Prognostic Implications of Extent of Resection in Glioblastoma: Analysis from a Large Database

Trifiletti, Daniel M.; Alonso, Clayton E.; Grover, Surbhi; Fadul, Camilo E.; Sheehan, Jason P.; Showalter, Timothy N.

doi:10.1016/j.wneu.2017.04.035

Cited by 77 publications

(32 citation statements)

References 18 publications

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“…This is in agreement with previous studies 16 , 17 . Patients who underwent total or subtotal resection lived longer, also in line with previously reported 18 , 19 . The survival was significantly shorter the worse patients’ general health status at diagnosis.…”

Section: Discussionsupporting

confidence: 88%

“…One hypothesis would be that the activity of MGMT promoter methylation is cancelled out by other yet unidentified effects. For example, it is known that epigenetic silencing of MGMT may have tumour-inducing effect 19 , and this could explain the lack of differences in our cohort. Another potential explanation for our results is that the regulation of MGMT methylation differs in our cohort.…”

Section: Discussionmentioning

confidence: 87%

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Methylation of MGMT promoter does not predict response to temozolomide in patients with glioblastoma in Donostia Hospital

Egaña

Auzmendi-Iriarte

Andermatten

et al. 2020

Sci Rep

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O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status has been considered a prognostic factor in newly diagnosed glioblastoma (GBM). In this study, we evaluated the prognostic and predictive value of MGMT promoter methylation in patients with glioblastoma in Donostia Hospital. Surprisingly, methylation of MGMT promoter did not predict response to temozolomide in patients with glioblastoma in Donostia Hospital. Specifically, overall survival (OS) and progression-free survival (PFS) did not differ significantly by MGMT methylation status in our cohort. In contrast, both were longer in patients who received treatment, received more TMZ cycles, had a better general status and perform at least a partial resection. No association was detected between methylation of MGMT promoter and molecular markers such as ATRX, IDH, p53 and Ki67. These results indicate that MGMT methylation did not influence in patient survival in our cohort.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 87%

Methylation of MGMT promoter does not predict response to temozolomide in patients with glioblastoma in Donostia Hospital

Egaña

Auzmendi-Iriarte

Andermatten

et al. 2020

Sci Rep

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“…Temozolomide treatment is more effective in female compared to male GBM patients Sex differences in GBM incidence have been repeatedly reported (5,(7)(8)(9)(10)(11). Moreover, several recent studies have suggested that being female is associated with better outcome from GBM in both adults and children (8)(9)(10)19). The introduction of temozolomide as a component of tri-modal care for adults with GBM has improved outcomes somewhat and highlighted factors, like MGMT promoter methylation, that significantly impact on response and survival (20,21).…”

Section: Resultsmentioning

confidence: 99%

“…While low-grade glioma incidence is nearly identical in males and females, malignant brain tumors in general occur more commonly in males, regardless of patient age or geographical location (6,15) (5,11). From multiple recent reports, GBM occurs with a male to female ratio of 1.6:1 (5,(8)(9)(10). More specifically, while concepts of molecular subtypes of GBM are still evolving (16), of the four originally described transcriptional subtypes of GBM, three -Mesenchymal, Proneural and Neural GBM -exhibit a 2:1 male to female incidence ratio, while Classical GBM occurs with equal incidence (17,18).…”

mentioning

confidence: 99%

“…In addition to sex differences in incidence, there are emerging analyses that suggest outcome from GBM may also differ between males and females. In a study analyzing more than 27,000 patients, Trifiletti et al found that female sex was associated with longer survival (10). Similarly, female patients exhibited longer survival from gliosarcoma (8), and being female was associated with better outcome in a newly developed nomogram for predicting GBM patient survival (9).…”

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confidence: 99%

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Clinically Important sex differences in GBM biology revealed by analysis of male and female imaging, transcriptome and survival data

Yang

Warrington

Taylor

et al. 2017

Preprint

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One Sentence Summary: Male and female glioblastoma are biologically distinct and maximal chances for cure may require sex-specific approaches to treatment. (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/232744 doi: bioRxiv preprint first posted online Dec. 12, 2017; 2 Abstract:Sex differences in the incidence and outcome of human disease are broadly recognized but in most cases not adequately understood to enable sex-specific approaches to treatment. Glioblastoma (GBM), the most common malignant brain tumor, provides a case in point. Despite well-established differences in incidence, and emerging indications of differences in outcome, there are few insights that distinguish male and female GBM at the molecular level, or allow specific targeting of these biological differences. Here, using a quantitative imaging-based measure of response, we found that temozolomide chemotherapy is more effective in female compared to male GBM patients. We then applied a novel computational algorithm to linked GBM transcriptome and outcome data, and identified novel sex-specific molecular subtypes of GBM in which cell cycle and integrin signaling were identified as the critical determinants of survival for male and female patients, respectively. The clinical utility of cell cycle and integrin signaling pathway signatures was further established through correlations between gene expression and in vitro chemotherapy sensitivity in a panel of male and female patient-derived GBM cell lines. Together these results suggest that greater precision in GBM molecular subtyping can be achieved through sex-specific analyses, and that improved outcome for all patients might be accomplished via tailoring treatment to sex differences in molecular mechanisms.All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

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Prognostic impact of glioblastoma stem cell markers OLIG2 and CCND2

et al. 2019

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Aims Glioblastoma (GBM) is the most common and lethal malignant brain tumor in adults. Glioma stem cells (GSCs) are implicated in this poor prognosis and in radio(chemo‐)resistance. We have previously demonstrated that among potentially highly specific GSC markers oligodendrocyte lineage transcription factor 2 (OLIG2) appears to be the most specific and cyclin D2 (CCND2) the only one related to cell cycle regulation. The purpose of this work was to investigate the clinical significance and the evolution of OLIG2 and CCND2 protein expression in GBM. Methods and results Immunohistochemical expression analysis of Olig2 and Ccnd2 was carried out on a cohort of human paired GBM samples comparing initial resections with local recurrent tumors after radiation therapy (RT) alone or radio‐chemotherapy with temozolomide (RT‐TMZ). Uni‐ and multivariate logistic regression analysis revealed that significant risk factors predicting early mortality (<12 months) are: subtotal surgery for recurrence, time to recurrence <6 months, Ccnd2 nuclear expression at initial surgery ≥30%, and Olig2 nuclear expression <30% at second surgery after RT alone and RT‐TMZ. Conclusions We demonstrated that patients for whom nuclear expression of Olig2 becomes low (<30%) after adjuvant treatments have a significantly shorter time to recurrence and survival reflecting most probably a proneural to mesenchymal transition of the GSCs population. We also highlighted the fact that at initial surgery, high nuclear expression (≥30%) of CCND2, a G1/S regulator specific of GSCs, has a prognostic value and is associated with early mortality (<12 months).

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Prognostic Implications of Extent of Resection in Glioblastoma: Analysis from a Large Database

Cited by 77 publications

References 18 publications

Methylation of MGMT promoter does not predict response to temozolomide in patients with glioblastoma in Donostia Hospital

Methylation of MGMT promoter does not predict response to temozolomide in patients with glioblastoma in Donostia Hospital

Clinically Important sex differences in GBM biology revealed by analysis of male and female imaging, transcriptome and survival data

Prognostic impact of glioblastoma stem cell markers OLIG2 and CCND2

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