Elsevier

World Neurosurgery

Volume 111, March 2018, Pages e323-e334
World Neurosurgery

Original Article
Survival of Ventricular and Periventricular High-Grade Gliomas: A Surveillance, Epidemiology, and End Results Program–Based Study

https://doi.org/10.1016/j.wneu.2017.12.052Get rights and content

Background

Aggressiveness of surgical resection for periventricular/ventricular high-grade gliomas (HGGs) is determined by operative risks and assumed effectiveness of radiation therapy (RT) on residual tumor. We aimed to clarify the impact of surgery and postoperative RT on patient survival in a population-based study.

Methods

This population-based study used the Surveillance, Epidemiology, and End Results (SEER) database. Patients with ventricular malignant tumors were screened for HGGs. In accordance with the World Health Organization (WHO) 2016 classification, we included cases with “diffuse astrocytic and oligodendroglial tumors,” “other astrocytic tumors,” “ependymal tumors,” and “other gliomas”. Tumor grading followed definitions established by the WHO with supplementation from SEER classifications. Only grades III and IV were included. Individual factors were assessed by hazard ratio (HR) from multivariable survival analysis using accelerated failure time (AFT) regression.

Results

We included 353 patients after application of inclusion and exclusion criteria. The mean patient age was 38.77 ± 24.95 years, and the cohort was 61.5% male. Overall median survival was 12 months, with notable improvement over the last 3 decades. In a multivariate AFT model, older age (per 10-year increase, HR, 1.19; P < 0.001) was the sole nontreatment variable found to predict survival, whereas postoperative RT had a significant survival benefit (HR, 0.50; P < 0.001). No tumor characteristic (e.g., size, extent of invasion) predicted prognosis. Interestingly, neither partial resection nor TR/GTR was associated with improved outcome.

Conclusions

The prognosis of ventricular HGGs is poor, with worse prognosis in older patients. We found no evidence to support aggressive surgical resection. Postoperative chemoradiation should be administered; however, the benefit of modification of the protocol for chemoradiation specifically for ventricular HGGs remains unknown and warrants further investigation.

Introduction

Intracranial gliomas are neuroepithelial tumors hypothesized to originate from neoplastic transformation of glial cells.1 High-grade glioma (HGG, or malignant glioma) is the most common brain glioma with an extremely malignant clinical course, with an annual incidence of 5 per 100,000, and constituting 70% of all brain gliomas.2, 3 According to the literature, the estimated median survival is 9–12 months for glioblastomas (GBMs) and 2 to 5 years for grade 3 anaplastic tumors.1, 2 although this has improves over the last decade owing to continuing optimization of treatment regimens and evolution of targets and delivery modalities in chemotherapy.4, 5, 6

Ventricular or periventricular HGGs typically involve the ventricular zone or subventricular zone (V-SVZ), and represent a special subcohort of HGGs with unique features. The V-SVZ is known to harbor neural stem cells of a multipotent nature, which increases the propensity to generate aggressively proliferating tumors.1, 7, 8, 9, 10 Indeed, in multiple studies, this location alone has been shown to significantly predict worse survival in patients with malignant gliomas.9, 10, 11, 12, 13 Management challenges arise when the poor prognosis of V-SVZ malignant gliomas is weighed against the increased surgical complexity and associated complications, owing to the deep location and risk for metastasis with opening of ventricles.7, 14 Although chemoradiation is considered the standard therapy for HGGs,15 controversy remains regarding the extent of resection and aggressiveness of postresection radiation therapy (RT) when the V-SVZ is involved (especially when ventricles are opened). Some authors have suggested aggressive resection without modification of post-treatment RT, whereas others have favored a more conservative surgical approach due to fear of leptomeningeal spread (LMS),16, 17 or a more aggressive RT protocol for survival benefit.6

A survival analysis for elucidation of survival and risk factors has yet to be performed in a population-based study. In the present study, we used the Surveillance, Epidemiology, and End Results Program (SEER) database to investigate and quantify the impact on survival of the extent of surgical resection and RT on a population-based scale.

Section snippets

Study Design and Patient Cohort Selection

This study was designed as an observational longitudinal survival study. Institutional Review Board approval was not required because we used publicly available data from the SEER database, which is administered by the National Cancer Institute, with patient data collected prospectively in 18 states. The data source was the SEER submission in 2015 which included a patient cohort covering the years 1973–2013. Patients with malignant brain tumors with location labeled as “ventricles” were first

Study Cohort and Histology

A total of 2009 patients with malignant ventricular or periventricular tumors were identified in the SEER database. After application of exclusion criteria, our cohort comprised 353 patients with high-grade V-SVZ gliomas. The patient selection process is illustrated in Figure E1, and included tumor histology is described in Table 1. As shown, the most prevalent histology in our cohort was glioblastoma (glioblastoma NOS plus giant cell glioblastoma; 48.7%), followed by anaplastic ependymoma

Summary of Key Results

Here we present the prognosis and factors predictive of survival in patients with ventricular or periventricular HGGs from a population-based perspective. To our knowledge, our series represents the largest cohort with this unique combination reported to date. We found that the HGGs in this location consist mainly of glioblastomas, followed by grade III anaplastic gliomas. Even with both grade III and grade IV gliomas, however, the overall median survival of the patients with V-SVZ HGGs was 12

Conclusions

In agreement with previous studies, we found better survival in younger patients with ventricular or periventricular HGGs compared with older patients; however, no tumor-related characteristics were predictive of survival. The management of ventricular or periventricular HGGs remains challenging and requires rigorous refinement of treatment regimens, especially regarding EOR. In this study, we found no evidence to support aggressive surgical resection, although postoperative RT was of

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    Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

    Wuyang Yang and Tao Xu contributed equally to this work.

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