The Prognostic Value of MRI Subventricular Zone Involvement and Tumor Genetics in Lower Grade Gliomas

Abstract

BACKGROUND AND PURPOSE: Glioblastomas (GBMs) that involve the subventricular zone (SVZ) have a poor prognosis, possibly due to recruitment of neural stem cells. The purpose of this study was to evaluate whether SVZ involvement by lower grade gliomas (LGG), WHO grade II and III, similarly predicts poorer outcomes. We further assessed whether tumor genetics and cellularity are associated with SVZ involvement and outcomes. METHODS: Forty-five consecutive LGG patients with preoperative imaging and next generation sequencing were included in this study. Regional SVZ involvement and whole tumor apparent diffusion coefficient (ADC) values, as a measure of cellularity, were assessed on magnetic resonance imaging. Progression was determined by RANO criteria. Kaplan-Meier curves and Cox regression analyses were used to determine the hazard ratios (HR) for progression and survival. RESULTS: Frontal, parietal, temporal, and overall SVZ involvement and ADC values were not associated with progression or survival (P ≥ .05). However, occipital SVZ involvement, seen in two patients, was associated with a higher risk of tumor progression (HR = 6.6, P = .016) and death (HR = 31.5, P = .015), CDKN2A/B mutations (P = .03), and lower ADC histogram values at the 5th (P = .026) and 10th percentiles (P = .046). Isocitrate dehydrogenase, phosphatase and tensin homolog, epidermal growth factor receptor, and cyclin-dependent kinase 4 mutations were also prognostic (P ≤ .05). CONCLUSIONS: Unlike in GBM, overall SVZ involvement was not found to strongly predict poor prognosis in LGGs. However, occipital SVZ involvement, though uncommon, was prognostic and found to be associated with CDKN2A/B mutations and tumor hypercellularity. Further investigation into these molecular mechanisms underlying occipital SVZ involvement in larger cohorts is warranted.

Impact of Relative T2-FLAIR Signal Intensity of Non-Enhancing Lesions Outside Residual Cavity in Early Follow-up MRI on Outcome of Lower Grade Gliomas

“…In this study, new SVZ involvement was detected as non-enhancing hyperintensity T2-FLAIR lesions in 80.65% patients (25/31). SVZ could increase invasiveness and migratory potential because it is the source of tumor precursor stem cells [11,23]. Thus, higher incidence of SVZ involvement (83.69%) in progression group in the present study, even without post-contrast enhancement, had adverse impaction on survival outcome of LGG patients.…”

“…From the date of surgery to the date of the last follow-up or death was de ned as overall survival (OS). From the date of surgery to the date of progression or the date of the last follow-up without progression was de ned as progression free survival (PFS) [11].…”

Irradiation of the Subventricular Zone and Subgranular Zone: an Atlas-based analysis on Overall Survival in High- and Low-Grade Glioma Patients

“…Furthermore, we show that SVZ contact to the GTV is associated with a 4.3 months lower median OS in HGG patients compared to patients that do not have SVZ contact with the GTV, which is in line with findings by Berendsen et al 6 However, we are aware that this may be misleading, as the SVZ is located centrally in the brain and it is suggested that central tumor location itself is associated with worse OS. 46 We performed similar analyses for LGG patients as well, following methods of Chiang et al 8 and Liu et al 7 but we did not find a relation between SVZ contact with GTV and survival in this patient group. The outcomes may be due to our LGG patient sample size which is less than half of the sample size used in the study of Liu et al 7 Another consideration is the atypical division of WHO grades in high-and low-grade, as Chiang et al 8 included WHO III patients as LGG patients and we included WHO III patients in the HGG cohort.…”

“…46 We performed similar analyses for LGG patients as well, following methods of Chiang et al 8 and Liu et al 7 but we did not find a relation between SVZ contact with GTV and survival in this patient group. The outcomes may be due to our LGG patient sample size which is less than half of the sample size used in the study of Liu et al 7 Another consideration is the atypical division of WHO grades in high-and low-grade, as Chiang et al 8 included WHO III patients as LGG patients and we included WHO III patients in the HGG cohort.…”

“…The hypothesis is based on previous pre-clinical and clinical research which showed that the SVZ might support the growth of LGG and HGG by providing the tumor with NSCs. [5][6][7][8]39 However, it remains controversial, as there is a limited number of previous studies that in contrast report that irradiation of the SVZ decreases OS for patients with HGG. [40][41][42][43] A preclinical study by Achanta et al reported a decrease of the proliferating cell marker Ki67 in a mouse model when the SVZ was irradiated, 44 41,42 Our study describes this negative correlation between SVZ irradiation and OS in HGG patients as well, involving a large number of patients (n = 226).…”