scholarly journals NCOG-76. BASELINE COGNITIVE ASSESSMENT IN GLIOMA PATIENTS WITH MGMT PROMOTOR METHYLATION AND/OR 1p19q CODELETION

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii146-ii146
Author(s):  
Sydney Park ◽  
Abigail Giles ◽  
Grace Liberatore ◽  
Katherine Morgan ◽  
Cynthia DeBruhl ◽  
...  
Keyword(s):  
Executive Functioning ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Neuropsychological Testing ◽  
Methylation Status ◽  
Cognitive Status ◽  
Term Survival ◽  
1P19q Codeletion ◽  
Karnofsky Performance Status Score ◽  
Chemotherapy Administration

Abstract INTRODUCTION Methylguanine methyltransferase (MGMT) methylation status is associated with better overall survival while 1p19q co-deletion is associated with long-term survival. Cognitive dysfunction is a common complication of brain tumors and treatment; however, information regarding the relationship between MGMT status, 1p19q codeletion, and cognition is limited. METHOD Baseline neuropsychological testing was performed in patients with malignant glioma prior to radiation and/or chemotherapy administration. A retrospective data analysis was conducted. We calculated composite and subdomain scores for attention/executive functioning, memory, and language in patients with or without MGMT promotor methylation and/or 1p19q codeletion. RESULTS Thirty-eight patients (Age M = 48.73 ± 14.98; 50% female) diagnosed with glioma (29% grade II, 16% grade III, 21% grade IV; Karnofsky Performance Status score (KPS) M = 88.75 ± 14.24) were selected from a retrospective. Memory was marginally significant, such that methylated participants performed better on memory tasks than the unmethylated group (p = .053). Independent samples t-test revealed no significant differences between either marker across the overall cognitive composite (methylated M = 41.35; unmethylated: M = 39.91; p = .955; 1p19q co-deleted: M = 50.94; 1p19q intact: M = 43.66; p = .158) and subdomains attention/executive functioning (p = .585; p = .157) and language (p = .581; p = .765). Logistic regression showed MGMT does not predict cognitive status (p =.052) and there were not enough cases to complete the model with 1p19q. CONCLUSION MGMT status may be correlated with baseline cognitive status as MGMT methylated patients had better memory scores than their unmethylated counterparts. We did not find any significant association between the remaining cognitive domains and MGMT or 1p19q although sample size is a significant limitation. These results suggest further assessment of changes in cognition during treatment through serial neuropsychological testing of glioma populations with defined marker status is warranted.

scholarly journals A-094 Isocitrate Dehydrogenase Status and Cognition in Glioma Patients

2020 ◽  
Vol 35 (6) ◽  
pp. 887-887
Author(s):  
Park S ◽  
Giles A ◽  
Liberatore M ◽  
Morgan K ◽  
Debruhl C ◽  
...  
Keyword(s):  
Isocitrate Dehydrogenase ◽  
Karnofsky Performance Status ◽  
Brain Connectivity ◽  
Performance Status ◽  
Improve Patient Care ◽  
Care Patient ◽  
Cognitive Status ◽  
Neuropsychological Battery ◽  
Karnofsky Performance Status Score ◽  
The Impact

Abstract Objective In gliomas, isocitrate dehydrogenase-wildtype (IDH-wt) is associated with poorer prognosis and is correlated with lower brain connectivity, implicating cognitive impairment. Little is known about the impact of IDH-wt on cognition. This study aimed to explore the relationship between IDH-wt and cognition. Method Thirty-eight patients (Age M = 48.73 ± 14.98; 50% female) diagnosed with a glioma (29% grade II, 16% grade III, 21% grade IV; Karnofsky Performance Status score (KPS) M = 88.75 ± 14.24) were selected from a retrospective data cohort. 34.2% of patients had left hemisphere tumors, 34.2% of tumors were in the frontal lobes, and 15.8% were temporal lobe tumors. Patients were assessed via abbreviated neuropsychological battery following surgical resection prior to radiation and/or chemotherapy. Results The overall cognitive composite was not statistically significant via independent samples t-test (IDH-wt+: M = 42.37; IDH-wt-: M = 39.29; p = 0.897). Subdomains for attention/executive functioning (p = 0.625), memory (p = 0.923), and language (p = 0.501) were not significantly different. Logistic regression was conducted to investigate how IDH status predicts cognitive status. The coefficient has a Wald statistic equal to 0.042 which is not significant (critical value of 0.837) [df = 1]. Of those with IDH-wt+, 57% were impaired and 43% remained intact. Conclusion We did not find a significant association between IDH status and cognition though sample size is a significant limitation of the present study. More investigations are needed given it is possible that cognitive performance is related to IDH status and knowledge in this area could improve patient care/patient education.

PATH-16. EVALUATION OF SEX-BASED DIFFERENCES IN CLINICAL OUTCOMES AND TUMOR GENOMICS IN PATIENTS WITH NEWLY DIAGNOSED IDH-WILDTYPE GLIOBLASTOMA RECEIVING CHEMORADIATION

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi118-vi118
Author(s):  
Diana Shi ◽  
Mary Jane Lim-Fat ◽  
Amin Nassar ◽  
Jared Woods ◽  
Gilbert Youssef ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Methylation Status ◽  
Multivariable Analysis ◽  
Extent Of Resection ◽  
Hazard Ratio ◽  
Newly Diagnosed ◽  
Loss Of Function ◽  
Female Sex

Abstract BACKGROUND We evaluated sex-based differences in clinical outcomes and tumor genomics in patients with newly-diagnosed GBM. METHODS We reviewed 665 IDH-wild type GBM patients with Karnofsky Performance Status (KPS) ≥60 treated at our institution from 2010-2019 including; 585 patients with targeted exome sequencing of 447 cancer associated genes (OncoPanel). Deleterious mutations were defined as homozygous deletions or loss of function mutations of known tumor suppressors (as reported in TCGA, ≥ 3 times in the COSMIC database, or predicted as “damaging” in SIFT and/or “probably damaging” in Polyphen 2) or known oncogenic mutations in proto-oncogenes (reported in TCGA or ≥ 3 times in COSMIC). RESULTS There were 384 (57.7%) males and 281 (42.3%) females. Median OS was 22.5 months for females and 19.3 months for males (hazard ratio [HR] 0.81, 95% CI 1.03-1.48, p = 0.02). On multivariable analysis adjusted for age, KPS ≥90, extent of resection, and MGMT methylation status, female sex (adjusted hazard ratio 0.78, 95% CI [0.64-0.95], p = 0.015) was associated with improved OS. Superior OS in females was observed in MGMT-unmethylated patients (HR 0.69, 95% CI [0.54-0.90], p = 0.005) but not MGMT-methylated patients. Thirteen genes were deleteriously altered in ≥5% of our cohort: CDK4 (12.1% male vs. 7.8% female), CDKN2A (46.5% vs. 45.7%), CDKN2B (41.8% vs. 43.3%), EGFR (34.7% vs. 40.0%, MTAP (18.2% vs. 18.8%), NF1 (11.5% vs. 9.4%), PTEN (28.2% vs. 29.8%), TP53 (28.2% vs. 30.2%), RB1 (5.6% vs. 6.5%), MDM4 (6.2% vs. 5.7%), ATM (5.9% vs. 3.7%), MDM2 (7.4% vs. 4.1%), PIK3R1 (6.2% vs. 4.1%). There were no differences in frequency of mutations in these individual genes between males and females (χ 2 [1, N=585] = 0.05-2.86, p = 0.09-0.86). CONCLUSIONS Female sex is associated with improved survival. We did not identify sex-based differences in deleterious genomic alterations amongst commonly altered genes in GBM.

Radiosurgery for parasagittal and parafalcine meningiomas

2013 ◽  
Vol 119 (4) ◽  
pp. 871-877 ◽  
Author(s):  
Dale Ding ◽  
Zhiyuan Xu ◽  
Ian T. McNeill ◽  
Chun-Po Yen ◽  
Jason P. Sheehan
Keyword(s):  
Cox Regression ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Tumor Control ◽  
Who Grade ◽  
Tumor Control Rate ◽  
Karnofsky Performance Status Score ◽  
Status Score ◽  
Performance Status Score

Object Parasagittal and parafalcine (PSPF) meningiomas represent the second most common location for intracranial meningiomas. Involvement of the superior sagittal sinus or deep draining veins may prevent gross-total resection of these tumors without significant morbidity. The authors review their results for treatment of PSPF meningiomas with radiosurgery. Methods The authors retrospectively reviewed the institutional review board–approved University of Virginia Gamma Knife database and identified 65 patients with 90 WHO Grade I parasagittal (59%) and parafalcine (41%) meningiomas who had a mean MRI follow-up of 56.6 months. The patients' mean age was 57 years, the median preradiosurgery Karnofsky Performance Status score was 80, and the median initial tumor and treatment volumes were 3 and 3.7 cm3, respectively. The median prescription dose was 15 Gy, isodose line was 40%, and the number of isocenters was 5. Kaplan-Meier analysis was used to determine progression-free survival (PFS). Univariate and multivariate Cox regression analyses were used to identify factors associated with PFS. Results The median overall PFS was 75.6 months. The actuarial tumor control rate was 85% at 3 years and 70% at 5 years. Parasagittal location, no prior resection, and younger age were found to be independent predictors of tumor PFS. For the 49 patients with clinical follow-up (mean 70.8 months), the median postradiosurgery Karnofsky Performance Status score was 90. Symptomatic postradiosurgery peritumoral edema was observed in 4 patients (8.2%); this group comprised 3 patients (6.1%) with temporary and 1 patient (2%) with permanent clinical sequelae. Two patients (4.1%) died of tumor progression. Conclusions Radiosurgery offers a minimally invasive treatment option for PSPF meningiomas, with a good tumor control rate and an acceptable complication rate comparable to most surgical series.

scholarly journals Survival benefits of hypofractionated radiotherapy combined with temozolomide or temozolomide plus bevacizumab in elderly patients with glioblastoma aged ≥ 75 years

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Makoto Ohno ◽  
Yasuji Miyakita ◽  
Masamichi Takahashi ◽  
Hiroshi Igaki ◽  
Yuko Matsushita ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Dna Methyltransferase ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Methylation Status ◽  
Progression Free Survival ◽  
Promoter Hypermethylation ◽  
Hypofractionated Radiotherapy ◽  
Methylguanine Dna Methyltransferase ◽  
Grade 3

Abstract Background and purpose The purpose of this study was to evaluate the outcomes of elderly patients (aged ≥75 years) with newly diagnosed glioblastoma (GBM), who were treated with hypofractionated radiotherapy comprising 45 Gy in 15 fractions combined with temozolomide (TMZ) or TMZ and bevacizumab (TMZ/Bev). Materials and methods Between October 2007 and August 2018, 30 patients with GBM aged ≥75 years were treated with hypofractionated radiotherapy consisting of 45 Gy in 15 fractions. Twenty patients received TMZ and 10 received TMZ/Bev as upfront chemotherapy. O-6-methylguanine DNA methyltransferase (MGMT) promoter methylation status was analyzed by pyrosequencing. The cutoff value of the mean level of methylation at the 16 CpG sites was 16%. Results Median overall survival (OS) and progression-free survival (PFS) were 12.9 months and 9.9 months, respectively. The 1-year OS and PFS rates were 64.7 and 34.7%, respectively. Median OS and PFS did not differ significantly between patients with MGMT promoter hypermethylation (N = 11) and those with hypomethylation (N = 16) (17.4 vs. 11.8 months, p = 0.32; and 13.1 vs. 7.3 months, p = 0.11, respectively). The median OS and PFS were not significantly different between TMZ (N = 20) and TMZ/Bev (N = 10) chemotherapy (median OS: TMZ 12.9 months vs. TMZ/Bev 14.6 months, p = 0.93, median PFS: TMZ 8.5 months vs TMZ/Bev 10.0 months, p = 0.64, respectively). The median time until Karnofsky performance status (KPS) score decreasing below 60 points was 7.9 months. The best radiological responses included 11 patients with a partial response (36.7%). Grade 3/4 toxicities included leukopenia in 15 patients (50%), anorexia in 4 (13.3%), and hyponatremia during concomitant chemotherapy in 3 (10%). Conclusion Our hypofractionated radiotherapy regimen combined with TMZ or TMZ/Bev showed benefits in terms of OS, PFS, and KPS maintenance with acceptable toxicities in elderly patients with GBM aged ≥75 years.

scholarly journals Comparative Analysis of Subventricular Zone Glioblastoma Contact and Ventricular Entry During Resection in Predicting Dissemination, Hydrocephalus, and Survival

Neurosurgery ◽  
2019 ◽  
Vol 85 (5) ◽  
pp. E924-E932 ◽  
Author(s):  
Akshitkumar M Mistry ◽  
Patrick D Kelly ◽  
Jean-Nicolas Gallant ◽  
Nishit Mummareddy ◽  
Bret C Mobley ◽  
...  
Keyword(s):  
Subventricular Zone ◽  
Independent Predictor ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Extent Of Resection ◽  
Outcome Analysis ◽  
Leptomeningeal Dissemination ◽  
Karnofsky Performance Status Score ◽  
Radiation Treatments ◽  
Distant Tumor

Abstract BACKGROUND Ventricular entry during glioblastoma resection and tumor contact with the subventricular zone (SVZ) have both been shown to associate with development of hydrocephalus, leptomeningeal dissemination, distant parenchymal recurrence, and decreased survival. However, prior studies did not analyze these variables together in a single-patient population; therefore, it is unknown which is an independent predictor of these outcomes. OBJECTIVE To conduct a comparative outcome analysis of surgical ventricular entry and SVZ contact by glioblastoma in a retrospective cohort of 232 patients. METHODS Outcomes studied included hydrocephalus, leptomeningeal dissemination, distant tumor recurrences, and progression-free (PFS) and overall (OS) survival. The Cox proportional regression analyses were adjusted for age at diagnosis, preoperative Karnofsky performance status score, extent of resection, temozolomide and radiation treatments, and tumor molecular status (specifically, IDH1/2 mutation and MGMT promoter methylation). RESULTS Surgical ventricular entry, SVZ-contacting glioblastoma, hydrocephalus, leptomeningeal dissemination, and distant recurrences were observed in 85 (36.6%), 114 (49.1%), 19 (8.2%), 78 (33.6%), and 59 (25.4%) patients, respectively. Multivariate, adjusted analysis revealed SVZ tumor contact—but not ventricular entry—associated with hydrocephalus (hazard ratio, HR, 4.20 [1.13-15.7], P = .03), leptomeningeal dissemination (HR 1.93 [1.14-3.28], P = .01), PFS (HR 2.10 [1.53-2.88], P < .001), and OS (HR 1.90 [1.35-2.67], P < .001). Distant recurrences were not associated with either. No interaction between the 2 variables was statistically noted. CONCLUSION SVZ contact by glioblastoma was independently associated with the development of hydrocephalus, leptomeningeal dissemination, and decreased survival. SVZ tumor contact was associated with ventricular entry during surgical resections, which did not independently correlate with these outcomes.

scholarly journals Is Function-Based Resection Using Intraoperative Awake Brain Mapping Feasible and Safe for Solitary Brain Metastases Within Eloquent Areas?

2021 ◽  
Author(s):  
Jean-Baptiste Pelletier ◽  
Alessandro Moiraghi ◽  
Marc Zanello ◽  
Alexandre Roux ◽  
Sophie Peeters ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Solitary Brain Metastasis ◽  
Neurological Condition ◽  
Eloquent Areas ◽  
Karnofsky Performance Status Score ◽  
Status Score ◽  
Performance Status Score

Abstract ObjectiveTo assess feasibility and safety of function-based resection under awake conditions for solitary brain metastasis patients.MethodsRetrospective, observational, single-institution case-control study (2014-2019). Inclusion criteria: adult patients, solitary brain metastasis, supratentorial location within eloquent areas, function-based awake resection. Case matching (1:1) criteria between metastasis group and control group (high-grade gliomas): sex, tumor location, tumor volume, preoperative Karnofsky Performance Status score, age, educational level.ResultsTwenty patients were included. Intraoperatively, all patients were cooperative, no obstacles precluded procedure from being performed. A positive functional mapping was achieved at both cortical and subcortical levels, allowing for a function-based resection in all patients. The case-matched analysis showed that intraoperative and postoperative events were similar, except for a shorter duration of the surgery (p<0.001) and of the awake phase (p<0.001) in the metastasis group. A total resection was performed in 18 cases (90%, including 10 supramarginal resections), and a partial resection was performed in two cases (10%). At three months postoperative months, none of the patients had worsening of their neurological condition or uncontrolled seizures, three patients had an improvement in their seizure control, and seven patients had a Karnofsky Performance Status score increase ≥10 points.ConclusionsFunction-based resection under awake conditions preserving the brain connectivity is feasible and safe in the specific population of solitary brain metastasis patients and allows for high resection rates within eloquent brain areas while preserving the overall and neurological condition of the patients. Awake craniotomy should be considered to optimize outcomes in brain metastases in eloquent areas.

scholarly journals P14.61 Tumor Treating Fields (TTFields) combined with lomustine (CCNU) and temozolomide (TMZ) in newly diagnosed glioblastoma (GBM) patients - a bi-centric analysis

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii81-iii81
Author(s):  
L Lazaridis ◽  
N Schäfer ◽  
T Schmidt ◽  
A Stoppek ◽  
J Weller ◽  
...  
Keyword(s):  
Combined Therapy ◽  
Performance Status ◽  
Methylation Status ◽  
Case Series ◽  
Low Grade ◽  
Newly Diagnosed ◽  
Skin Reactions ◽  
Term Survival ◽  
Tumor Treating Fields ◽  
Newly Diagnosed Glioblastoma

Abstract BACKGROUND TTFields combined with TMZ demonstrated significantly improved PFS, OS and long-term survival in newly diagnosed glioblastoma (ndGBM) patients, compared to TMZ monotherapy in the EF-14 trial; independent of MGMT-promotor methylation-status, age, grade of resection and performance status. Recently, improved efficacy of lomustine (CCNU)/TMZ compared to TMZ monotherapy in ndGBM patients with MGMT-promotor methylation was reported in the CeTeG trial (NOA-09). Taken into account that TTFields showed a strong safety profile as well as a high potential being combined with other modalities and the very encouraging results for methylated MGMT-promotor GBM patients in the CeTeG trial, there is a strong rationale in combining these treatment regimens. Here, we present a case series of patients receiving a combination of both modalities, TTFields and CCNU/TMZ. METHODS Patients with ndGBM and MGMT-promotor methylation underwent a combined therapy of TTFields plus CCNU/TMZ after surgery and radiochemotherapy. Safety, feasibility as well as first efficacy results of this combined therapy are reported at data cut-off (31.12.2018). Most recent data, including compliance to TTFields therapy, will be presented at the EANO annual meeting. RESULTS Twelve patients with MGMT-promotor methylated ndGBM (median, range: age 49.5, 26–69; KPS 90, 60–100) have been treated with a combination of TTFields plus CCNU/TMZ. The analysis included patients with complete resection (n=6), partial resection (n=5) as well as biopsy (n=1). CTCAE grade 3 hematotoxicities were observed in six patients, but were not considered to be related to the addition of TTFields to lomustine/TMZ. Medical device site reactions (low-grade skin reactions) were detected in five patients. At data cut-off, the analyzed patient population demonstrated a median PFS of 18.7 months, whereas the median OS was not yet reached. CONCLUSION The results of this analysis provide first indication that the combination of TTFields/lomustine/TMZ is safe and feasible. Moreover, the observed survival outcomes point to preliminary beneficial effects of the triple combination. Additional follow-up and a higher sample size is required and planned for further toxicity analysis and efficacy assessment of this combination.

IMMU-26. SAFETY AND EFFICACY OF PVSRIPO IN RECURRENT GLIOBLASTOMA: LONG-TERM FOLLOW-UP AND INITIAL MULTICENTER RESULTS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi97-vi97
Author(s):  
Annick Desjardins ◽  
Matthias Gromeier ◽  
Henry Friedman ◽  
Daniel Landi ◽  
Allan Friedman ◽  
...  
Keyword(s):  
Karnofsky Performance Status ◽  
Performance Status ◽  
Recurrent Glioblastoma ◽  
External Control ◽  
Published Data ◽  
Single Center ◽  
Term Survival ◽  
Long Term Survival

Abstract BACKGROUND Recurrent glioblastoma (rGBM) is rapidly fatal (median overall survival [mOS] of ~9 months; OS at 12 months [OS12] &lt; 35%) with approved therapies (lomustine±bevacizumab). PVSRIPO is an intratumoral immunotherapy targeting CD155 on antigen-presenting and malignant cells of solid tumors. Preclinically, PVSRIPO delivers a systemic, tumor antigen-specific, polyfunctional T-cell mediated anti-tumor response. Interim, single-center, phase (Ph) 1 results showed greater long-term survival with PVSRIPO vs. criteria-matched external control rGBM patients (Desjardins 2018). Updates to Ph1 safety (at the Ph2 dose) and efficacy and interim multicenter (Ph2) results are presented. METHODS Adults with histologically-confirmed rGBM, Karnofsky performance status ≥ 70, and an active, supratentorial, contrast-enhancing lesion (1-5.5cm) received PVSRIPO (5x107 TCID50) intratumorally via convection-enhanced delivery on Day 1, with a planned follow-up of 24 months. Safety (treatment-emergent adverse events [TEAEs]), efficacy (reported as OS12, OS24, mOS), and blood/tissue were assessed. RESULTS 149 patients (&gt;90% with 1-2 prior progressions, including failure of SOC and patients with prior bevacizumab failure) received the Ph2 dose of PVSRIPO (n=30 received other doses in Ph1 with safety summarized previously). Follow-up durations for surviving patients were 51-74 months (Ph1) and 10-44 months (Ph2). No dose-limiting toxicities occurred; up to 97% of patients experienced mostly grade 1-2 related TEAEs; ≤ 23% patients experienced grade ≥ 3 related events. Neurologic symptoms related to peritumoral edema were most common ( &gt; 90% patients) and were effectively managed with low-dose bevacizumab/corticosteroids. Survival estimates were: OS12: 54%, 50%; OS24: 18%, 17%; mOS: 12.3 (95% CI 10,15.3), 12 (10.6,13.7) months, for the Ph1 and Ph2 trials, respectively. Baseline correlates of longer survival included smaller lesions and methylated MGMT-promoter status. CONCLUSIONS The multicenter/Ph2 study replicated the single-center/Ph1 results. Relative to published data with approved therapies, PVSRIPO was associated with greater long-term survival and mOS in patients with rGBM and was generally well-tolerated.

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