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

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.

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Increased Subventricular Zone Radiation Dose Correlates With Survival in Glioblastoma Patients After Gross Total Resection

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2013.02.014 ◽

2013 ◽

Vol 86 (4) ◽

pp. 616-622 ◽

Cited By ~ 74

Author(s):

Linda Chen ◽

Hugo Guerrero-Cazares ◽

Xiaobu Ye ◽

Eric Ford ◽

Todd McNutt ◽

...

Keyword(s):

Radiation Dose ◽

Subventricular Zone ◽

Gross Total Resection ◽

Total Resection

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135 Pediatric Supratentorial Ependymoma: Clinical, Radiographic and Molecular Analysis

Neurosurgery ◽

10.1093/neuros/nyx417.135 ◽

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.

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Gross-total resection outcomes in an elderly population with glioblastoma: a SEER-based analysis

Journal of Neurosurgery ◽

10.3171/2013.9.jns13877 ◽

2014 ◽

Vol 120 (1) ◽

pp. 31-39 ◽

Cited By ~ 57

Author(s):

Abraham Noorbakhsh ◽

Jessica A. Tang ◽

Logan P. Marcus ◽

Brandon McCutcheon ◽

David D. Gonda ◽

...

Keyword(s):

Overall Survival ◽

Cox Regression ◽

Age Groups ◽

Gross Total Resection ◽

Subtotal Resection ◽

Total Resection ◽

Patient Age ◽

Surgical Practice ◽

Survival Difference ◽

Patient Âgé

Object There is limited information on the relationship between patient age and the clinical benefit of resection in patients with glioblastoma. The purpose of this study was to use a population-based database to determine whether patient age influences the frequency that gross-total resection (GTR) is performed, and also whether GTR is associated with survival difference in different age groups. Methods The authors identified 20,705 adult patients with glioblastoma in the Surveillance, Epidemiology, and End Results (SEER) registry (1998–2009). Surgical practice patterns were defined by the categories of no surgery, subtotal resection (STR), and GTR. Kaplan-Meier and multivariate Cox regression analyses were used to assess the pattern of surgical practice and overall survival. Results The frequency that GTR was achieved in patients with glioblastoma decreased in a stepwise manner as a function of patient age (from 36% [age 18–44 years] to 24% [age ≥ 75]; p < 0.001). For all age groups, glioblastoma patients who were selected for and underwent GTR showed a 2- to 3-month improvement in overall survival (p < 0.001) relative to those who underwent STR. These trends remained true after a multivariate analysis that incorporated variables including ethnicity, sex, year of diagnosis, tumor size, tumor location, and radiotherapy status. Conclusions Gross-total resection is associated with improved overall survival, even in elderly patients with glioblastoma. As such, surgical decisions should be individually tailored to the patient rather than an adherence to age as the sole clinical determinant.

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Multivariate Analysis of Associations between Clinical Sequencing and Outcome in Glioblastoma

Neuro-Oncology Advances ◽

10.1093/noajnl/vdac002 ◽

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.

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

World Neurosurgery ◽

10.1016/j.wneu.2020.06.029 ◽

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

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

Neuro-Oncology Practice ◽

10.1093/nop/npx025 ◽

2017 ◽

Vol 5 (2) ◽

pp. 96-103 ◽

Cited By ~ 1

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.

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

Neuro-Oncology ◽

10.1093/neuonc/noab195.049 ◽

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 <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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Long-term efficacy of surgical resection with or without adjuvant therapy for treatment of secondary glioblastoma in adults

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa098 ◽

2020 ◽

Vol 2 (1) ◽

Author(s):

Ruoyu Huang ◽

Guanzhang Li ◽

Yiming Li ◽

Yinyan Wang ◽

Pei Yang ◽

...

Keyword(s):

Survival Analysis ◽

Prognostic Factors ◽

Adjuvant Therapy ◽

Clinical Outcomes ◽

Cox Regression ◽

Postoperative Radiotherapy ◽

Gross Total Resection ◽

Subtotal Resection ◽

Total Resection ◽

Secondary Glioblastoma

Abstract Background There are limited studies on treatment strategies and associated clinical outcomes in patients with secondary glioblastoma (sGBM). We sought to investigate the prognostic factors and treatment decisions in a retrospective cohort of patients with sGBM. Methods One hundred and seventy-one patients with sGBM who met the screening criteria were included in this study. Kaplan–Meier survival analysis and Cox survival analysis were used to detect prognostic factors. R (v3.5.0) and SPSS software (v25.0, IBM) were used to perform statistical analyses. Results The median overall survival was 303 days (range 23–2237 days) and the median progression-free survival was 229 days (range 33–1964 days) in patients with sGBM. When assessing the relationship between adjuvant treatment outcome and extent of resection (EOR), the results showed that patients underwent gross total resection can benefit from postoperative radiotherapy and chemotherapy, but not in patients underwent subtotal resection. In addition, we also found that aggressive adjuvant therapy can significantly improve clinical outcomes of IDH1-mutated patients but no significant prognostic value for IDH1-wildtyped patients. The univariate Cox regression analyses demonstrated that EOR, adjuvant therapy, and postoperative Karnofsky Performance Scores were prognostic factors for patients with sGBM, and multivariate COX analysis confirmed that adjuvant therapy and EOR were independent prognostic factors. Conclusions For patients with sGBM, aggressive postoperative adjuvant therapy after gross total resection was recommended. However, we did not detect a benefit in IDH1-wildtype patients in our cohort.

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Tumor control after surgery for spinal myxopapillary ependymomas: distinct outcomes in adults versus children

Journal of Neurosurgery Spine ◽

10.3171/2013.6.spine12927 ◽

2013 ◽

Vol 19 (4) ◽

pp. 471-476 ◽

Cited By ~ 46

Author(s):

William B. Feldman ◽

Aaron J. Clark ◽

Michael Safaee ◽

Christopher P. Ames ◽

Andrew T. Parsa

Keyword(s):

Recurrence Rate ◽

Adjuvant Radiotherapy ◽

Pediatric Patients ◽

Cauda Equina ◽

Extent Of Resection ◽

Gross Total Resection ◽

Tumor Control ◽

Recurrence Rates ◽

Total Resection ◽

Who Grade

Object Myxopapillary ependymomas (MPEs) are rare WHO Grade I tumors found in the conus medullaris, cauda equina, and filum terminale. Treatment generally consists of resection with or without adjuvant radiotherapy. Evidence-based guidelines for surgical management are lacking due to the rarity of this tumor. Methods An English-language PubMed search was performed using the key words “myxopapillary” and “ependymoma.” Reports describing fewer than 3 patients or those lacking data on the extent of resection or radiotherapy were excluded. A total of 28 articles describing 475 patients met the authors' inclusion criteria. Patients were grouped by extent of resection and whether or not they underwent adjuvant radiotherapy. Differences in recurrence rates were assessed by chi-square test. Results The overall recurrence rate was 15.5% in patients treated by gross-total resection (GTR) and 32.6% in patients treated by subtotal resection (STR), irrespective of whether they underwent adjuvant therapy (p < 0.001). Regardless of the extent of resection, adjuvant radiotherapy was not associated with a decrease in recurrence rates. The overall recurrence rate was 15.6% in patients who underwent GTR and radiotherapy compared with 15.9% in patients who underwent GTR alone (p = 0.58), and it was 29.3% in patients who underwent STR and radiotherapy compared with 35.1% in those who underwent STR alone (p = 0.53). The difference between recurrence rates for patients who underwent GTR alone versus STR and radiotherapy was statistically significant (p = 0.02). Subgroup analysis demonstrated significantly higher recurrence rates in pediatric patients compared with adults (40.5% vs 23.4%, respectively; p = 0.02). Even in the setting of GTR alone, recurrence rates were higher in pediatric patients (65% vs 7.6%; p < 0.001). Conclusions Gross-total resection alone is associated with decreased recurrence rates compared with STR with or without radiotherapy. The authors' results suggest that treatment goals should include attempted GTR whenever possible. The observation that children benefitted from radiation therapy to a greater extent than did adults suggests that biological differences between tumors in these patient populations warrants more rigorous scientific studies.

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