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Nature Mar 2022Diffuse intrinsic pontine glioma (DIPG) and other H3K27M-mutated diffuse midline gliomas (DMGs) are universally lethal paediatric tumours of the central nervous system....
Diffuse intrinsic pontine glioma (DIPG) and other H3K27M-mutated diffuse midline gliomas (DMGs) are universally lethal paediatric tumours of the central nervous system. We have previously shown that the disialoganglioside GD2 is highly expressed on H3K27M-mutated glioma cells and have demonstrated promising preclinical efficacy of GD2-directed chimeric antigen receptor (CAR) T cells, providing the rationale for a first-in-human phase I clinical trial (NCT04196413). Because CAR T cell-induced brainstem inflammation can result in obstructive hydrocephalus, increased intracranial pressure and dangerous tissue shifts, neurocritical care precautions were incorporated. Here we present the clinical experience from the first four patients with H3K27M-mutated DIPG or spinal cord DMG treated with GD2-CAR T cells at dose level 1 (1 × 10 GD2-CAR T cells per kg administered intravenously). Patients who exhibited clinical benefit were eligible for subsequent GD2-CAR T cell infusions administered intracerebroventricularly. Toxicity was largely related to the location of the tumour and was reversible with intensive supportive care. On-target, off-tumour toxicity was not observed. Three of four patients exhibited clinical and radiographic improvement. Pro-inflammatory cytokine levels were increased in the plasma and cerebrospinal fluid. Transcriptomic analyses of 65,598 single cells from CAR T cell products and cerebrospinal fluid elucidate heterogeneity in response between participants and administration routes. These early results underscore the promise of this therapeutic approach for patients with H3K27M-mutated DIPG or spinal cord DMG.
Topics: Astrocytoma; Brain Stem Neoplasms; Child; Gangliosides; Gene Expression Profiling; Glioma; Histones; Humans; Immunotherapy, Adoptive; Mutation; Receptors, Chimeric Antigen; Spinal Cord Neoplasms
PubMed: 35130560
DOI: 10.1038/s41586-022-04489-4 -
The Pan African Medical Journal 2021
Topics: Humans; Neurilemmoma; Neurofibroma; Spinal Cord Neoplasms
PubMed: 34527162
DOI: 10.11604/pamj.2021.39.146.30169 -
Cureus Jul 2019Primary spinal astrocytoma is a subtype of glioma, the most common spinal cord tumor found in the intradural intramedullary compartment. Spinal astrocytomas account for... (Review)
Review
Primary spinal astrocytoma is a subtype of glioma, the most common spinal cord tumor found in the intradural intramedullary compartment. Spinal astrocytomas account for 6-8% of all spinal cord tumors and are primarily low grade (World Health Organization grade I (WHO I) or WHO II). They are seen in both the adult and pediatric population with the most common presenting symptoms being back pain, sensory dysfunction, or motor dysfunction. Magnetic Resonance Imaging (MRI) with and without gadolinium is the imaging of choice, which usually reveals a hypointense T1 weighted and hyperintense T2 weighted lesion with a heterogeneous pattern of contrast enhancement. Further imaging which may aid in surgical planning includes computerized tomography, diffusion tensor imaging, and tractography. Median survival in spinal cord astrocytomas ranges widely. The factors most significantly associated with poor prognosis and shorter median survival are older age at initial diagnosis, higher grade lesion based on histology, and extent of resection. The mainstay of treatment for primary spinal cord astrocytomas is surgical resection, with the goal of preservation of neurologic function, guided by intraoperative neuromonitoring. Adjunctive radiation has been shown beneficial and may increase overall survival. The role of adjunctive chemotherapy is employed, however, its benefit has not been clearly defined. Primary spinal cord astrocytomas are rare and challenging to treat. The gold standard treatment is surgical resection. Second-line treatments include radiation and chemotherapy, although, the optimal regimen for adjunctive therapy has not yet been clearly defined.
PubMed: 31565645
DOI: 10.7759/cureus.5247 -
Nature Communications Nov 2021Spinal ependymomas are the most common spinal cord tumors in adults, but their intratumoral cellular heterogeneity has been less studied, and how spinal microglia are...
Spinal ependymomas are the most common spinal cord tumors in adults, but their intratumoral cellular heterogeneity has been less studied, and how spinal microglia are involved in tumor progression is still unknown. Here, our single-cell RNA-sequencing analyses of three spinal ependymoma subtypes dissect the microenvironmental landscape of spinal ependymomas and reveal tumor-associated macrophage (TAM) subsets with distinct functional phenotypes. CCL2 TAMs are related to the immune response and exhibit a high capacity for apoptosis, while CD44 TAMs are associated with tumor angiogenesis. By combining these results with those of single-cell ATAC-sequencing data analysis, we reveal that TEAD1 and EGR3 play roles in regulating the functional diversity of TAMs. We further identify diverse characteristics of both malignant cells and TAMs that might underlie the different malignant degrees of each subtype. Finally, assessment of cell-cell interactions reveal that stromal cells act as extracellular factors that mediate TAM diversity. Overall, our results reveal dual functions of TAMs in tumor progression, providing valuable insights for TAM-targeting immunotherapy.
Topics: Apoptosis; Cell Communication; Ependymoma; Genetic Heterogeneity; Humans; Neovascularization, Pathologic; Phenotype; Single-Cell Analysis; Spinal Cord Neoplasms; Stromal Cells; Transcriptome; Tumor Microenvironment; Tumor-Associated Macrophages
PubMed: 34824203
DOI: 10.1038/s41467-021-27018-9 -
Medicine May 2020Intramedullary cervical spinal cord teratomas (ICTs) are extremely rare, and diagnosis and treatment are challenging. We conducted a systematic review of the literature...
BACKGROUND
Intramedullary cervical spinal cord teratomas (ICTs) are extremely rare, and diagnosis and treatment are challenging. We conducted a systematic review of the literature on the diagnosis and treatment of ICT.
METHOD
The presentation, imaging manifestations, diagnosis, management, surgery findings, prognosis and histology were reviewed following Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines. English-language studies and case reports published from inception to 2018 were retrieved. Data on presentation, imaging characteristics, diagnosis, management, surgery findings, outcomes, and histopathology were extracted.
RESULTS
Ten articles involving 10 patients were selected. The lesions were located in the upper cervical vertebrae in 4 cases, whereas in the lower cervical vertebrae in the remaining 6 cases. In 5 cases, the lesions were located on the dorsal side of the spinal cord, and in the center of the spinal cord in the remaining 5 cases. Quadriparesis (60%), paraplegia (30%), monoplegia (10%), and neck pain (50%) were the main presentations. The lesion appeared as a intramedullary heterogeneous signal during an MRI scan, and the lesion signal would be partially enhanced after the contrast medium was applied. All patients underwent surgical intervention through a posterior approach. Neurological function improved postoperatively in all patients. Two patients with pathology confirmed to be immature teratomas experienced recurrence.
CONCLUSION
ICTs are extremely rare entities that are mainly located in the center or dorsal part of the spinal cord which mainly manifest as quadriplegia and neck pain. MRI is a useful modality that provides diagnostic clues. Surgery from a posterior approach is the primary treatment, and the effect of adjuvant therapy remains uncertain. The prognosis is mainly related to the pathological nature of the tumor and not the method of resection.
Topics: Cervical Vertebrae; Humans; Spinal Cord Neoplasms; Teratoma
PubMed: 32358400
DOI: 10.1097/MD.0000000000020107 -
Physical Medicine and Rehabilitation... Feb 2017Spinal tumors are classically grouped into 3 categories: extradural, intradural extramedullary, and intradural intramedullary. Spinal tumors may cause spinal cord... (Review)
Review
Spinal tumors are classically grouped into 3 categories: extradural, intradural extramedullary, and intradural intramedullary. Spinal tumors may cause spinal cord compression and vascular compromise resulting in pain or neurologic compromise. They may also alter the architecture of the spinal column, resulting in spinal instability. Oncologic management of spinal tumors varies according to the stability of the spine, neurologic status, and presence of pain. Treatment options include surgical intervention, radiation therapy, chemotherapy, and hormonal manipulation. When combined with this management, rehabilitation can serve to relieve symptoms, improve quality of life, enhance functional independence, and prevent further complications in patients.
Topics: Humans; Pain Management; Quality of Life; Spinal Cord Neoplasms
PubMed: 27912991
DOI: 10.1016/j.pmr.2016.08.007 -
The Pan African Medical Journal 2018
Topics: Aged; Cauda Equina; Dementia; Ependymoma; Female; Humans; Hydrocephalus; Magnetic Resonance Imaging; Middle Aged; Neurilemmoma; Peripheral Nervous System Neoplasms; Spinal Cord; Spinal Cord Neoplasms
PubMed: 30100960
DOI: 10.11604/pamj.2018.29.206.10723 -
Frontiers in Oncology 2020Stereotactic radiation treatment can be used to treat spinal cord neoplasms in patients with either unresectable lesions or residual disease after surgical resection.... (Review)
Review
Stereotactic radiation treatment can be used to treat spinal cord neoplasms in patients with either unresectable lesions or residual disease after surgical resection. While treatment guidelines have been suggested for epidural lesions, the utility of stereotactic radiation for intradural and intramedullary malignancies is still debated. Prior reports have suggested that stereotactic radiation approaches can be used for effective tumor control and symptom management. Treatment-related toxicity has been documented in rare subsets of patients, though the incidences of injury are not directly correlated with higher radiation doses. Further studies are needed to assess the factors that influence the risk of radiation-induced myelopathy when treating spinal cord neoplasms with stereotactic radiation, which can include, but may not be limited to, maximum dose, dose-fractionation, irradiated volume, tumor location, histology and treatment history. This review will discuss evidence for current treatment approaches.
PubMed: 32582555
DOI: 10.3389/fonc.2020.00907 -
JPMA. the Journal of the Pakistan... Jul 2023Spinal meningiomas are relatively rare, benign, intradural, extramedullary tumours, that are typically slow-growing and well-defined. Surgery is always the first line...
Spinal meningiomas are relatively rare, benign, intradural, extramedullary tumours, that are typically slow-growing and well-defined. Surgery is always the first line for treating spinal meningiomas. Here, we have discussed the existing literature on spinal meningiomas and the role of surgery in determining the outcomes.
Topics: Humans; Meningioma; Spinal Cord Neoplasms; Meningeal Neoplasms
PubMed: 37469082
DOI: 10.47391/JPMA.23-52 -
Neuro-oncology Jul 2016Ependymomas are rare primary tumors of the central nervous system in children and adults that comprise histologically similar but genetically distinct subgroups. The... (Review)
Review
Ependymomas are rare primary tumors of the central nervous system in children and adults that comprise histologically similar but genetically distinct subgroups. The tumor biology is typically more associated with the site of origin rather than being age-specific. Genetically distinct subgroups have been identified by genomic studies based on locations in classic grade II and III ependymomas. They are supratentorial ependymomas with C11orf95-RELA fusion or YAP1 fusion, infratentorial ependymomas with or without a hypermethylated phenotype (CIMP), and spinal cord ependymomas. Myxopapillary ependymomas and subependymomas have different biology than ependymomas with typical WHO grade II or III histology. Surgery and radiotherapy are the mainstays of treatment, while the role of chemotherapy has not yet been established. An in-depth understanding of tumor biology, developing reliable animal models that accurately reflect tumor molecule features, and high throughput drug screening are essential for developing new therapies. Collaborative efforts between scientists, physicians, and advocacy groups will enhance the translation of laboratory findings into clinical trials. Improvements in disease control underscore the need to incorporate assessment and management of patients' symptoms to ensure that treatment advances translate into improvement in quality of life.
Topics: Animals; Brain Neoplasms; Disease Models, Animal; Ependymoma; Glioma, Subependymal; Humans; Quality of Life; Spinal Cord Neoplasms
PubMed: 27022130
DOI: 10.1093/neuonc/now016