RESEARCH ARTICLE
Anatomical Involvement of the Subventricular Zone Predicts Poor Survival Outcome in Low-Grade Astrocytomas Shuai Liu1, Yinyan Wang2,3, Xing Fan2, Jun Ma4, Wenbin Ma1, Renzhi Wang1*, Tao Jiang2,3,5* 1 Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 2 Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China, 3 Beijing Neurosurgical Institute, Capital Medical University, Beijing, China, 4 Department of Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China, 5 Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, Chin
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* [email protected] (RW); [email protected] (TJ)
Abstract OPEN ACCESS Citation: Liu S, Wang Y, Fan X, Ma J, Ma W, Wang R, et al. (2016) Anatomical Involvement of the Subventricular Zone Predicts Poor Survival Outcome in Low-Grade Astrocytomas. PLoS ONE 11(4): e0154539. doi:10.1371/journal.pone.0154539 Editor: Francis Szele, University of Oxford, UNITED KINGDOM Received: September 16, 2015 Accepted: April 14, 2016 Published: April 27, 2016 Copyright: © 2016 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The subventricular zone (SVZ) has been implicated in the origination, development, and biological behavior of gliomas. Tumor-SVZ contact is also postulated to be a poor prognostic factor in glioblastomas. We aimed to evaluate the prognostic consequence of the anatomical involvement of low-grade gliomas with the SVZ. To that end, we reviewed 143 patients with diffuse astrocytomas, and tumor lesions were manually delineated on magnetic resonance images. We initially investigated the prognostic role of SVZ contact in all patients. Additionally, we investigated the influence of the anatomical proximity of the tumor lesion centroids to the SVZ in the SVZ-involved patient cohorts, as well as location within the SVZ. We found SVZ contact with tumors to be a significant prognostic factor of overall survival in all patients with diffuse astrocytomas (p = 0.027). In the SVZ-involved cohort, a shorter distance from the tumor centroid to the SVZ (30 mm) correlated with shorter overall survival (p = 0.022) on univariate analysis. However, there was no significant difference in overall survival with respect to the SVZ region involved with the tumor (p = 0.930). Multivariate analysis showed that a shorter distance between the tumor centroid and the SVZ (p = 0.039) was significantly associated with poor overall survival in SVZ-involved patients. Hence, this study helps establish the prognostic role of the anatomical interaction of tumors with the SVZ in low-grade astrocytomas.
Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: Funding for this work was provided by the National 973 Program (No.2015CB755500) [Tao Jiang], http://www.973.gov.cn; and the Research Special Fund for Public Welfare industry of health (No. 201402008) [Wenbin Ma], http://www. shenjingzhongliu.org. Competing Interests: The authors have declared that no competing interests exist.
Introduction The tumorigenesis of gliomas is still not completely understood. Glial cells were once believed to be the only type of cells possessing proliferative capability in the adult brain, and gliomas were thought to originate from the neoplastic transformation of these fully differentiated glia [1,2]. Subsequently, investigators proposed the cancer stem cell (CSC) theory [3,4], which suggested that several primary brain tumors, including gliomas, are derived from the malignant transformation of multipotent neural stem cells (NSC) [1,5,6]. The brain’s subventricular zone
PLOS ONE | DOI:10.1371/journal.pone.0154539 April 27, 2016
1 / 11
SVZ Involvement and Survival in Low-Grade Astrocytomas
(SVZ), which contains a large amount of NSCs, was postulated to be the region that is involved in the formation of gliomas. Previous clinical studies investigated the relationship between gliomas and the SVZ. Tumors that are in contact with the SVZ exhibit unique biological characteristics; they are most likely to present multifocal lesions on magnetic resonance (MR) images at diagnosis [7] and to be associated with shorter overall survival (OS) [8–11]. Radiotherapy co-targeted to the SVZ improves the progression-free survival (PFS) of patients compared to radiotherapy targeted at the tumor alone [12]. Additionally, increasing the mean radiotherapy dose to the ipsilateral SVZ was associated with significantly improved OS [13,14]. Previous studies that investigated the association between the SVZ and gliomas mainly focused on glioblastoma, whereas low-grade gliomas were generally overlooked. The current clinical study enrolled a cohort of patients with diffuse astrocytomas (WHO grade II). The locations of tumor lesions were examined in relation to the SVZ using MR images to assess direct contact. In cases where tumor-SVZ contact was evident, the distance from the tumor centroid to the SVZ was measured, and the anatomical region of the SVZ that was involved with the tumor was determined. The prognostic roles of clinical characteristics and radiological features were evaluated using multivariate survival analyses.
Materials and Methods Patients We conducted a retrospective review of patients who were newly diagnosed with primary diffuse astrocytoma (WHO grade II) histopathologically and were treated at the Glioma Treatment Center of Beijing Tiantan Hospital between 2006 and 2010. One hundred and forty-three patients who met the following criteria were included: pathologically confirmed astrocytoma (WHO grade II), preoperative T2-weighted MR images of the brain, treated with surgical resection, and no prior craniotomy or stereotactic biopsy. Nineteen patients were lost to follow-up and thus excluded. The extent of surgical resection was determined by comparing the preoperative and postoperative MR images. The gross total resection (GTR) was defined by removing all the abnormalities on T2 weighted sequences. Meanwhile,
Anatomical Involvement of the Subventricular Zone Predicts Poor Survival Outcome in Low-Grade Astrocytomas Shuai Liu1, Yinyan Wang2,3, Xing Fan2, Jun Ma4, Wenbin Ma1, Renzhi Wang1*, Tao Jiang2,3,5* 1 Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 2 Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China, 3 Beijing Neurosurgical Institute, Capital Medical University, Beijing, China, 4 Department of Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China, 5 Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, Chin
a11111
* [email protected] (RW); [email protected] (TJ)
Abstract OPEN ACCESS Citation: Liu S, Wang Y, Fan X, Ma J, Ma W, Wang R, et al. (2016) Anatomical Involvement of the Subventricular Zone Predicts Poor Survival Outcome in Low-Grade Astrocytomas. PLoS ONE 11(4): e0154539. doi:10.1371/journal.pone.0154539 Editor: Francis Szele, University of Oxford, UNITED KINGDOM Received: September 16, 2015 Accepted: April 14, 2016 Published: April 27, 2016 Copyright: © 2016 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The subventricular zone (SVZ) has been implicated in the origination, development, and biological behavior of gliomas. Tumor-SVZ contact is also postulated to be a poor prognostic factor in glioblastomas. We aimed to evaluate the prognostic consequence of the anatomical involvement of low-grade gliomas with the SVZ. To that end, we reviewed 143 patients with diffuse astrocytomas, and tumor lesions were manually delineated on magnetic resonance images. We initially investigated the prognostic role of SVZ contact in all patients. Additionally, we investigated the influence of the anatomical proximity of the tumor lesion centroids to the SVZ in the SVZ-involved patient cohorts, as well as location within the SVZ. We found SVZ contact with tumors to be a significant prognostic factor of overall survival in all patients with diffuse astrocytomas (p = 0.027). In the SVZ-involved cohort, a shorter distance from the tumor centroid to the SVZ (30 mm) correlated with shorter overall survival (p = 0.022) on univariate analysis. However, there was no significant difference in overall survival with respect to the SVZ region involved with the tumor (p = 0.930). Multivariate analysis showed that a shorter distance between the tumor centroid and the SVZ (p = 0.039) was significantly associated with poor overall survival in SVZ-involved patients. Hence, this study helps establish the prognostic role of the anatomical interaction of tumors with the SVZ in low-grade astrocytomas.
Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: Funding for this work was provided by the National 973 Program (No.2015CB755500) [Tao Jiang], http://www.973.gov.cn; and the Research Special Fund for Public Welfare industry of health (No. 201402008) [Wenbin Ma], http://www. shenjingzhongliu.org. Competing Interests: The authors have declared that no competing interests exist.
Introduction The tumorigenesis of gliomas is still not completely understood. Glial cells were once believed to be the only type of cells possessing proliferative capability in the adult brain, and gliomas were thought to originate from the neoplastic transformation of these fully differentiated glia [1,2]. Subsequently, investigators proposed the cancer stem cell (CSC) theory [3,4], which suggested that several primary brain tumors, including gliomas, are derived from the malignant transformation of multipotent neural stem cells (NSC) [1,5,6]. The brain’s subventricular zone
PLOS ONE | DOI:10.1371/journal.pone.0154539 April 27, 2016
1 / 11
SVZ Involvement and Survival in Low-Grade Astrocytomas
(SVZ), which contains a large amount of NSCs, was postulated to be the region that is involved in the formation of gliomas. Previous clinical studies investigated the relationship between gliomas and the SVZ. Tumors that are in contact with the SVZ exhibit unique biological characteristics; they are most likely to present multifocal lesions on magnetic resonance (MR) images at diagnosis [7] and to be associated with shorter overall survival (OS) [8–11]. Radiotherapy co-targeted to the SVZ improves the progression-free survival (PFS) of patients compared to radiotherapy targeted at the tumor alone [12]. Additionally, increasing the mean radiotherapy dose to the ipsilateral SVZ was associated with significantly improved OS [13,14]. Previous studies that investigated the association between the SVZ and gliomas mainly focused on glioblastoma, whereas low-grade gliomas were generally overlooked. The current clinical study enrolled a cohort of patients with diffuse astrocytomas (WHO grade II). The locations of tumor lesions were examined in relation to the SVZ using MR images to assess direct contact. In cases where tumor-SVZ contact was evident, the distance from the tumor centroid to the SVZ was measured, and the anatomical region of the SVZ that was involved with the tumor was determined. The prognostic roles of clinical characteristics and radiological features were evaluated using multivariate survival analyses.
Materials and Methods Patients We conducted a retrospective review of patients who were newly diagnosed with primary diffuse astrocytoma (WHO grade II) histopathologically and were treated at the Glioma Treatment Center of Beijing Tiantan Hospital between 2006 and 2010. One hundred and forty-three patients who met the following criteria were included: pathologically confirmed astrocytoma (WHO grade II), preoperative T2-weighted MR images of the brain, treated with surgical resection, and no prior craniotomy or stereotactic biopsy. Nineteen patients were lost to follow-up and thus excluded. The extent of surgical resection was determined by comparing the preoperative and postoperative MR images. The gross total resection (GTR) was defined by removing all the abnormalities on T2 weighted sequences. Meanwhile,
