Subventricular zones: new key targets for glioblastoma treatment

Abstract

Background: We aimed to identify subventricular zone (SVZ)-related prognostic factors of survival and patterns of recurrence among patients with glioblastoma.

Methods: Forty-three patients with primary diagnosed glioblastoma treated in our Cancer Center between 2006 and 2010 were identified. All patients received surgical resection, followed by temozolomide-based chemoradiation. Ipsilateral (iSVZ), contralateral (cSVZ) and bilateral (bSVZ) SVZs were retrospectively segmented and radiation dose-volume histograms were generated. Multivariate analysis using the Cox proportional hazards model was assessed to examine the relationship between prognostic factors and time to progression (TTP) or overall survival (OS).

Results: Median age was 59 years (range: 25-85). Median follow-up, OS and TTP were 22.7 months (range 7.5-69.7 months), 22.7 months (95% CI 14.5-26.2 months) and 6.4 months (95% CI 4.4-9.3 months), respectively. On univariate analysis, initial contact to SVZ was a poor prognostic factor for OS (18.7 vs 41.7 months, p = 0.014) and TTP (4.6 vs 12.9 months, p = 0.002). Patients whose bSVZ volume receiving at least 20 Gy (V20Gy) was greater than 84% had a significantly improved TTP (17.7 months vs 5.2 months, p = 0.017). This radiation dose coverage was compatible with an hippocampal sparing. On multivariate analysis, initial contact to SVZ and V20 Gy to bSVZ lesser than 84% remained poor prognostic factors for TTP (HR = 3.07, p = 0.012 and HR = 2.67, p = 0.047, respectively).

Conclusion: Our results suggest that contact to SVZ, as well as insufficient bSVZ radiation dose coverage (V20Gy <84%), might be independent poor prognostic factors for TTP. Therefore, targeting SVZ could be of crucial interest for optimizing glioblastoma treatment.

Keywords: Glioblastoma; Prognostic factors; Radiotherapy; Stem-cell niche; Subventricular Zone.

Fig. 1

Planning computed tomography scan with three dimensional reconstruction illustrating both delineation methods for subventricular zone (SVZ). Ipsilateral and contralteral SVZ were contoured as 5 mm expansion along the lateral margins of lateral ventricles. Two delineation methods were used : TH+ method including temporal horns (a), and TH- method excluding them (b). Yellow: bilateral SVZ; Red : Clinical Target Volume

Fig. 2

Kaplan-Meier survival curve for time to progression (TTP) by bilateral subventricular zone (bSVZ) dose, with TH- delineation method (excluding temporal horns): V20 Gy to bSVZ > 84% (n = 8 patients) versus ≤ 84% (n = 32 patients). Patients with V20 Gy to bSVZ greater than 84% had a statistically significant improvement in TTP (17.7 months vs 5.2 months)