High-grade Spinal Glioma Research Articles

LGG-16. BRAFV600K LOW-GRADE GLIOMA EMERGENCE DURING THERAPY FOR BRAFV600E HIGH-GRADE GLIOMA

Abstract BACKGROUND BRAFV600E mutations are prevalent in pediatric brain tumors, constituting 20% of low-grade and 5% of high-grade gliomas. Other single-nucleotide substitutions in BRAF are described in adult cancers but rarely in pediatric brain tumors. Our case sheds light on a unique scenario—a patient with a BRAF-mutated high-grade spinal glioma who later developed slowly progressive intracranial low-grade glioma, subsequently undergoing rapid high-grade transformation. METHODS Case Report RESULTS Our patient initially presented as a thirteen-year-old male with a two-month history of progressive bilateral hand weakness/paresthesias. Spine MRI revealed a fusiform expansile intramedullary neoplasm from C3-T2, brain MRI was negative. Biopsy showed an anaplastic astrocytoma with BRAFV600E mutation and MYC-N amplification. Initial treatment included proton radiation and a 2-year course of Dabrafenib/Trametinib, maintaining disease stability. After four months off therapy, he developed local progression, and re-staging brain MRI showed new cerebellar/supratentorial lesions. Dabrafenib/Trametinib was re-started until progression two years later. He developed hydrocephalus and underwent ETV and brain tumor biopsy, which revealed a low-grade glioma with BRAFV600K mutation. At this point, Dabrafenib/Trametinib continued for another 1.5 years; he exhibited slow progression of the brain tumors before a cerebellar lesion developed rapid progression. He had GTR of the rapid-growing lesion, and pathology reported a Grade 4 invasive astrocytoma harboring BRAFV600E, two VUS MTOR mutations, and MGMT promoter methylation. Current treatment involves radiation therapy concurrent with temozolomide. CONCLUSIONS While combinatorial Dabrafenib/Trametinib is effective in glioma therapy, resistance and progression challenges persist. Our case presents a unique manifestation—a patient with a spinal high-grade glioma with BRAFV600E who developed a secondary low-grade glioma with BRAFV600K in the brain, which, after several years, transformed into a high-grade glioma. Future research is crucial for comprehending the intricate role of BRAF mutations in pediatric gliomas, paving the way for improved patient outcomes.

A multicenter analysis of the prognostic value of histone H3 K27M mutation in adult high-grade spinal glioma.

High-grade spinal glioma (HGSG) is a rare but aggressive tumor that occurs in both adults and children. Histone H3 K27M mutation correlates with poor prognosis in children with diffuse midline glioma. However, the role of H3 K27M mutation in the prognosis of adults with HGSG remains unclear owing to the rarity of this mutation, conflicting reports, and the absence of multicenter studies on this topic. The authors studied a cohort of 30 adult patients with diffuse HGSG who underwent histological confirmation of diagnosis, surgical intervention, and treatment between January 2000 and July 2020 at six tertiary academic centers. The primary outcome was the effect of H3 K27M mutation status on progression-free survival (PFS) and overall survival (OS). Thirty patients (18 males and 12 females) with a median (range) age of 50.5 (19-76) years were included in the analysis. Eighteen patients had H3 K27M mutation-positive tumors, and 12 had H3 K27M mutation-negative tumors. The median (interquartile range) PFS was 3 (10) months, and the median (interquartile range) OS was 9 (23) months. The factors associated with increased survival were treatment with concurrent chemotherapy/radiation (p = 0.006 for PFS, and p ≤ 0.001 for OS) and American Spinal Injury Association grade C or better at presentation (p = 0.043 for PFS, and p < 0.001 for OS). There were no significant differences in outcomes based on tumor location, extent of resection, sex, or H3 K27M mutation status. Analysis restricted to HGSG containing necrosis and/or microvascular proliferation (WHO grade IV histological features) revealed increased OS for patients with H3 K27M mutation-positive tumors (p = 0.017). Although H3 K27M mutant-positive HGSG was associated with poor outcomes in adult patients, the outcomes of patients with H3 K27M mutant-positive HGSG were somewhat more favorable compared with those of their H3 K27M mutant-negative HGSG counterparts. Further preclinical animal studies and larger clinical studies are needed to further understand the age-dependent effects of H3 K27M mutation.

Erratum. A multicenter analysis of the prognostic value of histone H3 K27M mutation in adult high-grade spinal glioma.

Erratum. A multicenter analysis of the prognostic value of histone H3 K27M mutation in adult high-grade spinal glioma.

Pediatric primary high-grade spinal glioma: a National Cancer Database analysis of current patterns in treatment and outcomes.

Pediatric primary high-grade spinal glioma (p-HGSG) is an extremely rare disease process, with little data within the current literature. Akin to primary high-grade gliomas, this cancer has been exemplified by dismal prognosis and poor response to modern treatment paradigms. This study seeks to investigate the current trends affecting overall survival using the National Cancer Database (NCDB). The NCDB was queried for p-HGSG between 2004 and 2016, by utilizing the designated diagnosis codes. Kaplan-Meier curves were generated, and log-rank testing was performed to analyze factors affecting overall survival. In addition, a Cox proportional-hazards model was used to perform multivariate regression analysis of survival outcomes. A cohort of 97 patients was identified with a histologically confirmed p-HGSG. The overall incidence of p-HGSG in all pediatric spinal cord tumors is 7.5%, with a mean survival time of 25.3months (SD, 21.0) and 5-year overall survival of 17.0%. The majority of patients underwent surgery (n = 87, 89.7%), radiotherapy (n = 73, 75.3%), and chemotherapy (n = 60, 61.9%). Univariate, multivariate, and Kaplan-Meier log-rank testing failed to demonstrate an association between performing surgery, extent of resection, radiotherapy, or chemotherapy with improved survival outcomes. The current study constitutes the largest retrospective analysis of p-HGSGs to date, finding that current treatment options of surgery, radiotherapy, and chemotherapy have unclear benefit. This disease process has a poor prognosis without a current modality of treatment that conclusively alters survival. The risks and side effects of these treatment modalities must be carefully considered in such a highly aggressive disease process, especially given potentially limited survival benefits.

Adult primary high-grade spinal glioma: a nationwide analysis of current trends in treatment and outcomes.

High-grade spinal glioma (HGSG) is an extremely rare, malignant neoplasm insufficiently described in the literature. We sought to investigate the effect of epidemiological risk factors and treatment strategies on the prognosis of HGSGs using the National Cancer Database (NCDB). Patients with diagnosis codes specific for HGSG were queried from the NCDB during the years 2004-2016. Kaplan-Meier curves were generated with log-rank testing performed to assess factors affecting survival. Univariate and multivariate Cox regression analysis was also performed to investigate overall survival. 396 patients were identified with a histologically-confirmed diagnosis of HGSG between 2004-2016. The mean survival time for all patients was 24.5months (SD: 20.3). Multivariate Cox proportional-hazards regression analysis revealed that tumor size of 26-50mm (HR 4.96, 95% CI 1.76-13.98, p < 0.01) and greater than 50mm (HR 4.67, 95% CI 1.43-15.23, p = 0.01) were associated with worsened overall survival in comparison to lesions less than 26mm. While quality of life was not investigated, both Kaplan-Meier log-rank testing and regression analysis failed to demonstrate an association of survival outcomes with extent of resection, radiotherapy, or chemotherapy. The current study represents the largest retrospective analysis of adult primary high-grade spinal glioma to date. Our analysis found no relationship between the extent of surgical resection and survival outcomes. In addition, we failed to show any statistically significant survival benefit with radiotherapy or chemotherapy. This disease process has a poor prognosis without a current modality of treatment that improves survival.

Comparison of Alterations in miRNA Expression in Matched Tissue and Blood Samples during Spinal Cord Glioma Progression

Abnormal expression of microRNAs (miRNAs) contributes to glioma initiation. However, the expression of miRNAs in tumour tissue or blood of spinal cord glioma (SCG) patients, particularly in high-grade spinal gliomas (Grade IV) known as glioblastoma (GBM), remains largely unknown. In this study we aimed to determine differentially expressed miRNAs (DEmiRNAs) in the tissue and blood between spinal cord glioblastoma (SC-GBM) patients and low grade SCG (L-SCG) patients. Additionally, we predicted key miRNA targets and pathways that may be critical in glioma development using pathway and gene ontology analysis. A total of 74 miRNAs were determined to be differentially expressed (25 upregulated and 49 downregulated) in blood, while 207 miRNAs (20 up-regulated and 187 down-regulated) were identified in tissue samples. Gene ontology analysis revealed multicellular organism development and positive regulation of macromolecule metabolic process to be primarily involved. Pathway analysis revealed “Glioma”, “Signalling pathways regulating pluripotency of stem cells” to be the most relevant pathways. miRNA-mRNA analysis revealed that hsa-miRNA3196, hsa-miR-27a-3p, and hsa-miR-3664-3p and their target genes are involved in cancer progression. Our study provides a molecular basis for SCG pathological grading based on differential miRNA expression.

Long-term cure of high-grade spinal cord glioma in a pediatric patient who underwent cordectomy.

High-grade spinal cord gliomas are rare and carry a poor prognosis. A number of treatment modalities exist for spinal cord gliomas, but no consensus exists regarding their management. Cordectomy represents a possible option for treating these lesions; however, few cases have been reported in adults, and none have been reported in the pediatric population. The authors describe the use of cordectomy for the treatment of a high-grade spinal glioma in a 9-year-old boy who remains cancer free 14 years following his initial presentation.