Driver safety in patients with primary brain tumors

Abstract Background Operating a motor vehicle involves multiple cognitive and sensorimotor faculties. Neurological conditions pose driving risk, but this has not been examined in patients with primary brain tumors. Methods Sixty-four patients with primary brain tumors (32 left hemisphere; 69% glioblastoma) completed the Cognitive Behavioral Driver’s Inventory (CBDI). A subset also completed broader cognitive testing. Patient characteristics, CBDI measures, and broader neuropsychological test scores were compared between Passing and Nonpassing groups. Follow-up logistic regression analyses identified patient characteristics and CBDI measures predictive of Pass/Nonpass outcome. Point-biserial correlations determined associations between neuropsychological tests and CBDI outcome. Results Sixty-nine percent of patients were classified as passing the CBDI. Nonpassing patients were older and more likely to have WHO grade IV and temporal lobe tumors. Age was the most salient predictor of CBDI performance. CBDI measures of speeded visual search and set-shifting, speeded response inhibition, vigilance and freedom from distractibility, and basic visual scanning speed were predictive of Pass/Nonpass outcome. Neuropsychological tests of memory in particular, but also speeded visual scanning and discrimination, executive function, basic visual attention, visuoconstruction, and manual dexterity (dominant hand), were associated with CBDI outcome. Conclusions A sizeable proportion of patients with primary brain tumors appear at risk of driving difficulty, particularly those with higher-grade tumors and of older age. Memory, visual attention, and executive difficulties appear to contribute most to driving safety risk as determined by the CBDI. These results highlight the importance of driving safety screening in this population.

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Apolipoprotein D Expression in Primary Brain Tumors: Analysis by Quantitative RT-PCR in Formalin-fixed, Paraffin-embedded Tissue

Journal of Histochemistry & Cytochemistry ◽

10.1369/jhc.4a6530.2005 ◽

2005 ◽

Vol 53 (8) ◽

pp. 963-969 ◽

Cited By ~ 6

Author(s):

Stephen B. Hunter ◽

Vijay Varma ◽

Bahig Shehata ◽

J.D.L. Nolen ◽

Cynthia Cohen ◽

...

Keyword(s):

Brain Tumors ◽

Tumor Type ◽

Rt Pcr ◽

Who Grade ◽

Primary Brain Tumors ◽

Formalin Fixed Paraffin ◽

Pilocytic Astrocytomas ◽

Formalin Fixed Paraffin Embedded ◽

Apolipoprotein D ◽

Formalin Fixed

Apolipoprotein D (apoD) expression has been shown to correlate both with cell cycle arrest and with prognosis in several types of malignancy, including central nervous system astrocytomas and medulloblastomas. ApoD expression was investigated by real-time quantitative RT-PCR using RNA extracted from 68 formalin-fixed, paraffin-embedded brain specimens. Glyceraldehyde phosphate dehydrogenase was used as an internal control. Quantitation was achieved on all specimens. Sixteen poorly infiltrating WHO grade I glial neoplasms (i.e., pilocytic astrocytomas and gangliogliomas) showed an average 20-fold higher apoD expression level compared with the 20 diffusely infiltrating glial neoplasms (i.e., glioblastoma, anaplastic astrocytoma, oligodendrogliomas; p=0.00004). A small number of exceptions (i.e., two high-expressing glioblastomas and three low-expressing gangliogliomas) were identified. Analyzed as individual tumor groups, poorly infiltrating grade I pilocytic astrocytomas and gangliogliomas differed significantly from each tumor type within the diffusely infiltrating higher-grade category ( p<0.05 for each comparison) but not from each other ( p>0.05). Conversely, each individual tumor type within the diffusely infiltrating category differed significantly from both pilocytic astrocytomas and gangliogliomas ( p<0.05) but did not vary from other infiltrating tumors ( p>0.05). Ependymomas, non-infiltrating grade II neoplasms, expressed levels of apoD similar to or lower than levels expressed by the diffusely infiltrating gliomas. Ten medulloblastomas with survival longer than 3 years averaged slightly higher apoD expression than four fatal medulloblastomas; however, this result was not statistically significant and individual exceptions were notable. In 17 of the medulloblastomas, MIB-1 proliferation rates quantitated by image cytometry did not correlate with apoD expression. In addition, apoD expression was 5-fold higher in the slowly proliferating grade I glial neoplasms compared with non-proliferating normal brain tissue ( p=0.01), suggesting that apoD expression is not simply an inverse measure of proliferation. ApoD expression measured by quantitative RT-PCR may be useful in the differential diagnosis of primary brain tumors, particularly pilocytic astrocytomas and gangliogliomas.

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Use of fluorescence to guide resection or biopsy of primary brain tumors and brain metastases

Neurosurgical FOCUS ◽

10.3171/2013.12.focus13464 ◽

2014 ◽

Vol 36 (2) ◽

pp. E10 ◽

Cited By ~ 80

Author(s):

Serge Marbacher ◽

Elisabeth Klinger ◽

Lucia Schwyzer ◽

Ingeborg Fischer ◽

Edin Nevzati ◽

...

Keyword(s):

Adverse Effects ◽

Brain Tumors ◽

Brain Metastases ◽

Low Grade ◽

High Grade ◽

Open Resection ◽

Who Grade ◽

Primary Brain Tumors ◽

High Grade Gliomas ◽

Surgical Adjunct

Object The accurate discrimination between tumor and normal tissue is crucial for determining how much to resect and therefore for the clinical outcome of patients with brain tumors. In recent years, guidance with 5-aminolevulinic acid (5-ALA)–induced intraoperative fluorescence has proven to be a useful surgical adjunct for gross-total resection of high-grade gliomas. The clinical utility of 5-ALA in resection of brain tumors other than glioblastomas has not yet been established. The authors assessed the frequency of positive 5-ALA fluorescence in a cohort of patients with primary brain tumors and metastases. Methods The authors conducted a single-center retrospective analysis of 531 patients with intracranial tumors treated by 5-ALA–guided resection or biopsy. They analyzed patient characteristics, preoperative and postoperative liver function test results, intraoperative tumor fluorescence, and histological data. They also screened discharge summaries for clinical adverse effects resulting from the administration of 5-ALA. Intraoperative qualitative 5-ALA fluorescence (none, mild, moderate, and strong) was documented by the surgeon and dichotomized into negative and positive fluorescence. Results A total of 458 cases qualified for final analysis. The highest percentage of 5-ALA–positive fluorescence in open resection was found in glioblastomas (96%, n = 99/103). Among other tumors, 5-ALA–positive fluorescence was detected in 88% (n = 21/32) of anaplastic gliomas (WHO Grade III), 40% (n = 8/19) of low-grade gliomas (WHO Grade II), no (n = 0/3) WHO Grade I gliomas, and 77% (n = 85/110) of meningiomas. Among metastases, the highest percentage of 5-ALA–positive fluorescence was detected in adenocarcinomas (48%, n = 13/27). Low rates or absence of positive fluorescence was found among pituitary adenomas (8%, n = 1/12) and schwannomas (0%, n = 0/7). Biopsies of high-grade primary brain tumors showed positive rates of fluorescence similar to those recorded for open resection. No clinical adverse effects associated with use of 5-ALA were observed. Only 1 patient had clinically silent transient elevation of liver enzymes. Conclusions Study findings suggest that the administration of 5-ALA as a surgical adjunct for resection and biopsy of primary brain tumors and brain metastases is safe. In light of the high rate of positive fluorescence in high-grade gliomas other than glioblastomas, meningiomas, and a variety of metastatic cancers, 5-ALA seems to be a promising tool for enhancing intraoperative identification of neoplastic tissue and optimizing the extent of resection.

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Correlation between hypoxic area in primary brain tumors and WHO grade: differentiation from malignancy using 18F-fluoromisonidazole positron emission tomography

Acta Radiologica ◽

10.1177/0284185117711474 ◽

2017 ◽

Vol 59 (2) ◽

pp. 229-235 ◽

Cited By ~ 5

Author(s):

Masafumi Kanoto ◽

Kazukuni Kirii ◽

Toshitada Hiraka ◽

Yuuki Toyoguchi ◽

Yukio Sugai ◽

...

Keyword(s):

Positron Emission Tomography ◽

Brain Tumor ◽

Brain Tumors ◽

Normal Control ◽

Emission Tomography ◽

Who Grade ◽

Positive Correlation ◽

Primary Brain Tumors ◽

Hypoxic Area ◽

Positron Emission

Background 18F-fluoromisonidazole positron emission tomography (FMISO-PET) has been used for identification of hypoxic areas in tumors, and since hypoxia causes hypoxia-inducible factor-1 and enhancement of tumor growth, identifying the hypoxic area in the tumor tissue is important. Purpose To evaluate the usefulness of FMISO-PET in the grading of primary brain tumors. Material and Methods FMISO-PET was performed preoperatively on 41 consecutive patients with pathologically confirmed brain tumor. A neuroradiologist retrospectively measured both maximum standardized uptake value (SUVmax) and mean SUV (SUVmean) in the tumor and normal cerebellar parenchyma. Maximum tumor/normal control ratio (T/Nmax) and mean tumor/normal control ratio (T/Nmean) were calculated and analyzed. Results There was a positive correlation between World Health Organization (WHO) grade and both T/Nmax and T/Nmean (r = 0.731 and 0.713, respectively). When all cases were divided into benign (WHO grade II) and malignant groups (III and IV), there were significant differences between the two groups in both T/Nmax and T/Nmean ( P < 0.001). If the cutoff value was defined as T/Nmax = 1.25 and T/Nmean = 1.23, T/Nmax had a sensitivity of 90.0% and a specificity of 90.9% while T/Nmean had a sensitivity of 93.3% and a specificity of 90.9% in differentiating the benign group from the malignant group. Conclusion Both T/Nmax and T/Nmean in FMISO-PET have a positive correlation with primary brain tumor grading, making FMISO-PET useful in diagnosing the malignancy of primary brain tumors.

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Sporadic and Lynch syndrome-associated mismatch repair-deficient brain tumors

Laboratory Investigation ◽

10.1038/s41374-021-00694-3 ◽

2021 ◽

Author(s):

Hyunhee Kim ◽

Ka Young Lim ◽

Jin Woo Park ◽

Jeongwan Kang ◽

Jae Kyung Won ◽

...

Keyword(s):

Brain Tumor ◽

Brain Tumors ◽

Lynch Syndrome ◽

Mismatch Repair ◽

Statistical Significance ◽

Biological Behavior ◽

Molecular Characteristics ◽

Genetic Profile ◽

Who Grade ◽

Primary Brain Tumors

AbstractMismatch repair-deficient (MMRD) brain tumors are rare among primary brain tumors and can be induced by germline or sporadic mutations. Here, we report 13 MMRD-associated (9 sporadic and 4 Lynch syndrome) primary brain tumors to determine clinicopathological and molecular characteristics and biological behavior. Our 13 MMRD brain tumors included glioblastoma (GBM) IDH-wildtype (n = 9) including 1 gliosarcoma, astrocytoma IDH-mutant WHO grade 4 (n = 2), diffuse midline glioma (DMG) H3 K27M-mutant (n = 1), and pleomorphic xanthoastrocytoma (PXA) (n = 1). Next-generation sequencing using a brain tumor-targeted gene panel, microsatellite instability (MSI) testing, Sanger sequencing for germline MMR gene mutation, immunohistochemistry of MMR proteins, and clinicopathological and survival analysis were performed. There were many accompanying mutations, suggesting a high tumor mutational burden (TMB) in 77%, but TMB was absent in one case of GBM, IDH-wildtype, DMG, and PXA, respectively. MSH2, MLH1, MSH6, and PMS2 mutations were found in 31%, 31%, 31% and 7% of patients, respectively. MSI-high and MSI-low were found in 50% and 8% of these gliomas, respectively and 34% was MSI-stable. All Lynch syndrome-associated GBMs had MSI-high. In addition, 77% (10/13) had histopathologically multinucleated giant cells. The progression-free survival tended to be poorer than the patients with no MMRD gliomas, but the number and follow-up duration of our patients were insufficient to get statistical significance. In the present study, we found that the most common MMRD primary brain tumor was GBM IDH-wildtype. The genetic profile of MMRD GBM was different from that of conventional GBM. MMRD gliomas with TMB and MSI-H may be sensitive to immunotherapy but resistant to temozolomide. Our findings can help develop better treatment options.

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CTNI-55. THE CDK4/6 INHIBITOR ABEMACICLIB IN PATIENTS WITH RECURRENT MENINGIOMA AND OTHER PRIMARY CNS TUMORS

Neuro-Oncology ◽

10.1093/neuonc/noab196.280 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi72-vi73

Author(s):

Elizabeth Coffee ◽

Katherine Panageas ◽

Robert Young ◽

Tara Morrison ◽

Ahmad Daher ◽

...

Keyword(s):

Brain Tumors ◽

Single Agent ◽

Pituitary Tumors ◽

Molecular Characteristics ◽

Multiple Cancer ◽

Who Grade ◽

Multiple Tumor ◽

Primary Brain Tumors ◽

Basket Trial ◽

Tumor Types

Abstract BACKGROUND Medical therapies for recurrent brain tumors are limited. Abemaciclib is a small molecule CDK4/6 inhibitor that has demonstrated antitumor activity in multiple cancer types and crosses the blood-brain barrier. METHODS We conducted a phase II trial of single-agent abemaciclib in patients with recurrent primary brain tumors utilizing a novel CNS basket trial design with multiple tumor types accrued to separate cohorts including patients with recurrent IDH-wildtype gliomas (Cohort A), any recurrent gliomas requiring cytoreductive surgery (Cohort B), and any other recurrent primary brain tumors (Cohort C) including IDH-mutant gliomas, meningiomas, and other tumor types. In all patients, abemaciclib was administered orally at 200mg twice daily for each 28-day cycle. In cohort B abemaciclib was administered 4-7 days prior to surgery then resumed after recovery. Neuroimaging disease assessments were performed every two cycles. Cohorts were individually assessed for efficacy, tumoral molecular characteristics, and exploratory biomarker analyses. Next generation sequencing was performed on patients who had prior surgery. RESULTS To date, a total of 61 patients have enrolled and initiated treatment with abemaciclib. Cohort A enrolled 9 patients with IDH-wildtype WHO grade II and III astrocytomas. Cohort B enrolled 10 patients with astrocytomas of varying IDH-status. Cohort C is a diverse group of 42 patients including 22 treatment-refractory meningiomas, 10 IDH-mutant gliomas (5 astrocytomas, 5 oligodendrogliomas), 3 ependymomas, 3 primary CNS lymphomas, 2 pituitary tumors, 1 glioneuronal rosette forming tumor, and 1 diffuse midline glioma. A total of 7 grade 3 toxicities occurred in 6 patients: fatigue (3), neutropenia (2), colitis (1) and seizure (1); no grade 4 toxicities occurred. CONCLUSIONS We present the results of a novel CNS basket trial looking at the efficacy of abemaciclib across multiple recurrent primary brain tumors. Efficacy results will be presented, highlighting an update on promising results in the 22 patients with recurrent meningiomas.

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Juvenile Pilocytic Astrocytoma in Association with Arteriovenous Malformation

Interventional Neuroradiology ◽

10.1177/159101991201800203 ◽

2012 ◽

Vol 18 (2) ◽

pp. 140-147 ◽

Cited By ~ 3

Author(s):

M. Soltanolkotabi ◽

S.E. Schoeneman ◽

A.J. Dipatri ◽

M.C. Hurley ◽

S.A. Ansari ◽

...

Keyword(s):

Brain Tumors ◽

Arteriovenous Malformation ◽

Pilocytic Astrocytoma ◽

Vascular Malformations ◽

Pediatric Population ◽

Etiologic Factor ◽

Who Grade ◽

Artery Pseudoaneurysm ◽

Primary Brain Tumors ◽

Juvenile Pilocytic Astrocytoma

Pilocytic astrocytomas are highly vascular, relatively common primary brain tumors in the pediatric population, but their association with a true arteriovenous malformation (AVM) is extremely rare. We describe an eight-year-old girl with a right supratentorial juvenile pilocytic astrocytoma (WHO grade I) with an angiographically documented AVM entangled in the tumor mass who presented with intracranial hemorrhage due to a ruptured anterior choroidal artery pseudoaneurysm encased in the lesion. The AVM nidus as well as the hemorrhage site was embolized with Onyx. A literature review revealed only one previous report of a true intermixture of these two lesions. We hypothesize whether the association of vascular malformations and primary brain tumors are merely coincidental or if they point to the existence of a distinct entity and/or a common etiologic factor.

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Durable Progression-Free Survival With the Use of BRAF and MEK Inhibitors in Four Cases With BRAF V600E-Mutated Gliomas

Cancer Control ◽

10.1177/10732748211040013 ◽

2021 ◽

Vol 28 ◽

pp. 107327482110400

Author(s):

Michael J. Fusco ◽

Yolanda Piña ◽

Robert J. Macaulay ◽

Solmaz Sahebjam ◽

Peter A. Forsyth ◽

...

Keyword(s):

Brain Tumors ◽

Mapk Pathway ◽

Case Series ◽

Progression Free Survival ◽

Mitogen Activated Protein Kinase ◽

Braf V600e ◽

Who Grade ◽

Free Survival ◽

Mek Inhibitors ◽

Primary Brain Tumors

Introduction BRAF V600 E mutations have been identified in a subset of patients with primary brain tumors. Combination therapy with BRAF and Mitogen-activated protein kinase (MEK) inhibitors (BRAF/MEKi) targeting sequential steps in the MAPK pathway has replaced BRAFi monotherapy as the standard of care in multiple tumors with BRAF V600 E mutations, and clinical evidence for this strategy continues to grow in primary brain tumors. Case series We describe four patients with BRAF V600 E mutated gliomas, including a 21-year-old woman with a ganglioglioma WHO grade I, a 19-year-old man with a pleomorphic xanthoastrocytoma WHO grade III, and 21-year-old and 33-year-old women with epithelioid GBM WHO grade IV, who achieved durable progression-free survival with combination BRAF/MEKi. Conclusion Combination of BRAF/MEK inhibition can be a novel, promising approach as targeted therapy in gliomas with BRAF V600 E mutations, especially those that are resistant to standard therapy. Our cases, along with other early reports utilizing dabrafenib/trametinib, highlight the importance of somatic next-generation sequencing, particularly in younger patients. Interim results from clinical trials utilizing dabrafenib/trametinib have been promising thus far, and our case series suggests that durable clinical benefit is possible, even in the setting of glioblastoma, WHO grade IV.

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Surgery for primary supratentorial brain tumors in the United States, 2000–2009: effect of provider and hospital caseload on complication rates

Journal of Neurosurgery ◽

10.3171/2014.9.jns131648 ◽

2015 ◽

Vol 122 (2) ◽

pp. 280-296 ◽

Cited By ~ 38

Author(s):

Victoria T. Trinh ◽

Jason M. Davies ◽

Mitchel S. Berger

Keyword(s):

Brain Tumors ◽

Hospital Mortality ◽

High Volume ◽

Patient Characteristics ◽

The United States ◽

Hospital Charges ◽

Wound Complications ◽

Complication Rates ◽

Primary Brain Tumors ◽

Supratentorial Brain Tumors

OBJECT The object of this study was to examine how procedural volume and patient demographics impact complication rates and value of care in those who underwent biopsy or craniotomy for supratentorial primary brain tumors. METHODS The authors conducted a retrospective cohort study using data from the Nationwide Inpatient Sample (NIS) on 62,514 admissions for biopsy or resection of supratentorial primary brain tumors for the period from 2000 to 2009. The main outcome measures were in-hospital mortality, routine discharge proportion, length of hospital stay, and perioperative complications. Associations between these outcomes and hospital or surgeon case volumes were examined in logistic regression models stratified across patient characteristics to control for presentation of disease and comorbid risk factors. The authors further computed value of care, defined as the ratio of functional outcome to hospital charges. RESULTS High-case-volume surgeons and hospitals had superior outcomes. After adjusting for patient characteristics, high-volume surgeon correlated with reduced complication rates (OR 0.91, p = 0.04) and lower in-hospital mortality (OR 0.43, p < 0.0001). High-volume hospitals were associated with reduced in-hospital mortality (OR 0.76, p = 0.003), higher routine discharge proportion (OR 1.29, p < 0.0001), and lower complication rates (OR 0.93, p = 0.04). Patients treated by high-volume surgeons were less likely to experience postoperative hematoma, hydrocephalus, or wound complications. Patients treated at high-volume hospitals were less likely to experience mechanical ventilation, pulmonary complications, or infectious complications. Worse outcomes tended to occur in African American and Hispanic patients and in those without private insurance, and these demographic groups tended to underutilize high-volume providers. CONCLUSIONS A high-volume status for hospitals and surgeons correlates with superior value of care, as well as reduced in-hospital mortality and complications. These findings suggest that regionalization of care may enhance patient outcomes and improve value of care for patients with primary supratentorial brain tumors.

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