Glioblastoma Recurrence Patterns Near Neural Stem Cell Regions

Purpose: Glioblastoma (GBM) cancer stem cells and their neural stem cell counterparts are hypothesized to contribute to tumor progression. We examined whether GBM contrast enhancement contact with neurogenic regions (NR) affect recurrence patterns, as contrast enhancement reflects regions of blood-brain barrier breakdown.

Methods: 102 patients with primary GBM, treated at Johns Hopkins Hospital between 2006 and 2009, were included. All patients underwent surgical resection followed by adjuvant IMRT (60 Gy/30 fractions) and concomitant temozolomide. Initial and recurrent tumor distance from the subventricular zone (SVZ) or subgranular zone (SGZ) was measured. Tumors were categorized as NR contacting or non-contacting. The chi-square test was used to analyze the association between tumor contact and recurrence pattern.

Results: 49 of 102 (48.0%, 95% CI: 0.386-0.576) tumors contacted NRs at initial presentation, and, of these tumors, 49/49 (100%) contacted NRs at recurrence. Of 53 tumors that were initially non-contacting, 37/53 (69.8%, 95% CI: 0.565-0.804) recurred contacting NRs. In total, 86/102 (84.3%, 95% CI: 0.760-0.901) recurrent GBM contacted NRs compared with 49/102 (48%, 95% CI: 0.386-0.576) at initial presentation. Of the recurrent tumors that did not contact NRs, 16/53 (30.1%, 95% CI: 0.195-0.435) recurred medially toward NRs with a significant decrease in distance between tumor contrast enhancement and NRs. 16/49 (32.6%, 95% CI: 0.212-0.466) initially NR-contacting GBMs recurred out-of field while 7/53 (13.2%, 95% CI: 0.0655-0.248) initially non-contacting recurred out of the radiation treatment field (p=0.0315, Odds ratio: 3.19, 95% CI: 1.18-8.62).

Conclusions: GBM contrast-enhancing recurrence is significantly associated with proximity to NRs. NR-contacting initial tumors were more likely to recur out of radiation treatment fields.