Genetic predictors of neurocognitive outcomes in survivors of pediatric brain tumors.

BACKGROUND: Neurocognitive deficits are common in pediatric brain tumor survivors. The use of single nucleotide polymorphism (SNP) analysis in DNA repair genes may identify children treated with radiation therapy for brain tumors at increased risk for treatment toxicity and adverse neurocognitive outcomes. MATERIALS: The Human 660W-Quad v1.0 DNA BeadChip analysis (Illumina) was used to evaluate 1048 SNPs from 59 DNA repair genes in 46 subjects. IQ testing was measured by the Wechsler Intelligence Scale for Children. Linear regression was used to identify the 10 SNPs with the strongest association with IQ scores while adjusting for radiation type. RESULTS: The low vs high IQ patient cohorts were well matched for time from first treatment to most recent IQ, first treatment age, sex, and treatments received. 5 SNPs on 3 different genes (CYP29, XRCC1, and BRCA1) and on 3 different chromosomes (10, 19, and 17) had the strongest association with most recent IQ score that was not modified by radiation type. Furthermore, 5 SNPs on 4 different genes (WRN, NR3C1, ERCC4, RAD51L1) on 4 different chromosomes (8, 5, 16, 14) had the strongest association with change in IQ independent of radiation type, first IQ, and years between IQ measures. CONCLUSIONS: SNPs offer the potential to predict adverse neurocognitive outcomes in pediatric brain tumor survivors. Our results require validation in a larger patient cohort. Improving the ability to identify children at risk of treatment related neurocognitive deficits could allow for better treatment stratification and early cognitive interventions.

Treatment of hydrocephalus following posterior fossa tumor resection: a multicenter collaboration from the Hydrocephalus Clinical Research Network.

OBJECTIVE: Persistent hydrocephalus following posterior fossa brain tumor (PFBT) resection is a common cause of morbidity in pediatric brain tumor patients, for which the optimal treatment is debated. The purpose of this study was to compare treatment outcomes between VPS and ETV in patients with persistent hydrocephalus following surgical resection of a PFBT. METHODS: A post-hoc analysis was performed of the Hydrocephalus Clinical Research Network (HCRN) prospective observational study evaluating VPS and ETV for pediatric patients. Children who experienced hydrocephalus secondary to PFBT from 2008 to 2021 were included. Primary outcomes were VPS/ETV treatment failure and time-to-failure (TTF). RESULTS: Among 241 patients, the VPS (183) and ETV (58) groups were similar in age, extent of tumor resection, and preoperative ETV Success Score. There was no difference in overall treatment failure between VPS and ETV (33.9% vs 31.0%, p = 0.751). However, mean TTF was shorter for ETV than VPS (0.45 years vs 1.30 years, p = 0.001). While major complication profiles were similar, compared to VPS, ETV patients had relatively higher incidence of minor CSF leak (10.3% vs. 1.1%, p = 0.003) and pseudomeningocele (12.1% vs 3.3%, p = 0.02). No ETV failures were identified beyond 3 years, while shunt failures occurred beyond 5 years. Shunt infections occurred in 5.5% of the VPS cohort. CONCLUSIONS: ETV and VPS offer similar overall success rates for PFBT-related postoperative hydrocephalus. ETV failure occurs earlier, while susceptibility to VPS failure persists beyond 5 years. Tumor histology and grade may be considered when selecting the optimal means of CSF diversion.

Pediatric pineal region masses: a single-center experience over 25 years.

PURPOSE: Pineal region tumors (PRT) represent less than 1% of brain neoplasms. The rare and heterogeneous nature of these tumors is reflected in the variety of treatment modalities employed. METHODS: A single-center retrospective review of all pediatric patients with pineal region tumors between November 1996 and June 2021 was performed. Fifty-six cases of pineal tumors were reviewed for age and symptoms upon presentation, diagnostic methods, imaging characteristics, histological classification, treatment modalities, recurrence, and mortality rates. RESULTS: The average age at diagnosis was 11.3 years. The majority of patients were male (82.1%) and Caucasian (73.2%). The most common presenting symptoms were headache (n = 38, 67.9%) and visual problems (n = 34, 60.7%). Hydrocephalus was present in 49 patients (87.5%). Germinoma (n = 20, 35.7%) and non-germinomatous germ cell tumor (NGGCT) (n = 17, 30.4%) were the most common tumors. Chemotherapy was employed for 54 patients (96.4%), radiation for 49 (87.5%), and surgical resection for 14 (25.0%). The average duration of treatment was 5.9 months. Progression-free survival was 74.4% at 5 years and 72.0% at 10 years. Overall survival was 85.7% at 5 years and 77.1% at 10 years. CONCLUSION: Treatment of pineal region tumors must be targeted to each patient based on presentation, subtype, presence of hydrocephalus, and extent of disease. Upfront surgical resection is usually not indicated. As advances in oncological care proceed, treatment modalities may continue to improve in efficacy.

Refining the role of cervical spine immobilization and stabilization in pediatric non-accidental trauma, a retrospective series of 1008 patients.

INTRODUCTION: Prompt detection of traumatic cervical spine injury is important as delayed or missed diagnosis can have disastrous consequences. Given the understood mechanism of non-accidental trauma (NAT), it is reasonable to suspect that cervical spine injury can occur. Current management of young children being evaluated for NAT includes placement of a rigid collar until clinical clearance or an MRI can be obtained. Currently, there exists a lack of robust data to guide cervical bracing. Anecdotally, our group has not observed a single patient with a diagnosis of NAT who required operative stabilization for cervical spine instability. This study will be the largest series to date and aims to systematically investigate this observation to determine the likelihood that children with a diagnosis of NAT harbor cervical spine instability related to their injuries. METHODS: Patient data from the Children's Hospital Colorado Trauma Registry diagnosed with non-burn-only NAT were reviewed retrospectively. Children less than 4 years of age pulled from the registry from January 1, 2005, to March 31, 2021, were included. Demographic, admission/discharge, imaging, and clinic management data were collected for each patient and analyzed. RESULTS: There were 1008 patients included in the cohort. The age at presentation ranged from 5 days to 4 years (mean 10.4 months). No patient had X-ray or CT findings concerning for cervical instability. Three patients had MRI findings concerning for cervical instability. Two of these underwent external bracing, and the third died from unrelated injuries during their hospitalization. Only four patients were discharged in a cervical collar, and all were ultimately cleared from bracing. No patient underwent a spinal stabilization procedure. CONCLUSIONS: While the mechanism of injury in many NAT cases would seem to make significant cervical spine injury possible, this single-center retrospective review of a large experience indicates that such injury is exceedingly rare. Further study is merited to understand the underlying pathophysiology. However, it is reasonable to consider cervical collar clearance in the setting of normal radiographs and a reassuring neurological exam. Furthermore, if concerns exist regarding cervical spine instability on MRI, an initial trial of conservative management is warranted.

"Growing cerebellum" requiring operative decompression following perinatal ventriculoperitoneal shunting.

INTRODUCTION: While cases of acquired Chiari I malformation following ventriculoperitoneal shunting for posthemorrhagic hydrocephalus have been reported, true disproportionate cerebellar growth is rare, with no previous cases requiring posterior fossa decompression reported. CLINICAL PRESENTATION: We present a premature neonate who underwent ventriculoperitoneal shunt placement for suspected posthemorrhagic hydrocephalus. He subsequently developed a symptomatic Chiari I malformation with volumetric measurements demonstrating disproportionate growth of the cerebellum. He did not demonstrate thickening of the supratentorial or posterior fossa cranium. The patient underwent an extradural posterior fossa decompression, with resolution of symptoms. OUTCOME AND CONCLUSIONS: We review the extant literature regarding the development of Chiari malformation type I as a manifestation of craniocerebral disproportion (CCD) following shunt placement for posthemorrhagic hydrocephalus of prematurity. Most previous reports reflect a mechanism that includes underdevelopment of the intracranial posterior fossa (or supratentorial) volume. The case presented in this report, as well as one additional case, indicates that there may exist a variant mechanism, characterized by rapid growth of the cerebellum itself, in the absence of one of the rare syndromes associated with primary macrocerebellum. While this case was effectively managed with extradural posterior fossa decompression, previous reports indicate that supratentorial cranial expansion procedures are preferable in some cases. As such, pediatric neurosurgeons should be able to distinguish the patterns of craniocerebral disproportion when considering treatment options for these patients. Further investigation regarding these uncommon patients may better describe the underlying mechanisms.

Machine learning predicts risk of cerebrospinal fluid shunt failure in children: a study from the hydrocephalus clinical research network.

PURPOSE: While conventional statistical approaches have been used to identify risk factors for cerebrospinal fluid (CSF) shunt failure, these methods may not fully capture the complex contribution of clinical, radiologic, surgical, and shunt-specific variables influencing this outcome. Using prospectively collected data from the Hydrocephalus Clinical Research Network (HCRN) patient registry, we applied machine learning (ML) approaches to create a predictive model of CSF shunt failure. METHODS: Pediatric patients (age < 19 years) undergoing first-time CSF shunt placement at six HCRN centers were included. CSF shunt failure was defined as a composite outcome including requirement for shunt revision, endoscopic third ventriculostomy, or shunt infection within 5 years of initial surgery. Performance of conventional statistical and 4 ML models were compared. RESULTS: Our cohort consisted of 1036 children undergoing CSF shunt placement, of whom 344 (33.2%) experienced shunt failure. Thirty-eight clinical, radiologic, surgical, and shunt-design variables were included in the ML analyses. Of all ML algorithms tested, the artificial neural network (ANN) had the strongest performance with an area under the receiver operator curve (AUC) of 0.71. The ANN had a specificity of 90% and a sensitivity of 68%, meaning that the ANN can effectively rule-in patients most likely to experience CSF shunt failure (i.e., high specificity) and moderately effective as a tool to rule-out patients at high risk of CSF shunt failure (i.e., moderately sensitive). The ANN was independently validated in 155 patients (prospectively collected, retrospectively analyzed). CONCLUSION: These data suggest that the ANN, or future iterations thereof, can provide an evidence-based tool to assist in prognostication and patient-counseling immediately after CSF shunt placement.

Targeted fusion analysis can aid in the classification and treatment of pediatric glioma, ependymoma, and glioneuronal tumors.

BACKGROUND: The use of next-generation sequencing for fusion identification is being increasingly applied and aids our understanding of tumor biology. Some fusions are responsive to approved targeted agents, while others have future potential for therapeutic targeting. Although some pediatric central nervous system tumors may be cured with surgery alone, many require adjuvant therapy associated with acute and long-term toxicities. Identification of targetable fusions can shift the treatment paradigm toward earlier integration of molecularly targeted agents. METHODS: Patients diagnosed with glial, glioneuronal, and ependymal tumors between 2002 and 2019 were retrospectively reviewed for fusion testing. Testing was done primarily using the ArcherDx FusionPlex Solid Tumor panel, which assesses fusions in 53 genes. In contrast to many previously published series chronicling fusions in pediatric patients, we compared histological features and the tumor classification subtype with the specific fusion identified. RESULTS: We report 24 cases of glial, glioneuronal, or ependymal tumors from pediatric patients with identified fusions. With the exception of BRAF:KIAA1549 and pilocytic/pilomyxoid astrocytoma morphology, and possibly QKI-MYB and angiocentric glioma, there was not a strong correlation between histological features/tumor subtype and the specific fusion. We report the unusual fusions of PPP1CB-ALK, CIC-LEUTX, FGFR2-KIAA159, and MN1-CXXC5 and detail their morphological features. CONCLUSIONS: Fusion testing proved to be informative in a high percentage of cases. A large majority of fusion events in pediatric glial, glioneuronal, and ependymal tumors can be identified by relatively small gene panels.

Adamantinomatous craniopharyngioma in the molecular age and the potential of targeted therapies: a review.

Pediatric adamantinomatous craniopharyngiomas (ACPs) are histologically benign brain tumors that often follow an aggressive clinical course. Arising in the sellar/suprasellar region, they grow in close proximity to critical neurological and vascular structures and can result in significant neuroendocrine morbidity. First-line treatment often involves surgical resection with or without radiotherapy and has been associated with significant morbidity and poor quality of life outcomes. As a result, the discovery of alternative effective and safe treatments is clearly desirable. In recent years, laboratory studies have harnessed sophisticated techniques to identify the upregulation of several markers that may represent potential therapeutic targets. These targets include IL-6, PD1/PD-L1, MEK, IDO-1, and others. Agents that target these pathways exist, and there is an opportunity to investigate their potential efficacy in the treatment of ACP. Trials investigating some of these agents as monotherapy and in combination for the treatment of pediatric ACP are underway or in development. If positive, these trials may result in a paradigm shift in treatment that will hopefully result in reduced morbidity and better outcomes for patients.

Utility of image fusion software in identifying shunt malfunction.

PURPOSE: Pediatric shunt malfunction occurs frequently and is important to recognize due to the high associated morbidity and mortality. Although neuroimaging plays a crucial role in the diagnosis, it remains imperfect. We sought to identify the effect of image fusion software in predicting shunt malfunction. METHODS: A total of 248 rapid shunt series brain MRIs performed between 2013 and 2017 were compared with prior neuroimaging for changes in ventricular size by two methods: radiology report and Brainlab fusion. Shunt malfunction was defined by an operative report confirming malfunction within 72 h of neuroimaging. The two methods were compared by logistic regression models, with sensitivity and specificity subsequently calculated. RESULTS: Shunt malfunction was identified in 40 cases (16.1%). Imaging report demonstrated a lower Akaike information criterion than the Brainlab fusion and is therefore a better fitting model. While sensitivity is similar for the two models, 0.94 (0.90 to 0.97, 95% CI) for imaging report, and 0.95 (0.91 to 0.98, 95% CI) for Brainlab, the specificity was significantly different, 0.50 (0.37 to 0.63, 95% CI) and 0.33 (0.24 to 0.44, 95% CI) respectively. CONCLUSIONS: Our data indicate that an increased ability to detect subtle changes in ventricular size does not translate to improved accuracy, but instead leads to decreased specificity, and therefore an overdiagnosis of shunt malfunction in children with normally functioning shunts. While imaging continues to play a prominent role in the identification of shunt malfunction, neurosurgical clinical evaluation remains crucial to the final diagnosis.

Evaluation of 2011 AAP cervical spine screening guidelines for children with Down Syndrome.

PURPOSE: Atlantoaxial instability (AAI) has a higher incidence rate among individuals with Down syndrome (DS) than the non-DS population. In 2011, the American Academy of Pediatrics (AAP) updated its AAI screening guidelines for children with DS from radiographic screening to radiographs only if there are clinical symptoms suggestive of cervical spine pathology. An assessment of whether this alteration has been associated with an increase in AAI-associated spinal cord injury has not been undertaken. METHODS: We provide the first neurosurgical review of a large experience implementing the 2011 AAP guidelines. We reviewed the courses of patients with DS seen at the Sie Center for Down Syndrome at Children's Hospital Colorado who were evaluated for cervical spine disease and determined whether screening radiographic imaging could have led to earlier diagnosis or prevented development of neurological deficits. We also report an illustrative case of a 5-year-old female with Down syndrome who presented with instability after normal screening radiographs per the pre-2011 guidelines. RESULTS: The clinical experience of the Sie Center demonstrates that even when limiting imaging to patients who show signs or symptoms of spine pathology, the vast majority of x-rays are negative. Our exemplary patient presented to the emergency department for neck pain without a history of significant trauma. She was diagnosed and treated for atlantoaxial subluxation associated with os odontoideum. CONCLUSION: Routine radiographic screening may not be sufficiently predictive of DS individuals at risk to develop AAI. This experience supports the appositeness of the de-escalation of care asserted by the guidelines.

Adamantinomatous craniopharyngioma: moving toward targeted therapies.

The evolving characterization of the biological basis of adamantinomatous craniopharyngioma (ACP) has provided insights critical for novel systemically delivered therapies. While current treatment strategies for ACP are associated with low mortality rates, patients experience severely lowered quality of life due to high recurrence rates and chronic sequelae, presenting a need for novel effective treatment regimens. The identification of various dysregulated pathways that play roles in the pathogenesis of ACP has prompted the investigation of novel treatment options. Aberrations in the CTNNB1 gene lead to the dysregulation of the Wnt pathway and the accumulation of nuclear ß-catenin, which may play a role in tumor invasiveness. While Wnt pathway/ß-catenin inhibition may be a promising treatment for ACP, potential off-target effects have limited its use in current intervention strategies. Promising evidence of the therapeutic potential of cystic proinflammatory mediators and immunosuppressants has been translated into clinical therapies, including interleukin 6 and IDO-1 inhibition. The dysregulation of the pathways of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), epidermal growth factor receptor (EGFR), and programmed cell death protein 1 and its ligand (PD-1/PD-L1) has led to identification of various therapeutic targets that have shown promise as clinical strategies. The Sonic Hedgehog (SHH) pathway is upregulated in ACP and has been implicated in tumorigenesis and tumor growth; however, inhibition of SHH in murine models decreased survival, limiting its therapeutic application. While further preclinical and clinical data are needed, systemically delivered therapies could delay or replace the need for more aggressive definitive treatments. Ongoing preclinical investigations and clinical trials of these prospective pathways promise to advance treatment approaches aimed to increase patients' quality of life.

Diagnostic accuracy of neuroimaging in pediatric optic chiasm/sellar/suprasellar tumors.

Preoperative diagnosis for tumors arising in the optic chiasm/sellar/suprasellar region in children is helpful to determine surgical necessity and approach, given the high operative risk in this area. We evaluated the ability to differentiate tumor type by preoperative neuroimaging. Thirty-eight of 53 tumors were correctly diagnosed by neuroimaging based on final pathologic diagnosis (prediction accuracy 72%). Prediction accuracies were 87% (20/23) for craniopharyngioma, 79% (11/14) for optic pathway glioma, 64% (7/11) for germ cell tumor, and 0% (0/5) for Langerhans cell histiocytosis. Diagnosis of optic chiasm/sellar/suprasellar tumors in children by imaging alone should be considered when biopsy is considered high risk.

Decision-Making About Intracranial Pressure Monitor Placement in Children With Traumatic Brain Injury.

OBJECTIVES: Little is known about how clinicians make the complex decision regarding whether to place an intracranial pressure monitor in children with traumatic brain injury. The objective of this study was to identify the decisional needs of multidisciplinary clinician stakeholders. DESIGN: Semi-structured qualitative interviews with clinicians who regularly care for children with traumatic brain injury. SETTING: One U.S. level I pediatric trauma center. SUBJECTS: Twenty-eight clinicians including 17 ICU nurses, advanced practice providers, and physicians and 11 pediatric surgeons and neurosurgeons interviewed between August 2017 and February 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Participants had a mean age of 43 years (range, 30-66 yr), mean experience of 10 years (range, 0-30 yr), were 46% female (13/28), and 96% white (27/28). A novel conceptual model emerged that related the difficulty of the decision about intracranial pressure monitor placement (y-axis) with the estimated outcome of the patient (x-axis). This model had a bimodal shape, with the most difficult decisions occurring for patients who 1) had a good opportunity for recovery but whose neurologic examination had not yet normalized or 2) had a low but uncertain likelihood of neurologically functional recovery. Emergent themes included gaps in medical knowledge and information available for decision-making, differences in perspective between clinical specialties, and ethical implications of decision-making about intracranial pressure monitoring. Experienced clinicians described less difficulty with decision-making overall. CONCLUSIONS: Children with severe traumatic brain injury near perceived transition points along a spectrum of potential for recovery present challenges for decision-making about intracranial pressure monitor placement. Clinician experience and specialty discipline further influence decision-making. These findings will contribute to the design of a multidisciplinary clinical decision support tool for intracranial pressure monitor placement in children with traumatic brain injury.

Increased complications without neurological benefit are associated with prophylactic spinal cord untethering prior to scoliosis surgery in children with myelomeningocele.

PURPOSE: Children with myelomeningocele (MMC) are at increased risk of developing neuromuscular scoliosis and spinal cord re-tethering (Childs Nerv Syst 12:748-754, 1996; Neurosurg Focus 16:2, 2004; Neurosurg Focus 29:1, 2010). Some centers perform prophylactic untethering on asymptomatic MMC patients prior to scoliosis surgery because of concern that additional traction on the cord may place the patient at greater risk of neurologic deterioration peri-operatively. However, prophylactic untethering may not be justified if it carries increased surgical risks. The purpose of this study was to determine if prophylactic untethering is necessary in asymptomatic children with MMC undergoing scoliosis surgery. METHODS: A multidisciplinary, retrospective cohort study from seven children's hospitals was performed including asymptomatic children with MMC < 21 years old, managed with or without prophylactic untethering prior to scoliosis surgery. Patients were divided into three groups for analysis: (1) untethering at the time of scoliosis surgery (concomitant untethering), (2) untethering within 3 months of scoliosis surgery (prior untethering), and (3) no prophylactic untethering. Baseline data, intra-operative reports, and 90-day post-operative outcomes were analyzed to assess for differences in neurologic outcomes, surgical complications, and overall length of stay. RESULTS: A total of 208 patients were included for analysis (mean age 9.4 years, 52% girls). No patient in any of the groups exhibited worsened motor or sensory function at 90 days post-operatively. However, comparing the prophylactic untethering groups with the group that was not untethered, there was an increased risk of surgical site infection (SSI) (31.3% concomitant, 28.6% prior untethering vs. 12.3% no untethering; p = 0.0104), return to the OR (43.8% concomitant, 23.8% prior untethering vs. 17.4% no untethering; p = 0.0047), need for blood transfusion (51.6% concomitant, 57.1% prior untethering vs. 33.8% no untethering; p = 0.04), and increased mean length of stay (LOS) (13.4 days concomitant, 10.6 days prior untethering vs. 6.8 days no untethering; p < 0.0001). In multivariable logistic regression analysis, prophylactic untethering was independently associated with increased adjusted relative risks of surgical site infection (aRR = 2.65, 95% CI 1.17-5.02), unplanned re-operation (aRR = 2.17, 95% CI 1.02-4.65), and any complication (aRR = 2.25, 95% CI 1.07-4.74). CONCLUSION: In this study, asymptomatic children with myelomeningocele who underwent scoliosis surgery developed no neurologic injuries regardless of prophylactic untethering. However, those who underwent prophylactic untethering were more likely to experience SSIs, return to the OR, need a blood transfusion, and have increased LOS than children not undergoing untethering. Based on these data, prophylactic untethering in asymptomatic MMC patients prior to scoliosis surgery does not provide any neurological benefit and is associated with increased surgical risks.

Pediatric versus adult meningioma: comparison of epidemiology, treatments, and outcomes using the Surveillance, Epidemiology, and End Results database.

Pediatric meningiomas, which account for < 1% of all meningiomas, are thought to have unique features, including being more aggressive than their adult counterparts. The goal of this investigation was to compare pediatric and adult meningiomas in a large head-to-head comparison. We used the Surveillance, Epidemiology, and End Result (SEER) datasets to compare meningioma demographics, first treatments, and outcomes among children/adolescents (0-21 years), young adults (22-45 years), and older adults (> 45 years). During 2004-2012, SEER contained 59148 patients age 0-107 years diagnosed with meningioma, with children/adolescents accounting for 381 (0.64%) patients. Unlike older and young adults, children/adolescents with meningioma did not demonstrate female predominance, and had an equal 1:1 male-to-female ratio. Children/adolescents also had almost three-times as many spinal tumors (13.1%) than young adults (4.2%) and older adults (4.4%). Both children/adolescents and young adults had undergone more gross total resections (both 43%) versus older adults (25%), and were treated more with radiation (14.6%, and 12.0% respectively) than their older counterparts (8.5%). In addition, both children/adolescents and young adults had significantly lower all-cause mortality (4.5% in both) than older adults (24.6%), during median 35-month follow-up. Inherent limitations of the SEER datasets restrict our ability to answer important questions regarding comparisons of tumor grading, histological diagnosis, cause-specific mortality, and neurofibromatosis status. Pediatric meningiomas appear distinct from their adult counterparts as they do not display the typical female predominance and include more clinically relevant spinal tumors. More extensive surgeries, greater use of radiation therapy, and lower all-cause mortality were seen in both children/adolescents and young adults, which raises questions regarding the perceived uniquely aggressive nature of pediatric meningiomas. However, due to the significant limitations of the SEER datasets, our results must be interpreted cautiously and stand only to foster novel questions, which would be better answered in well-designed, prospective studies.

Radiation-induced Cataracts in Children With Brain Tumors Receiving Craniospinal Irradiation.

Radiation is a well-known cause of the development of cataracts. For children with brain tumors, craniospinal irradiation (CSI) would be expected to result in a significant risk of cataract development. We reviewed the incidence of cataracts in children with brain tumors who received CSI at our institution. Of 45 children who received CSI and had ophthalmologic examinations, 13 developed cataracts. The median time to develop cataracts was 27.6 months. Seven children underwent surgery for cataract. Given this high incidence of cataracts, we suggest routine eye examinations for all children receiving CSI.

Intracranial Ewing sarcoma: four pediatric examples.

BACKGROUND: Ewing sarcoma typically arises in bone and is unrelated to intraparenchymal small blue cell embryonal central nervous system (CNS) tumors previously designated primitive neuroectodermal tumors (PNETs). When the CNS is impacted, it is usually secondary to local extension from either the epidural space, skull, or intracranial or spinal metastases. Primary examples within the cranial vault are rare, usually dural-based, and are largely case reports in the literature. We detail four pediatric patients with solitary, primary intracranial Ewing sarcoma, all manifesting the archetypal EWRS1 gene rearrangement that confirms diagnosis. PROCEDURE: Neurosurgical Department records, spanning 21 years (1995-2016), were reviewed to identify patients. Demographics, clinical history, pathological/genetic features, and clinical course were retrieved from the medical record and personal files of the authors. RESULTS: Four patients, one male and three females, age 5 to 16 years, were identified. One presented in extremis from a large lesion, two with soft tissue masses, and the fourth as an incidental finding after being involved in a motor vehicle collision. Three had clear bony involvement: a 10-year-old girl with a large left temporal lesion had clear origin in the skull, with spiculated calcified striations throughout the mass; a 9-year-old girl presented with a bony left petrous apex mass; and a 16-year-old girl presented with a left temporal mass with extension to the dura and underlying bone erosion. Only the 5-year-old boy had a large left frontoparietal mass traversing the falx with no bony contact. All four tumors manifested the diagnostic EWSR1 mutation and were treated with an Ewing sarcoma regimen. Outcomes were variable, with one patient showing progressive metastatic disease and death 3 years after presentation, one patient with disease-free survival 10.5 years after completion of therapy, and one alive and well at the completion of therapy 1 year after diagnosis. One patient completed therapy recently with post-therapy scans showing no evidence of disease. CONCLUSION: Testing for the EWSR1 mutation confirms the diagnosis of Ewing sarcoma and excludes other types of embryonal CNS tumors. Long-term disease-free survival is possible with adherence to the appropriate therapeutic regimen after gross surgical resection.

Hypofractionated re-irradiation to the brainstem in children with recurrent brain tumors.

To characterize radiation necrosis following hypofractionated brainstem re-irradiation in pediatric patients, we reviewed 23 cases with 28 tumors invading or abutting brainstem and treated with hypofractionated re-irradiation from 2004 to 2014. Re-irradiation delivered total doses of 16-30 Gy in two to five fractions. The most commons regimens used were 24 Gy in three fractions and 25 Gy in five fractions. At median follow-up of 12.8 months, median overall survival was 14.7 months and eight in-field recurrences were detected (median time 10.5 months). Five patients experienced symptomatic brainstem necrosis, and all having received 24 Gy in three fractions. Hypofractionated brainstem re-irradiation may be safer in five fractions.

Survival benefit of postoperative radiation in papillary meningioma: Analysis of the National Cancer Data Base.

AIM/BACKGROUND: Papillary meningioma represents a rare subset of World Health Organization (WHO) Grade III meningioma that portends an overall poor prognosis. There is relatively limited data regarding the benefit of postoperative radiation therapy (PORT). We used the National Cancer Data Base (NCDB) to compare overall survival (OS) outcomes of surgically resected papillary meningioma cases undergoing PORT compared to post-operative observation. MATERIALS AND METHODS: The NCDB was queried for patients with papillary meningioma, diagnosed between 2004 and 2013, who underwent upfront surgery with or without PORT. Overall survival (OS) was determined using the Kaplan-Meier method. Univariate (UVA) and multivariate (MVA) analyses were performed. RESULTS: In total, 190 patients were identified; 89 patients underwent PORT, 101 patients were observed. Eleven patients received chemotherapy (6 with PORT, 5 without). 2-Year OS was significantly improved with PORT vs. no PORT (93.0% vs. 74.4%), as was 5-year OS (78.5% vs. 62.5%) (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.27-0.85; p = 0.01). On MVA, patients receiving PORT had improved OS compared to observation (HR, 0.41; 95% CI, 0.22-0.76; p = 0.005). On subset analysis by age group, the benefit of PORT vs. no PORT was significant in patients ≤18 years (n = 13), with 2-year OS of 85.7% vs. 50.0% (HR, 0.08; 95% CI, 0.01-0.80; p = 0.032) and for patients >18 years (n = 184), with 2-year OS of 94.7% vs. 76.1% (HR, 0.55; 95% CI, 0.31-1.00; p = 0.049), respectively. CONCLUSIONS: In this large contemporary analysis, PORT was associated with improved survival for both adult and pediatric patients with papillary meningioma. PORT should be considered in those who present with this rare, aggressive tumor.

Hypofractionated Radiotherapy for Children With Diffuse Intrinsic Pontine Gliomas.

Children with diffuse intrinsic pontine gliomas have very poor outcomes, with nearly all children dying from disease. Standard therapy includes 6 weeks of radiation. There have been descriptions of using a shortened course of radiation. We describe our experience with a hypofractionated radiotherapy approach delivered over five treatments. In seven children, hypofractionated radiotherapy was well tolerated, but symptomatic radiation necrosis was seen in three of the children. Overall survival was slightly shorter than previously described in the literature. We are developing a prospective dose-finding protocol with the goal of tolerable short-course radiation treatment with outcomes comparable to conventional radiation.