Among patients with melanoma brain metastases (MBM), surgical intervention was not the only risk factor for developing leptomeningeal disease (LMD), according to a retrospective study published in Neuro-Oncology.

The study revealed that anatomical factors such as dural-based and intraventricular metastasis, as well as metastasis bordering a ventricle or cerebrospinal fluid (CSF) cistern, were associated with an increased risk of developing LMD.

LMD is a rare but serious complication that can occur in several types of solid tumor malignancies. In patients with MBM, LMD portends poor prognosis, with a mean survival of 3.5 months, even with treatment. Previous data suggested that surgical resection may increase the risk of LMD compared with focal radiation therapy (RT).

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For the current study, researchers sought to determine if the anatomic location of brain metastases and surgical intervention increased the risk of LMD in patients with metastatic melanoma.

The study included 827 patients with melanoma and intracranial metastatic disease who were treated at a single institution. Approximately 66.0% of patients were men, the average age was 60.0 years, and the median follow-up was 22.4 months.

The researchers found that surgery for resection of a metastatic tumor was not a statistically significant predictor for the development of LMD (odds ratio [OR], 1.19; 95% CI, 0.74-1.93; P =.476).

On multivariate analysis of the overall cohort, female sex (OR, 1.69; 95% CI, 1.05-2.81; P =.042), the presence of dural-based metastasis (OR, 2.33; 95% CI, 1.04-5.23; P =.041), intraventricular metastasis (OR, 4.48; 95% CI, 1.72-11.70; P =.002), and metastasis bordering a ventricle or major cistern (OR, 3.17; 95% CI, 1.90-5.30; P <.001) were all significantly associated with increased risk of LMD.

LMD Risk in Surgical Patients

Among patients who underwent surgical resection, location of resection adjacent to a CSF space as well as entry into the ventricle was associated with the development of LMD.

Dural-based metastasis (OR, 2.77; 95% CI, 1.04-7.35; P =.041), intraventricular metastasis (OR, 6.94; 95% CI, 1.86-25.88; P =.004), metastasis bordering a ventricular space (OR, 2.97; 95% CI, 1.46-6.02; P =.003), and ventricular entry during surgery (OR, 4.82; 95% CI, 2.15-10.82; P <.001) were all strongly correlated with LMD development.

LMD Risk in Nonsurgical Patients

Among patients who did not undergo surgery, sex (OR, 1.63; 95% CI, 0.83-3.32; P =.159) and presence of dural-based metastasis (OR, 2.07, 95% CI, 0.58-7.40; P =.265) were not associated with the development of LMD.

The presence of intraventricular metastasis (OR, 5.47; 95% CI, 1.60-18.71; P =.007) and metastasis bordering a ventricular space or cistern (OR, 4.64; 95% CI, 2.33-9.24; P <.001) were significantly associated with LMD development.

The presence of metastasis in the infratentorial space, the administration of RT, and the presence of tumor bordering the ventricle did not seem to have an impact on the development of LMD.

On multivariate analysis, chemotherapy after initial MBM diagnosis (OR, 2.12; 95% CI, 1.02-4.40; P =.044) and the presence of metastasis bordering a ventricle or cistern (OR, 4.38; 95% CI, 2.18-8.77; P <.001) were associated with an increased risk of developing LMD.

“The data presented demonstrate a correlation between anatomic location of brain metastases and the risk for development of LMD,” the researchers wrote. “These findings highlight the complex relationship between natural and iatrogenic tumor cell seeding into a CSF space as a direct cause of the development of LMD.”


Lowe SR, Wang CP, Brisco A, et al. Surgical and anatomic factors predict development of leptomeningeal disease in patients with melanoma brain metastases. Neuro Oncol. Published online January 29, 2022. doi:10.1093/neuonc/noac023