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.

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.

[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.

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.

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.

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.

Recent advances and new discoveries in the pipeline of the treatment of primary spinal tumors and spinal metastases: a scoping review of registered clinical studies from 2000 to 2020.

The field of spinal oncology has substantially evolved over the past decades. This review synthesizes and appraises what was learned and what will potentially be discovered from the recently completed and ongoing clinical studies related to the treatment of primary and secondary spinal neoplasms. This scoping review included all clinical studies on the treatment of spinal neoplasms registered in the ClinicalTrials.gov website from February 2000 to December 2020. The terms "spinal cord tumor," "spinal metastasis," and "metastatic spinal cord compression" were used. Of the 174 registered clinical studies on primary spinal tumors and spinal metastasis, most of the clinical studies registered in this American registry were interventional studies led by single institutions in North America (n = 101), Europe (n = 43), Asia (n = 24), or other continents (n = 6). The registered clinical studies mainly focused on treatment strategies for spinal neoplasms (90.2%) that included investigating stereotactic radiosurgery (n = 33), radiotherapy (n = 21), chemotherapy (n = 20), and surgical technique (n = 11). Of the 69 completed studies, the results from 44 studies were published in the literature. In conclusion, this review highlights the key features of the 174 clinical studies on spinal neoplasms that were registered from 2000 to 2020. Clinical trials were heavily skewed toward the metastatic population as opposed to the primary tumors which likely reflects the rarity of the latter condition and associated challenges in undertaking prospective clinical studies in this population. This review serves to emphasize the need for a focused approach to enhancing translational research in spinal neoplasms with a particular emphasis on primary tumors.

Evolution of a refractory prolactin-secreting pituitary adenoma into a pituitary carcinoma: report of a challenging case and literature review.

BACKGROUND: Pituitary carcinomas (PCs), defined as distant metastases of pituitary neoplasms, are very rare malignancies. Because the clinical presentation of PCs is variable, early diagnosis and management remain challenging. PCs are always refractory to comprehensive treatments, and patients with PCs have extremely poor prognoses. CASE PRESENTATION: We describe one case of a prolactin-secreting pituitary adenoma (PA) refractory to conventional therapy that evolved into a PC with intraspinal metastasis. A 34-year-old female was diagnosed with an invasive prolactin-secreting PA in 2009 and was unresponsive to medical treatment with bromocriptine. The tumor was gross totally removed via transsphenoidal surgery (TSS). However, the patient experienced multiple tumor recurrences or regrowth despite comprehensive treatments, including medical therapy, two gamma knife radiosurgeries (GKSs), and four frontal craniotomies. In 2016, she was found to have an intradural extramedullary mass at the level of the fourth lumbar vertebra. The intraspinal lesion was completely resected and was confirmed as a metastatic PC based on histomorphology and immunohistochemical staining. The literature on the diagnosis, molecular pathogenesis, treatment, and prognosis of patients with prolactin-secreting PCs was reviewed. CONCLUSION: PCs are very rare neoplasms with variable clinical features and poor prognosis. Most PCs usually arise from aggressive PAs refractory to conventional therapy. There is no reliable marker to identify aggressive PAs with a risk for progression to PCs; thus, it is difficult to diagnose these PCs early until the presence of metastatic lesions. It is still very challenging to manage patients with PCs due to a lack of standardized protocols for diagnosis and treatment. Establishing molecular biomarkers and the pathobiology of PCs could help in the early identification of aggressive PAs most likely to evolve into PCs.

Clinical management of pediatric chordomas: a comprehensive review.

Chordomas are malignant tumors derived from remnants of the notochord. These are extremely rare in pediatric patients, accounting for approximately 5% of all chordomas, with most lesions occupying the cranium. Chordomas also can occupy all levels of the spine, demonstrating a broad spectrum of neurologic presentation. Optimal treatment aims for gross total resection with accompanying radiation therapy to prevent recurrence. Their aggressive and infiltrative nature makes clinical management challenging, involving multiple disciplines and close monitoring to ensure optimal outcomes. This comprehensive review aims to cover the genetics, demographics, pathogenesis, neurologic sequelae, radiological considerations, chemotherapeutic management, surgical management, and post-operative considerations of pediatric chordoma patients.

Brain and Spinal Cord Tumors in Children.

This article provides general principles of managing children with central nervous system tumors. The distribution, diagnostic work-up, and key principles of treatment are reviewed, and special circumstances that may be encountered by pediatricians in the community are discussed.

Outcome in Patients with Spinal Cavernomas Presenting with Symptoms Due to Mass Effect and/or Hemorrhage: Conservative versus Surgical Management: Meta-analysis of Direct Comparison of Approach-Related Complications.

OBJECTIVE: We sought to examine the conservative treatment of symptomatic spinal cavernomas and evaluate the efficacy and safety of surgical management of spinal cord cavernous malformations. METHODS: This meta-analysis included articles comparing outcomes of conservative treatment and surgical management of spinal cavernomas, published in the full-text form (from 2000 to June 31, 2020). Collected variables included first author name, country, covered study period, publication year, the total number of patients and at follow-up, bleeding, motor weakness, pain, bladder and/or bowel dysfunction neurologic improvement or deterioration after discharge, and the need for reintervention after subtotal surgical resection or hemorrhage. RESULTS: After the initial searching and applying all exclusion and inclusion criteria, there were 9 articles left in the final article pool. The total number of patients was 396 with 264 (66.6%) undergoing surgical resection and 132 (33.4%) electing conservative management. Regarding motor weakness, bladder/bowel dysfunction, deterioration, and reintervention, the final results demonstrated no potential significant difference between the 2 groups. In regard to the subgroup of patients with bleeding, improvement, and pain, the results of the analysis showed a statistically significant difference between the 2 groups. CONCLUSIONS: Patients who have experienced a hemorrhagic episode should consider surgical intervention, which decreases the risk of recurrent hemorrhage and further neurologic deterioration. In addition, surgical decompression obtained by resection of the hemorrhage and cavernoma seems to lead to slight neurologic improvement in some patients. In nonhemorrhagic cavernomas, conservative treatment might be optimal due to surgery-related morbidity risks.

Intramedullary spinal cord lesions in children.

Paediatric intramedullary spinal cord lesions are uncommon pathologies, prone to result in dismal prognosis if not managed promptly and aggressively. While children usually present in good functional grades compared to adults, early recognition and treatment is important to improve outcomes. In this review, we present tumour demographics, patient factors, and treatment modalities of intramedullary spinal cord lesions in paediatric patients.

Challenges in diagnosis and management of adult spinal cord gliomas.

Intramedullary spinal cord gliomas have very low incidence rates. They are associated with difficulties in diagnosis and treatment, and cause significant morbidity. Their clinical presentation and their appearance at magnetic resonance imaging are not specific. They can mimic inflammatory, infectious, vascular disorders or other neoplastic lesions. Primary treatment is surgery. Surgical resection can often be total for ependymomas, but difficult for infiltrating astrocytomas. Radiotherapy is indicated for malignant tumors, but remains controversial in some indications. Chemotherapy is reserved for recurrence, but small retrospective series are available. Genetic studies have revealed genetic alterations which could have a potential impact on treatment in the near future.