Anaplastic Ependymoma Research Articles

Supratentorial Extraventricular Anaplastic Ependymoma Presenting with Repeated Intratumoral Hemorrhage

Supratentorial extraventricular anaplastic ependymomas are extremely rare. We report the case of a 23-year-old male with a supratentorial extraventricular anaplastic ependymoma that presented with repeated intratumoral hemorrhage. The patient was diagnosed with an intracerebral hematoma in the left occipital lobe and underwent operation. The hematoma did not reveal tumor cells, but a new tumor grew in the same location 5 years later. Magnetic resonance imaging showed a tumor with intratumoral hemorrhage. The patient underwent the tumor resection. Intraoperative findings showed that the tumor had no continuity with the ventricle. Histopathological examinations confirmed an anaplastic ependymoma. The spinal evaluation was unremarkable, and radiotherapy was administered to the left occipital lobe. Four years later, the tumor recurred at the cervicomedullary junction and T8-T9 levels. This case demonstrates that anaplastic ependymomas should be included in the differential diagnoses of supratentorial extraventricular tumors presenting with repeated intratumoral hemorrhage.

Gliosarcoma Arising in Anaplastic Ependymoma with Heterologous Sarcomatous Component: A Rare Phenomenon

Gliosarcoma Arising in Anaplastic Ependymoma with Heterologous Sarcomatous Component: A Rare Phenomenon Gliosarcoma is a highly aggressive tumor and a variant of glioblastoma multiforme. It mainly occurs in the age group of 40-60 years and has a male preponderance. It is however, rare in younger individuals. First described by Stroebe in 1895, this biphasic tumor is comprised of glial component and sarcomatous component. The glial component is usually of astrocytic nature whereas oligodendroglial and ependymal origin is very uncommon.

Extraneural Soft Tissue Metastasis in a Child with Anaplastic Ependymoma

Extraneural Soft Tissue Metastasis in a Child with Anaplastic Ependymoma We present the case of a 5 year old boy who presented to us with complaints of worsening headaches, vomiting, drowsiness and weight loss. He also had difficulty maintaining balance and fell down frequently. Examination revealed elevated blood pressure, sluggish pupils and bilateral grade 1 papilledema. Imaging of the brain showed a mass in the fourth ventricle causing non-communicating hydrocephalus. The mass was excised and histopathology showed features of anaplastic ependymoma.

A Phase II Study of Antineoplastons A10 and AS2-1 in Children with Recurrent, Refractory or Progressive Primary Brain Tumors—Final Report (Protocol BT-22)

Primary malignant brain tumors are a leading cause of cancer-related death in children. This Phase II study evaluated the efficacy and safety of Antineoplastons A10 and AS2-1 (ANP) in children who developed progression during standard treatment. A total of 43 children were recruited to the study, but only 41 met eligibility criteria. There were twelve cases of glioblastoma multiforme (GBM), eight anaplastic astrocytomas (AA), twelve diffuse intrinsic pontine gliomas (DIPG), three supertentorial primitive neuroectodermal tumors (sPNET), three cases of medulloblastoma and one case each of anaplastic ependymoma (AE), atypical teratoid rhabdoid tumor (AT/RT), and disseminated pilocytic astrocytoma (PAD). ANP was administered intravenously daily every four hours (median dose of A10 8.74 g/kg/d and AS2-1 0.35 g/kg/d), until objective response (OR) was documented, and then a further eight months. All enrolled patients were included in safety, but only eligible patients in the efficacy evaluation. A total of 12.2% of patients obtained OR; 2.4% complete response (CR) and 9.8% partial response (PR). Stable disease (SD) was determined in 17.1% and progressive disease (PD) in 43.9% of cases. There were 26.8% of nonevaluable (NE) cases due to premature discontinuation. Out of five OR cases, four patients were diagnosed with recurrent DIPG and one with recurrent AA. Median progression-free survival (PFS) was 2.5 months. Median overall survival was 4.8 months. OS at 6 months was 46.3%, one year was 12.2%, and 4.8% at two, five, and ten years. The longest survivor is a patient diagnosed with DIPG and gliosarcoma who remains alive more than 15 years. A group of eleven patients reported grade 3 and 4 toxicity including hypernatremia in eight cases, somnolence in two cases, and hypokalemia in one case. There were no chronic toxicities, and the quality of life was very good. The largest group of patients were represented by DIPG, GBM, and AA. The best results were obtained in the DIPG and AA groups. In the DIPG group, CR was in 8.3%, PR was 25%, median PFS was 4.8 months, median OS was 6.1 months, and OS at 6 months was 58.3%, at one year 25%, and 8.3% at two, five, and ten years. In the AA group, PR was 12.5%, median PFS was 3.7 months, median OS was 4.7 months, and OS at 6 months was 37.5%, and 12.5%, at one, two, five, and ten years. In conclusion, antineoplastons showed efficacy and acceptable toxicity in patients with recurrent, refractory or progressive primary brain tumors.

EP-1065: Reirradiation against recurrent anaplastic ependymoma with stereotactic radiotherapy using CyberKnife

EP-1065: Reirradiation against recurrent anaplastic ependymoma with stereotactic radiotherapy using CyberKnife

Supratentorial cortical ependymoma: Case series and review of the literature

Supratentorial cortical ependymoma (CE), a rare type of ependymoma, is located in the superficial cortex. We reported 11 patients (six female and five male) with CE. The age of the patients ranged from 2 to 63 years old with a median age of 47 years at the time of diagnosis. On MRI, enhancement was noted in all cases with solid appearance in six cases, and solid and cystic appearance in five cases. The frontal and parietal regions were the most common locations for CE. On histology, two were low-grade (WHO grade II) and nine were WHO grade III anaplastic ependymomas. Some tumors exhibited clear cell, spindle (tanycytic) and giant cell morphologies, as well as the classic ependymoma morphology. Dura-based tumor nodules and even tumor dissemination along the dura can be seen in CEs. Low grade CEs have a higher likelihood to present with seizures, a lower likelihood to cause brain edema, tumor recurrence and lower mortality than anaplastic ependymomas. While difficult, anaplastic CEs may be distinguished from glioblastoma by a clear interface between tumor and adjacent brain tissue, relative uniformity of tumor cell nuclei and immunopositivity for epithelial membrane antigen and/or CD99. As is the case for ependymomas in general, gross total resection is still the treatment of choice for CEs.

Spinal Anaplastic Ependymoma with Rapid Intracranial Ventricular Seeding-Case Report and Review of Literature

Ependymomas are slow-growing tumors in the central nervous system. In spinal cord, ependymoma is the most common neuroepithelial tumor (15% of all spinal cord tumors). Ependymoma of the spinal cord with retrograde intracranial metastasis is rare. This study reported a 31-year-old female with thoracic anaplastic ependymoma (WHO grade III) who had received surgical intervention for removal of thoracic ependymoma twice at an interval of seven months due to local recurrence. After the second operation, rapid progression of seeding from spinal cord to brain developed in three months. Other case reports of spinal ependymoma with intracranial metastasis were reviewed and seven other cases with interval of local recurrence, location of intracranial metastasis, outcome, and pathology were also collected.

Fourth ventricular ependymoma with a distant intraventricular metastasis: Report of a rare case

Ependymoma is one of the uncommon tumors of the central nervous system (CNS) in the adult age group. These tumors have a distinct propensity for metastasis, both within and outside the CNS. However, dissemination at the time of first presentation and retrograde dissemination of the tumor is rare. We report the case of a patient with fourth ventricular anaplastic ependymoma who presented with left lateral ventricular metastasis which was anatomically different from the primary tumor. We describe the clinic-pathological detail of the patient and discuss the probable pathophysiological basis for this rare presentation and its significance in management of the patient.

Histologically defined central nervous system primitive neuro-ectodermal tumours (CNS-PNETs) display heterogeneous DNA methylation profiles and show relationships to other paediatric brain tumour types

Histologically defined central nervous system primitive neuro-ectodermal tumours (CNS-PNETs) display heterogeneous DNA methylation profiles and show relationships to other paediatric brain tumour types

Study of chromosome 9q gain, Notch pathway regulators and Tenascin-C in ependymomas

Ependymomas are relatively uncommon tumours of the central nervous system which arise from the ependymal lining of the ventricles and spinal canal. The molecular changes leading to ependymal oncogenesis are not completely understood. We examined chromosome 9q33-34 locus for gain, potential oncogenes at this locus (Notch-1 and Tenascin-C) and Notch pathway target genes (Hes-1, Hey-2 & C-myc) in ependymomas by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC), respectively, to assess if they have any correlation with clinical characteristics. We analyzed 50 cases of ependymomas by FISH for 9q gain and by IHC for Notch-1 and its target gene proteins (Hes-1, Hey-2 and C-myc) expression. We also performed IHC for Tenascin-C to rule out any correlation with aggressiveness/grade of tumour. FISH study revealed significant chromosome 9q gain in ependymomas of adult onset (age > 18 years) and spinal cord origin. Notch-1 showed significantly more frequent immunohistochemical expression in supratentorial and anaplastic ependymomas. Tenascin-C (TN-C) expression was significant in intracranial, childhood (age ≤ 18 years) and anaplastic ependymomas. Of the three Notch pathway target gene proteins (Hes-1, Hey-2 and C-myc), Hes-1 and C-myc expression showed significant correlation with anaplastic and adult onset ependymomas, respectively. Genetic alterations are independent prognostic markers in ependymomas. A clinicopathological correlation with various molecular signatures may be helpful in the development of new therapeutic targets.

Cisplatin and Temozolomide Combination in the Treatment of Supratentorial Anaplastic Ependymoma

Anaplastic ependymomas are rare tumors in adult patients. Maximal safe resection and use of radiation therapy are standard treatment approaches in patients with anaplastic ependymoma. Recurrent anaplastic ependymomas are treated by reoperation when the tumors are surgically accessible, by radiotherapy if not previously administered and by salvage chemotherapy. However, the role of chemotherapy is still unclear. A few retrospective studies showed interesting results with platinum-based regimens, while the administration of temozolomide alone demonstrated conflicting results. We present, for the first time, the case of a patient with anaplastic ependymoma refractory to platinum-based chemotherapy and temozolomide only, but showing a prolonged reduction of the lesion after receiving combination chemotherapy with cisplatin and temozolomide. A brief review of the literature on the treatment of anaplastic ependymoma follows.

Prognostic relevance of global histone 3 lysine 9 acetylation in ependymal tumors

Ependymal tumors are highly variable in clinical and molecular behavior and affect both children and adults. Regarding the paucity of appropriate experimental models, the underlying molecular mechanisms of their behavioral variability are poorly understood. Considering the increasing evidence of epigenetic changes in various tumors, in addition to the preclinical success of epigenetic-based therapeutics in tumors of the CNS, epigenetic study of ependymal tumors is warranted. Using immunohistochemistry, the authors investigated the patterns of global acetylation of lysine position 9 of histone 3 (H3K9Ac), an epigenetic marker of active gene transcription, in 85 ependymal tumors with various WHO grades and clinicopathological characteristics. Most of the nuclei in all ependymal tumors were H3K9Ac negative (mean ± SD 65.9% ± 26.5 vs 34.1% ± 26.5% positive, p < 0.0001). Subependymomas had more H3K9Ac-positive nuclei (67.2% ± 10.2%) than myxopapillary ependymomas, ependymomas, and anaplastic ependymomas (p < 0.05). Additionally, intracranial parenchymal tumors had significantly fewer H3K9Ac-positive nuclei (13.1% ± 21.9%) than tumors of other CNS localizations (p < 0.001), and supratentorial ventricular tumors had the highest number of H3K9Ac-positive nuclei (66.4% ± 11.8%) among CNS ependymal tumors (p < 0.0001). The H3K9Ac pattern in ependymal tumors also revealed prognostic significance such that tumors with less than 20% acetylated nuclei had a higher probability of recurrence than tumors with 20% or more acetylated nuclei (p = 0.0327), and recurrent tumors had significantly fewer H3K9Ac-positive nuclei than primary ones (16% ± 22.5% vs. 38% ± 25.8%; p < 0.0001). However, the effect of tumor location on survival of patients was nonsignificant in a multivariate survival analysis, and H3K9 acetylation levels of tumors contributed independently to the survival of patients. In addition, ependymal tumors with more than or equal to 20% H3K9 acetylated cells had lower MIB-1 expression than those with less than 20% H3K9 acetylated cells (p < 0.01). Global H3K9Ac contributes independently to the prognosis of patients with ependymal tumors such that tumors with lower H3K9Ac values have a higher probability of recurrence and are more proliferative. Additionally, subependymomas have a higher H3K9Ac profile than other ependymal tumor subclasses, underlining their benign clinical behavior.

Досвід використання стереотаксичної техніки при хірургічному лікуванні кістозних вогнищевих утворень головного мозку

Вступ. Внутрішньомозкові кістозні вогнищеві утворення — ідеальна мішень для стереотаксичних втручань. Стереотаксична техніка при пункції та біопсії кістозних утворень головного мозку витісняє традиційні підходи до лікування цієї складної патології.Матеріали і методи. Матеріал дослідження — 24 хворі з кістозними вогнищевими утвореннями супратенторіальної локалізації, оперовані у клініці з 2009 по 2013 рік. Стереотаксичний супровід із використанням навігаційної системи Stealth Station® Treon® Plus фірми Medtroniс (США) та стереотаксичної системи Zamorano — Dujovny. Результати. Було проведено 20 втручань із використанням безрамної стереотаксичної техніки та 4 втручання з використанням рамного стереотаксису. Хворі були розподілені за діагнозами: абсцес головного мозку — 10, краніофарингеома — 5, анапластична астроцитома — 3, метастаз — 2, гематома — 2, анапластична епендимома — 1, астроцитома 2 ст. зл. — 1.Висновки. Лікування вогнищевих утворень головного мозку з використанням стереотаксичної техніки — сучасний, безпечний та ефективний вид хірургічного втручання.

P 189. The extent of perifocal edema in function associated motor fibers correlates to the primary motor deficit in patients with M1-adjacent intracerebral tumors. A volumetric analysis of presurgically acquired data based on MRI, FET-PET and navigated TMS on primary motor functions

Question Many patients with brain tumors adjacent to the primary motor (M1) region initially present with transient or permanent motor deficits. Factors like compression by tumor mass, tumor infiltration, as well as the extent of the perifocal edema might contribute to the motor deficit. In order to assess the relevance of these factors, we analyzed the spatial relationship between M1 cortical representation assessed with navigated transcranial magnetic stimulation (nTMS) and the anatomical and metabolic extension of tumors in the M1 region in patients prior to surgery. Methods To date, 21 patients with M1-adjacent tumors (glioblastoma ( n = 14), anaplastic astrocytoma ( n = 1), carcinoma metastasis ( n = 4), anaplastic ependymoma ( n = 1), lymphoma ( n = 1)) underwent an anatomical MRI protocol including a T2-weighted sequence, a gadolinium-contrast-enhanced sequence (GCE) and diffused tensor imaging as well as 18F-fluoroethyl-L-tyrosine (FET) PET for presurgical planning. Cortical M1 representations for the hand, foot and tongue were assessed by nTMS within 7 days. “Functional” fiber tracking of the corticospinal tract (CST) consisted of the following processing steps: (1) setting the seed points defined by the coordinate revealing the highest motor evoked potential (MEP) when stimulated by nTMS at 110% of the resting motor threshold and the surrounding 5 mm, according to the registration and E-field calculation mismatch and (2) a seed volume at the midbrain level. Total volumes and intersection volumes of the CST and the anatomically defined areas were expressed in cm 3 ±standard deviation (SD). Results 15 out of the 21 patients had a primary motor deficit recorded in either the upper or lower limb, the facial muscles or initially presented with a hemiparesis, 6 patients had not developed any deficit prior to or at admission to surgery. Neither the GCE ( p = .96) nor the FET ( p = .45) tumor volume statistically differed between the group of patients with a motor deficit (GCE: 19.7 ± 17.2 cm 3 ; FET: 9.6 ± 5.3 cm 3 , n = 15) compared to one without a motor deficit (GCE: 12.1 ± 16.8 cm 3 ; 6.4 ± 6.5 cm 3 , n = 6). The mean perifocal edema volume based on the T2-weighted MRI data was slightly greater in the motor deficit group (64.2 ± 38.1 cm 3 ) than in the group of patients without any motor deficit (43.4 ± 28.6 cm 3 ) but did again not pass the statistical threshold ( p = .37). However, the mean relative volume of functional fibers intersected by the T2-weighted edema volume was statistically greater in the primary motor deficit group (16.1 ± 13.1%) than in the one without motor deficits (0.1 ± 0.0%). By contrast, the mean relative volume of cortical M1 representation intersected by the edematous area did not statistically differ between the two groups ( p = .09). Nor the mean relative volume of functional fibers or functional motor cortex intersected by GCE or PET tumor volumes were statistically different between the two groups. Likewise, neither the mean absolute volume of supratentorial functional fibers nor of the cortical M1 representation volumes differed between the two groups. Conclusion The study implicates that neither direct tumor infiltration of the M1 region or the CST nor the tumor volume nor the extension of perifocal edema in total may be the main causes for the primary motor deficit of brain tumor patients at initial presentation. In contrast, the extent of the perifocal edema affecting CST fibers seems to be responsible for motor deficits prior to surgery.

A phase I clinical trial of veliparib and temozolomide in children with recurrent central nervous system tumors: A Pediatric Brain Tumor Consortium report.

2036 Background: A phase I trial of veliparib (ABT-888), an oral poly(ADP-ribose) polymerase (PARP) inhibitor, and temozolomide (TMZ) was conducted in children with recurrent brain tumors to: 1) estimate the maximum tolerated doses (MTD) or recommended phase II doses (RP2D) of veliparib and TMZ using the Continual Reassessment Method; 2) describe the toxicities of this regimen; and 3) evaluate plasma pharmacokinetics (PK) and peripheral blood mononuclear cell (PBMC) PARP inhibition after veliparib treatment. Methods: TMZ was given once daily and veliparib twice daily for 5 days, every 28 days. Five veliparib/TMZ dose levels were studied: 20/180; 15/180; 15/150; 20/135; and 25/135 mg/m2/dose, respectively. Baseline and serial veliparib PK samples were obtained on days 1 and 4. PBMC poly(ADP-ribose) (PAR) levels were also measured using an ELISA assay. A total of 12 subjects were enrolled at the RP2D. Results: Thirty-one patients (29 evaluable) with a median age of 7.0 years (range 1.3-19.8) were enrolled. Dose-limiting toxicities (DLT) included grade 4 neutropenia and thrombocytopenia at the 20/180 and 15/180 mg/m2/dose levels. Based on the toxicity profile, PKs and PBMC PAR results, the RP2D were veliparib, 25 mg/m2 BID, and TMZ, 135 mg/m2/day, for 5 days every 28 days. No objective responses were observed, although 4 subjects had SD &gt; 6 months duration, including one patient each with glioblastoma multiforme, anaplastic ependymoma, pilocytic astrocytoma, and optic pathway glioma. At the veliparib RP2D, the PK parameters included: Cmax, 1.2 ± 0.7 µM; AUC0-12 hr, 1.53 ± 0.61 µg•hr/mL; and Cl/F, 173 ± ml/min/m2. PARP inhibition was observed in PBMC but did not correlate with veliparib dose levels. Conclusions: The combination of veliparib and TMZ was well tolerated in children with recurrent CNS tumors. Veliparib PK parameters at RP2D are similar to those in adults. PBMC PARP inhibition did not correlate with veliparib dose levels, perhaps due to the smaller number of patients at each dose level and the technical limitations of specimen collection/processing and the ELISA assay. A phase II trial of veliparib/TMZ in children with recurrent primary brain tumors is planned. Clinical trial information: NCT00946335.

Chemopredictive assay for patients with primary brain tumors.

2089 Background: Cancer stem-like cells (CSLCs) in primary brain tumors can resist certain chemotherapies, thereby causing relapse of the disease. Thus, development of a test that identifies the most effective chemotherapy management offers great promise for personalized anticancer treatments. Methods: We have developed an ex vivo ChemoID assay designed to predict the sensitivity and resistance of CSLCs and bulk of tumor cells of a given patient's solid tumor to a variety of chemotherapy agents by measuring the percentage of cell death. In a retrospective study of five patients with malignancies of the central nervous system, we assessed the correlation between the results of the ChemoID assay and clinical response. Two anaplastic WHO grade-III ependymomas, two IDH-1 negative WHO grade 4 glioblastomas, and one medulloblastoma were tested. Tumors were classified as responsive (50-100% cell kill), intermediately responsive (30-50% cell kill), and nonresponsive (0-30% cell kill) to chemotherapy. Treatment selection was blinded to assay results. MRI and CT scan determined response to therapy. Results: The ChemoID assay performed on the tumor bulk produced a correct prediction in 4 out of 5 cases (p = 0.4, Fisher's Exact Test; PPV = 75%, NPV = 100%) when compared to the drugs received. The same assay performed on the CSLCs produced a correct prediction in all 5 cases (p = 0.1, Fisher's Exact Test; PPV=NPV=100%). Conclusions: An assay such as ChemoID that measures cell death of CSLCs and bulk of tumor cells appears to be beneficial in selecting specific standard chemotherapy agents ex vivo for patients with malignancies of the central nervous system.

Outcomes in treatment for primary spinal anaplastic ependymomas: a retrospective series of 20 patients

Little is known regarding the anaplastic variant of primary ependymomas that involve the spinal cord. The aim of this study was to evaluate the clinical characteristics and treatment outcomes of primary spinal anaplastic ependymomas (PSAEs). Medical records were reviewed in 20 patients with pathologically proven PSAEs who underwent surgical treatment at the Department of Neurosurgery in Huashan Hospital between 1999 and 2008. This series included 7 women and 13 men between the ages of 2 and 67 years (mean 31.9 years). The mean preoperative course was 9.3 months (range 20 days to 48 months). The most common PSAE locations were the cervical and thoracic spinal cords. The most common presenting symptom was weakness, followed by numbness, bowel or bladder dysfunction, and pain. Gross-total resection (GTR) was achieved in 17 patients, and a subtotal removal was performed in 3 patients. Nine patients received radiation therapy and/or chemotherapy. The mean follow-up duration was 83.5 months. Functional assessment of the 10 patients available at the latest follow-up evaluation showed that 2 had worsened and 8 remained unchanged from their preoperative status. There were 2 local recurrences and 1 lung metastasis. Patients with PSAEs presented with a much shorter preoperative course than patients with Grade II ependymomas in previous studies. Patients with tumors that involved the cervical spinal cord experienced a worse outcome. Surgical removal of PSAEs, with the goal of GTR, is beneficial to patients. The role of radiation therapy and chemotherapy in PSAEs remains to be determined in further studies.

Descriptive epidemiology of ependymal tumours in the United States

Background:Ependymomas are rare primary gliomas that commonly affect both children and adults, but unique as survival is worse in children.Methods:Data on brain and central nervous system primary malignant and non-malignant ependymal tumours from the Central Brain Tumor Registry of the United States analytic data set and primary malignant ependymal tumours from the SEER 13 registries research data file were used to evaluate incidence and survival, respectively.Results:The 2004–2009 average annual age-adjusted incidence rate of ependymal tumours was 0.41/100 000. Spinal cord/cauda equina was the primary site at diagnosis for 50–60% of ependymal tumours in adult age groups in contrast to about 20% in children and adolescents. Ependymoma was the most frequent histology in all age groups; however, anaplastic ependymoma comprised about 30% in cases 0–19 years of age compared with about 3–5% in adult age groups. Overall, relative survival was favourable with rates at ∼85% and 75% at 3 and 10 years post diagnosis, respectively. However, children and adolescents, the oldest adult age group, cases diagnosed with anaplastic ependymoma and/or tumour location in a brain site had lowest survival rates.Conclusion:Paediatric cases had worse outcomes compared with adults for numerous reasons including having a higher percentage of anaplastic ependymomas and greater percentage of cases of intracranial disease.

Local recurrence of primary central nervous system lymphoma due to tumor seeding

Local recurrence of primary central nervous system lymphoma due to tumor seeding

Abstract LB-82: Chromosome 1q gain as genetic marker for risk stratification of pediatric ependymoma patients - validation as an adverse prognostic marker in the German multicenter HIT2000 trial.

Abstract In contrast to histopathological grading which varied in respect to its prognostic value between different clinical trials, extent of resection was found to be consistently associated to the clinical outcome. In retrospective series, gain of genetic material of chromosome arm 1q was identified to predict worse outcome. This marker was mainly assessed by FISH analysis which typically showed failure rates of 15-20 % in archival material. To validate this marker in a homogenously treated patient cohort, we analysed chromosome 1qin 209 consecutive cases enrolled into the multicenter trial HIT2000 (postoperative chemotherapy and irradiation, in a sequence depending on age and extent of resection) in which formalin-fixed, paraffin embedded material was available for DNA extraction. By using multiplex ligation-dependent probe amplification (MLPA) for 5 markers located on chromosome 1q and control markers, we were able to analyse 206/209 samples (&amp;gt; 98 %) and found a gain of chromosome 1q in 35 cases (17 %). 135/206 ependymomas were located in the infratentorial region. 35 cases were diagnosed as WHO grade II ependymoma, 171 as anaplastic ependymoma (WHO grade III). Interestingly, only 2 of the 35 WHO grade II ependymomas had 1q gain (5.7%). At a median follow-up of 3.9 years for survivors, patients with tumors showing 1q gain had a significantly lower 4-year overall survival (OS) (±SE) of 58% +/- 9% compared to patients lacking this marker (89% +/- 3%, p=0.002). The distribution of this marker was similar when comparing patients with supra- and infratentorial tumors. Multivariable analysis demonstrated that residual tumor and infratentorial localization were independent risk factors for event-free survival, and gain of chromosome 1q for OS, respectively. In conclusion, we validated chromosomal 1q gain to be a useful independent genetic marker for risk stratification of pediatric ependymoma patients which can be evaluated by MLPA representing a robust, reliable and cost-efficient method. Citation Format: Torsten Pietsch, Evelyn Doerner, Anja zur Muehlen, Natalia Velez-Char, Monika Warmuth-Metz, Rolf-Dieter Kortmann, Katja von Hoff, Carsten Friedrich, Stefan Rutkowski, Andre O. von Bueren. Chromosome 1q gain as genetic marker for risk stratification of pediatric ependymoma patients - validation as an adverse prognostic marker in the German multicenter HIT2000 trial. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-82. doi:10.1158/1538-7445.AM2013-LB-82