Background: It has been suggested that an aggressive treatment of patients with leptomeningeal metastases (LM) that groups radiotherapy and intra-cerebrospinal fluid (intra-CSF) chemotherapy has improved treatment outcomes. Based on their previous series of 137 patients treated with such an intensive standard protocol, the authors expected 20% of the patients to maintain their responses for at least 6 months after withdrawal of therapy. They also observed that, in patients with solid tumors, a partial response was compatable with sustained off-therapy response and that the maximal response was reached soon after completion of radiotherapy. The authors concluded that the role of intra-CSF chemotherapy, with its associated high rate of complications, is unclear. In this study, which was a further evaluation of this dilemma, they compared the outcomes of two prospective treatment protocols that were identical in their use of radiotherapy and systemic chemotherapy and varied only in their inclusion or exclusion of intra-CSF chemotherapy.
Methods: Adult patients with LM from systemic solid tumors were prospectively included in the treatment protocol active at the time of their diagnosis. Group 1 comprised 54 patients treated by radiotherapy, intra-CSF chemotherapy, and systemic therapy, whereas Group 2 comprised 50 patients treated with radiotherapy, and systemic chemotherapy but no intra-CSF chemotherapy.
Results: The analysis of treatment outcomes was performed retrospectively. The median patient age and distribution of primary neoplasms did not differ between the two groups. The proportion of early deaths that occurred during radiotherapy was similar for the two groups, as was the overall rate of response to treatment. The two groups also had the same median survival, which was 4 months for both groups, as well as the same proportion of long term survivors. Thirty-one percent of patients in Group 1 developed early complications related to intra-CSF chemotherapy, whereas patients in Group 2 were spared these complications. Delayed symptomatic leukoencephalopathy was observed in 20% of Group 1 patients compared with none in Group 2 (P = 0.02).
Conclusions: The exclusion of intra-CSF chemotherapy from the treatment schedule of patients with LM does not change their overall response to treatment, their median survival, or the proportion of long term survivors. It does, however, significantly reduce the rate of early and delayed treatment-related complications.