Is there a role for whole brain radiotherapy in the treatment of leptomeningeal metastases?

Morris et al. are to be congratulated for their retrospective analysis of patients with non–small-cell lung cancer (NSCLC) and leptomeningeal metastases (LM). Several aspects regarding the study warrant commentary. First, this was a single-institution retrospective study in which all patients with LM (defined by cerebrospinal fluid [CSF] cytology or radiographic evidence of CSF-disseminated disease) were included. Consequently, the study cohort was heterogenous with respect to identified LM prognostic features (the presence or absence of radiographic bulky disease, carcinomatous encephalopathy, performance status, and burden of systemic disease), and none were identified in the present study. Consequently, it is unclear how many patients in the present study would be considered as favorable risk and considered for LM-directed therapy. Because the present study included patients with radiographically defined LM, it is unclear how many patients in this category (i.e., bulky disease) were represented. Because of the retrospective nature of the study, there were no a priori determinants of treatment such that treatment was defined individually without apparent standardization making cross comparisons between treatment groups problematic. This feature is perhaps most evident in the fact that only 6% of all patients were treated with intra-CSF chemotherapy that may reflect an institutional bias with respect to this modality of treatment of LM. Therefore, Figure 4 in the article by Morris et al. 1 is unlikely to be reflective of outcome of patients treated with intra-CSF chemotherapy because of the small number of patients treated and the unclear indications for this treatment. Admittedly, at present, there has not been a randomized study that conclusively establishes a role for intra-CSF chemotherapy in the treatment of solid-tumor– related LM. Patients receiving whole brain irradiation (WBI) were compared with patients not treated similarly, and the authors suggest no survival advantage to treatment of LM with WBI. Given that LM is a neuraxis disease with CSF dynamically circulating through the intracranial and intraspinal compartments, it is not surprising that treatment of only a single CSF compartment (the intracranial compartment) with WBI does not impact survival. As the authors point out, this does not exclude a potential palliative benefit for WBI, a component not addressed by the study. Complicating the administration of WBI in patients with NSCLC and LM is the frequent occurrence of parenchymal brain metastases that may precede or co-occur with the discovery of LM. Patients previously treated with WBI for brain metastases are not candidates in general for repeat WBI in the event of subsequent discovery of LM. The statement that there is no apparent survival benefit of WBI in the treatment of patients with NSCLC and LM needs to be tempered because the indications for WBI were not defined, and patients were not otherwise comparable with respect to prognostic features. Therefore, the utility of WBI in the management of LM is still uncertain. As the authors indicate, management of solid-tumor–related LM remains challenging because of a paucity of prospective trials and consequently the lack of standardization in LM-related treatment that is evidence based.