Chemoirradiation for Glioblastoma Multiforme: The National Cancer Institute Experience

Ho, Jennifer; Ondos, John; Ning, Holly; Smith, Sharon; Kreisl, Teri; Iwamoto, Fábio M.; Sul, Joohee; Kim, Lyndon; McNeil, Kate; Krauze, Andra; Shankavaram, Uma; Fine, Howard A.; Camphausen, Kevin

doi:10.1371/journal.pone.0070745

Cited by 12 publications

(9 citation statements)

References 33 publications

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“…Glioblastoma multiforme (GBM) is the most aggressive type of glioma, with a median survival of 15 months following standard treatment . The current multimodal treatment regimen—including surgical resection, concurrent chemo‐irradiation and adjuvant temozolomide—has yielded significant improvement in the patient survival . However, glioma invasion makes it difficult to be completely removed, resulting in relapse and death in patients with malignant glioma.…”

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confidence: 99%

Expression of Concern: HOXD‐AS1/miR‐130a sponge regulates glioma development by targeting E2F8

Chen

Zhao

Cui

et al. 2018

Intl Journal of Cancer

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Glioma development is an extremely complex process with changes occurring in numerous genes. HOXD antisense growth-associated long noncoding RNA (HOXD-AS1), an important long noncoding RNA (lncRNA), is known to regulate metastasis-related gene expression in bladder cancer, ovarian cancer and neuroblastoma. Here, we elucidated the function and possible molecular mechanisms of lncRNA HOXD-AS1 in human glioma cells. Our results proved that HOXD-AS1 expression was upregulated in glioma tissues and in glioma cell lines. HOXD-AS1 overexpression promoted cell migration and invasion in vitro, whereas knockdown of HOXD-AS1 expression repressed these cellular processes. Mechanistic studies further revealed that HOXD-AS1 could compete with the transcription factor E2F8 to bind with miR-130a, thus affecting E2F8 expression. Additionally, reciprocal repression was observed between HOXD-AS1 and miR-130a, and miR-130a mediated the tumor-suppressive effects of HOXD-AS1 knockdown. Taken together, these results provide a comprehensive analysis of the role of HOXD-AS1 in glioma cells and offer important clues to understand the key roles of competing endogenous RNA (ceRNA) mechanisms in human glioma.

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confidence: 99%

Expression of Concern: HOXD‐AS1/miR‐130a sponge regulates glioma development by targeting E2F8

Chen

Zhao

Cui

et al. 2018

Intl Journal of Cancer

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“…Lower KPS has been observed in patients with VSVZ + GBMs 5,9,11,16 , likely due to their more central location and larger size which could impair the function of the central neural tracts and basal nuclei. In addition, their larger volumes and deeper location may also decrease the likelihood of gross total resections 9,16,31–33 . Unlike prior efforts 5,6,15,16 , our analysis accounted for these and other molecular predictors and demonstrated that contact with the VSVZ by GBM is an independent, negative prognosticator.…”

Section: Discussionmentioning

confidence: 99%

Ventricular-Subventricular Zone Contact by Glioblastoma is Not Associated with Molecular Signatures in Bulk Tumor Data

Mistry

Wooten

Davis

et al. 2019

Sci Rep

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Whether patients with glioblastoma that contacts the ventricular-subventricular zone stem cell niche (VSVZ + GBM) have a distinct survival profile from VSVZ − GBM patients independent of other known predictors or molecular profiles is unclear. Using multivariate Cox analysis to adjust survival for widely-accepted predictors, hazard ratios (HRs) for overall (OS) and progression free (PFS) survival between VSVZ + GBM and VSVZ − GBM patients were calculated in 170 single-institution patients and 254 patients included in both The Cancer Genome (TCGA) and Imaging (TCIA) atlases. An adjusted, multivariable analysis revealed that VSVZ contact was independently associated with decreased survival in both datasets. TCGA molecular data analyses revealed that VSVZ contact by GBM was independent of mutational, DNA methylation, gene expression, and protein expression signatures in the bulk tumor. Therefore, while survival of GBM patients is independently stratified by VSVZ contact, with VSVZ + GBM patients displaying a poor prognosis, the VSVZ + GBMs do not possess a distinct molecular signature at the bulk sample level. Focused examination of the interplay between the VSVZ microenvironment and subsets of GBM cells proximal to this region is warranted.

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“…It is possible that identification of poor metabolic response could be effectively used as a risk-adaptive approach for utilization of agents like bevacizumab that are effective in recurrent settings (24, 25). Early application might benefit patients prior to having gross radiographic recurrence.…”

Section: Discussionmentioning

confidence: 99%

3-Dimensional Magnetic Resonance Spectroscopic Imaging at 3 Tesla for Early Response Assessment of Glioblastoma Patients During External Beam Radiation Therapy

Muruganandham

Clerkin

Smith

et al. 2014

International Journal of Radiation Oncology*Biology*Physics

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Purpose To evaluate the utility of 3D-MR proton spectroscopic imaging for treatment planning and its implications for early response assessment in glioblastoma multiforme. Methods and Materials Eighteen patients with newly diagnosed, histologically confirmed glioblastoma had 3D-MR proton spectroscopic imaging (MRSI) along with T2 and T1 gadolinium enhanced MR images at simulation and at boost treatment planning after 17-20 fractions of radiotherapy. All patients received standard radiotherapy with temozolomide and follow-up with every two month MR scans. Progression free survival was defined using MacDonald criteria. MRSI images obtained at initial simulation were analyzed for choline / N-acetylaspartate ratios (Cho/NAA) on a voxel by voxel basis with abnormal activity defined as Cho/NAA ≥ 2. These images were compared on anatomically matched MRSI data collected after 3 weeks of radiotherapy. Changes in Cho/NAA between pre-therapy and 3rd week RT scans were tested using Wilcoxon matched-pairs signed rank tests and correlated with progression free survival, radiation dose and location of recurrence using Cox proportional hazards regression. Results After 8.6 months (median follow-up), 50% of patients had progressed based on imaging. Patients with a decreased or stable mean or median Cho/NAA values had less risk of progression (p< 0.01). Patients with an increase in mean or median Cho/NAA values at the 3rd week RT scan had a significantly greater chance of early progression (p <0.01). An increased Cho/NAA at the 3rd week MRSI scan carried a hazard ratio of 2.72 (95% confidence interval 1.10-6.71, p= 0.03). Most patients received the prescription dose of RT to the Cho/NAA ≥ 2 volume, which was where recurrence most often occurred. Conclusion Change in mean and median Cho/NAA detected at 3 weeks was a significant predictor of early progression. The potential impact for risk-adaptive therapy based on early spectroscopic findings is suggested.

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Chemoirradiation for Glioblastoma Multiforme: The National Cancer Institute Experience

Cited by 12 publications

References 33 publications

Expression of Concern: HOXD‐AS1/miR‐130a sponge regulates glioma development by targeting E2F8

Expression of Concern: HOXD‐AS1/miR‐130a sponge regulates glioma development by targeting E2F8

Ventricular-Subventricular Zone Contact by Glioblastoma is Not Associated with Molecular Signatures in Bulk Tumor Data

3-Dimensional Magnetic Resonance Spectroscopic Imaging at 3 Tesla for Early Response Assessment of Glioblastoma Patients During External Beam Radiation Therapy

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