Clinical Factors Associated with Leptomeningeal Disease (LMD) in Patients Diagnosed with Melanoma Brain Metastasis (MBM)

Saturday, May 4, 2024

2:18 PM – 2:20 PM CT

Location: Booth 745 Neuro Spotlight

Presenting Author(s)

Merve Hasanov, MD (she/her/hers)

Assistant Professor
Division of Medical Oncology, Department of Internal Medicine, Ohio State University
Columbus, OH, US

Co-Author(s)

Christina Abi Faraj, MD (she/her/hers)

Postdoctoral research fellow.
Department of Neurosurgery, MD Anderson Cancer Center
Houston, TX, US
SF

Sherise D. Ferguson, MD

Associate Professor
Department of Neurosurgery, MD Anderson Cancer Center
Houston, Texas, United States
IG

Isabella C. Glitza Olivia, MD

Associate Professor
Department of Melanoma Medical Oncology, MD Anderson Cancer Center, United States
Merve Hasanov, MD (she/her/hers)

Assistant Professor
Division of Medical Oncology, Department of Internal Medicine, Ohio State University
Columbus, OH, US
Ian E. McCutcheon, MD

Professor
Department of Neurosurgery, MD Anderson Cancer Center
HOUSTON, TX, US
DM

Denai Milton, n/a

Principal Biostatistician
Department of Biostatistics, MD Anderson Cancer Center, United States
SS

Subhiksha Srinivasan, n/a

Medical Student
Department of Neurosurgery, MD Anderson Cancer Center, United States

Disclosure(s):

Merve Hasanov, MD: No financial relationships to disclose

Ian E. McCutcheon, MD: Merck: Consultant (Terminated, March 31, 2023), Speaker/Honoraria (Terminated, March 31, 2023)

Introduction: LMD is a subtype of metastatic disease with limited treatment options and poor prognosis. Melanoma has one of the highest rates of leptomeningeal dissemination among solid malignancies. Due to the high morbidity/mortality associated with LMD, it is important to consider clinical factors associated with LMD development in patients with known melanoma brain metastasis (MBM). We examined clinical factors associated with LMD in a large cohort of MBM patients.

Methods: 829 patients with MBM diagnosed at MD Anderson Cancer Center were identified using a retrospective chart review (1/1/2009-12/31/2018). The primary outcome measure was time-to-LMD. Cumulative incidence of LMD was determined using competing risks method, where death was the competing risk. Differences in cumulative incidences were assessed using Gray’s test, and associations between measures of interest and cumulative incidence were determined using proportional sub-distribution hazards regression models.

Results: Of 829 MBM patients identified, 129 developed LMD at the last follow-up (median follow-up 12 months [range: 0.03-156 months]). Median time between MBM diagnosis and LMD was 5.5 months. Of those with known mutation status (n=713), BRAF mutation was present in 74% of patients who developed LMD versus 50% in those who did not (p < 0.001). Multivariable analysis (MVA) showed that BRAF mutation (p = 0.009) and receiving a craniotomy (p = 0.035) were associated with LMD in patients with MBMs. We performed a sub-analysis of BRAF mutant patients (n = 380), as this was a higher risk population. MVA showed that primary melanoma site (upper extremity compared with head and neck) and number of brain metastases at diagnosis were both associated with LMD.

Conclusion : LMD is a dire consequence of advanced melanoma, yet the clinical features associated with its development are not fully characterized. Investigation of clinical factors associated with LMD can guide management of high-risk populations.