scholarly journals P.161 Management of recurrent glioblastoma multiforme: An inter-observer variability study

2021 ◽  
Vol 48 (s3) ◽  
pp. S66-S66
Author(s):  
M Patel ◽  
K Au ◽  
V Mehta ◽  
R Broad ◽  
MM Chow ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Randomized Trial ◽  
Controlled Trial ◽  
Significant Proportion ◽  
Kappa Statistics ◽  
Recurrent Glioblastoma Multiforme ◽  
Management Options ◽  
Repeat Surgery ◽  
Best Management ◽  
Recurrent Gbm

Background: A significant proportion of glioblastoma multiforme (GBM) patients are considered for repeat resection, but evidence regarding best management remains elusive. Methods: An electronic portfolio of MR images of 37 cases of pathologically confirmed recurrent GBM with an accompanying clinical vignette was constructed. Surgical responders from various countries, training backgrounds, and years’ experience were asked for each case to select: their chosen management (repeat surgery, chemotherapy, radiation, or conservative), confidence in recommended management, and whether they would include the patient in a randomized trial that gave a 50% chance of re-operation. Responses were evaluated with kappa statistics and values interpreted according to Landis and Koch (0–0.2, slight; 0.21–0.4, fair; 0.41–0.6, moderate; 0.61–0.8, substantial; 0.81-1.0 perfect agreement). Results: 26 surgeons responded to the survey. Agreement regarding best management of recurrent GBM was slight, even when management options were dichotomized (repeat surgery vs. all others) (k=0.198 (95%CI 0.133-0.276). Country of practice, years’ experience, and training background did not improve agreement. Responders were willing to include more than 70% of patients in a randomized trial. Conclusions: Only slight agreement exists regarding the question of re-operation for patients with recurrent GBM. This supports the need for a randomized controlled trial.

Recurrent glioblastoma multiforme: a review of natural history and management options

2006 ◽  
Vol 20 (4) ◽  
pp. E3 ◽  
Author(s):  
Lewis C. Hou ◽  
Anand Veeravagu ◽  
Andrew R. Hsu ◽  
Victor C. K. Tse
Keyword(s):  
Glioblastoma Multiforme ◽  
Natural History ◽  
Research Effort ◽  
Treatment Options ◽  
Recurrent Glioblastoma ◽  
Recurrent Glioblastoma Multiforme ◽  
Management Options ◽  
Fatal Disease ◽  
The Past ◽  
Recurrent Gbm

✓ Glioblastoma multiforme (GBM) is one of the most aggressive primary brain tumors, with a grim prognosis despite maximal treatment. Advancements in the past decades have not significantly increased the overall survival of patients with this disease. The recurrence of GBM is inevitable, its management often unclear and case dependent. In this report, the authors summarize the current literature regarding the natural history, surveillance algorithms, and treatment options of recurrent GBM. Furthermore, they provide brief discussions regarding current novel efforts in basic and clinical research. They conclude that although recurrent GBM remains a fatal disease, the literature suggests that a subset of patients may benefit from maximal treatment efforts. Nevertheless, further research effort in all aspects of GBM diagnosis and treatment remains essential to improve the overall prognosis of this disease.

scholarly journals Evaluating the Benefit of Repeat Surgery for Recurrent Glioblastoma Multiforme

Neurosurgery ◽  
2010 ◽  
Vol 67 (6) ◽  
pp. N16-N17 ◽  
Author(s):  
Ricardo J Komotar ◽  
Robert M Starke ◽  
E Sander Connolly ◽  
Michael B Sisti
Keyword(s):  
Glioblastoma Multiforme ◽  
Recurrent Glioblastoma ◽  
Recurrent Glioblastoma Multiforme ◽  
Repeat Surgery

scholarly journals Phase II Trial of Vorinostat in Recurrent Glioblastoma Multiforme: A North Central Cancer Treatment Group Study

2009 ◽  
Vol 27 (12) ◽  
pp. 2052-2058 ◽  
Author(s):  
Evanthia Galanis ◽  
Kurt A. Jaeckle ◽  
Matthew J. Maurer ◽  
Joel M. Reid ◽  
Matthew M. Ames ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Statistical Significance ◽  
Single Agent ◽  
Rest Period ◽  
Recurrent Glioblastoma ◽  
Pharmacokinetic Analysis ◽  
Hematologic Toxicity ◽  
Recurrent Glioblastoma Multiforme ◽  
Grade 3 ◽  
Recurrent Gbm

PurposeVorinostat, a histone deacetylase inhibitor, represents a rational therapeutic target in glioblastoma multiforme (GBM).Patients and MethodsPatients with recurrent GBM who had received one or fewer chemotherapy regimens for progressive disease were eligible. Vorinostat was administered at a dose of 200 mg orally twice a day for 14 days, followed by a 7-day rest period.ResultsA total of 66 patients were treated. Grade 3 or worse nonhematologic toxicity occurred in 26% of patients and consisted mainly of fatigue (17%), dehydration (6%), and hypernatremia (5%); grade 3 or worse hematologic toxicity occurred in 26% of patients and consisted mainly of thrombocytopenia (22%). Pharmacokinetic analysis showed lower vorinostat maximum concentration and area under the curve (0 to 24 hours) values in patients treated with enzyme-inducing anticonvulsants, although this did not reach statistical significance. The trial met the prospectively defined primary efficacy end point, with nine of the first 52 patients being progression-free at 6 months. Median overall survival from study entry was 5.7 months (range, 0.7 to 28+ months). Immunohistochemical analysis performed in paired baseline and post-vorinostat treatment samples in a separate surgical subgroup of five patients with recurrent GBM showed post treatment increase in acetylation of histones H2B and H4 (four of five patients) and of histone H3 (three of five patients). Microarray RNA analysis in the same samples showed changes in genes regulated by vorinostat, such as upregulation of E-cadherin (P = .02).ConclusionVorinostat monotherapy is well tolerated in patients with recurrent GBM and has modest single-agent activity. Histone acetylation analysis and RNA expression profiling indicate that vorinostat in this dose and schedule affects target pathways in GBM. Additional testing of vorinostat in combination regimens is warranted.

Phase II trial of Gliadel plus O6-benzylguanine (O6-BG) for patients with recurrent glioblastoma multiforme

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1568-1568 ◽  
Author(s):  
J. A. Quinn ◽  
J. J. Vredenburgh ◽  
J. N. Rich ◽  
D. A. Reardon ◽  
A. Desjardins ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Adverse Events ◽  
Median Survival ◽  
Controlled Trial ◽  
Recurrent Glioblastoma ◽  
Phase Iii ◽  
Csf Leak ◽  
Recurrent Glioblastoma Multiforme ◽  
Major Mechanism ◽  
Phase 2 Trial

1568 Background. The major mechanism of resistance to alkylnitrosourea therapy involves the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) which removes chloroethylation or methylation damage from the O6-position of guanine. O6-BG is an AGT substrate that inhibits AGT by suicide inactivation. A previous phase III randomized, placebo-controlled trial has shown that Gliadel wafer significantly prolongs 6-month survival (55.5% for Gliadel vs. 35.6% for placebo) and median survival (28 weeks for Gliadel vs. 20 weeks for placebo) in patients with recurrent glioblastoma multiforme (GBM) (Brem et al 1995). Despite the success of Gliadel in prolonging survival we may be able to improve on this success by depleting AGT. Methods. Thus, we have designed a phase 2 trial where we define the activity and the toxicity of Gliadel in combination with a 5-day infusion of O6-BG in patients with recurrent GBM. In a prior study the O6-BG dose found to be effective in depleting tumor AGT activity at 48 hours was an IV bolus of 120 mg/m2 over 1 hour followed by a continuous infusion of 30 mg/m2/d for 48 hours. In order to guarantee depletion of tumor AGT activity for at least 5 days after Gliadel placement, this O6-BG bolus was repeated on days 3 and 5 while continuing the infusion. Results. To date, 24 patients have been enrolled out of a planned accrual of 50 patients. Seventeen of these patients received prior nitrosourea therapy. The 6-month survival is 68% and the median survival is 36 weeks. The adverse events include the following: 2 episodes of CSF leak (8%), 4 episodes of wound infection at craniotomy site (16%), 5 episodes of grade ≥ 3 seizures (21%) and 3 episodes of hyponatremia (12%). These adverse events were similar in frequency to those seen in patients receiving Gliadel in prior placebo-controlled Gliadel trials. Conclusions. Thus far, this data demonstrates an increase in the efficacy of Gliadel when combined with O6-BG. Twenty-six additional patients will be enrolled for a total accrual of 50 patients. [Table: see text]

A stratified phase II study of cetuximab for the treatment of recurrent glioblastoma multiforme: Preliminary results

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1558-1558 ◽  
Author(s):  
J. Sadones ◽  
C. Chaskis ◽  
E. J. Joosens ◽  
L. A. Dhondt ◽  
J. Baurain ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Gene Copy Number ◽  
Growth Factor Receptor ◽  
Recurrent Glioblastoma ◽  
Gene Copy ◽  
Recurrent Glioblastoma Multiforme ◽  
Egfr Gene ◽  
Recurrent Gbm

1558 Background: The Epidermal Growth Factor Receptor (EGFR) gene is frequently amplified and mutated in high-grade gliomas. We are investigating the activity of the EGFR-targeted monoclonal antibody cetuximab for the treatment of patients (pts) with recurrent glioblastoma multiforme (GBM) following surgery, radiotherapy and chemotherapy. Methods: Adult pts with recurrent GBM are allocated to two parallel treatment strata according to the amplification status of the EGFR gene (determined by FISH). According to a Simon two-stage phase II study design 1 response in 13 pts/stratum is required to continue recruitment and complete the second stage of pt recruitment. Cetuximab is administered at 400 mg/m2 (2 hour infusion) day 1 and 250 mg/m2 day 8 and for all subsequent weekly doses (1 hour infusion). Results: Between May and December 2005, 17 pts were recruited (10 without EGFR-ampl, 4 with EGFR-ampl and 3 under investigation); 4F/13M; median age 51 years, range 32–67). Recruitment is ongoing. Sixteen pts initiated study treatment; 1 pt withdrew consent before the initiation of therapy. Treatment related toxicity in the first 94 treatment cycles consisted of grade 1/2 folliculitis/dermitis in all treated pts. Grade 3 adverse events consisted of thrombocytopenia (n=1 pt), diminished consciousness (n=1 pt), dizziness/confusion (n=1 pt), infectious bronchopneumonia (n=1 pt), and infectious cellulitis (n=1 pt). Thirteen pts have been evaluated for response ≤ week 8 of study treatment. Eleven pts had progression of disease. Two patients had SD at 8 weeks (follow-up is ongoing). Conclusions: These preliminary data suggest that cetuximab can be safely administered to pretreated patients with recurrent GBM. Updated results regarding safety and activity as well as a correlative study of EGFR and PTEN expression and gene copy number of the GBM and response to cetuximab will be presented at the meeting. No significant financial relationships to disclose.

Phase II trial of Gliadel plus O6-benzylguanic (O6-BG) for patients with recurrent glioblastoma multiforme

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2036-2036 ◽  
Author(s):  
J. A. Quinn ◽  
J. J. Vredenburgh ◽  
J. N. Rich ◽  
D. A. Reardon ◽  
A. Desjardins ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Median Survival ◽  
Controlled Trial ◽  
Recurrent Glioblastoma ◽  
Phase Iii ◽  
Csf Leak ◽  
Recurrent Glioblastoma Multiforme ◽  
Major Mechanism ◽  
Phase 2 Trial ◽  
Grade 3

2036 Background: The major mechanism of resistance to alkylnitrosourea therapy involves the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) which removes chloroethylation or methylation damage from the O6- position of guanine. O6-BG is an AGT substrate that inhibits AGT by suicide inactivation. A previous phase III randomized, placebo- controlled trial has shown that Gliadel wafer (G) significantly prolongs 6-month survival (55.5% for G vs. 35.6% for placebo) and median survival (28 weeks for G vs. 20 weeks for placebo) in patients with recurrent glioblastoma multiforme (GBM) (Brem et al 1995). Despite the success of G in prolonging survival we may be able to improve on this success by depleting AGT. Methods: Thus, we have designed a phase 2 trial where we define the activity and the toxicity of G in combination with a 5-day infusion of O6-BG in patients with recurrent GBM. In a prior study the O6-BG dose found to be effective in depleting tumor AGT activity at 48 hours was an IV bolus of 120 mg/m2 over 1 hour followed by a continuous infusion of 30 mg/m2/d for 48 hours. In order to guarantee depletion of tumor AGT activity for at least 5 days after G placement, this O6-BG bolus was repeated on days 3 and 5 while continuing the infusion. Results: To date, 47 patients have been enrolled out of a planned accrual of 50 patients. The 6-month survival is 80% and the median survival is 47 weeks. The adverse events include the following: 3 episodes of grade 3 CSF leak (6%), 7 episodes of grade 3 wound infection at craniotomy site (15%), 6 episodes of hyponatremia (13%), 3 episodes of hydrocephalus (6%), 1 episode of hygroma (2%), 1 episode of infectious meningitis (2%), 1 episode of arachnoiditis (2%), 1 episode of grade 3 fever (2%). Conclusions: Thus far, this data demonstrates an increase in the efficacy of G when combined with O6-BG. Three additional patients will be enrolled for a total accrual of 50 patients. [Table: see text]

Phase I/II dose-escalation study of VB-111, an antiangiogenic gene therapy, in patients with recurrent glioblastoma multiforme.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS2102-TPS2102 ◽  
Author(s):  
Andrew Jacob Brenner ◽  
Yael Cohen ◽  
James J Vredenburgh ◽  
Katherine B. Peters ◽  
Eyal Breitbart ◽  
...  
Keyword(s):  
Overall Survival ◽  
Glioblastoma Multiforme ◽  
Phase I ◽  
Dose Escalation ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
High Dose ◽  
Recurrent Glioblastoma Multiforme ◽  
Dose Escalation Study ◽  
Recurrent Gbm

TPS2102 Background: VB-111 is an anti-angiogenic agent consisting of a non-replicating adenovirus vector (Ad-5) with a modified murine pre-proendothelin promoter leading to apoptosis of tumor vasculature by expressing a fas-chimera transgene in angiogenic endothelial cells. In a phase I/II dose-escalation study, safety and efficacy of VB-111 in patients with recurrent Glioblastoma Multiforme (GBM) were evaluated. Methods: VB-111 was administered as a single intravenous infusion at escalating doses from 1x1012 to 3x1012 viral particles (VPs), followed by repeat doses of 3x1012 or 1x1013every 2 months. Assessments included safety, pharmacokinetics, tumor response (RANO criteria) and overall survival (OS). Results: Twenty eight patients aged 26 – 74 years at 3 medical centers in the US received up to 8 repeat doses of VB-111. The median OS was 360 [range: 70-574] and 266 days [range: 28-664] for patients receiving at least one dose of 1x1013VPs (high dose) vs. subjects who received lower doses, respectively (p NS). Progression free survival was 87 vs 55 days for patients who received high dose and for lower doses, respectively (p = 0.01). Median follow-up was 232 days. Three patients had a partial response (PR) at 82, 86 and 408 days post initial VB-111 dosing. Twenty one of the patients who progressed on VB-111 treatment received bevacizumab off study; 7 of the 15 evaluable patients (47%) had a PR compared to 30% expected according to literature. VB-111 was safe and well tolerated, 53 adverse events were reported, 14 were classified as possibly related to VB-111. All events were of CTCAE grade 1-2 except one grade 3 pulmonary embolism. There were no study related deaths. One patient developed peri-tumoral edema, which resolved with corticosteroid therapy. Events occurring in > 10% of the patients included headache and fatigue. Conclusions: VB-111 was safe and well tolerated in patients with recurrent GBM with repeat doses of up to 1x1013 VPs. Tumor responses were seen. Overall survival was about 3 months longer than historical data in recurrent GBM, including standard of care anti-angiogenic agents. Data suggests that VB-111 potentiates the response to bevacizumab given at further progression. Clinical trial information: NCT01260506.

Bevacizumab (BV) plus irinotecan (I) in recurrent glioblastoma multiforme (GBM): A single center experience.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13000-e13000
Author(s):  
Eluska Iruarrizaga ◽  
Eider Azkona ◽  
Unai Aresti ◽  
Itziar Rubio ◽  
Mikel Arruti ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Median Number ◽  
Primary Brain Tumor ◽  
Recurrent Glioblastoma ◽  
Recurrent Glioblastoma Multiforme ◽  
Single Center Experience ◽  
Flair Sequence ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Recurrent Gbm

e13000 Background: Glioblastoma multiforme constitutes the most common and malignant form of primary brain tumor. Median survival for recurrent disease is 3-9 months. Combining bevacizumab with irinotecan represents an option of treatment in recurrent GBM. Methods: We performed a retrospective review of patients with recurrent GBM treated with bevacizumab (10 mg/kg) and irinotecan (340 mg/m2 for patients receiving enzyme-inducing antiepileptic drugs –EIAEDs- and 125 mg/m2 for patients not receiving EIAEDs) every 14 days on a 4-week cycle. Inclusion criteria: age ≥ 18, histology of GBM, progression after radiotherapy and temozolomide and signed informed consent for bevacizumab compassionate use. MRI-FLAIR sequence was used every 8 weeks to assess response. Results: From October 2009 to December 2012, a total of 26 patients were included; 15 (57.7%) male/11 (42.3%) female. Median age of the patients was 52 years (32-69); ECOG 0/1/2/3: 7.7/46.2/38.5/7.7% respectively; 19.23 % of patients received EIAEDs. Median number of cycles was 2.5 (1-14). Response rate was 30.8% (23.1% PR; 7.7 % CR); SD 23.1 %. Median PFS was 23 weeks; median OS was 30 weeks. Most common grade 3 toxicities were: asthenia 26.9%, arthromyalgia 3.8%, diarrhea 3.8% and hepatotoxicity 15.4%; grade 2 thromboembolic complications: 3.8 %. Conclusions: Combination of bevacizumab and irinotecan is effective against recurrent GBM and prolongs PFS and OS compared with historical controls, with mild toxicity.

Phase II Trial of Temsirolimus (CCI-779) in Recurrent Glioblastoma Multiforme: A North Central Cancer Treatment Group Study

2005 ◽  
Vol 23 (23) ◽  
pp. 5294-5304 ◽  
Author(s):  
Evanthia Galanis ◽  
Jan C. Buckner ◽  
Matthew J. Maurer ◽  
Jeffrey I. Kreisberg ◽  
Karla Ballman ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Recurrent Glioblastoma ◽  
Hematologic Toxicity ◽  
Recurrent Glioblastoma Multiforme ◽  
Time Curve ◽  
P70s6 Kinase ◽  
Signal Abnormality ◽  
Grade 3 ◽  
Radiographic Improvement ◽  
Recurrent Gbm

Background Temsirolimus (CCI-779) is a small-molecule inhibitor of the mammalian target of rapamycin (mTOR) and represents a rational therapeutic target against glioblastoma multiforme (GBM). Methods Recurrent GBM patients with ≤ 1 chemotherapy regimen for progressive disease were eligible. Temsirolimus was administered in a 250-mg intravenous dose weekly. Results Sixty-five patients were treated. The incidence of grade 3 or higher nonhematologic toxicity was 51%, and consisted mostly of hypercholesterolemia (11%), hypertriglyceridemia (8%), and hyperglycemia (8%). Grade 3 hematologic toxicity was observed in 11% of patients. Temsirolimus peak concentration (Cmax), and sirolimus Cmax and area under the concentration-time curve were decreased in patients receiving p450 enzyme–inducing anticonvulsants (EIACs) by 73%, 47%, and 50%, respectively, but were still within the therapeutic range of preclinical models. Twenty patients (36%) had evidence of improvement in neuroimaging, consisting of decrease in T2 signal abnormality +/− decrease in T1 gadolinium enhancement, on stable or reduced steroid doses. Progression-free survival at 6 months was 7.8% and median overall survival was 4.4 months. Median time to progression (TTP) for all patients was 2.3 months and was significantly longer for responders (5.4 months) versus nonresponders (1.9 months). Development of grade 2 or higher hyperlipidemia in the first two treatment cycles was associated with a higher percentage of radiographic response (71% v 31%; P = .04). Significant correlation was observed between radiographic improvement and high levels of phosphorylated p70s6 kinase in baseline tumor samples (P = .04). Conclusion Temsirolimus is well tolerated in recurrent GBM patients. Despite the effect of EIACs on temsirolimus metabolism, therapeutic levels were achieved. Radiographic improvement was observed in 36% of temsirolimus–treated patients, and was associated with significantly longer TTP. High levels of phosphorylated p70s6 kinase in baseline tumor samples appear to predict a patient population more likely to derive benefit from treatment. These findings should be validated in other studies of mTOR inhibitors.

scholarly journals ATIM-11. TUMOR-INFILTRATING LYMPHOCYTES EXPRESSING ANTI-PD-1 ANTIBODY EXHIBIT A PROMISING EFFICACY AND SURVIVAL BENEFIT IN PATIENTS WITH RECURRENT GLIOBLASTOMA MULTIFORME

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi3-vi4
Author(s):  
Chao Tang ◽  
Zhi Zhang ◽  
Di Chen ◽  
Kai Ji ◽  
Chunxia Ji ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Genomic Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Recurrent Glioblastoma ◽  
Autologous Tumor ◽  
Recurrent Glioblastoma Multiforme ◽  
Cell Therapies ◽  
Cutaneous Toxicities ◽  
Infiltrating Lymphocytes ◽  
Recurrent Gbm

Abstract Adoptive cell therapies utilizing autologous tumor-infiltrating lymphocytes (TIL) have been demonstrated to be safe and promising in anti-tumor activities; However, their efficiency was still low in treating glioblastoma multiforme (GBM) because of immunosuppression microenvironment. In this study, we proposed a new strategy to enhance the anti-tumor immune response by using modified TIL expressing anti-PD-1 antibody (anti-PD1-TIL), which could reverse immunosuppression in tumor microenviroment. From April 2017 to April 2018，a total of 8 patients with recurrent GBM were enrolled and received more than one cycles of anti-PD1-TIL immunotherapy after surgery and chemotherapy with a median follow-up of 20 months. The anti-PD1-TIL immunotherapy was well tolerated. Two patients suffered grade 1 and 2 adverse events, including fatigue, mucosal/cutaneous toxicities. The median overall survival time was 16.1（95% CL: 15.4–16.7）months. By iRANO criteria, one patient experienced a partial response (PR), and three patients experienced stable disease (SD) after anti-PD-1-TIL immunotherapy. Genomic analysis by whole exome sequencing revealed an enrichment of MUC12 mutation in responders (p< 0.01), and an enrichment of TMEM125 (p< 0.01) and HIST2H3A/C amplification (p< 0.05) associated with immunosuppressive signature in non-responders. Taken together, the anti-PD1-TIL immunotherapy is a safe and promising strategy with durable efficacy to treat patients with recurrent GBM. Clinicaltrials.gov identifier: NCT 03347097.

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