Prospective Study of Irradiation of Potential Stem Cell Niches in Glioblastoma

Malik, Monica; Akram, K.S.; Joseph, Deepa; Valiyaveettil, Deepthi; Ahmed, Syed Fayaz

doi:10.1016/j.ijrobp.2015.07.265

Cited by 14 publications

(10 citation statements)

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“…Our results are contrary to prior studies that suggested higher dose to the SVZ improves outcome [20, 22-26]. However, these studies were small, and used variable inclusion criteria.…”

Section: Discussioncontrasting

confidence: 99%

“…Discrepancy exists among studies of SVZ irradiation. Although some demonstrate benefit [20, 22-26], others have found no association between dose to the SVZ and outcome [18], and one conversely suggested high SVZ dose was associated with worse prognosis [17]. There is also disagreement within the positive studies as to which SVZ target volume may be associated with outcome (ipsilateral [22, 23, 25, 26], contralateral [22], or bilateral [24]).…”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately, there is limited data on the impact of dose to the SVZ, which consists of mostly small, retrospective studies with conflicting results [16-26]. Some of these studies suggest that higher dose to the SVZ is associated with better outcome, raising the possibility that targeted inclusion of this area into the treatment volume may improve survival [20, 22-26]. The largest of these studies assessed 173 subjects, and found that a higher ipsilateral SVZ dose correlated with better progression-free survival (PFS) and overall survival (OS) [25].…”

Section: Introductionmentioning

confidence: 99%

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Subventricular Zone Radiation Dose and Outcome for Glioblastoma Treated Between 2006 and 2012

Murchison¹,

Wiksyk²,

Gossman³

et al. 2018

Cureus

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ObjectiveStem cells residing in the subventricular zone (SVZ) may be related to recurrence, potentially affecting outcome in glioblastoma (GBM). This study investigated the relationship of SVZ radiation dose and survival in a large cohort treated with surgery and chemoradiotherapy (CRT).MethodsPatients with GBM treated between 2006 and 2012 (n = 370) were identified. SVZs were contoured from planning computed tomography (CT) with magnetic resonance imaging (MRI) registration where available. Dose was extracted from dose volume histograms. Kaplan-Meier (KM) progression-free survival (PFS) and overall survival (OS) estimates were compared with log-rank tests for SVZ doses. Multivariate analysis (MVA) identified clinical and treatment-related factors significantly associated with outcome.ResultsMedian follow-up was 16.4 months, 48.1% underwent gross total resection (GTR), 37.5% subtotal resection, and 14.4% biopsy without resection. Median PFS was 8.9 months (95% CI: 8.3–9.8 months), and OS was 16.5 months (95% CI: 15.2–17.6 months). PFS was significantly lower for older age (>50 years, P = 0.045), poor Karnofsky performance status (KPS, P = 0.049), multifocality (P < 0.001), and incomplete adjuvant chemotherapy (P < 0.001). Worse OS was associated with poor KPS (P = 0.001), biopsy only (P = 0.003), multifocality (P = 0.009), and failure to complete adjuvant chemotherapy (P < 0.001). SVZ dose was not associated with outcome for any of the dose levels assessed. On MVA, multifocality was associated with worse PFS (P < 0.01). Poor performance status and biopsy only were associated with worse OS (both P < 0.01).ConclusionIn this analysis of a large cohort of GBM treated with surgery and CRT, increased SVZ dose was not associated with improved survival.

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“…Our results are contrary to prior studies that suggested higher dose to the SVZ improves outcome [20, 22-26]. However, these studies were small, and used variable inclusion criteria.…”

Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Subventricular Zone Radiation Dose and Outcome for Glioblastoma Treated Between 2006 and 2012

Murchison¹,

Wiksyk²,

Gossman³

et al. 2018

Cureus

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“…Interim analysis of our study data (54 patients) investigating planned neural stem cell niche irradiation in glioblastoma [25] showed mean dose of 58 Gy or greater to the iSVZ correlated positively with improved OS (16 months versus 14 months, p = 0.03).…”

Section: Evidence Supporting Improved Survival With Higher Svz and Pvmentioning

confidence: 81%

Prospective study to assess the survival outcomes of planned irradiation of ipsilateral subventricular and periventricular zones in glioblastoma

Valiyaveettil¹,

Malik²,

Akram³

et al. 2020

ecancer

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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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“…94e96 At this time, there are two ongoing clinical trials to investigate the clinical efficacy of explicitly targeting or sparing the V-SVZ during irradiation (NCT02177578 and NCT01478854, respectively). The results of the only prospective clinical trial investigating neural stem cell niche irradiation in GBM 97 are promising, reporting significantly improved overall survival when the V-SVZ was irradiated and a trend toward improved survival when the SGZ was irradiated.…”

Section: The Niche As a Refugementioning

confidence: 99%

Space Invaders

Sinnaeve

Mobley

Ihrie

2018

The American Journal of Pathology

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Increasing evidence indicates that the adult neurogenic niche of the ventricular-subventricular zone (V-SVZ), beyond serving as a potential site of origin, affects the outcome of malignant brain cancers. Glioma contact with this niche predicts worse prognosis, suggesting a supportive role for the V-SVZ environment in tumor initiation or progression. In this review, we describe unique components of the V-SVZ that may permit or promote tumor growth within the region. Cell-cell interactions, soluble factors, and extracellular matrix composition are discussed, and the role of the niche in future therapies is explored. The purpose of this review is to highlight niche intrinsic factors that may promote or support malignant cell growth and maintenance, and point out how we might leverage these features to improve patient outcome.

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Prospective Study of Irradiation of Potential Stem Cell Niches in Glioblastoma

Cited by 14 publications

References 0 publications

Subventricular Zone Radiation Dose and Outcome for Glioblastoma Treated Between 2006 and 2012

Subventricular Zone Radiation Dose and Outcome for Glioblastoma Treated Between 2006 and 2012

Prospective study to assess the survival outcomes of planned irradiation of ipsilateral subventricular and periventricular zones in glioblastoma

Space Invaders

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