Anaplastic Ependymoma Research Articles

Dissemination of intramedullary anaplastic ependymomas

Two cases of 6 years old and 20 years of ages were operated for intramedullary anaplastic ependymomas. A gross total microsurgical excision of their tumors was achieved in both the cases, barring the infiltrated nerve roots of one case (6 years old, child). Standard doses of irradiation were offered to both the cases following surgery. The dissemination of disease occurred at six months and one year and 10 months duration in both. An extensive spread of ependymoma involved full spinal cord and brain stem in the first case, while malignant meningitis, mild hydrocephalus and a distal recurrence occurred in another case. It was concluded that (1) anaplastic ependymomas have high potential for dissemination anywhere in neuraxis (2) dissemination may occur without a local recurrence of tumor at primary site (3) gross total microsurgical excision and irradiation does not offer resistance to dissemination.

Supratentorial Anaplastic Ependymoma with Bilateral Papilledema

Ependymomas constitute the third most common histological type of CNS tumor in children. Compared to classic cellular ependymoma (WHO grade II), anaplastic ependymoma is a more aggressive and less common subtype of ependymal neoplasm. We report a case of a supratentorial anaplastic ependymoma in a child presenting with a right sixth nerve palsy with bilateral papilledema. To our knowledge, the ophthalmic findings presented herein have not been previously reported in the context of this tumor type.

Surgical Technique and Outcome in the Treatment of Spinal Ependymomas: A Retrospective Analysis of 23 Cases Treated

Introduction Spinal ependymomas are from 3 to 6% of all tumors of the central nervous system and 15% of all spinal cord tumors. The WHO classifies ependymomas in the following four distinct subtypes: subependymoma, ependymoma myxopapillare, classic ependymoma, and anaplastic ependymoma. Spinal ependymomas are typically present in adults and include the following two subtypes: myxopapillary and classic. This review reports the data obtained on 23 patients treated for spinal ependymoma at our department of Neurosurgery from 2000 to 2012, describing the type of surgical treatment and clinical outcome with a mean follow-up of 4 years. Materials and Methods Among 53 cases of intramedullary tumors, 23 (43%) were ependymomas. The average age of patients with spinal ependymoma was 42.65 years with a range between 18 and 71 years. The main locations were cauda equina (70%), medullary cone (13%), and cervical region (13%). Neurological examination of each patient at the entrance, in the postoperative and last –follow-up was determined using the McCormick grading scales. All patients underwent surgical removal of the tumor and the McCormick grading was evaluated with multiple follow-up. The extent of resection and surgical results were evaluated with postoperative MRI. Results As evidenced in some tables, we performed gross-total removal (GTR) in 21 patients (91%) and subtotal removal (STR) in only 2 patients (9%). None of patient was treated with adjuvant radiotherapy and/or chemotherapy. There were no recurrences. No patient's follow-up showed signs of postoperative instability of the spine. Some particular surgical techniques in removal of this tumor are reported. Conclusion This study underlines some aspects of the surgical treatment of spinal ependymomas. Patients who underwent total removal had a clear neurological improvement. As evidenced in tables, patients who had McCormick II–III at the entrance improved significantly. To achieve good functional results, an early diagnosis and a prompt surgery are important. In case of a good surgical removal, postoperative radiotherapy is not indicated.

Predictors of survival in patients with spinal ependymoma

Objectives:We aimed to examine the impact of demographic and treatment factors on overall survival among spinal ependymoma patients.Methods:Using data from Surveillance, Epidemiology, and End Results (SEER) from 1990–2008, we evaluated subjects with histologically confirmed spinal cord ependymoma.Results:We identified 1,353 patients with spinal ependymoma (mean age 43.5 years). Among these, 26 had anaplastic ependymoma (AE), 374 had myxopapillary ependymoma (MPE), and 953 had other low-grade ependymoma (non-MPE). Median follow-up was 61 months. Overall survival at 5 years was 97% for MPE, 92% for low-grade non-MPE, and 73% for AE. Gross total resection (GTR) was achieved in 58% of subjects with MPE, 51% with low-grade non-MPE, and 50% with AE. Radiation occurred more often after subtotal resection (STR) than after GTR, and more often among those with anaplastic histology. Histology and extent of surgical resection were significant prognostic factors in multivariate analyses. Compared to MPE, subjects with low-grade non-MPE had a higher risk of mortality at 5 years (HR 2.35, P = 0.03), as did subjects with AE (HR 8.63, P < 0.01). Compared to GTR, STR was associated with an increased risk of mortality at 5 years (HR 2.2, P = 0.01), as was biopsy only (HR 2.05, P = 0.03) and no surgery (HR 4.97, P < 0.01). Among patients with either STR or GTR, adjuvant radiotherapy did not confer a survival benefit at 5 years (STR: HR 2.29, P = 0.07, and GTR: HR 2.2, P = 0.12).Discussion:We found that lower grade histology and higher extent of surgical resection were significant prognostic factors for more favourable survival outcomes for spinal ependymoma patients.

EP-02 * MOLECULAR CLASSIFICATION OF EPENDYMOMAS IN A JAPANESE COHORT

INTRODUCTION: Based on a series of extensive molecular analysis in the recent years, a scheme of molecular classification for ependymomas has been proposed. The efficacy of the classification however needs to be validated in an independent cohort of different ethnicity. For this purpose, Japan Pediatric Molecular Neuro-Oncology Group (JPMNG) has been established as a joint project of Japan Society of Neuro-Oncology (JSNO) and Japan Society of Pediatric Neurosurgery (JSPN) in order to centrally collect tumor samples and patient information and to provide a standardized molecular classification in pediatric brain tumors. METHODS: We studied genome-wide methylation analysis in ependymomas by using Infinium HumanMethylation450K BeadChip (HM450K). To detect C11orf95-RELA fusions and YAP1 associated fusions, we performed FISH and RT-PCR followed by Sanger sequencing,. Array CGH was used to assess chromothripsis in the cases with RELA or YAP1 fusions. RESULTS: The number of samples collected so far is 96. Among them, 64 samples (fresh frozen 53, FFPE 11) were analyzed with HM450K array. Posterior fossa (PF) ependymomas were subdivided into two groaups. One group, which clusters with reported PFA tumors, included all infantile-onset cases and histopathologically most anaplastic ependymoma (WHO grade3). The other includes most adult cases, ependymoma (WHO grade2) cases, and all primary spinal tumor cases and clustered with the PFB tumors. Supratentorial (ST) ependymomas had generally higher levels of methylation than either PFA or PFB tumors. C11orf95-RELA fusion gene were detected in 7 of 11 ST tumors. There were no C11orf95-YAP1 fusion positive cases examined by RT-PCR. Chromothripsis was detected in 2 out of 6 fusion-positive tumors. CONCLUSIONS: Japanese PF ependymomas were successfully classified into PFA and PFB by methylation profiling. C11orf95-RELA fusions were only observed in ST ependymomas but they may not be always associated with chromothripsis detected by array CGH. The pathogenesis of fusion-negative ST ependymomas needs further investigation.

Anaplastic ependymoma of spinal cord presented with low back pain

Anaplastic ependymoma of spinal cord presented with low back pain

An integrative analysis of treatment, outcomes and prognostic factors for primary spinal anaplastic ependymomas

The aim of this study was to elucidate the role of treatment modalities in primary spinal anaplastic ependymomas (PSAE) and identify promising prognostic factors. PSAE are rare tumors of the central nervous system with poorly understood clinical characteristics and treatment outcomes. We reviewed the literature in PubMed, Web of Science and Scopus databases to identify patients with PSAE. Multivariate Cox proportional hazards analysis and univariate Kaplan–Meier analysis were performed on the PSAE patients and overall survival (OS) and progression-free survival (PFS) were assessed to evaluate the clinical outcomes. Of the 40 patients with PSAE, the tumors were mostly intramedullary (n=19; 47.5%) and frequently involved the thoracic cord (n=25; 62.5%). Eighteen patients suffered recurrence during the follow-up with a median PFS of 24 months. The 1, 2, and 5year OS rates of the PSAE patients were 91.5%, 82.1%, and 63.1%, respectively. Gross total resection (GTR) was independently associated with prolonged PFS (hazard ratio [HR] 0.11; p=0.004) and OS (HR 0.11; p=0.003) in the multivariate analysis. Adjuvant radiotherapy also conferred improved PFS (HR 0.15; p=0.008) and OS (HR 0.16; p=0.022). Age, sex, tumor location and chemotherapy did not influence the outcomes in this group. The results of our study suggest that GTR and adjuvant radiotherapy are strong prognostic indicators in patients with PSAE and the role of chemotherapy is yet to be defined.

NHERF1/EBP50 is an organizer of polarity structures and a diagnostic marker in ependymoma.

NHERF1/EBP50, an adaptor protein required for epithelial morphogenesis, has been implicated in the progression of various human malignancies. NHERF1-deficient mice have intestinal brush border structural defects and we report here that they also have disorganized ependymal cilia with development of non-obstructive hydrocephalus. Examination of mouse and human brain tissues revealed highest NHERF1 expression at the apical plasma membrane of ependymal cells. In ependymal tumors, NHERF1 expression was retained in polarized membrane structures, such as microlumens, rosettes and canals, where it co-localized with some of its ligands, such as moesin and PTEN. Analysis of a comprehensive panel of 113 tumors showed robust NHERF1 labeling of microlumens in 100% of ependymomas, subependymomas, and pediatric anaplastic ependymomas, and in 67% of adult anaplastic ependymomas. NHERF1 staining was present in 35% of ependymoma cases that lacked reactivity for EMA, the routine immunohistochemical marker used for ependymoma diagnosis. NHERF1 labeling of microlumens was either absent or rarely seen in other types of brain tumors analyzed, denoting NHERF1 as a reliable diagnostic marker of ependymal tumors. Anaplastic foci and a subset of adult anaplastic ependymomas showed complete absence of NHERF1-labeled polarity structures, consistent with a loss of differentiation in these aggressive tumors. These data highlight a role for NHERF1 in ependymal morphogenesis with direct application to the diagnosis of ependymal tumors.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-015-0197-z) contains supplementary material, which is available to authorized users.

Evaluación de la utilidad del coeficiente de difusión aparente en resonancia magnética para la diferenciación del grado tumoral de los tumores cerebrales pediátricos

BackgroundThe apparent diffusion coefficient (ADC) in MRI seems to be related to cellularity in brain tumours. Its utility as a tool for distinguishing between histological types and tumour stages remains controversial. ProceduresWe retrospectively evaluated children diagnosed with CNS tumours between January 2008 and December 2013. Data collected were age, sex, histological diagnosis, and location of the tumour. We evaluated the ADC and ADC ratio and correlated those values with histological diagnoses. ResultsThe study included 55 patients with a median age of 6 years. Histological diagnoses were pilocytic astrocytoma (40%), anaplastic ependymoma (16.4%), ganglioglioma (10.9%), glioblastoma (7.3%), medulloblastoma (5.5%), and other (20%). Tumours could also be classified as low-grade (64%) or high-grade (36%). Mean ADC was 1.3 for low-grade tumours and 0.9 for high-grade tumours (p=.004). Mean ADC ratios were 1.5 and 1.2 for low and high-grade tumours respectively (p=.025). There were no significant differences in ADC/ADC ratio between different histological types. ConclusionADC and ADC ratio may be useful in imaging-study based differential diagnosis of low and high-grade tumours, but they are not a substitute for an anatomical pathology study.

MRI findings of olivary degeneration after surgery for posterior fossa tumours in children: incidence, time course and correlation with tumour grading.

Olivary degeneration is due to many posterior cranial fossa (PCF) lesions affecting the dentato-rubro-olivary pathway, also known as Guillain-Mollaret triangle. Triangle damage results in hyperexcitation and consequently in hypertrophy of the inferior olivary nucleus (ION). The aim of our study was to evaluate the incidence of magnetic resonance (MR) imaging changes in the ION after surgery in a large cohort of paediatric patients and to determine their correlation with tumour grade. We retrospectively evaluated 58 patients treated surgically for PCF tumours who underwent MR imaging between 2007 and 2014, 1week to 5years after surgery. Histopathology revealed 29 medulloblastomas (WHO IV), 6 ependymomas (WHO II), 2 anaplastic ependymomas (WHO III) and 21 pilocytic astrocytomas (WHO I). ION MR imaging changes were correlated with surgery-to-MR interval and with tumour grading. ION MR imaging changes were observed in 19/64 (33%), and all consisted of T2 signal alterations, 15 bilateral and four unilateral, with dentate nucleus damage in all cases. Olivary enlargement was observed in few cases only (7/19). ION T2 hyperintensity was always present between 1 and 6months after surgery with a trend to decrease, becoming faint after 1year. The Fisher test demonstrated a significant (p=0.005) correlation between ION MR imaging changes and high tumour grade. Our results demonstrate that olivary degeneration, with or without hypertrophy, is a relatively frequent consequence of posterior fossa surgery, particularly in children treated for high-grade tumours. Knowledge of this condition can prevent misdiagnoses and unnecessary investigations.

Supratentorial Parenchymal Ependymomas in Children: Experience with 14 Patients at a Single Institute.

To study the clinical features, imaging findings, treatment methods and results, and prognosis of supratentorial parenchymal ependymomas in children. Fourteen children with supratentorial parenchymal ependymomas were treated by the senior author at Tiantan Hospital between October 2004 and May 2010. The clinical manifestations, neuroimaging findings, treatment methods, and therapeutic results were retrospectively reviewed. The study included 11 boys and three girls. The patients were aged from 1 to 14 years with an average age of 6.1 years. Gross total surgical removal (GTR) was achieved in 10 cases, and subtotal removal (STR) was achieved in four cases. There were six ependymomas, seven anaplastic ependymomas, and one subependymoma. The mean follow-up duration was 78.9 months (range, 4?122 months). During the follow-up period, 10 patients who underwent GTR (71.4%; only 1 patient had a recurrent tumor during this time) had an excellent postoperative outcome (Karnofsky Performance Status ? 80), while four patients who underwent STR (28.6%) developed recurrent tumors and died. The preoperative diagnosis of supratentorial parenchymal ependymomas is difficult. GTR can be achieved with a favorable long-term outcome using an improved microsurgical technique.

21. Audit of primary brain tumours at royal north shore hospital from 2007 to 2011

Accurate pathological diagnosis and classification of brain tumours guides therapy and underpins translational research. We reviewed the pathological diagnosis of all primary brain tumours undergoing resection or biopsy at the Royal North Shore Hospital, an adult tertiary referral institution with a catchment population of 1.2 million during the period 2007 to 2011. Patients age ranged from 15 to 92. There were 779 cases, comprising 382 (49.04%) astrocytic, 11 (1.41%) oligoastrocytic, 35 (4.49%) oligodendroglial (0.13%) choroid plexus, 7 (0.90%) embryonal, 34 (4.36%) ependymal, 14 (1.80%) haemangioblastoma, 276 (35.43%) meningeal, 11 (1.41%) 15 (1.93%) neuronal and mixed neuronal-glial, 35 (4.49%) and 1 (0.13%) pineal. Of the astrocytic tumours 84% were glioblastoma, 10.5% anaplastic astrocytoma, 3% diffuse astrocytoma and 2% pilocytic astrocytoma. Meningeal tumours were subtyped into the following breakdowns: (72%) meningioma, (19%) atypical meningioma, (4.8%) haemangio-pericytoma, (2.8%) anaplastic meningioma, (0.7%) papillary, meningioma, (0.7%) anaplastic haemangiopericytoma and (0.34%) rhabdoid meningioma. Oligodendroglial tumours were subtyped into the following breakdowns: (74%) anaplastic oligodendroglioma, (26%) oligo-dendroglioma. Ependymal tumours were broken down into the following subcategories: (62%) ependymoma, (32%) myxopapillary ependymoma, (3%) anaplastic ependymoma and (3%) subependymoma. The incidence of most tumour subtypes in our audit was comparable to published rates in large-scale hospital-based studies. The most notable exception to this was the unusually high proportion of glioblastomas and haemangioblastomas which occurred at a rate that was double that seen in similar studies presumably because of a referral bias towards this quaternary centre.

Brain tumors in infants.

Background:Brain tumors in infants have different clinical presentations, anatomical distribution, histopathological diagnosis, and clinical prognosis compared with older children.Materials and Methods:A retrospective analysis was done in patients <12 months old who were operated on for primary brain tumor in Children's Hospital Medical Center since 2008 to 2014.Results:Thirty-one infants, 20 males and 11 females, with the mean age of 7.13 months (0.5–12) were enrolled. There were 16 supratentorial and 15 infratentorial tumors. The presenting symptoms included increased head circumference (16); bulge fontanel (15); vomiting (15); developmental regression (11); sunset eye (7); seizure (4); loss of consciousness (4); irritability (3); nystagmus (2); visual loss (2); hemiparesis (2); torticollis (2); VI palsy (3); VII, IX, X nerve palsy (each 2); and ptosis (1). Gross total and subtotal resection were performed in 19 and 11 cases, respectively. Fourteen patients needed external ventricular drainage in the perioperative period, from whom four infants required a ventriculoperitoneal shunt. One patient underwent ventriculoperitoneal shunting without tumor resection. The most common histological diagnoses were primitive neuroectodermal tumor (7), followed by anaplastic ependymoma (6) and grade II ependymoma. The rate of 30-day mortality was 19.3%. Eighteen patients are now well-controlled with or without adjuvant therapy (overall survival; 58%), from whom 13 cases are tumor free (disease free survival; 41.9%), 3 cases have residual masses with fixed or decreased size (progression-free survival; 9.6%), and 2 cases are still on chemotherapy.Conclusion:Brain tumors in infants should be treated with surgical resection, followed by chemotherapy when necessary.

Anaplastic ependymoma: A rare brain tumor in a neonate

A term male baby weighing 2.7 kg was brought to emergency with a history of increasing head size. Magnetic resonance imaging of the brain revealed enhancing hemorrhagic lesion with areas of necrosis involving septum pellucidum, predominantly in right frontal horn extending into 3 rd ventricle with obstructive hydrocephalus. Tumor was decompressed and biopsy of the tumor revealed anaplastic ependymoma.

MS-09 * PROGNOSTIC IMPLICATIONS OF HISTOLOGICAL CLEAR CELLS IN HIGH GRADE INTRACRANIAL EPENDYMAL TUMORS: A RETROSPECTIVE ANALYSIS FROM A TERTIARY CARE HOSPITAL IN PAKISTAN

Clear Cell variant in Ependymal tumors is rare. We aim to compare the features & clinical outcomes of Clear Cell variant with the Classic pathology of high grade intracranial Ependymal tumors in Pakistan. A retrospective cohort study conducted at the Department of Neurosurgery, Aga Khan University. The medical record files from 2003 - 2013 were reviewed, MRI/C.T scans and Histopathological slides of WHO grade III Ependymal tumors were reviewed. Patients lost to follow-up were contacted. Analysis was done on SPSS 20.There were 10 cases of clear cell variant and 23 cases of classic Anaplastic Ependymoma. The median age of Clear Cell variant was 52 years (range 24years-72 years),whereas of Anaplastic Ependymoma was 37 years (range 3 months to 65 years). Symptoms included Headache 66% in CCE and 63% in AE, Seizures 30% in CCE and 22% in AE, and raised ICP in 30% in CCE and 54% of AE. CCE was Supratentorial in 70% cases, intracranial Anaplastic Ependymoma was supratentorial in 58% of cases. Gross Total Resection was achieved in 55% cases in CCE and 26% cases in AE. Subtotal resection was done in 45% cases in CCE and 65% in AE. Radiotherapy was given in 60% patients in CCE and in 50% in AE. Recurrence was there in 80% cases of CCE and 55% in AE. Repeat Surgery was done in 30% cases of CCE and 34% cases of AE. Median Progression free survival was 8 months(range 3-28 months), and Overall survival was 10 months(range 3-41 months) in CCE. Median Progression free survival was 4 months (range 0.5-53 months), Overall survival was 14 months (range 1.5- 36 months) in AE. The median Progression free survival was better in Clear Cell variant than Anaplastic Ependymoma, this could be explained by a higher Gross total resection in CCE, whereas the median Overall survival was worse in Clear Cell variant group.

AT-47 * PHASE I TRIAL OF INTRATHECAL TRASTUZUMAB IN HER2 POSITIVE LEPTOMENINGEAL METASTASES

INTRODUCTION: Trastuzimab is a humanized monoclonal antibody against Her2 whose limitation is central nervous system penetration that often leads to brain and leptomeningeal metastases (LM) in the setting to controlled systemic HER2 positive breast cancer. We performed a phase I clinical trial of intrathecal (IT) trastuzumab in patients with HER2 positive breast cancer and LM. METHODS: IRB consented patients were treated at defined dose levels; protocol was modified to accelerate dose escalation and increase IT dosage. Dose levels of IT treatment 10 mg, 20 mg, 40 mg, 60 mg and 80 mg were examined. Treatment was given twice a week x4 weeks, then once a week x4 weeks then every other week until progressive disease. MRI was done at 4 week intervals x2 then every 8 weeks. CSF was assessed every other week x2 then every 4 weeks. RESULTS: 13 women with HER2 positive breast cancer, 1 man with a glioblastoma, and one woman with anaplastic ependymoma were enrolled with a median age of 55 (42-67) and median KPS of 80 (60-90). Three patients were treated at the 10mg dose level, three at 20mg, one at 40mg, one at 60mg and 7 at 80mg. At the 80 mg dose level a patient was added as one patient was removed before complete evaluation and another patient had a grade 4 DLT of arachnoiditis. One patient had the Ommaya reservoir removed for infection unrelated to treatment. Data on CSF levels shows therapeutic levels in the patients treated with 10 mg, 20 mg and 40 mg; data analysis on CSF at 60 and 80 mg is pending. CONCLUSION: IT Trastuzumab is well tolerated up to 80 mg IT. Complete CSF PK data will be presented. A phase II study is underway at the 80 mg dose.

PT-10 * THE ROLE OF SURGERY IN PEDIATRIC BRAIN TUMORS IN POSTERIOR FOSSA

INTRODUCTION: Intracranial tumors are the most common solid tumors in children. The infratentorial compartment will be the primary site for 60 - 70% of these tumors. Recent advances in the categorization of childhood brain tumors have improved risk-based treatment planning. The purpose of this study was to provide a review of the treatment of pediatric brain tumors in posterior fossa with emphasis on the role of surgery in the hierarchy of treatment option. MATERIALS AND METHODS: Twelve children ranging in the age from 7 months to 14 years were enrolled in this study. They were divided into 3 groups according to the following criteria; group I: tumors that currently have promising standard therapy; group II: tumors that currently have no or few promising standard therapy; group III: pathologically benign tumors. RESULTS: Four children with medulloblastoma were categorized into group I and all survived. Group II was constituted by many tumors, including AT/RT, GBM, anaplastic ependymoma, and ependymoma. The prognosis in group II was dismal. Two children with astrocytoma and oligodendroglial gliomatosis were categorized into group III and all survived. CONCLUSIONS: Adjuvant therapies, including radiotherapy and chemotherapy were effective in group I and III, therefore, tumor resection must be performed to avoid neurological sequelae and late effects. In group II, neurosurgery plays an important role for improving survival rate. Since each tumor has a different therapeutic schema and purpose of surgery, therefore, must be different, neurosurgeon should perform surgery with deep consideration in terms of the therapeutic history of each tumor.

CN-09 * POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME AND PRIMARY BRAIN TUMORS

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a neurotoxic encephalopathic state associated with reversible cerebral vasogenic edema. It is an increasingly recognized occurrence in the oncology population. However, it is very uncommon in patients with primary brain tumors (PBT). The aim of this study is to analyze the clinical manifestations, radiological features and report clinical outcomes of PRES in PBT patients. METHODS: In this retrospective review, we identified 4 patients with PBTs who developed PRES at MDACC between 2012 and 2014. Clinical and radiographic data were abstracted from their records. In addition, we also solicited 2 cases from the literature. RESULTS: The median age at diagnosis of PRES was 47 years (range 5-62), the male:female ratio was 1:5 and occurred in patients with glioblastoma (N = 3), diffuse intrinsic pontine glioma (N = 1), anaplastic ependymoma (N = 1) and atypical meningioma (N = 1). The two cases from literature review had received bevacizumab, and only one case received chemotherapy (cisplatin/etoposide/temozolomide) before the symptoms onset. Clinical presentation included seizures (N = 3), altered mental status (N = 3), headache (N = 2) and focal neurologic deficits (N = 2). All of the patients presented with elevated blood pressure. Three patients had atypical imaging findings, one of them also developed infarctions in those areas. Three of our MDACC patients recovered completely in 3 to 4 weeks after the symptoms onset. One patient died due to active cancer and several comorbidities including PRES. CONCLUSIONS: HTN seems to be the most important co-existent risk factor for development of PRES. The clinical and radiological course of PRES in PBT patients did not vary from the classical descriptions of PRES found in other causes. Resolution of PRES was an independent process even to that of tumor progression. PRES distribution did not correlate with the brain tumor location. Delay in diagnosis can result in permanent residual deficits.

CN-03 * LONG-TERM FOLLOW-UP OF ENDOCRINE FUNCTION AMONG YOUNG CHILDREN WITH NEWLY-DIAGNOSED MALIGNANT CENTRAL NERVOUS SYSTEM (CNS) TUMORS TREATED WITH IRRADIATION-AVOIDING REGIMENS: THE CHILDREN'S HOSPITAL LOS ANGELES (CHLA) EXPERIENCE

BACKGROUND: The adverse effects of radiation therapy on endocrine function among pediatric brain tumor patients have been well-documented. Brief (less than 5 months) intensive induction chemotherapy followed by marrow-ablative chemotherapy with autologous hematopoietic cell rescue (AuHCR) and avoidance of CNS irradiation has demonstrated efficacy in the treatment of very young children (less than 6 years of age) with malignant CNS tumors. This study assessed the long-term growth and endocrine effects of young children following chemotherapy-only treatment regimens. METHODS: A retrospective chart review was performed on 99 patients less than 6 years of age with newly-diagnosed malignant brain tumors between May 1991 and October 2010 treated with irradiation-avoiding strategies at CHLA. Thirty patients survived relapse-free post-AuHCR without cranial irradiation for a mean of 8.1 years (range 3.0–22.25 years); one patient expired of a TP53-related adrenocortical carcinoma. The patient cohort consisted of 18 males and 12 females with a mean age at AuHCR of 2.5 years (range: 0.8 to 5.1 years). Tumor pathologies included 20 medulloblastomas, 6 choroid plexus carcinomas, 3 CNS PNET and 1 anaplastic ependymoma. RESULTS: All patients had documented normal age-related free T4, TSH, IGFBP3, prolactin, testosterone and estradiol levels. IGF1 age-related levels were abnormal in one child. FSH and LH levels among females, and cortisol levels, were normal in 93%, 97% and 97%, respectively. Growth charts demonstrated age-associated growth within 2 standard deviations of the mean in 67% patients. Of 10 patients (33%) with short stature, 6 had proportional diminutions in both height and weight. CONCLUSIONS: These findings demonstrate that the use of relatively brief, intensive chemotherapy regimens including marrow-ablative chemotherapy with AuHCR, results in less endocrine and growth abnormalities than treatment schemes utilizing CNS irradiation. However, the documented adverse impact upon physical growth in a proportion of survivors needs to be evaluated further.

ED-29 * THE INCIDENCE OF ADULT AND PEDIATRIC INTRACRANIAL EPENDYMOMAS WITHIN THE SCOTT AND WHITE INTEGRATED HEALTHCARE SYSTEM

INTRODUCTION: Ependymomas are characterized by their higher incidence in children and by their rarity, especially among adult groups. Indeed, it has been difficult to reach a consensus on the most effective treatments. The purpose of this study was to determine how the outcome of adult and pediatric ependymomas is affected by various factors including age, ethnicity, tumor grade, and tumor type. METHODS: We conducted a retrospective analysis of ependymoma patients within the Scott and White brain tumor registry from 1976-2011. Data was analyzed regarding age, ethnicity, treatment interval, geographic distribution, tumor grade (Grade I - anaplastic), and tumor type (ependymoma and subependymoma). Analyses included univariate and multivariate methods. RESULTS: This study includes 28 patients within the Scott and White brain tumor registry from 1976-2011. All of the patients were subject to the same analyses. Of those 28 patients, 5 had subependymomas. 0f the 23 ependymoma cases, 2 were anaplastic. The remaining were either Grade I or Grade II. 19 of the 28 patients, or 68%, were of white ethnicity, the remainder of black, Hispanic, or other/unknown ethnicity. Additionally, 40% of the subependymoma patients were of white ethnicity. Survival rates were found to be in concordance with the current standards: 40-65% for pediatric cases and 55-90% for adult cases. We observed no death among the subependymoma group and thus a concurrent increase in the median survival of this group. The median survival time of the anaplastic ependymoma group was more difficult to quantify due to a limited number of cases and because the patients of this group are still alive. CONCLUSION: This study suggests that age is intimately involved with the development of ependymomas and subependymomas. White/Caucasian ethnicity also seems to correlate with the growth of subependymomas and ependymomas moreso than is seen in the other ethnicities of this study.