Novel treatment vs. standard of care in melanoma-associated leptomeningeal metastases: a systematic review and network meta-analysis.

Background: Melanoma stands out as a prevalent instigator of leptomeningeal disease (LMD) within the realm of cancer. Given the poor prognosis accompanying this condition, ongoing trials are exploring a spectrum of treatment modalities in pursuit of more effective interventions. To ascertain the most effective therapeutic strategies, we aim to compare novel treatments against the current standard of care for melanoma-associated LMD.

Methods: A comprehensive search was conducted across multiple databases, including PubMed/Medline, EMBASE, Scopus, ScienceDirect and Web of Science for relevant studies published from January 2014 to September 2024. We included primary research studies, including observational studies, randomised control trials, quasi-experimental design studies, clinical trials, and experimental studies focusing on LMD caused by metastatic melanoma. Data extraction was conducted according to PRISMA guidelines and quality assessment/risk of bias was performed individually using the GRADE method. A network meta-analysis is conducted to evaluate the effects of multiple interventions within the study. Overall survival outcomes were quantified using log hazard ratio. The protocol for this study was registered on PROSPERO (CRD42024529626).

Results: Out of 843 records screened for eligibility, seven carefully chosen studies, meeting our specific inclusion criteria, provided insights into the management of 397 patients grappling with LMD due to metastatic melanoma. These studies vary in design: one observational cohort study with 29 participants, a clinical trial with 25 patients, four retrospective cohort studies ranging from 39 to 190 participants and one experimental study with 24 patients. The chosen studies contain moderate to high risks of bias, with low heterogeneity (I2=13.4%). Immunotherapy with or without targeted therapy is the most effective intervention.

Conclusions: Despite the escalating breakthroughs of treatment options in melanoma-associated LMD, further studies may be imperative to conclusively determine whether the newer therapeutic options yield superior outcomes compared to the current standard of care.