Subventricular Zone Radiation Dose and Outcome for Glioblastoma Treated Between 2006 and 2012.

Sonja C Murchison,Bradley Wiksyk,Stacey Gossman,Pauline T Truong,Brigit Jensen,Mary Lesperance,Dorothy Sayers,Abraham Alexander

doi:10.7759/cureus.3618

Abstract

ObjectiveStem cells residing in the subventricular zone (SVZ) may be related to recurrence, potentially affecting outcome in glioblastoma (GBM). This study investigated the relationship of SVZ radiation dose and survival in a large cohort treated with surgery and chemoradiotherapy (CRT).MethodsPatients with GBM treated between 2006 and 2012 (n = 370) were identified. SVZs were contoured from planning computed tomography (CT) with magnetic resonance imaging (MRI) registration where available. Dose was extracted from dose volume histograms. Kaplan-Meier (KM) progression-free survival (PFS) and overall survival (OS) estimates were compared with log-rank tests for SVZ doses. Multivariate analysis (MVA) identified clinical and treatment-related factors significantly associated with outcome.ResultsMedian follow-up was 16.4 months, 48.1% underwent gross total resection (GTR), 37.5% subtotal resection, and 14.4% biopsy without resection. Median PFS was 8.9 months (95% CI: 8.3–9.8 months), and OS was 16.5 months (95% CI: 15.2–17.6 months). PFS was significantly lower for older age (>50 years, P = 0.045), poor Karnofsky performance status (KPS, P = 0.049), multifocality (P < 0.001), and incomplete adjuvant chemotherapy (P < 0.001). Worse OS was associated with poor KPS (P = 0.001), biopsy only (P = 0.003), multifocality (P = 0.009), and failure to complete adjuvant chemotherapy (P < 0.001). SVZ dose was not associated with outcome for any of the dose levels assessed. On MVA, multifocality was associated with worse PFS (P < 0.01). Poor performance status and biopsy only were associated with worse OS (both P < 0.01).ConclusionIn this analysis of a large cohort of GBM treated with surgery and CRT, increased SVZ dose was not associated with improved survival.

Highlights

Standard treatment for glioblastoma (GBM) in patients younger than 65–70 years involves maximal surgical resection plus radical long-course chemoradiotherapy, followed by adjuvant chemotherapy with temozolomide [1]
This study investigates whether subventricular zone (SVZ) dose is correlated with survival outcomes in a large cohort of GBM patients treated with radical long-course CRT and concomitant temozolomide
Between 2006 and 2012, all patients above age 18 with pathologically proven GBM treated at the institution with long-course CRT, who completed the full course of radiotherapy and at least 50% of the concurrent chemotherapy, were retrospectively reviewed (n = 370)

Summary

Introduction

Standard treatment for glioblastoma (GBM) in patients younger than 65–70 years involves maximal surgical resection plus radical long-course chemoradiotherapy, followed by adjuvant chemotherapy with temozolomide [1]. TLSC have been isolated and extensively studied in GBM [2,3,4,5]. Research suggests they may contribute to negative outcomes associated with this disease. In both cultured cells and mice models, neural stem cells (NSC) and TLSC both express CD133, which is correlated with greater radioresistance, repopulation, and DNA damage checkpoint response [6]. Tumor proximity or involvement of the SVZ has been related to poorer prognosis [13,14,15]

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Conclusion