scholarly journals Clinical Implications of Girdin Protein Expression in Glioma

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Liwei Zhao ◽  
Shuyin Ma ◽  
Qing Liu ◽  
Peng Liang
Keyword(s):  
Protein Expression ◽  
Cox Regression ◽  
Strong Predictor ◽  
Extent Of Resection ◽  
Biological Behavior ◽  
Low Grade ◽  
Who Grade ◽  
Cox Regression Analysis ◽  
The Relationship ◽  
Expression Status

Objective. To investigate the expression status of Girdin in glioma and the relationship between Girdin expression and the biological behavior of glioma.Materials and methods. The expression status of Girdin in glioma from 560 cases was evaluated by RT-PCR, Western Blot and immunohistochemistry. The relationship between Girdin expression and clinic-pathological parameters as well as prognosis was also studied.Results. The expression of Girdin in high grade glioma was significantly higher than low grade glioma. After universal analysis, the expression of Girdin protein is closely related to KPS score, extent of resection, Ki67 and WHO grade, but it was not related to sex and age. Finally, extent of resection, Ki67 and WHO grade were indentified to be related to the Girdin protein expression in logistic regression. Interestingly, we found that the expression of Girdin is significantly related to the distant metastasis of glioma. After COX regression analysis, KPS score, Extent of resection, Ki67, WHO grade as well as Girdin were observed to be independent prognostic factors.Conclusions. Girdin is differential expressed in the glioma patients and closely related to the biological behavior of Glioma. Finally, Girdin was found to be a strong predictor for the post-operative prognosis.

scholarly journals The Role of Extent of Resection in IDH1 Wild-Type or Mutant Low-Grade Gliomas

Neurosurgery ◽  
2017 ◽  
Vol 82 (6) ◽  
pp. 808-814 ◽  
Author(s):  
Toral Patel ◽  
Evan D Bander ◽  
Rachael A Venn ◽  
Tiffany Powell ◽  
Gustav Young-Min Cederquist ◽  
...  
Keyword(s):  
Cox Regression ◽  
Extent Of Resection ◽  
World Health ◽  
Low Grade ◽  
Wild Type ◽  
Who Grade ◽  
Cox Regression Analysis ◽  
Low Grade Gliomas ◽  
Grade Ii ◽  
The Impact

Abstract BACKGROUND Maximizing extent of resection (EOR) improves outcomes in adults with World Health Organization (WHO) grade II low-grade gliomas (LGG). However, recent studies demonstrate that LGGs bearing a mutation in the isocitrate dehydrogenase 1 (IDH1) gene are a distinct molecular and clinical entity. It remains unclear whether maximizing EOR confers an equivalent clinical benefit in IDH mutated (mtIDH) and IDH wild-type (wtIDH) LGGs. OBJECTIVE To assess the impact of EOR on malignant progression-free survival (MPFS) and overall survival (OS) in mtIDH and wtIDH LGGs. METHODS We performed a retrospective review of 74 patients with WHO grade II gliomas and known IDH mutational status undergoing resection at a single institution. EOR was assessed with quantitative 3-dimensional volumetric analysis. The effect of predictor variables on MPFS and OS was analyzed with Cox regression models and the Kaplan–Meier method. RESULTS Fifty-two (70%) mtIDH patients and 22 (30%) wtIDH patients were included. Median preoperative tumor volume was 37.4 cm3; median EOR of 57.6% was achieved. Univariate Cox regression analysis confirmed EOR as a prognostic factor for the entire cohort. However, stratifying by IDH status demonstrates that greater EOR independently prolonged MPFS and OS for wtIDH patients (hazard ratio [HR] = 0.002 [95% confidence interval {CI} 0.000-0.074] and HR = 0.001 [95% CI 0.00-0.108], respectively), but not for mtIDH patients (HR = 0.84 [95% CI 0.17-4.13] and HR = 2.99 [95% CI 0.15-61.66], respectively). CONCLUSION Increasing EOR confers oncologic and survival benefits in IDH1 wtLGGs, but the impact on IDH1 mtLGGs requires further study.

390 The Impact of Extent of Resection on IDH1 Wild-Type or Mutant Low-Grade Gliomas

Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 293-294 ◽  
Author(s):  
Toral R Patel ◽  
Evan D Bander ◽  
Rachael A Venn ◽  
Tiffany L Powell Avila ◽  
Gustav Y Cederquist ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Cox Regression ◽  
Extent Of Resection ◽  
Low Grade ◽  
Wild Type ◽  
Who Grade ◽  
Cox Regression Analysis ◽  
Grade Ii ◽  
The Impact ◽  
Who Grade Ii Gliomas

Abstract INTRODUCTION Accumulating evidence suggests that maximizing extent of resection (EOR) improves outcomes for patients with WHO grade II low-grade gliomas (LGG). However, recent studies demonstrate that LGGs bearing a mutation in the isocitrate dehydrogenase 1 (IDH1) gene are a distinct molecular and clinical entity. It remains unclear whether maximizing EOR confers an equivalent clinical benefit in IDH mutated (mtIDH) and IDH wild-type (wtIDH) LGGs. To answer this question, we evaluated a cohort of patients with surgically-resection WHO grade II gliomas and known IDH1 mutation status, to assess the impact of EOR on malignant progression-free survival (MPFS) and overall survival (OS). METHODS We performed a retrospective review of 74 patients with WHO grade II gliomas and known IDH mutational status undergoing surgical resection at a single institution. EOR was assessed with quantitative three-dimensional volumetric analysis. The effect of predictor variables on MPFS and OS was analyzed with Cox regression models and the Kaplan-Meier method. RESULTS >52 (70%) mtIDH patients and 22 (30%) wtIDH patients were included. Median pre-operative tumor volume was 37.4 cm3 (range: 0.9-190.2 cm3). Median EOR was 57.6% (range: 0.08% 99.3%). Median follow-up was 44.4 months. Malignant progression was identified in 31 patients and 17 patients died. Univariate Cox regression analysis confirmed EOR as a prognostic factor for the entire cohort. However, Cox regression analysis stratified by IDH status demonstrated that a greater EOR independently prolonged MPFS and OS for wtIDH patients (HR = 0.002 [95% CI 0.000 - 0.074] and HR = 0.001 [95% CI 0.00 - 0.108], respectively), but not for mtIDH patients (HR = 0.84 [95% CI 0.17 - 4.13] and HR = 2.99 [95% CI 0.15 - 61.66], respectively). CONCLUSION Increasing EOR confers oncologic and survival benefits in IDH1 wild-type LGGs. However, the impact of EOR on IDH1 mutant LGGs is less significant and requires further study.

Short-term outcomes associated with temozolomide or PCV chemotherapy for 1p/19q-codeleted WHO grade 3 oligodendrogliomas: a national evaluation

2022 ◽  
Author(s):  
Nayan Lamba ◽  
Malia McAvoy ◽  
Vasileios K Kavouridis ◽  
Timothy R Smith ◽  
Mehdi Touat ◽  
...  
Keyword(s):  
Cox Regression ◽  
Extent Of Resection ◽  
First Line ◽  
Short Term ◽  
Who Grade ◽  
Cox Regression Analysis ◽  
Significant Difference ◽  
Pcv Chemotherapy ◽  
Grade 3 ◽  
National Analysis

Abstract Background The optimal chemotherapy regimen between temozolomide and procarbazine, lomustine, and vincristine (PCV) remains uncertain for W.H.O. grade 3 oligodendroglioma (Olig3) patients. We therefore investigated this question using national data. Methods Patients diagnosed with radiotherapy-treated 1p/19q-codeleted Olig3 between 2010-2018 were identified from the National Cancer Database. The OS associated with first-line single-agent temozolomide vs. multi-agent PCV was estimated by Kaplan-Meier techniques and evaluated by multivariable Cox regression. Results 1,596 radiotherapy-treated 1p/19q-codeleted Olig3 patients were identified: 88.6% (n=1,414) treated with temozolomide and 11.4% (n=182) with PCV (from 5.4% in 2010 to 12.0% in 2018) in the first-line setting. The median follow-up was 35.5 months (interquartile range [IQR] 20.7-60.6 months) with 63.3% of patients alive at time of analysis. There was a significant difference in unadjusted OS between temozolomide (5yr-OS 58.9%, 95%CI: 55.6-62.0) and PCV (5yr-OS 65.1%, 95%CI: 54.8-73.5; p=0.04). However, a significant OS difference between temozolomide and PCV was not observed in the Cox regression analysis adjusted by age and extent of resection (PCV vs. temozolomide HR 0.81, 95%CI: 0.59-1.11, p=0.18). PCV was more frequently used for younger Olig3s, but otherwise was not associated with patient’s insurance status or care setting. Conclusions In a national analysis of Olig3s, first-line PCV chemotherapy was associated with a slightly improved unadjusted short-term OS compared to temozolomide; but not following adjustment by patient age and extent of resection. There has been an increase in PCV utilization since 2010. These findings provide preliminary data while we await the definitive results from the CODEL trial.

scholarly journals Contemporary assessment of extent of resection in molecularly defined categories of diffuse low-grade glioma: a volumetric analysis

2020 ◽  
Vol 133 (5) ◽  
pp. 1291-1301 ◽  
Author(s):  
Vasileios K. Kavouridis ◽  
Alessandro Boaro ◽  
Jeffrey Dorr ◽  
Elise Y. Cho ◽  
J. Bryan Iorgulescu ◽  
...  
Keyword(s):  
Tumor Volume ◽  
Cox Regression ◽  
Molecular Subtypes ◽  
Progression Free Survival ◽  
Residual Tumor ◽  
Extent Of Resection ◽  
Low Grade Glioma ◽  
Low Grade ◽  
Who Grade ◽  
Free Survival

OBJECTIVEWhile the effect of increased extent of resection (EOR) on survival in diffuse infiltrating low-grade glioma (LGG) patients is well established, there is still uncertainty about the influence of the new WHO molecular subtypes. The authors designed a retrospective analysis to assess the interplay between EOR and molecular classes.METHODSThe authors retrospectively reviewed the records of 326 patients treated surgically for hemispheric WHO grade II LGG at Brigham and Women’s Hospital and Massachusetts General Hospital (2000–2017). EOR was calculated volumetrically and Cox proportional hazards models were built to assess for predictive factors of overall survival (OS), progression-free survival (PFS), and malignant progression–free survival (MPFS).RESULTSThere were 43 deaths (13.2%; median follow-up 5.4 years) among 326 LGG patients. Median preoperative tumor volume was 31.2 cm3 (IQR 12.9–66.0), and median postoperative residual tumor volume was 5.8 cm3 (IQR 1.1–20.5). On multivariable Cox regression, increasing postoperative volume was associated with worse OS (HR 1.02 per cm3; 95% CI 1.00–1.03; p = 0.016), PFS (HR 1.01 per cm3; 95% CI 1.00–1.02; p = 0.001), and MPFS (HR 1.01 per cm3; 95% CI 1.00–1.02; p = 0.035). This result was more pronounced in the worse prognosis subtypes of IDH-mutant and IDH-wildtype astrocytoma, for which differences in survival manifested in cases with residual tumor volume of only 1 cm3. In oligodendroglioma patients, postoperative residuals impacted survival when exceeding 8 cm3. Other significant predictors of OS were age at diagnosis, IDH-mutant and IDH-wildtype astrocytoma classes, adjuvant radiotherapy, and increasing preoperative volume.CONCLUSIONSThe results corroborate the role of EOR in survival and malignant transformation across all molecular subtypes of diffuse LGG. IDH-mutant and IDH-wildtype astrocytomas are affected even by minimal postoperative residuals and patients could potentially benefit from a more aggressive surgical approach.

scholarly journals TMOD-01. A PROGNOSTIC NOMOGRAM MODEL AND ONLINE SOFTWARE FOR PATIENTS WITH NEWLY DIAGNOSED LOWER-GRADE GLIOMAS

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i35-i35
Author(s):  
Mingzhi Han
Keyword(s):  
Cox Regression ◽  
Molecular Subtype ◽  
Age At Diagnosis ◽  
Calibration Plot ◽  
Low Grade ◽  
Lower Grade ◽  
Newly Diagnosed ◽  
Who Grade ◽  
Cox Regression Analysis ◽  
Survival Probabilities

Abstract The nomogram represents a statistical model that incorporates multiple risk factors to estimate individualized survival probabilities. In this study, we developed a nomogram which provides an important tool for individulized survival predicition for newly diagnosed low-grade gliomas (LGG). A total number of 582 newly diagnosed LGG patients were included; the median age was 39.93 years and 42% were female. Cox regression analysis showed that younger age at diagnosis, WHO grade II vs. III, the IDHmut-codel vs. the IDHwt, and the IDHmut-non-codel vs. the IDHwt were significantly associated with better prognosis. The adjuvant treatment following surgery showed a trend towards improved survival. Subsequently, the nomogram to estimate 60-, 90-, and 120-month survival probabilities was established. Our data showed that the age at diagnosis was the largest contributor to patient survival, followed by molecular subtype, WHO grade, treatment and gender. The calibration plot showed that the observed and the nomogram predicted OS curves were well-aligned. In addition, we also validated our nomogram for LGG patients who received postsurgical adjuvant therapy through cross-validation and the calibration plot. Finally, we developed a free online tool for this nomogram (softwarewebsite:https://rrlnnomogram.shinyapps.io/LGG_Nom_Asian/). Overall, this model should be a useful tool for counseling patients in clinical practice including treatment decisions, follow-up, and prognosis.

scholarly journals Calumenin contributes to epithelial-mesenchymal transition and predicts poor survival in glioma

2021 ◽  
Vol 12 (1) ◽  
pp. 67-75
Author(s):  
Ying Yang ◽  
Jin Wang ◽  
Shihai Xu ◽  
Fei Shi ◽  
Aijun Shan
Keyword(s):  
Cox Regression ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Gliomas ◽  
Strongly Correlated ◽  
Who Grade ◽  
Mesenchymal Transition ◽  
Cox Regression Analysis ◽  
R Language ◽  
Biological Adhesion ◽  
Tcga Dataset

Abstract Background Calumenin (CALU) has been reported to be associated with invasiveness and metastasis in some malignancies. However, in glioma, the role of CALU remains unclear. Methods Clinical and transcriptome data of 998 glioma patients, including 301 from CGGA and 697 from TCGA dataset, were included. R language was used to perform statistical analyses. Results CALU expression was significantly upregulated in more malignant gliomas, including higher grade, IDH wildtype, mesenchymal, and classical subtype. Gene Ontology analysis revealed that CALU-correlated genes were mainly enriched in cell/biological adhesion, response to wounding, and extracellular matrix/structure organization, all of which were strongly correlated with the epithelial-mesenchymal transition (EMT) phenotype. GSEA further validated the profound involvement of CALU in EMT. Subsequent GSVA suggested that CALU was particularly correlated with three EMT signaling pathways, including TGFβ, PI3K/AKT, and hypoxia pathway. Furthermore, CALU played synergistically with EMT key markers, including N-cadherin, vimentin, snail, slug, and TWIST1. Survival and Cox regression analysis showed that higher CALU predicted worse survival, and the prognostic value was independent of WHO grade and age. Conclusions CALU was correlated with more malignant phenotypes in glioma. Moreover, CALU seemed to serve as a pro-EMT molecular target and could contribute to predict prognosis independently in glioma.

scholarly journals Association of ST6GAL1 and CYP19A1 polymorphisms in the 3′-UTR with astrocytoma risk and prognosis in a Chinese Han population

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tuo Wang ◽  
Yao Sun ◽  
Zichao Xiong ◽  
Jiamin Wu ◽  
Xiaoying Ding ◽  
...  
Keyword(s):  
Cox Regression ◽  
Chinese Han Population ◽  
Low Grade ◽  
Central Nervous System Tumor ◽  
Chinese Han ◽  
Cox Regression Analysis ◽  
Han Population ◽  
Potential Biomarker ◽  
Codominant Model ◽  
System Tumor

Abstract Background Astrocytoma is a common type of central nervous system tumor. In this study, we investigated the correlation between ST6GAL1 and CYP19A1 polymorphisms and the risk and prognosis of astrocytoma. Methods A total of 365 astrocytoma patients and 379 healthy controls were genotyped using the Agena MassARRAY system. The correlation between ST6GAL1 and CYP19A1 variants and astrocytoma risk was calculated using logistic regression. The survival rate of patients with astrocytoma was analyzed to evaluate prognosis. Results We found that the ST6GAL1-rs2239611 significantly decreased the risk of astrocytoma in the codominant model (p = 0.044) and dominant model (p = 0.049). In stratified analyses, CYP19A1-rs2255192 might be associated with a higher risk of astrocytoma among the low-grade subgroup under recessive (p = 0.034) and additive (p = 0.030) models. However, CYP19A1-rs4646 had a risk-decreasing effect on the high-grade subgroup in the codominant model (p = 0.044). The results of Cox regression analysis showed that the CYP19A1-rs2239611 and -rs1042757 polymorphisms were significantly correlated with the prognosis of astrocytoma. Conclusion Our results suggest that ST6GAL1 and CYP19A1 genes may be a potential biomarker of genetic susceptibility and prognosis to astrocytoma in the Chinese Han population.

scholarly journals The Clinical Value of PET with Amino Acid Tracers for Gliomas WHO Grade II

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Anja Smits ◽  
Brigitta G. Baumert
Keyword(s):  
Amino Acid ◽  
Hot Spot ◽  
Imaging Techniques ◽  
Biological Behavior ◽  
Optimal Timing ◽  
Low Grade ◽  
Clinical Value ◽  
Who Grade ◽  
Positron Emission ◽  
Therapeutic Procedures

The clinical management of adults with low-grade gliomas (LGGs) remains a challenge. There is no curative treatment, and management of individual patients is a matter of deciding optimal timing as well as right treatment modality. In addition to conventional imaging techniques, positron emission tomography (PET) with amino acid tracers can facilitate diagnostic and therapeutic procedures. In this paper, the clinical applications of PET with amino acid tracers 11C-methyl-L-methionine (MET) and 18F-fluoro-ethyl-L-tyrosine (FET) for patients with LGG are summarized. We also discuss the value of PET for the long-term followup of this patient group. Monitoring metabolic activity by PET in individual patients during course of disease will provide insight in the biological behavior and evolution of these tumors. As such, spatial changes in tumor activity over time, including shifts of hot-spot regions within the tumor, may reflect intratumoral heterogeneity and correlate to clinical parameters.

Predictors of tumor progression among children with gangliogliomas

2009 ◽  
Vol 3 (6) ◽  
pp. 461-466 ◽  
Author(s):  
Mostafa El Khashab ◽  
Lynn Gargan ◽  
Linda Margraf ◽  
Korgun Koral ◽  
Farideh Nejat ◽  
...  
Keyword(s):  
Risk Factors ◽  
Tumor Progression ◽  
Cox Regression ◽  
Tumor Resection ◽  
Progression Free Survival ◽  
Initial Presentation ◽  
Subtotal Resection ◽  
Low Grade ◽  
Cox Regression Analysis ◽  
Presenting Symptoms

Object Few reports describe the outcome and prognostic factors for children with gangliogliomas. The objective of this report was to describe the progression-free survival (PFS) for children with low-grade gangliogliomas and identify risk factors for tumor progression. Methods A retrospective study was performed in children with low-grade gangliogliomas who were evaluated and treated in the neuro-oncology department between 1986 and 2006 to determine risk factors for subsequent tumor progression. Results A total of 38 children with newly diagnosed gangliogliomas were included in this report. Thirty-four children were treated with surgery alone, 3 with subtotal resection and radiation therapy, and 1 with subtotal resection and chemotherapy. The follow-up ranged from 4 months to 15.8 years (mean 5.7 ± 4.2 years [± SD]). Seven children have experienced tumor progression, and 1 child died after his tumor subsequently underwent malignant transformation. The 5-year PFS was calculated to be 81.2% using Kaplan-Meier survival analysis. Initial presentation with seizures (p = 0.004), tumor location in the cerebral hemisphere (p = 0.020), and complete tumor resection (p = 0.035) were associated with prolonged PFS. Further analysis of the above significant variables by a Cox regression model identified initial presentation with seizures as being associated with prolonged PFS (p = 0.028). Conclusions The PFS and overall survival of children with gangliogliomas are good. Tumors located in the cerebral hemispheres, the achievement of total resection, and seizures at presentation were associated with prolonged PFS. Cox regression analysis identified presenting symptoms including seizures as significant predictive factors of PFS. Prospective studies with larger numbers of children are needed to define the significant factors of tumor progression.

The Role of Surgery in IDH-Wild-Type Lower-Grade Gliomas: Threshold at a High Extent of Resection Should be Pursued

Neurosurgery ◽  
2021 ◽  
Author(s):  
Peng Wang ◽  
Chen Luo ◽  
Peng-jie Hong ◽  
Wen-ting Rui ◽  
Shuai Wu
Keyword(s):  
Cox Regression ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Lower Grade ◽  
Wild Type ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Lower Grade Glioma ◽  
Clinical Benefits

Abstract BACKGROUND While maximizing extent of resection (EOR) is associated with longer survival in lower-grade glioma (LGG) patients, the number of cases remains insufficient in determining a EOR threshold to elucidate the clinical benefits, especially in IDH-wild-type LGG patients. OBJECTIVE To identify the effects of EOR on the survival outcomes of IDH-wild-type LGG patients. METHODS IDH-wild-type LGG patients were retrospectively reviewed. The effect of EOR and other predictor variables on overall survival (OS) and progression-free survival (PFS) was analyzed using Cox regression models and the Kaplan-Meier method. RESULTS A total of 94 patients (median OS: 48.9 mo; median follow-up: 30.6 mo) were included in this study. In the multivariable Cox regression analysis, postoperative residual volume was associated with prolonged OS (HR = 2.238; 95% confidence interval [CI], 1.130-4.435; P = .021) and PFS (HR = 2.075; 95% CI, 1.113-3.869; P = .022). Thresholds at a minimum EOR of 97.0% or a maximum residue of 3.0 cm3 were necessary to impact OS positively. For the telomerase reverse transcriptase (TERT)p-wild-type group, such an association was absent. Significant differences in survival existed between the TERTp-wild-type and mutant patients who underwent relatively incomplete resections (residual ≥2.0 cm3 + TERTp wild type: median OS of 62.6 mo [95% CI: 39.7-85.5 mo]; residual ≥2.0 cm3 + TERTp mutant: median OS of 20.0 mo [95% CI:14.6-25.4 mo]). CONCLUSION Our results support the core role of maximal safe resection in the treatment of IDH-wild-type LGGs, especially for IDH-wild-type + TERTp-mutant LGGs. Importantly, the survival benefits of surgery could only be elucidated at a high EOR cut-off point.

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