Pediatric thalamic incidentalomas: an international retrospective multicenter study

OBJECTIVE Widespread use of modern neuroimaging has led to a surge in diagnosing pediatric brain incidentalomas. Thalamic lesions have unique characteristics such as deep location, surgical complexity, and proximity to eloquent neuronal structures. Currently, the natural course of incidental thalamic lesions is unknown. Therefore, the authors present their experience in treating such lesions. METHODS A retrospective, international multicenter study was carried out in 8 tertiary pediatric centers from 5 countries. Patients were included if they had an incidental thalamic lesion suspected of being a tumor and were diagnosed before the age of 20 years. Treatment strategy, imaging characteristics, pathology, and the outcome of operated and unoperated cases were analyzed. RESULTS Overall, 58 children (23 females and 35 males) with a mean age of 10.8 ± 4.0 years were included. The two most common indications for imaging were nonspecific reasons (n = 19; e.g., research and developmental delay) and headache unrelated to small thalamic lesions (n = 14). Eleven patients (19%) underwent early surgery and 47 were followed, of whom 10 underwent surgery due to radiological changes at a mean of 11.4 ± 9.5 months after diagnosis. Of the 21 patients who underwent surgery, 9 patients underwent resection and 12 underwent biopsy. The two most frequent pathologies were pilocytic astrocytoma and WHO grade II astrocytoma (n = 6 and n = 5, respectively). Three lesions were high-grade gliomas. CONCLUSIONS The results of this study indicate that pediatric incidental thalamic lesions include both low- and high-grade tumors. Close and long-term radiological follow-up is warranted in patients who do not undergo immediate surgery, as tumor progression may occur.

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P14.60 FET PET response upon radiochemotherapy followed by Tumor Treating Fields (TTFields) in a patient with progressive high-grade glioma

Neuro-Oncology ◽

10.1093/neuonc/noz126.295 ◽

2019 ◽

Vol 21 (Supplement_3) ◽

pp. iii81-iii81

Author(s):

A F Keßler ◽

J Weiland ◽

T Linsenmann ◽

R Ernestus ◽

C Hagemann ◽

...

Keyword(s):

Tumor Progression ◽

Treatment Response ◽

High Grade Glioma ◽

High Grade ◽

Who Grade ◽

Fet Pet ◽

Tumor Treating Fields ◽

Grade Ii ◽

The Right ◽

Pet Scans

Abstract BACKGROUND The addition of Tumor Treating Fields (TTFields) to the first-line therapy in glioblastoma (GBM) demonstrated significantly improved progression free survival, overall survival and longterm survival rates in the EF-14 phase 3 trial. However, responder analysis of patients with recurrent GBM (rGBM) treated with TTFields monotherapy (in the EF-11 trial) revealed delayed response monitored by MRI analysis. More recent data suggests that O-(2-18F-fluoroethyl)-L-tyrosine (FET) PET may add valuable information for monitoring therapy response of glioblastoma patients treated with TTFields. Here, we report on FET PET response in a patient with progressive anaplastic astrocytoma WHO grade III (AA) treated with TTFields in combination with temozolomide (TMZ) chemotherapy. METHODS We present a 38-year old patient with an initial diagnosis of a diffuse astrocytoma WHO grade II in 2011, and malignisation to an AA on progression. The treatment regimen included initially radio-chemotherapy (RCT) with TMZ. On further progression of the AA in 2017, TTFields were added to another 6 cycles of TMZ. Several FET PET scans for differentiation of tumor progression from treatment-related changes were performed over time. The definitive diagnosis (tumor progression and grading) was confirmed by histopathology after stereotactic biopsy (SB). RESULTS In 2012, the patient was first diagnosed with a low grade astrocytoma WHO grade II of the right frontal, temporal and parietal lobe including infiltration of thalamus and corpus was confirmed by SB, followed by irradiation. On progression in 2015, a FET PET Scan showed FET avidity in all tumor affected regions of the brain. SB confirmed an AA, while FET PET scans showed only a mild response in the temporoparietal region after 6 cycles of TMZ. In 2017, the next progression without further malignisation was confirmed by SB and treated RCT with 41.4 Gy and TMZ chemotherapy, followed by application of TTFields with an average usage rate of 85.7 % over 6 months. Thus, the TTFields adherence was well above the independent prognostic threshold of 75 %. No additional adverse events due to the combined therapy of TTFields and TMZ were observed. Due to a new contrast enhancing lesion in the right frontal lobe (10x7mm), another FET PET scan was performed 1.5 years later. In this scan, obtained after combined TTFields and RCT therapy a strong response regarding FET avidity was observed. CONCLUSION In summary, FET PET is able to add important additional information for evaluation of treatment response in high grade glioma patients, in particular for TTFields treated patients, while adding TTFields to radiochemotherapy might even enhance treatment response of high grade glioma. Further studies might elucidate the role of FET PET imaging for therapy monitoring in high grade glioma patients treated with TTFields.

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The Value of 5-Aminolevulinic Acid in Low-grade Gliomas and High-grade Gliomas Lacking Glioblastoma Imaging Features: An Analysis Based on Fluorescence, Magnetic Resonance Imaging, 18F-Fluoroethyl Tyrosine Positron Emission Tomography, and Tumor Molecular Factors

Neurosurgery ◽

10.1227/neu.0000000000001020 ◽

2015 ◽

Vol 78 (3) ◽

pp. 401-411 ◽

Cited By ~ 60

Author(s):

Mohammed Jaber ◽

Johannes Wölfer ◽

Christian Ewelt ◽

Markus Holling ◽

Martin Hasselblatt ◽

...

Keyword(s):

Aminolevulinic Acid ◽

Methylation Status ◽

Imaging Features ◽

High Grade ◽

Ki 67 ◽

Who Grade ◽

Fet Pet ◽

Grade Ii ◽

Grade Iii ◽

Mib 1

Abstract BACKGROUND: Approximately 20% of grade II and most grade III gliomas fluoresce after 5-aminolevulinic acid (5-ALA) application. Conversely, approximately 30% of nonenhancing gliomas are actually high grade. OBJECTIVE: The aim of this study was to identify preoperative factors (ie, age, enhancement, 18F-fluoroethyl tyrosine positron emission tomography [18F-FET PET] uptake ratios) for predicting fluorescence in gliomas without typical glioblastomas imaging features and to determine whether fluorescence will allow prediction of tumor grade or molecular characteristics. METHODS: Patients harboring gliomas without typical glioblastoma imaging features were given 5-ALA. Fluorescence was recorded intraoperatively, and biopsy specimens collected from fluorescing tissue. World Health Organization (WHO) grade, Ki-67/MIB-1 index, IDH1 (R132H) mutation status, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and 1p/19q co-deletion status were assessed. Predictive factors for fluorescence were derived from preoperative magnetic resonance imaging and 18F-FET PET. Classification and regression tree analysis and receiver-operating-characteristic curves were generated for defining predictors. RESULTS: Of 166 tumors, 82 were diagnosed as WHO grade II, 76 as grade III, and 8 as glioblastomas grade IV. Contrast enhancement, tumor volume, and 18F-FET PET uptake ratio >1.85 predicted fluorescence. Fluorescence correlated with WHO grade (P < .001) and Ki-67/MIB-1 index (P < .001), but not with MGMT promoter methylation status, IDH1 mutation status, or 1p19q co-deletion status. The Ki-67/MIB-1 index in fluorescing grade III gliomas was higher than in nonfluorescing tumors, whereas in fluorescing and nonfluorescing grade II tumors, no differences were noted. CONCLUSION: Age, tumor volume, and 18F-FET PET uptake are factors predicting 5-ALA-induced fluorescence in gliomas without typical glioblastoma imaging features. Fluorescence was associated with an increased Ki-67/MIB-1 index and high-grade pathology. Whether fluorescence in grade II gliomas identifies a subtype with worse prognosis remains to be determined.

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Method for temporal keyhole lobectomies in resection of low- and high-grade gliomas

Journal of Neurosurgery ◽

10.3171/2016.12.jns162168 ◽

2018 ◽

Vol 128 (5) ◽

pp. 1388-1395 ◽

Cited By ~ 4

Author(s):

Andrew K. Conner ◽

Joshua D. Burks ◽

Cordell M. Baker ◽

Adam D. Smitherman ◽

Dillon P. Pryor ◽

...

Keyword(s):

Ventriculoperitoneal Shunt ◽

Extent Of Resection ◽

Senior Author ◽

High Grade ◽

Who Grade ◽

Prior Surgery ◽

Grade Ii ◽

Keyhole Craniotomy ◽

Invasive Techniques

OBJECTIVEThe purpose of this study was to describe a method of resecting temporal gliomas through a keyhole lobectomy and to share the results of using this technique.METHODSThe authors performed a retrospective review of data obtained in all patients in whom the senior author performed resection of temporal gliomas between 2012 and 2015. The authors describe their technique for resecting dominant and nondominant gliomas, using both awake and asleep keyhole craniotomy techniques.RESULTSFifty-two patients were included in the study. Twenty-six patients (50%) had not received prior surgery. Seventeen patients (33%) were diagnosed with WHO Grade II/III tumors, and 35 patients (67%) were diagnosed with a glioblastoma. Thirty tumors were left sided (58%). Thirty procedures (58%) were performed while the patient was awake. The median extent of resection was 95%, and at least 90% of the tumor was resected in 35 cases (67%). Five of 49 patients (10%) with clinical follow-up experienced permanent deficits, including 3 patients (6%) with hydrocephalus requiring placement of a ventriculoperitoneal shunt and 2 patients (4%) with weakness. Three patients experienced early postoperative anomia, but no patients had a new speech deficit at clinical follow-up.CONCLUSIONSThe authors provide their experience using a keyhole lobectomy for resecting temporal gliomas. Their data demonstrate the feasibility of using less invasive techniques to safely and aggressively treat these tumors.

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Endoscopic Trimodal Imaging Improves the Detection of High-Grade Dysplasia (HGD) and Early Cancer (EC) in Barrett’s Esophagus: An International Multicenter Study

Gastroenterology ◽

10.1053/j.gastro.2007.04.021 ◽

2007 ◽

Vol 132 (7) ◽

pp. 2586 ◽

Cited By ~ 3

Author(s):

W.L. Curvers ◽

P. Fockens ◽

J.J. Bergman ◽

R. Singh ◽

K. Ragunath ◽

...

Keyword(s):

Barrett’S Esophagus ◽

Multicenter Study ◽

Barrett's Esophagus ◽

Early Cancer ◽

High Grade Dysplasia ◽

High Grade ◽

International Multicenter Study ◽

International Multicenter

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Patterns of recurrence after stereotactic radiosurgery for treatment of meningiomas

Neurosurgical FOCUS ◽

10.3171/2013.8.focus13283 ◽

2013 ◽

Vol 35 (6) ◽

pp. E14 ◽

Cited By ~ 15

Author(s):

Elizabeth N. Kuhn ◽

Glen B. Taksler ◽

Orrin Dayton ◽

Amritraj G. Loganathan ◽

Tamara Z. Vern-Gross ◽

...

Keyword(s):

Stereotactic Radiosurgery ◽

Local Control ◽

Retrospective Chart Review ◽

Distant Recurrence ◽

High Grade ◽

Who Grade ◽

Distant Failure ◽

Grade Ii ◽

Male Sex ◽

Multifocal Disease

Object The purpose of this study was to evaluate patterns of failure after stereotactic radiosurgery (SRS) for meningiomas and factors that may influence these outcomes. Methods Based on a retrospective chart review, 279 patients were treated with SRS for meningiomas between January 1999 and March 2011 at Wake Forest Baptist Health. Disease progression was determined using serial imaging, with a minimum follow-up of 6 months (median 34.2 months). Results The median margin dose was 12.0 Gy (range 8.8–20 Gy). Local control rates for WHO Grade I tumors were 96.6%, 84.4%, and 75.7% at 1, 3, and 5 years, respectively. WHO Grade II and III tumors had local control rates of 72.3%, 57.7%, and 52.9% at 1, 3, and 5 years, respectively. Tumors without pathological grading had local control rates of 98.7%, 97.6%, and 94.2% at 1, 3, and 5 years, respectively. Of the local recurrences, 63.1% were classified as marginal (within 2 cm of treatment field). The 1-, 3-, and 5-year rates of distant failure were 6.5%, 10.3%, and 16.6%, respectively, for Grade I tumors and 11.4%, 17.2%, and 22.4%, respectively, for Grade II/III tumors. Tumors without pathological grading had distant failure rates of 0.7%, 3.2%, and 6.5% at 1, 3, and 5 years, respectively. Wilcoxon analysis revealed that multifocal disease (p < 0.001) and high-grade histology (WHO Grade II or III; p < 0.001) were significant predictors of local recurrence. Additionally, male sex was a significant predictor of distant recurrence (p = 0.04). Multivariate analysis also showed that doses greater than or equal to 12 Gy were associated with improved local control (p = 0.015). Conclusions In this patient series, 12 Gy was the minimum sufficient margin dose for the treatment of meningiomas. Male sex is a risk factor for distant failure, whereas high-grade histology and multifocal disease are risk factors for local failure.

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Microneurosurgical removal of thalamic lesions: surgical results and considerations from a large, single-surgeon consecutive series

Journal of Neurosurgery ◽

10.3171/2020.6.jns20524 ◽

2020 ◽

pp. 1-11

Author(s):

Carlo Serra ◽

Hatice Türe ◽

Cumhur Kaan Yaltırık ◽

Mehmet Volkan Harput ◽

Uğur Türe

Keyword(s):

High Grade Glioma ◽

Extent Of Resection ◽

Intraoperative Mri ◽

Consecutive Series ◽

Thalamic Lesion ◽

High Grade ◽

Surgical Results ◽

The Mean ◽

Thalamic Lesions

OBJECTIVEThe object of this study was to present the surgical results of a large, single-surgeon consecutive series of patients who had undergone transcisternal (TCi) or transcallosal-transventricular (TCTV) endoscope-assisted microsurgery for thalamic lesions.METHODSThis is a retrospective study of a consecutive series of patients harboring thalamic lesions and undergoing surgery at one institution between February 2007 and August 2019. All surgical and patient-related data were prospectively collected. Depending on the relationship between the lesion and the surgically accessible thalamic surfaces (lateral ventricle, velar, cisternal, and third ventricle), one of the following surgical TCi or TCTV approaches was chosen: anterior interhemispheric transcallosal (AIT), posterior interhemispheric transtentorial subsplenial (PITS), perimedian supracerebellar transtentorial (PeST), or perimedian contralateral supracerebellar suprapineal (PeCSS). Since January 2018, intraoperative MRI has also been part of the protocol. The main study outcome was extent of resection. Complete neurological examination took place preoperatively, at discharge, and 3 months postoperatively. Descriptive statistics were calculated for the whole cohort.RESULTSIn the study period, 92 patients underwent surgery for a thalamic lesion: 81 gliomas, 6 cavernous malformations, 2 germinomas, 1 metastasis, 1 arteriovenous malformation, and 1 ependymal cyst. In none of the cases was a transcortical approach adopted. Thirty-five patients underwent an AIT approach, 35 a PITS, 19 a PeST, and 3 a PeCSS. The mean follow-up was 38 months (median 20 months, range 1–137 months). No patient was lost to follow-up. The mean extent of resection was 95% (median 100%, range 21%–100%), and there was no surgical mortality. Most patients (59.8%) experienced improvement in their Karnofsky Performance Status. New permanent neurological deficits occurred in 8 patients (8.7%). Early postoperative (< 3 months after surgery) problems in CSF circulation requiring diversion occurred in 7 patients (7.6%; 6/7 cases in patients with high-grade glioma).CONCLUSIONSEndoscope-assisted microsurgery allows for the removal of thalamic lesions with acceptable morbidity. Surgeons must strive to access any given thalamic lesion through one of the four accessible thalamic surfaces, as they can be reached through either a TCTV or TCi approach with no or minimal damage to normal brain parenchyma. Patients harboring a high-grade glioma are likely to develop a postoperative disturbance of CSF circulation. For this reason, the AIT approach should be favored, as it facilitates a microsurgical third ventriculocisternostomy and allows intraoperative MRI to be done.

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RADT-38. ADJUVANT RADIOTHERAPY FOR INTRACRANIAL ATYPICAL AND MALIGNANT MENINGIOMAS IN ADULT PATIENTS

Neuro-Oncology ◽

10.1093/neuonc/noaa215.791 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii189-ii190

Author(s):

Ansley Unterberger ◽

Aditya Kondajji ◽

Daniel Kulinich ◽

Courtney Duong ◽

Isaac Yang

Keyword(s):

Median Time ◽

Primary Brain Tumor ◽

Adjuvant Radiation ◽

High Grade ◽

Inclusion Criteria ◽

Who Grade ◽

Time To Recurrence ◽

Grade Ii ◽

Grade Iii

Abstract BACKGROUND Meningiomas, the most common primary brain tumor, account for more than one third of all primary CNS tumors. High-grade meningiomas, WHO grade II and III, comprise between 16%-24% of total meningiomas and are more aggressive, recur more frequently, and portend a worse prognosis than WHO grade I meningiomas. Adjuvant radiation of high-grade meningiomas, while not uncommon, remains variably described in current literature. To assess our institution’s radiation protocol, we examined our cohort of over 200 high-grade meningiomas. METHODS We queried our hospital’s EHR system for surgically resected meningiomas from January 2013 to December 2019. Of 286 results identified, 24 patients met the inclusion criteria: 1) histologically confirmed WHO grade II or III meningioma, 2) primary resection coupled with adjuvant radiation therapy, and 3) no chemotherapy. Only one WHO grade III meningioma met inclusion criteria. Patients with NF2 were excluded. Patient demographics, radiation dosage, fraction number, and dates of surgery, radiation onset, recurrence, and most recent follow-up were recorded. RESULTS Median age at surgery was 56.2 years (± 11.1, range 37.8 – 81.7), and males comprised 70.8% (n = 17) of the population. Only FSRT or IMRT were employed. The most frequent dosage was 55.8 Gy across 31 fractions with a median time to radiation of 2.7 months (± 3.0, range 1.0 – 12.6). 5 out of 24 patients experienced recurrence, which did not include the WHO III tumor. Median time to recurrence was 3.0 years (± 2.0, range .3 – 5.8). Median follow up was 3.5 years (± 2.2, range .3 – 9.3). CONCLUSIONS A fraction of our population experienced recurrence, regardless of grade II or grade III pathology. FSRT remains a safe and effective adjuvant therapy for high-grade meningioma after surgical resection. Future prospective studies comparing differing radiation modalities should be conducted.

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PATH-61. IMMUNOHISTOCHEMICAL PHENOTYPING AND SURVIVAL ANALYSIS OF WHO GRADE II-IV GLIOMAS

Neuro-Oncology ◽

10.1093/neuonc/noz175.656 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi157-vi157

Author(s):

Nora Poulos ◽

Srikar Sattiraju ◽

Charles Opalak ◽

Mikhail Dozmorov ◽

Jason Harrison ◽

...

Keyword(s):

Overall Survival ◽

Wilms Tumor ◽

Positive Staining ◽

High Grade ◽

Wild Type ◽

Isocitrate Dehydrogenase 1 ◽

Who Grade ◽

Clinical Prognosis ◽

Grade Ii ◽

Grade Iii

Abstract INTRODUCTION Specific genetic mutations are linked to clinical prognosis in gliomas. There has been increasing demand to understand the association between tissue biomarker expression and survival. Using patient-derived samples, WHO grade II-IV gliomas were evaluated by the protein-staining pattern of molecular markers of interest across tumor grade, and the association between their expression and survival was investigated. METHODS Tissue microarrays (TMA) containing duplicate 1 mm cores were generated from 78 gliomas (WHO grade II-IV) using an automated TMA system. Immunohistochemistry was performed per the manufactures recommendation to evaluate expression of: Wilms tumor 1 (WT1), platelet endothelial cell adhesion molecule (CD31), adhesion G protein-coupled receptor E5 (CD97), complement decay-accelerating factor (CD55), hypoxia inducible factor 1 subunit alpha (HIF1α), EGF-like module-containing mucin-like hormone receptor-like 3 (EMR3), integrin, and isocitrate dehydrogenase 1 (IDH1). Samples with moderate (+1) or intense (+2) staining to WT1, CD31, CD97, CD55, or HIF1α, or any staining to EMR3 or IDH1 mutation, were considered positive. RESULTS Of the 78 tumor samples, there were 11 (14%) WHO grade II, 22 (28%) grade III, and 45 (59%) grade IV gliomas. Across grade III gliomas, anaplastic astrocytomas had significantly higher positive WT1 (p=0.04), CD31 (p=0.002) and IDH1 wild-type (p< 0.0001) staining. High-grade (III & IV) gliomas had significantly higher positive staining for WT1 (p=0.013), CD31 (0.024), integrin (p=0.021), and IDH1 wild type (p=0.044). In all gliomas, positive staining for WT1 (p< 0.0001), CD31 (p=0.009), CD97 (p=0.024), EMR3 (p=0.036), and IDH1 wild type (p=0.0006) were associated with worse overall survival. After adjusting for patient age, positive staining for WT1 (p=0.003) was associated with worse overall survival. CONCLUSION Using immunohistochemistry, unique biomarker staining patterns were identified for WHO grade III anaplastic astrocytomas and for high-grade gliomas. Irrespective of grade, staining for WT1, CD97, CD31, EMR3, and IDH1 wild-type were associated with worse overall survival.

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Cerebellopontine angle ependymoma presenting as isolated hearing loss in an elderly patient: A case report and literature review

Surgical Neurology International ◽

10.25259/sni_781_2021 ◽

2021 ◽

Vol 12 ◽

pp. 572

Author(s):

Khaled Dibs ◽

Rahul Neal Prasad ◽

Kajal Madan ◽

Kevin Liu ◽

Will Jiang ◽

...

Keyword(s):

Hearing Loss ◽

Local Recurrence ◽

Cerebellopontine Angle ◽

Case Reports ◽

Disease Recurrence ◽

World Health ◽

Adjuvant Radiation ◽

Who Grade ◽

Imaging Characteristics ◽

Grade Ii

Background: Ependymoma is an uncommon tumor accounting for approximately 1.9% of all adult central nervous system tumors. Ependymomas at the cerebellopontine angle (CPA) are even more rare and only previously described in isolated case reports. Typically, acoustic neuromas and meningiomas represent the bulk of adult CPA tumors. Diagnosis can be challenging, as ependymomas have clinical findings and imaging characteristics that overlap with more common tumor histologies at the CPA. Case Description: We present the case of a 70-year-old male patient with progressive, isolated left-sided hearing loss found to have a World Health Organization (WHO) Grade II CPA ependymoma, representing one of the oldest recorded patients presenting with this primarily pediatric malignancy in this unique location. The patient presentation with isolated hearing loss was particularly unusual. When associated with neurologic deficits, CPA ependymomas more characteristically result in facial nerve impairment with fully preserved hearing, while vestibular schwannomas tend to present with isolated hearing loss. The standard of care for pediatric ependymomas is maximal safe resection with adjuvant radiotherapy, but treatment paradigms in adult CPA ependymoma are not well defined particularly for WHO Grade II disease. After resection, he received adjuvant radiation to decrease the risk of local recurrence. Twenty-nine months after resection, the patient remains free of treatment-related toxicity or disease recurrence. Conclusion: We review this patient’s clinical course in the context of the literature to highlight the challenges associated with timely diagnosis of this rare tumor and the controversial role of adjuvant therapy in preventing local recurrence in these patients.

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