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Pediatric Brain Tumors: Application of Stratification Criteria to Refine Patient Management

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Pediatric Cancer, Volume 2

Part of the book series: Pediatric Cancer ((PECA,volume 2))

Abstract

Current treatment strategies for children with brain tumors focus on improving outcome for tumor types that have historically been relatively resistant to therapy, and reducing treatment-related sequelae for children with therapy-responsive tumors. Refinements in clinical and molecular stratification for many types of childhood brain tumors have facilitated these efforts to achieve risk-adapted treatment planning. In some instances, molecular characterization approaches have also yielded insights into new therapeutic targets. This chapter reviews advances in stratification approaches for several of the most common types of childhood brain tumors, including high- and low-grade gliomas, medulloblastomas and other primitive neuroectodermal tumors (PNETs), and infant brain tumors, and discusses how new information regarding the biological features critical to tumorigenesis is being translated into novel therapeutic approaches for these challenging tumors.

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References

  • Ater J, Mazewski C, Roberts W, Sposto R, Zhou T, Freyer D, Jakacki R, Kadota R, Lazarus K, Packer R, Pearce J, Prados M, Ettinger A, Vezina G, Wisoff J, Yates A, Pollack I (2007) Phase 3 randomized study of two chemotherapy regimens for treatment of progressive low-grade glioma in young children: preliminary report from the Children’s Oncology Group protocol A9952. Neuro Oncol 9:204

    Google Scholar 

  • Biegel JA, Zhou J-Y, Rorke LB, Stenstrom C, Wainwright LM, Fogelgren B (1999) Germline and acquired mutations of INI1 in atypical teratoid and rhabdoid tumors. Cancer Res 59:74–79

    PubMed  CAS  Google Scholar 

  • Bradley KA, Pollack IF, Reid JM, Adamson PC, Ames MM, Vezina G, Blaney S, Ivy P, Zhou T, Krailo M, Reaman G, Mehta MP (2008) Motexafin gadolinium and involved field radiation therapy for intrinsic pontine glioma of childhood: a Children’s Oncology Group Phase 1 study. Neuro Oncol 10:752–758

    Article  PubMed  CAS  Google Scholar 

  • Cohen KJ, Heideman R, Zhou T, Holmes E, Burger PC, Brat DJ, Rosenblum M, Pollack IF (2007) Should temozolomide be the standard of care for children with newly diagnosed high-grade gliomas? Results of the Children’s Oncology Group ACNS0126 study. Neuro-oncology 9:188

    Google Scholar 

  • Duffner PK, Horowitz ME, Krischer JP, Friedman HS, Burger PC, Cohen ME, Sanford RA, Mulhern RK, James HE, Freeman CR, Seidel FG, Kun LE (1993) Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med 328:1725–1731

    Article  PubMed  CAS  Google Scholar 

  • Finlay JL, Boyett JM, Yates AJ, Milstein JM, Geyer JR, Bertolone SJ, McGuire P, Cherlow JM, Tefft M (1995) Randomized phase III trial in childhood high-grade astrocytoma comparing vincristine, lomustine, and prednisone with the eight-drugs-in-1-day regimen. J Clin Oncol 13:112–123

    PubMed  CAS  Google Scholar 

  • Geyer JR, Sposto R, Jennings M, Boyett JM, Axtell RA, Breiger D, Broxsonm E, Donahue B, Finlay JL, Goldwein JW, Heier LA, Johnson D, Mazewski C, Miller DC, Packer R, Puccetti D, Radcliffe J, Tao ML, Shiminski-Maher T (2005) Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the Children’s Cancer Group. J Clin Oncol 23:7621–7631

    Article  PubMed  Google Scholar 

  • Hartmann C, Meyer J, Balss J, Capper D, Mueller W, Christians A, Felsberg J, Wolter M, Mawrin C, Wick W, Weller M, Herold-Mende C, Unterberg A, Jeuken JWM, Wesseling P, Reifenberger G, von Deimling A (2009) Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas. Acta Neuropathol 118:469–474

    Article  PubMed  Google Scholar 

  • Jakacki R, Burger P, Zhou T, Holmes E, Packer R, Goldwein J, Mehta M, Pollack I (2007) Outcome for metastatic (M+) medulloblastoma (MB) treated with carboplatin during craniospinal radiotherapy (CSRT) followed by cyclophosphamide (CPM) and vincristine (VCR). J Clin Oncol 25:75S

    Google Scholar 

  • Jakacki R, Yates A, Blaney S, Zhou T, Timmerman RD, Ingle AM, Flom L, Prados M, Adamson PC, Pollack I (2008) A phase I trial of temozolomide and CCNU in newly diagnosed high-grade gliomas of childhood: a report from the Children’s Oncology Group. Neuro-oncology 10:569–576

    Article  PubMed  CAS  Google Scholar 

  • Jennings MT, Sposto R, Boyett JM, Vezina LG, Holmes E, Berger MS, Bruggers CS, Bruner JM, Chan K-W, Dusenbery KE, Ettinger LJ, Fitz CR, Lafond D, Mandelbaum DE, Massey V, McGuire W, McNeely L, Moulton T, Pollack IF, Shen V (2002) Preradiation chemotherapy in primary high-risk brain stem tumors: phase II study CCG-9941 of the Children’s Cancer Group. J Clin Oncol 20:3431–3437

    Article  PubMed  CAS  Google Scholar 

  • Jones DT, Kocialkowski S, Liu L, Pearson DM, Backlund LM, Ichimura K, Collins VP (2008) Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas. Cancer Res 68:8673–8677

    Article  PubMed  CAS  Google Scholar 

  • Judkins AR, Burger PC, Hamilton RL, Kleinschmidt-DeMasters B, Perry A, Pomeroy SL, Rosenblum MK, Yachnis AT, Zhou H, Rorke LB, Biegel JA (2005) INI1 protein expression distinguishes atypical teratoid/rhabdoid tumor from choroid plexus carcinoma. J Neuropathol Exp Neurol 64:391–397

    PubMed  CAS  Google Scholar 

  • Kool M, Koster J, Bunt J, Hasselt NE, Lakeman A, van Sluis P, Troost D, Schouten-van Meeteren N, Caron HN, Cloos J, Mrsic A, Ylstra B, Grajkowska W, Hartmann W, Pietsch T, Ellison D, Clifford SC, Versteeg R (2008) Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features. PLoS One 3(8):e3088

    Article  PubMed  Google Scholar 

  • Lam C, Bouffet E, Tabori U, Mabbott D, Taylor M, Bartels U (2010) Rapamycin (sirolimus) in tuberous sclerosis associated pediatric central nervous system tumors. Pediatr Blood Cancer 54:476–479

    Article  PubMed  Google Scholar 

  • MacDonald T, Arenson EB, Ater J, Sposto R, Bevan HE, Bruner J, Deutsch M, Kurczynski E, Luerssen T, McGuire-Cullen P, O-Brien R, Shah N (2005) Phase II study of high-dose chemotherapy before radiation in children with newly diagnosed high-grade astrocytoma: final analysis of Children’s Cancer Group study 9933. Cancer 104:2862–2871

    Article  PubMed  CAS  Google Scholar 

  • Packer RJ, Ater J, Allen J, Phillips P, Geyer R, Nicholson HS, Jakacki R, Kurczynski E, Needle M, Finlay J, Reaman G, Boyett JM (1997) Carboplatin and vincristine chemotherapy for children with newly-diagnosed progressive low-grade gliomas. J Neurosurg 86:747–754

    Article  PubMed  CAS  Google Scholar 

  • Packer R, Gajjar A, Vezina G, Rorke-Adams L, Burger P, Robertson P, Bayer L, LaFond D, Donahue B, Marymont M, Muraszko K, Langston JW, Sposto R (2006) Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy regimens for newly diagnosed average-risk medulloblastoma. J Clin Oncol 24:4202–4208

    Article  PubMed  CAS  Google Scholar 

  • Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, Olivi A, McLendon R, Rasheed BA, Keirm S, Nikolskaya T, Nikolsky Y, Busam DA, Tekleab H, Diaz LA Jr, Hartigan J, Smith DR, Strausberg RL, Marie SK, Shinjo SM, Yan H, Riggins GJ, Bigner DD, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807–1812

    Article  PubMed  CAS  Google Scholar 

  • Pizer BL, Weston CL, Robinson KJ, Ellison DW, Ironside J, Saran F, Lashford LS, Tait D, Lucraft H, Walker DA, Bailey CC, Taylor RE (2006) Analysis of patients with supratentorial primitive neuro-ectodermal tumours entered into the SIOP/UKCCSG PNET 3 study. Eur J Cancer 42:1120–1128

    Article  PubMed  Google Scholar 

  • Pollack IF (1994) Brain tumors in children. N Engl J Med 337:1500–1507

    Article  Google Scholar 

  • Pollack IF, Finkelstein SD, Woods J, Burnham J, Holmes EJ, Hamilton RL, Yates AJ, Boyett JM, Finlay JL, Sposto R (2002) Expression of p53 and prognosis in malignant gliomas in children. N Engl J Med 346:420–427

    Article  PubMed  CAS  Google Scholar 

  • Pollack IF, Hamilton RL, James CD, Finkelstein SD, Burnham J, Yates AJ, Holmes EJ, Zhou T, Finlay JL (2006a) Rarity of PTEN deletions and EGFR amplification in malignant gliomas of childhood: results from the Children’s Cancer Group 945 cohort. J Neurosurg Pediatr 105:3431–3437

    Article  Google Scholar 

  • Pollack IF, Hamilton RL, Sobol RW, Burnham J, Yates AJ, Holmes EJ, Zhou T, Finlay JL (2006b) MGMT expression strongly correlates with outcome in childhood malignant gliomas: results from the CCG-945 cohort. J Clin Oncol 24:3431–3437

    Article  PubMed  CAS  Google Scholar 

  • Pollack IF, Jakacki RI, Blaney SM, Hancock ML, Kieran MW, Phillips P, Kun LE, Friedman H, Packer R, Banerjee A, Geyer JR, Goldman S, Young-Poussaint T, Krasin MJ, Wang Y, Hayes M, Murgo A, Weiner S, Boyett JM (2007) Phase I trial of imatinib in children with newly diagnosed brainstem and recurrent malignant gliomas: a Pediatric Brain Tumor Consortium report. Neuro Oncol 9:145–160

    Article  PubMed  CAS  Google Scholar 

  • Pomeroy S, Tamayo P, Gaasenbeek M, Sturla LM, Angelo M, McLaughlin ME, Kim JYH, Goumnerova LC, Black PM, Lau C, Allen JC, Zagzag D, Olson JM, Curran T, Wetmore C, Biegel JA, Poggio T, Mukherjee S, Rifkin A, Califano A, Stolovitzky G, Louis DN, Mesirov JP, Lander ES, Golub TR (2002) Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature 415:436–442

    Article  PubMed  CAS  Google Scholar 

  • Raffel C, Jenkins RB, Frederick L, Hebrink D, Alderete B, Fults DW, James CD (1997) Sporadic medulloblastomas contain PTCH mutations. Cancer Res 57:842–845

    PubMed  CAS  Google Scholar 

  • Romer J, Curran T (2005) Targeting medulloblastoma: small-molecule inhibitors of the Sonic hedgehog pathway as potential cancer therapeutics. Cancer Res 65:4975–4978

    Article  PubMed  CAS  Google Scholar 

  • Rudin CM, Hann CL, Laterra J, Yauch RL, Callahan CA, Fu L, Holcomb T, Stinson J, Gould SE, Coleman B, LoRusso PM, Von Hoff DD, deSauvage FJ, Low JA (2009) Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449. N Engl J Med 361:1173–1178

    Article  PubMed  CAS  Google Scholar 

  • Rutkowski S, Bode U, Deinlein F, Ottensmeier H, Warmuth-Metz M, Soerensen N, Graf N, Emser A, Pietsch T, Wolff JE, Kortmann RD, Kuehl J (2005) Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med 352:978–986

    Article  PubMed  CAS  Google Scholar 

  • Sanford A, Kun L, Sposto R, Holmes E, Wisoff JH, Heier L, McGuire-Cullen P (2002) Low-grade gliomas of childhood: impact of surgical resection. A report from the Children’s Oncology Group. J Neurosurg 96:427–428

    Google Scholar 

  • Sposto R, Ertel IJ, Jenkin RD, Boesel CP, Venes JL, Ortega JA, Evans AE, Wara W, Hammond D (1989) The effectiveness of chemotherapy for treatment of high grade astrocytoma in children: results of a randomized trial. A report from the Childrens Cancer Study Group. J Neurooncol 7:165–177

    Article  PubMed  CAS  Google Scholar 

  • Tait DM, Thornton-Jones H, Bloom HJG, Lemerle J, Morris-Jones P (1990) Adjuvant chemotherapy for medulloblastoma: the first multi-centre control trial of the International Society of Paediatric Oncology (SIOP I). Eur J Cancer 26:464–469

    PubMed  CAS  Google Scholar 

  • Taylor RE, Bailey CC, Robinson KJ, Weston CL, Walker DA, Ellison D, Ironside J, Pizer BL, Lashford LS (2005) Outcome for patients with metastatic (M2-3) medulloblastoma treated with SIOP/UKCCSG PNET-3 chemotherapy. Eur J Cancer 41:727–734

    Article  PubMed  CAS  Google Scholar 

  • Tekautz TM, Fuller CE, Blaney S, Fouladi M, Broniscer A, Merchant TE, Krasin M, Dalton J, Hale G, Kun LE, Wallace D, Gilbertson RJ, Gajjar A (2005) Atypical teratoid/rhabdoid tumors (ATRT): improved survival in children 3 years of age and older with radiation therapy and high-dose alkylator-based chemotherapy. J Clin Oncol 23:1491–1499

    Article  PubMed  CAS  Google Scholar 

  • Thomas RM, Deutsch M, Kepner JL, Boyett JM, Krischer P, Aronin P, Albright AL, Allen JC, Packer RJ, Linggood R, Mulhern R, Stehbens JA, Langston J, Stanley P, Duffner P, Rorke L, Cherlow J, Friedman HS, Finlay JL, Vietti TJ, Kun LE (2000) Low-stage medulloblastoma: final analysis of trial comparing standard-dose with reduced dose neuraxis irradiation. J Clin Oncol 18:3004–3011

    PubMed  CAS  Google Scholar 

  • Thompson MC, Fuller C, Hogg TL, Dalton J, Finkelstein D, Lau CC, Chintagumpala M, Adesina A, Ashley DM, Kellie SJ, Taylor MD, Curran T, Gajjar A, Gilbertson RJ (2006) Genomics identifies medulloblastoma subgroups that are enriched for specific genetic alterations. J Clin Oncol 24:1924–1931

    Article  PubMed  CAS  Google Scholar 

  • Verhaak RGW, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, Miller CR, Ding L, Golub T, Mesirov JP, Alexe G, Lawrence M, O’Kelly M, Tamayo P, Weir BA, Gabriel S, Winckler W, Gupta S, Jakkula L, Feiler HS, Hodgson JG, James CD, Sarkaria JN, Brennan C, Kahn A, Spellman PT, Wilson RK, Speed TP, Gray JW, Meyerson M, Getz G, Perou CM, Hayes DN (2010) Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFR, IDH1, EGFR, and NF1. Cancer Cell 17:98–110

    Article  PubMed  CAS  Google Scholar 

  • Zeltzer PM, Boyett JM, Finlay JL, Albright AL, Rorke LB, Milstein JM, Allen JC, Stevens KR, Stanley P, Li H, Wisoff JH, Geyer JR, McGuire-Cullen P, Stehbens JA, Shurin SB, Packer RJ (1999) Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children: conclusions from the Children’s Cancer Group 921 randomized phase III study. J Clin Oncol 17:832–845

    PubMed  CAS  Google Scholar 

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Acknowledgment

This work was supported in part by National Institutes of Health grants P01NS40923 and R01NS37704.

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  1. Department of Neurosurgery, Children’s Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA

    Ian F. Pollack

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  1. Ian F. Pollack
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Correspondence to Ian F. Pollack .

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  1. , Kean University, Room 213, Library building, Morris Avenue 1000, Union, 07083, New Jersey, USA

    M.A. Hayat

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Pollack, I.F. (2012). Pediatric Brain Tumors: Application of Stratification Criteria to Refine Patient Management. In: Hayat, M. (eds) Pediatric Cancer, Volume 2. Pediatric Cancer, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2957-5_21

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