Pediatric Spinal Cord Tumors Research Articles

The disparity in pediatric spinal cord tumor clinical trials: A scoping review of registered clinical trials from 1989 to 2023.

Spinal cord tumors (SCTs) comprise 10% of all central nervous system (CNS) tumors. Pediatric SCTs are often excluded and underrepresented in clinical trials though exclusion rates haven't been reported. We reviewed all interventional clinical trials recruiting patients <21 years with SCTs on ClinicalTrials.gov between 1989 and 2023. Five hundred and two CNS tumor trials were identified, of which 255 included SCTs and/or spincal metastases. Among these, 96.5% were open to all CNS tumors (brain or spine); however, only 3.5% were exclusive to spine tumors. One trial was specific to pediatric spine tumors (inclusive of bone, soft tissue, and neural tumors); no trial was specific to primary pediatric SCTs. Most trials were located in North America, with multisite investigations being more common than single-institution designs. Trials frequently evaluated interventions/treatments (89%), supportive care/quality of life measures (7.1%), or diagnostic protocols (3.1%). Among included treatment paradigms, systemic therapies using cytotoxic chemotherapies, targeted therapies, and/or immunotherapies were more common among brain/spine trials, while radiotherapy, surgical adjuncts, and/or local drug delivery more frequently occurred in spinal tumor trials. Though SCTs comprise 10% of pediatric CNS tumors, they remain underrepresented in clinical trials. This lack of trials specific to advancing pediatric SCTs management highlights an area of clinical and research need.

Patient factors influencing a delay in diagnosis in pediatric spinal cord tumors.

ABSTRACTThe diagnosis of pediatric spinal cord tumor is frequently delayed due to the presence of non-specific symptoms. We investigated the factors influencing the delay between the first symptom presentation and the diagnosis for pediatric spinal cord tumor. We retrospectively analyzed 31 patients of age <20 years (18 men, 13 women) who underwent surgery for spinal cord tumor at a single center during 1998–2018. We extracted the relevant data on patients’ symptoms, affected spinal location (cervical: C1-7, thoracic: T1-T12, and lumbosacral: L1-S), and tumor anatomical location (extradural, intradural extramedullary, and intramedullary tumor) that could potentially affect the duration of symptom presentation prior to the diagnosis. The most common symptom presented in the patients was pain (n = 22, 71.0 %). Motor symptoms such as paralysis was associated with early diagnosis (P = 0.039). The duration of symptoms prior to diagnosis was found to be significantly longer in patients with spinal tumor in the lumbar-sacral region than in those with the involvement of the cervical and thoracic regions (2.1 ± 1.7 months vs 13.6 ± 12.1 months; P = 0.006 and 2.9 ± 2.2 months vs 13.6 ± 12.1 months; P = 0.012, respectively). Our study results demonstrated that pain was the most common symptom in the examined patients, although it did not affect the delay in diagnosis, whereas the presentation of motor symptoms was helpful in the diagnosis of pediatric spinal cord tumor and the diagnosis could be delayed in lumbar-sacral spinal tumors.

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.

Pediatric intramedullary spinal cord tumor outcomes using the WeeFIM scale.

The Functional Independence Measure for children (WeeFIM) is a user-friendly functional outcomes tool that has been validated across other traditional functional scales. Historically, the significant neurologic and functional deficits of intramedullary spinal cord tumors (IMSCTs) have been monitored by coarse or overbearing functional outcomes tools that make it difficult to measure the slow improvement/decline seen in these patients. This study is the first to report WeeFIM outcomes on a series of IMSCTs with emphasis on an aggressive surgical strategy. A retrospective review from 2005 to 2014 was performed for nine patients who underwent resective surgery for intramedullary spinal cord tumors with intraoperative ultrasound and neurophysiologic monitoring. WeeFIM scales were assessed at admission and discharge to evaluate changes in severity of disability and need for assistance. At the time of this submission, 7/9 patients are alive. The mean WeeFIM improvement was 27 points (8-50 points) with a mean WeeFIM efficiency of 2.0 points/day. The WeeFIM scale is an appropriate and useful scale for measuring postoperative improvements in patients with IMSCTs undergoing aggressive resective surgery. Attention to intraoperative spinal cord monitoring and prevention of spinal column instability may prevent morbidity related to surgery, and functional outcomes do not appear to be compromised by an aggressive surgical approach.

25. Intraoperative neurophysiology in pediatric neurosurgery

Intraoperative neurophysiological monitoring (IONM) techniques commonly used in adults should be tailored to pediatric patients. Below the age of 5–6 years, the classical Penfield’s method for cortical mapping often fails to elicit a muscle response due to the immaturity of the motor cortex and the corticospinal tract, while the motor evoked potential (MEP) short-train technique seems more effective. The use of awake surgery in children remains anecdotal and whenever cognitive function need to be investigated, a two-stage surgical approach with the use of subdural grids represents a valid alternative. In brainstem surgery, mapping techniques are valuable in selecting safe entry zones to the dorsal brainstem and during the removal of fourth ventricle tumors infiltrating the brainstem. Combination of direct mapping and subcontinuous monitoring of the corticobulbar MEPs for lower motor cranial nerves minimizes the risk of compromising swallowing and coughing reflexes. In spinal cord surgery, is difficult to record the D-wave in children younger than two years, but its critical role in predicting long-term motor outcome is confirmed in pediatric spinal cord tumors. During surgery of the conus-cauda for spinal dysraphisms, mapping techniques are essential to identify and spare functional neural tissue and, vice versa, to cut non functional structures that may contribute to cord tethering.

A Population-based Study on Pediatric Spinal Cord Tumors, with Emphasis on Intramedullary Ones

Purpose: Pediatric spinal cord tumors are rare accounting for 4-6% of all primary CNS tumors in this age group. Collecting large number of cases has always been difficult due to their scarcity. SEER database provides a source on varioustumors. Methods: We performed analysis on tumors of the spinal cord in patients between births to 20 years of age using the SEER data available for the period 1973-2005. Analysis of the incidence rate, the frequency of the most common types, the age, gender, treatment modality including radiotherapy and surgery is provided. In addition; the overall survival and the median survival has been analyzed for each tumor type and comparison between various types is performed. Results: There were 483 cases of spinal cord tumors with available data, representing 4.7% of all pediatric central nervous system tumors diagnosed over the same period. They predominated in males and in whites. The median age for diagnosis was 10 years, with two age peaks noted; in <3 years old and in adolescents 12 to 17 years old. Of intramedullary tumors astrocytoma was the most common histology followed by ependymoma. Low grade tumors predominated. Of all variables examined; histologic type, grade, gross total resection and not receiving radiotherapy showed significant association with outcome. Conclusions: Low- grade astrocytoma is the most common intramedullary tumor in first 2 decades of life, while ependymoma is mostly seen in the second decade of life. Assigning the appropriate histologic type and grade is important in determining the outcome of the patients.

A pediatric intramedullary spinal cord tumor with unusual solid-cystic and papillary features: A case report

Spinal cord tumors are rare in children. We report a novel case of pediatric intramedullary spinal cord tumor with unusual solid-cystic and papillary features. Clinically, the patient presented at the age of 3 years with motor deficit and urinary incontinence, and MRI demonstrated multilocular cystic lesions in the thoracic spine. Histologically the tumor consisted of solid, sheet-like components and branching papillary structures, and immunohistochemistry demonstrated positive reactivity for epithelial membrane antigen, cytokeratins (7, AE1/3, CAM5.2), E-cadherin and transthyretin, and negativity for GFAP, S-100 protein, synaptophysin and neurofilament. These histological and immunohistochemical findings appeared to be unique, and were not compatible with the features of classical ependymoma or choroid plexus papilloma. The clinical behavior, characterized by relatively rapid tumor regrowth after surgical resection and a relatively high MIB-1 labeling index, suggest that this tumor might have had moderate malignant potential. This pediatric case appears to be particularly informative with regard to the tumor biology or tumorigenesis of intramedullary spinal cord tumor with unusual solid-cystic and papillary features.

Papillary Tumor of the Spinal Cord

Intramedullary spinal cord tumors constitute a small fraction of central nervous system tumors in the pediatric population; of these, the majority are ependymomas or astrocytomas. We report 2 pediatric spinal cord tumor cases with unique morphologic and immunohistochemical features. The first patient presented at age 7 with an intramedullary tumor of the thoracic spine. She suffered lumbar, cerebellar, and temporal lobe recurrences despite surgical resection and radiation. The second patient presented at age 17 with an intramedullary tumor of the cervical spine. The tumor recurred locally and in the cerebellum. Magnetic resonance imaging studies demonstrated gadolinium enhancement in each case. Microscopy showed papillary and solid cytoarchitecture with monomorphous epithelioid cells arranged around vascular papillae. Immunohistochemistry in each case revealed diffuse epithelial membrane antigen, cytokeratin, and E-cadherin reactivity. Glial fibrillary acidic protein staining was focal in case 1 and completely negative in case 2. Neural cell adhesion molecule showed patchy membranous reactivity and synaptophysin was negative. Electron microscopy showed ependymal differentiation. The clinical features, including propensity for recurrence and remote subarachnoid spread, and the pathologic features of these tumors are reminiscent of papillary tumor of the pineal region, ependymoma, and choroid plexus papilloma. The cases presented may constitute a new neoplastic entity within the recently described spectrum of central nervous system tumors with ependymal features.

Efficacy of Spinal Instrumentation and Fusion in the Prevention of Postlaminectomy Spinal Deformity in Children With Intramedullary Spinal Cord Tumors

Postlaminectomy spinal deformity is a frequent problem after resection of a pediatric spinal cord tumor. However, the use of spinal fusion done at the time of resection in preventing the development of deformity is unknown. The purpose of our study was to assess the effectiveness of single-stage laminectomy, spinal cord decompression, and fusion for the prevention of postlaminectomy spinal deformity in children with intramedullary spinal cord tumors. Clinical charts and radiographs of 33 children with spinal cord tumors were reviewed for treatment description, preoperative spinal alignment, postoperative spinal alignment, and subsequent medical and surgical treatment. Spinal deformity was graded by predefined criteria. Significant spinal deformity developed in 10 of 17 children with laminectomy only, 3 of 4 children with laminoplasty, and 3 of 12 children with spinal fusion (2/6 with instrumentation, 1/6 with in situ fusion). Excluding patients that progressed to paraplegia, 9 of 16 patients treated with resection without fusion compared with 1 of 10 patients treated with resection and fusion developed a spinal deformity (P = 0.04). Among skeletally mature children that did not progress to paraplegia, 9 of 15 treated with resection without fusion compared with 1 of 7 patients treated with resection and fusion developed a deformity (P = 0.05). Removal of greater than 4 laminae (P = 0.03) was found to be associated with the development of postresection spinal deformity.

Pediatric Spinal Cord Tumors and Masses

Background/Objective: Spinal cord tumors are a relatively rare diagnosis, accounting for 1% to 10% of all pediatric central nervous system tumors. Understanding the etiology and clinical outcomes of these tumors is therefore very important. This study presents detailed information regarding clinical presentation, histological findings, outcomes, functional assessment, and management of a series of patients with this diagnosis.Method: Retrospective, descriptive study.Subjects: Thirty-five children with a final diagnosis of spinal cord tumor or mass, excluding dysraphism.Results: Neurodevelopmental tumors (dermoid tumors, epidermoid tumors, and teratomas) were the most common tumor type (31 %), followed by astrocytomas (29%) and neuroblastomas (14%). Other types included schwannomas, meningiomas, giant cell tumors, extradural cystic masses, leukemic-related masses, and masses related to neurofibromatosis. Mean age at diagnosis was 6.6 years (SD = 5.5 y) and did not vary significantly by tumor type except for children with neuroblastoma (mean = 0.4 y, SD = 0.5 y). More boys (57%) were identified in the series than girls (43%); however, there was no association between tumor type and sex. Presenting complaints of pain were noted in 57% and were localized to the back, neck, or extremities. Extremity weakness was reported as an initial presenting symptom in 46%. Three children had scoliosis as a presenting issue and 14 had gait abnormalities. Regardless of treatment modality, mobility was retained in 83% of children with or without gait aids. Neurogenic bowel and/or bladder were present in 23% of the population.Conclusions: This study corroborates other studies indicating that intramedullary tumors are the predominant form of pediatric spinal cord tumor. This population, however, presented with an unusually large number of developmental tumors, contrary to several published studies. The disparity may be the result of this institution acting as a regional referral center, thus increasing the number of this type of patient. The population is too small to make any other conjecture. The predominance of astrocytomas and neuroblastomas among those patients with poor outcomes and the prevalence of developmental tumors suggest the need for broader investigation. Although, in general, spinal cord tumors are relatively rare, this preliminary study supports the need to further evaluate associations between tumor type, presenting symptoms, treatment, and functional outcome in children with spinal cord tumors.

Pediatric Low-Grade and Ependymal Spinal Cord Tumors

Our institutional experience with pediatric spinal cord tumors includes 25 patients with the diagnosis of ependymoma (EP; n = 4), myxopapillary ependymoma (MPEP; n = 4), juvenile pilocytic astrocytoma (JPA; n = 5), nonpilocytic astrocytoma (WHO grade I or II, n = 6), and other nonastrocytic spinal cord tumors (n = 6) treated during the period 1974–1999. Nineteen patients required radiation therapy (RT). The median progression-free survival following RT was 65 months (range 1–206 months). Seven patients recurred at an average of 22 months. The EP patients recurred at an average of 8.5 months, while the patients with low-grade astrocytoma recurred at an average of 42 months. Including the 6 nonsurviving patients, the median overall survival was 96 months. Two EP patients died with a progression-free survival of 9 months. One patient with MPEP died of other causes at 7 months. The treatment of pediatric spinal cord tumors should be individualized based on the histologic type. Radical surgery is indicated for nonmyxopapillary EP and low-grade astrocytic tumors. The need for adjuvant therapy most often depends on the extent of resection as well as the tumor type. Patients with disseminated EP, MPEP, JPA and nonpilocytic astrocytoma may achieve long-term progression-free survival with craniospinal irradiation.

High-Grade Pediatric Spinal Cord Tumors

Our institutional experience with high-grade pediatric spinal cord tumors includes 11 children treated during the period of 1981-1997. All patients underwent a biopsy or an attempt at resection and received postoperative radiation therapy. Three patients had a gross-total resection of their primary tumor, 6 patients had a subtotal resection and the remaining 2 were biopsied. Histologically, these tumors were characterized as anaplastic astrocytoma (n = 6), glioblastoma multiforme (n = 3) or anaplastic oligodendroglioma (n = 2). Three patients were treated with craniospinal irradiation (38-48 Gy) in addition to a boost to the residual tumor. The median dose to the primary site for all patients was 48.6 Gy (range 38-55 Gy). The median overall survival was 13 months (range 8-149 months). Only 2 patients were alive at 138 and 149 months following radiation therapy. The median progression-free survival following radiation therapy was 10 months (range 2-80 months). There was no difference in progression-free or overall survival for those diagnosed with glioblastoma multiforme when compared to patients diagnosed with anaplastic astrocytoma or anaplastic oligodendroglioma. The pattern of failure was either diffuse or local. For the patients who failed diffusely (n = 6), the median progression-free survival was 2 months compared to 23 months for those whose failure was entirely local (p < 0.01). The median overall survival was significantly shorter for those who failed diffusely compared to those who failed locally (10 vs. 37 months, p < 0.01). High-grade spinal cord tumors in children have a poor prognosis based on this report. It is important to document the extent of disease accurately prior to the initiation of radiation therapy, since a subset of these patients progress rapidly outside of the field of irradiation.

Pediatric Spinal Axis Tumors

Pediatric spinal cord tumors occur in the intramedullary or extramedullary spaces. The extramedullary tumors are further divided into those in intradural-extramedullary or extradural locations. Tumors in the intradural-extramedullary region include nerve sheath tumors, meningiomas, and "embryonal" tumors. In the extradural space are neuroblastomas, sarcomas, and other primary tumors of bone. The radiographic findings, histology, and management of each type of tumor are included in this article, which focuses on extramedullary tumors.

Pediatric Spinal Cord Tumor Surgery

This article discusses our experience in managing pediatric spinal cord tumors. A description of the clinical presentation of children with such lesions and of the radiological characteristics of these tumors is given. Emphasis is placed on treatment philosophy and objectives as well as on surgical technique. Our results and the complications in treating 95 children with spinal cord tumors are outlined.

Lasers in pediatric neurosurgery.

The carbon dioxide (CO2) laser is a microsurgical instrument to be used in conjunction with good neurosurgical technique. Laser surgery has special applications in pediatric neurosurgery because of the type and location of many pediatric tumors as well as the laser qualities of precision and decreased tissue trauma. The CO2 laser has proven to be a valuable surgical tool in this series of pediatric spinal cord and brain tumor patients. The areas of most effective laser treatment were the posterior fossa, ventricles, spinal cord and the suprasellar area. The laser was least helpful in tumors of the hemispheres and the hypothalamus. Criteria need to be developed for absolute and relative indications for CO2 laser use.