neoplastic meningitis. Am J Med. 1982;73:641–7.CrossRefPubMedGoogle Scholar
  49. 49.
    Siegal T, Lossos A, Pfeffer M. Leptomeningeal metastases: analysis of 31 patients with sustained off-therapy response following combined modality therapy. Neurology. 1994;44:1463–9.CrossRefPubMedGoogle Scholar
  50. 50.
    Boogerd W, van den Bent M, Koehler P, et al. The relevance of intraventricular chemotherapy for leptomeningeal metastasis in breast cancer: a randomized study. Eur J Cancer. 2004;40:2726–33.CrossRefPubMedGoogle Scholar
  51. 51.
    Aisner J, Ostrow S, Govindan S, et al. Leptomeningeal carcinomatosis in small cell carcinoma of the lung. Med Pediatr Oncol. 1981;9:47–59.CrossRefPubMedGoogle Scholar
  52. 52.
    Jo K, Lim D, Kim S, et al. Leptomeningeal seeding in patients with brain metastases treated by gamma knife radiosurgery. J Neurooncol. 2012;109:293–9.CrossRefPubMedGoogle Scholar
  53. 53.
    Hashimoto K, Narita Y, Miyakita Y, et al. Comparison of clinical outcomes of surgery followed by local brain radiotherapy and surgery followed by whole brain radiotherapy in patients with a single brain metastasis: Single Centre retrospective analysis. Int J Radiat Oncol Biol Phys. 2011;81:E475–80.CrossRefPubMedGoogle Scholar
  54. 54.
    Suki D, Abouassi H, Patel A, et al. Comparative risk of leptomeningeal disease after resection or stereotactic radiosurgery for solid tumour metastasis to the posterior fossa. J Neurosurg. 2008;108:248–57.CrossRefPubMedGoogle Scholar
  55. 55.
    Sause W, Crowley J, Eyre H, et al. Whole brain irradiation and intrathecal methotrexate in the treatment of solid tumour leptomeningeal metastases – a Southwest Oncology Group study. J Neurooncol. 1988;6:107–12.CrossRefPubMedGoogle Scholar
  56. 56.
    Victoria Hospice Society Learning Centre for Palliative Care. In: Downing GM, Wainwright W, editors. Medical care of the dying. 4th ed. Victoria: Victoria Hospice Society; 2006.Google Scholar
  57. 57.
    Dudani S, Mazzarello S, Hilton J, et al. Optimal management of leptomeningeal carcinomatosis in breast cancer patients: a systematic review. Clin Breast Cancer. 2016;16(6):456–70.CrossRefPubMedGoogle Scholar
  58. 58.
    Heathfield K, Williams J. Carcinomatosis of the meninges: clinical and pathological aspects. Br Med J. 1956;1(4962):328–40.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Emoto S, Ishigami H, Yamaguchi H, et al. Frequent development of leptomeningeal carcinomatosis in patients with peritoneal dissemination of gastric cancer. Gastric Cancer. 2011;14:390–5.CrossRefPubMedGoogle Scholar
  60. 60.
    Lukas R, Mata-Machado N, Nicholas M, et al. Leptomeningeal carcinomatosis in esophagus cancer: a case series and systematic review of the literature. Dis Esophagus. 2015;28:772–81.CrossRefPubMedGoogle Scholar
  61. 61.
    Grommes C, Oxnard G, Kris M, et al. Pulsatile high-dose weekly erlotinib for CNS metastases from EGFR mutant non-small cell lung cancer. Neuro Oncol. 2011;13(12):1364–9.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Eichler A, Kahle K, Wang D, et al. EGFR mutation status and survival after diagnosis of brain metastasis in non-small cell lung cancer. Neuro Oncol. 2010;12:1193–9.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Hata A, Katakami N, Kaji R, et al. Erlotinib for whole brain radiotherapy refractory leptomeningeal metastases after gefitinib failure in a lung adenocarcinoma patient. J Thorac Oncol. 2012;7(4):770–1.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Radiation OncologyCross Cancer InstituteEdmontonCanada

Personalised recommendations