Leptomeningeal carcinomatosis (LC) is a rare complication of cancer in which the disease spreads to the meninges surrounding the brain and spinal cord. It is a highly fatal condition that occurs in up to 23% of melanoma patients, and the prognosis for patients with LC and melanoma is generally just a few weeks.
Even with the advent of novel therapies, the prognosis remains dismal, according to a new study presented at the Society for Melanoma Research 2015 Congress in San Francisco.
Improved treatment for LC is urgently needed, said study author Ryan J. Sullivan, MD, assistant in medicine and member of the Center for Melanoma and Teermer Center for Targeted Therapy at the Massachusetts General Hospital in Boston.
"It is a dreadful complication of melanoma," he told Medscape Medical News.
LC consists of metastatic tumor cells that are attached to the pia mater, which covers the brain and spinal cord, or that float unattached in the cerebrospinal fluid. The management of these patients is not uniform; instead, it is multifaceted and complex. But even with an aggressive approach, outcomes tend to be poor, the authors note.
In the retrospective analysis of 25 women and 41 men with melanoma who developed LC from 1993 to 2014, there was no significant difference in survival between patients diagnosed before 2011 and those diagnosed and treated with novel agents after 2011.
The pathophysiology, prognostic factors, and the most effective treatments for LC are currently not well understood, Dr Sullivan explained.
"Major risk factors are unknown, but certainly patients with CNS metastases have a higher risk," he told Medscape Medical News.
It is also unclear why this complication develops in some patients, he said. "Some influence regarding certain signaling pathways may be responsible, but a major focus of our research is trying to figure this out."
Disappointing Results With Novel Therapies
In their study, Dr Sullivan and his colleagues sought to characterize overall survival in patients with melanoma who developed LC before and after the introduction of novel agents. Another objective was to identify prognostic factors for survival.
Of the 66 patients who met the inclusion criteria, 40 patients were diagnosed with LC before 2011 and 26 were diagnosed after 2011.
Table. Commonly Used Therapies for LC
| Therapy | Pre-2011 Cohort, % | Post-2011 Cohort, % |
| Radiation | 47.5 | 50.0 |
| Chemotherapy | 25.0 | 11.5 |
| Intrathecal chemotherapy | 12.5 | 0.0 |
| Targeted therapy | 0.0 | 15.4 |
| Immunotherapy | 0.0 | 19.2 |
| No treatment | 21.2 | 20.0 |
Despite the use of new therapies after 2011, there was no significant difference in survival between the two cohorts.
In the study cohort, median overall survival from diagnosis of LC to death was 9.7 weeks (95% confidence interval [CI], 8.7 - 14.3). In the pre-2011 cohort, median overall survival was 9.6 weeks (95% CI, 8.4 - 23.7), and in the post-2011 cohort, median overall survival was 14.3 weeks (95% CI, 7.6 - 12.4).
Median time from the diagnosis of primary melanoma to LC was 27.3 months (range, 0 - 109), and from the diagnosis of stage IV melanoma to LC was 7.5 months (range, 0 - 46).
The only negative prognostic factor for survival in patients who received treatment for LC was lactate dehydrogenase.
In contrast, positive prognostic factors for survival were treatment with chemotherapy (hazard ratio [HR], 0.193; 95% CI, 0.057 - 0.465; P = .0007), treatment with targeted therapy (HR, 0.092; 95% CI, 0.016 - 0.522; P = .007), and time from melanoma to LC diagnosis (P = .02). Other types of treatment and whether LC was diagnosed before or after 2011 had no effect on survival.
"We have done a number of analyses and have not found one specific therapy that is better than another, but the numbers of patients are small," said Dr Sullivan. "BRAF-mutated patients tend to get BRAF targeted therapy, and immune therapy may work, but there is very little clinical data available."
"Basically, we give whatever we can," he noted. "We and others are just now opening trials to test how well our various therapies work."
Society for Melanoma Research (SMR) 2015 Congress.
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