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1. Otero-Rodríguez A, Hinojosa J, Esparza J, Muñoz MJ, Iglesias S, Rodríguez-Gil Y, Ricoy JR: Purely intramedullary spinal cord primitive neuroectodermal tumor: case report and review of the literature. Neurocirugia (Astur); 2009 Aug;20(4):381-6; discussion 386-7
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  • [Title] Purely intramedullary spinal cord primitive neuroectodermal tumor: case report and review of the literature.
  • INTRODUCTION: Primitive neuroectodermal tumors (PNETs) are malign neoplasms of the central nervous system which mainly locate in cerebellum (medulloblastoma).
  • The pathological diagnosis was PNET.
  • Subsequent chemotherapy was recommended.
  • Outcome is dismal: most patients die within two years in spite of surgical resection followed by radiotherapy and chemotherapy.
  • [MeSH-major] Neuroectodermal Tumors, Primitive / pathology. Spinal Cord Neoplasms / pathology. Thoracic Vertebrae
  • [MeSH-minor] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carboplatin / administration & dosage. Cisplatin / administration & dosage. Combined Modality Therapy. Cyclophosphamide / administration & dosage. Disease Progression. Etoposide / administration & dosage. Humans. Infant. Magnetic Resonance Imaging. Male. Methotrexate / administration & dosage. Paraparesis / etiology. Prognosis

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  • (PMID = 19688140.001).
  • [ISSN] 1130-1473
  • [Journal-full-title] Neurocirugía (Asturias, Spain)
  • [ISO-abbreviation] Neurocirugia (Astur)
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Review
  • [Publication-country] Spain
  • [Chemical-registry-number] 6PLQ3CP4P3 / Etoposide; 8N3DW7272P / Cyclophosphamide; BG3F62OND5 / Carboplatin; Q20Q21Q62J / Cisplatin; YL5FZ2Y5U1 / Methotrexate
  • [Number-of-references] 19
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2. Ulbright TM, Hattab EM, Zhang S, Ehrlich Y, Foster RS, Einhorn LH, Cheng L: Primitive neuroectodermal tumors in patients with testicular germ cell tumors usually resemble pediatric-type central nervous system embryonal neoplasms and lack chromosome 22 rearrangements. Mod Pathol; 2010 Jul;23(7):972-80
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  • [Title] Primitive neuroectodermal tumors in patients with testicular germ cell tumors usually resemble pediatric-type central nervous system embryonal neoplasms and lack chromosome 22 rearrangements.
  • Primitive neuroectodermal tumors (PNETs) are one of the most frequent types of 'non-germ cell' tumor in patients with testicular germ cell tumors and have a guarded prognosis when present in metastatic sites after cisplatin-based chemotherapy.
  • Improved treatments, including targeted therapy, require understanding the biology of these neoplasms.
  • Using standard light microscopic criteria for central nervous system and peripheral PNETs, we classified nine tumors as medulloepithelioma, three as medulloblastoma/supratentorial PNET, one as neuroblastic tumor with abundant neuropil and true rosettes and one as small cell embryonal tumor/PNET (Ewing sarcoma-like).
  • Only 1 tumor, classified as medulloepithelioma, was scored positive for chromosome 22 translocation (22% rearranged cells) and the remaining 13 were negative, including the one case that resembled peripheral PNET.
  • We conclude that PNETs derived from testicular germ cell tumors mostly resemble central nervous system PNETs and generally lack the chromosome 22 translocation of peripheral PNETs.
  • Future treatment strategies should take these findings into account.
  • [MeSH-major] Neoplasms, Germ Cell and Embryonal / pathology. Neoplasms, Multiple Primary / pathology. Neuroectodermal Tumors, Primitive, Peripheral / pathology. Testicular Neoplasms / pathology
  • [MeSH-minor] Adult. Biomarkers, Tumor / analysis. Chromosomes, Human, Pair 22 / genetics. Gene Rearrangement. Humans. Immunohistochemistry. In Situ Hybridization, Fluorescence. Male. Young Adult

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  • (PMID = 20348883.001).
  • [ISSN] 1530-0285
  • [Journal-full-title] Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
  • [ISO-abbreviation] Mod. Pathol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Biomarkers, Tumor
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3. Frühwald MC, Rickert CH, O'Dorisio MS, Madsen M, Warmuth-Metz M, Khanna G, Paulus W, Kühl J, Jürgens H, Schneider P, Müller HL: Somatostatin receptor subtype 2 is expressed by supratentorial primitive neuroectodermal tumors of childhood and can be targeted for somatostatin receptor imaging. Clin Cancer Res; 2004 May 1;10(9):2997-3006
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  • [Title] Somatostatin receptor subtype 2 is expressed by supratentorial primitive neuroectodermal tumors of childhood and can be targeted for somatostatin receptor imaging.
  • PURPOSE: Although gliomas predominate among central nervous system (CNS) neoplasms in adulthood, embryonal tumors are the most common malignant brain tumors in children.
  • Despite novel treatment approaches, including improved radiotherapy and high-dose chemotherapy, survival rates remain unsatisfactory.
  • The timely diagnosis of residual or recurrent embryonal CNS tumors and thus the earliest possible time point for intervention is often hampered by inaccuracies of conventional imaging techniques.
  • Here, we evaluated somatostatin receptor type 2 (sst(2)) expression using an antibody in an array of CNS tumors of childhood.
  • Eight high-grade gliomas, 4 atypical teratoid/rhabdoid tumors, 7 supratentorial primitive neuroectodermal tumors (stPNET), 1 medulloepithelioma (ME), and 8 ependymomas were screened.
  • RESULTS: Abundant expression of somatostatin receptor type 2 in stPNET, a ME, and ependymomas warranted in vivo imaging of 7 stPNET, 1 rhabdomyosarcoma, 3 ependymomas, 1 ME, and 1 glioblastoma.
  • In selected cases SRI was more sensitive in the detection of relapse than conventional imaging by magnetic resonance imaging and computed tomography.
  • CONCLUSIONS: SRI should be considered in the evaluation of residual or recurrent embryonal CNS tumors, especially stPNET.
  • The strengths of SRI lie in the differentiation of reactive tissue changes versus residual or recurrent tumor, the detection of small lesions, and possibly in the distinction of stPNET from gliomas.
  • [MeSH-major] Neuroectodermal Tumors, Primitive / pathology. Receptors, Somatostatin / biosynthesis. Supratentorial Neoplasms / pathology
  • [MeSH-minor] Central Nervous System Neoplasms / metabolism. Central Nervous System Neoplasms / pathology. Central Nervous System Neoplasms / radionuclide imaging. Child. Child, Preschool. Female. Humans. Immunohistochemistry. Infant. Male. Tomography, Emission-Computed, Single-Photon / methods

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  • (PMID = 15131035.001).
  • [ISSN] 1078-0432
  • [Journal-full-title] Clinical cancer research : an official journal of the American Association for Cancer Research
  • [ISO-abbreviation] Clin. Cancer Res.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Receptors, Somatostatin; 0 / somatostatin receptor 2
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4. Ferri Niguez B, Martínez-Lage JF, Almagro MJ, Fuster JL, Serrano C, Torroba MA, Sola J: Embryonal tumor with abundant neuropil and true rosettes (ETANTR): a new distinctive variety of pediatric PNET: a case-based update. Childs Nerv Syst; 2010 Aug;26(8):1003-8
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  • [Title] Embryonal tumor with abundant neuropil and true rosettes (ETANTR): a new distinctive variety of pediatric PNET: a case-based update.
  • BACKGROUND: Embryonal central nervous system (CNS) tumors are currently classified into three types: medulloblastoma, atypical rhabdoid/teratoid tumors, and primitive neuroectodermal tumor (PNET).
  • A distinctive subtype of PNET called "embryonal tumor with abundant neuropil and true rosettes" (ETANTR) was reported in 2000.
  • DISCUSSION: ETANTR is a recently described variety of PNET that combines microscopic features of neuroblastoma and ependymoblastoma, demonstrating areas of fine fibrillary neuropil intermingled with cellular zones and ependymoblastic rosettes.
  • It has been suggested that this neoplasm should be considered as a separate entity.
  • ETANTR is an eminently pediatric tumor that has been reported exclusively in children younger than 4 years.
  • ILLUSTRATIVE CASES: A 9-month-old girl underwent subtotal resection of a brainstem neoplasm.
  • A 23-month-old girl was submitted to surgery for a frontoparietal tumor.
  • Both children were treated with chemotherapy and one with radiotherapy.
  • CONCLUSIONS: By reporting these two new instances of ETANTR, we want to contribute to the knowledge of this highly malignant CNS embryonal neoplasm that occurs only in young children, given its present lethal prognosis, the scarcity of reported cases, and the lack of treatment guidelines.
  • [MeSH-major] Brain Neoplasms / pathology. Neuroectodermal Tumors, Primitive / pathology. Neuropil / pathology
  • [MeSH-minor] Antineoplastic Agents / therapeutic use. Combined Modality Therapy. Fatal Outcome. Female. Humans. Infant. Neurosurgical Procedures. Radiotherapy

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  • [Cites] Am J Surg Pathol. 2009 Feb;33(2):211-7 [18987548.001]
  • [Cites] Acta Neuropathol. 2009 Apr;117(4):457-64 [19057917.001]
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  • (PMID = 20499240.001).
  • [ISSN] 1433-0350
  • [Journal-full-title] Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery
  • [ISO-abbreviation] Childs Nerv Syst
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antineoplastic Agents
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5. Kellie SJ, Koopmans P, Earl J, Nath C, Roebuck D, Uges DR, De Graaf SS: Increasing the dosage of vincristine: a clinical and pharmacokinetic study of continuous-infusion vincristine in children with central nervous system tumors. Cancer; 2004 Jun 15;100(12):2637-43
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  • [Title] Increasing the dosage of vincristine: a clinical and pharmacokinetic study of continuous-infusion vincristine in children with central nervous system tumors.
  • Therefore, the authors explored the neurotoxicity and pharmacokinetics of VCR administered via a 96-hour continuous infusion after administration of a conventional bolus dose in a pediatric population.
  • The diagnoses included intrinsic pontine glioma (n = 4), ependymoma (n = 5), astrocytoma (n = 3), medulloblastoma/primitive neuroectodermal tumor (PNET; n = 2), ganglioglioma (n = 1), and choroid plexus carcinoma (n = 1).
  • Treatment included cyclophosphamide 65 mg/kg administered intravenously over 1 hour on Day 1, a bolus of VCR 1.5 mg/m(2) administered intravenously on Day 2, and VCR 0.5 mg/m(2) per 24 hours administered via continuous intravenous infusion on Days 2-5.
  • Fifteen patients received 2 courses of treatment at 21-28-day intervals, and a total of 31 treatment courses were administered.
  • A complete response was noted in one patient (astrocytoma), a partial response in three patients (one each with astrocytoma, ependymoma, and PNET), stable disease in seven patients, and disease progression in three patients.
  • CONCLUSIONS: Continuous infusion of VCR after a conventional bolus dose plus cyclophosphamide for children with tumors of the central nervous system did not result in significant neurotoxicity and appeared to be a safe strategy for achieving increased systemic exposure.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Brain Neoplasms / drug therapy. Cyclophosphamide / administration & dosage. Vincristine / administration & dosage. Vincristine / pharmacokinetics
  • [MeSH-minor] Adolescent. Child. Child, Preschool. Humans. Infant. Infusions, Intravenous. Male. Treatment Outcome

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  • [Copyright] Copyright 2004 American Cancer Society.
  • (PMID = 15197807.001).
  • [ISSN] 0008-543X
  • [Journal-full-title] Cancer
  • [ISO-abbreviation] Cancer
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 5J49Q6B70F / Vincristine; 8N3DW7272P / Cyclophosphamide
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6. Hong TS, Mehta MP, Boyett JM, Donahue B, Rorke LB, Zeltzer PM: Patterns of treatment failure in infants with primitive neuroectodermal tumors who were treated on CCG-921: a phase III combined modality study. Pediatr Blood Cancer; 2005 Oct 15;45(5):676-82
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  • [Title] Patterns of treatment failure in infants with primitive neuroectodermal tumors who were treated on CCG-921: a phase III combined modality study.
  • PURPOSE: To analyze patterns of treatment failure in infants with primitive neuroectodermal tumors (PNETs) who were treated primarily with chemotherapy in a large multi-institutional study.
  • MATERIALS AND METHODS: Sixty-five prospectively staged patients with PNET confirmed by central pathology review, who were 18 months or younger were treated on Children's Cancer Group Study 921 (CCG-921) primarily with chemotherapy.
  • Patterns of sites of initial treatment failure were analyzed and compared to failure patterns of 180 older children who had PF-PNETs, and 44 older children with ST-PNETs who were treated on the same protocol.
  • Cumulative 5-year relapse incidence (+/-SE) for younger patients with PF-PNETs was 64.5 +/- 8.9% for patients without metastases (M0) compared to 71.4 +/- 13.4% for patients with metastases (M+).
  • The overall treatment failure rate was significantly higher for younger compared to older patients with PF-PNET and ST-PNET.
  • All patients had a high risk of recurrence at primary tumor site.
  • CONCLUSIONS: Despite aggressive chemotherapy, younger children with PNETs have high rates of treatment failure and fare worse than high-risk, older patients with PF-PNETs, indicating the need to maximize local, regional, and systemic therapies.
  • [MeSH-major] Brain Neoplasms / therapy. Neuroectodermal Tumors, Primitive / therapy
  • [MeSH-minor] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Clinical Trials, Phase III as Topic. Combined Modality Therapy. Disease Progression. Disease-Free Survival. Humans. Infant. Infratentorial Neoplasms / mortality. Infratentorial Neoplasms / pathology. Infratentorial Neoplasms / therapy. Neoplasm Recurrence, Local. Supratentorial Neoplasms / mortality. Supratentorial Neoplasms / pathology. Supratentorial Neoplasms / therapy. Survival Rate. Treatment Failure

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  • (PMID = 16007595.001).
  • [ISSN] 1545-5009
  • [Journal-full-title] Pediatric blood & cancer
  • [ISO-abbreviation] Pediatr Blood Cancer
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA21765
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
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7. Lober R, Sharma S, Bell B, Free A, Figueroa R, Sheils CW, Lee M, Cowell J: Pediatric primary intramedullary spinal cord glioblastoma. Rare Tumors; 2010 Sep 30;2(3):e48
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  • [Title] Pediatric primary intramedullary spinal cord glioblastoma.
  • Spinal cord tumors in pediatric patients are rare, representing less than 1% of all central nervous system tumors.
  • Two cases of pediatric primary intramedullary spinal cord glioblastoma at ages 14 and 8 years are reported.
  • Case #1 had a small cell component (primitive neuroectodermal tumor-like areas), higher Ki67, and p53 labeling indices, and a relatively stable karyotype with only minimal single copy losses involving regions: Chr8;pter-30480019, Chr16;pter-29754532, Chr16;56160245-88668979, and Chr19;32848902-qter on retrospective comparative genomic hybridization using formalin-fixed, paraffin-embedded samples.
  • Both underwent multimodal therapy including gross total resection, postoperative radiation and chemotherapy.
  • However, there was no significant improvement in neurological deficits, and overall survival in both cases was 14 months.This report highlights the broad histological spectrum and poor overall survival despite multi modality therapy.
  • The finding of relatively unique genotypic abnormalities resembling pediatric embryonal tumors in one case may highlight the value of genome-wide profiling in development of effective therapy.

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  • (PMID = 21139963.001).
  • [ISSN] 2036-3613
  • [Journal-full-title] Rare tumors
  • [ISO-abbreviation] Rare Tumors
  • [Language] ENG
  • [Grant] United States / NINDS NIH HHS / NS / F30 NS052070
  • [Publication-type] Journal Article
  • [Publication-country] Italy
  • [Other-IDs] NLM/ PMC2994522
  • [Keywords] NOTNLM ; glioblastoma / intramedullary / pediatric / spinal cord
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8. Eberhart CG, Brat DJ, Cohen KJ, Burger PC: Pediatric neuroblastic brain tumors containing abundant neuropil and true rosettes. Pediatr Dev Pathol; 2000 Jul-Aug;3(4):346-52
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  • [Title] Pediatric neuroblastic brain tumors containing abundant neuropil and true rosettes.
  • We have encountered a series of seven unusual neuroblastic pediatric central nervous system (CNS) neoplasms with a unique constellation of histologic, immunohistochemical, and ultrastructural features.
  • True rosettes with well-formed central lumens often filled with granular debris were present, along with perivascular pseudorosettes and occasional Homer-Wright rosettes.
  • Immunohistochemically, the neuropil-like areas as well as the perinuclear cytoplasm of many embryonal tumor cells were positive for synaptophysin and neurofilament protein.
  • Ultrastructurally, the tumor cells showed microtubule-containing neuronal processes, some with neurosecretory granules.
  • The clinical outcome was poor, with five patients dead from their disease 5 to 14 months after initial presentation and one patient with recurrent disease 7 months after resection and chemotherapy.
  • These lesions present distinctive histological features within the group of primitive neuroectodermal tumors.
  • [MeSH-major] Brain Neoplasms / pathology. Neuroectodermal Tumors, Primitive / pathology
  • [MeSH-minor] Apoptosis. Brain / metabolism. Brain / pathology. Child, Preschool. Female. Glial Fibrillary Acidic Protein / analysis. Humans. Infant. Magnetic Resonance Imaging. Male. Neutrophils. Rosette Formation. Treatment Outcome

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  • (PMID = 10890250.001).
  • [ISSN] 1093-5266
  • [Journal-full-title] Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society
  • [ISO-abbreviation] Pediatr. Dev. Pathol.
  • [Language] eng
  • [Publication-type] Case Reports; Comparative Study; Journal Article
  • [Publication-country] UNITED STATES
  • [Chemical-registry-number] 0 / Glial Fibrillary Acidic Protein
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9. Hargrave DR, Zacharoulis S: Pediatric CNS tumors: current treatment and future directions. Expert Rev Neurother; 2007 Aug;7(8):1029-42

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  • [Title] Pediatric CNS tumors: current treatment and future directions.
  • Pediatric CNS tumors are the most common solid tumor of childhood and are the leading cause of cancer-related death in this age group.
  • Current management strategies rely on surgery, radiotherapy and conventional cytotoxic chemotherapy, and although ongoing clinical trials continue to refine these treatments, newer approaches are required.
  • This article will discuss current treatment standards for the most common pediatric CNS tumors: astrocytomas (low- and high-grade glioma), ependymoma and primitive neuroectodermal tumors (medulloblastoma), as well as future biological-based novel therapies.
  • [MeSH-major] Central Nervous System Neoplasms / therapy

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  • (PMID = 17678498.001).
  • [ISSN] 1744-8360
  • [Journal-full-title] Expert review of neurotherapeutics
  • [ISO-abbreviation] Expert Rev Neurother
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Number-of-references] 147
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10. Norris LS, Snodgrass S, Miller DC, Wisoff J, Garvin J, Rorke LB, Finlay JL: Recurrent central nervous system medulloepithelioma: response and outcome following marrow-ablative chemotherapy with stem cell rescue. J Pediatr Hematol Oncol; 2005 May;27(5):264-6
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  • [Title] Recurrent central nervous system medulloepithelioma: response and outcome following marrow-ablative chemotherapy with stem cell rescue.
  • Medulloepithelioma is a rare primitive neuroectodermal tumor of the central nervous system usually developing in childhood, displaying highly malignant behavior, with early progression or recurrence.
  • The purpose of this study was to evaluate the efficacy of high-dose, marrow-ablative chemotherapy with autologous hemopoietic stem cell rescue in the treatment of recurrent central nervous system medulloepithelioma.
  • Three young children with recurrent central nervous system medulloepithelioma received high-dose marrow-ablative chemotherapy with thiotepa and etoposide either alone (one patient) or with the addition of carboplatin (two patients).
  • One child with residual radiographic tumor at the time of treatment could be evaluated for response and showed complete resolution of leptomeningeal disease after receiving marrow-ablative chemotherapy.
  • Two children developed tumor recurrence at 2.0 and 5.5 months after receiving marrow-ablative chemotherapy.
  • The third child continues free of tumor beyond 12 years from treatment.
  • The authors' experience with marrow-ablative chemotherapy and autologous hemopoietic stem cell rescue suggests that this treatment strategy might be beneficially incorporated into the initial treatment approach for young children with medulloepithelioma.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carcinoma / therapy. Central Nervous System Neoplasms / therapy. Neoplasm Recurrence, Local. Stem Cell Transplantation
  • [MeSH-minor] Child, Preschool. Combined Modality Therapy. Female. Humans. Magnetic Resonance Imaging. Male. Time Factors. Treatment Outcome

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  • (PMID = 15891561.001).
  • [ISSN] 1077-4114
  • [Journal-full-title] Journal of pediatric hematology/oncology
  • [ISO-abbreviation] J. Pediatr. Hematol. Oncol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
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11. Schniederjan MJ, Shehata B, Brat DJ, Esiashvili N, Janss AJ: De novo germline TP53 mutation presenting with synchronous malignancies of the central nervous system. Pediatr Blood Cancer; 2009 Dec 15;53(7):1352-4
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  • [Title] De novo germline TP53 mutation presenting with synchronous malignancies of the central nervous system.
  • We present a case of a 14-year-old male with a germline TP53 mutation who presented with synchronous primitive neuroectodermal tumor and choroid plexus carcinoma.
  • Within 5 months of presentation, the child developed widely metastatic alveolar rhabdomyosarcoma.
  • This case identifies a rare, de novo, germline TP53 mutation presenting with synchronous CNS malignancies and exhibiting a more fulminant course than typical cases of Li-Fraumeni syndrome.
  • [MeSH-major] Brain Neoplasms / genetics. Carcinoma / genetics. Choroid Plexus Neoplasms / genetics. Codon, Nonsense. Genes, p53. Germ-Line Mutation. Neoplasms, Multiple Primary / genetics. Neuroectodermal Tumors, Primitive / genetics. Rhabdomyosarcoma, Alveolar / genetics. Rhabdomyosarcoma, Alveolar / secondary
  • [MeSH-minor] Adolescent. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cisplatin / administration & dosage. Combined Modality Therapy. Cranial Irradiation. Fatal Outcome. Frontal Lobe / pathology. Frontal Lobe / surgery. Humans. Lomustine / administration & dosage. Male. Neoplasms, Unknown Primary / genetics. Radiotherapy, Adjuvant. Spinal Neoplasms / drug therapy. Spinal Neoplasms / radiotherapy. Spinal Neoplasms / secondary. Vincristine / administration & dosage

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  • [Copyright] (c) 2009 Wiley-Liss, Inc.
  • (PMID = 19711436.001).
  • [ISSN] 1545-5017
  • [Journal-full-title] Pediatric blood & cancer
  • [ISO-abbreviation] Pediatr Blood Cancer
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Codon, Nonsense; 5J49Q6B70F / Vincristine; 7BRF0Z81KG / Lomustine; Q20Q21Q62J / Cisplatin
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12. Partap S, Murphy PA, Vogel H, Barnes PD, Edwards MS, Fisher PG: Efficacy and tolerability of intrathecal liposomal cytarabine for central nervous system embryonal tumors. J Clin Oncol; 2009 May 20;27(15_suppl):2064

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  • [Title] Efficacy and tolerability of intrathecal liposomal cytarabine for central nervous system embryonal tumors.
  • : 2064 Background: Liposomal cytarabine (DepoCyt) is a sustained-release intrathecal (IT) preparation of cytarabine, formulated by encapsulating the drug in spherical aqueous chambers within a lipid matrix.
  • While proven effective in lymphomatous meningitis, this drug has shown some activity in medulloblastoma (MB) with spinal metastases in limited pediatric phase I study.
  • METHODS: We reviewed all patients at our institution treated with liposomal cytarabine for primary central nervous system (CNS) embryonal tumors-MB, primitive neuroectodermal tumor (PNET), and atypical teratoid rhabdoid tumor (ATRT).
  • RESULTS: A cohort of 17 patients were treated with liposomal cytarabine at diagnosis of CNS embryonal tumor (2 PNET, 3 ATRT) or relapse (12 MB [7 average-risk, 5 high-risk]); nine had leptomeningeal metastases.
  • Drug was dosed at 2 mg/kg up to 50, every 2 weeks to monthly, along with dexamethasone.
  • Concurrent systemic chemotherapy was given in 16 patients.
  • A total of 102 doses were administered (lumbar IT 76, Ommaya intraventricular 36) with a mean of six treatments (range 1-16).
  • No patient developed malignant CSF cytology while receiving liposomal cytarabine.
  • Ten patients developed progressive disease and died, with only one later recurrence in the spinal fluid.
  • All patients with neoplastic meningitis cleared malignant cells from their spinal fluid after treatment with IT liposomal cytarabine and systemic chemotherapy.
  • Our findings warrant a phase II trial of liposomal cytarabine in newly diagnosed or recurrent CNS embryonal tumors.

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  • (PMID = 27964690.001).
  • [ISSN] 1527-7755
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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13. Hadfield MG, Quezado MM, Williams RL, Luo VY: Ewing's family of tumors involving structures related to the central nervous system: a review. Pediatr Dev Pathol; 2000 May-Jun;3(3):203-10

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  • [Title] Ewing's family of tumors involving structures related to the central nervous system: a review.
  • This review consolidates information gleaned from several case reports and larger series on Ewing's sarcoma family of tumors (EFT) involving structures related to and found in the central nervous system (CNS).
  • These tumors involve the skull, the spinal column, adjacent soft tissues, the meninges, and the brain.
  • We have separated the cases by skull region and spinal column level, and we discuss the attendant differences in prognosis following treatment by neurosurgery, radiation, and chemotherapy.
  • Light and electron microscopic features can be used to differentiate EFT from other small round blue cell tumors that involve the CNS (central primitive neuroectodermal tumor, lymphoma, etc.).
  • We conclude that EFT involving the CNS and adjacent structures is not so rare as previously stated and that the prognosis is more favorable, as a rule, than for the more common examples arising in the long bones and pelvis.
  • [MeSH-major] Central Nervous System Neoplasms / diagnosis. Sarcoma, Ewing / diagnosis
  • [MeSH-minor] Adolescent. Child. Diagnosis, Differential. Epidural Neoplasms / diagnosis. Female. Genetic Techniques. Humans. Immunohistochemistry. Infant. Jaw Neoplasms / diagnosis. Male. Microscopy, Electron. Neuroectodermal Tumors, Primitive / diagnosis. Prognosis. Skull Neoplasms / diagnosis. Soft Tissue Neoplasms / diagnosis. Soft Tissue Neoplasms / secondary. Spinal Neoplasms / diagnosis

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  • (PMID = 10742406.001).
  • [ISSN] 1093-5266
  • [Journal-full-title] Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society
  • [ISO-abbreviation] Pediatr. Dev. Pathol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] UNITED STATES
  • [Number-of-references] 122
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14. Varan A, Akalan N, Söylemezoğlu F, Zorlu F, Yalçin B, Akyüz C, Kutluk T, Büyükpamukçu M: Central nervous system tumors in patients under three years of age: treatment results of a single institute. Pediatr Neurosurg; 2006;42(2):89-94
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  • [Title] Central nervous system tumors in patients under three years of age: treatment results of a single institute.
  • Eighty-six patients under 3 years of age with central nervous system tumors were retrospectively analyzed between 1972 and 2003.
  • Surgical resection was done in all patients except for those with optic glioma, pons glioma and pineal tumor.
  • Three different chemotherapy regimens were used in different time periods.
  • In 48 patients, the tumor was located in the posterior fossa, and 29 patients had a supratentorial tumor.
  • We had 32 (37.2%) patients with embryonic tumors (21 medulloblastoma, 4 ependymoblastoma, 5 with atypical teratoid rhabdoid and 2 with supratentorial primitive neuroectodermal tumors), 21 (24.4%) with ependymoma, 14 (16.3%) with optic glioma, 10 (11.6%) with astrocytoma, 3 (3.5%) with pons glioma and 6 (7.0%) with others.
  • OS rates according to the tumor localizations were 40.9 and 68.1% in the posterior fossa and supratentorial localizations, respectively (p=0.001).
  • OS rates were 33.7, 41.3 and 88.8% for the medulloblastoma+primitive neuroectodermal tumor groups, ependymoma and astrocytoma, respectively (p=0.0001).
  • Most of the patients had primitive embryonic tumors (37.2%).
  • The best prognostic factors were tumor localization and histology.
  • [MeSH-major] Central Nervous System Neoplasms / mortality. Central Nervous System Neoplasms / therapy. Neoplasms, Germ Cell and Embryonal / mortality. Neoplasms, Germ Cell and Embryonal / therapy
  • [MeSH-minor] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Child, Preschool. Female. Humans. Infant. Infant, Newborn. Male. Prognosis. Retrospective Studies. Rhabdoid Tumor / mortality. Rhabdoid Tumor / pathology. Rhabdoid Tumor / therapy. Survival Rate

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  • [Copyright] Copyright (c) 2006 S. Karger AG, Basel.
  • (PMID = 16465077.001).
  • [ISSN] 1016-2291
  • [Journal-full-title] Pediatric neurosurgery
  • [ISO-abbreviation] Pediatr Neurosurg
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Switzerland
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15. Wang CH, Hsu TR, Wong TT, Chang KP: Efficacy of temozolomide for recurrent embryonal brain tumors in children. Childs Nerv Syst; 2009 May;25(5):535-41
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  • OBJECTIVE: The salvage therapy of recurrent embryonal brain tumors in children is disappointing.
  • Temozolomide is a newly developed chemotherapeutic agent in central nervous system tumors.
  • This study analyzed the efficacy of temozolomide on the treatment of recurrent embryonal brain tumors in children.
  • MATERIALS AND METHODS: There were eight patients, including four with medulloblastoma (MB), three with atypical teratoid/rhabdoid tumor (AT/RT) and one with supratentorial primitive neuroectodermal tumor, whose tumors recurred after surgery and radiotherapy, with or without conventional intravenous cisplatin-based chemotherapy.
  • RESULTS: The median treatment cycles received by these eight patients were 17 (range from two to 59 cycles).
  • The follow-up MRI showed no tumor progression in five patients at 6 months and four patients at 12 months.
  • The observed adverse effects of temozolomide included nausea, vomiting, headache, constipation, mild marrow suppression, and decreased activity; none of them was severe enough to discontinue the treatment.
  • When conventional chemotherapy fails and/or the adverse response is too severe to tolerate, temozolomide is a reasonable alternative.
  • [MeSH-major] Antineoplastic Agents, Alkylating / therapeutic use. Brain Neoplasms / drug therapy. Dacarbazine / analogs & derivatives. Medulloblastoma / drug therapy. Neuroectodermal Tumors, Primitive / drug therapy. Rhabdoid Tumor / drug therapy. Teratoma / drug therapy
  • [MeSH-minor] Administration, Oral. Adolescent. Disease-Free Survival. Female. Follow-Up Studies. Headache / chemically induced. Humans. Magnetic Resonance Imaging. Male. Nausea / chemically induced. Treatment Outcome. Vomiting / chemically induced

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  • Hazardous Substances Data Bank. DACARBAZINE .
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  • (PMID = 19107490.001).
  • [ISSN] 1433-0350
  • [Journal-full-title] Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery
  • [ISO-abbreviation] Childs Nerv Syst
  • [Language] eng
  • [Publication-type] Journal Article
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  • [Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; 7GR28W0FJI / Dacarbazine; YF1K15M17Y / temozolomide
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16. Kalifa C, Grill J: The therapy of infantile malignant brain tumors: current status? J Neurooncol; 2005 Dec;75(3):279-85
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  • [Title] The therapy of infantile malignant brain tumors: current status?
  • Malignant brain tumors are not uncommon in infants as their occurrence before the age of three represents 20-25% of all malignant brain tumors in childhood [1].
  • In addition, sequelae from tumor and its treatment are more severe at this age [2].
  • Thus, malignant brain tumors represent a true therapeutic challenge in neuro-oncology.
  • Since the end of the 80s, noninvasive imaging procedures produce accurate diagnosis of brain tumors and improvement in neurosurgery, neuroanesthesia and perioperative intensive care permit safe tumor resections or at least biopsies.
  • Consequently, the pediatric oncologists are more often confronted with very young children who need a complementary treatment.
  • Before the development of specific approaches for this age group, these children received the same kind of treatment than the older children did, but their survival and quality of life were significantly worse.
  • The reasons of these poor results were probably due in part to the fear of late effects induced by radiation therapy, leading to decrease the necessary doses of irradiation which increased treatment failures without avoiding treatment related complications [3].
  • At the end of the 80s, pilot studies were performed using postoperative chemotherapy in young medulloblastoma patients.
  • Subsequently, the pediatric oncology cooperative groups studies have designed therapeutic trials for very young children with malignant brain tumors.
  • Different approaches have been explored: * Prolonged postoperative chemotherapy and delayed irradiation as designed in the POG (Pediatric Oncology Group).
  • * Postoperative chemotherapy without irradiation in the SFOP (Société Française d'Oncologie Pédiatrique) and in the GPO (German Pediatric Oncology) studies.
  • * The role of high-dose chemotherapy with autologous stem cells transplantation was explored in different ways: High-dose chemotherapy given in all patients as proposed in the Head Start protocol.
  • High-dose chemotherapy given in relapsing patients as salvage treatment in the French strategy.
  • In the earliest trials, the same therapy was applied to all histological types of malignant brain tumors and whatever the initial extension of the disease.
  • This attitude was justified by the complexity of the classification of all brain tumors that has evolved over the past few decades leading to discrepancy between the diagnosis of different pathologists for a same tumor specimen.
  • However, in the analysis of these trials an effort was made to give the results for each histological groups, according to the WHO classification and after a central review of the tumor specimens.
  • All these collected data have brought to an increased knowledge of infantile malignant brain tumors in terms of diagnosis, prognostic factors and response to chemotherapy.
  • Prospective study of sequelae can bring information on the impact of the different factors as hydrocephalus, location of the tumor, surgical complications, chemotherapy toxicity and irradiation modalities.
  • With these informations it is now possible to design therapeutic trials devoted to each histological types, adapted to pronostic factors and more accurate treatment to decrease long term sequelae.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Brain Neoplasms / drug therapy. Brain Neoplasms / surgery
  • [MeSH-minor] Cerebellar Neoplasms / drug therapy. Cerebellar Neoplasms / radiotherapy. Cerebellar Neoplasms / surgery. Combined Modality Therapy. Glioma / drug therapy. Glioma / radiotherapy. Glioma / surgery. Humans. Infant. Infant, Newborn. Infant, Newborn, Diseases. Medulloblastoma / drug therapy. Medulloblastoma / radiotherapy. Medulloblastoma / surgery. Neuroectodermal Tumors, Primitive / drug therapy. Neuroectodermal Tumors, Primitive / radiotherapy. Neuroectodermal Tumors, Primitive / surgery. Prognosis. Stem Cell Transplantation

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  • (PMID = 16195802.001).
  • [ISSN] 0167-594X
  • [Journal-full-title] Journal of neuro-oncology
  • [ISO-abbreviation] J. Neurooncol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 40
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17. Sklar CA: Childhood brain tumors. J Pediatr Endocrinol Metab; 2002 May;15 Suppl 2:669-73
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  • [Title] Childhood brain tumors.
  • Primary malignant tumors of the central nervous system (CNS) account for about 16% of all childhood malignancies.
  • These tumors are the second most common type of childhood cancer and the most frequent of the solid tumors.
  • CNS tumors are diverse, representing many histological types and arising in a variety of anatomic sites.
  • The most common malignant tumors include astrocytomas (52%), medulloblastomas/primitive neuroectodermal tumors (PNETs) (21%), gliomas (19%), and ependymomas (9%).
  • The current 5-year survival rate for all pediatric CNS tumors is 67%, but rates differ considerably among tumor types.
  • Treatment modalities also differ according to histological type.
  • Currently, about 25% of patients are treated with surgery alone, 40% undergo surgery plus radiation, and 30% are treated with surgery, radiation, and chemotherapy.
  • Survivors of childhood brain tumors are at substantial risk for increased morbidity and late mortality.
  • Five-year survivors of brain tumors are 13 times more likely to die than healthy age- and sex-matched peers.
  • Neurological, neurocognitive, and endocrine disturbances are the most prevalent disabilities observed among long-term survivors of pediatric brain tumors.
  • [MeSH-minor] Child. Humans. Hypothalamus / pathology. Pituitary Neoplasms / pathology. Treatment Outcome

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  • (PMID = 12092679.001).
  • [ISSN] 0334-018X
  • [Journal-full-title] Journal of pediatric endocrinology & metabolism : JPEM
  • [ISO-abbreviation] J. Pediatr. Endocrinol. Metab.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Number-of-references] 20
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18. Dang T, Vassilyadi M, Michaud J, Jimenez C, Ventureyra EC: Atypical teratoid/rhabdoid tumors. Childs Nerv Syst; 2003 Apr;19(4):244-8
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  • DISCUSSION: Over the past decade, atypical teratoid/rhabdoid tumors (ATRTs) of the central nervous system have emerged as a distinct entity.
  • This tumor is typically misdiagnosed as a primitive neuroectodermal tumor (PNET)/medulloblastoma.
  • The unique immunohistochemistry profile of an ATRT helps distinguish it from a PNET/medulloblastoma.
  • This is of clinical importance because the prognosis of a patient with an ATRT is worse than that of a PNET/medulloblastoma despite aggressive surgical treatment with or without adjuvant chemotherapy and radiation therapy.
  • [MeSH-major] Brain Neoplasms. Rhabdoid Tumor. Teratoma
  • [MeSH-minor] Child, Preschool. Diagnosis, Differential. Female. Humans. Immunohistochemistry. Infant. Magnetic Resonance Imaging. Male. Medulloblastoma / diagnosis. Prognosis. Tomography, X-Ray Computed. Treatment Outcome

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  • (PMID = 12682757.001).
  • [ISSN] 0256-7040
  • [Journal-full-title] Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery
  • [ISO-abbreviation] Childs Nerv Syst
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Germany
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19. Gardner SL: Application of stem cell transplant for brain tumors. Pediatr Transplant; 2004 Jun;8 Suppl 5:28-32
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  • Brain tumors are the second most common malignancy in children and the most common solid tumor.
  • The majority of children are treated with surgery alone or in combination with radiation and/or chemotherapy.
  • Recently investigators have used high dose chemotherapy with autologous stem cell rescue (ASCR) in patients with malignant brain tumors.
  • This approach has been most successful in chemosensitive tumors including medulloblastoma, supratentorial primitive neuroectodermal tumors (SPNET) and central nervous system germ cell tumors (CNS GCT).
  • In addition, the use of high dose chemotherapy has enabled the reduction and in many cases elimination of radiation therapy to very young children.
  • To date there have been no prospective randomized studies comparing high dose chemotherapy and ASCR with conventional therapy.
  • Radiation therapy is often not an option for patients with recurrent disease and conventional dose chemotherapy rarely if ever results in long-term survival.
  • Unfortunately, the majority of studies using conventional therapy in order to delay irradiation in young children newly diagnosed with malignant brain tumors have been unsuccessful.
  • Although the numbers are small, preliminary data suggest that not only is survival but also quality of life is superior with the use of high dose chemotherapy.
  • In addition, through the use of peripheral blood stem cells and improvements in supportive care, multiple courses of high dose chemotherapy can be administered.
  • High dose chemotherapy with ASCR is a foundation upon which many different types of therapies can be built.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Brain Neoplasms / therapy. Hematopoietic Stem Cell Transplantation
  • [MeSH-minor] Combined Modality Therapy. Humans. Pediatrics

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  • (PMID = 15125703.001).
  • [ISSN] 1397-3142
  • [Journal-full-title] Pediatric transplantation
  • [ISO-abbreviation] Pediatr Transplant
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Denmark
  • [Number-of-references] 25
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20. Marcus KJ, Goumnerova L, Billett AL, Lavally B, Scott RM, Bishop K, Xu R, Young Poussaint T, Kieran M, Kooy H, Pomeroy SL, Tarbell NJ: Stereotactic radiotherapy for localized low-grade gliomas in children: final results of a prospective trial. Int J Radiat Oncol Biol Phys; 2005 Feb 1;61(2):374-9
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  • PURPOSE: To evaluate the efficacy of stereotactic radiotherapy (SRT) for small, localized, pediatric brain tumors and to determine the patterns of failure.
  • Of the 81 patients, 50 had low-grade astrocytoma, 23 had residual or recurrent craniopharyngioma, 4 had posterior fossa ependymoma, and 4 had other histologic types.
  • All patients underwent biopsy for diagnosis, with the exception of patients with neurofibromatosis and radiographic evidence of an optic system tumor.
  • The indications for treatment of patients with low-grade gliomas were progression during or after chemotherapy or progression after surgery alone.
  • CT and MRI fusion was used for treatment planning.
  • The target volume generally included the preoperative tumor plus a 2-mm margin for the planning target volume.
  • Three to nine arcs were used to deliver a mean total dose of 52.2 Gy in 1.8-Gy daily fractions.
  • Five patients, all with optic system/hypothalamic primary tumors, developed central nervous system dissemination 1.0-7.4 years after SRT.
  • One patient developed a presumed radiation-induced primitive neuroectodermal tumor 6 years after initial treatment.
  • Six patients died, three of dissemination, two of progression to higher grade tumors, and one of a secondary radiation-induced tumor.
  • All 6 cases of local progression were within the primary tumor bed at the time of progression and had received the full prescription dose.
  • [MeSH-minor] Adolescent. Adult. Child. Child, Preschool. Confidence Intervals. Disease Progression. Disease-Free Survival. Female. Humans. Male. Neoplasm Recurrence, Local / drug therapy. Prospective Studies. Radiotherapy Dosage

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  • MedlinePlus Health Information. consumer health - Childhood Brain Tumors.
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  • (PMID = 15667955.001).
  • [ISSN] 0360-3016
  • [Journal-full-title] International journal of radiation oncology, biology, physics
  • [ISO-abbreviation] Int. J. Radiat. Oncol. Biol. Phys.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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21. Benesch M, Siegler N, Hoff Kv, Lassay L, Kropshofer G, Müller H, Sommer C, Rutkowski S, Fleischhack G, Urban C: Safety and toxicity of intrathecal liposomal cytarabine (Depocyte) in children and adolescents with recurrent or refractory brain tumors: a multi-institutional retrospective study. Anticancer Drugs; 2009 Oct;20(9):794-9
Hazardous Substances Data Bank. CYTARABINE .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • Nineteen heavily pretreated patients (males, n = 14; females, n = 5; median age at diagnosis 8.5 years; range, 1.4-22 years) were given intrathecal liposomal cytarabine on a compassionate use basis for recurrent refractory medulloblastoma (n = 12), mixed germ cell tumor (n = 2), central nervous system primitive neuroectodermal tumors of the pons (n = 1), anaplastic ependymoma (n = 1), anaplastic oligodendroglioma (n = 1), atypical teratoid rhabdoid tumor (n = 1), or rhabdoid papillary meningioma (n = 1).
  • Duration of treatment ranged from (1/2) to 10 months.
  • Eleven patients (57.9%) did not show any side effects, whereas eight patients (42.1%) developed side effects related to either chemical arachnoiditis (n = 4) or neurological progression (n = 2).
  • Less typical treatment-related symptoms (e.g. lethargy, ataxia, and slurred speech) were observed in two patients.
  • Treatment with intrathecal liposomal cytarabine was discontinued twice because of side effects.
  • [MeSH-major] Antimetabolites, Antineoplastic / adverse effects. Brain Neoplasms / drug therapy. Cytarabine / administration & dosage. Cytarabine / adverse effects
  • [MeSH-minor] Adolescent. Child. Child, Preschool. Compassionate Use Trials. Delayed-Action Preparations. Drug Resistance, Neoplasm. Female. Humans. Infant. Injections, Spinal. Liposomes / administration & dosage. Male. Retrospective Studies. Salvage Therapy. Young Adult

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  • (PMID = 19617818.001).
  • [ISSN] 1473-5741
  • [Journal-full-title] Anti-cancer drugs
  • [ISO-abbreviation] Anticancer Drugs
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Multicenter Study
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antimetabolites, Antineoplastic; 0 / Delayed-Action Preparations; 0 / Liposomes; 04079A1RDZ / Cytarabine
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