Predictors of survival and time to progression following operative management of intramedullary spinal cord astrocytomas

Hersh, Andrew; Antar, Albert; Pennington, Zach; Aygün, Nafi; Patel, Jaimin; Goldsborough, Earl; Porras, Jose L.; Elsamadicy, Aladine A.; Lubelski, Daniel; Wolinsky, Jean-Paul; Jallo, George I.; Gokaslan, Ziya L.; Lo, Sheng-Fu Larry; Sciubba, Daniel M.

doi:10.1007/s11060-022-04017-4

Cited by 10 publications

(17 citation statements)

References 37 publications

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“…Furthermore, most investigations into GSCs have focused on intracranial GBM. Although spinal cord GBM is associated with similarly poor overall survival, the generalizability of intracranial results to intramedullary pathology is unclear, and investigations into spinal cord tumors are warranted [ 295 ].…”

Section: Targeted Therapymentioning

confidence: 99%

Molecular Pathways and Genomic Landscape of Glioblastoma Stem Cells: Opportunities for Targeted Therapy

Hersh

Gaitsch

Alomari

et al. 2022

Cancers

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Glioblastoma (GBM) is an aggressive tumor of the central nervous system categorized by the World Health Organization as a Grade 4 astrocytoma. Despite treatment with surgical resection, adjuvant chemotherapy, and radiation therapy, outcomes remain poor, with a median survival of only 14-16 months. Although tumor regression is often observed initially after treatment, long-term recurrence or progression invariably occurs. Tumor growth, invasion, and recurrence is mediated by a unique population of glioblastoma stem cells (GSCs). Their high mutation rate and dysregulated transcriptional landscape augment their resistance to conventional chemotherapy and radiation therapy, explaining the poor outcomes observed in patients. Consequently, GSCs have emerged as targets of interest in new treatment paradigms. Here, we review the unique properties of GSCs, including their interactions with the hypoxic microenvironment that drives their proliferation. We discuss vital signaling pathways in GSCs that mediate stemness, self-renewal, proliferation, and invasion, including the Notch, epidermal growth factor receptor, phosphatidylinositol 3-kinase/Akt, sonic hedgehog, transforming growth factor beta, Wnt, signal transducer and activator of transcription 3, and inhibitors of differentiation pathways. We also review epigenomic changes in GSCs that influence their transcriptional state, including DNA methylation, histone methylation and acetylation, and miRNA expression. The constituent molecular components of the signaling pathways and epigenomic regulators represent potential sites for targeted therapy, and representative examples of inhibitory molecules and pharmaceuticals are discussed. Continued investigation into the molecular pathways of GSCs and candidate therapeutics is needed to discover new effective treatments for GBM and improve survival.

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Section: Targeted Therapymentioning

confidence: 99%

Molecular Pathways and Genomic Landscape of Glioblastoma Stem Cells: Opportunities for Targeted Therapy

Hersh

Gaitsch

Alomari

et al. 2022

Cancers

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“…Surgical intervention is considered the mainstay of treatment in patients with intramedullary astrocytomas experiencing neurological deficits or myelopathy, with a less clear role for patients with pain or incidental findings. Although GTR is believed to improve local tumor control, it often cannot be achieved without risking significant post-operative morbidity to patients, given the infiltrative nature of astrocytomas and lack of clear margins ( 24 – 26 ). Consequently, surgeons must balance the potential improvement in survival from more extensive resections with the increased risk of worsening and/or new neurological deficits ( 27 ).…”

Section: Managementmentioning

confidence: 99%

“…Several studies have failed to observe a significant effect of extent of resection in patients with intramedullary astrocytomas, and some have shown surgery to worsen functional outcomes ( 6 , 21 , 50 ). In contrast, others have identified a role for extent of resection independent of underlying histology for improving post-operative survival ( 24 , 51 ). A national database study of 348 patients by Luksik et al.…”

Section: Managementmentioning

confidence: 99%

“…Their 10-year survival rate was 55%, although patients who survived 10 years largely had WHO Grades 1 and 2 tumors, as higher-grade tumor patients had shorter overall survival ( 17 ). Higher tumor grades were also significantly associated with shorter time to tumor progression after surgery, and chemotherapy did not improve survival ( 24 ). Separately, a French multi-center study of 95 patients achieved a GTR rate of 38% with 10-year survival of 77% ( 53 ).…”

Section: Managementmentioning

confidence: 99%

“…Similarly, the efficacy of chemotherapy is unclear, with limited data supporting its use ( 67 ). It is usually reserved for high-grade lesions that recur or progress despite resection or RT, or for pediatric patients less than 3 years old in whom RT is contraindicated ( 17 , 21 , 24 , 68 ). Some case series have reported promising results using chemotherapy for intramedullary astrocytomas, favoring its use for recurrent or unresectable lesions ( 21 , 62 , 69 ).…”

Section: Managementmentioning

confidence: 99%

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Surgical approaches to intramedullary spinal cord astrocytomas in the age of genomics

2022

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Intramedullary astrocytomas represent approximately 30%–40% of all intramedullary tumors and are the most common intramedullary tumor in children. Surgical resection is considered the mainstay of treatment in symptomatic patients with neurological deficits. Gross total resection (GTR) can be difficult to achieve as astrocytomas frequently present as diffuse lesions that infiltrate the cord. Therefore, GTR carries a substantial risk of new post-operative deficits. Consequently, subtotal resection and biopsy are often the only surgical options attempted. A midline or paramedian sulcal myelotomy is frequently used for surgical resection, although a dorsal root entry zone myelotomy can be used for lateral tumors. Intra-operative neuromonitoring using D-wave integrity, somatosensory, and motor evoked potentials is critical to facilitating a safe resection. Adjuvant radiation and chemotherapy, such as temozolomide, are often administered for high-grade recurrent or progressive lesions; however, consensus is lacking on their efficacy. Biopsied tumors can be analyzed for molecular markers that inform clinicians about the tumor’s prognosis and response to conventional as well as targeted therapeutic treatments. Stratification of intramedullary tumors is increasingly based on molecular features and mutational status. The landscape of genetic and epigenetic mutations in intramedullary astrocytomas is not equivalent to their intracranial counterparts, with important difference in frequency and type of mutations. Therefore, dedicated attention is needed to cohorts of patients with intramedullary tumors. Targeted therapeutic agents can be designed and administered to patients based on their mutational status, which may be used in coordination with traditional surgical resection to improve overall survival and functional status.

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Intramedullary pediatric low-grade glioma of the spine

Lu,

Jallo,

Shimony

2024

Childs Nerv Syst

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Predictors of survival and time to progression following operative management of intramedullary spinal cord astrocytomas

Cited by 10 publications

References 37 publications

Molecular Pathways and Genomic Landscape of Glioblastoma Stem Cells: Opportunities for Targeted Therapy

Molecular Pathways and Genomic Landscape of Glioblastoma Stem Cells: Opportunities for Targeted Therapy

Surgical approaches to intramedullary spinal cord astrocytomas in the age of genomics

Intramedullary pediatric low-grade glioma of the spine

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