In Reply: Ventricular Entry During Glioblastoma Resection is Associated With Reduced Survival and Increased Risk of Distant Recurrence

To the Editor: We sincerely thank Van Der Veken et al1 for their thoughtful letter regarding our article, “Ventricular Entry During Glioblastoma Resection is Associated with Reduced Survival and Increased Risk of Distant Recurrence.”1,2 We are encouraged that our findings have stimulated academic dialog that may ultimately advance our understanding of this challenging disease. We read with great interest the study by Stringer et al3 cited in their letter. In this work, the authors demonstrated that cerebrospinal fluid (CSF) exposure in 25 patients was associated with increased resistance to chemoradiotherapy and identified nuclear protein 1, a transcription factor, as a mediator of this resistance.3 Importantly, inhibition of nuclear protein 1 with trifluoperazine enhanced the killing of glioblastoma cells resistant to chemoradiation in CSF.3 The authors concluded that CSF exposure may modulate tumor behavior. Additional evidence further indicates that CSF may activate malignancy-promoting pathways, enhancing glioblastoma cell invasion and migration.4,5 Most recently, Riviere-Cazaux et al6 demonstrated that CSF composition varies substantially in glioma patients by anatomic site (ventricular, subarachnoid, lumbar) and across pre-, early-, and delayed-resection time points, underscoring its dynamic nature and potential value as a medium to study the temporal effects of resection. Such mechanisms may help further explain the survival differences we observed between patients with and without ventricular entry. Further research is needed to clarify the cellular consequences of ventricular entry, which may provide a foundation for identifying therapeutic targets and refining surgical techniques to improve treatment strategies for these patients. Importantly, prospective studies will be essential to establish the extent to which these cellular alterations ultimately translate into patient outcomes depending on tumor- and treatment-related factors. It should be acknowledged that maximal safe resection should be pursued whenever possible in surgical treatment of gliomas, and the implications of surgical ventricular entry should be strongly considered. Neurosurgeons and neuro-oncologists should be aware of and vigilant about the possible consequences associated with this approach. When gross total resection of the contrast-enhancing tumor can be accomplished without ventricular entry, favoring such an approach is reasonable. In circumstances where ventricular entry is unavoidable, prospective, well-designed studies should rigorously evaluate whether resection of the non–contrast-enhancing component confers a survival advantage. We firmly believe that our study will foster continued discussion and generate new hypotheses, all in pursuit of improving patient outcomes.