To The Editor,

I'd like to congratulate Jamison and colleagues on their article [1] evaluating the available evidence for the use of intrathecal (IT) thiotepa in hematologic malignancies and non-the central nervous system (CNS) solid tumors with leptomeningeal disease metastases (LMD). They reported that IT thiotepa is a reasonable alternative in hematologic malignancies and LMD due to solid organ malignancies. The authors described several studies in which metastatic breast cancer (MBC) patients were treated with IT thiotepa for LMD. But it's important to note a recent study where the authors assessed the largest real-world sample of MBC patients receiving IT therapy to date [2]. 312 patients who received IT therapy out of the 22 266 patients who were included in the database between 2008 and 2016 were chosen for analysis. On multivariable analysis, they discovered that the triple-negative subtype (HR 1.81, 95% CI 1.32–2.47), treatment line ≥ 3 (HR 1.88, 95% CI 1.30–2.73), ≥ 3 other metastatic sites (HR 1.33, 95% CI 1.01–1.74), and IT cytarabine or thiotepa versus methotrexate (HR 1.68, 95% CI 1.28–2.22) were significant prognostic factors linked to a worse outcome. They proposed that concurrent systemic therapy (apart from in patients with TN subtype) and the use of IT methotrexate (instead of thiotepa) could improve overall survival. As a whole, IT methotrexate—rather than IT thiotepa—should be regarded as the first-line IT medication. This issue merits further investigation.