Predictors of survival in metastatic melanoma patients with leptomeningeal disease (LMD)

  • Sherise D. FergusonEmail author
  • Shivani Bindal
  • Roland L. BassettJr.
  • Lauren E. Haydu
  • Ian E. McCutcheon
  • Amy B. Heimberger
  • Jing Li
  • Barbara J. O’Brien
  • Nandita Guha-Thakurta
  • Michael T. Tetzlaff
  • Hussein Tawbi
  • Michael A. Davies
  • Isabella C. Glitza
Clinical Study



Although the survival of most melanoma patients diagnosed with leptomeningeal disease (LMD) is short, some patients can have better outcomes and prolonged survival. A large retrospective cohort of patients was analyzed to identify features associated with survival with LMD from melanoma.


Clinical characteristics, treatments and survival were collected for melanoma patients diagnosed with LMD from 1999 to 2015. The Kaplan–Meier method was used to estimate overall survival (OS) and Cox proportional hazards regression was used to test statistical significance of associations with survival. Multivariate analysis was performed using Cox proportional regression modeling.


178 melanoma patients with LMD were identified. Median age at LMD diagnosis was 51 years. Most (n = 153) patients received at least one treatment for LMD, including radiation (n = 98), chemotherapy (n = 89), targeted therapy (n = 60), immunotherapy (n = 12), or intrathecal (IT) therapy (n = 64). Median OS from LMD diagnosis was 3.5 months. One-, two-, and five-year OS rates were 22%, 14%, and 9%, respectively. Factors significantly associated with OS on multivariate analysis included Eastern Cooperative Oncology Group [ECOG] performance status > 0 (HR 2.1, P < 0.0001); neurological symptoms (HR 1.6, P < 0.0001); absent systemic disease (HR 0.4, P < 0.0001); and LMD treatment (HR 0.4, P = 0.0024), targeted therapy (HR 0.6, P = 0.0060), or IT therapy (HR 0.5, P = 0.0019).


Despite their overall poor prognosis a subset of melanoma patients with LMD achieve longer survival. The factors associated with outcomes may be used to guide patient management and to inform the design of future clinical trials for this population.


Melanoma Leptomeningeal disease Intrathecal therapy Targeted therapy Immunotherapy 



We thank David M. Wildrick, Ph.D., for editorial assistance.


Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; the AIM at Melanoma Foundation; and philanthropic support from the MD Anderson Melanoma Moon Shot Program.

Compliance with ethical standards

Conflict of interest

Dr. Davies has served on the advisory boards for BMS, Norvartis, Roche/Genetech, GSK, Sanofi-Aventis, Vaccinex and Syndax and has been the PI of institution grants from BMS, Astrzeneca, GSK, Roche/Genetech, Myriad and Oncothyreon. Dr. Tetzlaff has advisory board relationships with Novartis, Myriad and Seattle Genetics.

Ethical approval

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

Supplementary material

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Supplementary material 1 (DOCX 21 KB)
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Supplementary material 2 (PNG 7550 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Sherise D. Ferguson
    • 1
    • 9
    Email author
  • Shivani Bindal
    • 1
  • Roland L. BassettJr.
    • 2
  • Lauren E. Haydu
    • 3
  • Ian E. McCutcheon
    • 1
  • Amy B. Heimberger
    • 1
  • Jing Li
    • 4
  • Barbara J. O’Brien
    • 5
  • Nandita Guha-Thakurta
    • 6
  • Michael T. Tetzlaff
    • 7
  • Hussein Tawbi
    • 8
  • Michael A. Davies
    • 8
  • Isabella C. Glitza
    • 8
  1. 1.Department of NeurosurgeryThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Department of BiostatisticsThe University of Texas MD Anderson Cancer CenterHoustonUSA
  3. 3.Department of Surgical OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  4. 4.Department of Radiation OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  5. 5.Department of Neuro-OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  6. 6.Department of Diagnostic RadiologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  7. 7.Department of PathologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  8. 8.Department of Melanoma Medical OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  9. 9.The University of Texas MD Anderson Cancer CenterHoustonUSA

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