What is the role of the subventricular zone in radiotherapy of glioblastoma patients?

Bender, Katja; Träger, Malte; Wahner, Helena; Onken, Julia; Scheel, Michael; Beck, Marcus; Ehret, Felix; Budach, Volker; Kaul, David

doi:10.1016/j.radonc.2021.02.017

Cited by 10 publications

(7 citation statements)

References 47 publications

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“…However, SVZ involvement and radiation of it is more common for gliomas, too, given the necessary safety margins and respective contouring guidelines. For example, a study from our institution comprising 200 glioblastoma patients found that 66.0% of the tumors had contact to the SVZ [ 56 ]. Similarly, Roux et al [ 63 ] found SVZ involvement in 63% of 392 patients with newly-diagnosed isocitrate dehydrogenase (IDH) wild-type supratentorial glioblastoma.…”

Section: Discussionmentioning

confidence: 99%

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Histopathologically confirmed radiation-induced damage of the brain – an in-depth analysis of radiation parameters and spatio-temporal occurrence

Kossmann,

Ehret,

Roohani

et al. 2023

Radiat Oncol

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Background Radiation-induced damage (RID) after radiotherapy (RT) of primary brain tumors and metastases can be challenging to clinico-radiographically distinguish from tumor progression. RID includes pseudoprogression and radiation necrosis; the latter being irreversible and often associated with severe symptoms. While histopathology constitutes the diagnostic gold standard, biopsy-controlled clinical studies investigating RID remain limited. Whether certain brain areas are potentially more vulnerable to RID remains an area of active investigation. Here, we analyze histopathologically confirmed cases of RID in relation to the temporal and spatial dose distribution. Methods Histopathologically confirmed cases of RID after photon-based RT for primary or secondary central nervous system malignancies were included. Demographic, clinical, and dosimetric data were collected from patient records and treatment planning systems. We calculated the equivalent dose in 2 Gy fractions (EQD22) and the biologically effective dose (BED2) for normal brain tissue (α/β ratio of 2 Gy) and analyzed the spatial and temporal distribution using frequency maps. Results Thirty-three patients were identified. High-grade glioma patients (n = 18) mostly received one normofractionated RT series (median cumulative EQD22 60 Gy) to a large planning target volume (PTV) (median 203.9 ccm) before diagnosis of RID. Despite the low EQD22 and BED2, three patients with an accelerated hyperfractionated RT developed RID. In contrast, brain metastases patients (n = 15; 16 RID lesions) were often treated with two or more RT courses and with radiosurgery or fractionated stereotactic RT, resulting in a higher cumulative EQD22 (median 162.4 Gy), to a small PTV (median 6.7 ccm). All (n = 34) RID lesions occurred within the PTV of at least one of the preceding RT courses. RID in the high-grade glioma group showed a frontotemporal distribution pattern, whereas, in metastatic patients, RID was observed throughout the brain with highest density in the parietal lobe. The cumulative EQD22 was significantly lower in RID lesions that involved the subventricular zone (SVZ) than in lesions without SVZ involvement (median 60 Gy vs. 141 Gy, p = 0.01). Conclusions Accelerated hyperfractionated RT can lead to RID despite computationally low EQD22 and BED2 in high-grade glioma patients. The anatomical location of RID corresponded to the general tumor distribution of gliomas and metastases. The SVZ might be a particularly vulnerable area.

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Section: Discussionmentioning

confidence: 99%

“…White matter, cortex, and basal ganglia involvement was assessed by visual inspection. SVZ involvement was determined by contouring a 5 mm margin along the lateral walls of the lateral ventricles as previously described [ 55 , 56 ].…”

Section: Methodsmentioning

confidence: 99%

Histopathologically confirmed radiation-induced damage of the brain – an in-depth analysis of radiation parameters and spatio-temporal occurrence

Kossmann,

Ehret,

Roohani

et al. 2023

Radiat Oncol

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“…The latest study by Katja Bender et al found that iSVZ or cSVZ dose had no significant effect on OS and PFS. They suggested that the higher mean SVZ dose was a result of tumor central location and larger tumor size [ 68 ].…”

Section: Preclinical and Clinical Evidence Of Svz As The Potential Th...mentioning

confidence: 99%

Targeting the neural stem cells in subventricular zone for the treatment of glioblastoma: an update from preclinical evidence to clinical interventions

Dong

Pan

et al. 2023

Stem Cell Res Ther

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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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“…Glioma tumors in contact with the ventricles are often more multifocal and can recur distally from the primary tumor. Therapeutic resistance, tumor aggressiveness, and shorter patient survival are all associated with tumors in contact with ventricles [28][29][30][31][32].…”

Section: The Accumulation Of 11 C-methionine By Glioblastoma Tumor Ce...mentioning

confidence: 99%

Glioblastoma and Methionine Addiction

Sowers

2022

IJMS

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Glioblastoma is a fatal brain tumor with a bleak prognosis. The use of chemotherapy, primarily the alkylating agent temozolomide, coupled with radiation and surgical resection, has provided some benefit. Despite this multipronged approach, average patient survival rarely extends beyond 18 months. Challenges to glioblastoma treatment include the identification of functional pharmacologic targets as well as identifying drugs that can cross the blood-brain barrier. To address these challenges, current research efforts are examining metabolic differences between normal and tumor cells that could be targeted. Among the metabolic differences examined to date, the apparent addiction to exogenous methionine by glioblastoma tumors is a critical factor that is not well understood and may serve as an effective therapeutic target. Others have proposed this property could be exploited by methionine dietary restriction or other approaches to reduce methionine availability. However, methionine links the tumor microenvironment with cell metabolism, epigenetic regulation, and even mitosis. Therefore methionine depletion could result in complex and potentially undesirable responses, such as aneuploidy and the aberrant expression of genes that drive tumor progression. If methionine manipulation is to be a therapeutic strategy for glioblastoma patients, it is essential that we enhance our understanding of the role of methionine in the tumor microenvironment.

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What is the role of the subventricular zone in radiotherapy of glioblastoma patients?

Cited by 10 publications

References 47 publications

Histopathologically confirmed radiation-induced damage of the brain – an in-depth analysis of radiation parameters and spatio-temporal occurrence

Histopathologically confirmed radiation-induced damage of the brain – an in-depth analysis of radiation parameters and spatio-temporal occurrence

Targeting the neural stem cells in subventricular zone for the treatment of glioblastoma: an update from preclinical evidence to clinical interventions

Glioblastoma and Methionine Addiction

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