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 ◽  
...  

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.

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii146-ii146
Author(s):  
Sydney Park ◽  
Abigail Giles ◽  
Grace Liberatore ◽  
Katherine Morgan ◽  
Cynthia DeBruhl ◽  
...  

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.


2013 ◽  
Vol 119 (4) ◽  
pp. 871-877 ◽  
Author(s):  
Dale Ding ◽  
Zhiyuan Xu ◽  
Ian T. McNeill ◽  
Chun-Po Yen ◽  
Jason P. Sheehan

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.


Author(s):  
Alessandro Moiraghi ◽  
Francesco Prada ◽  
Alberto Delaidelli ◽  
Ramona Guatta ◽  
Adrien May ◽  
...  

Abstract BACKGROUND Maximizing extent of resection (EOR) and reducing residual tumor volume (RTV) while preserving neurological functions is the main goal in the surgical treatment of gliomas. Navigated intraoperative ultrasound (N-ioUS) combining the advantages of ultrasound and conventional neuronavigation (NN) allows for overcoming the limitations of the latter. OBJECTIVE To evaluate the impact of real-time NN combining ioUS and preoperative magnetic resonance imaging (MRI) on maximizing EOR in glioma surgery compared to standard NN. METHODS We retrospectively reviewed a series of 60 cases operated on for supratentorial gliomas: 31 operated under the guidance of N-ioUS and 29 resected with standard NN. Age, location of the tumor, pre- and postoperative Karnofsky Performance Status (KPS), EOR, RTV, and, if any, postoperative complications were evaluated. RESULTS The rate of gross total resection (GTR) in NN group was 44.8% vs 61.2% in N-ioUS group. The rate of RTV > 1 cm3 for glioblastomas was significantly lower for the N-ioUS group (P < .01). In 13/31 (42%), RTV was detected at the end of surgery with N-ioUS. In 8 of 13 cases, (25.8% of the cohort) surgeons continued with the operation until complete resection. Specificity was greater in N-ioUS (42% vs 31%) and negative predictive value (73% vs 54%). At discharge, the difference between pre- and postoperative KPS was significantly higher for the N-ioUS (P < .01). CONCLUSION The use of an N-ioUS-based real-time has been beneficial for resection in noneloquent high-grade glioma in terms of both EOR and neurological outcome, compared to standard NN. N-ioUS has proven usefulness in detecting RTV > 1 cm3.


Neurosurgery ◽  
2019 ◽  
Vol 85 (5) ◽  
pp. E924-E932 ◽  
Author(s):  
Akshitkumar M Mistry ◽  
Patrick D Kelly ◽  
Jean-Nicolas Gallant ◽  
Nishit Mummareddy ◽  
Bret C Mobley ◽  
...  

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.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2755-2755
Author(s):  
Jeff P. Sharman ◽  
Donald E. Tsai ◽  
Clare J. Twist ◽  
Steven M. Horwitz ◽  
Carol D. Jones ◽  
...  

Abstract Background: PTLDs are typically B-cell neoplasms occurring as uncommon but serious complications of reduced T-cell immune surveillance associated with organ transplantation. RIS benefits only a subset of PTLD patients and cytotoxic therapy may be poorly tolerated. Therefore, in October 1998 we initiated a prospective study of rituximab in patients who failed or were unable to receive RIS and now report mature results. Methods: Patients with CD20+ PTLD were eligible if they had failed to completely respond to RIS or RIS was contraindicated and had Karnofsky performance status >60, age 3–70 years (y), measurable disease, and no change in immunosuppression for at least 2 weeks and no cytotoxic therapy within 4 weeks. Rituximab was given as 375 mg/m2 weekly x 4 with disease evaluation at 1, 3, 6, 9, 12 and 18 months. Response data, survival curves, and the impact of clinical and pathological factors were evaluated. Results: 24 of 26 enrolled pt were eligible and evaluable. Median age was 42y with 5 <17 y, 18 were male, and 14 progressed on RIS. Median time to PTLD from transplant was 47 months (m) (8 <24 m). 17/22 were EBV+, 17 were large cell or Burkitt histology, and 10 PTLD occurred in the allograft site. Response rate was 63% (46 %CR, 17% PR) and CRs were durable (1/11 progressed). With median follow-up of 65 m (range 44–82), outcomes at 5 y are: overall survival 48%, freedom from progression 41% and failure-free survival 21%. 7 pt died without progression, yielding 5 y cause-specific survival of 69%. Nine of 13 pt with disease progression were successfully salvaged with second-line therapy. In univariate analysis PTLD characteristics did not significantly correlate with outcome but 2/2 Burkitt pt quickly progressed. Conclusions: Rituximab provided effective, durable treatment for ~40% of pt failing RIS in this series of mainly late PTLD and a majority of pt progressing after rituximab could be treated successfully. However, overall and failure-free survival reflect significant co-morbidity in this population.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5118-5118
Author(s):  
Joseph R. Mikhael ◽  
Donna E. Reece ◽  
Andrew Belch ◽  
Nizar J. Bahlis ◽  
Deepa Sharma

Abstract Background: Bortezomib (VELCADE™) is a reversible proteasome inhibitor that has been shown to be safe and efficacious in patients (pts) with relapsed and/or refractory multiple myeloma (MM) using a dose of 1.3 mg/m2 on days 1, 4, 8 & 11 of a 21-day cycle. Certain cytogenetic abnormalities are associated with poor prognosis in MM, including deletion 13, t(4;14) and the p53 deletion.(Stewart et al, JCO2005; 23(26):6339–44). Bortezomib has demonstrated the ability to overcome the poor prognosis associated with deletion 13 (Jagannath, JCO2005; 23(16S) 6501). The impact of bortezomib on a broader range of cytogenetic abnormalities, such as t(4;14) has yet to be determined. Methods: In this multicentre, open-label, non-randomized, phase 3b study, pts with MM across 13 centres in Canada, who had received at least 2 previous lines of therapy and who were refractory to or had relapsed after their last therapy were enrolled. Pts received up to eight 3-week cycles of bortezomib on days 1, 4, 8 & 11. Dexamethasone 20 mg PO was administered on each day of and day after bortezomib administration if the pts either experienced progressive disease after receiving at least 2 treatment cycles of bortezomib or had no change in disease status from baseline after receiving at least 4 treatment cycles of bortezomib. Results: 104 pts were enrolled; the mean age in this cohort was 60.7 years, and 65 (62.5%) were male. Approximately 30% of pts had a Karnofsky performance status of 70 or less at baseline. 71 pts (68.3%) had received prior thalidomide therapy, 32 (30.8%) had received a prior autotransplant and 4 (3.8%) had received prior bortezomib treatment. 74 (71.2%) received 3 or more lines of prior MM therapy. During the study, mean number of bortezomib cycles completed was 4.6 (range, 0–11 cycles), and the number of pts that completed 8 cycles of therapy was 36 (34.6%). 15.2% of pts received dexamethasone at cycle 3 and 19.2% at cycle 5. Cytogenetic analysis was performed on approximately half of the pts. Response data for cycle 5 is currently available for 69/99 (69.7%) of evaluable pts (see Table 1). Overall, 76.9% of the pts experienced Grade 3 & 4 adverse events. Safety profile observed is similar to past trial results with bortezomib. Conclusion: In this large Canadian cohort of extensively pre-treated patients with mulitple myeloma, bortezomib demonstrated good response, consistent with previous studies. Analysis correlating cytogenetic profile and response rate is ongoing and will be available at the time of conference. In addition, a detailed safety analysis and impact of prior treatment on response will be analyzed and made available at the time of conference. Table 1. Response to Bortezomib Category of Response* No. of Patients (%) *Modified SWOG: CR 100% M-protein reduction; R 75–99%; PR 50–74%; MR 25–49%; SD<25%, PD increasing M-protein Any Response (CR + VGPR + PR + MR) 47 (68.1) ---Complete Response (CR) + Very Good Partial Response (VGPR) ---22 (31.9) ---Partial Response (PR) + Minimal Response (MR) ---25 (36.2) Stable Disease 10 (14.5) Progressive Disease 12 (17.4)


2018 ◽  
Vol 129 (1) ◽  
pp. 50-59 ◽  
Author(s):  
Rupesh Kotecha ◽  
Jacob A. Miller ◽  
Vyshak A. Venur ◽  
Alireza M. Mohammadi ◽  
Samuel T. Chao ◽  
...  

OBJECTIVEThe goal of this study was to investigate the impact of stereotactic radiosurgery (SRS), BRAF status, and targeted and immune-based therapies on the recurrence patterns and factors associated with overall survival (OS) among patients with melanoma brain metastasis (MBM).METHODSA total of 366 patients were treated for 1336 MBMs; a lesion-based analysis was performed on 793 SRS lesions. The BRAF status was available for 78 patients: 35 had BRAFmut and 43 had BRAF wild-type (BRAF-WT) lesions. The Kaplan-Meier method evaluated unadjusted OS; cumulative incidence analysis determined the incidences of local failure (LF), distant failure, and radiation necrosis (RN), with death as a competing risk.RESULTSThe 12-month OS was 24% (95% CI 20%–29%). On multivariate analysis, younger age, lack of extracranial metastases, better Karnofsky Performance Status score, and fewer MBMs, as well as treatment with BRAF inhibitors (BRAFi), anti–PD-1/CTLA-4 therapy, or cytokine therapy were significantly associated with OS. For patients who underwent SRS, the 12-month LF rate was lower among those with BRAFmut lesions (6%, 95% CI 2%–11%) compared with those with BRAF-WT lesions (22%, 95% CI 13%–32%; p < 0.01). The 12-month LF rates among lesions treated with BRAFi and PD-1/CTLA-4 agents were 1% (95% CI 1%–4%) and 7% (95% CI 1%–13%), respectively. On multivariate analysis, BRAF inhibition within 30 days of SRS was protective against LF (HR 0.08, 95% CI 0.01–0.55; p = 0.01). The 12-month rates of RN were low among lesions treated with BRAFi (0%, 95% CI 0%–0%), PD-1/CTLA-4 inhibitors (2%, 95% CI 1%–5%), and cytokine therapies (6%, 95% CI 1%–13%).CONCLUSIONSPrognostic schema should incorporate BRAFi or immunotherapy status and use of targeted therapies. Treatment with a BRAF inhibitor within 4 weeks of SRS improves local control without an increased risk of RN.


2021 ◽  
Author(s):  
Jean-Baptiste Pelletier ◽  
Alessandro Moiraghi ◽  
Marc Zanello ◽  
Alexandre Roux ◽  
Sophie Peeters ◽  
...  

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.


2021 ◽  
Author(s):  
Saviola Alessia ◽  
Schipilliti Francesca Matilde ◽  
Isca Chrystel ◽  
Massimiliano Salati ◽  
Daniele Dini ◽  
...  

Abstract PurposePalliative sedation (PS) plays a critical role to give suffering relief from refractory symptoms at the end of life. Our audit aimed to assess and improve quality of PS at the Department of Oncology and Hematology of University Hospital of Modena, to verify the adherence to international guidelines, the cooperation among members of care team, focusing with attention on family’s perception of this delicate situation. MethodsFrom December 2016 to June 2019, data of patients undergoing PS in the Department were collected by an electronic folder tool, “Sedation Tool” (ST), that recorded clinical and PS informations, D-PaP, Rudkin Score and family’s perception. Results245 patients were enrolled. 82% had a Karnofsky Performance Status 10-20%. The most common cancer types were lung and gastro-intestinal carcinomas (27% and 21% respectively). Refractory symptoms observed were confusion and agitation (76%), dyspnea (39%), pain (15%), delirium (10%), psychological distress (5%). Midazolam was the drug of choice for PS. Most of patients had Rudkin score 5 after 24 hours and 33% had terminal event within a period of 24 hours from the beginning of PS. During PS most of Patient’s relatives reported peacefulness (65%), agitation/impatience in 6% of cases, concern for suffering (16%). ConclusionPS is used in case of worsening general conditions at the end-stage disease to relieve refractory symptoms with dignity. The ST can become a simple instrument to evaluate and improve PS quality, providing more attention on the impact of PS on relatives to then possibly develop new supportive procedures for patients and their families.


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