AB008. Intramedullary spinal cord metastases in breast cancer with multiple central nervous system (CNS) metastases: a case report.

BACKGROUND: Although vertebral and epidural metastases are common, intramedullary metastases are rare. Intramedullary spinal cord metastases (ISCM) account for only 0.1-0.4% of metastasis tumors. About 26.5% of the tumour primaries are from breast cancer. Due to rapid neurological deficit deterioration, followed by short life expectancy, early diagnosis should be made to treat the tumor as any other central nervous system (CNS) metastases. CASE DESCRIPTION: A 50-year-old woman with a history of invasive ductal breast carcinoma, T2N3M0, grade III, luminal B (ER and HER2 positive) subtype who had previously undergone a mastectomy, presented with 1 month onset of bilateral leg weakness and sphincter compromise. The symptoms preceded by a burning sensation in the buttocks radiate to both legs. There was a history of dizziness and diplopia. Neurological examination showed paraparesis with hyperreflexia, hypoesthesia below L1 dermatome distribution, lateral gaze palsy of the right eye and hemifacial sensory deficit. A whole spine magnetic resonance imaging (MRI) shows multiple intramedullar enhancing lesions at the level of C4, C6, T2-T7, conus medullaris, and cauda equina. Brain MRI revealed multiple lesions in left hemicerebellum and temporal lobe with diffuse meningeal enhancement. The patient completed 5-fractionated 20 Gy whole spine radiotherapy with corticosteroid as an adjunct, followed by 30 Gy whole brain radiotherapy. At the 2-month follow-up, the motor weakness worsened and her clinical condition continued to deteriorate with multiple systemic complications until she died 3 months after ISCM diagnosis. CONCLUSIONS: ISCM is associated with aggressive progression. Only 1-year span from breast cancer until the patient is diagnosed with ISCM. Although CNS metastases are mostly found in HER2-positive breast cancers, data on ISCM is still limited. Most cases of ISCM have additional CNS metastases, leading to severe neurological deficits up to life-threatening conditions. A clear standard therapeutic protocol for ISCM has not yet been defined. Widespread metastasis and systemic disease progression were the main cause of death. The treatment goal is to preserve neurological function and improve patient's quality of life. Studies to generate evidence-based data with an algorithm to choose an appropriate treatment for ISCM is needed.

AB088. Spinal cord diffuse midline glioma in adults: a case report and literature review.

BACKGROUND: Spinal cord diffuse midline gliomas are rare, infiltrative entities with an extremely grim prognosis. Standard of care is limited and extrapolated from those for intracranial gliomas, focusing on maximal safe resection, chemotherapy and radiation therapy. These do not prolong survival significantly and while advances in molecular profiling and targeted therapy have been promising, further research still needs to be performed. Here, we present a case of a young lady with a cervical cord diffuse midline glioma, along with a literature review of the disease and treatment options. CASE DESCRIPTION: A 35-year-old female presented with progressive neck pain and left sided weakness. MRI revealed an intramedullary cervical spinal cord lesion. The lesion progressed rapidly to the medulla, resulting in lower cranial nerve palsies and left hemiplegia. Investigations for autoimmune and infective causes were negative. Cervical laminectomy and debulking was performed. Histological analysis showed high grade diffuse glioma, IDH-wildtype, loss of H3K27me3 staining and H3K27M positivity. The patient was treated with fractionated radiation and temozolamide, followed by lomustine and bevacizumab. A literature review was performed to better understand the molecular features, natural history and treatment options for spinal cord high grade gliomas. Our case highlights the importance of maintaining broad differentials for patients exhibiting features of cervical myelopathy. Malignant spinal cord tumours could be a differential. Molecular testing can aid in achieving an accurate diagnosis to better understand prognosis and determine treatment options. Early, function-preserving debulking with neuromonitoring is feasible. Adjuvant therapy with chemotherapy and radiation can prolong survival. CONCLUSIONS: Spinal cord diffuse midline gliomas H3 K27-altered demonstrate rapid progression and a poor prognosis. They should be considered as a differential in patients with cervical myelopathy. Molecular testing for H3 K27 alterations facilitates an accurate diagnosis. Surgical debulking and adjuvant therapy are viable treatment options.

Understanding spinal cord astrocytoma: Molecular mechanism, therapy, and comprehensive management.

Spinal cord astrocytoma is a rare and highly debilitating tumor, yet our knowledge of its clinical characteristics, molecular features, and pathogenesis remains limited compared to that of its counterparts in the brain. Current diagnostic and therapeutic approaches for spinal cord astrocytomas are primarily based on established guidelines for brain astrocytomas. However, recent studies have revealed unique clinical and pathological attributes that distinguish spinal cord astrocytomas from their corresponding brain counterparts. These findings underscore the inadequacy of directly applying the clinical guidelines developed for brain astrocytomas to spinal astrocytomas. In this review, we provided an up-to-date overview of the advancements in understanding spinal cord astrocytomas. We also discussed the challenges and future research prospects in this field with the aim of improving the precision of diagnosis and therapy for these tumors. Specifically, we emphasized the importance of enhancing our understanding of the molecular heterogeneity, immune characteristics, and clinical trials of spinal cord astrocytomas.

Advances in Molecular Pathology, Diagnosis and Treatment of Spinal Cord Astrocytomas.

Spinal cord astrocytoma (SCA) is a rare subtype of astrocytoma, posing challenges in diagnosis and treatment. Low-grade SCA can achieve long-term survival solely through surgery, while high-grade has a disappointing prognosis even with comprehensive treatment. Diagnostic criteria and standard treatment of intracranial astrocytoma have shown obvious limitations in SCA. Research on the molecular mechanism in SCA is lagging far behind that on intracranial astrocytoma. In recent years, huge breakthroughs have been made in molecular pathology of astrocytoma, and novel techniques have emerged, including DNA methylation analysis and radiomics. These advances are now making it possible to provide a precise diagnosis and develop corresponding treatment strategies in SCA. Our aim is to review the current status of diagnosis and treatment of SCA, and summarize the latest research advancement, including tumor subtype, molecular characteristics, diagnostic technology, and potential therapy strategies, thus deepening our understanding of this uncommon tumor type and providing guidance for accurate diagnosis and treatment.

Pediatric intramedullary spinal cord tumors: A national cancer database analysis of demographics, patterns of care, and survival.

OBJECTIVE: Query the National Cancer Database (NCDB) to delineate epidemiologic frequency, care patterns, and survival outcomes of pediatric intramedullary spinal cord tumors (IMSCTs). METHODS: IMSCTs included ependymoma, astrocytoma, and hemangioblastoma. We examined data from the NCDB spanning 2004-2018, focusing on IMSCT in children aged 0-21 years. Our analysis included logistic and Poisson regression, Kaplan-Meier survival estimates, and Cox proportional hazards models. RESULTS: This study included 1066 patients aged 0-21 years. 59.4 % of patients were male, while 83.1 % were white. The most common tumor histology was ependymoma (57.5 %), followed by astrocytoma (36.1 %) and hemangioblastoma (6.4 %). 24.9 % of patients received radiotherapy, with radiotherapy utilization being highest among patients aged 6-10 years. Chemotherapy utilization was highest in patients aged 0-5 years. 87.2 % of patients underwent surgical resection, with higher rates in patients aged 16-21 years. Overall survival did not differ significantly between resected and non-resected patients (p = 0.315). Patients in rural areas had worse OS than those in metro areas (HR = 4.42, p = 0.048). Patients with astrocytoma had worse OS compared to other histologies (HR = 2.21, p = 0.003). Astrocytoma patients were over twice as likely to have prolonged LOS compared to ependymoma patients (OR = 2.204, p < 0.001). CONCLUSIONS: In summary, our analysis utilizing the NCDB database provides a comprehensive overview of demographics, care patterns, and outcomes for the largest cohort of pediatric IMSCTs to date. These insights underscore the complexity of managing IMSCTs and emphasize the need for tailored approaches to improve patient outcomes.

Characterizing the presentation, management, and clinical outcomes of patients with intradural spinal chordomas: a systematic review.

OBJECTIVE: Chordomas are locally aggressive neoplasms of the spine or skull base that arise from embryonic remnants of the notochord. Intradural chordomas represent a rare subset of these neoplasms, and few studies have described intradural chordomas in the spine. This review evaluates the presentation, management, and outcomes of intradural spinal chordomas. METHODS: A systematic review of PubMed/MEDLINE, EMBASE, Cochrane Library, Scopus, and Web of Science was performed. Studies describing at least 1 case of intradural chordomas anywhere in the spine were included. Extracted details included presenting symptoms, radiological findings, treatment course, follow-up, and disease progression. RESULTS: Thirty-one studies, with a total of 41 patients, were included in this review. Seventy-six percent (31/41) of patients had primary intradural tumors, whereas 24% (10/41) presented with metastasis. The most common signs and symptoms were pain (n = 27, 66%); motor deficits (n = 20, 49%); sensory deficits (n = 17, 42%); and gait disturbance (n = 10, 24%). The most common treatment for intradural chordoma was resection and postoperative radiotherapy. Sixty-six percent (19/29) of patients reported improvement or complete resolution of symptoms after surgery. The recurrence rate was 37% (10/27), and the complication rate was 25% (6/24). The median progression-free survival was 24 months (range 4-72 months). Four patient deaths were reported. The median follow-up time was 12 months (range 13 days-84 months). CONCLUSIONS: Treatment of intradural spinal chordomas primarily involves resection and radiotherapy. A significant challenge and complication in management is spinal tumor seeding after resection, with 9 studies proposing seeding as a mechanism of tumor metastasis in 11 cases. Factors such as tumor size, Ki-67 positivity, and distant metastasis may correlate with worse outcomes and demonstrate potential as prognostic indicators for intradural spinal chordomas. Further research is needed to improve understanding of this tumor and develop optimal treatment paradigms for these patients.

Synchronous skull base and spinal metastases in a patient with treatment-resistant, high-grade serous adenocarcinoma of tubo-ovarian origin.

Brain metastases (BMs) arising from ovarian cancer remain rare. Spinal cord metastases are even rarer, accounting for just 0.4% of total metastatic spinal cord compressions. In this report, we describe a case of a woman in her 70s who developed sequential brain and spinal cord metastases during her treatment for high-grade serous ovarian cancer, without a germline or somatic BRCA mutation. Following completion of neoadjuvant chemotherapy, interval debulking surgery and adjuvant chemotherapy, relapsed disease was ultimately identified as a single BM, curiously mimicking an acoustic neuroma. Subsequently, spinal cord metastases rapidly developed. Throughout, multidisciplinary team meetings guided decisions on patient management. In this report, we highlight the rarity of such a presentation and discuss the possible role of disease pathophysiology, associated systemic anticancer therapy resistance, and treatment possibilities for both cerebral and spinal metastases.

Spinal Cord Neoplasms.

OBJECTIVE: This article discusses the diagnostic approach to patients with suspected neoplasms of the spinal cord and reviews the most common primary and metastatic spinal neoplasms and their presentations. LATEST DEVELOPMENTS: Neoplasms of the spinal cord are rare entities that can involve the spinal cord parenchyma, the dura and leptomeninges, or the extradural space. The most common intramedullary spinal cord neoplasms are primary spinal cord tumors, including ependymomas, pilocytic astrocytomas, and diffuse midline gliomas. The most common primary neoplasms of the spine are intradural extramedullary spinal meningiomas, whereas primary neoplasms of the leptomeninges are rare. Advances in molecular characterization of spinal cord tumors and recent clinical trials of these rare entities are expanding the repertoire of systemic therapy options for primary spinal cord neoplasms. Metastases to the spine most often affect the extradural space. Metastatic epidural spinal cord compression is a neurologic emergency that requires a rapid, multidisciplinary response to preserve neurologic function. ESSENTIAL POINTS: Neurologists should understand the diagnostic approach to neoplasms of the spinal cord. Knowledge of the most common spinal cord neoplasms will allow for appropriate management and optimal patient care.

Diffuse Midline H3K27-Altered Gliomas in the Spinal Cord: A Systematic Review.

PURPOSE: To systematically review the clinical features, management, and outcomes of diffuse midline H3K27-altered gliomas of the spinal cord (DMG-SCs). METHODS: PubMed, Ovid EMBASE, Scopus, and Web of Science were searched from database inception to 23 September 2023 for histologically confirmed cases of DMG-SC. Patient demographics, tumor characteristics, management information, and survival outcomes were extracted and analyzed. RESULTS: A total of 279 patients from 39 studies were collected. Patients were mostly male (61%), with an average age of 32 years. Patients were treated with surgery, radiotherapy, and chemotherapy combined (31%) or surgery only (24%), and extent of resection was most often subtotal (38%). Temozolomide was the most common chemotherapeutic agent (81%). Radiation therapy was delivered with mean dose of 47 Gy in 23 fractions. At mean follow-up time of 21 months, 13% of patients were alive. Average median overall survival was 24 months (range of 13 to 40 months) with a median progression-free survival of 14 months. Historical WHO grades of 2 or 3 appeared to exhibit a longer average median overall survival time than that of grade 4 DMG-SCs (32 vs. 23 months, p = 0.009). CONCLUSIONS: Outcomes for DMG-SCs are poor overall but appear to be favorable compared to intracranial DMGs. Despite the recent WHO 2021 grade 4 classification for all DMGs, given the differences in overall survival reported based on historical grading systems, future studies on DMG-SCs are needed to further define if DMG-SCs may represent a heterogeneous group of tumors with different prognoses.

El papel de la cirugía mínimamente invasiva de columna en el tratamiento de las metástasis vertebrales (parte 1): una revisión clínica / The role of minimally invasive spine surgery in the treatment of vertebral metastasis (part 1): A clinical review

Las metástasis espinales representan una importante carga sobre la calidad de vida en los pacientes afectados por una enfermedad oncológica activa, debido a la alta incidencia de síndromes dolorosos, deformidad espinal y deterioro neurológico. La cirugía juega un papel determinante a la hora de mejorar la calidad de vida mediante el control del dolor, el restablecimiento de la función neurológica y el mantenimiento de la estabilidad espinal, además de contribuir a la respuesta de la terapia médica. La cirugía mínimamente invasiva (MIS) es una opción de tratamiento en determinados pacientes con alto riesgo quirúrgico, ya que tiene una baja tasa de complicaciones, de sangrado intraoperatorio, de estancia hospitalaria y ofrece resultados similares a la cirugía abierta. Presentamos en esta revisión el papel de la MIS en esta enfermedad, y algunos casos tratados en nuestro centro hospitalario.(AU)

Spinal metastases represent a significant burden on the quality of life in patients affected by active oncological disease due to the high incidence of pain syndromes, spinal deformity, and neurological impairment. Surgery plays a decisive role in improving quality of life by controlling pain, restoring neurological function and maintaining spinal stability, as well as contributing to the response to medical therapy. Minimally invasive surgery (MIS) is a treatment option in certain patients with high surgical risk since it has a low rate of complications, intraoperative bleeding, hospital stay, and offers similar results to open surgery. In this review, we present the role of MIS in this pathology and some cases treated in our hospital.(AU)

[Translated article] The role of minimally invasive spine surgery in the treatment of vertebral metastasis (Part 1): A clinical review / El papel de la cirugía mínimamente invasiva de columna en el tratamiento de las metástasis vertebrales (parte 1): una revisión clínica

Las metástasis espinales representan una importante carga sobre la calidad de vida en los pacientes afectados por una enfermedad oncológica activa, debido a la alta incidencia de síndromes dolorosos, deformidad espinal y deterioro neurológico. La cirugía juega un papel determinante a la hora de mejorar la calidad de vida mediante el control del dolor, el restablecimiento de la función neurológica y el mantenimiento de la estabilidad espinal, además de contribuir a la respuesta de la terapia médica. La cirugía mínimamente invasiva (MIS) es una opción de tratamiento en determinados pacientes con alto riesgo quirúrgico, ya que tiene una baja tasa de complicaciones, de sangrado intraoperatorio, de estancia hospitalaria y ofrece resultados similares a la cirugía abierta. Presentamos en esta revisión el papel de la MIS en esta enfermedad, y algunos casos tratados en nuestro centro hospitalario.(AU)

Spinal metastases represent a significant burden on the quality of life in patients affected by active oncological disease due to the high incidence of pain syndromes, spinal deformity, and neurological impairment. Surgery plays a decisive role in improving quality of life by controlling pain, restoring neurological function and maintaining spinal stability, as well as contributing to the response to medical therapy. Minimally invasive surgery (MIS) is a treatment option in certain patients with high surgical risk since it has a low rate of complications, intraoperative bleeding, hospital stay, and offers similar results to open surgery. In this review, we present the role of MIS in this pathology and some cases treated in our hospital.(AU)

[Pediatric spinal tumors]. / Spinale Tumoren im Kindesalter.

Pediatric spinal tumors are rare and manifest frequently with unspecific symptoms, frequently resulting in delayed diagnosis. Many spinal tumor entities in children and adults are similar, but the lesions demonstrate a different prevalence and sometimes a different molecular genetic profile in children. For radiological evaluation of spinal tumor lesions, it is helpful to define the affected anatomical compartment. Important intradural pediatric tumor entities are astrocytomas, ependymomas, nerve sheath tumors, and liquorgenic metastases of intracranial neoplasms. Extradural masses are mostly primary tumors originating from osseous elements of the spine. Bone metastases are rare in children and can occur, for example, in neuroblastoma. Magnetic resonance imaging (MRI) is the most important noninvasive method for radiological spinal tumor evaluation.

A current review of spinal meningiomas: epidemiology, clinical presentation and management.

PURPOSE: To provide an up-to-date review of the epidemiology, histopathology, molecular biology, and etiology of spinal meningiomas, as well as discuss the clinical presentation, clinical evaluation, and most recent treatment recommendations for these lesions. METHODS: PubMed and Google Scholar search was performed for studies related to meningiomas of the spine. The terms "meningioma," "spinal meningioma," "spine meningioma," "meningioma of the spine," "benign spinal tumors," and "benign spine tumors," were used to identify relevant studies. All studies, including primary data papers, meta-analyses, systematic reviews, general reviews, case reports, and clinical trials were considered for review. RESULTS: Eighty-four studies were identified in the review. There were 22 studies discussing adverse postoperative outcomes, 21 studies discussing tumor genetics, 19 studies discussing epidemiology and current literature, 9 studies discussing radiation modalities and impact on subsequent tumor development, 5 studies on characteristic imaging findings, 5 studies discussing hormone use/receptor status on tumor development, 2 discussing operative techniques and 1 discussing tumor identification. CONCLUSION: Investigations into spinal meningiomas generally lag behind that of intracranial meningiomas. Recent advancements in the molecular profiling of spinal meningiomas has expanded our understanding of these tumors, increasing our appreciation for their heterogeneity. Continued investigation into the defining characteristics of different spinal meningiomas will aid in treatment planning and prognostication.

Intramedullary Spinal Cord Metastases from Breast Cancer: A Systematic Review.

BACKGROUND/AIM: Intramedullary spinal cord metastases (ISCM) are deemed extremely aggressive, as confirmed by the low life expectancy since the diagnosis. Up to 26.5% of total ISCM stem from breast cancer (BC), representing the second most frequent primary site after the lung. The increasing incidence of BC and the widespread use of MRI for the diagnosis could therefore lead to an earlier diagnosis and, therefore, to a progressively longer survival in patients affected by ISCM from BC. This systematic review is intended to provide an orientation through a management algorithm for the most appropriate therapeutic approach in these patients. MATERIALS AND METHODS: The research strategy initially relied on title and abstract analysis. The article's full text was retrieved for further investigation if the title and abstract met the inclusion criteria. The extracted data included the following: authors, publication time, study design, patient characteristics, ISCM location, treatment modalities, time interval from initial cancer diagnosis to ISCM diagnosis, clinical outcomes, and survival time. RESULTS: This systematic search regarding ISCM from BC yielded 574 articles. After screening, a total of 44 studies were included in this systematic review. A total of 123 patients were evaluated. The mean patient age was 53.2 years with a standard deviation of 10.4 years. Female patients were 122. There was only one male patient. CONCLUSION: ISCM from BC have a better prognosis than lung metastases and, thanks to recent advances in diagnostic imaging and intraoperative planning and neuromonitoring, an early diagnosis and a prompt multidisciplinary treatment may be accomplished. Prospective studies to generate evidence-based data regarding the most appropriate treatment for ISCM are mandatory.

Brain and Spinal Cord Tumors Among the Life-Threatening Health Problems: An Introduction.

As one of the global concerns, cancers, including brain and spinal cord tumors, are responsible for mortalities and irreversible morbidities in the affected patients. Although advancements in molecular pathology and imaging of tumors may have influenced the incidence rate due to higher diagnosis in early stages, exposure to environmental risk factors could be another explanation for increased incidence of these tumors over the past decades. Similar to many other tumors, the CNS tumors begin in cellular dimension with activation of different molecular pathways. Several genetic, epigenetic, and immunologic pathways and processes are already discovered to play roles in pathophysiology of these tumors, which mostly will eventually become symptomatic. Each of these tumors may exhibit imaging characteristics, making it possible to list a series of differential diagnosis before histopathologic examination. Advances in molecular pathology have resulted in better understanding and categorization of CNS tumors, leading to better decision-making on the most appropriate therapeutic approach for each category, as well as proposing new therapeutic modalities to treat these tumors. As an introduction to the 2-volume book, this chapter addressed different types of human brain and spinal cord tumors based on the fifth version of WHO classification of CNS tumors.

Stem Cells and Targeted Gene Therapy in Brain and Spinal Cord Tumors.

The CNS tumors, in particular those with malignant characteristics, are prominent burdens around the world with high mortality and low cure rate. Given that, researchers were curious about novel treatments with promising effectiveness which resulted in shifting the dogmatism era of neurogenesis to the current concept of postnatal neurogenesis. Considering all existing stem cells, various strategies are available for treating CNS cancers, including hematopoietic stem cells transplantation, mesenchymal stem cells transplantation, neural stem cells (NSCs) transplantation, and using stem cells as genetic carriers called "suicide gene therapy". Despite some complications, this ongoing therapeutic method has succeeded in decreasing tumor volume, inhibiting tumor progression, and enhancing patients' survival. These approaches could lead to acceptable results, relatively better safety, and tolerable side effects compared to conventional chemo and radiotherapy. Accordingly, this treatment will be applicable to a wide range of CNS tumors in the near future. Furthermore, tumor genomic analysis and understanding of the underlying molecular mechanisms will help researchers determine patient selection criteria for targeted gene therapy.

Intradural Extramedullary Spinal Metastases from Non-neurogenic Primary Tumors: A Systematic Review.

BACKGROUND/AIM: Intradural extramedullary spinal metastases (IESMs) may severely affect quality-of-life of oncological patients. Several treatments are available but their impact on prognosis is unclear. We systematically reviewed the literature on IESMs of non-neurogenic origin. MATERIALS AND METHODS: PubMed, Ovid EMBASE, Scopus, and Web-of-Science were screened to include articles reporting patients with IESMs from non-neurogenic primary tumors. Clinico-radiological presentation, treatments, and outcomes were analyzed. RESULTS: We included 51 articles encompassing 130 patients of a median age of 62 years (range=32-91 years). The most common primary neoplasms were pulmonary (26.2%), renal (20%), and breast (13.8%) carcinomas. Median time interval from primary tumor to IESMs was 18 months (range=0-240 months). The most common symptoms were sensory (58.3%) and motor (54.2%) deficits. Acute cauda equina syndrome was reported in 29 patients (37.7%). Lesions were diagnosed at magnetic resonance imaging (93.3%), myelography (25%), or computed tomography (16.7%). All patients underwent decompressive laminectomy with tumor resection, partial (54.6%) more frequently than complete (43.1%). Adjuvant radiation (67.5%) and/or systemic (13.3%) therapies were administered. After treatment, most patients had symptom improvement (70.8%) and optimal radiological response (64.2%). Four patients experienced IESMs recurrences (3.1%) with median local tumor control of 14.5 months (range=0.1-36 months). Deaths occurred in 50% of patients, with median overall survival of 6.7 months (range=0.1-108 months). CONCLUSION: Patients with IESMs have significant tumor burden with poor prognoses. Resection and locoregional radiation may offer favorable clinico-radiological responses but are limited in achieving optimal local control and survival.

Systemic considerations for the surgical treatment of spinal metastatic disease: a scoping literature review.

Systemic assessment is a pillar in the neurological, oncological, mechanical, and systemic (NOMS) decision-making framework for the treatment of patients with spinal metastatic disease. Despite this importance, emerging evidence relating systemic considerations to clinical outcomes following surgery for spinal metastatic disease has not been comprehensively summarised. We aimed to conduct a scoping literature review of this broad topic. We searched MEDLINE, Embase, Scopus, Cochrane Central Register of Controlled Trials, Web of Science, and CINAHL databases from Jan 1, 2000, to July 31, 2021. 61 articles were included, accounting for a total of 22 335 patients. Preoperative systemic variables negatively associated with postoperative clinical outcomes included demographics (eg, older age [>60 years], Black race, male sex, low or elevated body-mass index, and smoking status), medical comorbidities (eg, cardiac, pulmonary, hepatic, renal, endocrine, vascular, and rheumatological), biochemical abnormalities (eg, hypoalbuminaemia, atypical blood cell counts, and elevated C-reactive protein concentration), low muscle mass, generalised motor weakness (American Spinal Cord Injury Association Impairment Scale grade and Frankel grade) and poor ambulation, reduced performance status, and systemic disease burden. This is the first comprehensive scoping review to broadly summarise emerging evidence relevant to the systemic assessment component of the widely used NOMS framework for spinal metastatic disease decision making. Medical, surgical, and radiation oncologists can consider these findings when prognosticating spinal metastatic disease-related surgical outcomes on the basis of patients' systemic condition. These factors might inform a shared decision-making approach with patients and their families.

GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas.

Diffuse intrinsic pontine glioma (DIPG) and other H3K27M-mutated diffuse midline gliomas (DMGs) are universally lethal paediatric tumours of the central nervous system1. 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 cells2, 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 × 106 GD2-CAR T cells per kg administered intravenously). Patients who exhibited clinical benefit were eligible for subsequent GD2-CAR T cell infusions administered intracerebroventricularly3. 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.

Leptomeningeal Metastases of the Spine: A Systematic Review.

BACKGROUND/AIM: Leptomeningeal metastases (LMs) of the spine have complex management. We reviewed the literature on spine LMs. MATERIALS AND METHODS: PubMed, EMBASE, Scopus, Web-of-Science, and Cochrane were searched following the PRISMA guidelines to include studies of spine LMs. RESULTS: We included 46 studies comprising 72 patients. The most frequent primary tumors were lung (19.4%) and breast cancers (19.4%). Median time from primary tumors was 12 months (range=0-252 months). Cauda equina syndrome occurred in 34 patients (48.6%). Nodular spine LMs (63.6%) were more frequent. Concurrent intracranial LMs were present in 27 cases (50.9%). Cerebrospinal fluid cytology was positive in 31 cases (63.6%). Cases were managed using palliative steroids (73.6%) with locoregional radiotherapy (55.6%) chemotherapy (47.2%), or decompressive laminectomy (8.3%). Post-treatment symptom improvement (32%) and favorable radiological response (28.3%) were not different based on treatment (p=0.966; p=0.727). Median overall-survival was 3 months (range=0.3-60 months), not significantly different between radiotherapy and chemotherapy (p=0.217). CONCLUSION: Spine LMs have poor prognoses. Radiotherapy, chemotherapy, and surgery are only palliative, as described for intracranial LMs.