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REVIEW ARTICLE
Year : 2006  |  Volume : 1  |  Issue : 1  |  Page : 5-10
 

Primer on pediatric intracranial ependymomas


Department of Neurosurgery, Himalayan Institute of Medical Sciences, Dehradun, UA, India

Correspondence Address:
K K Bansal
Department of Neurosurgery, Himalayan Institute of Medical Sciences, Dehradun, UA
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1817-1745.22940

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  Abstract 

Aims and Objectives: To review the clinical features and current understanding of the biology and management of pediatric ependymoma, critically analysing the different treatment modalities. Materials and Methods: The MEDLINE database, bibliographies of selected articles, and current English-language texts on the subject were reviewed. A Pubmed search was made with keywords pediatric, intracranial, ependymoma, surgery, chemotherapy, and radiotherapy. Most recent articles and also significant older articles having all above said words were selected and their results were compared in detail. Results: Almost all articles stress the complete or near total resection of the tumor at first surgery followed by radiotherapy in patients older than 3 years of age and chemotherapy in younger children. Conformal radiation therapy (CRT) is a technique which has promising results. Conclusion: Local tumor control is single most important prognostic factor. This is best achieved through gross total tumor resection wherever possible. Radiotherapy should be offered to all patients (>3-years age) with focused dose (CRT) to tumor bed. Chemotherapy with the current agents does not appear to hold much promise. However, it may be useful in the context of providing the surgeon with an opportunity to do further surgery on a tumor that is less vascularized.


Keywords: Pediatric, intracranial, ependymoma, surgery, chemotherapy, and radiotherapy


How to cite this article:
Bansal K K. Primer on pediatric intracranial ependymomas. J Pediatr Neurosci 2006;1:5-10

How to cite this URL:
Bansal K K. Primer on pediatric intracranial ependymomas. J Pediatr Neurosci [serial online] 2006 [cited 2017 Jul 24];1:5-10. Available from: http://www.pediatricneurosciences.com/text.asp?2006/1/1/5/22940



  Incidence and Natural History Top


Ependymomas are one of the most common primary brain tumors of children younger than 5 year of age, accounting for 10-12% of all brain tumors in the pediatric population and 2.5% of all intracranial gliomas. Ependymomas develop from the oncogenetic event that transforms cells of ependymal lineage,[1] which line the ventricles of the brain and central canal of the spinal cord. Location of these tumors typically shows preference based on age, with supratentorial and spinal compartments more often affected in adults and fourth ventricular involvement more in children. Ninety percent of these tumors occur intracranially, two thirds of which are infratentorial. The mean age at the time of diagnosis is between 3-6 years and more then one fourth of them are diagnosed at younger than 3-years.[2]

Sixty percent of supratentorial tumors may arise from lateral or third ventricle but 40% arise from extra-ventricular cerebral parenchyma even without ventricular proximity.[3],[4] There is no sex preference for ependymoma and it occurs with equal frequency in both the sexes.

Infratentorial ependymomas typically arise from one of the three specific sites in the fourth ventricle: 60% from the floor, 30% the lateral aspect and 10% from roof.[5],[6] Usually occurring sporadically, they can be associated with Neurofibromatosis Type-II. There are no known definite causative agents although there are suggestions that certain viruses may play a role. [7],[8],[9] Epidemiological studies lately have suggested geographical (common in northern India) or racial (rare in migrant ethnic Chinese) distribution in its occurrence but the extent and importance of this is presently inconclusive.

The younger the child the worse the prognosis; it is uncertain whether this is due to tumors being more malignant at an early age or delayed administration of radiation therapy or chemotherapy in younger children. [10],[11],[12] Posterior fossa tumors usually occupy and grow within the fourth ventricle but they can extend through the foramen of Magendie inferiorly, foramen of Luschka laterally and into the cerebellopontine CP angle. These tumors may spread along the CSF axis before, during or after the surgery. Ependymomas developing in the supratentorial compartment usually to be low-grade tumors and a have better prognosis.[13],[14] The 5-year progression free survival after treatment in ependymoma is ranging from 23% to 45% and the 5-year survival estimate is 50% to 60% in various major series.[10],[11], [15],[16],[17] The median time to local recurrence is within the first 2 years.[10],[11],[15],[16],[18],[19]

Clinical presentation

Age at the time of diagnosis has been considered an important prognostic factor.[10] Ependymomas of the fourth ventricle frequently produces hydrocephalus due to hindrance of the CSF outflow and initially present with general signs of increased intracranial tension.[20] Intractable paroxysmal vomiting not related to particular time of the day or posture is more pronounced and often it is the first symptom, perhaps due to their attachment with floor of the fourth ventricle. Neonates may present with macromania, lethargy and failure to thrive. Papilloedema is an indirect sign of hydrocephalus while a bulging fontanelle is a direct sign. Enlarging head circumference is seen in children those who present prior to closure of cranial sutures. Due to direct involvement of local neural structures, there may be signs of cerebellar and brainstem compression, along with long tract signs and lower cranial nerve involvement.[11] Ataxia, nystagmus and 6th nerve involvement are seen in posterior fossa tumors; less common is torticollis indicating tonsillar impaction.

Those occurring in the supratentorial compartment generally present with focal neurological deficits, seizures, and raised intracranial pressure from mass effect. Headaches are usually intermittent and may be worse in the morning. Though uncommon, CSF dissemination can occur with patients presenting with signs of meningismus or nerve root involvement.

Histopathology/biology/molecular characterization

Grossly, ependymomas are grayish-red tumors that frequently appear well circumscribed. Histologically, they are characterized by the presence of perivascular pseudo-rosettes and true ependymal rosettes (Homer-Wright). Several different subtypes have been identified that tend to occur at particular locations and ages. Classic and anaplastic ependymomas generally occur in children and young adults in the cerebral hemispheres and cerebellum, myxo-papillary ependymomas occur in the conus-medullaris of young adults and sub-ependymomas tend to arise in the fourth ventricle of the elderly.

The World Health Organization (WHO) divides ependymomas into three grades: WHO grade-I (sub-ependymoma and myxo-papillary ependymoma), WHO grade-II, which has four variants (cellular, papillary, clear and tanycytic) and grade-III (anaplastic ependymoma).[21]

The diagnosis of WHO grade-II is based on infrequent or absent mitoses, occasional non-palisading foci of necrosis and nodules with better cellularity and mitotic activity present.[21] Anaplastic ependymoma includes tumors with clearly defined ependymal differentiation showing perivascular pseudorosettes and increased cellularity, cytological atypia, and micro-vascular proliferation.

Ependymomas characteristically have homogeneous cells, infrequent mitoses and little necrosis. The nuclei of ependymal cells are oval and have dense clumps of chromatin as seen in other glial cells. Microscopic examination demonstrates a predominant glial pattern, studded with islands of cells with epithelial features, which makes the diagnosis of ependymoma. Pseudorosettes are the most common epithelial features; they appear as eosinophilic zones surrounding blood vessels. A tanycyte is an immature, bipolar, glial fibrillary acidic protein (GFAP)-positive cell that may symbolize an intermediate phase in the development of an ependymal cell. Clear cell ependymomas have the same "fried egg" appearance of Oligodendrogliomas. Papillary ependymomas may be superficially difficult to distinguish from choroid plexus papilloma but the fronds of a papillary ependymoma contain ependymal cells.

Ependymomas may spread by local invasion or CSF dissemination. Up to one fifth of the patients will show evidence of CSF spread at the time of diagnosis by positive CSF cytology or contrast enhanced MRI suggestive of metastatic spread. [22],[23],[24]

The oncogenic simian virus 40 (SV40) has been identified in a significant proportion of sporadic ependymoma specimens.[25],[26] Its large T-antigen viral protein binds to and neutralizes both p53 and retinoblastoma protein leading to disordered DNA repair mechanisms and cell-cycle regulation, respectively.[27] Rats inoculated intracerebrally with SV40 virus develop ependymomas.[28],[29]

Genetic aberrations in ependymomas include loss of chromosome 6q, 22q, and the X-chromosome and the gains of 1q or 9q. The frequency of 22q abnormality is much higher in spinal ependymomas.[30],[31] The gain of 1q seen in childhood anaplastic ependymomas appears to be associated with posterior fossa tumor.

While there is still much to discover, the molecular cell-biology of this tumor is becoming better known. Cytogenetically, i n situ hybridization studies have demonstrated several non-random chromosomal imbalances in sporadic ependymoma, the most common of which is loss of chromosome 22q.[32],[33] Though both cranial and spinal ependymomas occur in patients with NF2, the locus involved in sporadic tumors seems to be different from the NF2 gene locus as sporadic tumors harboring 22q loss occur almost exclusively in the spine. [34],[35],[36] Gain of 1q is seen frequently in ependymomas of the fourth ventricle and has been linked with a more anaplastic phenotype and may thus contain genes necessary for tumor progression.[30],[37],[38],[39] Recently, co-over-expression of certain receptor tyrosine kinases, ERBB2 and ERBB4, has been demonstrated to correlate with proliferative indices and worsened patient prognosis.[40] Although no specific tumor suppressor gene has been identified for ependymomas, CDKN2A, CDKN2B and p14ARF expression are frequently silenced by aberrant methylation.[41],[42]

Neuro imaging

Ependymomas typically appear as isodense to heterogeneously enhancing midline cerebellar or hemispheric tumors on both CT and MRI [Figure - 1]a, b. In the posterior fossa, they typically take origin on the floor of the fourth ventricle and grow to take up it completely. On non-contrast computed tomography scan the tumor is heterogeneous, seen in midline posterior fossa with varying amount of cysts, necrosis and calcification, and the solid portion enhances well after contrast injection. The imaging modality of choice is a bi/tri-planar gadolinium-enhanced MRI, which, because of its better anatomical resolution, demonstrates the extent of the tumor and its relationship to the brainstem and spinal cord. MRI with all available sequences, including enhanced, un-enhanced T1 and T2 weighted imaging, proton density, and fluid attenuated inversion recovery (FLAIR) are capable of water suppression to clearly differentiate the tumor borders. MR spectroscopy can be used as an adjunct to MRI in the evaluation of ependymomas, but there is limited data available of its usefulness. In addition to cranial imaging, an MRI of the spine should be performed pre-operatively to assess the presence of possible CSF metastases in the nerve roots, as their presence significantly worsens prognosis and likely nullifies the benefits that might have otherwise be gained by complete resection. Neuro-navigation or Intra-operative ultrasound can be useful for defining the relationship of tumors to the surface of the brain prior to entering the nervous system as well as potentially increasing the chances of total resection by demonstrating possible residual tumor.[43] Post surgical MR examination should be done within 48-72 hrs of surgery, which minimizes post-surgical changes and demonstrate residual tumor if any.

Treatment

These are comparatively slow growing tumors but have a tendency for local invasion or local recurrence.[44] For ependymomas, the ultimate goal of treatment should be total micro-surgical resection [Figure - 2]. The extent of surgical resection has been considered the most significant determinant with increased survival in almost every large series of pediatric ependymoma.[16],[18],[45],[46],[47] This is achieved by aggressive primary resection, immediate second look surgery if a post-operative residual tumor is identified and re-surgery at time of recurrence. Unfortunately, the ability to totally resect these tumors differs based on their location. Overall, between 35-50% of posterior fossa ependymomas can be resected completely but only 23-40% of those occurring adjacent to the brainstem in the fourth ventricle can be completely resected safely.[16],[48],[49] Complete resection is more easily achieved for supratentorial tumors, between 60-85% of these ependymomas can be completely removed.[49] Aggressive attempts to remove tumors in other locations, including those involving lower cranial nerves, are associated with increased morbidity.

Sutton reported 5-year progression free survival of 80% for patients who underwent gross total resections of the tumor but this reduced to 48%, 22%, and 0% for near-total resections, partial resections and biopsies, respectively.[50] Pollack's series showed a sudden drop in 5-year progression free survivals from 80% to 8.9% with total and subtotal tumor removal, respectively.[11] Perilongo et al[19] retrospectively analyzed 92 children with ependymoma who participated in the Italian pediatric Neuro-oncology Group. For patients who underwent gross total resection, the 10-year survival estimate was 70%, and the progression free survival was 57%; for patients who had undergone subtotal resection, the 10-year survival estimate was 32%, and the 10-year progression free survival estimate was 11% only. Finally, Robertson et al[16] prospectively treated 32 patients and they notice that 5-year progression free survival was 66% for patients with residual tumor measuring 1.5 cm 2sub or less and 11% for those with residual tumor measuring more than 1.5 cm 2sub , all of whom were treated with post-operative radiation.

The outcomes for this tumor also depend on the age of the patient and the location. Children have a more guarded prognosis as compared to adults, with the worst outcomes in patients under the age of two. Spinal ependymomas and supratentorial ependymomas usually have a better outcome than those in the infratentorial compartment, probably because they are more amenable to gross-total resection. Successful treatment of intracranial ependymoma by resection alone has been reported by different groups.[13],[14] Their patients with supratentorial ependymoma had prolonged recurrence free survival after gross total resection only. These findings signify that some patients with low-grade supratentorial ependymoma require resection only. Dhellemmes et al[50] recently reported the results of re-surgery and achieved total resection in recurrences and had more than 50% survival at 74.7 months follow-up after re-operation. Because maximal surgical extirpation is so critical to long-term outcome, it is now advocated that a post-operative enhanced MRI be obtained within 48 hours of surgery with the view of a second operation should operable tumor be evident on the imaging. Up to 71% of patients with partial resections had evidence of CSF dissemination whereas 83% of patients who had total tumor removal were free of CSF spread.[51]

There is much debate currently on the role of adjuvant treatment for ependymoma. It is commonly recommended that post-operative radiation be used following resection. Multiple resections may be required as palliative therapy during the course of the disease. The role of chemotherapy is less well demonstrated. However, patients under 3 are generally treated with chemotherapy as a method of delaying radiotherapy until the brain further matures.

Radiation therapy

Mork et al[52] were the first to show that post-operative radiation improves outcome in ependymoma. Since then, post-operative radiation therapy has been considered customary treatment for patients operated for ependymoma. They reported a survival estimate of 17% for patients who underwent resection alone versus 40% for those who received cranial radiation in addition. Radiation therapy may be recommended for patients older than 3, although there remains a risk for neuro-cognitive sequelae.

The pediatric oncology group study has shown that children with completely resected ependymoma in whom radiation therapy (RT) was delayed for 2 years experienced a worse outcome than those in whom therapy was delayed for 1 year (5-year survival 38% versus 88%).[45] Pediatric oncology group presented data on standard radiotherapy and Hyper-fractionated radiation therapy (HFRT) dose did not show any difference in the outcome.[53] A phase II trial of conformal radiation therapy (CRT) has shown that 3-year progression free survival was 74.7 5.7% after median follow-up of 38.2 months.[54] They have treated with 59.4 Gy CRT to 80% of their patients, localized to gross tumor volume and a margin of 10 mm. The incidence of local failure at 3 year was 14.8 4.0%.

Radiation dose is another controversial issue in ependymoma. Various studies have shown a dose-dependent response level for ependymoma, indicating a dose threshold of 45 to 50 Gy.[55],[56] Recent studies have proven that dose escalation in sub-totally resected tumors is favorable in posterior fossa ependymoma, 50%, 4-year event free survival with 69.6 Gy (POG 9132) in comparison to 24%, 4-year survival (POG 8532) after using lower dose of radiation.[57] This has also been shown by retrospective analyses that increase in radiation dose to the primary site appears to improve local control.[58],[59] Stereotactic radiosurgery is now increasingly becoming used in patients with residual, unresectable or recurrent tumor. [60],[61],[62],[63]

Adjuvant chemotherapy

Although the role of chemotherapy is not yet convincingly established, in younger children it may be given until the child's brain becomes mature enough to tolerate cranial radiation, usually at 3 years of age. Various retrospective and prospective trials have been published showing minimal benefit in terms of improving long-term disease free survival.[49],[64] At least four cycles of combination of multiagent drugs has been tried. The main chemotherapeutic agents used were vincristine, ifosfomide, etoposide and carboplatine in a variety of schedules.[65] Their patients received vincristine at same time during radiation but combination chemotherapy was started 4-6 weeks after completion of RT. Myelosupression is the major toxicity noticed during combination chemotherapy. They found 5-year progression free survival (PFS) of 74%, which is a bit better than RT alone in completely resected tumor. The PFS for children with postoperative residual tumor treated with RT and chemotherapy in this study was higher than literature for RT alone.[65]

Regardless of some combinations showing marginal effectiveness in the adjuvant treatment, childhood intracranial ependymomas may, in general, be considered as chemo-resistant. The over-expression of the multi-drug resistance-1 gene and the 06-methylguanine-DNA methyl transferase has been blamed as possible mechanisms for this phenomenon.[66] Cisplatin is the only agent that has reproducibly shown some worth in ependymoma with a cumulative response rate of 34%.[66] The children cancer group (CCG) 942 is the only randomized trial, which compared survival after radiation alone, and survival after combination of radiotherapy with chemotherapy, did not show improved outcome.[2]


  Conclusion Top


Utmost local control of the tumor is single most important prognostic factor. This is achieved by gross total, if feasible, or near total surgical resection, which can offer long-term disease free survival. Radiotherapy should be offered to all patients (>3 years age) with focused dose (CRT) to tumor bed. Second look surgery in immediate post-operative period for residual tumor if any or surgery for recurrences is reasonable. In an attempt to facilitate the second surgery, chemotherapy may be given but as such chemotherapy has failed to improve overall survival.

 
  References Top

1.Pollack IF: Brain tumors in children. N Eng J Med 1994;331:1500-7.  Back to cited text no. 1    
2.Evans AE, Anderson JR, Lefkowitz-Boudreaux IB, Finlay JL. Adjuvant chemotherapy of childhood ependymomas: cranio-spinal irradiation with or without CCNU, Vincristine, and Prednisone: a children's cancer group study. Med Pediatr Oncol 1996;27:8-14.  Back to cited text no. 2  [PUBMED]  
3.Nazar GB, Hoffman HJ, Becker LE, Jenkin D, Humphreys RP, Hendrick EB. Infra-tentorial ependymoma in childhood: Prognostic factors and treatment. J Neurosurg 1990;72:408-17.  Back to cited text no. 3  [PUBMED]  
4.Ries LA, et al. Cancer statistics review, 1973-1997. National Cancer Institute: Bethesda, Md; 2000.  Back to cited text no. 4    
5.Ikezaki K, Matsushima T, Inoue T, Yokoyama N, Kaneko Y, Fukui M. Correlation of micro-anatomical localization with postoperative survival in posterior fossa ependymomas. Neurosurgery 1993;32:38-44.  Back to cited text no. 5  [PUBMED]  
6.Sanford RA, Gajjar A. Ependymomas. Clin Neurosurg 199744:559-70.  Back to cited text no. 6    
7.Mautner VF, Tatagiba M, Guthoff R, Samii M, Pulst SM. Neurofibromatosis 2 in the pediatric age group. Neurosurgery 1993;33:92-6.  Back to cited text no. 7  [PUBMED]  
8.Sieb JP, Pulst SM, Buch A. Familial CNS tumors. J Neurol 1992;239:343-4.  Back to cited text no. 8  [PUBMED]  
9.Teo C, Nakaji P, Symons P, Tobias V, Cohn R, Smee R. Ependymoma. Childs Nerv Syst 2003;19:270-85.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]
10.Horn B, Heideman R, Geyer R, Pollack I, Packer R, Goldwein J, et al. A multi-institutional retrospective study of intracranial ependymoma in children: identification of risk factors. J Pediatr Hematol Oncol 1999;21:203-11.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]
11.Pollack IF, Gerszten PC, Martinez AJ, Lo KH, Shultz B, Albright AL, et al. Intracranial ependymomas of childhood: long-term outcome and prognostic factors. Neurosurgery 1995;37:655-66.  Back to cited text no. 11  [PUBMED]  
12.Sala F, Talacchi A, Mazza C, Prisco R, Ghimenton C, Bricolo A. Prognostic factors in childhood intracranial ependymoma. Pediatr Neurosurg 1998;28:135-42.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]
13.Hukin J, Epstein F, Lefton D, Allen J. Treatment of intracranial ependymoma by surgery alone. Pediatr Neurosurg 1998;29:40-5.  Back to cited text no. 13  [PUBMED]  [FULLTEXT]
14.Palma L, Celli P, Mariottini A, Zalaffi A, Schettini G. The importance of surgery in supratentorial ependymomas: Long term survival in a series of 23 cases. Childs Nerv Syst 2000;16:170-5.  Back to cited text no. 14  [PUBMED]  [FULLTEXT]
15.Foreman NK, Love S, Thorne R. Intracranial ependymomas: analysis of prognostic factors in a population based series. Pediatr Neurosurg 1996;24:119-25.  Back to cited text no. 15  [PUBMED]  
16.Robertson PL, Zeltzer PM, Boyett JM, Rorke LB, Allen JC, Geyer JR, et al. Survival and prognostic factors following radiation therapy and chemotherapy for ependymomas in children: a report of the Children's Cancer Group. J Neurosurg 1998;88:695-703.  Back to cited text no. 16  [PUBMED]  
17.Rousseau P, Habrand J, Sarrazin D, Kalifa C, Terrier-Lacombe MJ, Rekacewicz C, et al. Treatment of intracranial ependymomas of children: review of a 15-year experience. Int J Radiat Biol Phys 1994;28:381-6.  Back to cited text no. 17    
18.Needle MN, Goldwein JW, Grass J, Cnaan A, Bergman I, Molloy P, et al. Adjuvant chemotherapy for the treatment of intracranial ependymoma of childhood. Cancer 1997;80:341-7.  Back to cited text no. 18  [PUBMED]  [FULLTEXT]
19.Perilongo G, Massimino M, Sotti G, Belfontali T, Masiero L, Rigobello L, et al. Analysis of prognostic factors in a retrospective review of 92 children with ependymoma: Italian Pediatric neurooncology group. Med Pediatr Oncol 1997;29:79-85.  Back to cited text no. 19  [PUBMED]  [FULLTEXT]
20.Kovalic JJ, Flaris N, Grigsby PW, Pirkowski M, Simpson JR, Roth KA. Intracranial ependymoma long-term outcome, patterns of failure. J Neurooncol 1993;15:125-31.  Back to cited text no. 20  [PUBMED]  
21.Kleihues P, Sobin LH. World Health Organization Classification of Tumors. Cancer 2000;88:2887.  Back to cited text no. 21  [PUBMED]  [FULLTEXT]
22.Grabb PA, Albright AL, Pang D. Dissemination of supratentorial malignant gliomas via the cerebrospinal fluid in children. Neurosurgery 1992;30:64-71.   Back to cited text no. 22  [PUBMED]  
23.Ito U, Tomita H, Yamazaki S, Takada Y, Inaba Y. CT findings of leptomeningeal and periventricular dissemination of tumors. Report of four cases. Clin Neurol Neurosurg 1986;88:115-20.  Back to cited text no. 23  [PUBMED]  
24.Naganska E, Matyja E, Zabek M, Jagielski J. Disseminated spinal and cerebral ependymoma with unusual histological pattern: clinico-pathological study of a case with retrograde tumor spread. Folia Neuropathol 2000;38:135-41.  Back to cited text no. 24  [PUBMED]  
25.Carbone M, Rizzo P, Pass HI. Simian virus 40, poliovaccines and human tumors: A review of recent developments. Oncogene 1997;15:1877-8.  Back to cited text no. 25  [PUBMED]  [FULLTEXT]
26.Croul S, Otte J, Khalili K. Brain tumors and polyomaviruses. J Neurovirol 2003;9:173-82.  Back to cited text no. 26  [PUBMED]  [FULLTEXT]
27.Zhen HN, Zhang X, Bu XY, Zhang ZW, Huang WJ, Zhang P, et al. Expression of the simian virus 40 large tumor antigen (Tag) and formation of Tag-p53 and Tag-pRb complexes in human brain tumors. Cancer 1999;86:2124-32.  Back to cited text no. 27  [PUBMED]  [FULLTEXT]
28.Kirchstein RL, Rabson AS, O'Conor GT. Ependymomas produced in Syrian hamsters by adenovirus 7, strain E46 ("hybrid" of adenovirus 7 and SV40). Proc Soc Exp Biol Med 1965;120:484-7.  Back to cited text no. 28  [PUBMED]  
29.Kirschstein RL, Gerber P. Ependymomas produced after intracerebral inoculation of SV40 into new-born hamsters. Nature 1962;195:299-300.  Back to cited text no. 29  [PUBMED]  
30.Carter M, Nicholson J, Ross F, Crolla J, Allibone R, Balaji V, et al. Genetic abnormalities detected in ependymomas by comparative genomic hybridisation. Br J Cancer 2002;86:929-39.  Back to cited text no. 30  [PUBMED]  
31.Reardon DA, Entrekin RE, Sublett J, Ragsdale S, Li H, Boyett J, et al. Chromosome arm 6q loss is the most common recurrent Autosomal alteration detected in primary pediatric ependymoma. Genes Chromosomes Cancer 1999;24:230-7.  Back to cited text no. 31  [PUBMED]  [FULLTEXT]
32.Huang B, Starostik P, Kuhl J, Tonn JC, Roggendorf W. Loss of heterozygosity on chromosome 22 in human ependymomas. Acta Neuropathol (Berl) 2002;103:415-20.  Back to cited text no. 32  [PUBMED]  [FULLTEXT]
33.Koschny R, Koschny T, Froster UG, Krupp W, Zuber MA. Comparative genomic hybridization in glioma: a meta-analysis of 509 cases. Cancer Genet Cytogenet 2002;135:147-59.  Back to cited text no. 33  [PUBMED]  [FULLTEXT]
34.Yokota T, Tachizawa T, Fukino K, Teramoto A, Kouno J, Matsumoto K, et al. A family with spinal anaplastic ependymoma: evidence of loss of chromosome 22q in tumor. J Hum Genet 2003;48:598-602.  Back to cited text no. 34  [PUBMED]  [FULLTEXT]
35.Jeuken JW, Sprenger SH, Gilhuis J, Teepen HL, Grotenhuis AJ, Wesseling P. Correlation between localization, age, and chromosomal imbalances in ependymal tumors as detected by CGH. J Pathol 2002;197:238-44.  Back to cited text no. 35  [PUBMED]  [FULLTEXT]
36.Ebert C, von Haken M, Meyer-Puttlitz B, Wiestler OD, Reifenberger G, Pietsch T, et al. Molecular genetic analysis of ependymal tumors. NF2 mutations and chromosome 22q loss occur preferentially in intramedullary spinal ependymomas. Am J Pathol 1999;155:627-32.  Back to cited text no. 36  [PUBMED]  [FULLTEXT]
37.Grill J, Avet-Loiseau H, Lellouch-Tubiana A, Sevenet N, Terrier-Lacombe MJ, Venuat AM, et al. Comparative genomic hybridization detects specific cytogenetic abnormalities in pediatric ependymomas and Choroid plexus papillomas. Cancer Genet Cytogenet 2002;136:121-5.  Back to cited text no. 37  [PUBMED]  [FULLTEXT]
38.Granzow M, Popp S, Weber S, Schoell B, Holtgreve-Grez H, Senf L, et al. Isochromosome 1q as an early genetic event in a child with intracranial ependymoma characterized by molecular cytogenesis. Cancer Genet Cytogenet 2001;130:79-83.  Back to cited text no. 38  [PUBMED]  [FULLTEXT]
39.Ward S, Harding B, Wilkins P, Harkness W, Hayward R, Darling JL, et al. Gain of 1q and loss of 22 are the most common changes detected by comparative genomic hybridisation in paediatric ependymoma. Genes Chromosomes Cancer 2001;32:59-66.  Back to cited text no. 39  [PUBMED]  
40.Gilbertson RJ, Bentley L, Hernan R, Junttila TT, Frank AJ, Haapasalo H, et al. ERBB receptor signaling promotes ependymoma cell proliferation and represents a potential novel therapeutic target for this disease. Clin Cancer Res 2002;8:3054-64.  Back to cited text no. 40  [PUBMED]  [FULLTEXT]
41.Bortolotto S, Chiado-Piat L, Cavalla P, Bosone I, Mauro A, Schiffer D. CDKN2A/p16 in ependymomas. J Neurooncol 2001;54:9-13.  Back to cited text no. 41  [PUBMED]  [FULLTEXT]
42.Rousseau E, Ruchoux MM, Scaravilli F, Chapon F, Vinchon M, De Smet C, et al. CDKN2A, CDKN2B and p14ARF are frequently and differentially methylated in ependymal tumors. Neuropathol Appl Neurobiol 2003;29:574-83.  Back to cited text no. 42  [PUBMED]  [FULLTEXT]
43.Friedman JA, Wetjen NM, Atkinson JL. Utility of intra-operative ultrasound for tumors of the cauda equina. Spine 2003;28:288-90 discussion 91.   Back to cited text no. 43  [PUBMED]  [FULLTEXT]
44.Akyuz C, Emir S, Akalan N, Soylemezoglu F, Kutluk T, Buyukpamukcu M. Intracranial ependymomas in childhood-a retrospective review of sixty-two children. Acta Oncol 2000;39:97-100.   Back to cited text no. 44  [PUBMED]  [FULLTEXT]
45.Duffner PK, Krischer JP, Sanford RA, Horowitz ME, Burger PC, Cohen ME, et al. Prognostic factor in infants and very young children with intracranial ependymomas. Pediatr neurosurg 1998;28:215-22.  Back to cited text no. 45  [PUBMED]  [FULLTEXT]
46.Vinchon M, Leblond P, Noudel R, Dhellemmes P. Intracranial ependymomas in childhood: recurrence, reoperation, and outcome. Childs Nerv Syst 2005;21:221-6. Epub 2004 Dec 14.  Back to cited text no. 46    
47.Rogers L, Pueschel J, Spetzler R, Shapiro W, Coons S, Thomas T, et al. Is gross-total resection sufficient treatment for posterior fossa ependymomas? J Neurosurg 2005;102:629-36.  Back to cited text no. 47  [PUBMED]  
48.Ernestus RI, Schroder R, Stutzer H, Klug N. Prognostic relevance of localization and grading in intracranial ependymomas of childhood. Childs Nerv Syst 1996;12:522-6.  Back to cited text no. 48  [PUBMED]  
49.Sutton LN, Goldwein J, Perilongo G, Lang B, Schut L, Rorke L, et al. Prognostic factors in childhood ependymomas. Pediatr Neurosurg 1990;16:57-65.  Back to cited text no. 49  [PUBMED]  
50.Vinchon M, Leblond P, Noudel R, Dhellemmes P. Intracranial ependymomas in childhood: recurrence, reoperation, and outcome. Childs Nerv Syst 2005;21:221-6. Epub 2004 Dec 14.  Back to cited text no. 50    
51.Rezai AR, Woo HH, Lee M, Cohen H, Zagzag D, Epstein FJ. Disseminated ependymomas of the central nervous system . J Neurosurg 1996;85:618-24.  Back to cited text no. 51  [PUBMED]  
52.Mork SJ, Loken AC. Ependymoma: A follow up study of 101 cases. Cancer 1977;40:907-15.  Back to cited text no. 52  [PUBMED]  
53.Kovnar EH. Hyper-fractionated irradiation for childhood ependymoma: early results of a phase II Pediatric Oncology Group study. Presented at the Seventh International Symposium on Pediatric Neuro-Oncology : Washington, DC; May 15-18, 1996.  Back to cited text no. 53    
54.Merchant TE, Mulhern RK, Krasin MJ, Kun LE, Williams T, Li C, et al. Preliminary results from a phase II trial of conformal radiation therapy and evaluation of radiation related CNS effects for pediatric patients with localized ependymoma. J Clin Oncol 2004;22:3156-62.  Back to cited text no. 54  [PUBMED]  [FULLTEXT]
55.Chiu JK, Woo SY, Ater J, Connelly J, Bruner JM, Maor MH, et al. Intracranial ependymoma in children: analysis of prognostic factors. J Neurooncol 1992;13:283-90.  Back to cited text no. 55  [PUBMED]  
56.Goldwein JW, Leahy JM, Packer RJ, Sutton LN, Curran WJ, Rorke LB, et al. Intracranial ependymomas in children. Int J Radiat Oncol Biol Phys 1990;19:1497-502.  Back to cited text no. 56  [PUBMED]  
57.Kovnar E, Curran W, Tomita. Hyper-fractionated irradiation for childhood ependymoma: improved local control in sub-totally resected tumors. Childs Nerv Syst 1998;14:489.  Back to cited text no. 57    
58.Merchant TE, Haida T, Wang MH, Finlay JL, Leibel SA. Anaplastic ependymoma: Treatment of pediatric patients with or without cranio-spinal radiation therapy. J Neurosurg 1997;86:943-9.  Back to cited text no. 58  [PUBMED]  
59.Shuman RM, Alvord EC, Leech RW. The biology of childhood ependymomas. Arch Neurol 1975;32:731-9.  Back to cited text no. 59    
60.Mansur DB, Drzymala RE, Rich KM, Klein EE, Simpson JR. The efficacy of stereotactic radiosurgery in the management of intracranial ependymoma. J Neurooncol 2003;66:187-90.  Back to cited text no. 60    
61.Endo H, Kumabe T, Jokura H, Shirane R, Tominaga T. Stereotactic radiosurgery for nodular dissemination of anaplastic ependymoma. Acta Neurochir (Wien) 2004;146:291-8.  Back to cited text no. 61  [PUBMED]  [FULLTEXT]
62.Weil MD. Advances in stereotactic radiosurgery for brain neoplasms. Curr Neurol Neurosci Rep 2001;1:233-7.  Back to cited text no. 62  [PUBMED]  
63.Hodgson DC, Goumnerova LC, Loeffler JS, Dutton S, Black PM, Alexander E 3rd, et al. Radiosurgery in the management of pediatric brain tumors. Int J Radiat Oncol Biol Phys 2001;50:929-35.  Back to cited text no. 63  [PUBMED]  [FULLTEXT]
64.Krieger MD, Bowen IE. Effects of surgical resection and adjuvant therapy on pediatric intracranial ependymomas. Expert Rev Neurother . 2005;5:465-71.   Back to cited text no. 64  [PUBMED]  [FULLTEXT]
65.Needle MN, Goldwein JW, Grass J, Cnaan A, Bergman I, Molloy P, et al. Adjuvant chemotherapy for the treatment of intracranial ependymoma of childhood. Cancer 1997;80:341-7.  Back to cited text no. 65  [PUBMED]  [FULLTEXT]
66.Grill J, Pascal C, Chantal K. Childhood ependymoma: a systematic review of treatment options and strategies. Paediatr Drugs 2003;5:533-43.  Back to cited text no. 66  [PUBMED]  


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