scholarly journals Independently validated sex-specific nomograms for predicting survival in patients with newly diagnosed glioblastoma: NRG Oncology RTOG 0525 and 0825

2021 ◽  
Author(s):  
Nirav Patil ◽  
Eashwar Somasundaram ◽  
Kristin A. Waite ◽  
Justin D. Lathia ◽  
Mitchell Machtay ◽  
...  
Keyword(s):  
Selection Procedure ◽  
Extent Of Resection ◽  
Newly Diagnosed ◽  
Online Application ◽  
Survival Probabilities ◽  
Oncology Clinical Trials ◽  
Newly Diagnosed Glioblastoma ◽  
Cox Proportional Hazard Models ◽  
Using Data ◽  
User Friendly

Abstract Background/purpose Glioblastoma (GBM) is the most common primary malignant brain tumor. Sex has been shown to be an important prognostic factor for GBM. The purpose of this study was to develop and independently validate sex-specific nomograms for estimation of individualized GBM survival probabilities using data from 2 independent NRG Oncology clinical trials. Methods This analysis included information on 752 (NRG/RTOG 0525) and 599 (NRG/RTOG 0825) patients with newly diagnosed GBM. The Cox proportional hazard models by sex were developed using NRG/RTOG 0525 and significant variables were identified using a backward selection procedure. The final selected models by sex were then independently validated using NRG/RTOG 0825. Results Final nomograms were built by sex. Age at diagnosis, KPS, MGMT promoter methylation and location of tumor were common significant predictors of survival for both sexes. For both sexes, tumors in the frontal lobes had significantly better survival than tumors of multiple sites. Extent of resection, and use of corticosteroids were significant predictors of survival for males. Conclusions A sex specific nomogram that assesses individualized survival probabilities (6-, 12- and 24-months) for patients with GBM could be more useful than estimation of overall survival as there are factors that differ between males and females. A user friendly online application can be found here—https://npatilshinyappcalculator.shinyapps.io/SexDifferencesInGBM/.

scholarly journals PC3 - 152 Impact of Extent of Resection Upon Outcome in Newly Diagnosed Glioblastoma: A Study in the Molecular Era

2016 ◽  
Vol 43 (S4) ◽  
pp. S17-S18
Author(s):  
W.M.H. Sayeed ◽  
E. Batuyong ◽  
J.C. Easaw ◽  
M. Pitz ◽  
J.J.P. Kelly
Keyword(s):  
Multivariable Analysis ◽  
Extent Of Resection ◽  
Postal Code ◽  
Newly Diagnosed ◽  
Presenting Symptoms ◽  
Tumour Location ◽  
Newly Diagnosed Glioblastoma ◽  
Molecular Marker Analysis

For decades, debate has persisted regarding the role of surgical resection in newly diagnosed glioblastoma. There is increasing evidence that extent of resection (EoR) is an independent prognostic factor. Previous work has proposed the inclusion of EoR in a risk stratification algorithm but does not incorporate account recent advances in the molecular characterization of tumours. We set out to investigate the effect of EoR on overall survival (OS), and to develop a stratification algorithm incorporating both EoR and modern molecular markers for prognostication. HYPOTHESIS: Greater EoR is independently associated with improved OS. METHODS: We examined 190 consecutive cases of histopathologically confirmed newly-diagnosed glioblastoma who were operated upon between January 1, 2012 and December 31, 2014. Variables including age, sex, postal code, KPS, tumour location, presenting symptoms, treatment history, date of progression, date of reoperation, as well as MGMT, IDH, 1p/19q codeletion, and ATRX status were recorded. Preoperative and postoperative MRIs were reviewed and volumetric tumour burden will be analyzed and EoR will be calculated. RESULTS: Preliminary EoR calculations (n=18) show a positive correlation between EoR and OS. CONCLUSION: A correlation exists between EoR and OS, although multivariable analysis is planned to exclude potential confounders. MRI review, chart review including molecular marker analysis and EoR calculations are ongoing.

scholarly journals SURG-02. A NOVEL RISK MODEL TO DEFINE THE RELATIVE BENEFIT OF MAXIMAL EXTENT OF RESECTION WITHIN PROGNOSTIC GROUPS IN NEWLY DIAGNOSED GLIOBLASTOMA

2018 ◽  
Vol 20 (suppl_6) ◽  
pp. vi250-vi250
Author(s):  
Annette Molinaro ◽  
Shawn Hervey-Jumper ◽  
Seunggu J. Han ◽  
Ramin Morshed ◽  
Marisa Lafontaine ◽  
...  
Keyword(s):  
Risk Model ◽  
Extent Of Resection ◽  
Newly Diagnosed ◽  
Relative Benefit ◽  
Prognostic Groups ◽  
Newly Diagnosed Glioblastoma ◽  
Maximal Extent

Impact of EGFR amplification status in newly diagnosed glioblastoma treated with Stupp protocol.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13569-e13569
Author(s):  
Addison Barnett ◽  
Anas Saeed Bamashmos ◽  
Assad Ali ◽  
Xuefei Jia ◽  
Wei (Auston) Wei ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Tertiary Care ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Egfr Amplification ◽  
Newly Diagnosed Glioblastoma ◽  
Cox Proportional Hazard Models ◽  
Tertiary Care Institution ◽  
Stupp Protocol

e13569 Background: Standard post-surgical glioblastoma (GBM) treatment, per Stupp protocol, includes six-weeks of concurrent Temozolomide chemoradiation followed by at least six cycles of adjuvant-Temozolomide. Previous investigations into epidermal growth factor receptor (EGFR) amplification as a prognostic factor in GBM have yielded contradicting results, requiring further investigation. The primary aim of this study was to determine the degree to which EGFR amplification, in newly diagnosed GBM, impacted progression free survival (PFS) and overall survival (OS). Methods: Data from 582 patients who underwent surgical intervention for GBM at a tertiary care institution between 2012 and 2018 were analyzed. Only adult patients who underwent treatment per Stupp protocol and had pathological analysis on EGFR and CEP7 were included. Amplification and non-amplification status was calculated by a ratio of EGFR/CEP7 > 2 and < 2, respectively. PFS and OS outcomes were compared using Cox proportional hazard models stratified by surgery type and sex. Results: Of the original 582 patients, 122 were treated per Stupp protocol and had documented EGFR analysis. Of patients who were EGFR amplified, 41 (58.5%) were male and 25 (48.1%) were female (p = 0.38) and median amplification was 1.07 and 1.16 (p < 0.001), respectively. EGFR non-amplified patients had a PFS hazard ratio, HR = 0.70 (95% CI = 0.44 – 1.12, p = 0.14); and an OS HR = 0.60 (95% CI = 0.35 – 1.03, p = 0.065). When the EGFR/CEP7 ratio was stratified by quartile, it was found that Q4 compared to Q1 (Q4 > 6.50 vs 0 < Q1 ≤ 1.06) had a PFS HR = 2.1 (95% CI = 1.11 – 4.07, p = 0.024); and an OS HR = 2.48 (95% CI = 1.10 – 5.60, p = 0.028). Conclusions: There was no statistical difference in prevalence of EGFR amplification by sex. However, despite statistical significance, there was minimal difference in median degree of amplification by sex (0.09). Trends begin to show that patients who were EGFR non-amplified had better PFS and OS outcomes than patients who were EGFR amplified, although this was not statistically significant. Patients with very high EGFR amplification (Q4) had significantly poorer PFS and OS outcomes than patients with very low EGFR amplification (Q1).

scholarly journals Extent of Resection in Newly Diagnosed Glioblastoma: Impact of a Specialized Neuro-Oncology Care Center

2017 ◽  
Vol 8 (1) ◽  
pp. 5 ◽  
Author(s):  
Amer Haj ◽  
Christian Doenitz ◽  
Karl-Michael Schebesch ◽  
Denise Ehrensberger ◽  
Peter Hau ◽  
...  
Keyword(s):  
Care Center ◽  
Extent Of Resection ◽  
Newly Diagnosed ◽  
Newly Diagnosed Glioblastoma ◽  
Oncology Care

Impact of Postoperative Dexamethasone on Survival, Steroid Dependency, and Infections in Newly Diagnosed Glioblastoma Patients

2021 ◽  
Author(s):  
Akshitkumar M Mistry ◽  
Sumeeth V Jonathan ◽  
Meredith A Monsour ◽  
Bret C Mobley ◽  
Stephen W Clark ◽  
...  
Keyword(s):  
Tumor Volume ◽  
Cohort Analysis ◽  
Absolute Lymphocyte Count ◽  
Extent Of Resection ◽  
Newly Diagnosed ◽  
Steroid Dependency ◽  
A Value ◽  
Retrospective Cohort Analysis ◽  
Newly Diagnosed Glioblastoma ◽  
Outpatient Prescriptions

Abstract Background We examine the effect of dexamethasone prescribed in the initial 3 postoperative weeks on survival, steroid dependency, and infection in glioblastoma patients. Methods In this single-center retrospective cohort analysis, we electronically retrieved inpatient administration and outpatient prescriptions of dexamethasone and laboratory values from the medical record of 360 glioblastoma patients. We correlated total dexamethasone prescribed from postoperative day (POD) 0 to 21 with survival, dexamethasone prescription from POD30 to POD90, and diagnosis of an infection by POD90. These analyses were adjusted for age, KPS, tumor volume, extent of resection, IDH1/2 tumor mutation, tumor MGMT promoter methylation, temozolomide and radiotherapy initiation, and maximum blood glucose level. Results Patients were prescribed a median of 159 mg [109-190] of dexamethasone cumulatively by POD21. Every 16mg increment (4mg every 6 hours/day) of total dexamethasone associated with a 4% increase in mortality (95% confidence interval, CI, 1–7%, P&lt;0.01), 12% increase in the odds of being prescribed dexamethasone from POD30-POD90 (95% CI 6–19%, P&lt;0.01), and a 10% increase in the odds of being diagnosed with an infection (95% CI, 4–17%, P&lt;0.01). Of the 175 patients who had their absolute lymphocyte count measured in the preoperative week, 80 (45.7%) had a value indicative of lymphopenia. In the POD1-POD28 period, this proportion was 82/167 (49.1%). Conclusions Lower survival, steroid dependency, and higher infection rate in glioblastoma patients associated with higher dexamethasone administration in the initial 3 postoperative weeks. Nearly half of the glioblastoma patients are lymphopenic preoperatively and up to one month postoperatively.

Galectin-1 (Gal-1) expression as a prognostic factor in patients with newly diagnosed glioblastoma (GB) treated with Stupp regimen (GLIOCAT study).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13526-e13526
Author(s):  
Noelia Vilarino ◽  
Neus Martinez-Bosch ◽  
Carmen Balana ◽  
Francesc Alameda ◽  
Anna Estival ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Prognostic Factor ◽  
Clinical Outcome ◽  
Methylation Status ◽  
Prognostic Significance ◽  
Tumor Grade ◽  
Extent Of Resection ◽  
Newly Diagnosed ◽  
Initial Surgery ◽  
Newly Diagnosed Glioblastoma

e13526 Background: Gal-1 is a β-galactoside binding protein that plays an important role in cancer, promoting cell invasion, proliferation, migration, angiogenesis and evasion of the immune response. Gal-1 is involved in glioma progression and is related to tumor grade and poor clinical outcome. Gal-1 has been implicated in resistance to chemotherapy and as a potential mediator of resistance to anti-VEGF therapy. The aim of our study was to evaluate the prognostic significance of Gal-1 in a homogenous cohort of GB patients and to analyze its potential predictive value of response to bevacizumab at recurrence. Methods: A substudy of GLIOCAT, a multicenter study of newly diagnosed GB patients treated with standard Stupp regimen (previously reported). GLIOCAT enrolled 432 patients between 2005-2014. Tissue was available from 243 cases, from which a tissue microarray (TMA) was constructed. Gal-1 expression in tissue from initial surgery was analyzed by immunohistochemistry. Results were evaluated by three reviewers and quantified by H-score. Expression levels were correlated with clinical outcome, known GB prognostic factors and response to bevacizumab. Results: We defined a cut off for Gal-1 H-Score of >60 (cytoplasm) and >25 (nucleus). HighcytoplasmicGal-1 expression significantly correlated with worse OS and with a trend for shorter PFS. In the multivariate analysis KPS, age, MGMT methylation status and, extent of resection but not Gal-1 expression were independent prognostic factors for survival. Of 92 patients who received bevacizumab at recurrence, only 54 were included in the TMA, and only 1 had low Gal-1 expression. We couldn’t find any relationship with OS or PFS in this population. Conclusions: Gal-1 expression may represent a prognostic factor for GB patients treated with standard therapy. [Table: see text]

Study Protocol: Early Stereotactic Gamma Knife Radiosurgery to Residual Tumor After Surgery of Newly Diagnosed Glioblastoma (Gamma-GBM)

Neurosurgery ◽  
2018 ◽  
Vol 84 (5) ◽  
pp. 1133-1137
Author(s):  
Stefanie Brehmer ◽  
Mario Alexander Grimm ◽  
Alex Förster ◽  
Marcel Seiz-Rosenhagen ◽  
Grit Welzel ◽  
...  
Keyword(s):  
External Beam Radiotherapy ◽  
Gamma Knife Radiosurgery ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Residual Tumor ◽  
Extent Of Resection ◽  
Subtotal Resection ◽  
Newly Diagnosed ◽  
Open Label ◽  
Newly Diagnosed Glioblastoma

Abstract BACKGROUND Glioblastoma (GBM) is the most common malignant brain tumor in adult patients. Tumor recurrence commonly occurs around the resection cavity, especially after subtotal resection (STR). Consequently, the extent of resection correlates with overall survival (OS), suggesting that depletion of postoperative tumor remnants will improve outcome. OBJECTIVE To assess safety and efficacy of adding stereotactic radiosurgery (SRS) to the standard treatment of GBM in patients with postoperative residual tumor. METHODS Gamma-GBM is a single center, open-label, prospective, single arm, phase II study that includes patients with newly diagnosed GBM (intraoperative via frozen sections) who underwent STR (residual tumor will be identified by native and contrast enhanced T1-weighted magnetic resonance imaging scans). All patients will receive SRS with 15 Gy (prescribed to the 50% isodose enclosing all areas of residual tumor) early (within 24-72 h) after surgery. Thereafter, all patients undergo standard-of-care therapy for GBM (radiochemotherapy with 60 Gy external beam radiotherapy [EBRT] plus concomitant temozolomide and 6 cycles of adjuvant temozolomide chemotherapy). The primary outcome is median progression-free survival, secondary outcomes are median OS, occurrence of radiation induced acute (<3 wk), early delayed (<3 mo), and late (>3 mo post-SRS) neurotoxicity and incidence of symptomatic radionecrosis. EXPECTED OUTCOMES We expect to detect efficacy and safety signals by the immediate application of SRS to standard-of-care therapy in newly diagnosed GBM. DISCUSSION Early postoperative SRS to areas of residual tumor could bridge the therapeutic gap between surgery and adjuvant therapies.

scholarly journals A Nomogram Predicts Individual Prognosis in Patients With Newly Diagnosed Glioblastoma by Integrating the Extent of Resection of Non-Enhancing Tumors

2020 ◽  
Vol 10 ◽  
Author(s):  
Zhe Zhang ◽  
Zeping Jin ◽  
Dayuan Liu ◽  
Yang Zhang ◽  
Chunzhao Li ◽  
...  
Keyword(s):  
Dna Methyltransferase ◽  
Proportional Hazards Model ◽  
Predictive Accuracy ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Extent Of Resection ◽  
Cox Proportional Hazards Model ◽  
Newly Diagnosed ◽  
Discriminative Ability ◽  
Newly Diagnosed Glioblastoma

BackgroundThe extent of resection of non-contrast enhancing tumors (EOR-NCEs) has been shown to be associated with prognosis in patients with newly diagnosed glioblastoma (nGBM). This study aimed to develop and independently validate a nomogram integrated with EOR-NCE to assess individual prognosis.MethodsData for this nomogram were based on 301 patients hospitalized for nGBM from October 2011 to April 2019 at the Beijing Tiantan Hospital, Capital Medical University. These patients were randomly divided into derivation (n=181) and validation (n=120) cohorts at a ratio of 6:4. To evaluate predictive accuracy, discriminative ability, and clinical net benefit, concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were calculated for the extent of resection of contrast enhancing tumor (EOR-CE) and EOR-NCE nomograms. Comparison between these two models was performed as well.ResultsThe Cox proportional hazards model was used to establish nomograms for this study. Older age at diagnosis, Karnofsky performance status (KPS)&lt;70, unmethylated O6-methylguanine-DNA methyltransferase (MGMT) status, wild-type isocitrate dehydrogenase enzyme (IDH), and lower EOR-CE and EOR-NCE were independent factors associated with shorter survival. The EOR-NCE nomogram had a higher C-index than the EOR-CE nomogram. Its calibration curve for the probability of survival exhibited good agreement between the identical and actual probabilities. The EOR-NCE nomogram showed superior net benefits and improved performance over the EOR-CE nomogram with respect to DCA and ROC for survival probability. These results were also confirmed in the validation cohort.ConclusionsAn EOR-NCE nomogram assessing individualized survival probabilities (12-, 18-, and 24-month) for patients with nGBM could be useful to provide patients and their relatives with health care consultations on optimizing therapeutic approaches and prognosis.

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