Cognitive Function as a Predictor of Survival in Patients With Recurrent Malignant Glioma

2000 ◽  
Vol 18 (3) ◽  
pp. 646-646 ◽  
Author(s):  
Christina A. Meyers ◽  
Kenneth R. Hess ◽  
W.K. Alfred Yung ◽  
Victor A. Levin
Keyword(s):  
Cognitive Function ◽  
Verbal Memory ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Clinical Information ◽  
Recurrent Glioblastoma ◽  
Recurrent Glioblastoma Multiforme ◽  
Clinical Variables ◽  
Treatment Regimens ◽  
Karnofsky Performance Status Score

PURPOSE: To determine the contribution of cognitive function in predicting the survival of patients with recurrent malignant brain tumors.PATIENTS AND METHODS: A total of 80 patients with recurrent glioblastoma multiforme or anaplastic astrocytoma were seen for baseline evaluations before beginning a phase I or phase II clinical trial. Each patient received a battery of nine brief tests measuring cognitive function, ability to perform activities of daily living (ADLs), and quality of life (QOL). Tests were given monthly after treatment was begun.RESULTS: Performance on a test of verbal memory was independently and strongly related to survival after accounting for age, Karnofsky performance status score, histology, and time since diagnosis. Models incorporating three of nine and all nine tests in the battery accounted for significantly more variance in survival than did the clinical variables alone. Measures of QOL and ADLs (bathing, feeding, and so on) were not independently related to survival, although they provide clinical information that is important for patient care.CONCLUSION: These results indicate that a multifaceted assessment of cognition, QOL, and patient function is practical for brain tumor patients in clinical trials and can provide information regarding the relative risks versus benefits of new treatment regimens that supplements the information from the usual clinical variables.

Bevacizumab and irinotecan in patients (pts) with recurrent glioblastoma multiforme (GBM)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2078-2078 ◽  
Author(s):  
S. Raval ◽  
S. Hwang ◽  
L. Dorsett
Keyword(s):  
Cognitive Function ◽  
Functional Status ◽  
Response Rate ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Recurrent Glioblastoma ◽  
Recurrent Glioblastoma Multiforme ◽  
Pre Treatment ◽  
Grade 3 ◽  
The Impact

2078 Background: Primary GBM exhibits overexpression or amplification of the epidermal growth factor gene. The effectiveness of bevacizumab and irinotecan in pts with relapsed GBM was first reported in 2005 (Stark-Vance, et al, Neuro-Oncol, 2005). In this report, we assess the effects of combination of bevacizumab and irinotecan on overall responses, toxicity, cognitive function and functional status in recurrent GBM pts. Methods: From August 2005 to December 2006, 22 consecutive GBM pts failed > 1 prior chemotherapy with measurable disease on MRI were included. Each patient received bevacizumab 5mg/kg IV and irinotecan 125mg/m2 IV infusion every 2 weeks until disease progression or developed unacceptable toxicity. The response was determined by MRI every 2 cycles. Cognitive function was assessed by Blessed Orientation-Memory-Concentration Test (BOMC) and functional status was assessed by Karnofsky performance status (KPS), Barthel Index (BI) and Instrumental Activities of Daily Living (IADL) prior to each cycle of treatment. Descriptive statistics analysis was used. Results: All pts failed temozolomide and radiation therapy; 1 pt had prior BCNU and 2 pts had prior irinotecan treatment. The median (M) age was 55 years (37-77) with pre treatment M KPS 80 (40–80), BOMC 7 (0–28), BI 85 (10–100) and IADL 6 (0–17); 12 pts exhibited mild (3 pts), moderate (7 pts) to severe (2 pts) cognitive impairment. The M number of cycles received was 8 (2–27); 21 pts are evaluable for MRI responses with 95.2% response rate (2CR’s + 14PR’s + 4 minimal responses). Seven pts have expired; the M length of survival was 4.6 months (range 1.1–15.4+) and the M time to progression was 3 months (0.5–13.8+). There were only two grade 3 thrombocytopenia and one grade 3 neutropenia. Improvement in BOMC score was seen in 15 pts (62%) with M improvement of 7 point. Improvement in functional status was seen in 18 pts (85.7%) with M improvement in KPS by 10 point, BI by 8 points and IADL by 2 point. Conclusions: The combination of bevacizumab and irinotecan is well tolerated and safe. The overall response rate was 95.2% and significant improvements in cognitive functional and functional status were demonstrated. The longer follow up will determine the impact of this most active combination. No significant financial relationships to disclose.

Phase II open-label, safety, pharmacokinetic and efficacy study of 2-methoxyestradiol nanocrystal colloidal dispersion administered orally to patients with recurrent glioblastoma multiforme

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2065-2065 ◽  
Author(s):  
J. Kirkpatrick ◽  
A. Desjardins ◽  
J. Quinn ◽  
J. Rich ◽  
J. Vredenburgh ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Tumor Regression ◽  
Cell Damage ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Recurrent Glioblastoma ◽  
Recurrent Glioblastoma Multiforme ◽  
Open Label ◽  
Minor Response ◽  
Grade 3

2065 Background: 2-methoxyestradiol (2ME2) inhibits tumor cell proliferation and induces apoptosis by inhibiting microtubule polymerization and increasing reactive oxygen species-induced cell damage. In addition, 2ME2 downregulates HIF-1a at the posttranscriptional level and inhibits HIF-1a-mediated VEGF expression. Preclinical studies confirm significant in vitro and in vivo anti-glioma activity including tumor regression in combination with temozolomide. We therefore performed a single-center, phase 2 study to evaluate 2ME2 in recurrent glioblastoma multiforme (GBM) patients. Methods: Key eligibility include: adults with GBM at first or second recurrence; measurable disease; Karnofsky performance status = 70% and adequate organ function. 2ME2 was given orally 4 times/day at a dose of 1000mg for the first 11 patients and then escalated to 1500 mg for remaining patients. Patients are evaluated after every 28-day cycle. The primary efficacy endpoint is 6-month progression-free survival. Results: Sixteen patients (14 male) have been enrolled, including 7 at first recurrence and 9 at second recurrence. The median age is 52 years (range, 32–64 years). Thirty-five cycles have been administered to date. Grade II-IV, attributable toxicities include transaminase elevation (grade 3, n=3; grade 2, n=1); hypophosphatemia (grade 3, n=1); anorexia (grade 2, n=1) and rash (grade 2, n=1). Six patients (38%) have achieved stable disease including one minor response. PK studies revealed similar 2ME2 exposures to those achieved among solid tumor patients treated at the same dose level and no differences between GBM patients on or not on CYP3A-inducing anti-epileptic agents. Further accrual and follow-up is ongoing. Conclusions: Continuous daily 2ME2 dosing, administered as a monotherapeutic, is well tolerated and is associated with modest anti-tumor activity among recurrent GBM patients. Combination studies with temozolomide are underway. No significant financial relationships to disclose.

scholarly journals Results of the NeuroBlate System first-in-humans Phase I clinical trial for recurrent glioblastoma

2013 ◽  
Vol 118 (6) ◽  
pp. 1202-1219 ◽  
Author(s):  
Andrew E. Sloan ◽  
Manmeet S. Ahluwalia ◽  
Jose Valerio-Pascua ◽  
Sunil Manjila ◽  
Mark G. Torchia ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Dose Escalation ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Recurrent Glioblastoma ◽  
Thermal Therapy ◽  
Laser Interstitial Thermal Therapy ◽  
Karnofsky Performance Status Score ◽  
Performance Status Score

Object Laser interstitial thermal therapy has been used as an ablative treatment for glioma; however, its development was limited due to technical issues. The NeuroBlate System incorporates several technological advances to overcome these drawbacks. The authors report a Phase I, thermal dose–escalation trial assessing the safety and efficacy of NeuroBlate in recurrent glioblastoma multiforme (rGBM). Methods Adults with suspected supratentorial rGBM of 15- to 40-mm dimension and a Karnofsky Performance Status score of ≥ 60 were eligible. After confirmatory biopsy, treatment was delivered using a rigid, gas-cooled, side-firing laser probe. Treatment was monitored using real-time MRI thermometry, and proprietary software providing predictive thermal damage feedback was used by the surgeon, along with control of probe rotation and depth, to tailor tissue coagulation. An external data safety monitoring board determined if toxicity at lower levels justified dose escalation. Results Ten patients were treated at the Case Comprehensive Cancer Center (Cleveland Clinic and University Hospitals–Case Medical Center). Their average age was 55 years (range 34–69 years) and the median preoperative Karnofsky Performance Status score was 80 (range 70–90). The mean tumor volume was 6.8 ± 5 cm3 (range 2.6–19 cm3), the percentage of tumor treated was 78% ± 12% (range 57%–90%), and the conformality index was 1.21 ± 0.33 (range 1.00–2.04). Treatment-related necrosis was evident on MRI studies at 24 and 48 hours. The median survival was 316 days (range 62–767 days). Three patients improved neurologically, 6 remained stable, and 1 worsened. Steroid-responsive treatment-related edema occurred in all patients but one. Three had Grade 3 adverse events at the highest dose. Conclusions NeuroBlate represents new technology for delivering laser interstitial thermal therapy, allowing controlled thermal ablation of deep hemispheric rGBM. Clinical trial registration no.: NCT00747253 (ClinicalTrials.gov).

scholarly journals Retrospective Analysis of Bevacizumab in Combination with Fotemustine in Chinese Patients with Recurrent Glioblastoma Multiforme

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Zhiguang Liu ◽  
Guanqun Zhang ◽  
Liang Zhu ◽  
Jiangbo Wang ◽  
Dongbo Liu ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Response Rate ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Promoter Hypermethylation ◽  
Recurrent Glioblastoma ◽  
Chinese Patients ◽  
Recurrent Glioblastoma Multiforme ◽  
Clinical Benefits ◽  
Recurrent Gbm

The aim of this study was to assess the activity and safety of bevacizumab (BEV) and fotemustine (FTM) for the treatment of recurrent glioblastoma multiforme (GBM) patients and explore the potential prognostic parameters on survival. This study retrospectively analyzed all patients with GBM who were treated with at least one cycle of BEV and FTM from July 2010 to October 2012. A total of 176 patients with recurrent GBM were enrolled. The response rate and disease control rate were 46.6% and 90.9%, respectively. A 6-month PFS rate of 33.3% (95% CI: 26.5%–40.3%) and a median PFS of 5.0 (95% CI: 2.4–7.5) months were observed. The median OS was 8.0 (95% CI: 6.7–9.2) months. Multivariate analysis showed that risk factors with a significant influence on the PFS of all patients were Karnofsky Performance Status (KPS) (≥70 versus <70,HR=0.53, 95% CI: 0.39–0.73, andP=0.01) and MGMT status (methylated versus unmethylated,HR=0.69, 95% CI: 0.52–0.97, andP=0.04). The most common treatment-related adverse events were fatigue, proteinuria, hypophonia, hypertension, thrombocytopenia, anemia, and neutropenia. In conclusion, combination of BEV with FTM is well tolerated and may derive some clinical benefits in recurrent GBM patients. Higher KPS and MGMT promoter hypermethylation were suggested to be associated with prolonged survival.

scholarly journals Scale to Predict Survival After Surgery for Recurrent Glioblastoma Multiforme

2010 ◽  
Vol 28 (24) ◽  
pp. 3838-3843 ◽  
Author(s):  
John K. Park ◽  
Tiffany Hodges ◽  
Leopold Arko ◽  
Michael Shen ◽  
Donna Dello Iacono ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Surgical Resection ◽  
Median Survival ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Recurrent Glioblastoma ◽  
Postoperative Survival ◽  
Recurrent Glioblastoma Multiforme ◽  
Factors Associated ◽  
Recurrent Gbm

Purpose Despite initial treatment with surgical resection, radiotherapy, and chemotherapy, glioblastoma multiforme (GBM) virtually always recurs. Surgery is sometimes recommended to treat recurrence. In this study, we sought to devise a preoperative scale that predicts survival after surgery for recurrent glioblastoma multiforme. Patients and Methods The preoperative clinical and radiographic data of 34 patients who underwent re-operation of recurrent GBM tumors were analyzed using Kaplan-Meier survival analysis and Cox proportional hazards regression modeling. The factors associated with decreased postoperative survival (P < .05) were used to devise a prognostic scale which was validated with a separate cohort of 109 patients. Results The factors associated with poor postoperative survival were: tumor involvement of prespecified eloquent/critical brain regions (P = .021), Karnofsky performance status (KPS) ≤ 80 (P = .030), and tumor volume ≥ 50 cm3 (P = .048). An additive scale (range, 0 to 3 points) comprised of these three variables distinguishes patients with good (0 points), intermediate (1 to 2 points), and poor (3 points) postoperative survival (median survival, 10.8, 4.5, and 1.0 months, respectively; P < .001). The scale identified three statistically distinct groups within the validation cohort as well (median survival, 9.2, 6.3, and 1.9 months, respectively; P < .001). Conclusion We devised and validated a preoperative scale that identifies patients likely to have poor, intermediate, and good relative outcomes after surgical resection of a recurrent GBM tumor. Application of this simple scale may be useful in counseling patients regarding their treatment options and in designing clinical trials.

First-Line Chemotherapy With Cisplatin Plus Fractionated Temozolomide in Recurrent Glioblastoma Multiforme: A Phase II Study of the Gruppo Italiano Cooperativo di Neuro-Oncologia

2004 ◽  
Vol 22 (9) ◽  
pp. 1598-1604 ◽  
Author(s):  
Alba A. Brandes ◽  
Umberto Basso ◽  
Michele Reni ◽  
Francesca Vastola ◽  
Alicia Tosoni ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Hematologic Toxicity ◽  
Recurrent Glioblastoma Multiforme

Purpose Cisplatin and temozolomide (TMZ) are active in glioblastoma multiforme (GBM), with different profiles of toxicity. A bid regimen of TMZ achieves a strong inhibition of O6-alkylguanine DNA-alkyl transferase (AGAT), and cisplatin reduces AGAT activity in vitro, suggesting a possible synergic interaction. The primary end point of the present multicenter phase II study was progression-free survival (PFS) at 6 months (PFS-6); secondary end points included response, toxicity, and overall survival. Patients and Methods Chemotherapy-naive patients with GBM who experienced disease recurrence or progression after surgery and standard radiotherapy were eligible. Chemotherapy cycles consisted of cisplatin 75 mg/m2 on day 1, TMZ 130 mg/m2 bolus followed by nine doses of 70 mg/m2 every 12 hours (total of 5 days) from day 2 every 4 weeks. In the absence of hematologic toxicity, TMZ was escalated to 1,000 mg/m2 in 5 days. Results A total of 50 patients (median age, 53.4 years; range, 27 to 70 years; median Karnofsky performance status, 80; range, 60 to 100) were accrued in the study. PFS-6 was 34% (95% CI, 23% to 50%), and PFS-12 was 4% (95% CI, 0.3% to 16%). Median PFS was 18.4 weeks (95% CI, 13 to 25.9 weeks). Among 49 assessable patients, one complete response and nine partial responses were obtained, with an overall response rate of 20.4% (95% CI, 7.7% to 33%). Among 203 treatment cycles delivered, the most common grade 3 or grade 4 events included granulocytopenia in 7.9% of cycles, thrombocytopenia in 4%, and neurologic toxicity in three patients (6%). Conclusion The new cisplatin plus bid TMZ regimen appears active in chemotherapy-naive patients with recurrent GBM and incurs an acceptable toxicity.

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.

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 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 &lt; .001), and OS (HR 1.90 [1.35-2.67], P &lt; .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.

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