Pediatric high-grade astrocytoma with piloid features of the spinal cord: A report of two cases and literature review

The purpose of this study was to devise an improved method of treating high-grade gliomas of the spinal cord in children who have a dismal prognosis following conventional treatment. Eighteen children with newly diagnosed high-grade astrocytomas arising in the spinal cord were enrolled in the Children's Cancer Group (CCG) protocol 945. Following surgery, they were all assigned to receive two courses of “8-drugs-in-1-day” (8-in-1) chemotherapy prior to radiotherapy and eight additional courses thereafter. A centralized neuropathology review was used to confirm the diagnosis of high-grade astrocytoma in 13 of the 18 children: anaplastic astrocytoma, (eight patients), glioblastoma multiforme (four patients), and mixed malignant glioma (one patient). Diagnoses were discordant in five patients. There were eight boys and five girls in the group with confirmed diagnoses, with a median age of 7 years (range 1-15 years). The extent of resection was confirmed by computerized tomography or magnetic resonance (MR) evaluation in five of 13 patients. There were six gross-total or near-total resections (>90%), four partial or subtotal resections (10-90%), and three biopsies. Six patients showed evidence of leptomeningeal metastases at diagnosis based on staging MR examinations. Eight of the 13 patients completed at least eight of the prescribed 10 courses of chemotherapy; five received craniospinal radiotherapy and five spinal radiotherapy. The 5-year progression-free and total survival rates for the 13 children were 46 ± 14% and 54 ± 14%, respectively. Seven patients suffered a relapse at the primary site, four of whom also had leptomeningeal metastases. Seven of the 13 patients (54%) remain alive at the time of this report at a median of 76 months (range 51-93 months) from study entry. Six patients died between 8 and 38 months after diagnosis, all with active disease. Intensification of therapy may further improve outcome in this high-risk population.

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Treatment of high-grade spinal cord astrocytoma of childhood with “8-in-1” chemotherapy and radiotherapy: a pilot study of CCG-945

Journal of Neurosurgery ◽

10.3171/jns.1998.88.2.0215 ◽

1998 ◽

Vol 88 (2) ◽

pp. 215-220 ◽

Cited By ~ 98

Author(s):

Jeffrey C. Allen ◽

Shraga Aviner ◽

Allan J. Yates ◽

James M. Boyett ◽

Joel M. Cherlow ◽

...

Keyword(s):

Spinal Cord ◽

Survival Rates ◽

Extent Of Resection ◽

Leptomeningeal Metastases ◽

High Risk Population ◽

High Grade ◽

Content Type ◽

High Grade Astrocytoma ◽

Dismal Prognosis ◽

Fine Print

Object. The purpose of this study was to devise an improved method of treating high-grade gliomas of the spinal cord in children who have a dismal prognosis following conventional treatment. Methods. Eighteen children with newly diagnosed high-grade astrocytomas arising in the spinal cord were enrolled in the Children's Cancer Group (CCG) protocol 945. Following surgery, they were all assigned to receive two cycles of “8-drugs-in-1-day” (8-in-1) chemotherapy prior to radiotherapy and eight additional cycles thereafter. A centralized neuropathology review was used to confirm the diagnosis of high-grade astrocytoma in 13 of the 18 children: anaplastic astrocytoma (eight patients), glioblastoma multiforme (four patients), and mixed malignant glioma (one patient). Diagnoses were discordant in five patients. There were eight boys and five girls in the group with confirmed diagnoses, with a median age of 7 years (range 1–15 years). The extent of resection was confirmed by computerized tomography or magnetic resonance (MR) evaluation in five of 13 patients. There were six gross-total or near-total resections (> 90%), four partial or subtotal resections (10–90%), and three biopsies. Six patients showed evidence of leptomeningeal metastases at diagnosis based on staging MR examinations. Eight of the 13 patients completed at least eight of the prescribed 10 cycles of chemotherapy; five received craniospinal radiotherapy and five spinal radiotherapy. Conclusions. The 5-year progression-free and total survival rates for the 13 children were 46 ± 14% and 54 ± 14%, respectively. Seven patients suffered a relapse at the primary site, four of whom also had leptomeningeal metastases. Seven of the 13 patients (54%) remain alive at the time of this report at a median of 76 months (range 51–93 months) from study entry. Six patients died between 8 and 38 months after diagnosis, all with active disease. Intensification of therapy may further improve outcome in this high-risk population.

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Recombinant interferon beta: a phase I-II trial in children with recurrent brain tumors.

Journal of Clinical Oncology ◽

10.1200/jco.1991.9.5.783 ◽

1991 ◽

Vol 9 (5) ◽

pp. 783-788 ◽

Cited By ~ 34

Author(s):

J Allen ◽

R Packer ◽

A Bleyer ◽

P Zeltzer ◽

M Prados ◽

...

Keyword(s):

Spinal Cord ◽

Phase I ◽

Dose Escalation ◽

Interferon Beta ◽

Maintenance Phase ◽

High Grade ◽

Recombinant Interferon ◽

Initiation Phase ◽

High Grade Astrocytoma ◽

Dose Levels

A multicenter phase I-II trial of intravenous (IV) human recombinant interferon beta (rIFN-beta; Betaseron; Triton Bioscience Inc, Almeda, CA) was conducted in children with recurrent or progressive primary brain and spinal cord tumors. A total of 29 patients were enrolled: high-grade astrocytoma (12), brainstem glioma (nine), and primitive neuroectadermal tumor (three), ependymoma (two), germ cell (two), and spinal cord astrocytoma (one). Betaseron was given by IV infusion over 30 minutes 3 times per week (Monday-Wednesday-Friday [MWF]). Four dose levels were studied, and at least three patients were entered at each dose level. The treatment plan began with a three-step dose escalation for each patient over 6 weeks (initiation phase). The dose-escalation schema for the four dose levels was: 50-100-200, 100-200-400, 200-300-500, and 300-400-600 x 10(6) (M) IU/m2. Patients experiencing an objective response or stable disease after 6 weeks entered the maintenance phase at the final escalated dose, ie, 200, 400, 500, or 600 mlU/m2 (MWF). Common transient effects included chills, fever, and fatigue. Dose-limiting toxicities were hematologic, hepatic, and CNS. The maintenance maximum-tolerable dose (MTD) was 500 mlU/m2, ie, dose level 3. Response was assessed at completion of the initiation phase and at 2-month intervals during the maintenance phase. Objective partial responses were seen in patients with high-grade astrocytoma (two) and brain-stem glioma (two). Thus, four of 21 (19%) assessable patients had partial responses for a median of 4 months. Eight patients had stable disease for a median of 5+ (2 to 14+) months. Antineoplastic activity has been identified in children with high-grade astrocytomas and brainstem gliomas in a dose-intensive regimen.

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Proliferation-dominant high-grade astrocytoma: survival benefit associated with extensive resection of FLAIR abnormality region

Journal of Neurosurgery ◽

10.3171/2018.12.jns182775 ◽

2020 ◽

Vol 132 (4) ◽

pp. 998-1005 ◽

Cited By ~ 4

Author(s):

Haihui Jiang ◽

Yong Cui ◽

Xiang Liu ◽

Xiaohui Ren ◽

Mingxiao Li ◽

...

Keyword(s):

Survival Benefit ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Characteristic Curve ◽

Extent Of Resection ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

High Grade ◽

Extensive Resection ◽

High Grade Astrocytoma

OBJECTIVEThe aim of this study was to investigate the relationship between extent of resection (EOR) and survival in terms of clinical, molecular, and radiological factors in high-grade astrocytoma (HGA).METHODSClinical and radiological data from 585 cases of molecularly defined HGA were reviewed. In each case, the EOR was evaluated twice: once according to contrast-enhanced T1-weighted images (CE-T1WI) and once according to fluid attenuated inversion recovery (FLAIR) images. The ratio of the volume of the region of abnormality in CE-T1WI to that in FLAIR images (VFLAIR/VCE-T1WI) was calculated and a receiver operating characteristic curve was used to determine the optimal cutoff value for that ratio. Univariate and multivariate analyses were performed to identify the prognostic value of each factor.RESULTSBoth the EOR evaluated from CE-T1WI and the EOR evaluated from FLAIR could divide the whole cohort into 4 subgroups with different survival outcomes (p < 0.001). Cases were stratified into 2 subtypes based on VFLAIR/VCE-T1WIwith a cutoff of 10: a proliferation-dominant subtype and a diffusion-dominant subtype. Kaplan-Meier analysis showed a significant survival advantage for the proliferation-dominant subtype (p < 0.0001). The prognostic implication has been further confirmed in the Cox proportional hazards model (HR 1.105, 95% CI 1.078–1.134, p < 0.0001). The survival of patients with proliferation-dominant HGA was significantly prolonged in association with extensive resection of the FLAIR abnormality region beyond contrast-enhancing tumor (p = 0.03), while no survival benefit was observed in association with the extensive resection in the diffusion-dominant subtype (p=0.86).CONCLUSIONSVFLAIR/VCE-T1WIis an important classifier that could divide the HGA into 2 subtypes with distinct invasive features. Patients with proliferation-dominant HGA can benefit from extensive resection of the FLAIR abnormality region, which provides the theoretical basis for a personalized resection strategy.

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Spinal Cord Stimulation: A Contemporary Series

Neurosurgery ◽

10.1227/00006123-199101000-00011 ◽

1991 ◽

Vol 28 (1) ◽

pp. 65-71 ◽

Cited By ~ 78

Author(s):

Roberto Spiegelmann ◽

William A. Friedman

Keyword(s):

Spinal Cord ◽

Chronic Pain ◽

Pain Relief ◽

Literature Review ◽

General Anesthesia ◽

Detailed Analysis ◽

Spinal Cord Stimulation ◽

Significant Pain ◽

Experience Pain

Abstract Forty-three patients with chronic pain disorders of different causes were selected for spinal cord stimulation. All underwent implantation of a ribbon electrode through a small laminotomy, under general anesthesia. Thirteen patients (30%) failed to obtain significant pain relief during a period of trial stimulation, and their electrodes were removed. The remainder underwent a definitive implant and were followed for a mean of 13 months (range, 3-33 months). Nineteen of them (63%) continued to experience pain relief. A detailed analysis of this series, as well as a literature review, is presented.

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Pain Relief and Safety Outcomes with Cervical 10 kHz Spinal Cord Stimulation: Systematic Literature Review and Meta-analysis

Pain and Therapy ◽

10.1007/s40122-021-00269-6 ◽

2021 ◽

Author(s):

Ganesan Baranidharan ◽

Beatrice Bretherton ◽

Craig Montgomery ◽

John Titterington ◽

Tracey Crowther ◽

...

Keyword(s):

Spinal Cord ◽

Pain Relief ◽

Literature Review ◽

Systematic Literature Review ◽

Spinal Cord Stimulation ◽

Meta Analysis ◽

Safety Outcomes

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High-grade astrocytoma with piloid features (HGAP): the Charité experience with a new central nervous system tumor entity

Journal of Neuro-Oncology ◽

10.1007/s11060-021-03749-z ◽

2021 ◽

Author(s):

Katja Bender ◽

Eilís Perez ◽

Mihaela Chirica ◽

Julia Onken ◽

Johannes Kahn ◽

...

Keyword(s):

Dna Methylation ◽

Central Nervous System ◽

Nervous System ◽

World Health ◽

Central Nervous System Tumor ◽

High Grade ◽

Thoracic Spinal Cord ◽

High Grade Astrocytoma ◽

Tumor Entity

Abstract Purpose High-grade astrocytoma with piloid features (HGAP) is a recently described brain tumor entity defined by a specific DNA methylation profile. HGAP has been proposed to be integrated in the upcoming World Health Organization classification of central nervous system tumors expected in 2021. In this series, we present the first single-center experience with this new entity. Methods During 2017 and 2020, six HGAP were identified. Clinical course, surgical procedure, histopathology, genome-wide DNA methylation analysis, imaging, and adjuvant therapy were collected. Results Tumors were localized in the brain stem (n = 1), cerebellar peduncle (n = 1), diencephalon (n = 1), mesencephalon (n = 1), cerebrum (n = 1) and the thoracic spinal cord (n = 2). The lesions typically presented as T1w hypo- to isointense and T2w hyperintense with inhomogeneous contrast enhancement on MRI. All patients underwent initial surgical intervention. Three patients received adjuvant radiochemotherapy, and one patient adjuvant radiotherapy alone. Four patients died of disease, with an overall survival of 1.8, 9.1, 14.8 and 18.1 months. One patient was alive at the time of last follow-up, 14.6 months after surgery, and one patient was lost to follow-up. Apart from one tumor, the lesions did not present with high grade histology, however patients showed poor clinical outcomes. Conclusions Here, we provide detailed clinical, neuroradiological, histological, and molecular pathological information which might aid in clinical decision making until larger case series are published. With the exception of one case, the tumors did not present with high-grade histology but patients still showed short intervals between diagnosis and tumor progression or death even after extensive multimodal therapy.

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Molecular diagnostics helps to identify distinct subgroups of spinal astrocytomas

Acta Neuropathologica Communications ◽

10.1186/s40478-021-01222-6 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Annamaria Biczok ◽

Felix L. Strübing ◽

Julia M. Eder ◽

Rupert Egensperger ◽

Oliver Schnell ◽

...

Keyword(s):

Spinal Cord ◽

Molecular Markers ◽

Prognostic Significance ◽

The Elderly ◽

Molecular Profile ◽

Diffuse Astrocytoma ◽

Molecular Alterations ◽

High Grade Astrocytoma ◽

Dismal Prognosis ◽

Few Data

AbstractPrimary spinal cord astrocytomas are rare, hence few data exist about the prognostic significance of molecular markers. Here we analyze a panel of molecular alterations in association with the clinical course. Histology and genome sequencing was performed in 26 spinal astrocytomas operated upon between 2000 and 2020. Next-generation DNA/RNA sequencing (NGS) and methylome analysis were performed to determine molecular alterations. Histology and NGS allowed the distinction of 5 tumor subgroups: glioblastoma IDH wildtype (GBM); diffuse midline glioma H3 K27M mutated (DMG-H3); high-grade astrocytoma with piloid features (HAP); diffuse astrocytoma IDH mutated (DA), diffuse leptomeningeal glioneural tumors (DGLN) and pilocytic astrocytoma (PA). Within all tumor entities GBM (median OS: 5.5 months), DMG-H3 (median OS: 13 months) and HAP (median OS: 8 months) showed a fatal prognosis. DMG-H3 tend to emerge in adolescence whereas GBM and HAP develop in the elderly. HAP are characterized by CDKN2A/B deletion and ATRX mutation. 50% of PA tumors carried a mutation in the PIK3CA gene which is seemingly associated with better outcome (median OS: PIK3CA mutated 107.5 vs 45.5 months in wildtype PA). This exploratory molecular profiling of spinal cord astrocytomas allows to identify distinct subgroups by combining molecular markers and histomorphology. DMG-H3 tend to develop in adolescence with a similar dismal prognosis like GBM and HAP in the elderly. We here describe spinal HAP with a distinct molecular profile for the first time.

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“Proximalization is Advancement”—Zone 3 Frozen Elephant Trunk vs Zone 2 Frozen Elephant Trunk: A Literature Review

Vascular and Endovascular Surgery ◽

10.1177/15385744211002493 ◽

2021 ◽

pp. 153857442110024

Author(s):

Rozina Yasmin Choudhury ◽

Kamran Basharat ◽

Syeda Anum Zahra ◽

Tien Tran ◽

Lara Rimmer ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Surgical Treatment ◽

Literature Review ◽

Treatment Options ◽

Frozen Elephant Trunk ◽

Elephant Trunk ◽

Descending Aorta ◽

Cord Injury ◽

Aortic Pathologies

Over the decades, the Frozen Elephant Trunk (FET) technique has gained immense popularity allowing simplified treatment of complex aortic pathologies. FET is frequently used to treat aortic conditions involving the distal aortic arch and the proximal descending aorta in a single stage. Surgical preference has recently changed from FET procedures being performed at Zone 3 to Zone 2. There are several advantages of Zone 2 FET over Zone 3 FET including reduction in spinal cord injury, visceral ischemia, neurological and cardiovascular sequelae. In addition, Zone 2 FET is a technically less complicated procedure. Literature on the comparison between Zone 3 and Zone 2 FET is scarce and primarily observational and anecdotal. Therefore, further research is warranted in this paradigm to substantiate current surgical treatment options for complex aortic pathologies. In this review, we explore literature surrounding FET and the reasons for the shift in surgical preference from Zone 3 to Zone 2.

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