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High-Grade Gliomas

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Pediatric CNS Tumors

Part of the book series: Pediatric Oncology ((PEDIATRICO))

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Abstract

This chapter focuses on pediatric high-grade gliomas, with the exception of diffuse intrinsic pontine gliomas, which will be covered in a different chapter of this text. Gliomas arise from glial cells, which support and protect neurons and are most commonly differentiated along the astrocytic or oligodendroglial lineage. The World Health Organization (WHO) classification divides gliomas into low (WHO grade I and II)- and high-grade subgroups (Luis et al. 2007). High-grade pediatric central nervous system (CNS) tumors are comprised primarily of anaplastic astrocytomas (AA, WHO grade III) and glioblastomas (GBM, WHO grade IV), as anaplastic tumors with an oligodendroglial component are very uncommon in children (Hyder et al. 2007). High-grade gliomas can either present as high-grade disease, or they can result from transformation of a low-grade tumor, although the latter is less common in children. In contrast to the adult population, high-grade gliomas in children are relatively infrequent, representing less than 20 % of cases (Pollack 1994; Packer 1999). The etiology for most pediatric CNS tumors is unknown, although some genetic syndromes are associated with an increased risk. Despite advances in treatment for other childhood tumors, patients with high-grade gliomas invariably have a poor outcome, and 5-year survival rates remain less than 20 %.

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References

  • Armstrong CL, Gyato K et al (2004) A critical review of the clinical effects of therapeutic irradiation damage to the brain: the roots of controversy. Neuropsychol Rev 14(1):65–86

    Article  PubMed  Google Scholar 

  • Barani IJ, Cuttino LW et al (2007) Neural stem cell-preserving external-beam radiotherapy of central nervous system malignancies. Int J Radiat Oncol Biol Phys 68(4):978–985

    Article  PubMed  Google Scholar 

  • Bax DA, Gaspar N et al (2009) EGFRvIII deletion mutations in pediatric high-grade glioma and response to targeted therapy in pediatric glioma cell lines. Clin Cancer Res 15:5753–5761

    Article  CAS  PubMed  Google Scholar 

  • Bax DA, Mackay A et al (2010) A distinct spectrum of copy number aberrations in pediatric high-grade gliomas. Clin Cancer Res 16(13):3368–3377

    Google Scholar 

  • Benesch M, Wagner S et al (2005) Primary dissemination of high-grade gliomas in children: experiences from four studies of the Pediatric Oncology and Hematology Society of the German Language Group (GPOH). J Neurooncol 72(2):179–183

    Article  PubMed  Google Scholar 

  • Bredel M, Pollack IF et al (1999) Epidermal growth factor receptor expression and gene amplification in high-grade non-brainstem gliomas of childhood. Clin Cancer Res 5(7):1786–1792

    CAS  PubMed  Google Scholar 

  • Chapman PB, Hauschild A et al (2011) Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 364(26):2507–2516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheng Y, Ng HK, Zhang SF et al (1999) Genetic alterations in pediatric high-grade astrocytomas. Hum Pathol 30:1284–1290

    Article  CAS  PubMed  Google Scholar 

  • Cohen KJ, Pollack IF et al (2011) Temozolomide in the treatment of high-grade gliomas in children: a report from the Children’s Oncology Group. Neuro-Oncology 13:317–323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Donson AM, Addo-Yobo SO, Handler MH, Gore L, Foreman NK (2007) MGMT promoter methylation correlates with survival benefit and sensitivity to temozolomide in pediatric glioblastoma. Pediatr Blood Cancer 48:403–407

    Article  PubMed  Google Scholar 

  • Duffner PK (2007) Diagnosis of brain tumors in children. Expert Rev Neurother 7(7):875–885

    Article  PubMed  Google Scholar 

  • Duffner PK, Krischer JP et al (1996) Treatment of infants with malignant gliomas: the Pediatric Oncology Group experience. J Neuro-Oncol 28(2–3):245–256

    CAS  Google Scholar 

  • Estlin EJ, Lashford L et al (1998) Phase I study of temozolomide in paediatric patients with advanced cancer. United Kingdom Children’s Cancer Study Group. Br J Cancer 78(5):652–661

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Faury D, Nantel A et al (2007) Molecular profiling identifies prognostic subgroups of pediatric glioblastoma and shows increased YB-1 expression in tumors. J Clin Oncol 25(10):1196–1208

    Article  CAS  PubMed  Google Scholar 

  • Finlay JL, Boyett JM et al (1995) Randomized phase III trial in childhood high-grade astrocytoma comparing vincristine, lomustine, and prednisone with the eight-drugs-in-1-day regimen. Childrens Cancer Group. J Clin Oncol 13(1):112–123

    CAS  PubMed  Google Scholar 

  • Flaherty KT, Infante JR et al (2012) Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med 367:1694–1703

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fulton DS, Urtasun RC et al (1992) Increasing radiation dose intensity using hyperfractionation in patients with malignant glioma. Final report of a prospective phase I–II dose response study. J Neurooncol 14(1):63–72

    Article  CAS  PubMed  Google Scholar 

  • Ganigi PM, Santosh V, Anandh B, Chandramouli BA, Sastry Kolluri VR (2005) Expression of p53, EGFR, pRb and bcl-2 proteins in pediatric glioblastoma multiforme: a study of 54 patients. Pediatr Neurosurg 41:292–299

    Article  CAS  PubMed  Google Scholar 

  • Geyer JR, Finlay JL et al (1995) Survival of infants with malignant astrocytomas. A report from the Childrens Cancer Group. Cancer 75(4):1045–1050

    Article  CAS  PubMed  Google Scholar 

  • Grovas AC, Boyett JM et al (1999) Regimen-related toxicity of myeloablative chemotherapy with BCNU, thiotepa, and etoposide followed by autologous stem cell rescue for children with newly diagnosed glioblastoma multiforme: report from the Children’s Cancer Group. Med Pediatr Oncol 33(2):83–87

    Article  CAS  PubMed  Google Scholar 

  • Gutierrez AN, Westerly DC et al (2007) Whole brain radiotherapy with hippocampal avoidance and simultaneously integrated brain metastases boost: a planning study. Int J Radiat Oncol Biol Phys 69(2):589–597

    Article  PubMed  PubMed Central  Google Scholar 

  • Hamilton SR, Liu B et al (1995) The molecular basis of Turcot’s syndrome. N Engl J Med 332(13):839–847

    Article  CAS  PubMed  Google Scholar 

  • Harrow S, Papanastassiou et al (2004) HSV1716 injection into the brain adjacent to tumour following surgical resection of high-grade glioma: safety data and long-term survival. Gene Ther 11:1648–1658

    Article  CAS  PubMed  Google Scholar 

  • Hegde MR, Chong B et al (2005) A homozygous mutation in MSH6 causes Turcot syndrome. Clin Cancer Res 11(13):4689–4693

    Article  CAS  PubMed  Google Scholar 

  • Heideman RL, Kuttesch J Jr et al (1997) Supratentorial malignant gliomas in childhood: a single institution perspective. Cancer 80(3):497–504

    Article  CAS  PubMed  Google Scholar 

  • Hyder DJ, Sung L et al (2007) Anaplastic mixed gliomas and anaplastic oligodendroglioma in children: results from the CCG 945 experience. J Neuro-Oncol 83:1–8

    Article  Google Scholar 

  • Lashford LS, Thiesse P et al (2002) Temozolomide in malignant gliomas of childhood: a United Kingdom Children’s Cancer Study Group and French Society for Pediatric Oncology Intergroup Study. J Clin Oncol 20(24):4684–4691

    Article  CAS  PubMed  Google Scholar 

  • Li FP, Fraumeni JF Jr et al (1988) A cancer family syndrome in twenty-four kindreds. Cancer Res 48(18):5358–5362

    CAS  PubMed  Google Scholar 

  • Liang M-L, Ma J et al (2008) Tyrosine kinase expression in pediatric high grade astrocytoma. J Neuro-Oncol 87:247–253

    Article  Google Scholar 

  • Luis DN, Ohgaki H et al (2007) The WHO classification of tumors of the nervous system. Acta Neuropathol 114(2):97–109

    Article  Google Scholar 

  • Marachelian A, Butturini A et al (2008) Myeloablative chemotherapy with autologous hematopoietic progenitor cell rescue for childhood central nervous system tumors. Bone Marrow Transplant 41(2):167–172

    Article  CAS  PubMed  Google Scholar 

  • Massimino M, Gandola L et al (2005) Sequential chemotherapy, high-dose thiotepa, circulating progenitor cell rescue, and radiotherapy for childhood high-grade glioma. Neuro-Oncology 7(1):41–48

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mehta V, Chapman A et al (2002) Latency between symptom onset and diagnosis of pediatric brain tumors: an Eastern Canadian geographic study. Neurosurgery 51(2):365–372; discussion 372–373

    PubMed  Google Scholar 

  • Merchant TE, Hua CH et al (2008) Proton versus photon radiotherapy for common pediatric brain tumors: comparison of models of dose characteristics and their relationship to cognitive function. Pediatr Blood Cancer 51(1):110–117

    Article  PubMed  Google Scholar 

  • Mueller S, Phillips J et al (2012) PTEN promoter methylation and activation of the PI3K/Akt/mTOR pathway in pediatric gliomas and influence on clinical outcome. Neuro-Oncology 14(9):1146–1152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakamura M, Shimada K et al (2007) Molecular pathogenesis of pediatric astrocytic tumors. Neuro-Oncology 9(2):113–123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nicholson HS, Kretschmar CS et al (2007) Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors: a report from the Children’s Oncology Group. Cancer 110(7):1542–1550

    Article  CAS  PubMed  Google Scholar 

  • Nicoliades TP, Li H et al (2011) Targeted therapy for BRAF V600E malignant astrocytoma. Clin Cancer Res 21(6):7595–7604

    Article  Google Scholar 

  • Packer RJ (1999) Primary central nervous system tumors in children. Curr Treat Options Neurol 1(5):395–408

    Article  PubMed  Google Scholar 

  • Packer RJ, Boyett JM et al (1993) Hyperfractionated radiation therapy (72 Gy) for children with brain stem gliomas. A Childrens Cancer Group phase I/II trial. Cancer 72(4):1414–1421

    Article  CAS  PubMed  Google Scholar 

  • Palucka K, Banchereau J (2012) Cancer immunotherapy via dendritic cells. Nat Rev Cancer 12:265–277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paugh BS, Qu C et al (2010) Integrated molecular genetic profiling of pediatric high-grade gliomas reveals key differences with the adult disease. J Clin Oncol 28(18):3061–3068

    Article  PubMed  PubMed Central  Google Scholar 

  • Pettorini BL, Park YS et al (2008) Radiation-induced brain tumours after central nervous system irradiation in child-hood: a review. Childs Nerv Syst 24(7):793–805

    Article  PubMed  Google Scholar 

  • Pollack IF (1994) Brain tumors in children. N Engl J Med 331(22):1500–1507

    Article  CAS  PubMed  Google Scholar 

  • Pollack IF, Finkelstein SD et al (2001) Age and TP53 mutation frequency in childhood malignant gliomas: results in a multiinstitutional cohort. Cancer Res 61(20):7404–7407

    CAS  PubMed  Google Scholar 

  • Pollack IF, Finkelstein SD et al (2002a) Expression of p53 and prognosis in children with malignant gliomas. N Engl J Med 346(6):420–427

    Article  CAS  PubMed  Google Scholar 

  • Pollack IF, Hamilton RL et al (2002b) Impact of proliferation index on outcome in childhood malignant gliomas: results in a multi-institutional cohort. Neurosurgery 50(6):1238–1244; discussion 1244–1245

    PubMed  Google Scholar 

  • Pollack IF, Hamilton RL et al (2006a) Rarity of PTEN deletions and EGFR amplification in malignant gliomas of childhood: results from the Children’s Cancer Group 945 cohort. J Neurosurg 105(5 Suppl):418–424

    PubMed  Google Scholar 

  • Pollack IF, Hamilton RL et al (2006b) O6-methylguanine-DNA methyltransferase expression strongly correlates with outcome in childhood malignant gliomas: results from the CCG-945 cohort. J Clin Oncol 24(21):3431–3437

    Article  CAS  PubMed  Google Scholar 

  • Pollack IF, Hamilton RL et al (2010) Akt activation is a common event in pediatric malignant gliomas and a potential adverse prognostic marker: a report from the Children’s Oncology Group. J Neuro-Oncol 99:155–163

    Article  CAS  Google Scholar 

  • Pollack IF, Hamilton RL et al (2011) IDH1 mutations are common in malignant gliomas arising in adolescents: a report from the Children’s Oncology Group. Childs Nerv Syst 27(1):87–94

    Article  PubMed  Google Scholar 

  • Pollack IF, Jakacki RI et al (2014) Antigen-specific immune responses and clinical outcome after vaccination with glioma-associated antigen peptides and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in children with newly diagnosed malignant brainstem and nonbrainstem gliomas. J Clin Oncol 32(19):2050–2058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raffel C, Frederick L, O’Fallon JR et al (1999) Analysis of oncogene and tumor suppressor gene alterations in pediatric malignant astrocytomas reveals reduced survival for patients with PTEN mutations. Clin Cancer Res 5:4085–4090

    CAS  PubMed  Google Scholar 

  • Robinson GW, Orr BA, Gajjar A (2014) Complete clinical regression of a BRAF B600E-mutant pediatric glioblastoma multiforme after BRAF inhibitor therapy. BMC Cancer 14:258

    Article  PubMed  PubMed Central  Google Scholar 

  • Schiffman JD, Hodgson JG et al (2010) Oncogenic BRAF mutation with CDKN2A inactivation is characteristic of a subset of pediatric malignant astrocytomas. Cancer Res 70:512–519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schwartzentruber J, Korshunov A et al (2012) Driver mutations in histone H3.3 and chromatin remodeling genes in paediatric glioblastoma. Nature 482(7384):226–231

    Article  CAS  PubMed  Google Scholar 

  • Setty P, Hammes J et al (2010) A pyrosequencing-based assay for the rapid detection of IDH1 mutations in clinical samples. J Mol Diagn 12(6):750–756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sposto R, Ertel IJ et al (1989) The effectiveness of chemotherapy for treatment of high grade astrocytoma in children: results of a randomized trial. A report from the Children’s Cancer Study Group. J Neurooncol 7(2):165–177

    Article  CAS  PubMed  Google Scholar 

  • Stupp R, Dietrich PY et al (2002) Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. J Clin Oncol 20(5):1375–1382

    Article  CAS  PubMed  Google Scholar 

  • Stupp R, Mason WP et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):997–1003

    Article  PubMed  Google Scholar 

  • Sturm D, Witt H et al (2012) Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell 22(4):425–437

    Article  CAS  PubMed  Google Scholar 

  • Sure U, Ruedi D, Tachibana O et al (1997) Determination of p53 mutations, EGFR overexpression, and loss of p16 expression in pediatric glioblastomas. J Neuropathol Exp Neurol 56:782–789

    Article  CAS  PubMed  Google Scholar 

  • Tamber MS, Rutka JT (2003) Pediatric supratentorial high grade gliomas. Neurosurg Focus 14(2):e1

    Article  PubMed  Google Scholar 

  • Thorarinsdottir HK, Santi M et al (2008) Protein expression of platelet-derived growth factor receptor correlates with malignant histology and PTEN with survival in childhood gliomas. Clin Cancer Res 14(11):3386–3394

    Google Scholar 

  • Turcot J, Despres JP et al (1959) Malignant tumors of the central nervous system associated with familial polyposis of the colon: report of two cases. Dis Colon Rectum 2:465–468

    Article  CAS  PubMed  Google Scholar 

  • Varley JM, McGown G et al (1997) Germ-line mutations of TP53 in Li-Fraumeni families: an extended study of 39 families. Cancer Res 57(15):3245–3252

    CAS  PubMed  Google Scholar 

  • Warren KE, Gururangan S et al (2011) A phase II study of O6-benzylguanine and temozolomide in pediatric patients with recurrent or progressive high-grade gliomas and brainstem gliomas: a Pediatric Brain Tumor Consortium study. J Neuro-Oncol 106(3):643–649

    Article  Google Scholar 

  • Wisoff JH, Boyett JM et al (1998) Current neurosurgical management and the impact of the extent of resection in the treatment of malignant gliomas of childhood: a report of the Children’s Cancer Group trial no. CCG-945. J Neurosurg 89(1):52–59

    Article  CAS  PubMed  Google Scholar 

  • Wolff JE, Gnekow AK et al (2002) Preradiation chemotherapy for pediatric patients with high-grade glioma. Cancer 94(1):264–271

    Article  CAS  PubMed  Google Scholar 

  • Wolff JE, Driever PH et al (2010) Intensive chemotherapy improves survival in pediatric high-grade glioma after gross total resection: results of the. HIT-GBM-C Protoc 116(3):705–712

    Google Scholar 

  • Wu G, Broniscer A et al (2012) Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 44(3):251–253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang T, Temkin N et al (2013) Gross total resection correlates with long-term survival in pediatric patients with glioblastoma. World Neurosurg 79(3–4):537–544

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Radiation Oncology, University of California San Francisco & UCSF Benioff Children’s Hospital, 1600 Divisadero Street, Suite H1031, San Francisco, CA, 94115, USA

    Jennifer S. Chang MD, PhD

  2. Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Boston Children’s Hospital, 450 Brookline Ave. D1622, Boston, MA, 02215-5418, USA

    Daphne A. Haas-Kogan MD

  3. Departments of Neurology, Neurosurgery and Pediatrics, University of California San Francisco & UCSF Benioff Children’s Hospital, 625 Nelson Rising Lane, Room 402C, Sandler Neuroscience Building, San Francisco, CA, 94158, USA

    Sabine Mueller MD, PhD, MAS

Authors
  1. Jennifer S. Chang MD, PhD
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  2. Daphne A. Haas-Kogan MD
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  3. Sabine Mueller MD, PhD, MAS
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Correspondence to Jennifer S. Chang MD, PhD .

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Editors and Affiliations

  1. San Francisco, California, USA

    Nalin Gupta

  2. San Francisco, California, USA

    Anuradha Banerjee

  3. Boston, Massachusetts, USA

    Daphne A. Haas-Kogan

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Chang, J.S., Haas-Kogan, D.A., Mueller, S. (2017). High-Grade Gliomas. In: Gupta, N., Banerjee, A., Haas-Kogan, D. (eds) Pediatric CNS Tumors. Pediatric Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-30789-3_2

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  • DOI: https://doi.org/10.1007/978-3-319-30789-3_2

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