Spinal Glioblastoma Research Articles

The Role of Radiotherapy, Chemotherapy, and Targeted Therapies in Adult Intramedullary Spinal Cord Tumors.

Intramedullary primary spinal cord tumors are rare in adults and their classification has recently evolved. Their treatment most frequently relies on maximal safe surgical resection. Herein, we review, in light of the WHO 2021 classification of central nervous system tumors, the knowledge regarding the role of radiotherapy and systemic treatments in spinal ependymomas, spinal astrocytomas (pilocytic astrocytoma, diffuse astrocytoma, spinal glioblastoma IDH wildtype, diffuse midline glioma H3-K27M altered, and high-grade astrocytoma with piloid features), neuro-glial tumors (ganglioglioma and diffuse leptomeningeal glioneuronal tumor), and hemangioblastomas. In spinal ependymomas, radiotherapy is recommended for incompletely resected grade 2 tumors, grade 3 tumors, and recurrent tumors not amenable to re-surgery. Chemotherapy is used in recurrent cases. In spinal astrocytomas, radiotherapy is recommended for incompletely resected grade 2 astrocytomas and grade 3 or 4 tumors as well as recurrent tumors. Chemotherapy is indicated for newly diagnosed high-grade astrocytomas and recurrent cases. In hemangioblastomas not amenable to surgery, radiotherapy is an effective alternative option. Targeted therapies are playing an increasingly important role in the management of some intramedullary primary spinal cord tumor subtypes. BRAF and/or MEK inhibitors have demonstrated efficacy in pilocytic astrocytomas and glioneuronal tumors, belzutifan in von Hippel-Lindau-related hemangioblastomas, and promising results have been reported with ONC201 in diffuse midline glioma H3-K27M altered.

Primary spinal glioblastoma multiforme in a pediatric patient: A case report

Primary spinal glioblastoma multiforme in a pediatric patient: A case report

Spinal Glioblastoma Mimicking Myelin Oligodendrocyte Glycoprotein Antibody Disease Transverse Myelitis (P13-5.021)

<h3>Objective:</h3> To present a case of spinal glioblastoma mimicking myelin oligodendrocyte glycoprotein antibody disease (MOGAD). <h3>Background:</h3> Spinal cord lesions have a broad differential, with inflammatory, vascular, and malignant causes often misdiagnosed. MOGAD is an inflammatory disease responsive to immunosuppressant therapy, while malignancies require surgery, radiation, and chemotherapy. Positive antibody titers support the diagnosis of MOGAD, but false positive results have been reported at low titers. Studies on primary spinal glioblastoma are limited with no reported cases of positive MOG antibodies. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 55-year old male presented with two months of leg weakness, paresthesias, and urinary retention. MR imaging showed longitudinally extensive abnormal cord signal from C3–C4 to T12 with 4.9×1.1cm rim-enhancing intramedullary lesion at T5–T6. MOG antibody titer was 1:40; other work up including cytology was negative. High dose steroids and three days of plasmapheresis (stopped due to allergic reaction) led to improved strength and cord edema regression, and the patient transitioned to a prednisone taper. Two weeks later, the patient developed arm weakness. Imaging showed progressive spinal cord edema. Additional history revealed symptoms developed a year before initially reported. Repeat testing was negative except unchanged MOG titer. After additional immunosuppressant therapy, imaging demonstrated unchanged enhancing spine lesion. Spinal biopsy revealed glioblastoma. <h3>Conclusions:</h3> Spinal cord malignancy can mimic MOGAD transverse myelitis. Chronicity and progression can aid in the diagnosis. This case highlights two atypical features for MOGAD: recurrence of cord signal changes and symptoms despite treatment, and the low elevation of MOG antibody titers, which raised suspicion for an alternative diagnosis. When atypical features are present in suspected inflammatory myelitis, a broad differential should be maintained. Studies show that patients with primary CNS malignancies can have signs of increased immune response, indicating that malignancy and autoimmune processes cause chronic immunologic dysfunction. <b>Disclosure:</b> Dr. Breitenbucher has nothing to disclose. Dr. Welsh has nothing to disclose. The institution of Dr. Robers has received research support from National Multiple Sclerosis Society. The institution of Dr. Robers has received research support from Bristol Myers Squibb Foundation. The institution of Dr. Robers has received research support from Barrow Neurological Foundation.

Natural Course and Prognosis of Primary Spinal Glioblastoma: A Nationwide Study.

Primary spinal glioblastoma (PsGBM) is extremely rare. The dramatic neurologic deterioration and unresectability of PsGBM makes it a particularly disabling malignant neoplasm. Because it is a rare and heterogeneous disease, the assessment of prognostic factors remains limited. PsGBMs were identified from the French Brain Tumor Database and the Club de Neuro-Oncologie of the Société Française de Neurochirurgie retrospectively. Inclusion criteria were age 18 years or older at diagnosis, spinal location, histopathologic diagnosis of newly glioblastoma according to the 2016 World Health Organization classification, and surgical management between 2004 and 2016. Diagnosis was confirmed by a centralized neuropathologic review. The primary outcome was overall survival (OS). Therapeutic interventions and neurologic outcomes were also collected. Thirty-three patients with a histopathologically confirmed PsGBM (median age 50.9 years) were included (27 centers). The median OS was 13.1 months (range 2.5-23.7), and the median progression-free survival was 5.9 months (range 1.6-10.2). In multivariable analyses using Cox model, Eastern Cooperative Oncology Group (ECOG) performance status at 0-1 was the only independent predictor of longer OS (hazard ratio [HR] 0.13, 95% CI 0.02-0.801; p = 0.02), whereas a Karnofsky performance status (KPS) score <60 (HR 2.89, 95% CI 1.05-7.92; p = 0.03) and a cervical anatomical location (HR 4.14, 95% CI 1.32-12.98; p = 0.01) were independent predictors of shorter OS. The ambulatory status (Frankel D-E) (HR 0.38, 95% CI 0.07-1.985; p = 0.250) was not an independent prognostic factor, while the concomitant standard radiochemotherapy with temozolomide (Stupp protocol) (HR 0.35, 95% CI 0.118-1.05; p = 0.06) was at the limit of significance. Preoperative ECOG performance status, KPS score, and the location are independent predictors of OS of PsGBMs in adults. Further analyses are required to capture the survival benefit of concomitant standard radiochemotherapy with temozolomide.

Intensity Modulated Radiotherapy in a Rare Case of Spinal Glioblastoma Multiforme: A Case Report

Primary spinal cord glioblastoma multiforme(GBM) is a rare clinical entity with an aggressive course andan invariably dismal prognosis. There are around 200 reportedcases of spinal cord GBM in total and approximately 70 casesin the cervical region. Median survival for this disorder is only12 months. We report a case of a 36 year old female patientwith primary spinal cord GBM.

Primary spinal cord glioblastoma multiforme: a single-center experience

Introduction Primary spinal glioblastoma (GBM) are very rare tumors of the spinal cord, with dismal prognosis and their exact management is controversial. We attempt to formulate treatment guidelines for these extremely rare tumors based on our institutional experience and a comprehensive review of the literature. Materials and methods In this retrospective study from 2008 to 2020, all the patients diagnosed with primary spinal GBM who underwent surgery at our institution were included. Clinical data were retrieved from case files, outpatient records and telephonic follow-up. Data on postoperative chemoradiation was noted in all the patients. The final diagnosis of spinal GBM was confirmed as per the histopathology reports. Patients who could not be followed up and those with prior history of cranial GBM were excluded from the study. Results Nine patients were followed up and a median survival of 11 months was noted. Chemotherapy with TMZ and radiotherapy to the whole craniospinal axis significantly improved survival in these patients. The extent of surgical resection was not shown to be significant. Intracranial metastasis was the leading cause of mortality in such patients. Three patients developed documented intracranial metastasis during the course of the disease. Conclusions Low threshold must be kept in mind in diagnosing patients with high-grade spinal cord intramedullary tumors in view of the rapidly progressing nature of the disease. In case of positive histopathological diagnosis of spinal GBM, the whole craniospinal axis should be imaged and any cranial metastasis which was originally missed during initial workup could be given appropriate radiotherapy.

Clinical Profile and Outcomes of Primary Immunodeficiency and Malignancy in Childhood at a Tertiary Oncology Center in Developing Country

Primary immune deficiencies are a group of heterogenous genetic disorders characterized by frequent infections, autoimmunity and malignancy. In this study, we aimed to evaluate clinical characteristics, outcomes of children with malignancy developed on background of primary immunodeficiency and compare survival rates of patients between malignant lymphoma with primary immunodeficiency and without immunodeficiency from tertiary oncology center in a developing country. A total 23 patients with primary immunodeficiency and malignancy were evaluated retrospectively. A total of 26 malignancies (first or second) in 23 patients were determined. The median age at the time of the first malignancy was 8 years (ranges 2–18 years) with increased male ratio (M/F:14/9). Non-Hodgkin lymphoma (n = 17; 65%) was the most common malignancy, followed by Hodgkin lymphoma (n = 5), anaplastic ependymoma (n = 1), spinal glioblastoma multiforme (n = 1), retinoblastoma (n = 1) and intracranial hemangiopericytoma (n = 1). The median follow-up time of patients was 25 months (ranges between 1 and 189 months). The 5-year overall survival rate of patients with malignant lymphoma associated with primary immunodeficiency (41%) were lower than immunocompetent patients with malignant lymphoma (80%) (p = 0.000). The 5-year overall survival of patients was diagnosed between 2021 and 2013 years (62%) was higher than previous years (22%) (p = 0.03). In conclusion, non-Hodgkin lymphomas were the most common histopathologic type in patients with malignancy associated with primary immunodeficiency in the present study. The survival of patients with malignant lymphoma associated with primary immunodeficiency has improved in recent years, yet it is still lower than immunocompetent patients with lymphoma and new targeted drugs are required for better survival rates.

A Rare Case of Dissemination of Primary Spinal Glioblastoma

Abstract Background Primary spinal glioblastoma is a rare lesion which constitutes only 1.5% of all spinal tumors. Diagnosis is challenging due to absence of any radiological hallmark of the disease. Even though surgery combined with chemoradiotherapy is the optimal management for these tumors, prognosis is still poor. Dissemination of glioblastoma is reported several times in the literature, which is correlated with worse prognosis and outcome. This case report that we are presenting is the first case where dissemination of primary spinal glioblastoma dissemination is limited only to spinal cord, without intracranial invasion, and regression was achieved with chemoradiotherapy. Case Report In this article, a patient with primary spinal glioblastoma who presented with paraparesia is presented. Patient underwent surgery for resection of the tumor and received adjuvant radiotherapy. However, 9 months postoperatively, dissemination was detected in epidural and subdural spaces of spinal canal, with concomitant compression of spinal cord. There was no radiographically detected lesion in cranial MRI. He underwent second session of radiotherapy, combined with chemotherapy and steroid. Five months later, regression of metastatic disseminated lesions was observed. Conclusion Primary spinal glioblastoma is a rare pathology and known to have a poor prognosis, notably with dissemination of the disease. Even though further biomolecular studies are necessary to explain the pathophysiology better, chemotherapy and radiotherapy may be effective in regression of disseminated lesions.

NTRK Fusion-Positive Congenital Spinal Glioblastoma treated with Carboplatin, Etoposide, and Larotrectinib

NTRK Fusion-Positive Congenital Spinal Glioblastoma treated with Carboplatin, Etoposide, and Larotrectinib

Primary spinal glioblastoma multiforme. Single center experience and literature review

ObjectivesSpinal glioblastomas represent a rare entity accounting for ca 1–3% of all intramedullary tumors; data about survival, prognostic factors and therapeutic protocols are quite poor. Even with an aggressive multimodal management the spinal glioblastoma patients’ survival remains poor, with rapid progression of the disease. This study reports our experience with the management of the primary intramedullary glioblastomas, also in regard to the current literature data. Patients and MethodsWe retrospectively analyzed the medical records of 5 patients treated at the Department for Neuro-oncology and Spine Surgery of the Clinical Center of Belgrade, Serbia, between January 2007 and December 2016 for a primary intramedullary glioblastoma. Demographic characteristics, pre-operative data and post-operative results were then compared with previous literature regarding spinal GBMs and attempt to identify potential prognostic factors. ResultsGross total resection was achieved in two patients, while a subtotal resection was performed in the latter 3 cases; as per protocol, all patients underwent to surgery, followed by radio and chemotherapy. There were no intraoperative complications and no patients developed a new postoperative neurological defect; the median overall survival was 6 months. Progression or recurrence of disease was noted in all patients at the 3-months follow-up, despite the adjuvant treatments. ConclusionsTo the date, there is a lack of consensus on specific management of spinal glioblastomas: the extent of resection can play an important role, but it appears to be not preeminent. A shorter interval between symptoms onset and treatment and a smaller extension of the tumor seem to be correlated with better outcomes and a longer overall survival. However, there is not an adjunctive viable standardized postoperative therapy yet, which results in concrete and persistent improvement of overall survival and progression free survival.

Intramedullary spinal glioblastoma metastasis from a brainstem anaplastic astrocytoma: A case report and review of the literature

Intramedullary spinal glioblastoma metastasis from a brainstem anaplastic astrocytoma: A case report and review of the literature

Treatment of a Rare Intramedullary Primary Spinal Glioblastoma Multiforme Lesion in an Adult Patient

Treatment of a Rare Intramedullary Primary Spinal Glioblastoma Multiforme Lesion in an Adult Patient

Glioblastoma multiforme of the conus medullaris with leptomeningeal dissemination that presented as intracranial hypertension: A case report and literature review

Spinal glioblastoma multiforme (GBM) that originates from the conus medullaris is rare as only 28 cases have been reported. It is highly aggressive and usually initially presents with low back pain, sensory and motor impairment of the lower extremities, and bladder dysfunction. We herein report a unique case of GBM in the conus medullaris with leptomeningeal dissemination that initially presented with increased intracranial pressure without hydrocephalus. The patient was first diagnosed with tuberculous meningitis and received antituberculosis therapy, but the symptoms did not resolve and even worsened. Subsequent radiological imaging clearly disclosed an intramedullary lesion at the T12 level with the progression of leptomeningeal enhancement. Subtotal resection of the intramedullary lesion was performed, and pathological examination revealed the presence of GBM. To our knowledge, our case was the first with holocordal and intracranial leptomeningeal dissemination that initially presented with intracranial hypertension in the absence of hydrocephalus. Awareness of this unusually lethal condition is significant for proper diagnosis, timely treatment, and consideration of clinical prognosis.

INNV-04. CONGENITAL SPINAL GLIOBLASTOMA WITH SUSTAINED RESPONSE TO TROPOMYOSIN RECEPTOR KINASE (TRK) INHIBITION: A CASE REPORT

Abstract Large scale genomic efforts have shown that a significant percentage of infant high-grade gliomas (HGG) carry targetable gene fusions. Given the rarity of congenital spinal HGGs, little is known about the molecular features of these tumors and their response to treatment. We describe a case of a patient with congenital spinal glioblastoma. A full-term female infant with symmetric IUGR was noted to have weakness with little movement of her upper extremities. MRI of the spine showed an infiltrative and hemorrhagic intraspinal cervicothoracic neoplasm with a large hemorrhagic intramedullary component. A biopsy was done and revealed a high-grade glial neoplasm with pan-TRK expression. Next generation sequencing (NGS) confirmed a MEF2D-NTRK1 gene fusion. Prior to the result of her molecular testing, the patient clinically deteriorated with decreased movement and increased apneic episodes despite steroid treatment. She was then started on treatment with carboplatin and etoposide per Macy et al 1. After one cycle of chemotherapy and given the results of NGS, targeted therapy with larotrectinib was added to her treatment. The patient showed a response (clinical and imaging) following cycle 1 with chemotherapy, and a marked response following cycle 2 with both chemotherapy and targeted TRK inhibition. The patient completed six cycles of chemotherapy and has continued on daily oral larotrectinib. She continues to tolerate the targeted therapy well and currently is 8 months old, growing and developing well. She has regained much of her movement and is eating and growing with apparent normal development. This case provides an example of a patient with congenital glioblastoma with TRK gene fusion that showed an impressive response to targeted therapy combined with more conventional chemotherapy. 1Macy M, et al. Clinical and molecular characteristics of congenital glioblastoma. Neuro Oncol. Jul;14 (7) 931–941, 2012).

Predictors of mortality in patients with primary spinal cord glioblastoma.

Primary spinal cord glioblastoma (GBM) is a rare and devastating disease. Little attention was ever paid to this rare disease. As a result, the standard treatment protocol and prognostic factors of primary spinal cord GBM were not well established. The aim of this study was to determine the predictors associated with survival in patients with primary spinal cord GBM. A total of 122 patients with primary spinal cord GBM from Surveillance, Epidemiology, and End Results database and our institution were included in this retrospective analysis. Information about age, sex, race, tumor invasion, extent of resection, radiation, chemotherapy and year of diagnosis was collected. Univariate and multivariate accelerated failure time (AFT) regression model was performed to identify prognostic factors. Of the 122 patients, 102 (83.6%) expired at the time of data collection. Overall survival at 1year, 2years, 3years and 5years was 48.4%, 22.8%, 17.1% and 8.4%, respectively, and median survival time was 12months. Only radiation was found to be associated with survival in the AFT regression model (time ratio 1.94, 95% CI 1.01-3.72, p < 0.05). Radiotherapy could improve survival slightly; patients who received RT survived approximately two times as long as patients who did not receive RT, but the advantage was short term. The survival of primary spinal cord GBM is poor in the current treatment strategy. Radiotherapy was associated with better survival, but the advantage was short term.

Dilemmas in primary spinal glioblastoma management during pregnancy

Primary spinal glioblastoma (GBM) is a clinically rare entity with rapid progression and a dismal outcome despite aggressive treatment. In a pregnant woman, this malignancy is particularly dramatic because the potential benefits to the mother offered by standard GBM treatment must be balanced against the risks to the fetus. There is little guidance in the literature on how to manage pregnant patients with malignant neuraxial tumours and, to the authors' knowledge, no reports have been published so far regarding this specific neoplasm in such population. This case report describes the management of a pregnant patient with a previously undiagnosed and rapidly progressive intramedullary GBM submitted to an elective caesarean delivery to allow subsequent onset of oncological treatment. Dilemmas faced by anaesthetists are discussed in hope to provide guidance for future decisions and optimize outcomes.

P15 - Patterns of Care and Survival Outcomes for Patients with Primary Spinal Glioblastoma Multiforme

P15 - Patterns of Care and Survival Outcomes for Patients with Primary Spinal Glioblastoma Multiforme

Retraction Note to: The Critical Role of SRPK1 in EMT of Human Glioblastoma in the Spinal Cord.

Up to now, the serine-arginine protein kinase 1 (SRPK1) has been suggested as an important signal mediator, which is implicated in the development of cancers. Unfortunately, some molecular pathways in SRPK1-mediated epithelial-mesenchymal transition (EMT) in human spinal glioblastoma have been not elucidated. In this work, we detected the expression of SRPK1 in human spinal glioblastoma tissues and GBM cell lines and analyzed the relevant molecular proteins using in vitro experiments, including RT-PCR, gene silencing, and Western blot. In this study, RT-PCR and Western blot revealed that the expression of SRPK1 mRNA and protein became higher in all six spinal glioblastoma specimens; however, its expression was low in matched normal specimens. We also demonstrated SRPK1 expression facilitated the proliferation of U87 and U251 cells and inhibited the apoptosis in U87 and U251 cells. Also, SRPK1 promoted the expression of EMT-regulating markers, involving N-cadherin, Snail, and MMP9 and decreased the expression of mesenchymal marker E-cadherin. Moreover, knockdown of SRPK1 significantly inhibited the expression levels of p-Akt rather than t-Akt. In conclusion, knockdown of SRPK1 inhibited glioblastoma cell proliferation, invasion, and EMT process via suppressing p-Akt signaling pathway. This study also lays a new foundation for the clinically biological treatment.

Cervical spinal glioblastoma multiforme in the elderly

Spinal glioblastoma multiforme (GBM) is uncommon, and its diagnosis may be challenging. This is especially true in the elderly population. Best management strategy remains to be defined. The purpose of...

A systematic review of overall survival in pediatric primary glioblastoma multiforme of the spinal cord.

OBJECTIVE The incidence of primary spinal cord glioblastoma multiforme (GBM) in the pediatric age group is very rare. Only a few case series and case reports have been published in the literature; therefore, overall survival (OS) outcome and the as-yet poorly defined management options are not discussed in detail. The authors performed a cumulative survival analysis of all reported cases of pediatric spinal cord GBM to identify the predictive factors related to final survival outcome. METHODS A comprehensive search for relevant articles was performed on PubMed's electronic database MEDLINE for the period from 1950 to 2015 using the search words "malignant spinal cord tumor" and "spinal glioblastoma multiforme." This study was limited to patients younger than 18 years of age. Survival rates for children with various tumor locations and treatments were collected from the published articles and analyzed. RESULTS After an extensive literature search, 29 articles met the study inclusion criteria. From the detailed information in these articles, the authors found 53 children eligible for the survival analysis. The majority (45%) of the children were more than 12 years old. Thirty-four percent of the cases were between 7 and 12 years of age, and 21% were younger than 7 years. In the Kaplan-Meier survival analysis, children younger than 7 years of age had better survival (13 months) than the children older than 7 years (7-12 years: 10 months, > 12 years: 9 months; p = 0.01, log-rank test). Fifty-five percent of the children were female and 45% were male. A cervical tumor location (32%) was the most common, followed by thoracic (28.3%). Cervicothoracic (18.9%) and conus (18.8%) tumor locations shared the same percentage of cases. Cervical tumors had a worse outcome than tumors in other locations (p = 0.003, log-rank test). The most common presenting symptom was limb weakness (53%), followed by sensory disturbances (25%). Median OS was 10 months. The addition of adjuvant therapy (radiotherapy [RT] and/or chemotherapy [CT]) after surgery significantly improved OS (p = 0.01, log-rank test). Children who underwent gross-total resection and RT had better outcomes than those who underwent subtotal resection and RT (p = 0.04, log-rank test). Cerebrospinal fluid spread, hydrocephalus, brain metastasis, and spinal metastasis were not correlated with OS in primary spinal GBM. CONCLUSIONS Adjuvant therapy after surgery had a beneficial effect on overall outcome of spinal GBM in the pediatric age group. Gross-total resection followed by RT produced a better outcome than subtotal resection with RT. Further large-scale prospective study is required to establish the genetic and molecular factors related to OS in primary GBM of the spinal cord in pediatric patients.