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Mesny E, Jacob J, Noël G, Bernier MO, Ricard D. Specific radiosensitivity of brain structures (areas or regions) and cognitive impairment after focal or whole brain radiotherapy: A review. Cancer Radiother 2025; 29:104625. [PMID: 40378621 DOI: 10.1016/j.canrad.2025.104625] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2025] [Revised: 04/04/2025] [Accepted: 04/04/2025] [Indexed: 05/19/2025]
Abstract
Delayed neurocognitive impairment is observed following encephalic radiotherapy, including brain parts (areas), leading to a substantial deterioration of the quality of life. These delayed radiotherapy side effects are variable in terms of intensity of symptoms and time of occurrence, characterized by minor-to-severe cognitive deficits, such as attention or memory disorders and/or dysexecutive syndrome. However, the precise mechanisms leading to these cognitive disorders remain mostly unknown. Various tissue alterations have been reported after brain radiotherapy, in specific brain structures as the hippocampus, the cerebral white matter or the cerebral cortex. Sparing these structures during brain radiotherapy may be a potential approach to limit the development of late cognitive impairment; however, few dose constraints have been published regarding brain areas (regions) involved in cognitive functions. The main purposes of this literature review are to report the pathophysiological process leading to the radiation-induced cognitive impairment, to describe the tolerance and radiological modifications induced by radiation of specific healthy cerebral tissues, to better understand their radiosensitivity and to describe potential improvements.
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Affiliation(s)
- Emmanuel Mesny
- Université Paris Saclay, université Paris Cité, ENS Paris Saclay, CNRS, SSA, Inserm, centre Borelli, 91190 Gif-sur-Yvette, France; Radiation Oncology department, Hospices civils de Lyon, centre hospitalier Lyon Sud, Oullins-Pierre-Bénite, France.
| | - Julian Jacob
- Sorbonne Université, hôpital de La Pitié-Salpêtrière, Department of Radiation Oncology, 47-83, boulevard de l'Hôpital, 75013 Paris, France
| | - Georges Noël
- Radiotherapy Department, Institut de cancérologie Strasbourg Europe (ICANS), 17, rue Albert-Calmette, BP 23025, 67033 Strasbourg, France; Faculté de médecine, université de Strasbourg, 4, rue Kirschleger, 67000 Strasbourg, France; Europe (ICANS), Radiobiology Laboratory, Unicancer, 67000 Strasbourg, France; Université de Strasbourg, ICube, imagerie multimodale intégrative en santé (Imis), 300, boulevard Sébastien-Brant, 67400 Illkirch-Graffenstaden, France
| | - Marie-Odile Bernier
- Institut de radioprotection et de sûreté nucléaire, Fontenay-aux-Roses, France
| | - Damien Ricard
- Université Paris Saclay, université Paris Cité, ENS Paris Saclay, CNRS, SSA, Inserm, centre Borelli, 91190 Gif-sur-Yvette, France; Service de neurologie, Service de santé des armées, hôpital d'instruction des armées Percy, 92140 Clamart, France; Service de santé des armées, École du Val-de-Grâce, 75005 Paris, France
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Sun F, Zhu Y, Gan G, Xu Y, Xu X. Therapeutic and prognostic impact of target volume delineation in postoperative radiotherapy for high-grade glioma patients with subventricular zone involvement. Radiat Oncol 2025; 20:24. [PMID: 39972483 PMCID: PMC11841192 DOI: 10.1186/s13014-025-02601-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2024] [Accepted: 02/09/2025] [Indexed: 02/21/2025] Open
Abstract
OBJECTIVE This study aimed to analyze the effect of target volumes for radiotherapy and dose on the prognosis of high-grade glioma (HGG) patients when the tumor involves the subventricular zone (SVZ), and to provide a reference for postoperative target volume delineation in HGG patients with SVZ involvement. METHODS The clinical and pathological data were collected from 50 HGG patients with SVZ involvement were collected in the Department of Neurosurgery of the First Affiliated Hospital of Soochow University during the period from January 1, 2017 to December 31, 2020. The average dose (Dmean) of the whole ipsilateral and contralateral SVZs as well as the V45Gy and V60Gy of the whole ipsilateral SVZs of the tumor were derived from the dose-volume histograms (DVH). The Kaplan-Meier analysis was applied to compare the survival differences between groups under different factors. The Cox proportional risk regression model was used to analyze the influencing factors of progression-free survival (PFS) and overall survival (OS). The correlation between the size of the ipsilateral SVZ target area range and the progression pattern was tested by chi-square test. RESULTS Univariate analysis revealed that the potential predictors of PFS of HGG patients with tumor involvement in SVZ were as follows: multiple lesions, tumor size > 3.5 cm and total resection; the potential predictors of OS were multiple lesions, surgical approaches to the lateral ventricles and the dose of contralateral SVZ > 37.33 Gy. Multibariate analysis showed that tumor size > 3.5 cm and total resection were the independent prognostic factors of PFS; multiple lesions was the independent prognostic factors of OS. The Kaplan-Meier method showed that the median PFS and OS of HGG patients with V60Gy ≥ 50% was higher than that of patients with V60Gy < 50% but the difference was not statistically significant. Subgroup analysis showed that patients with V60Gy ≥ 50% had significantly higher PFS in the age < 60 years subgroup (P = 0.006), WHO IV grade (P = 0.006), and surgical penetration of the lateral ventricle subgroup (P = 0.034) than in the V60Gy < 50%. Patients with V60Gy ≥ 50% had significantly higher OS in the WHO IV grade subgroup (P = 0.035), surgically penetrated lateral ventricle subgroup (P = 0.008), IDH1 wild-type subgroup (P = 0.012), and MGMT unmethylated subgroup (P = 0.047) than in V60Gy < 50%. A volume of ≥ 50% of the ipsilateral SVZ receiving a 60 Gy irradiation dose improves local control and reduces the risk of local recurrence in patients with SVZ involvement in HGG. CONCLUSIONS For SVZ-involved HGG patients, the whole ipsilateral SVZ receiving 60 Gy irradiation dose in ≥ 50% of the volume prolonged PFS in those with age < 60 years, WHO IV grade and surgically penetrating lateral ventricles and prolonged OS in those with WHO IV grade, surgically penetrating lateral ventricles, IDH1 wild-type and MGMT unmethylated.
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Affiliation(s)
- Fei Sun
- Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Yan Zhu
- Department of Radiation Oncology, The Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China
| | - Guanghui Gan
- Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Yuan Xu
- Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
| | - Xiaoting Xu
- Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
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Laviv Y, Regev O, Kanner AA, Fichman S, Limon D, Siegal T, Yust-Katz S, Benouaich-Amiel A. Stem the blood flow: beneficial impact of bevacizumab on survival of subventricular zone glioblastoma patients. J Neurooncol 2025; 171:201-211. [PMID: 39316315 DOI: 10.1007/s11060-024-04828-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Accepted: 09/10/2024] [Indexed: 09/25/2024]
Abstract
PURPOSE Angiogenesis is a crucial step in tumorigenesis of glioblastoma (GBM). Bevacizumab, an anti-vascular endothelial growth factor drug, is approved for second-line therapy for GBM. Glioma stem cells, presumably the cell of origin of GBM, take an active role in angiogenesis. The subventricular zone (SVZ) is the brain's largest reservoir of neural stem cells, and GBM near this region (SVZ GBM) is associated with a poor prognosis. This study aims to evaluate the potential impact of second-line bevacizumab treatment on survival in patients with SVZ GBM. METHODS The electronic medical records of adult patients with newly diagnosed SVZ GDM under treated between 1/2011 and 12/2021 were retrospectively reviewed. Clinical, surgical, radiological, and outcome parameters were compared between patients treated with bevacizumab after first relapse to patients without such treatment. RESULTS The cohort included 67 patients. 45 (67.1%) were treated with bevacizumab after the first relapse while 22 (32.9%) were not. The only statistically significant difference between groups was the rate of re-surgery, which was higher in the non-bevacizumab group (40.9% vs. 15.6%; p = 0.023), indicating that the groups were quite homogenous. In general, bevacizumab as a second-line treatment did not affect OS in SVZ GBM cases. However, it significantly prolongs survival time from 1st relapse by an average of more than 4 months, including after adjustment to re-surgery variable (HR = 0.57, 95% CI 0.34-0.94, p = 0.028 and HR = 0.57, 95%CI = 0.34-0.97, PV = 0.038; respectively). Furthermore, when adjusting to time from diagnosis to 1st relapse, bevacizumab treatment was also associated with prolonged OS (HR = 0.58; p = 0.043). In a subgroup analysis, comparing patients treated with both re-surgery and bevacizumab to patients treated in any other way, patients with the combined treatment had the longest mean OS of the entire cohort (22.16 ± 7.81 m vs. 13.60 ± 6.86, p = 0.049; HR = 0.361 95%CI 0.108-1.209, p = 0.085). CONCLUSIONS The use of bevacizumab as a second-line therapy in SVZ GBM cases may positively affect survival after relapse, even when given as a monotherapy. Additionally, in certain yet-to-be-identified sub-populations, bevacizumab may even extend overall survival. Further research is required to accurately identify SVZ GBM patients who would benefit most from anti-angiogenic therapy.
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Affiliation(s)
- Yosef Laviv
- Neurosurgery department, Beilinson hospital, Rabin Medical Center, 39 Zeev Jabotinsky St, Petach Tikva, 4941492, Israel.
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
| | - Ohad Regev
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Meir Medical Center, Kfar Saba, Israel
| | - Andrew A Kanner
- Neurosurgery department, Beilinson hospital, Rabin Medical Center, 39 Zeev Jabotinsky St, Petach Tikva, 4941492, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Susana Fichman
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Pathology department, Beilinson hospital, Rabin Medical Center, Petah Tikva, Israel
| | - Dror Limon
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Neuro-Oncology Unit, Davidoff Cancer Center, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel
| | - Tali Siegal
- Neuro-Oncology Unit, Davidoff Cancer Center, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel
- Hebrew University, Jerusalem, Israel
| | - Shlomit Yust-Katz
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Neuro-Oncology Unit, Davidoff Cancer Center, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel
| | - Alexandra Benouaich-Amiel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Neuro-Oncology Unit, Davidoff Cancer Center, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel
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Griessmair M, Schramm S, Ziegenfeuter J, Canisius J, Jung K, Delbridge C, Schmidt-Graf F, Mitsdoerffer M, Zimmer C, Meyer B, Metz MC, Wiestler B. Advanced imaging reveals enhanced malignancy in glioblastomas involving the subventricular zone: evidence of increased infiltrative growth and perfusion. J Neurooncol 2025; 171:343-350. [PMID: 39387957 PMCID: PMC11695386 DOI: 10.1007/s11060-024-04849-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Accepted: 09/30/2024] [Indexed: 10/12/2024]
Abstract
BACKGROUND Glioblastoma's infiltrative growth and heterogeneity are influenced by neural, molecular, genetic, and immunological factors, with the precise origin of these tumors remaining elusive. Neurogenic zones might serve as the tumor stem cells' nest, with tumors in contact with these zones exhibiting worse outcomes and more aggressive growth patterns. This study aimed to determine if these characteristics are reflected in advanced imaging, specifically diffusion and perfusion data. METHODS In this monocentric retrospective study, 137 glioblastoma therapy-naive patients (IDH-wildtype, grade 4) with advanced preoperative MRI, including perfusion and diffusion imaging, were analyzed. Tumors and neurogenic zones were automatically segmented. Advanced imaging metrics, including cerebral blood volume (CBV) from perfusion imaging, tissue volume mask (TVM), and free water corrected fractional anisotropy (FA-FWE) from diffusion imaging, were extracted. RESULTS SVZ infiltration positively correlated with CBV, indicating higher perfusion in tumors. Significant CBV differences were noted between high and low SVZ infiltration cases at specific percentiles. Negative correlation was observed with TVM and positive correlation with FA-FWE, suggesting more infiltrative tumor growth. Significant differences in TVM and FA-FWE values were found between high and low SVZ infiltration cases. DISCUSSION Glioblastomas with SVZ infiltration exhibit distinct imaging characteristics, including higher perfusion and lower cell density per voxel, indicating a more infiltrative growth and higher vascularization. Stem cell-like characteristics in SVZ-infiltrating cells could explain the increased infiltration and aggressive behavior. Understanding these imaging and biological correlations could enhance the understanding of glioblastoma evolution.
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Affiliation(s)
- Michael Griessmair
- Dept. of Neuroradiology, Klinikum Rechts der Isar, TU Munich, Ismaningerstr. 22, 81675, Munich, Germany.
| | - Severin Schramm
- Dept. of Neuroradiology, Klinikum Rechts der Isar, TU Munich, Ismaningerstr. 22, 81675, Munich, Germany
| | - Julian Ziegenfeuter
- Dept. of Neuroradiology, Klinikum Rechts der Isar, TU Munich, Ismaningerstr. 22, 81675, Munich, Germany
| | - Julian Canisius
- Dept. of Neuroradiology, Klinikum Rechts der Isar, TU Munich, Ismaningerstr. 22, 81675, Munich, Germany
| | - Kirsten Jung
- Dept. of Neuroradiology, Klinikum Rechts der Isar, TU Munich, Ismaningerstr. 22, 81675, Munich, Germany
| | | | | | - Meike Mitsdoerffer
- Dept. of Neurology, Klinikum Rechts der Isar, TU Munich, 81675, Munich, Germany
| | - Claus Zimmer
- Dept. of Neuroradiology, Klinikum Rechts der Isar, TU Munich, Ismaningerstr. 22, 81675, Munich, Germany
| | - Bernhard Meyer
- Dept. of Neurosurgery, Klinikum Rechts der Isar, TU Munich, 81675, Munich, Germany
| | - Marie-Christin Metz
- Dept. of Neuroradiology, Klinikum Rechts der Isar, TU Munich, Ismaningerstr. 22, 81675, Munich, Germany
| | - Benedikt Wiestler
- Dept. of Neuroradiology, Klinikum Rechts der Isar, TU Munich, Ismaningerstr. 22, 81675, Munich, Germany
- TranslaTUM, TU Munich, 81675, Munich, Germany
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5
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Griessmair M, Delbridge C, Ziegenfeuter J, Jung K, Mueller T, Schramm S, Bernhardt D, Schmidt-Graf F, Kertels O, Thomas M, Zimmer C, Meyer B, Combs SE, Yakushev I, Wiestler B, Metz MC. Exploring molecular glioblastoma: Insights from advanced imaging for a nuanced understanding of the molecularly defined malignant biology. Neurooncol Adv 2024; 6:vdae106. [PMID: 39114182 PMCID: PMC11304596 DOI: 10.1093/noajnl/vdae106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/10/2024] Open
Abstract
Background Molecular glioblastoma (molGB) does not exhibit the histologic hallmarks of a grade 4 glioma but is nevertheless diagnosed as glioblastoma when harboring specific molecular markers. MolGB can easily be mistaken for similar-appearing lower-grade astrocytomas. Here, we investigated how advanced imaging could reflect the underlying tumor biology. Methods Clinical and imaging data were collected for 7 molGB grade 4, 9 astrocytomas grade 2, and 12 astrocytomas grade 3. Four neuroradiologists performed VASARI-scoring of conventional imaging, and their inter-reader agreement was assessed using Fleiss κ coefficient. To evaluate the potential of advanced imaging, 2-sample t test, 1-way ANOVA, Mann-Whitney U, and Kruskal-Wallis test were performed to test for significant differences between apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) that were extracted fully automatically from the whole tumor volume. Results While conventional VASARI imaging features did not allow for reliable differentiation between glioma entities, rCBV was significantly higher in molGB compared to astrocytomas for the 5th and 95th percentile, mean, and median values (P < .05). ADC values were significantly lower in molGB than in astrocytomas for mean, median, and the 95th percentile (P < .05). Although no molGB showed contrast enhancement initially, we observed enhancement in the short-term follow-up of 1 patient. Discussion Quantitative analysis of diffusion and perfusion parameters shows potential in reflecting the malignant tumor biology of molGB. It may increase awareness of molGB in a nonenhancing, "benign" appearing tumor. Our results support the emerging hypothesis that molGB might present glioblastoma captured at an early stage of gliomagenesis.
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Affiliation(s)
- Michael Griessmair
- Department of Neuroradiology, Klinikum Rechts der Isar, TU Munich, Munich, Germany
| | | | - Julian Ziegenfeuter
- Department of Neuroradiology, Klinikum Rechts der Isar, TU Munich, Munich, Germany
| | - Kirsten Jung
- Department of Neuroradiology, Klinikum Rechts der Isar, TU Munich, Munich, Germany
| | - Tobias Mueller
- Department of Neuroradiology, Klinikum Rechts der Isar, TU Munich, Munich, Germany
| | - Severin Schramm
- Department of Neuroradiology, Klinikum Rechts der Isar, TU Munich, Munich, Germany
| | - Denise Bernhardt
- Department of Radiation Oncology, Klinikum Rechts der Isar, TU Munich, Munich, Germany
| | | | - Olivia Kertels
- Department of Neuroradiology, Klinikum Rechts der Isar, TU Munich, Munich, Germany
| | - Marie Thomas
- Department of Neuroradiology, Klinikum Rechts der Isar, TU Munich, Munich, Germany
| | - Claus Zimmer
- Department of Neuroradiology, Klinikum Rechts der Isar, TU Munich, Munich, Germany
| | - Bernhard Meyer
- Department of Neurosurgery, Klinikum Rechts der Isar, TU Munich, Munich, Germany
| | - Stephanie E Combs
- Department of Radiation Oncology, Klinikum Rechts der Isar, TU Munich, Munich, Germany
| | - Igor Yakushev
- Department of Nuclear Medicine, Klinikum Rechts der Isar, TU Munich, Munich, Germany
| | - Benedikt Wiestler
- Department of Neuroradiology, Klinikum Rechts der Isar, TU Munich, Munich, Germany
| | - Marie-Christin Metz
- Department of Neuroradiology, Klinikum Rechts der Isar, TU Munich, Munich, Germany
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Kahng JY, Kang BH, Lee ST, Choi SH, Kim TM, Park CK, Won JK, Park SH, Son J, Lee JH. Clinicogenetic characteristics and the effect of radiation on the neural stem cell niche in subventricular zone-contacting glioblastoma. Radiother Oncol 2023; 186:109800. [PMID: 37423479 DOI: 10.1016/j.radonc.2023.109800] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Revised: 06/26/2023] [Accepted: 07/03/2023] [Indexed: 07/11/2023]
Abstract
BACKGROUND AND PURPOSE Neural stem cells (NSCs) in the subventricular zone (SVZ) are recognized as the cellular origin of glioblastoma (GBM) and a potential therapeutic target. However, the characteristics of SVZ contacting GBM (SVZ + GBM) and radiotherapeutic strategies for NSCs are still controversial. Here, we investigated the clinicogenetic features of SVZ + GBM and evaluated the dose effect of NSC irradiation depending on SVZ involvement. MATERIALS AND METHODS We identified 125 patients with GBM treated with surgery followed by chemoradiotherapy. The genomic profiles were obtained by next-generation sequencing targeting 82 genes. NSCs in the SVZ and hippocampus were contoured using standardized methods, and dosimetric factors were analyzed. SVZ + GBM was defined as GBM with SVZ involvement in a T1 contrast-enhanced image. Progression-free survival (PFS) and overall survival (OS) were used as endpoints. RESULTS The number of patients with SVZ + GBM was 95 (76%). SVZ + GBM showed lower PFS than GBM without SVZ involvement (SVZ-GBM) (median 8.6 vs. 11.5 months, p = 0.034). SVZ contact was not associated with any specific genetic profile but was an independent prognostic factor in multivariate analysis. In SVZ + GBM, patients receiving high doses to the ipsilateral NSC region showed significantly better OS (HR = 1.89, p = 0.011) and PFS (HR = 1.77, p = 0.013). However, in SVZ-GBM, high doses to the ipsilateral NSC region were associated with worse OS (HR = 0.27, p = 0.013) and PFS (HR = 0.37, p = 0.035) in both univariate and multivariate analyses. CONCLUSION SVZ involvement in GBM was not associated with distinct genetic features. However, irradiation of NSCs was associated with better prognosis in patients with tumors contacting the SVZ.
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Affiliation(s)
- Jee Ye Kahng
- Department of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Byung-Hee Kang
- Department of Radiation Oncology, Ewha Womans University Medical Center Seoul Hospital, Seongnam, Republic of Korea
| | - Soon-Tae Lee
- Departments of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Seung Hong Choi
- Departments of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Tae Min Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Chul-Kee Park
- Departments of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jae-Kyung Won
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Sung-Hye Park
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jaeman Son
- Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Joo Ho Lee
- Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
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Parker M, Kalluri A, Materi J, Gujar SK, Schreck K, Mukherjee D, Weingart J, Brem H, Redmond KJ, Lucas CHG, Bettegowda C, Rincon-Torroella J. Management and Molecular Characterization of Intraventricular Glioblastoma: A Single-Institution Case Series. Int J Mol Sci 2023; 24:13285. [PMID: 37686092 PMCID: PMC10488126 DOI: 10.3390/ijms241713285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Revised: 08/13/2023] [Accepted: 08/22/2023] [Indexed: 09/10/2023] Open
Abstract
While the central nervous system (CNS) tumor classification has increasingly incorporated molecular parameters, there is a paucity of literature reporting molecular alterations found in intraventricular glioblastoma (IVGBM), which are rare. We present a case series of nine IVGBMs, including molecular alterations found in standardized next-generation sequencing (NGS). We queried the clinical charts, operative notes, pathology reports, and radiographic images of nine patients with histologically confirmed IVGBM treated at our institution (1995-2021). Routine NGS was performed on resected tumor tissue of two patients. In this retrospective case series of nine patients (22% female, median (range) age: 64.3 (36-85) years), the most common tumor locations were the atrium of the right lateral ventricle (33%) and the septum pellucidum (33%). Five patients had preoperative hydrocephalus, which was managed with intraoperative external ventricular drains in three patients and ventriculoperitoneal shunts in one patient. Hydrocephalus was managed with subtotal resection of a fourth ventricular IVGBM in one patient. The most common surgical approach was transcortical intraventricular (56%). Gross total resection was achieved in two patients, subtotal resection was achieved in six patients, and one patient received a biopsy only. Immunohistochemistry for IDH1 R132H mutant protein was performed in four cases and was negative in all four. Genetic alterations common in glioblastoma, IDH-wildtype, were seen in two cases with available NGS data, including EGFR gene amplification, TERT promoter mutation, PTEN mutation, trisomy of chromosome 7, and monosomy of chromosome 10. Following surgical resection, four patients received adjuvant chemoradiation. Median survival among our cohort was 4.7 months (IQR: 0.9-5.8 months). Management of IVGBM is particularly challenging due to their anatomical location, presentation with obstructive hydrocephalus, and fast growth, necessitating prompt intervention. Additional studies are needed to better understand the genetic landscape of IVGBM compared to parenchymal glioblastoma and may further elucidate the unique pathophysiology of these rare tumors.
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Affiliation(s)
- Megan Parker
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Anita Kalluri
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Joshua Materi
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Sachin K. Gujar
- Division of Neuroradiology, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Karisa Schreck
- Department of Neurology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Debraj Mukherjee
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Jon Weingart
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Henry Brem
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Kristin J. Redmond
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Calixto-Hope G. Lucas
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Chetan Bettegowda
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Jordina Rincon-Torroella
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
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Li S, Dong L, Pan Z, Yang G. Targeting the neural stem cells in subventricular zone for the treatment of glioblastoma: an update from preclinical evidence to clinical interventions. Stem Cell Res Ther 2023; 14:125. [PMID: 37170286 PMCID: PMC10173522 DOI: 10.1186/s13287-023-03325-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Accepted: 04/03/2023] [Indexed: 05/13/2023] Open
Abstract
BACKGROUND Glioblastoma is one of the most common and aggressive adult brain tumors. The conventional treatment strategy, surgery combined with chemoradiotherapy, did not change the fact that the recurrence rate was high and the survival rate was low. Over the years, accumulating evidence has shown that the subventricular zone has an important role in the recurrence and treatment resistance of glioblastoma. The human adult subventricular zone contains neural stem cells and glioma stem cells that are probably a part of reason for therapy resistance and recurrence of glioblastoma. MAIN BODY Over the years, both bench and bedside evidences strongly support the view that the presence of neural stem cells and glioma stem cells in the subventricular zone may be the crucial factor of recurrence of glioblastoma after conventional therapy. It emphasizes the necessity to explore new therapy strategies with the aim to target subventricular zone to eradicate neural stem cells or glioma stem cells. In this review, we summarize the recent preclinical and clinical advances in targeting neural stem cells in the subventricular zone for glioblastoma treatment, and clarify the prospects and challenges in clinical application. CONCLUSIONS Although there remain unresolved issues, current advances provide us with a lot of evidence that targeting the neural stem cells and glioma stem cells in subventricular zone may have the potential to solve the dilemma of glioblastoma recurrence and treatment resistance.
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Affiliation(s)
- Sijia Li
- Jilin Provincial Key Laboratory of Radiation Oncology and Therapy, Department of Radiation Oncology and Therapy, The First Hospital of Jilin University, Changchun, 130021 China
| | - Lihua Dong
- Jilin Provincial Key Laboratory of Radiation Oncology and Therapy, Department of Radiation Oncology and Therapy, The First Hospital of Jilin University, Changchun, 130021 China
| | - Zhenyu Pan
- Department of Radiation Oncology, Huizhou Third People’s Hospital, Guangzhou Medical University, Huizhou, 516000 China
| | - Guozi Yang
- Jilin Provincial Key Laboratory of Radiation Oncology and Therapy, Department of Radiation Oncology and Therapy, The First Hospital of Jilin University, Changchun, 130021 China
- Department of Radiation Oncology, Huizhou Third People’s Hospital, Guangzhou Medical University, Huizhou, 516000 China
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9
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Ermiş E, Althaus A, Blatti M, Uysal E, Leiser D, Norouzi S, Riggenbach E, Hemmatazad H, Ahmadli U, Wagner F. Therapy Resistance of Glioblastoma in Relation to the Subventricular Zone: What Is the Role of Radiotherapy? Cancers (Basel) 2023; 15:cancers15061677. [PMID: 36980563 PMCID: PMC10046464 DOI: 10.3390/cancers15061677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Revised: 03/02/2023] [Accepted: 03/05/2023] [Indexed: 03/12/2023] Open
Abstract
Glioblastoma is a highly heterogeneous primary malignant brain tumor with marked inter-/intratumoral diversity and a poor prognosis. It may contain a population of neural stem cells (NSC) and glioblastoma stem cells that have the capacity for migration, self-renewal and differentiation. While both may contribute to resistance to therapy, NSCs may also play a role in brain tissue repair. The subventricular zone (SVZ) is the main reservoir of NSCs. This study investigated the impact of bilateral SVZ radiation doses on patient outcomes. We included 147 patients. SVZs were delineated and the dose administered was extracted from dose–volume histograms. Tumors were classified based on their spatial relationship to the SVZ. The dose and outcome correlations were analyzed using the Kaplan–Meier and Cox proportional hazards regression methods. Median progression-free survival (PFS) was 7 months (range: 4–11 months) and median overall survival (OS) was 14 months (range: 9–23 months). Patients with an ipsilateral SVZ who received ≥50 Gy showed significantly better PFS (8 versus 6 months; p < 0.001) and OS (16 versus 11 months; p < 0.001). Furthermore, lower doses (<32 Gy) to the contralateral SVZ were associated with improved PFS (8 versus 6 months; p = 0.030) and OS (15 versus 11 months; p = 0.001). Targeting the potential tumorigenic cells in the ipsilateral SVZ while sparing contralateral NSCs correlated with an improved outcome. Further studies should address the optimization of dose distribution with modern radiotherapy techniques for the areas surrounding infiltrated and healthy SVZs.
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Affiliation(s)
- Ekin Ermiş
- Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
- Correspondence:
| | - Alexander Althaus
- Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
| | - Marcela Blatti
- Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
| | - Emre Uysal
- Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
| | - Dominic Leiser
- Center for Proton Therapy, Paul Scherrer Institute, 5232 Villigen, Switzerland
| | - Shokoufe Norouzi
- Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
| | - Elena Riggenbach
- Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
| | - Hossein Hemmatazad
- Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
| | - Uzeyir Ahmadli
- Department of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
| | - Franca Wagner
- Department of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
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10
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Jovanovich N, Habib A, Head J, Anthony A, Edwards L, Zinn PO. Opinion: Bridging gaps and doubts in glioblastoma cell-of-origin. Front Oncol 2022; 12:1002933. [PMID: 36338762 PMCID: PMC9634038 DOI: 10.3389/fonc.2022.1002933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 09/30/2022] [Indexed: 11/24/2022] Open
Affiliation(s)
- Nicolina Jovanovich
- Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Ahmed Habib
- Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
- Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Jeffery Head
- Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Austin Anthony
- Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Lincoln Edwards
- Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
- Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Pascal O. Zinn
- Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
- Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
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11
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Beiriger J, Habib A, Jovanovich N, Kodavali CV, Edwards L, Amankulor N, Zinn PO. The Subventricular Zone in Glioblastoma: Genesis, Maintenance, and Modeling. Front Oncol 2022; 12:790976. [PMID: 35359410 PMCID: PMC8960165 DOI: 10.3389/fonc.2022.790976] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Accepted: 02/07/2022] [Indexed: 12/13/2022] Open
Abstract
Glioblastoma (GBM) is a malignant tumor with a median survival rate of 15-16 months with standard care; however, cases of successful treatment offer hope that an enhanced understanding of the pathology will improve the prognosis. The cell of origin in GBM remains controversial. Recent evidence has implicated stem cells as cells of origin in many cancers. Neural stem/precursor cells (NSCs) are being evaluated as potential initiators of GBM tumorigenesis. The NSCs in the subventricular zone (SVZ) have demonstrated similar molecular profiles and share several distinctive characteristics to proliferative glioblastoma stem cells (GSCs) in GBM. Genomic and proteomic studies comparing the SVZ and GBM support the hypothesis that the tumor cells and SVZ cells are related. Animal models corroborate this connection, demonstrating migratory patterns from the SVZ to the tumor. Along with laboratory and animal research, clinical studies have demonstrated improved progression-free survival in patients with GBM after radiation to the ipsilateral SVZ. Additionally, key genetic mutations in GBM for the most part carry regulatory roles in the SVZ as well. An exciting avenue towards SVZ modeling and determining its role in gliomagenesis in the human context is human brain organoids. Here we comprehensively discuss and review the role of the SVZ in GBM genesis, maintenance, and modeling.
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Affiliation(s)
- Jamison Beiriger
- Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
- Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh PA, United States
| | - Ahmed Habib
- Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
- Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh PA, United States
| | - Nicolina Jovanovich
- Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
- Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh PA, United States
| | - Chowdari V. Kodavali
- Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
- Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh PA, United States
| | - Lincoln Edwards
- Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
- Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh PA, United States
| | - Nduka Amankulor
- Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
- Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh PA, United States
| | - Pascal O. Zinn
- Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
- Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh PA, United States
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12
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Zhang GL, Wang CF, Qian C, Ji YX, Wang YZ. Role and mechanism of neural stem cells of the subventricular zone in glioblastoma. World J Stem Cells 2021; 13:877-893. [PMID: 34367482 PMCID: PMC8316865 DOI: 10.4252/wjsc.v13.i7.877] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 05/16/2021] [Accepted: 06/18/2021] [Indexed: 02/06/2023] Open
Abstract
Glioblastoma multiforme (GBM), the most frequently occurring malignant brain tumor in adults, remains mostly untreatable. Because of the heterogeneity of invasive gliomas and drug resistance associated with the tumor microenvironment, the prognosis is poor, and the survival rate of patients is low. Communication between GBMs and non-glioma cells in the tumor microenvironment plays a vital role in tumor growth and recurrence. Emerging data have suggested that neural stem cells (NSCs) in the subventricular zone (SVZ) are the cells-of-origin of gliomas, and SVZ NSC involvement is associated with the progression and recurrence of GBM. This review highlights the interaction between SVZ NSCs and gliomas, summarizes current findings on the crosstalk between gliomas and other non-glioma cells, and describes the links between SVZ NSCs and gliomas. We also discuss the role and mechanism of SVZ NSCs in glioblastoma, as well as the interventions targeting the SVZ and their therapeutic implications in glioblastoma. Taken together, understanding the biological mechanism of glioma-NSC interactions can lead to new therapeutic strategies for GBM.
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Affiliation(s)
- Gui-Long Zhang
- Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China
| | - Chuan-Fang Wang
- Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China
| | - Cheng Qian
- Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China
| | - Yun-Xiang Ji
- Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China
| | - Ye-Zhong Wang
- Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China
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13
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Hallaert G, Pinson H, Van den Broecke C, Sweldens C, Van Roost D, Kalala JP, Boterberg T. Survival impact of incidental subventricular zone irradiation in IDH-wildtype glioblastoma. Acta Oncol 2021; 60:613-619. [PMID: 33689536 DOI: 10.1080/0284186x.2021.1893899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
BACKGROUND AND PURPOSE The subventricular zone (SVZ) is an important niche for neural stem cells but probably also for brain tumor propagating cells, including the glioblastoma stem cell. The SVZ may become a target for radiation therapy in glioblastoma patients. However, reports studying the effect of irradiation of the SVZ on glioblastoma patient survival show conflicting results. We studied the correlation between incidental SVZ radiation dose and survival in a cohort of isocitrate dehydrogenase-wildtype (IDHwt) glioblastoma patients with inclusion of important survival prognosticators. PATIENTS AND METHODS In this retrospective analysis, only adult patients with supratentorial IDHwt glioblastoma were included who were treated with temozolomide-based chemoradiotherapy after surgery. The SVZ was contoured on the radiotherapy planning imaging. Cox proportional regression overall survival (OS) analysis was used to study the correlation between SVZ dose and survival. Age, Karnofsky Performance Score, extent of resection and O6-methylguanine-methyl-DNA-transferase gene promoter (MGMTp) methylation were used as covariates in multivariate analysis. RESULTS In total, 137 patients were included. Median OS was 13.3 months. The MGMTp methylation was present in 40% of cases. Ipsilateral SVZ (iSVZ) mean dose was 44.4 Gy and 27.2 Gy for the contralateral SVZ (cSVZ). Univariate survival analysis showed an inverse relationship between cSVZ mean dose and OS (HR 1.029 (1.003-1.057); p= .032). However, there was no correlation between cSVZ mean dose and OS in multivariate analysis. iSVZ dose did not correlate with survival. CONCLUSION In this cohort of 137 IDHwt glioblastoma patients, iSVZ did not correlate with OS. Higher cSVZ dose was inversely correlated with OS in univariate survival analysis but lost its significance in multivariate analysis, including MGMTp-methylation. Hence, the correlation between SVZ radiation and glioblastoma patient survival remains unclear. Carefully designed prospective studies are needed to provide unequivocal results on this controversial topic.
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Affiliation(s)
- Giorgio Hallaert
- Department of Neurosurgery, Ghent University Hospital, Ghent, Belgium
| | - Harry Pinson
- Department of Neurosurgery, Ghent University Hospital, Ghent, Belgium
| | - Caroline Van den Broecke
- Department of Pathology, AZ St Lucas Gent, Gent, Belgium
- Department of Pathology, Ghent University Hospital, Ghent, Belgium
| | | | - Dirk Van Roost
- Department of Neurosurgery, Ghent University Hospital, Ghent, Belgium
| | | | - Tom Boterberg
- Department of Radiation Oncology, Ghent University Hospital, Ghent, Belgium
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14
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Carrano A, Zarco N, Phillipps J, Lara-Velazquez M, Suarez-Meade P, Norton ES, Chaichana KL, Quiñones-Hinojosa A, Asmann YW, Guerrero-Cázares H. Human Cerebrospinal Fluid Modulates Pathways Promoting Glioblastoma Malignancy. Front Oncol 2021; 11:624145. [PMID: 33747938 PMCID: PMC7969659 DOI: 10.3389/fonc.2021.624145] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Accepted: 02/05/2021] [Indexed: 01/07/2023] Open
Abstract
Glioblastoma (GBM) is the most common and devastating primary cancer of the central nervous system in adults. High grade gliomas are able to modify and respond to the brain microenvironment. When GBM tumors infiltrate the Subventricular zone (SVZ) they have a more aggressive clinical presentation than SVZ-distal tumors. We suggest that cerebrospinal fluid (CSF) contact contributes to enhance GBM malignant characteristics in these tumors. We evaluated the impact of human CSF on GBM, performing a transcriptome analysis on human primary GBM cells exposed to CSF to measure changes in gene expression profile and their clinical relevance on disease outcome. In addition we evaluated the proliferation and migration changes of CSF-exposed GBM cells in vitro and in vivo. CSF induced transcriptomic changes in pathways promoting cell malignancy, such as apoptosis, survival, cell motility, angiogenesis, inflammation, and glucose metabolism. A genetic signature extracted from the identified transcriptional changes in response to CSF proved to be predictive of GBM patient survival using the TCGA database. Furthermore, CSF induced an increase in viability, proliferation rate, and self-renewing capacity, as well as the migratory capabilities of GBM cells in vitro. In vivo, GBM cells co-injected with human CSF generated larger and more proliferative tumors compared to controls. Taken together, these results provide direct evidence that CSF is a key player in determining tumor growth and invasion through the activation of complex gene expression patterns characteristic of a malignant phenotype. These findings have diagnostic and therapeutic implications for GBM patients. The changes induced by CSF contact might play a role in the increased malignancy of SVZ-proximal GBM.
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Affiliation(s)
- Anna Carrano
- Department of Neurological Surgery, Mayo Clinic, Jacksonville, FL, United States
| | - Natanael Zarco
- Department of Neurological Surgery, Mayo Clinic, Jacksonville, FL, United States
| | - Jordan Phillipps
- Department of Neurological Surgery, Mayo Clinic, Jacksonville, FL, United States
| | | | - Paola Suarez-Meade
- Department of Neurological Surgery, Mayo Clinic, Jacksonville, FL, United States
| | - Emily S Norton
- Department of Neurological Surgery, Mayo Clinic, Jacksonville, FL, United States.,Neuroscience Graduate Program, Mayo Clinic Graduate School of Biochemical Sciences, Mayo Clinic, Jacksonville, FL, United States.,Regenerative Sciences Training Program, Center for Regenerative Medicine, Mayo Clinic, Jacksonville, FL, United States
| | - Kaisorn L Chaichana
- Department of Neurological Surgery, Mayo Clinic, Jacksonville, FL, United States
| | | | - Yan W Asmann
- Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL, United States
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15
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Bender K, Träger M, Wahner H, Onken J, Scheel M, Beck M, Ehret F, Budach V, Kaul D. What is the role of the subventricular zone in radiotherapy of glioblastoma patients? Radiother Oncol 2021; 158:138-145. [PMID: 33636228 DOI: 10.1016/j.radonc.2021.02.017] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2020] [Revised: 01/28/2021] [Accepted: 02/13/2021] [Indexed: 01/06/2023]
Abstract
BACKGROUND AND PURPOSE Current glioblastoma (GBM) therapies prolong survival, but overall prognosis is still poor. Irradiation of the subventricular zone (SVZ) has recently been discussed as a promising concept as this tissue harbors stem cells which seem to play a role in the initiation and recurrence of GBM. In this study, we retrospectively examined the relationship of SVZ irradiation dose and survival in a large, homogeneous GBM patient cohort. MATERIALS AND METHODS We included 200 GBM patients who had been treated at our institution with trimodal therapy (surgery, radiotherapy and chemotherapy) between 2009 and 2020. The SVZ was delineated, and dose-volume histograms were calculated and extracted. Tumors were classified according to their contact with the SVZ. The Kaplan-Meier method was used for survival analysis, and univariable and multivariable Cox regression (MVA) were used to determine prognostic effects on progression-free survival (PFS) and overall survival (OS). RESULTS Median PFS of the study group was 7.2 months; median OS was 15.1 months. In MVA (with mean dose to the ipsilateral SVZ as a continuous covariable), PFS was significantly lower for patients with a Karnofsky performance status (KPS) < 70% and without MGMT promoter methylation. Factors prognostic for shorter OS were old age, lower KPS, unmethylated MGMT status, SVZ contact and biopsy instead of subtotal- or gross total resection. There was no significant correlation between survival and SVZ dose. CONCLUSION In this cohort, an increased mean dose to the ipsilateral or contralateral SVZ did not correlate with improved survival in irradiated GBM patients in MVA. Patients whose tumor directly involved the SVZ showed worse OS in MVA.
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Affiliation(s)
- Katja Bender
- Department of Radiation Oncology Charité- Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany
| | - Malte Träger
- Department of Radiation Oncology Charité- Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany
| | - Helena Wahner
- Department of Radiation Oncology Charité- Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany
| | - Julia Onken
- Department of Neurosurgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; German Cancer Consortium (DKTK), partner site Berlin, Germany
| | - Michael Scheel
- Department of Neuroradiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany
| | - Marcus Beck
- Department of Radiation Oncology Charité- Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany
| | - Felix Ehret
- Department of Radiation Oncology Charité- Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany
| | - Volker Budach
- Department of Radiation Oncology Charité- Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany
| | - David Kaul
- Department of Radiation Oncology Charité- Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; German Cancer Consortium (DKTK), partner site Berlin, Germany.
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16
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Valiyaveettil D, Malik M, Akram KS, Ahmed SF, Joseph DM. Prospective study to assess the survival outcomes of planned irradiation of ipsilateral subventricular and periventricular zones in glioblastoma. Ecancermedicalscience 2020; 14:1021. [PMID: 32256704 PMCID: PMC7105331 DOI: 10.3332/ecancer.2020.1021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2019] [Indexed: 12/14/2022] Open
Abstract
Purpose/objective(s) Retrospective evidence suggests that the irradiation of stem cells in the periventricular zone (PVZ), specifically the subventricular zone (SVZ), to higher doses may be associated with improved outcomes. Materials/methods This was a prospective study, done from 2012 to 2017 in glioblastoma patients to assess the efficacy of planned irradiation of ipsilateral PVZ and SVZ on survival outcomes. The clinical target volume included the tumour bed with a 1.5–2 cm margin, perilesional oedema and was expanded to encompass the ipsilateral PVZ (5 mm lateral expansion adjacent to the ventricles, including the SVZ, which was a 5 mm expansion lateral to lateral ventricle). The ipsilateral PVZ was planned to receive a dose of ≥50 Gy. Results 89 patients were recruited of which 74 patients were available for the analysis. Median age was 48 years. Mean doses to ipsilateral PVZ and SVZ were 56.2 and 55.1Gy, respectively. Median overall survival in the entire group was 13 months. There was no significant correlation between survival and doses to ipsilateral, contralateral, or bilateral PVZ and SVZ. Median survival was 16, 12 and 6 months for Eastern Cooperative Oncology Group (ECOG) PS 1, 2 and 3, respectively (p = 0.05). Conclusion Planned irradiation of potential stem cell niches in the ipsilateral cerebral hemisphere did not result in improved survival as suggested by retrospective studies. Doses to contralateral or bilateral PVZ or SVZ also did not influence survival.
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Affiliation(s)
- Deepthi Valiyaveettil
- Department of Radiation Oncology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad 500082, India
| | - Monica Malik
- Department of Radiation Oncology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad 500082, India
| | - Kothwal Syed Akram
- Department of Radiation Oncology, Yashoda Superspeciality Hospital, Malakpet, Hyderabad 500036, India
| | - Syed Fayaz Ahmed
- Department of Radiation Oncology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad 500082, India
| | - Deepa M Joseph
- Department of Radiation Oncology, All India Institute of Medical Sciences, Rishikesh, India
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