Publications by authors named "David Schiff"

244 Publications

Correction to: Incidence, risk factors and management of venous thromboembolism in patients with primary CNS lymphoma.

J Neurooncol 2021 Jul 14. Epub 2021 Jul 14.

Divison of Neuro-Oncology, Department of Neurology, University of Virginia, PO Box 800432, Charlottesville, VA, 22908-0432, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11060-021-03809-4DOI Listing
July 2021

SNO and EANO practice guideline update: Anticonvulsant prophylaxis in patients with newly diagnosed brain tumors.

Neuro Oncol 2021 Jun 26. Epub 2021 Jun 26.

Pappas Center for Neuro-Oncology, Massachusetts General Hospital, Boston, MA, USA and Harvard Medical School, Boston, MA, USA.

Objective: To update the 2000 American Academy of Neurology (AAN) practice parameter on anticonvulsant prophylaxis in patients with newly diagnosed brain tumors.

Methods: Following the 2017 AAN methodologies, a systematic literature review utilizing PubMed, EMBASE, Cochrane, and Web of Science databases was performed. The studies were rated based on the AAN therapeutic or causation classification of evidence (Class I-IV).

Results: Thirty-seven articles were selected for final analysis. There were limited high level, Class I studies and mostly Class II and III studies. The AAN affirmed the value of these guidelines.

Recommendations: In patients with newly diagnosed brain tumors who have not had a seizure, clinicians should not prescribe anti-epileptic drugs (AEDs) to reduce the risk of seizures (Level A). In brain tumor patients undergoing surgery, there is insufficient evidence to recommend prescribing AEDs to reduce the risk of seizures in the peri- or postoperative period (Level C). There is insufficient evidence to support prescribing valproic acid or levetiracetam with the intent to prolong progression-free or overall survival (Level C). Physicians may consider use of levetiracetam over older AEDs to reduce side effects (Level C). There is insufficient evidence to support using tumor location, histology, grade, molecular/imaging features, when deciding whether or not to prescribe prophylactic AEDs (Level U).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuonc/noab152DOI Listing
June 2021

Incidence, risk factors and management of venous thromboembolism in patients with primary CNS lymphoma.

J Neurooncol 2021 Jun 23. Epub 2021 Jun 23.

Divison of Neuro-Oncology, Department of Neurology, University of Virginia, PO Box 800432, Charlottesville, VA, 22908-0432, USA.

Introduction: Venous thromboembolism (VTE) is a known complication of malignancy. While brain tumors in general predispose to VTE, the incidence in primary central nervous system lymphoma (PCNSL) is poorly characterized. We sought to characterize incidence, risk factors, management, and outcome of VTE in PCNSL METHOD: Retrospective study of 78 PCNSL patients from 2/1/2002 to 4/1/2020 at the University of Virginia RESULTS: 31% (24/78) of patients developed VTE. 12.8% (10/78) had deep venous thrombosis (DVT) alone, 11.5% (9/78) isolated pulmonary embolism (PE) and 6.4% (5/78) both. The median time from PCNSL diagnosis to VTE was 3 months. In a univariate competing risks analysis, previous VTE (p < 0.001), impaired ambulation (p = 0.035), baseline hemoglobin < 10 g/dL (p = 0.025) and history of diabetes mellitus (type 1 or 2) (p = 0.007) were associated with increased VTE risk. 34.8% were anticoagulated acutely with heparin (8/23) or 65.2% LMWH (15/23), and 25.0% (6/24) received warfarin, 41.7% (10/24) LMWH, and 33.3% (8/24) DOACs long-term. One adverse event was attributable to anticoagulation (arm hematoma with hemoglobin decrease). Five patients received IVC filters with concomitant oral anticoagulation; one experienced IVC thrombosis after anticoagulation discontinuation. Six of the 24 patients experienced recurrent VTE, four while anticoagulated.

Conclusion: Patients with PCNSL are at high risk of VTE, most of which accrues in the first few months. History of VTE, diabetes mellitus (type 1 or 2), impaired ambulatory status, or hemoglobin < 10 g/dL may predispose patients to this complication. While optimal management is uncertain, anticoagulation prevented recurrent VTE in most patients without intracranial bleeding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11060-021-03791-xDOI Listing
June 2021

The state of neuro-oncology during the COVID-19 pandemic: a worldwide assessment.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab035. Epub 2021 Feb 20.

Departments of Medicine and Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.

Background: It remains unknown how the COVID-19 pandemic has changed neuro-oncology clinical practice, training, and research efforts.

Methods: We performed an international survey of practitioners, scientists, and trainees from 21 neuro-oncology organizations across 6 continents, April 24-May 17, 2020. We assessed clinical practice and research environments, institutional preparedness and support, and perceived impact on patients.

Results: Of 582 respondents, 258 (45%) were US-based and 314 (55%) international. Ninety-four percent of participants reported changes in their clinical practice. Ninety-five percent of respondents converted at least some practice to telemedicine. Ten percent of practitioners felt the need to see patients in person, specifically because of billing concerns and pressure from their institutions. Sixty-seven percent of practitioners suspended enrollment for at least one clinical trial, including 62% suspending phase III trial enrollments. More than 50% believed neuro-oncology patients were at increased risk for COVID-19. Seventy-one percent of clinicians feared for their own personal safety or that of their families, specifically because of their clinical duties; 20% had inadequate personal protective equipment. While 69% reported increased stress, 44% received no psychosocial support from their institutions. Thirty-seven percent had salary reductions and 63% of researchers temporarily closed their laboratories. However, the pandemic created positive changes in perceived patient satisfaction, communication quality, and technology use to deliver care and mediate interactions with other practitioners.

Conclusions: The pandemic has changed treatment schedules and limited investigational treatment options. Institutional lack of support created clinician and researcher anxiety. Communication with patients was satisfactory. We make recommendations to guide clinical and scientific infrastructure moving forward and address the personal challenges of providers and researchers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/noajnl/vdab035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928618PMC
February 2021

Glioblastoma cell populations with distinct oncogenic programs release podoplanin as procoagulant extracellular vesicles.

Blood Adv 2021 03;5(6):1682-1694

Department of Experimental Medicine, McGill University, Montreal, QC, Canada.

Vascular anomalies, including local and peripheral thrombosis, are a hallmark of glioblastoma (GBM) and an aftermath of deregulation of the cancer cell genome and epigenome. Although the molecular effectors of these changes are poorly understood, the upregulation of podoplanin (PDPN) by cancer cells has recently been linked to an increased risk for venous thromboembolism (VTE) in GBM patients. Therefore, regulation of this platelet-activating protein by transforming events in cancer cells is of considerable interest. We used single-cell and bulk transcriptome data mining, as well as cellular and xenograft models in mice, to analyze the nature of cells expressing PDPN, as well as their impact on the activation of the coagulation system and platelets. We report that PDPN is expressed by distinct (mesenchymal) GBM cell subpopulations and downregulated by oncogenic mutations of EGFR and IDH1 genes, along with changes in chromatin modifications (enhancer of zeste homolog 2) and DNA methylation. Glioma cells exteriorize their PDPN and/or tissue factor (TF) as cargo of exosome-like extracellular vesicles (EVs) shed from cells in vitro and in vivo. Injection of glioma-derived podoplanin carrying extracelluar vesicles (PDPN-EVs) activates platelets, whereas tissue factor carrying extracellular vesicles (TF-EVs) activate the clotting cascade. Similarly, an increase in platelet activation (platelet factor 4) or coagulation (D-dimer) markers occurs in mice harboring the corresponding glioma xenografts expressing PDPN or TF, respectively. Coexpression of PDPN and TF by GBM cells cooperatively affects tumor microthrombosis. Thus, in GBM, distinct cellular subsets drive multiple facets of cancer-associated thrombosis and may represent targets for phenotype- and cell type-based diagnosis and antithrombotic intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2020002998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993100PMC
March 2021

Predictors of early, recurrent, and intractable seizures in low-grade glioma.

Neurooncol Pract 2021 Feb 29;8(1):40-47. Epub 2020 Aug 29.

Department of Neurology, Division of Neuro-Oncology, University of Virginia, Charlottesville, Virginia.

Background: Seizures are common among patients with low-grade glioma (LGG) and can significantly affect morbidity. We sought to determine the association between the clinical and molecular factors with seizure incidence and refractoriness in LGG patients.

Methods: We conducted a retrospective review at the University of Virginia in patients with LGG (World Health Organization, WHO Grade II) evaluated between 2002 and 2015. Descriptive statistics were calculated for variables of interest, and the Kaplan-Meier method was used to estimate survival curves, which were compared with the log-rank test.

Results: A total of 291 patients were included; 254 had molecular testing performed for presence of an isocitrate dehydrogenase () mutation and/or 1p/19q codeletion. Sixty-eight percent of patients developed seizures prior to LGG diagnosis; 41% of all patients had intractable seizures. Using WHO 2016 integrated classification, there was no significant difference in seizure frequency during preoperative and postoperative periods or in developing intractable seizures, though a trend toward increased preoperative seizure incidence among patients with the mutation was identified ( = .09). Male sex was significantly associated with higher seizure incidence during preoperative ( < .001) and postoperative periods ( < .001); men were also more likely to develop intractable seizures ( = .01).

Conclusions: Seizures are common among patients with LGG. Differences in preoperative or postoperative and intractable seizure rates by WHO 2016 classification were not detected. Our data showed a trend toward higher seizure incidence preoperatively in patients with -mutant LGG. We describe a unique association between male sex and seizure incidence and intractability that warrants further study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nop/npaa054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906271PMC
February 2021

Fluid attenuation in non-contrast-enhancing tumor (nCET): an MRI Marker for Isocitrate Dehydrogenase (IDH) mutation in Glioblastoma.

J Neurooncol 2021 May 4;152(3):523-531. Epub 2021 Mar 4.

Department of Radiology, New York University School of Medicine, 550 1st Avenue, New York, NY, 10016, USA.

Purpose: The WHO 2016 update classifies glioblastomas (WHO grade IV) according to isocitrate dehydrogenase (IDH) gene mutation status. We aimed to determine MRI-based metrics for predicting IDH mutation in glioblastoma.

Methods: This retrospective study included glioblastoma cases (n = 199) with known IDH mutation status and pre-operative MRI (T1WI, T2WI, FLAIR, contrast-enhanced T1W1 at minimum). Two neuroradiologists determined the following MRI metrics: (1) primary lobe of involvement (frontal or non-frontal); (2) presence/absence of contrast-enhancement; (3) presence/absence of necrosis; (4) presence/absence of fluid attenuation in the non-contrast-enhancing tumor (nCET); (5) maximum width of peritumoral edema (cm); (6) presence/absence of multifocal disease. Inter-reader agreement was determined. After resolving discordant measurements, multivariate association between consensus MRI metrics/patient age and IDH mutation status was determined.

Results: Among 199 glioblastomas, 16 were IDH-mutant. Inter-reader agreement was calculated for contrast-enhancement (ĸ = 0.49 [- 0.11-1.00]), necrosis (ĸ = 0.55 [0.34-0.76]), fluid attenuation in nCET (ĸ = 0.83 [0.68-0.99]), multifocal disease (ĸ = 0.55 [0.39-0.70]), and primary lobe (ĸ = 0.85 [0.80-0.91]). Mean difference for peritumoral edema width between readers was 0.3 cm [0.2-0.5], p < 0.001. Multivariate analysis uncovered significant associations between IDH-mutation and fluid attenuation in nCET (OR 82.9 [19.22, ∞], p < 0.001), younger age (OR 0.93 [0.86, 0.98], p = 0.009), frontal lobe location (OR 11.08 [1.14, 352.97], p = 0.037), and less peritumoral edema (OR 0.15 [0, 0.65], p = 0.044).

Conclusions: Conventional MRI metrics and patient age predict IDH-mutation status in glioblastoma. Among MRI markers, fluid attenuation in nCET represents a novel marker with high inter-reader agreement that is strongly associated with Glioblastoma, IDH-mutant.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11060-021-03720-yDOI Listing
May 2021

Phase I Assessment of Safety and Therapeutic Activity of BAY1436032 in Patients with IDH1-Mutant Solid Tumors.

Clin Cancer Res 2021 May 23;27(10):2723-2733. Epub 2021 Feb 23.

Pharmaceuticals Division, Bayer HealthCare Pharmaceuticals, Inc., Whippany, New Jersey.

Purpose: BAY1436032, an inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1), was active against multiple IDH1-R132X solid tumors in preclinical models. This first-in-human study was designed to determine the safety and pharmacokinetics of BAY1436032, and to evaluate its potential pharmacodynamics and antitumor effects.

Patients And Methods: The study comprised of dose escalation and dose expansion cohorts. BAY1436032 tablets were orally administered twice daily on a continuous basis in subjects with m solid tumors.

Results: In dose escalation, 29 subjects with various tumor types were administered BAY1436032 across five doses (150-1,500 mg twice daily). BAY1432032 exhibited a relatively short half-life. Most evaluable subjects experienced target inhibition as indicated by a median maximal reduction of plasma R-2-hydroxyglutarate levels of 76%. BAY1436032 was well tolerated and an MTD was not identified. A dose of 1,500 mg twice daily was selected for dose expansion, where 52 subjects were treated in cohorts representing four different tumor types [lower grade glioma (LGG), glioblastoma, intrahepatic cholangiocarcinoma, and a basket cohort of other tumor types]. The best clinical outcomes were in subjects with LGG ( = 35), with an objective response rate of 11% (one complete response and three partial responses) and stable disease in 43%. As of August 2020, four of these subjects were in treatment for >2 years and still ongoing. Objective responses were observed only in LGG.

Conclusions: BAY1436032 was well tolerated and showed evidence of target inhibition and durable objective responses in a small subset of subjects with LGG.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-20-4256DOI Listing
May 2021

Encephalomyeloradiculoneuropathy Revealing a Rare Case of Intravascular Large B-Cell Lymphoma.

Cureus 2021 Jan 17;13(1):e12749. Epub 2021 Jan 17.

Neurology, University of Virginia, Charlottesville, USA.

Intravascular large B cell lymphoma (IVLBCL) is a rare form of extranodal non-Hodgkin's lymphoma, usually of B-cell lineage. Several organs are affected, most commonly the skin and the nervous system. We report a case of a 52-year-old man, with no medical history admitted with a five-month history of back pain with lower extremity numbness and tingling evolved to weakness associated with urinary retention, constipation and abdominal pain. Spinal magnetic resonance imaging (MRI) showed a gadolinium-enhancing lesion in the conus medullaris (CM). Electromyography (EMG) and nerve conduction velocity (NCV) test was consistent with demyelinating polyradiculoneuropathy in lower limbs. Slight clinical improvement with corticosteroids was observed. Three months after discharge, he presented a generalized tonic-clonic seizure. Cerebral MRI showed patchy lesions in the subcortical white matter with infiltration of the internal table of the skull with elevated serum lactate dehydrogenase (LDH). Calvarial biopsy revealed an intravascular large B-cell lymphoma. Treatment with cyclophosphamide and high-dose corticosteroids was initiated but the patient developed impaired consciousness and died of respiratory and circulatory failure six weeks after his readmission. Intravascular large B cell lymphoma should be considered in patients with a rapidly progressive severe encephalomyeloradiculoneuropathy. A biopsy of involved organs including the brain should not be delayed when IVLBCL is suspected, to initiate prompt systemic therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7759/cureus.12749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886601PMC
January 2021

Risk of Venous Thromboembolism in Grade II-IV Gliomas as a Function of Molecular Subtype.

Neurology 2021 02 22;96(7):e1063-e1069. Epub 2020 Dec 22.

From the Division of NeuroOncology (D.S.), Department of Neurology (M.D., J.J.), and Department of Public Health Sciences, Division of Biostatistics (M.S., S.J.R.), University of Virginia, Charlottesville. M.D. is currently affiliated with the Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY. J.J. is currently affiliated with the Department of Internal Medicine, Division of Hematology and Oncology, East Carolina University/Vidant Medical Center, Greenville, NC.

Objective: To determine the incidence of venous thromboembolism (VTE) in lower-grade gliomas (LGGs, WHO grades II-III) and to stratify the risk of VTE by molecular subtype in gliomas grade II-IV, we performed a retrospective review of a large cohort of patients with glioma.

Methods: We performed a retrospective analysis of a cohort of 635 adult patients with glioma with molecular testing seen at the University of Virginia with a diagnosis of diffuse glioma established from January 2005 to August 2017. Estimates of cumulative incidence of VTE were calculated with death as competing risk; significance was determined using the Fine and Gray model.

Results: Of 256 patients with LGG, 81 were isocitrate dehydrogenase (IDH) wild-type; 113 IDH mutant, 1p/19q codeleted; and 62 IDH mutant, 1p/19q intact. With a median follow-up of 17.9 months, the overall cumulative incidence of VTE was 8.2% for grade II (147 patients), 9.2% for grade III (109 patients), and 30.5% for grade IV (334 patients). In grade II-IV patients, absence of an IDH mutation was associated with a threefold increase in VTE risk when compared to IDH-mutant patients (hazard ratio 3.06, 95% confidence interval 2.03-4.64). In patients with glioblastoma, there was no difference in VTE incidence according to O6-methylguanine-DNA methyltransferase () promoter methylation status.

Conclusion: Patients with LGG have a higher VTE risk compared to the general population, which is decreased, but not eliminated, in the presence of an IDH mutation. promoter methylation in glioblastoma does not affect the incidence of VTE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000011414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055337PMC
February 2021

Automated apparent diffusion coefficient analysis for genotype prediction in lower grade glioma: association with the T2-FLAIR mismatch sign.

J Neurooncol 2020 Sep 9;149(2):325-335. Epub 2020 Sep 9.

Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, 22908, USA.

Purpose: The prognosis of lower grade glioma (LGG) patients depends (in large part) on both isocitrate dehydrogenase (IDH) gene mutation and chromosome 1p/19q codeletion status. IDH-mutant LGG without 1p/19q codeletion (IDHmut-Noncodel) often exhibit a unique imaging appearance that includes high apparent diffusion coefficient (ADC) values not observed in other subtypes. The purpose of this study was to develop an ADC analysis-based approach that can automatically identify IDHmut-Noncodel LGG.

Methods: Whole-tumor ADC metrics, including fractional tumor volume with ADC > 1.5 × 10mm/s (V), were used to identify IDHmut-Noncodel LGG in a cohort of N = 134 patients. Optimal threshold values determined in this dataset were then validated using an external dataset containing N = 93 cases collected from The Cancer Imaging Archive. Classifications were also compared with radiologist-identified T2-FLAIR mismatch sign and evaluated concurrently to identify added value from a combined approach.

Results: V classified IDHmut-Noncodel LGG in the internal cohort with an area under the curve (AUC) of 0.80. An optimal threshold value of 0.35 led to sensitivity/specificity = 0.57/0.93. Classification performance was similar in the validation cohort, with V ≥ 0.35 achieving sensitivity/specificity = 0.57/0.91 (AUC = 0.81). Across both groups, 37 cases exhibited positive T2-FLAIR mismatch sign-all of which were IDHmut-Noncodel. Of these, 32/37 (86%) also exhibited V ≥ 0.35, as did 23 additional IDHmut-Noncodel cases which were negative for T2-FLAIR mismatch sign.

Conclusion: Tumor subregions with high ADC were a robust indicator of IDHmut-Noncodel LGG, with V achieving > 90% classification specificity in both internal and validation cohorts. V exhibited strong concordance with the T2-FLAIR mismatch sign and the combination of both parameters improved sensitivity in detecting IDHmut-Noncodel LGG.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11060-020-03611-8DOI Listing
September 2020

CODEL: phase III study of RT, RT + TMZ, or TMZ for newly diagnosed 1p/19q codeleted oligodendroglioma. Analysis from the initial study design.

Neuro Oncol 2021 03;23(3):457-467

Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio, USA.

Background: We report the analysis involving patients treated on the initial CODEL design.

Methods: Adults (>18) with newly diagnosed 1p/19q World Health Organization (WHO) grade III oligodendroglioma were randomized to radiotherapy (RT; 5940 centigray ) alone (arm A); RT with concomitant and adjuvant temozolomide (TMZ) (arm B); or TMZ alone (arm C). Primary endpoint was overall survival (OS), arm A versus B. Secondary comparisons were performed for OS and progression-free survival (PFS), comparing pooled RT arms versus TMZ-alone arm.

Results: Thirty-six patients were randomized equally. At median follow-up of 7.5 years, 83.3% (10/12) TMZ-alone patients progressed, versus 37.5% (9/24) on the RT arms. PFS was significantly shorter in TMZ-alone patients compared with RT patients (hazard ratio [HR] = 3.12; 95% CI: 1.26, 7.69; P = 0.014). Death from disease progression occurred in 3/12 (25%) of TMZ-alone patients and 4/24 (16.7%) on the RT arms. OS did not statistically differ between arms (comparison underpowered). After adjustment for isocitrate dehydrogenase (IDH) status (mutated/wildtype) in a Cox regression model utilizing IDH and RT treatment status as covariables (arm C vs pooled arms A + B), PFS remained shorter for patients not receiving RT (HR = 3.33; 95% CI: 1.31, 8.45; P = 0.011), but not OS ((HR = 2.78; 95% CI: 0.58, 13.22, P = 0.20). Grade 3+ adverse events occurred in 25%, 42%, and 33% of patients (arms A, B, and C). There were no differences between arms in neurocognitive decline comparing baseline to 3 months.

Conclusions: TMZ-alone patients experienced significantly shorter PFS than patients treated on the RT arms. The ongoing CODEL trial has been redesigned to compare RT + PCV versus RT + TMZ.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuonc/noaa168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992874PMC
March 2021

Correction to: Neurological and Medical Complications in Brain Tumor Patients.

Curr Neurol Neurosci Rep 2020 Jul 14;20(9):40. Epub 2020 Jul 14.

Department of Neurology, University of Virginia, P.O. Box 800432, Charlottesville, VA, 22908, USA.

The order of the authors was inadvertently inverted; Dr. Alyahya is the intended first author.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11910-020-01066-yDOI Listing
July 2020

Neurological and Medical Complications in Brain Tumor Patients.

Curr Neurol Neurosci Rep 2020 06 29;20(8):33. Epub 2020 Jun 29.

Department of Neurology, University of Virginia, P.O. Box 800432, Charlottesville, VA, 22908, USA.

Purpose Of Review: Patients with brain tumors are susceptible to multiple complications that can affect their survival or quality of life. The scope of these complications is widening due to prolonged overall survival and improved therapies. In this review, we discuss the most common complications in this patient population focusing on the recent literature. We specifically concentrated on tumor-related epilepsy, vasogenic edema, infectious, vascular, chemotherapeutic, radiation, endocrine, and cognitive complications.

Recent Findings: Molecular biomarkers play a role in epileptogenicity in brain tumor patients, and anti-epileptic drugs may cause neuro-cognitive side effects independent of other factors. The pathophysiology of vasogenic edema remains complex and poorly understood. Limited data suggest that newer oral anticoagulants appear to be safe and effective in venous and arterial thromboembolic complications. Brain tumor patients are prone to a wide variety of complications, including some related to new therapies. Optimal management of these complications improves quality of life, and in some cases overall survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11910-020-01054-2DOI Listing
June 2020

Glioblastoma in adults: a Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions.

Neuro Oncol 2020 08;22(8):1073-1113

Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.

Glioblastomas are the most common form of malignant primary brain tumor and an important cause of morbidity and mortality. In recent years there have been important advances in understanding the molecular pathogenesis and biology of these tumors, but this has not translated into significantly improved outcomes for patients. In this consensus review from the Society for Neuro-Oncology (SNO) and the European Association of Neuro-Oncology (EANO), the current management of isocitrate dehydrogenase wildtype (IDHwt) glioblastomas will be discussed. In addition, novel therapies such as targeted molecular therapies, agents targeting DNA damage response and metabolism, immunotherapies, and viral therapies will be reviewed, as well as the current challenges and future directions for research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuonc/noaa106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594557PMC
August 2020

Volumetric analysis of IDH-mutant lower-grade glioma: a natural history study of tumor growth rates before and after treatment.

Neuro Oncol 2020 12;22(12):1822-1830

Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.

Background: Lower-grade gliomas (LGGs) with isocitrate dehydrogenase 1 and/or 2 (IDH1/2) mutations have long survival times, making evaluation of treatment efficacy difficult. We investigated the volumetric growth rate of IDH mutant gliomas before and after treatment with established glioma therapies to determine whether a significant change in growth rate could be documented and perhaps be used in the future to evaluate treatment response to investigational agents in LGG trials.

Methods: In this multicenter retrospective study, 230 adult patients with IDH1/2 mutated LGGs (World Health Organization grade II or III) undergoing surgery, radiation, or chemotherapy for progressive non-enhancing tumor were identified. Subjects were required to have 3 MRI scans containing T2/fluid attenuated inversion recovery imaging spanning a minimum of 6 months prior to treatment. A mixed-effect model was used to estimate tumor growth prior to treatment. A subset of 95 patients who received chemotherapy, radiotherapy, or chemoradiotherapy and had 2 posttreatment imaging time points available were evaluated for change in pre- and posttreatment volumetric growth rates using a piecewise mixed model.

Results: The pretreatment volumetric growth rate across all 230 patients was 27.37%/180 days (95% CI: [23.36%, 31.51%]). In the 95 patients with both pre- and posttreatment scans available, there was a significant difference in volumetric growth rates before (26.63%/180 days, 95% CI: [19.31%, 34.40%]) and after treatment (-15.24% /180 days, 95% CI: [-21.37%, -8.62%]) (P < 0.0001). The growth rates for patient subgroup with 1p/19q codeletion (N = 118) was significantly slower than the rate of the 1p/19q non-codeleted group (N = 68) (22.84% vs 35.49%, P = 0.0108).

Conclusion: In this study, we evaluated the growth rates of IDH mutant gliomas before and after standard therapy. Further study is needed to establish whether a change in growth rate is associated with patient survival and its use as a surrogate endpoint in clinical trials for IDH mutant LGGs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuonc/noaa105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746936PMC
December 2020

Urgent Considerations for the Neuro-oncologic Treatment of Patients with Gliomas During the COVID-19 Pandemic.

Neuro Oncol 2020 Apr 11. Epub 2020 Apr 11.

Department of Neurosurgery, Inova Neuroscience and Spine Institute, Virginia Commonwealth University.

The COVID-19 outbreak is posing unprecedented risks and challenges for all communities and healthcare systems, worldwide. There are unique considerations for many adult patients with gliomas who are vulnerable to the novel coronavirus due to older age and immunosuppression. As patients with terminal illnesses, they present ethical challenges for centers that may need to ration access to ventilator care due to insufficient critical care capacity. It is urgent for the neuro-oncology community to develop a pro-active and coordinated approach to the care of adults with gliomas in order to provide them with the best possible oncologic care while also reducing their risk of viral infection during times of potential healthcare system failure. In this article, we present an approach developed by an international multi-disciplinary group to optimize the care of adults with gliomas during this pandemic. We recommend measures to promote strict social distancing and minimize exposures for patients, address risk and benefit of all therapeutic interventions, pro-actively develop end of life plans, educate patients and caregivers and ensure the health of the multi-disciplinary neuro-oncology workforce. This pandemic is already changing neuro-oncologic care delivery around the globe. It is important to highlight opportunities to maximize the benefit and minimize the risk of glioma management during this pandemic and potentially, in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuonc/noaa090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184330PMC
April 2020

Checkpoint inhibitor failure in hypermutated and mismatch repair-mutated recurrent high-grade gliomas.

Neurooncol Pract 2019 Dec 7;6(6):424-427. Epub 2019 Apr 7.

University of Virginia School of Medicine, Division of Neuro-Oncology, Department of Neurology, University of Virginia, Charlottesville.

Background: Recurrent high-grade gliomas in adults remain a deadly cancer with median survival of less than 1 year. In the absence of effective agents, immunotherapy with checkpoint inhibitors has been adopted as a potentially beneficial next step for recurrences with hypermutated or mismatch repair-mutated phenotypes. The rationale for their use, however, is based on case reports and studies with other types of cancer.

Methods: We reviewed 4 cases of hypermutated or mismatch repair-mutated recurrent high-grade gliomas treated with checkpoint inhibitors.

Results: All cases had recurrent high-grade glioma that harbored either a hypermutated phenotype and/or a mismatch repair mutation. Treatment with checkpoint inhibitor therapy resulted in no significant response.

Conclusions: In our experience, hypermutated or mismatch repair-mutated high-grade gliomas in adults do not respond to checkpoint inhibitors alone. This lack of efficacy is in agreement with underwhelming results of clinical trials examining checkpoint inhibitors in high-grade gliomas. The case reports of responders have been in pediatric patients with glioma and are likely a different subtype altogether.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nop/npz016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899050PMC
December 2019

MRI and CT Identify Isocitrate Dehydrogenase -Mutant Lower-Grade Gliomas Misclassified to 1p/19q Codeletion Status with Fluorescence in Situ Hybridization.

Radiology 2020 01 12;294(1):160-167. Epub 2019 Nov 12.

From the Department of Radiology and Medical Imaging (S.H.P., P.P.B., T.J.D.), Department of Pathology, Divisions of Neuropathology and Molecular Diagnostics (E.K.S.M., M.B.S.L., E.S.W.), Department of Neurology, Division of Neuro-Oncology (D.S., C.E.F.), and Department of Public Health Sciences (J.T.P.), University of Virginia Health System, PO Box 800170, Charlottesville, VA 22908; and Department of Radiology and Neurosurgery, NYU Langone Medical Center, New York, NY (R.J.).

Background Fluorescence in situ hybridization (FISH) is a standard method for 1p/19q codeletion testing in diffuse gliomas but occasionally renders erroneous results. Purpose To determine whether MRI/CT analysis identifies isocitrate dehydrogenase ()-mutant gliomas misassigned to 1p/19q codeletion status with FISH. Materials and Methods Data in patients with -mutant lower-grade gliomas (World Health Organization grade II/III) and 1p/19q codeletion status determined with FISH that were accrued from January 1, 2010 to October 1, 2017, were included in this retrospective study. Two neuroradiologist readers analyzed the pre-resection MRI findings (and CT findings, when available) to predict 1p/19q status (codeleted or noncodeleted) and provided a prediction confidence score (1 = low, 2 = moderate, 3 = high). Percentage concordance between the consensus neuroradiologist 1p/19q prediction and the FISH result was calculated. For gliomas where consensus neuroradiologist 1p/19q prediction differed from the FISH result and consensus neuroradiologist confidence score was 2 or greater, further 1p/19q testing was performed with chromosomal microarray analysis (CMA). Nine control specimens were randomly chosen from the remaining study sample for CMA. Percentage concordance between FISH and CMA among the CMA-tested cases was calculated. Results A total of 112 patients (median age, 38 years [interquartile range, 31-51 years]; 57 men) were evaluated (112 gliomas). Percentage concordance between the consensus neuroradiologist 1p/19q prediction and the FISH result was 84.8% (95 of 112; 95% confidence interval: 76.8%, 90.9%). Among the 17 neuroradiologist-FISH discordances, there were nine gliomas associated with a consensus neuroradiologist confidence score of 2 or greater. In six (66.7%) of these nine gliomas, the 1p/19q codeletion status as determined with CMA disagreed with the FISH result and agreed with the consensus neuroradiologist prediction. For the nine control specimens, there was 100% agreement between CMA and FISH for 1p/19q determination. Conclusion MRI and CT analysis can identify diffuse gliomas misassigned to 1p/19q codeletion status with fluorescence in situ hybridization (FISH). Further molecular testing should be considered for gliomas with discordant neuroimaging and FISH results. © RSNA, 2019
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2019191140DOI Listing
January 2020

Oligodendroglioma confers higher risk of radiation necrosis.

J Neurooncol 2019 Nov 23;145(2):309-319. Epub 2019 Sep 23.

Department of Neurology, Division of Neuro-Oncology, University of Virginia Health System, P.O. Box 800432, Charlottesville, VA, 22908, USA.

Background: Radiation therapy (RT) remains a mainstay for the treatment of lower grade gliomas. Radiation neurotoxicity is a serious complication, carrying high morbidity in the absence of tumor progression. The incidence remains poorly categorized and known risk factors identified are related to the radiation modality. We hypothesized that patients with oligodendroglioma have a higher risk of radiation necrosis (RN) as compared to patients with astrocytoma.

Methods: We conducted a retrospective review of adults with lower grade diffuse gliomas over a 10-year span. The primary outcome was RN, either pathologically confirmed or clinically diagnosed. Cases without pathological confirmation must have been symptomatic, requiring administration of bevacizumab or high-dose steroids. Cox proportional hazard ratios were used for multivariate analyses.

Results: In 319 patients, we identified RN in 41 patients (12.9%): 28 patients (21.3%) with oligodendroglioma and 13 (6.9%) with astrocytoma (HR 3.42, p < 0.001). Patients with oligodendroglioma who received > 54 Gy had a higher incidence (31.2%) than those receiving ≤ 54 Gy (14.3%, HR 6.9, p = 0.002). There was no similar correlation among patients with astrocytoma. There was no difference in incidence based on use of concomitant temozolomide. Radiation necrosis appeared within 24 months from radiation in 80.5% of patients.

Conclusion: Our study suggests that patients with oligodendroglioma are at higher risk of developing RN. The incidence increases with increasing radiation dose in patients with oligodendroglioma but not with astrocytoma. RN usually appears within 24 months from RT. Patients with oligodendroglioma receiving > 54 Gy are at highest risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11060-019-03297-7DOI Listing
November 2019

Increased intratumoral infiltration in IDH wild-type lower-grade gliomas observed with diffusion tensor imaging.

J Neurooncol 2019 Nov 17;145(2):257-263. Epub 2019 Sep 17.

Department of Radiology, University of Virginia, Charlottesville, VA, 22908, USA.

Purpose: Diffuse lower grade gliomas (LGG) with isocitrate dehydrogenase (IDH) gene mutations (IDH) have a distinct survival advantage compared with IDH wild-type (IDH) cases but the mechanism underlying this disparity is not well understood. Diffusion Tensor Imaging (DTI) has identified infiltrated non-enhancing tumor regions that are characterized by low isotropic (p) and high anisotropic (q) diffusion tensor components that associate with poor survival in glioblastoma. We hypothesized that similar regions are more prevalent in IDH (vs. IDH) LGG.

Methods: p and q maps were reconstructed from preoperative DTI scans in N = 41 LGG patients with known IDH mutation and 1p/19q codeletion status. Enhancing and non-enhancing tumor volumes were autosegmented from standard (non-DTI) MRI scans. Percentage non-enhancing tumor volumes exhibiting low p and high q (V) were then determined using threshold values (p = 2 × 10mm/s, q = 3 × 10 mm/s) and compared between IDH and IDH LGG, and between IDH LGG with and without 1p/19q codeletion.

Results: V volumes were significantly larger in IDH LGG than in IDH LGG (35.4 ± 18.3% vs. 15.9 ± 7.6%, P < 0.001). V volumes did not significantly differ between IDH LGG with and without 1p/19q codeletion (17.1 ± 9.5% vs. 14.8 ± 5.8%, P = 1.0).

Conclusion: IDH LGG exhibited larger volumes with suppressed isotropic diffusion (p) and high anisotropic diffusion (q) which reflects regions with increased cell density but non-disrupted neuronal structures. This may indicate a greater prevalence of infiltrative tumor in IDH LGG.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11060-019-03291-zDOI Listing
November 2019

Tumor pharmacokinetics and pharmacodynamics of the CDK4/6 inhibitor ribociclib in patients with recurrent glioblastoma.

J Neurooncol 2019 Sep 9;144(3):563-572. Epub 2019 Aug 9.

Department of Neurology, Division of Neuro-Oncology, University of Virginia Health System, P.O. Box 800432, Charlottesville, VA, 22908, USA.

Introduction: We conducted a phase Ib study (NCT02345824) to determine whether ribociclib, an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), penetrates tumor tissue and modulates downstream signaling pathways including retinoblastoma protein (Rb) in patients with recurrent glioblastoma (GBM).

Methods: Study participants received ribociclib (600 mg QD) for 8-21 days before surgical resection of their recurrent GBM. Total and unbound concentrations of ribociclib were measured in samples of tumor tissue, plasma, and cerebrospinal fluid (CSF). We analyzed tumor specimens obtained from the first (initial/pre-study) and second (recurrent/on-study) surgery by immunohistochemistry for Rb status and downstream signaling of CDK4/6 inhibition. Participants with Rb-positive recurrent tumors continued ribociclib treatment on a 21-day-on, 7-day-off schedule after surgery, and were monitored for toxicity and disease progression.

Results: Three participants with recurrent Rb-positive GBM participated in this study. Mean unbound (pharmacologically active) ribociclib concentrations in plasma, CSF, MRI-enhancing, MRI-non-enhancing, and tumor core regions were 0.337 μM, 0.632 μM, 1.242 nmol/g, 0.484 nmol/g, and 1.526 nmol/g, respectively, which exceeded the in vitro IC (0.04 μM) for inhibition of CDK4/6 in cell-free assay. Modulation of pharmacodynamic markers of ribociclib CDK 4/6 inhibition in tumor tissues were inconsistent between study participants. No participants experienced serious adverse events, but all experienced early disease progression.

Conclusions: This study suggests that ribociclib penetrated recurrent GBM tissue at concentrations predicted to be therapeutically beneficial. Our study was unable to demonstrate tumor pharmacodynamic correlates of drug activity. Although well tolerated, ribociclib monotherapy seemed ineffective for the treatment of recurrent GBM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11060-019-03258-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863163PMC
September 2019

A phase 1 and randomized, placebo-controlled phase 2 trial of bevacizumab plus dasatinib in patients with recurrent glioblastoma: Alliance/North Central Cancer Treatment Group N0872.

Cancer 2019 11 10;125(21):3790-3800. Epub 2019 Jul 10.

Department of Neurology, University of Virginia Medical Center, Charlottesville, Virginia.

Background: Src signaling is markedly upregulated in patients with invasive glioblastoma (GBM) after the administration of bevacizumab. The Src family kinase inhibitor dasatinib has been found to effectively block bevacizumab-induced glioma invasion in preclinical models, which led to the hypothesis that combining bevacizumab with dasatinib could increase bevacizumab efficacy in patients with recurrent GBM.

Methods: After the completion of the phase 1 component, the phase 2 trial (ClinicalTrials.gov identifier NCT00892177) randomized patients with recurrent GBM 2:1 to receive 100 mg of oral dasatinib twice daily (arm A) or placebo (arm B) on days 1 to 14 of each 14-day cycle combined with 10 mg/kg of intravenous bevacizumab on day 1 of each 14-day cycle. The primary endpoint was 6-month progression-free survival (PFS6).

Results: In the 121 evaluable patients, the PFS6 rate was numerically, but not statistically, higher in arm A versus arm B (28.9% [95% CI, 19.5%-40.0%] vs 18.4% [95% CI, 7.7%-34.4%]; P = .22). Similarly, there was no significant difference in the median overall survival noted between the treatment arms (7.3 months and 7.7 months, respectively; P = .93). The objective response rate was 15.7% in arm A and 26.3% in arm B (P = .52), but with a significantly longer duration in patients treated on arm A (16.3 months vs 2 months). The incidence of grade ≥3 toxicity was comparable between treatment arms, with hematologic toxicities occurring more frequently in arm A versus arm B (15.7% vs 7.9%) (adverse events were assessed as per the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). Correlative tissue analysis demonstrated an association between pSRC/LYN signaling in patient tumors and outcome.

Conclusions: Despite upregulation of Src signaling in patients with GBM, the combination of bevacizumab with dasatinib did not appear to significantly improve the outcomes of patients with recurrent GBM compared with bevacizumab alone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.32340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788934PMC
November 2019

Multimodality Therapy of Patients with Refractory Meningiomas.

Curr Treat Options Oncol 2019 05 9;20(6):50. Epub 2019 May 9.

Division of Neuro-Oncology, School of Medicine, University of Virginia, PO Box 800432, Charlottesville, VA, 22908, USA.

Opinion Statement: Recurrent and refractory meningiomas are a clinical challenge and treatment at the time of recurrence is not well delineated. Treatment with surgery and/or radiation remain the mainstay, but each has their limitations and risks. The search for an adjuvant systemic therapy continues and as many of the initially promising approaches have not had reproducible responses. Bevacizumab has shown some efficacy in controlling recurrent disease and could be useful in disease that is multifocal or in close proximity to critical structures. Other targeted therapies, as well as immunotherapy, are being studied and trials are in development. Though we are hopeful that these novel therapies will benefit patients with refractory meningiomas, we approach them with some trepidation. This is due to prior failures of immunotherapy and targeted therapy in central nervous system disease. In addition, there is known difficulty in developing trials and assessing response with these slow-growing tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11864-019-0648-zDOI Listing
May 2019

Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT): A Bayesian Adaptive Platform Trial to Develop Precision Medicines for Patients With Glioblastoma.

JCO Precis Oncol 2019 27;3. Epub 2019 Mar 27.

Dana-Farber Cancer Institute, Boston, MA.

Purpose: Adequately prioritizing the numerous therapies and biomarkers available in late-stage testing for patients with glioblastoma (GBM) requires an efficient clinical testing platform. We developed and implemented INSIGhT (Individualized Screening Trial of Innovative Glioblastoma Therapy) as a novel adaptive platform trial (APT) to develop precision medicine approaches in GBM.

Methods: INSIGhT compares experimental arms with a common control of standard concurrent temozolomide and radiation therapy followed by adjuvant temozolomide. The primary end point is overall survival. Patients with newly diagnosed unmethylated GBM who are R132H mutation negative and with genomic data available for biomarker grouping are eligible. At the initiation of INSIGhT, three experimental arms (neratinib, abemaciclib, and CC-115), each with a proposed genomic biomarker, are tested simultaneously. Initial randomization is equal across arms. As the trial progresses, randomization probabilities adapt on the basis of accumulating results using Bayesian estimation of the biomarker-specific probability of treatment impact on progression-free survival. Treatment arms may drop because of low probability of treatment impact on overall survival, and new arms may be added. Detailed information on the statistical model and randomization algorithm is provided to stimulate discussion on trial design choices more generally and provide an example for other investigators developing APTs.

Conclusion: INSIGhT (NCT02977780) is an ongoing novel biomarker-based, Bayesian APT for patients with newly diagnosed unmethylated GBM. Our goal is to dramatically shorten trial execution timelines while increasing scientific power of results and biomarker discovery using adaptive randomization. We anticipate that trial execution efficiency will also be improved by using the APT format, which allows for the collaborative addition of new experimental arms while retaining the overall trial structure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/PO.18.00071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448806PMC
March 2019

Anticonvulsant prophylaxis and steroid use in adults with metastatic brain tumors: summary of SNO and ASCO endorsement of the Congress of Neurological Surgeons guidelines.

Neuro Oncol 2019 03;21(4):424-427

Cleveland Clinic, Cleveland, OH, USA.

Background: The Congress of Neurological Surgeons (CNS) has developed a series of guidelines on the treatment of adults with metastatic brain tumors, including systemic therapy and supportive care topics. ASCO has a policy and set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations.

Methods: Two CNS Guidelines were reviewed for developmental rigor by methodologists and an independent multi-disciplinary Expert Panel was formed to review the content and assess agreement with the recommendations. The expert panel voted to endorse the two guidelines and ASCO and SNO independently reviewed and approved the ASCO/SNO guideline endorsement.

Results: The ASCO/SNO Expert Panel determined that the recommendations from the CNS anticonvulsants and steroids guidelines, published January 9, 2019, are clear, thorough, and based upon the most relevant scientific evidence. ASCO/SNO endorsed these two CNS guidelines, with minor alterations.

Conclusions: Key recommendations include: prophylactic anti-epileptic drugs were not recommended for routine use; corticosteroids (specifically dexamethasone) were recommended for temporary symptomatic relief in patients with neurologic symptoms and signs related to mass effect from brain metastases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuonc/noz034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422436PMC
March 2019

Anticonvulsant Prophylaxis and Steroid Use in Adults With Metastatic Brain Tumors: ASCO and SNO Endorsement of the Congress of Neurological Surgeons Guidelines.

J Clin Oncol 2019 05 18;37(13):1130-1135. Epub 2019 Mar 18.

3 Cleveland Clinic, Cleveland, OH.

Purpose: The Congress of Neurological Surgeons (CNS) has developed a series of guidelines for the treatment of adults with metastatic brain tumors, including systemic therapy and supportive care topics. ASCO has a policy and set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations.

Methods: Two CNS guidelines were reviewed for developmental rigor by methodologists, and an independent multidisciplinary Expert Panel was formed to review the content and assess agreement with the recommendations. The Expert Panel voted to endorse the two guidelines, and ASCO and Society for Neuro-Oncology (SNO) independently reviewed and approved the ASCO/SNO guideline endorsement.

Results: The ASCO/SNO Expert Panel determined that the recommendations from the CNS anticonvulsants and steroids guidelines, published January 9, 2019, are clear, thorough, and based on the most relevant scientific evidence. ASCO/SNO endorsed these two CNS guidelines with minor alterations.

Recommendations: Key recommendations include the following: prophylactic antiepileptic drugs were not recommended for routine use; and corticosteroids, specifically dexamethasone, were recommended for temporary symptomatic relief in patients with neurologic symptoms and signs related to mass effect from brain metastases. Additional information is available at www.asco.org/neurooncology-guidelines .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.18.02085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098828PMC
May 2019

Recent developments and future directions in adult lower-grade gliomas: Society for Neuro-Oncology (SNO) and European Association of Neuro-Oncology (EANO) consensus.

Neuro Oncol 2019 07;21(7):837-853

Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

The finding that most grades II and III gliomas harbor isocitrate dehydrogenase (IDH) mutations conveying a relatively favorable and fairly similar prognosis in both tumor grades highlights that these tumors represent a fundamentally different entity from IDH wild-type gliomas exemplified in most glioblastoma. Herein we review the most recent developments in molecular neuropathology leading to reclassification of these tumors based upon IDH and 1p/19q status, as well as the potential roles of methylation profiling and deletional analysis of cyclin-dependent kinase inhibitor 2A and 2B. We discuss the epidemiology, clinical manifestations, benefit of surgical resection, and neuroimaging features of lower-grade gliomas as they relate to molecular subtype, including advanced imaging techniques such as 2-hydroxyglutarate magnetic resonance spectroscopy and amino acid PET scanning. Recent, ongoing, and planned studies of radiation therapy and both cytotoxic and targeted chemotherapies are summarized, including both small molecule and immunotherapy approaches specifically targeting the mutant IDH protein.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuonc/noz033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620638PMC
July 2019

FDG PET/MRI Coregistration Helps Predict Response to Gamma Knife Radiosurgery in Patients With Brain Metastases.

AJR Am J Roentgenol 2019 02 13;212(2):425-430. Epub 2018 Nov 13.

8 Department of Neurology, Neuro-Oncology Center, University of Virginia, Charlottesville, VA.

Objective: The purpose of this study was to determine whether relative standardized uptake value (SUV) measurements at FDG PET/MRI coregistration are predictive of local tumor control in patients with brain metastases treated with stereotactic radiosurgery (SRS).

Materials And Methods: A retrospective review was conducted of the images and clinical characteristics of a cohort of patients with brain metastases from non-CNS neoplasms treated with gamma knife radiosurgery (GKRS) who underwent posttherapy FDG PET because of MRI findings concerning for progression. The PET and contrast-enhanced MR images were fused. Relative SUV measurements were calculated from ROIs placed in the area of highest FDG uptake within the enhancing lesion and in the contralateral normal-appearing white matter. Relative SUV was defined as the ratio of maximum SUV in the tumor to maximum SUV in healthy white matter. Two independent readers evaluated response to GKRS using serial posttherapy MRI performed at least 3 months after GKRS completion. The relation between relative SUV and local tumor progression was evaluated with respect to treatment effect.

Results: Eighty-five patients (48 [56.5%] women, 37 [43.5%] men; mean age at diagnosis, 60.5 ± 11.3 years) met the inclusion criteria. Thirty-three (38.8%) lesions progressed after SRS. There was a significant association between relative SUV and local tumor control (p = 0.035). Relative SUV provided a diagnostic ROC AUC of 0.67 (95% CI, 0.55-0.79).

Conclusion: Quantitative relative SUV at posttherapy FDG PET serves as a biomarker of response to SRS in patients with brain metastases in cases in which lesion growth is identified at follow-up MRI. This prognostic data may affect management, supporting the need for further therapeutic actions for selected patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2214/AJR.18.20006DOI Listing
February 2019