Skip to main content

Advertisement

SpringerLink
Log in

Diagnosis and treatment patterns for patients with leptomeningeal metastasis from solid tumors across Europe

  • Clinical Study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Leptomeningeal metastases are a late manifestation of systemic cancer which affects up to 10% of patients with solid tumors. Prognosis is poor, and overall survival at 1 year is only approximately 10%. Management depends mainly on general and neurological condition, primary tumor, and patterns of metastasis, notably absence or presence of concurrent systemic or solid brain metastases. Here we set out to characterize current practice patterns of diagnosis and treatment of patients with leptomeningeal metastasis in Europe. We prepared a web-based survey including 25 simple or multiple choices questions on best practice supplemented by eight case vignettes with various diagnosis and management options. The survey was sent to the membership of the European Association of Neuro-Oncology and the European Organisation for Research and Treatment of Cancer Brain Tumor Group. Between April 7, 2016 and August 8, 2016, 224 colleagues from 26 countries initiated the survey, 115 colleagues completed the whole survey. There were major differences both in the general diagnostic and therapeutic approach, e.g., regarding the use of cerebrospinal fluid (CSF) flow studies, intra-CSF chemotherapy, various types of radiotherapy, and even more so when selecting decisions on diagnostic and therapeutic measures for single case vignettes. Diagnosis and treatment decisions for patients with leptomeningeal metastasis from solid tumors vary widely across Europe. Standardization of diagnosis and evaluation tools as well as controlled studies to improve the level of evidence for all therapeutic approaches to LM are required.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Chamberlain M, Junck L, Brandsma et al (2016) Leptomeningeal metastases: a RANO proposal for response criteria. Neuro Oncol. doi:10.1093/neuonc/now183

    PubMed Central  Google Scholar 

  2. Le Rhun E, Galanis E (2016) Leptomeningeal metastases of solid cancer. Curr Opin Neurol 29:797–805. doi:10.1097/WCO.0000000000000393

    Article  CAS  PubMed  Google Scholar 

  3. Regierer AC, Stroux A, Kühnhardt D et al (2008) Contrast-enhancing meningeal lesions are associated with longer survival in breast cancer-related leptomeningeal metastasis. Breast Care Basel Switz 3:118–123. doi:10.1159/000121688

    Article  Google Scholar 

  4. Gauthier H, Guilhaume MN, Bidard FC et al (2010) Survival of breast cancer patients with meningeal carcinomatosis. Ann Oncol 21:2183–2187. doi:10.1093/annonc/mdq232

    Article  CAS  PubMed  Google Scholar 

  5. Lee S, Ahn HK, Park YH et al (2011) Leptomeningeal metastases from breast cancer: intrinsic subtypes may affect unique clinical manifestations. Breast Cancer Res Treat 129:809–817. doi:10.1007/s10549-011-1682-0

    Article  PubMed  Google Scholar 

  6. de Azevedo CRAS, Cruz MRS, Chinen LTD et al (2011) Meningeal carcinomatosis in breast cancer: prognostic factors and outcome. J Neurooncol 104:565–572. doi:10.1007/s11060-010-0524-y

    Article  PubMed  Google Scholar 

  7. Yust-Katz S, Garciarena P, Liu D et al (2013) Breast cancer and leptomeningeal disease (LMD): hormone receptor status influences time to development of LMD and survival from LMD diagnosis. J Neurooncol 114:229–235. doi:10.1007/s11060-013-1175-6

    Article  CAS  PubMed  Google Scholar 

  8. Le Rhun E, Taillibert S, Zairi F et al (2013) A retrospective case series of 103 consecutive patients with leptomeningeal metastasis and breast cancer. J Neurooncol 113:83–92. doi:10.1007/s11060-013-1092-8

    Article  CAS  PubMed  Google Scholar 

  9. Abouharb S, Ensor J, Loghin ME et al (2014) Leptomeningeal disease and breast cancer: the importance of tumor subtype. Breast Cancer Res Treat 146:477–486. doi:10.1007/s10549-014-3054-z

    Article  CAS  PubMed  Google Scholar 

  10. Morris PG, Reiner AS, Szenberg OR et al (2012) Leptomeningeal metastasis from non-small cell lung cancer: survival and the impact of whole brain radiotherapy. J Thorac Oncol 7:382–385. doi:10.1097/JTO.0b013e3182398e4f

    Article  PubMed  Google Scholar 

  11. Umemura S, Tsubouchi K, Yoshioka H et al (2012) Clinical outcome in patients with leptomeningeal metastasis from non-small cell lung cancer: Okayama Lung Cancer Study Group. Lung Cancer 77:134–139. doi:10.1016/j.lungcan.2012.03.002

    Article  PubMed  Google Scholar 

  12. Gwak H-S, Joo J, Kim S et al (2013) Analysis of treatment outcomes of intraventricular chemotherapy in 105 patients for leptomeningeal carcinomatosis from non-small-cell lung cancer. J Thorac Oncol 8:599–605. doi:10.1097/JTO.0b013e318287c943

    Article  CAS  PubMed  Google Scholar 

  13. Riess JW, Nagpal S, Iv M et al (2014) Prolonged survival of patients with non-small-cell lung cancer with leptomeningeal carcinomatosis in the modern treatment era. Clin Lung Cancer 15:202–206. doi:10.1016/j.cllc.2013.12.009

    Article  PubMed  Google Scholar 

  14. Kuiper JL, Hendriks LE, van der Wekken AJ et al (2015) Treatment and survival of patients with EGFR-mutated non-small cell lung cancer and leptomeningeal metastasis: a retrospective cohort analysis. Lung Cancer 89:255–261. doi:10.1016/j.lungcan.2015.05.023

    Article  PubMed  Google Scholar 

  15. Harstad L, Hess KR, Groves MD (2008) Prognostic factors and outcomes in patients with leptomeningeal melanomatosis. Neuro-Oncology 10:1010–1018. doi:10.1215/15228517-2008-062

    Article  PubMed  PubMed Central  Google Scholar 

  16. Geukes Foppen MH, Brandsma D, Blank CU et al (2016) Targeted treatment and immunotherapy in leptomeningeal metastases from melanoma. Ann Oncol 27:1138–1142. doi:10.1093/annonc/mdw134

    Article  CAS  PubMed  Google Scholar 

  17. Rudnicka H, Niwińska A, Murawska M (2007) Breast cancer leptomeningeal metastasis—the role of multimodality treatment. J Neurooncol 84:57–62. doi:10.1007/s11060-007-9340-4

    Article  PubMed  Google Scholar 

  18. Niwińska A, Rudnicka H, Murawska M (2013) Breast cancer leptomeningeal metastasis: propensity of breast cancer subtypes for leptomeninges and the analysis of factors influencing survival. Med Oncol 30:408. doi:10.1007/s12032-012-0408-4

    Article  PubMed  PubMed Central  Google Scholar 

  19. Meattini I, Livi L, Saieva C et al (2012) Prognostic factors and clinical features in patients with leptominengeal metastases from breast cancer: a single center experience. J Chemother 24:279–284. doi:10.1179/1973947812Y.0000000034

    Article  PubMed  Google Scholar 

  20. Lara-Medina F, Crismatt A, Villarreal-Garza C et al (2012) Clinical features and prognostic factors in patients with carcinomatous meningitis secondary to breast cancer. Breast J 18:233–241. doi:10.1111/j.1524-4741.2012.01228.x

    Article  PubMed  Google Scholar 

  21. Park JH, Kim YJ, Lee J-O et al (2012) Clinical outcomes of leptomeningeal metastasis in patients with non-small cell lung cancer in the modern chemotherapy era. Lung Cancer 76:387–392. doi:10.1016/j.lungcan.2011.11.022

    Article  PubMed  Google Scholar 

  22. Kwon J, Chie EK, Kim K et al (2014) Impact of multimodality approach for patients with leptomeningeal metastases from solid tumors. J Korean Med Sci 29:1094–1101. doi:10.3346/jkms.2014.29.8.1094

    Article  PubMed  PubMed Central  Google Scholar 

  23. Glantz MJ, Cole BF, Glantz LK et al (1998) Cerebrospinal fluid cytology in patients with cancer: minimizing false-negative results. Cancer 82:733–739

    Article  CAS  PubMed  Google Scholar 

  24. Rogers LR, Duchesneau PM, Nunez C et al (1992) Comparison of cisternal and lumbar CSF examination in leptomeningeal metastasis. Neurology 42:1239–1241

    Article  CAS  PubMed  Google Scholar 

  25. Dux R, Kindler-Röhrborn A, Annas M et al (1994) A standardized protocol for flow cytometric analysis of cells isolated from cerebrospinal fluid. J Neurol Sci 121:74–78

    Article  CAS  PubMed  Google Scholar 

  26. Zairi F, Le Rhun E, Bertrand N et al (2015) Complications related to the use of an intraventricular access device for the treatment of leptomeningeal metastases from solid tumor: a single centre experience in 112 patients. J Neurooncol. doi:10.1007/s11060-015-1842-x

    PubMed  Google Scholar 

  27. Kennedy BC, Brown LT, Komotar RJ, McKhann GM (2016) Stereotactic catheter placement for Ommaya reservoirs. J Clin Neurosci 27:44–47. doi:10.1016/j.jocn.2015.11.005

    Article  PubMed  Google Scholar 

  28. Morgenstern PF, Connors S, Reiner AS, Greenfield JP (2016) Image guidance for the placement of Ommaya reservoirs: a comparison of fluoroscopy and frameless stereotactic navigation in 145 patients. World Neurosurg. doi:10.1016/j.wneu.2016.04.090

    PubMed  Google Scholar 

  29. Hitchins RN, Bell DR, Woods RL, Levi JA (1987) A prospective randomized trial of single-agent versus combination chemotherapy in meningeal carcinomatosis. J Clin Oncol 5:1655–1662

    Article  CAS  PubMed  Google Scholar 

  30. Grossman SA, Finkelstein DM, Ruckdeschel JC et al (1993) Randomized prospective comparison of intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis. Eastern Cooperative Oncology Group. J Clin Oncol 11:561–569

    Article  CAS  PubMed  Google Scholar 

  31. Glantz MJ, Jaeckle KA, Chamberlain MC et al (1999) A randomized controlled trial comparing intrathecal sustained-release cytarabine (DepoCyt) to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors. Clin Cancer Res 5:3394–3402

    CAS  PubMed  Google Scholar 

  32. Boogerd W, van den Bent MJ, Koehler PJ et al (2004) The relevance of intraventricular chemotherapy for leptomeningeal metastasis in breast cancer: a randomised study. Eur J Cancer 40:2726–2733. doi:10.1016/j.ejca.2004.08.012

    Article  CAS  PubMed  Google Scholar 

  33. Shapiro WR, Schmid M, Glantz M, Miller JJ (2006) A randomized phase III/IV study to determine benefit and safety of cytarabine liposome injection for treatment of neoplastic meningitis. J Clin Oncol 24:1528

    Article  Google Scholar 

  34. Glantz MJ, LaFollette S, Jaeckle KA et al (1999) Randomized trial of a slow-release versus a standard formulation of cytarabine for the intrathecal treatment of lymphomatous meningitis. J Clin Oncol 17:3110–3116. doi:10.1200/jco.1999.17.10.3110

    Article  CAS  PubMed  Google Scholar 

  35. Chamberlain M, Soffietti R, Raizer J et al (2014) Leptomeningeal metastasis: a response assessment in neuro-oncology critical review of endpoints and response criteria of published randomized clinical trials. Neuro-Oncology 16:1176–1185. doi:10.1093/neuonc/nou089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Abrey LE, Louis DN, Paleologos N, Lassman AB, Raizer JJ, Mason W, Finlay J, Mac Donald DR, De Angelis LM, Cairncross JG, Oligodendroglioma Study Group (2007) Survey of treatment recommendations for anaplastic oligodendroglioma. Neuro-Oncology 9(3):314–318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank Maryline Vo and the North East Neuro-Oncology Group (NENO) (Nancy, France) for creating and supporting the web-based survey tool. The authors thank all participants for time and effort to work on the questionnaire.

Author information

Authors and Affiliations

  1. Lille University, Inserm U1191 PRISM, Villeneuve d’Ascq, France

    Emilie Le Rhun

  2. Neuro-Oncology, Department of Neurosurgery, Rue Emile Laine, University Hospital – CHRU, 59037, Lille Cedex, France

    Emilie Le Rhun

  3. Breast Unit, Department of Medical Oncology, Oscar Lambret Center, Lille, France

    Emilie Le Rhun

  4. Department of Neurology, University Hospital and University of Zurich, Clinical Neuroscience Center, Zurich, Switzerland

    Emilie Le Rhun & Michael Weller

  5. Department of Neuro-Oncology, City of Health and Science and University of Turin, Turin, Italy

    Roberta Rudà & Riccardo Soffietti

  6. Lille University, CHU Lille, EA 2694 - Santé publique: épidémiologie et qualité des soins, 59000, Lille, France

    Patrick Devos

  7. Department of Neuro-Oncology Marazin, Pitie-Salpetriere Hospital and University Pierre et Marie Curie, Paris VI (on behalf of the Association de Neuro-Oncologie d’Expression Française (ANOCEF)), Paris, France

    Khê Hoang-Xuan

  8. Department of Neuro-Oncology, Netherlands Cancer Institute/Antoni van Leeuwenhoek (on behalf of the Dutch Neuro-Oncology Group), Amsterdam, The Netherlands

    Dieta Brandsma

  9. Medical Oncology Department, Hospital Clínico San Carlos (on behalf of Spanish Group of Investigation in Neurooncology (GEINO)), Madrid, Spain

    Pedro Pérez Segura

Authors
  1. Emilie Le Rhun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roberta Rudà
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Patrick Devos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Khê Hoang-Xuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dieta Brandsma
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Pedro Pérez Segura
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Riccardo Soffietti
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Michael Weller
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Emilie Le Rhun.

Ethics declarations

Conflict of interest

Emilie Le Rhun: research funding (Mundipharma); Dieta Brandsma: research funding (BBB pharmaceuticals); Roberta Rudà, Patrick Devos, Riccardo Soffietti, Michael Weller: no conflict of interest.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Le Rhun, E., Rudà, R., Devos, P. et al. Diagnosis and treatment patterns for patients with leptomeningeal metastasis from solid tumors across Europe. J Neurooncol 133, 419–427 (2017). https://doi.org/10.1007/s11060-017-2452-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-017-2452-6

Keywords

Search

Navigation