Correlation of anatomical involvement patterns of insular gliomas with subnetworks of the limbic system

Abstract

OBJECTIVE Gliomas frequently involve the insula both primarily and secondarily by invasion. Despite the high connectivity of the human insula, gliomas do not spread randomly to or from the insula but follow stereotypical anatomical involvement patterns. In the majority of cases, these patterns correspond to the intrinsic connectivity of the limbic system, except for tumors with aggressive biology. On the basis of these observations, the authors hypothesized that these different involvement patterns may be correlated with distinct outcomes and analyzed these correlations in an institutional cohort. METHODS Fifty-nine patients who had undergone surgery for insular diffuse gliomas and had complete demographic, pre- and postoperative imaging, pathology, molecular genetics, and clinical follow-up data were included in the analysis (median age 37 years, range 21-71 years, M/F ratio 1.68). Patients with gliomatosis and those with only minor involvement of the insula were excluded. The presence of T2-hyperintense tumor infiltration was evaluated in 12 anatomical structures. Hierarchical biclustering was used to identify co-involved structures, and the findings were correlated with established functional anatomy knowledge. Overall survival was evaluated using Kaplan-Meier and Cox proportional hazards regression analysis (17 parameters). RESULTS The tumors involved the anterior insula (98.3\%), posterior insula (67.8\%), temporal operculum (47.5\%), amygdala (42.4\%), frontal operculum (40.7\%), temporal pole (39\%), parolfactory area (35.6\%), hypothalamus (23.7\%), hippocampus (16.9\%), thalamus (6.8\%), striatum (5.1\%), and cingulate gyrus (3.4\%). A mean 4.2 +/- 2.6 structures were involved. On the basis of hierarchical biclustering, 7 involvement patterns were identified and correlated with cortical functional anatomy (pure insular {[}11.9\%], olfactocentric {[}15.3\%], olfactoopercular {[}33.9\%], operculoinsular {[}15.3\%], striatoinsular {[}3.4\%], translimbic {[}11.9\%], and multifocal {[}8.5\%] patterns). Cox regression identified hippocampal involvement (p = 0.006) and postoperative tumor volume (p = 0.027) as significant negative independent prognosticators of overall survival and extent of resection (p = 0.015) as a significant positive independent prognosticator. CONCLUSIONS The study findings indicate that insular gliomas primarily involve the olfactocentric limbic girdle and that involvement in the hippocampocentric limbic girdle is associated with a worse prognosis.