Comparative Analysis of Subventricular Zone Glioblastoma Contact and Ventricular Entry During Resection in Predicting Dissemination, Hydrocephalus, and Survival

Abstract

Background: Ventricular entry during glioblastoma resection and tumor contact with the subventricular zone (SVZ) have both been shown to associate with development of hydrocephalus, leptomeningeal dissemination, distant parenchymal recurrence, and decreased survival. However, prior studies did not analyze these variables together in a single-patient population; therefore, it is unknown which is an independent predictor of these outcomes.

Objective: To conduct a comparative outcome analysis of surgical ventricular entry and SVZ contact by glioblastoma in a retrospective cohort of 232 patients.

Methods: Outcomes studied included hydrocephalus, leptomeningeal dissemination, distant tumor recurrences, and progression-free (PFS) and overall (OS) survival. The Cox proportional regression analyses were adjusted for age at diagnosis, preoperative Karnofsky performance status score, extent of resection, temozolomide and radiation treatments, and tumor molecular status (specifically, IDH1/2 mutation and MGMT promoter methylation).

Results: Surgical ventricular entry, SVZ-contacting glioblastoma, hydrocephalus, leptomeningeal dissemination, and distant recurrences were observed in 85 (36.6%), 114 (49.1%), 19 (8.2%), 78 (33.6%), and 59 (25.4%) patients, respectively. Multivariate, adjusted analysis revealed SVZ tumor contact-but not ventricular entry-associated with hydrocephalus (hazard ratio, HR, 4.20 [1.13-15.7], P = .03), leptomeningeal dissemination (HR 1.93 [1.14-3.28], P = .01), PFS (HR 2.10 [1.53-2.88], P < .001), and OS (HR 1.90 [1.35-2.67], P < .001). Distant recurrences were not associated with either. No interaction between the 2 variables was statistically noted.

Conclusion: SVZ contact by glioblastoma was independently associated with the development of hydrocephalus, leptomeningeal dissemination, and decreased survival. SVZ tumor contact was associated with ventricular entry during surgical resections, which did not independently correlate with these outcomes.

Keywords: Dissemination; Glioblastoma; Glioma; Hydrocephalus; Lateral ventricle; Subventricular zone; Survival.

Copyright © 2019 by the Congress of Neurological Surgeons.

Figures

FIGURE 1.

Time-dependent incidence of primary outcomes of interest based on SVZ glioblastoma contact and ventricular entry. Kaplan–Meier incidence curves are plotted with tick marks to indicate censored values. These include A, hydrocephalus based on ventricular entry; B, hydrocephalus based on SVZ contact; C, leptomeningeal dissemination based on ventricular entry; D, leptomeningeal dissemination based on SVZ contact; E, distant parenchymal recurrence based on ventricular entry; F, distant parenchymal recurrence based on SVZ contact. Vertical dashed lines, when present, delineate median (50% probability) time values for the outcomes. P values from a log-rank test are provided for each plot. Vent = ventricular.

FIGURE 2.

Interaction between SVZ contact and ventricular entry in predicting A, hydrocephalus and B, leptomeningeal dissemination. Kaplan–Meier incidence curves are plotted with tick marks to indicate censored values. Vertical dashed lines, when present, delineate median (50% probability) time values for the outcomes. P values from a log-rank test for a trend are provided for each plot. VE = ventricular entry.

FIGURE 3.

Forest plot of HR derived from multivariable, adjusted analyses. Forest plot depicts HR with 95% confidence intervals of 5 outcomes for the 2 primary variables of interest. These results are adjusted for age at diagnosis, preoperative KPS, extent of resection, administration of postoperative temozolomide and radiation, and tumor molecular status (specifically, IDH1/2 mutation and MGMT promoter methylation). Refer to Methods section and Table, Supplemental Digital Content 3, for statistical details and numerical results. SVZ = subventricular zone.

FIGURE 4.

Patient survival based on SVZ glioblastoma contact and ventricular entry. Kaplan–Meier survival curves are plotted with tick marks to indicate censored values. These include A, OS and B, PFS based on ventricular entry and C, OS and D, PFS based on SVZ contact. Vertical dashed lines delineate median (50% probability) time values for the outcomes. P values from a log-rank test are provided for each plot. Vent = ventricular.