scholarly journals PATH-20. INVESTIGATION OF CLINICALLY AGGRESSIVE SPINAL CORD EPENDYMOMA THROUGH METHYLATION ANALYSIS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi147-vi147
Author(s):  
Nicole Briceno ◽  
Zied Abdullaev ◽  
Elizabeth Vera ◽  
Francine Blumental De Abreu ◽  
Martha Quezado ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Progression Free Survival ◽  
Research Network ◽  
Mycn Amplification ◽  
Low Grade ◽  
Methylation Analysis ◽  
Clinical Criteria ◽  
Spinal Ependymoma ◽  
The Poor ◽  
High Level

Abstract Spinal ependymoma is a rare, often low-grade tumor, for which the clinical course and prognosis has been poorly defined. Classification has relied on histological criteria, as there are few defining molecular mutations, causing controversy in diagnosis and grading. DNA methylation analysis with the brain tumor classifier was used on tumor tissue from 37 patients identified from the Neuro-Oncology Branch Natural History Study and selected Collaborative Ependymoma Research Network (CERN) Tissue Repository. These were histologically diagnosed with non-myxopapillary spinal ependymoma (92% grade II and 8% grade III), with 12 designated “poor performers” (50% male, median age 30 years) defined by a progression free survival of less than two years (median 7 months) with at least one recurrence. Alternatively, the 25 “good performers” (56% male, median age 43 years) had no progression with a follow-up time greater than 5 years (median 84 months). Methylation classification matched to “spinal ependymoma” in 33% of the poor performer cases while 8% matched myxopapillary or RELA-fusion ependymoma and 50% were no-match. For the good performers, 52% agreed with histological diagnosis, 28% matched myxopapillary and 20% were no-match. Interestingly, we noted high-level MYCN amplification by copy number analysis in two (17%) cases, neither of which matched to a defined methylation class, and both of which were in the poor performers group. Overall, methylation results reveal complex biology in conventional spinal cord ependymomas, most evident in an increase of no-match cases in the poor performers group. Of importance, the no-match cases contain evidence of a potentially new diagnostic entity characterized by both a poor prognosis and MYCN amplification. For further elucidation of this entity, a larger cohort of patients with expanded clinical criteria has been identified for further testing.

scholarly journals A Phase II Study of Dose-Dense Temozolomide and Lapatinib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial, and Spinal Cord Ependymoma

2020 ◽  
Author(s):  
Mark R Gilbert ◽  
Ying Yuan ◽  
Jimin Wu ◽  
Tito Mendoza ◽  
Elizabeth Vera ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Phase Ii ◽  
Objective Response ◽  
Symptom Burden ◽  
Adult Patients ◽  
Research Network ◽  
Clinical Activity ◽  
Low Grade ◽  
Recurrent Ependymoma ◽  
Dose Dense

Abstract Background No standard medical treatment exists for adult patients with recurrent ependymoma and prospective clinical trials in this population have not succeeded because of its rarity and challenges in accruing patients. The Collaborative Ependymoma Research Network (CERN) conducted a prospective phase II clinical trial of dose-dense temozolomide and lapatinib, targeting the unmethylated MGMT promoter status and increased expression of ErbB2 (HER2) and ErbB1 (EGFR) in ependymomas. Methods Patients age 18 or older with histologically proven and progressive ependymoma or anaplastic ependymoma were eligible and received dose-dense temozolomide and daily lapatinib. The primary outcome measure was median progression-free survival (PFS). Landmark 6- and 12-month PFS and objective response were measured. Serial assessments of symptom burden using the MDASI-BT/MDASI-SP were collected. Results The 50 patients enrolled had a median age of 43.5 years, median Karnofsky Performance Status of 90, and a median of 2 prior relapses. Twenty patients had grade III, 16 grade II, and 8 grade I ependymoma. Half had spinal cord tumors; 15 had a supratentorial tumor, 8 infratentorial, and 2 had disseminated disease. Treatment was well tolerated. The median PFS was 7.8 months (95% CI 5.5,12.2); the 6-and 12-month PFS rates were 55% and 38%; with 2 complete and 6 partial responses. Measures of symptom burden showed reduction in moderate-severe pain and other disease-related symptoms in most patients. Conclusions This treatment, with demonstrated clinical activity with objective responses and prolonged disease control associated with disease-related symptom improvements is an option as a salvage regimen for adult patients with recurrent ependymoma.

scholarly journals Intramedullary spinal cord tumor resection

2012 ◽  
Vol 33 (Suppl1) ◽  
pp. 1
Author(s):  
Mari L. Groves ◽  
Patricia L. Zadnik ◽  
Pablo F. Recinos ◽  
Violette Renard ◽  
George I. Jallo
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Tumor ◽  
Tumor Resection ◽  
Progression Free Survival ◽  
Low Grade ◽  
High Definition ◽  
En Bloc ◽  
Intramedullary Spinal Cord ◽  
Free Survival ◽  
Intramedullary Spinal Cord Tumor

The authors present a case of a 27-year-old patient who presented with spastic gait and worsening difficulty walking over a 6 month period. Spinal MR imaging revealed a heterogeneously enhancing intramedullary spinal cord tumor (IMSCT) with associated syrinx in the cervical spine. The lesion was resected through posterior en bloc laminotomy, durotomy, and microscopic resection of the intramedullary component followed by laminoplasty reconstruction. Surgical resections with a goal of gross total resection can significantly improve overall survival and progression free survival in patients with low-grade IMSCT. The procedure is presented in an edited, high-definition format with accompanying narrative. The video can be found here: http://youtu.be/Ui9bn82PtP8.

Survival and functional outcome of childhood spinal cord low-grade gliomas

2009 ◽  
Vol 4 (3) ◽  
pp. 254-261 ◽  
Author(s):  
Katrin Scheinemann ◽  
Ute Bartels ◽  
Annie Huang ◽  
Cynthia Hawkins ◽  
Abhaya V. Kulkarni ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Pediatric Patients ◽  
Progression Free Survival ◽  
Spinal Tumors ◽  
High Morbidity ◽  
Low Grade ◽  
Aggressive Approach ◽  
Intramedullary Spinal Cord ◽  
Free Survival ◽  
Low Grade Gliomas

Object Intramedullary spinal cord low-grade gliomas (LGGs) are rare CNS neoplasms in pediatric patients, and there is little information on therapy for and outcome of these tumors in this population. Furthermore, most patient series combine adult and pediatric patients or high- and low-grade tumors, resulting in controversial data regarding optimal treatment of these children. To clarify these issues, the authors performed a regional population-based study of spinal cord LGGs in pediatric patients. Methods All pediatric patients with LGGs treated during the MR imaging era (1985–2007) were identified in the comprehensive database of the Hospital for Sick Children in Toronto. Data on demographics, pathology, treatment details, and outcomes were collected. Results Spinal cord LGGs in pediatric patients constituted 29 (4.6%) of 635 LGGs. Epidemiological and clinical data in this cohort were different than in patients with other spinal tumors and strikingly similar to data from pediatric patients with intracranial LGGs. The authors observed an age peak at 2 years and a male predominance in patients with these tumors. Histological testing revealed a Grade I astrocytoma in 86% of tumors. Although 5-year progression-free survival for the entire group was 48 ± 9%, all patients were alive at a median follow-up of 8.2 years. Five-year progression-free survival was 88 ± 13% for patients undergoing gross-total resection and 34 ± 11% for those undergoing all other therapies, respectively (p = 0.02). Chemotherapy and radiation therapy showed similar efficacy, achieving sustained tumor control in most patients. However, this excellent survival rate was associated with an 83% rate of significant neurological and orthopedic sequelae. Conclusions This study provides basic data on the incidence, clinical course, and outcome of spinal cord LGGs in pediatric patients. The similarities between spinal and intracranial LGGs in pediatric patients showing excellent survival but high morbidity suggest that a less aggressive approach may be the preferable treatment option for these patients.

scholarly journals High level MYCN amplification and distinct methylation signature define an aggressive subtype of spinal cord ependymoma

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Mark Raffeld ◽  
Zied Abdullaev ◽  
Svetlana D. Pack ◽  
Liqiang Xi ◽  
Sushma Nagaraj ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Mycn Amplification ◽  
Spinal Cord Ependymoma ◽  
High Level ◽  
Aggressive Subtype

scholarly journals Spinal Cord Ependymomas With MYCN Amplification Show Aggressive Clinical Behavior

2019 ◽  
Vol 78 (9) ◽  
pp. 791-797 ◽  
Author(s):  
Amy A Swanson ◽  
Aditya Raghunathan ◽  
Robert B Jenkins ◽  
Martina Messing-Jünger ◽  
Torsten Pietsch ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Adolescent And Young Adult ◽  
World Health ◽  
Gross Total Resection ◽  
Mycn Amplification ◽  
Chromosomal Microarray Analysis ◽  
Adjuvant Radiation ◽  
Low Grade ◽  
Adult Women ◽  
Total Resection

Abstract Adult spinal cord ependymomas are typically low grade and have a relatively favorable clinical course following gross total resection. We report 4 cases of anaplastic spinal cord ependymoma with MYCN amplification, an exceptionally rare finding. All cases occurred in the spinal cord of adolescent and young adult women and had morphological and immunohistochemical features of anaplastic ependymomas (World Health Organization grade III). Chromosomal microarray analysis demonstrated amplification of 2p24 (including MYCN) in all cases. One patient died 6 months after surgery. Another patient recently had removal of metastatic nodules in the thoracic region, following gross total resection and adjuvant radiation therapy of a lumbar ependymoma 1 year previously. One patient responded well after chemotherapy but died after multiple relapses 82 months after diagnosis. We found MYCN amplification reported in 2 other ependymomas, both anaplastic and arising in the spinal cord of adult females (Brain Pathol 2001;11:133–43). One patient had multiple recurrences in the spinal cord and an intracranial metastasis. Although MYCN amplification is rare in ependymomas, the current and previously reported cases suggest that this is associated with higher-grade histology, spinal location, and often unfavorable prognosis. The clinical significance and therapeutic implications of MYCN amplification in ependymomas require further evaluation.

scholarly journals PATH-66. THE GENOMIC LANDSCAPE OF SPINAL CORD EPENDYMOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi158-vi158
Author(s):  
Biswarathan Ramani ◽  
Javier Villanueva-Meyer ◽  
Christine Glastonbury ◽  
Ece Meram ◽  
Kyle Walsh ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Progression Free Survival ◽  
Suppressor Gene ◽  
Tumor Location ◽  
Genetic Alterations ◽  
Lumbar Spinal Cord ◽  
Small Subset ◽  
Mycn Amplification ◽  
Chromosome 22Q ◽  
Significant Difference

Abstract INTRODUCTION Ependymomas are seen throughout the neural axis but spinal cord is most common in adults. A subset arises in the setting of neurofibromatosis 2, whereas most are sporadic, potentially with somatic NF2 inactivation. The genetic drivers in NF2 wildtype tumors are unknown, as is the spectrum of cooperating genetic alterations. METHODS We performed targeted next-generation sequencing (NGS) to assess mutations, rearrangements, and chromosomal copy number alterations in 46 adult spinal cord ependymomas. RESULTS The 24 females and 22 males ranged from 20–73 (median 46) years of age. Tumors were in the cervical (n=24), thoracic (n=12), and lumbar (n=10) spinal cord. Nine tumors (20%) harbored truncating NF2 mutations with loss of the remaining wildtype allele, with frequent monosomy 13q. Thirteen NF2-wildtype tumors (28%) showed monosomy 22q with frequent monosomy 13q and trisomy 7, 9, and 12. Seventeen tumors (37%) carried a near-tetraploid genome, likely due to genomic reduplication with frequent preservation of diploidy in chromosomes 13q (77%), 14q (88%), 21q (53%) and 22q (65%). Remaining cases did not show a recurrent pattern, but one harbored focal high-level MYCN amplification. Three of the six recurrences were seen in the last subgroup; however, there was no significant difference for progression-free survival between four subgroups. None of the NF2-mutant tumors were in lumbar spinal cord, but there was no difference for tumor location or patient age between four subgroups. DISCUSSION Biallelic NF2 mutational inactivation characterizes only a subset of spinal cord ependymomas, and MYCN amplification is likely a genetic driver in a small subset of NF2 wildtype cases. The high frequency of chromosome 22q loss even in NF2-wildtype tumors raises the possibility of cryptic alterations in the NF2 gene not detected by our panel, or perhaps implicates the presence of another as yet unidentified tumor suppressor gene on chromosome 22q.

scholarly journals NCOG-38. CLINICAL CHARACTERISTICS OF LOW GRADE GLIOMA PATIENTS WITH NON-CANONICAL IDH1 AND IDH2 MUTATIONS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii137-ii137
Author(s):  
Katherine Peters ◽  
Eric Lipp ◽  
Gloria Broadwater ◽  
James Herndon ◽  
Margaret Johnson ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Point Mutations ◽  
Progression Free Survival ◽  
Idh1 Mutation ◽  
Low Grade ◽  
Isocitrate Dehydrogenase 1 ◽  
Who Grade ◽  
Targeted Mutation ◽  
Kaplan Meier ◽  
Idh1 And Idh2 Mutations

Abstract BACKGROUND Low grade gliomas (LGGs) develop in young adults and represent 10-15% of all glial tumors. While LGG patients can have longer survival than higher grade tumors, progression, transformation, and ultimately mortality occurs. Mutations in Isocitrate dehydrogenase 1/2 (IDH1/IDH2) are prevalent in LGG and are responsible for gliomagenesis. The classic IDH1 mutation is located at 132 codon and represented as p.Arg132His, but there are non-canonical IDH1 and IDH2 mutations. We sought to compare clinical characteristics of LGG patients with classic IDH1 p.Arg132His mutation to LGG patients with non-canonical IDH1 and IDH2 mutations. METHODS We queried an IRB-approved registry retrospectively from 12/2004- 9/2019. We included IDH1/IDH2 mutant LGG (WHO grade II) and known IDH1 and IDH2 targeted mutation analysis using standard PCR followed by DNA sequencing to detect point mutations in IDH1/IDH2 genes. We obtained available clinical and histopathological data. We estimated progression-free survival (PFS), time to transformation (TT), and overall survival (OS) using Kaplan-Meier methods. RESULTS We identified 267 LGG patients with median follow-up of 9.1 yrs (95%CI 8.4-9.9 yrs). Classic IDH1 p.Arg132His mutation occurred in 223 (83.9%) patients. IDH2 mutations occurred in 14 (5.2%) patients. Non-canonical IDH1 mutations were in 30 (11.2%) patients and included the following mutations: p.Arg132Cys (13), p.Arg132Gly (10), p.Arg132Ser (4), p.Arg132Leu (1), p.Arg119Gln (1), and p.Arg172Met (1). Initial presentation, OS, and TT did not differ between IDH1/IDH2 groups. PFS differed significantly between groups with improved median PFS in IDH2 mutant LGG (5.4 yrs; 95%CI 3.5-25.2) versus classic IDH1 mutant LGG (4.1 yrs; 95%CI 3.7-4.9 yrs) and non-canonical IDH1 mutant LGG (2.6 yrs; 95%CI 2.1-4.8) (log-rank p=0.019). Notably, non-canonical mutations were more common in astrocytoma (22/30; 73.3%) than other LGG histologies (p=0.018). CONCLUSIONS In this cohort, LGG patients with non-canonical mutations have a shorter time to progression than patients with classic p.Arg132His mutation and IDH2 mutations.

scholarly journals A survival analysis of surgically treated incidental low-grade glioma patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lingcheng Zeng ◽  
Qi Mei ◽  
Hua Li ◽  
Changshu Ke ◽  
Jiasheng Yu ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Low Grade Glioma ◽  
Low Grade ◽  
Total Resection ◽  
Surgical Timing ◽  
Asymptomatic Group ◽  
Free Survival ◽  
Symptomatic Group ◽  
Significant Difference ◽  
Asymptomatic Phase

AbstractTo evaluate the surgical effect on survival in patients with incidental low-grade glioma (LGG) through comparison between asymptomatic and symptomatic patients. The medical records of surgically treated adult cerebral incidental LGG (iLGG) patients in our department between January 2008 and December 2015 were retrospectively reviewed. The survival of patients was calculated starting from the initial imaging diagnosis. Factors related to progression-free survival (PFS), overall survival (OS) and malignant progression-free survival (MPFS) were statistically analyzed. Seventy-five iLGG patients underwent surgery: 49 in the asymptomatic group, who underwent surgery in the asymptomatic period, and 26 in the symptomatic group, who underwent surgery after the tumor had grown and the patients had developed tumor-related symptoms. Significantly more tumors were initially located adjacent to the functional area in the symptomatic group than in the asymptomatic group (P < 0.05), but there was no significant difference in the total resection rate between the two groups. The incidence of postoperative complications (15.4%) and postoperative epilepsy (23.1%) was higher in the symptomatic group than in the asymptomatic group (4.1% and 10.2%, respectively). Multivariate analysis showed that surgical timing, namely, surgery performed before or after symptom occurrence, had no significant effect on PFS, OS or MPFS, while total resection significantly prolonged PFS, OS and MPFS, and the pathology of oligodendroglioma was positively correlated with PFS and OS (P < 0.05). Surgical timing for iLGGs should facilitate total resection. If total resection can be achieved, even after symptom occurrence, patients can achieve comparable survival benefits to those treated with surgery in the asymptomatic phase.

scholarly journals RTID-05. INDIGO: A GLOBAL, RANDOMIZED, DOUBLE-BLIND, PHASE 3 STUDY OF VORASIDENIB (AG-881) VS PLACEBO IN PATIENTS WITH RESIDUAL/RECURRENT GRADE II GLIOMA WITH AN ISOCITRATE DEHYDROGENASE 1/2 (IDH1/2) MUTATION

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii194-ii194
Author(s):  
Ingo Mellinghoff ◽  
Martin van den Bent ◽  
Jennifer Clarke ◽  
Elizabeth Maher ◽  
Katherine Peters ◽  
...  
Keyword(s):  
High Risk ◽  
Dose Escalation ◽  
Objective Response ◽  
Data Monitoring Committee ◽  
Progression Free Survival ◽  
High Risk Population ◽  
Low Grade ◽  
Who Grade ◽  
Free Survival ◽  
Grade Ii

Abstract BACKGROUND Low-grade gliomas (LGGs; WHO grade II) are incurable and ultimately progress to high-grade gliomas. The current treatment options are surgery followed by observation (“watch and wait”) for patients with lower risk for disease progression or postoperative chemoradiotherapy (high-risk population). There are no approved targeted therapies. IDH1 and IDH2 mutations (mIDH1/2) occur in approximately 80% and 4% of LGGs, respectively, and promote tumorigenesis via neomorphic production of D-2-hydroxyglutarate. Vorasidenib, an oral, potent, reversible, brain-penetrant pan-inhibitor of mIDH1/2, was evaluated in 76 patients with glioma in two phase 1 studies (dose escalation and perioperative) and was associated with a favorable safety profile at daily doses below 100 mg. Preliminary clinical activity was observed in non-enhancing glioma patients in both studies, with an objective response rate (ORR) of 18.2% and median progression-free survival of 31.4 months in the dose escalation study. METHODS Approximately 366 patients will be randomized 1:1 to vorasidenib (50 mg QD) or matched placebo and stratified by 1p19q status (intact vs co-deleted). Key eligibility criteria: age ≥ 12 years; grade II oligodendroglioma or astrocytoma (per WHO 2016 criteria) not in need of immediate treatment and without high-risk features; centrally confirmed mIDH1/2 status; ≥ 1 surgery for glioma with most recent ≥ 1 year but ≤ 5 years before randomization, and no other anticancer therapy; Karnofsky performance status ≥ 80%; and centrally confirmed measurable, non-enhancing disease evaluable by magnetic resonance imaging. Crossover from placebo to the vorasidenib arm is permitted upon centrally confirmed radiographic progression per RANO-LGG criteria. Primary endpoint: progression-free survival assessed by independent review. Secondary endpoints: safety and tolerability, tumor growth rate assessed by volume, ORR, overall survival, and quality of life. Clinical data will be reviewed regularly by an independent data monitoring committee. The study is currently enrolling patients in the US, with additional countries planned (NCT04164901).

scholarly journals A comparison of the demographics, injury patterns and outcome data for patients injured in motor vehicle collisions who are trapped compared to those patients who are not trapped

2021 ◽  
Vol 29 (1) ◽  
Author(s):  
Tim Nutbeam ◽  
Rob Fenwick ◽  
Jason Smith ◽  
Omar Bouamra ◽  
Lee Wallis ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Blood Loss ◽  
Injury Severity ◽  
Spinal Cord Injuries ◽  
Motor Vehicle ◽  
Tension Pneumothorax ◽  
Research Network ◽  
Motor Vehicle Collisions ◽  
Vehicle Collisions ◽  
Time Critical

Abstract Background Motor vehicle collisions (MVCs) are a common cause of major trauma and death. Following an MVC, up to 40% of patients will be trapped in their vehicle. Extrication methods are focused on the prevention of secondary spinal injury through movement minimisation and mitigation. This approach is time consuming and patients may have time-critical injuries. The purpose of this study is to describe the outcomes and injuries of those trapped following an MVC: this will help guide meaningful patient-focused interventions and future extrication strategies. Methods We undertook a retrospective database study using the Trauma Audit and Research Network database. Patients were included if they were admitted to an English hospital following an MVC from 2012 to 2018. Patients were excluded when their outcomes were not known or if they were secondary transfers. Results This analysis identified 426,135 cases of which 63,625 patients were included: 6983 trapped and 56,642 not trapped. Trapped patients had a higher mortality (8.9% vs 5.0%, p < 0.001). Spinal cord injuries were rare (0.71% of all extrications) but frequently (50.1%) associated with other severe injuries. Spinal cord injuries were more common in patients who were trapped (p < 0.001). Injury Severity Score (ISS) was higher in the trapped group 18 (IQR 10–29) vs 13 (IQR 9–22). Trapped patients had more deranged physiology with lower blood pressures, lower oxygen saturations and lower Glasgow Coma Scale, GCS (all p < 0.001). Trapped patients had more significant injuries of the head chest, abdomen and spine (all p < 0.001) and an increased rate of pelvic injures with significant blood loss, blood loss from other areas or tension pneumothorax (all p < 0.001). Conclusion Trapped patients are more likely to die than those who are not trapped. The frequency of spinal cord injuries is low, accounting for < 0.7% of all patients extricated. Patients who are trapped are more likely to have time-critical injuries requiring intervention. Extrication takes time and when considering the frequency, type and severity of injuries reported here, the benefit of movement minimisation may be outweighed by the additional time taken. Improved extrication strategies should be developed which are evidence-based and allow for the expedient management of other life-threatening injuries.

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