Glioblastoma Recurrence Patterns After Radiation Therapy With Regard to the Subventricular Zone

Adeberg, Sebastian; König, Laila; Bostel, Tilman; Harrabi, Semi; Welzel, Thomas; Debus, Jürgen; Combs, Stephanie E.

doi:10.1016/j.ijrobp.2014.07.027

Cited by 107 publications

(90 citation statements)

References 26 publications

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“…These persisting cells, away from the initial tumor site (TM) might therefore play a key role in GBM recurrence and might corroborate with late periventricular patterns of recurrence observed in GBM patients every so often. 16 …”

Section: Resultsmentioning

confidence: 99%

CXCL12 mediates glioblastoma resistance to radiotherapy in the subventricular zone

et al. 2016

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). † These authors contributed equally to the present work. AbstractBackground. Patients with glioblastoma (GBM) have an overall median survival of 15 months despite multimodal therapy. These catastrophic survival rates are to be correlated to systematic relapses that might arise from remaining glioblastoma stem cells (GSCs) left behind after surgery. In this line, it has recently been demonstrated that GSCs are able to escape the tumor mass and preferentially colonize the adult subventricular zone (SVZ). At a distance from the initial tumor site, these GSCs might therefore represent a high-quality model of clinical resilience to therapy and cancer relapses as they specifically retain tumor-initiating abilities. Method. While relying on recent findings that have validated the existence of GSCs in the human SVZ, we questioned the role of the SVZ niche as a potential GSC reservoir involved in therapeutic failure.Results. Our results demonstrate that (i) GSCs located in the SVZ are specifically resistant to radiation in vivo, (ii) these cells display enhanced mesenchymal roots that are known to be associated with cancer radioresistance, (iii) these mesenchymal traits are specifically upregulated by CXCL12 (stromal cell-derived factor-1) both in vitro and in the SVZ environment, (iv) the amount of SVZ-released CXCL12 mediates GBM resistance to radiation in vitro, and (v) interferes with the CXCL12/CXCR4 signalling system, allowing weakening of the tumor mesenchymal roots and radiosensitizing SVZ-nested GBM cells. Conclusion. Together, these data provide evidence on how the adult SVZ environment, through the release of CXCL12, supports GBM therapeutic failure and potential tumor relapse. Key wordsCXCL12 | glioblastoma | mesenchymal activation | radioresistance | subventricular zone Primary brain tumors are considered as one of the nastiest scourges faced in oncology. Their most aggressive form, glioblastoma (GBM, WHO grade IV), is also regarded as the most common and lethal subtype. 1 Patients' poor survival rates are typically correlated with unsatisfactory therapeutic strategies leading to systematic GBM relapses. 2 Trying to better

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Section: Resultsmentioning

confidence: 99%

CXCL12 mediates glioblastoma resistance to radiotherapy in the subventricular zone

et al. 2016

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“…In a few studies some patients received additional non-conventional therapies. In the Adeberg et al study [19], 37 patients received either bevacizumab, cetuximab, cilengitide, imatinib, or temsirolimus. All 91 patients in Jafri et al [18] received either erlotinib, cis-retinoic acid, or enzastaurin.…”

Section: Resultsmentioning

confidence: 99%

“…When data were categorized according to the group I–IV GBM classification scheme described in Lim et al [9], data were combined for groups I and II (representing LV+GBMs) and groups III and IV (LV−GBMs). Compared to the published data, near accurate reconstructed Kaplan–Meier curves (Supplementary Figure S2) and summary survival statistics (Supplementary Tables S1 and S2) were generated in all studies except one [19], which was the only study included in the analysis that did not plot censored values on its Kaplan–Meier curves. Therefore, an assumption of no censored values was made when reconstructing individual patient data, as suggested in published methodologies [27], resulting in an error of 7 % in LV+GBM and 3 % in LV−GBM median survival values.…”

Section: Methodsmentioning

confidence: 99%

Influence of glioblastoma contact with the lateral ventricle on survival: a meta-analysis

et al. 2016

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The ventricular-subventricular zone (V-SVZ), which lies in the walls of the lateral ventricles (LV), is the largest neurogenic niche within the adult brain. Whether radiographic contact with the LV influences survival in glioblastoma (GBM) patients remains unclear. We assimilated and analyzed published data comparing survival in GBM patients with (LV+GBM) and without (LV−GBM) radiographic LV contact. PubMed, EMBASE, and Cochrane electronic databases were searched. Fifteen studies with survival data on LV+GBM and LV−GBM patients were identified. Their Kaplan–Meier survival curves were digitized and pooled for generation of median overall (OS) and progression free (PFS) survivals and log-rank hazard ratios (HRs). The log-rank and reported multivariate HRs after accounting for the common predictors of GBM survival were analyzed separately by meta-analyses. The calculated median survivals (months) from pooled data were 12.95 and 16.58 (OS), and 4.54 and 6.25 (PFS) for LV+GBMs and LV−GBMs, respectively, with an overall log-rank HRs of 1.335 [1.204–1.513] (OS) and 1.387 [1.225–1.602] (PFS). Meta-analysis of log-rank HRs resulted in summary HRs of 1.58 [1.35–1.85] (OS, 10 studies) and 1.41 [1.22–1.64] (PFS, 5 studies). Meta-analysis of multivariate HRs resulted in summary HRs of 1.35 [1.14–1.58] (OS, 6 studies) and 1.64 [0.88–3.05] (PFS, 3 studies). Patients with GBM contacting the LV have lower survival. This effect may be independent of the common predictors of GBM survival, suggesting a clinical influence of V-SVZ contact on GBM biology.

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“…The fact that GBM tumors are frequently found in the periventricular zone or in direct contact with the subventricular zone supports this hypothesis. [151026] Genetic models in mice have raised the possibility that oligodendrocyte progenitors may also represent a putative cell-of-origin in GBM. [30] Other studies have suggested that even terminally differentiated brain cells, such as neurons and astrocytes, can give rise to GBM by undergoing dedifferentiation driven by genetic alterations.…”

Section: Discussionmentioning

confidence: 99%

Traumatic brain injury and subsequent glioblastoma development: Review of the literature and case reports

et al. 2016

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Background:Previous reports have proposed an association between traumatic brain injury (TBI) and subsequent glioblastoma (GBM) formation.Methods:We used literature searches and radiographic evidence from two patients to assess the possibility of a link between TBI and GBM.Results:Epidemiological studies are equivocal on a possible link between brain trauma and increased risk of malignant glioma formation. We present two case reports of patients with GBM arising at the site of prior brain injury.Conclusion:The hypothesis that TBI may predispose to gliomagenesis is disputed by several large-scale epidemiological studies, but supported by some. Radiographic evidence from two cases presented here suggest that GBM formed at the site of brain injury. We propose a putative pathogenesis model that connects post-traumatic inflammation, stem and progenitor cell transformation, and gliomagenesis.

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Glioblastoma Recurrence Patterns After Radiation Therapy With Regard to the Subventricular Zone

Cited by 107 publications

References 26 publications

CXCL12 mediates glioblastoma resistance to radiotherapy in the subventricular zone

CXCL12 mediates glioblastoma resistance to radiotherapy in the subventricular zone

Influence of glioblastoma contact with the lateral ventricle on survival: a meta-analysis

Traumatic brain injury and subsequent glioblastoma development: Review of the literature and case reports

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