scholarly journals Multivariate Analysis of Associations between Clinical Sequencing and Outcome in Glioblastoma

2022 ◽  
Author(s):  
Peter H Yang ◽  
Yu Tao ◽  
Jingqin Luo ◽  
Mounica Paturu ◽  
Hsiang-Chih Lu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Next Generation Sequencing ◽  
High Throughput ◽  
Prognostic Value ◽  
Extent Of Resection ◽  
Gross Total Resection ◽  
Total Resection ◽  
Mutant Genes ◽  
Generation Sequencing

Abstract Background Many factors impact survival in patients with glioblastoma, including age, Karnofsky Performance Status, post-operative chemoradiation, IDH1/2 mutation status, MGMT promoter methylation status, and extent of resection. High-throughput next generation sequencing is a widely available diagnostic tool, but the independent impact of tumors harboring specific mutant genes on survival and the efficacy of extent of resection are not clear. Methods We utilized a widely available diagnostic platform (FoundationOne CDx) to perform high-throughput next generation sequencing on 185 patients with newly diagnosed glioblastoma in our tertiary care center. We performed multivariate analysis to control for clinical parameters with known impact on survival to elucidate the independent prognostic value of prevalent mutant genes and the independent impact of gross total resection. Results When controlling for factors with known prognostic significance including IDH1/2 mutation and after multiple comparisons analysis, CDKN2B and EGFR mutations were associated with reduced overall survival while PTEN mutation was associated with improved overall survival. Gross total resection, compared to other extent of resection, was associated with improved overall survival in patients with tumors harboring mutations in CDKN2A, CDKN2B, EGFR, PTEN, TERT promoter, and TP53. All patients possessed at least one of these six mutant genes. Conclusions This study verifies the independent prognostic value of several mutant genes in glioblastoma. Six commonly found mutant genes were associated with improved survival when gross total resection was achieved. Thus, even when accounting for known predictors of survival and multiple mutant gene comparisons, extent of resection continues to be strongly associated with survival.

scholarly journals P14.116 Lack of correlation between incidental ipsilateral subventricular zone radiation dose and overall survival in glioblastoma patients

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii95-iii96
Author(s):  
G Hallaert ◽  
H Pinson ◽  
D Vanhauwaert ◽  
L Staelens ◽  
C Vandenbroecke ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Dose ◽  
Subventricular Zone ◽  
Cox Regression ◽  
Extent Of Resection ◽  
Gross Total Resection ◽  
Karnofsky Performance Score ◽  
Mgmt Methylation ◽  
Gene Methylation ◽  
Total Resection

Abstract BACKGROUND The role of the subventricular zone (SVZ) in glioblastoma (GBM) is controversial. The past decade, several retrospective studies were published concerning the potential correlation between incidental radiation of the SVZ and survival in GBM patients. Although these publications showed conflicting results, a large study claimed an overall survival (OS) benefit for GBM patients after gross total resection if the ipsilateral SVZ received a higher dose than 40 Gy. We investigated this finding in our own population of GBM patients. MATERIAL AND METHODS A multicenter retrospective study was conducted including all adult patients treated for histologically proven GBM from 2003–2014. All patients received 60 Gy radiation therapy after surgery and concomitant temozolomide. Exclusion criteria were: infratentorial GBM; presence of other neoplasm(s); known previous history of low grade glioma; incomplete radiotherapy data. Demographic data were collected from the patient charts. O6-methylguanin-DNA-methyltransferase-promotor-gene (MGMT) methylation was determined on stored tumor samples using semi quantitative methylation-specific polymerase chain reaction (qMSP). SVZs (ipsilateral, contralateral and bilateral) were contoured on radiotherapy treatment plans. Multivariate Cox regression analysis was used to study the correlation between incidental SVZ radiation dose and OS. Age (cut-off 65 years), Karnofsky Performance Score (KPS; cut-off 70), methylation of the MGMT-promotor gene and extent of resection (biopsy; subtotal resection, groos total resection) were used as covariates. Patients alive at time of database closure were censored for analysis. RESULTS 183 patients were eligible for analysis. Mean age at diagnosis was 62 years, with an average KPS of 70. In 34% of patients, gross total resection (GTR) was achieved, while in 28% only a biopsy was taken. MGMT-promoter gene methylation was present in 39% of cases. Median ipsilateral, contralateral and bilateral SVZ doses were 46.1 Gy, 25.35 Gy and 34.8 Gy resp. In multivariate Cox regression, all covariates (age, P = 0.011; KPS, P = 0.001; MGMT methylation, P = 0.000; extent of resection, P = 0.000) were significantly associated with OS. Mean OS was 23 months, but median OS 13 months. There was no correlation between incidental radiation dose of the ipsilateral SVZ and OS for 46 Gy or 40 Gy (hazard ratio 0.82 (0.6–1.1), P = 0.225 and 0.89 (0.63–1.23), P = 0.52 resp.) for the whole group nor for the subgroup of gross total resection. CONCLUSION In this group of GBM patients, age, KPS, extent of resection and methylation of the MGMT-promotor gene were significantly correlated with OS, but not incidental ipsilateral SVZ radiation dose. The previously published positive results may result from bias, possibly arising from lack of inclusion of MGMT-promotor gene methylation as an important independent prognostic factor.

Real-World Data From a Molecular Tumor Board: Improved Outcomes in Breast and Gynecologic Cancers Patients With Precision Medicine

2022 ◽  
Author(s):  
Lindsey M. Charo ◽  
Ramez N. Eskander ◽  
Jason Sicklick ◽  
Ki Hwan Kim ◽  
Hyo Jeong Lim ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Next Generation Sequencing ◽  
Tumor Board ◽  
Breast Cancers ◽  
Next Generation ◽  
Overall Response ◽  
Improved Outcomes ◽  
Molecular Tumor Board ◽  
Generation Sequencing

PURPOSE Next-generation sequencing is increasingly used in gynecologic and breast cancers. Multidisciplinary Molecular Tumor Board (MTB) may guide matched therapy; however, outcome data are limited. We evaluate the effect of the degree of matching of tumors to treatment as well as compliance to MTB recommendations on outcomes. METHODS Overall, 164 patients with consecutive gynecologic and breast cancers presented at MTB were assessed for clinicopathologic data, next-generation sequencing results, MTB recommendations, therapy received, and outcomes. Matching score (MS), defined as percentage of alterations targeted by treatment over total pathogenic alterations, and compliance to MTB recommendations were analyzed in context of oncologic outcomes. RESULTS Altogether, 113 women were evaluable for treatment after MTB; 54% received matched therapy. Patients with MS ≥ 40% had higher overall response rate (30.8% v 7.1%; P = .001), progression-free survival (PFS; hazard ratio [HR] 0.51; 95% CI, 0.31 to 0.85; P = .002), and a trend toward improved overall survival (HR 0.64; 95% CI, 0.34 to 1.25; P = .082) in univariate analysis. The PFS advantage remained significant in multivariate analysis (HR 0.5; 95% CI, 0.3 to 0.8; P = .006). Higher MTB recommendation compliance was significantly associated with improved median PFS (9.0 months for complete; 6.0 months for partial; 4.0 months for no compliance; P = .004) and overall survival (17.1 months complete; 17.8 months partial; 10.8 months none; P = .046). Completely MTB-compliant patients had higher MS ( P < .001). In multivariate analysis comparing all versus none MTB compliance, overall response (HR 9.5; 95% CI, 2.6 to 35.0; P = .001) and clinical benefit (HR 8.8; 95% CI, 2.4 to 33.2; P = .001) rates were significantly improved with higher compliance. CONCLUSION Compliance to MTB recommendations resulted in higher degrees of matched therapy and correlates with improved outcomes in patients with gynecologic and breast cancers.

135 Pediatric Supratentorial Ependymoma: Clinical, Radiographic and Molecular Analysis

Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 231-231
Author(s):  
Jock Lillard ◽  
Paul Klimo ◽  
Garrett Thomas Venable
Keyword(s):  
Overall Survival ◽  
Molecular Analysis ◽  
Progression Free Survival ◽  
Tumor Grade ◽  
Extent Of Resection ◽  
Gross Total Resection ◽  
Total Resection ◽  
Free Survival ◽  
Favorable Prognosis ◽  
Supratentorial Ependymoma

Abstract INTRODUCTION Recent molecular analyses support a behavioral and clinical distinction between supratentorial and infratentorial ependymomas, with supratentorial tumors, in general, having a more favorable prognosis. The goal of this study was todescribe our experience managing supratentorial ependymoma in children. METHODS A prospectively maintained neurooncology database was queried to identify cases ofsupratentorial ependymoma treated atSt Jude Children's Research Hospital (SJCRH) and LeBonheur from 1990 through December 31, 2014. Clinical, operative, and radiographic information were reviewed. Outcome measures, determined by review of clinic notes and subsequent imaging, included extent of resection, progression free survival (PFS), overall survival (OS), recurrence of disease and method of post-failure treatment, seizures, requirement of anti-seizure medications, hydrocephalus requiring shunt placement, and death.Detection ofthe C11or95-RELA fusion or rearrangement was performed using iFISH in those patients whose tumor tissue was still available. RESULTS >Seventy-four cases (42% male) of supratentorial ependymoma were identified. Median age at diagnosis was 6.8 years. In total, 59 (79.7%) of 74 patients underwent gross total resection (GTR). Overall survival was a median of 7.4 years. Fifteen patients died of disease. Progression free survival was a median of 3.6 years. Eighty percent of those children whose initial resection was subtotal developed recurrence compared to 50.8% in those who had a GTR. For those patients that recurred, all 42 received further treatment, including further resection, chemotherapy and radiation. Molecular analysis was available for 52 patients (70.3%). Age less than 3, gross total resection, and tumor grade were not associated with improved PFS or OS. Absence of C11-or95-RLEA fusion was associated with a significantly worse PFS, although OS was similar. CONCLUSION Supratentorial ependymoma often have a more favorable prognosis compared toinfratentorial variants. Like many pediatric tumors, supratentorial ependymomas can bestratified based on clinical, surgical and possibly molecular variables.

Next-Generation Sequencing: An Emerging Tool for Drug Designing

2019 ◽  
Vol 25 (31) ◽  
pp. 3350-3357 ◽  
Author(s):  
Pooja Tripathi ◽  
Jyotsna Singh ◽  
Jonathan A. Lal ◽  
Vijay Tripathi
Keyword(s):  
Next Generation Sequencing ◽  
High Throughput ◽  
Large Scale ◽  
Massively Parallel Sequencing ◽  
Genomic Research ◽  
Biological Research ◽  
Next Generation ◽  
Human Welfare ◽  
Drug Designing ◽  
Generation Sequencing

Background: With the outbreak of high throughput next-generation sequencing (NGS), the biological research of drug discovery has been directed towards the oncology and infectious disease therapeutic areas, with extensive use in biopharmaceutical development and vaccine production. Method: In this review, an effort was made to address the basic background of NGS technologies, potential applications of NGS in drug designing. Our purpose is also to provide a brief introduction of various Nextgeneration sequencing techniques. Discussions: The high-throughput methods execute Large-scale Unbiased Sequencing (LUS) which comprises of Massively Parallel Sequencing (MPS) or NGS technologies. The Next geneinvolved necessarily executes Largescale Unbiased Sequencing (LUS) which comprises of MPS or NGS technologies. These are related terms that describe a DNA sequencing technology which has revolutionized genomic research. Using NGS, an entire human genome can be sequenced within a single day. Conclusion: Analysis of NGS data unravels important clues in the quest for the treatment of various lifethreatening diseases and other related scientific problems related to human welfare.

Letter to the Editor Regarding “Association Between Facility Volume and Overall Survival for Patients with Grade II Meningioma after Gross Total Resection”

2020 ◽  
Vol 142 ◽  
pp. 537
Author(s):  
Gustavo Correa Lordelo ◽  
Victor Salviato Nespoli ◽  
Iuri Santana Neville ◽  
Wellingson Silva Paiva
Keyword(s):  
Overall Survival ◽  
Gross Total Resection ◽  
Total Resection ◽  
Letter To The Editor ◽  
Grade Ii

scholarly journals Advances in genetics and molecular breeding of three legume crops of semi-arid tropics using next-generation sequencing and high-throughput genotyping technologies

2012 ◽  
Vol 37 (5) ◽  
pp. 811-820 ◽  
Author(s):  
Rajeev K Varshney ◽  
Himabindu Kudapa ◽  
Manish Roorkiwal ◽  
Mahendar Thudi ◽  
Manish K Pandey ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
High Throughput ◽  
Molecular Breeding ◽  
Next Generation ◽  
Legume Crops ◽  
Generation Sequencing ◽  
Semi Arid

scholarly journals Profound hearing loss following surgery in pediatric patients with posterior fossa low-grade glioma

2017 ◽  
Vol 5 (2) ◽  
pp. 96-103 ◽  
Author(s):  
Yahya Ghazwani ◽  
Ibrahim Qaddoumi ◽  
Johnnie K Bass ◽  
Shengjie Wu ◽  
Jason Chiang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Posterior Fossa ◽  
Extent Of Resection ◽  
Tumor Location ◽  
Low Grade Glioma ◽  
Gross Total Resection ◽  
Subtotal Resection ◽  
Low Grade ◽  
Total Resection ◽  
Profound Hearing Loss

Abstract Background Hearing loss may occur in patients with posterior fossa low-grade glioma who undergo surgery. Methods We retrospectively reviewed 217 patients with posterior fossa low-grade glioma, including 115 for whom results of hearing tests performed after surgery and before chemotherapy or radiation therapy were available. We explored the association of UHL with age at diagnosis, sex, race, tumor location, extent of resection, posterior fossa syndrome, ventriculoperitoneal shunt placement, and histology. Results Of the 115 patients, 15 (13.0%: 11 male, 6 black, 8 white, 1 multiracial; median age 7 years [range, 1.3–17.2 years]) had profound UHL after surgery alone or before receiving ototoxic therapy. Median age at tumor diagnosis was 6.8 years (range, 0.7–14.1 years), and median age at surgery was 6.8 years (range, 0.7–14.1 years). Patients with UHL had pathology characteristic of pilocytic astrocytoma (n = 10), ganglioglioma (n = 4), or low-grade astrocytoma (n = 1). Of these 15 patients, 4 underwent biopsy, 1 underwent gross total resection, 1 underwent near-total resection, and 9 underwent subtotal resection. UHL was more frequent in black patients than in white patients (OR 7.3, P = .007) and less frequent in patients who underwent gross total resection or near-total resection than in those who underwent subtotal resection (OR 0.11, P = .02). Conclusions Children undergoing surgery for posterior fossa low-grade glioma are at risk for UHL, which may be related to race or extent of resection. These patients should receive postoperative audiologic testing, as earlier intervention may improve outcomes.

scholarly journals Extent of resection in glioblastoma: a 10-year local survival analysis

2021 ◽  
Vol 23 (Supplement_4) ◽  
pp. iv19-iv19
Author(s):  
Theodore Hirst ◽  
Patrick McAleavey ◽  
Tom Flannery
Keyword(s):  
Neurological Deficit ◽  
Survival Benefit ◽  
Extent Of Resection ◽  
Cox Proportional Hazards ◽  
Partial Resection ◽  
Gross Total Resection ◽  
Molecular Profile ◽  
Total Resection ◽  
Local Survival ◽  
The Impact

Abstract Aims The impact on extent of resection (EOR) in glioblastoma has been well documented. It is clear that gross-total resection (GTR) confers best overall survival (OS), however the minimum EOR required to confer a survival benefit over biopsy is debated. Recent studies favour partial resection (PR) over biopsy for IDH-wildtype, MGMT-unmethylated tumours. We describe our experiences locally with these principles in mind. Method Retrospective evaluation of a single surgeon cohort. All patients over 18 years old, undergoing a surgical treatment for histologically confirmed GBM in the stated period were included. We collected information on demographics, tumour volume, EOR, complications, adjuvant therapies, molecular profile, and OS. We used log rank tests and Cox Proportional Hazards Models to identify factors associated with OS. Results The patient and tumour characteristics of our cohort were similar to those documented in the literature. The mean age was 56.6 years. 72 patients underwent biopsy and 202 had debulking surgery. Median OS was 11 months. Of those debulked, gross-total resection was achieved in 41 patients (20%); associated median OS was 29 months. Patients receiving partial resection (defined as EOR &lt;80%) had no clear survival benefit over patients undergoing biopsy (median OS 6 vs 5 months) but had a higher rate of post-op neurological deficit (3% vs 12%). Tumour molecular profile appeared to influence survival outcome in a manner comparable to worldwide experience. Conclusion In our experience, partial resection is not a justifiable surgical aim in the typical glioblastoma cohort. The limited benefit that it may confer over biopsy appears to be outweighed by the risk of neurological deficit that affects quality and probably quantity of life. This finding applies to our glioblastoma population in general as well as those specifically with an MGM-unmethylated tumour.

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