Sex, Age, Anatomic Location, and Extent of Resection Influence Outcomes in Children With High-grade Glioma

McCrea, Heather J.; Bander, Evan D; Venn, Rachael A.; Reiner, Anne S.; Iorgulescu, J. Bryan; Puchi, Luis A; Schaefer, Peter M.; Cederquist, Gustav Y.; Greenfield, Jeffrey P.

doi:10.1227/neu.0000000000000845

Cited by 47 publications

(46 citation statements)

References 23 publications

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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%

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 (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint .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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Section: Resultsmentioning

confidence: 99%

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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“…Gliomas constitute 60% of all primary brain tumors [26]. The maximum resection of the tumor remains the key point in the management of gliomas with a direct influence on the survival of patients [23]. The progress made over the last two decades in surgical techniques including microsurgery by the operating microscope, preoperative functional imaging (e.g., functional MRI, MRI tractography), intraoperative electrical stimulation in awakened craniotomy and intraoperative imaging (surgery guided by real-time imaging using neuronavigation or intraoperative MRI) have largely contributed to significantly increase resected tumor volume while improving morbidity and mortality [33].…”

Section: Introductionmentioning

confidence: 99%

Machine Learning Assisted Intraoperative Assessment of Brain Tumor Margins Using HRMAS NMR Spectroscopy

Cakmakci

Karakaslar

Ruhland

et al. 2020

Preprint

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Complete resection of the tumor is important for survival in glioma patients. Even if the gross total resection was achieved, left-over micro-scale tissue in the excision cavity risks recurrence. High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (HRMAS NMR) technique can distinguish healthy and malign tissue efficiently using peak intensities of biomarker metabolites. The method is fast, sensitive and can work with small and unprocessed samples, which makes it a good fit for real-time analysis during surgery. However, only a targeted analysis for the existence of known tumor biomarkers can be made and this requires a technician with chemistry background, and a pathologist with knowledge on tumor metabolism to be present during surgery. Here, we show that we can accurately perform this analysis in real-time and can analyze the full spectrum in an untargeted fashion using machine learning. We work on a new and large HRMAS NMR dataset of glioma and control samples (n = 568), which are also labeled with a quantitative pathology analysis. Our results show that a random forest based approach can distinguish samples with tumor cells and controls accurately and effectively with a mean AUC of 85.6% and AUPR of 93.4%. We also show that we can further distinguish benign and malignant samples with a mean AUC of 87.1% and AUPR of 96.1%. We analyze the feature (peak) importance for classification to interpret the results of the classifier. We validate that known malignancy biomarkers such as creatine and 2-hydroxyglutarate play an important role in distinguish tumor and normal cells and suggest new biomarker regions. The code is released at http://github.com/ciceklab/HRMAS_NC.

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“…For example, boys constitute the majority of group 3 and 4 medulloblastomas, with peak incidences less than 5 years of age and in the peripubertal period (10,11). Moreover, boys with high-grade gliomas have significantly reduced overall and progression-free survival relative to girls (12). These findings suggest that existing sex disparities, at least in the case of brain cancers, are not completely attributable to the actions of circulating sex hormones.…”

Section: Introductionmentioning

confidence: 99%

Sexual dimorphism in glioma glycolysis underlies sex differences in survival

Ippolito¹,

Yim²,

Luo

et al. 2017

JCI Insight

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Sex, Age, Anatomic Location, and Extent of Resection Influence Outcomes in Children With High-grade Glioma

Cited by 47 publications

References 23 publications

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

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

Machine Learning Assisted Intraoperative Assessment of Brain Tumor Margins Using HRMAS NMR Spectroscopy

Sexual dimorphism in glioma glycolysis underlies sex differences in survival

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