Assessing efficacy of intrathecal chemotherapy in patients with leptomeningeal metastases: A systematic review and meta-analysis.

Abstract

e14000 Background: Leptomeningeal metastasis (LM) is a rare and severe complication of cancer, characterized by the spread of malignant cells to the meninges of the brain and spinal cord. Often associated with a poor prognosis, radiotherapy is the commonly used measure for control. This systematic review and meta-analysis aims to assess the efficacy of intrathecal (IT) administration of chemotherapeutic agents in patients with LM. Methods: A comprehensive literature search was conducted across three databases to identify original studies employing the use of IT chemotherapy in patients with diagnosed LM. Extracted data was expressed as odd’s ratio and 95% confidence interval (CI), and analyzed using proportional meta-analysis in R employing a random-effects model. Results: A total of 30 studies comprising 1,258 patients were included for quantitative analysis. These patients were administered drugs like pemetrexed, thiotepa, cytarabine, and methotrexate via the IT route. An overall partial response of 24%[95% CI: 0.14, 0.39] was recorded among the patients, with 21%[95% CI: 0.16, 0.26] achieving complete response. Stable disease was noted in 40% of all patients [95% CI: 0.31, 0.5]. While 49%[95% CI: 0.35, 0.64] of the patients recorded an improvement in their neurological status, clinical stability, identified by neurological status stabilization, was noted in 28% of the patients [95%CI: 0.19, 0.4]. Response to chemotherapy was also recorded based on radiological signs; while 32% of the patients experienced radiologically progressive response, 23% of the patients noted progression of the disease [95% CI: 0.16, 0.32]. Among adverse events, a high incidence of mortality was observed (47%[95% CI: 0.22, 0.75]). Among specific chemotherapy-induced adverse events, the incidence of permanent myelosuppression was the highest (20%[95% CI: 0.11, 0.36]), followed by vomiting (14%[95% CI: 0.08, 0.22]). Intractable vomiting was recorded in only 3% of these cases. In general, neurological adverse events were rare, with only 9% of the patients reporting meningitis. Incidence of leukoencephalopathy and seizures was at 6% each, while radiculopathy was observed in only 3% of the patients [95% CI: 0.01, 0.07]. Conclusions: Our findings conclude the high immediate response to intrathecal chemotherapy, with high levels of stable disease or complete response among patients. IT chemotherapy significantly improved neurological status as well, resulting in considerable stabilization. However, radiological improvement was still sparse, with many undergoing the progression of the disease. The risk of mortality, myelosuppression, and vomiting was significantly high with the use of IT chemotherapy. Further trials evaluating the comparative efficacy of IT chemotherapy vis-à-vis radiotherapy or systemic chemotherapy must be conducted.