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Child's Nervous System

, Volume 36, Issue 1, pp 133–144 | Cite as

Subgroup-specific outcomes of children with malignant childhood brain tumors treated with an irradiation-sparing protocol

  • Eveline Teresa HidalgoEmail author
  • Matija Snuderl
  • Cordelia Orillac
  • Svetlana Kvint
  • Jonathan Serrano
  • Peter Wu
  • Matthias A. Karajannis
  • Sharon L. Gardner
Original Article

Abstract

Purpose

Molecular subgroups of pediatric brain tumors associated with divergent biological, clinical, and prognostic features have been identified. However, data regarding the impact of subgroup affiliation on the outcome of children with malignant brain tumors treated with radiation-sparing protocol is limited. We report long-term clinical outcomes and the molecular subgroups of malignant brain tumors in young children whose first-line treatment was high-dose chemotherapy without irradiation.

Methods

Tumor subclassification was performed using the Illumina HumanMethylation450 BeadChip (450k) genome-wide methylation array profiling platform. Clinical information was obtained from chart review.

Results

Methylation array profiling yielded information on molecular subgroups in 22 children. Median age at surgery was 26 months (range 1–119 months). Among medulloblastomas (MB), all 6 children in the infant sonic hedgehog (SHH) subgroup were long-term survivors, whereas all 4 children in subgroup 3 MB died. There was one long-term survivor in subgroup 4 MB. One out of five children with ependymoma was a long-term survivor (RELPOS). Both children with primitive neuroectodermal tumors died. One child with ATRT TYR and one child with choroid plexus carcinoma were long-term survivors.

Conclusions

The efficacy of high-dose chemotherapy radiation-sparing treatment appears to be confined to favorable molecular subgroups of pediatric brain tumors, such as infant SHH MB. Identification of molecular subgroups that benefit from radiation-sparing therapy will aid in the design of prospective, “precision medicine”–driven clinical trials.

Keywords

Pediatric brain tumor Clinical outcome Molecular subgroups 

Notes

Acknowledgments

We thank Dr. Jeffrey H. Wisoff and Dr. Jeffrey Allen for their assistance in acquiring patient data, Dr. Shiyang Wang for assistance in acquiring tissue from the CBRD (Center for Biospecimen Research & Development), Dr. Cheddhi Thomas for identifying the samples and reviewing tissue specimen, and Dr. Christopher Bowman for assistance in developing bioinformatics analysis.

Funding information

This publication is supported by the NYU CTSA grant UL1TR001445 from the National Center for Advancing Translational Sciences, National Institutes of Health, and in part by the NYUCI Center Support Grant “NIH/NCI 5 P30CA16087-31.”

S.L.G. and E.T.H. received grants from the Making Headway Foundation and M.S. from the Sohn Conference Foundation and the Friedberg Charitable Foundation.

Compliance with ethical standards

The study was approved by the NYU Institutional Review Board (IRB no. S14-00948).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institution and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Formal consent is not required for this type of study.

Supplementary material

381_2019_4305_MOESM1_ESM.pdf (427 kb)
ESM 1 (PDF 427 kb)

References

  1. 1.
    Packer RJ, Meadows AT, Rorke LB, Goldwein JL, D’Angio G (1987) Long-term sequelae of cancer treatment on the central nervous system in childhood. Med Pediatr Oncol 15(5):241–253PubMedGoogle Scholar
  2. 2.
    Meadows A, Massari D, Fergusson J, Gordon J, Littman P, Moss K (1981) Declines in IQ scores and cognitive dysfunctions in children with acute lymphocytic leukaemia treated with cranial irradiation. Lancet. 318(8254):1015–1018Google Scholar
  3. 3.
    Ris MD, Packer R, Goldwein J, Jones-Wallace D, Boyett JM (2001) Intellectual outcome after reduced-dose radiation therapy plus adjuvant chemotherapy for medulloblastoma : a Children’s Cancer Group study. J Clin Oncol 19(15):3470–3476PubMedGoogle Scholar
  4. 4.
    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(24):1725–1731PubMedGoogle Scholar
  5. 5.
    Geyer JR, Sposto R, Jennings M, Boyett JM, Axtell RA, Breiger D, Broxson 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, Children’s Cancer Group (2005) Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the Children’s Cancer Group. J Clin Oncol 23(30):7621–7631PubMedGoogle Scholar
  6. 6.
    Geyer JR, Zeltzer PM, Boyett JM, Rorke LB, Stanley P, Albright AL, Wisoff JH, Milstein JM, Allen JC, Finlay JL (1994) Survival of infants with primitive neuroectodermal tumors or malignant ependymomas of the CNS treated with eight drugs in 1 day: a report from the Childrens Cancer Group. J Clin Oncol 12(8):1607–1615PubMedGoogle Scholar
  7. 7.
    Cohen BH, Geyer JR, Miller DC, Curran JG, Zhou T, Holmes E et al (2015) Pilot study of intensive chemotherapy with peripheral hematopoietic cell support for children less than 3 years of age with malignant brain tumors, the CCG-99703 phase I/II study. A report from the Children’s Oncology Group. Pediatr Neurol. Elsevier Inc 53(1):31–46PubMedPubMedCentralGoogle Scholar
  8. 8.
    Dhall G, Grodman H, Ji L, Sands S, Gardner S, Dunkel IJ, McCowage GB, Diez B, Allen JC, Gopalan A, Cornelius AS, Termuhlen A, Abromowitch M, Sposto R, Finlay JL (2008) Outcome of children less than three years old at diagnosis with non-metastatic medulloblastoma treated with chemotherapy on the “Head Start” I and II protocols. Pediatr Blood Cancer 50(6):1169–1175PubMedGoogle Scholar
  9. 9.
    Altshuler C, Haley K, Dhall G, Vasquez L, Gardner SL, Stanek J et al (2016) Decreased morbidity and mortality of autologous hematopoietic transplants for children with malignant central nervous system tumors: the ‘Head Start’ trials, 1991–2009. Bone Marrow Transplant 51(7):945–948PubMedGoogle Scholar
  10. 10.
    Chi SN, Gardner SL, Levy AS, Knopp EA, Miller DC, Wisoff JH, Weiner HL, Finlay JL (2004) Feasibility and response to induction chemotherapy intensified with high-dose methotrexate for young children with newly diagnosed high-risk disseminated medulloblastoma. J Clin Oncol 22(24):4881–4887PubMedGoogle Scholar
  11. 11.
    Gardner SL, Asgharzadeh S, Green A, Horn B, McCowage G, Finlay J (2008) Intensive induction chemotherapy followed by high dose chemotherapy with autologous hematopoietic progenitor cell rescue in young children newly diagnosed with central nervous system atypical teratoid rhabdoid tumors. Pediatr Blood Cancer 51(2):235–240PubMedGoogle Scholar
  12. 12.
    Rutkowski S, Bode U, Deinlein F, Ottensmeier H, Warmuth-Metz M, Soerensen N, Graf N, Emser A, Pietsch T, Wolff JEA, Kortmann RD, Kuehl J (2005) Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med 352(10):978–986PubMedGoogle Scholar
  13. 13.
    Venkatramani R, Ji L, Lasky J, Haley K, Judkins A, Zhou S, Sposto R, Olshefski R, Garvin J, Tekautz T, Kennedy G, Rassekh SR, Moore T, Gardner S, Allen J, Shore R, Moertel C, Atlas M, Dhall G, Finlay J (2013) Outcome of infants and young children with newly diagnosed ependymoma treated on the “Head Start” III prospective clinical trial. J Neuro-Oncol 113(2):285–291Google Scholar
  14. 14.
    Zaky W, Dhall G, Ji L, Haley K, Allen J, Atlas M, Bertolone S, Cornelius A, Gardner S, Patel R, Pradhan K, Shen V, Thompson S, Torkildson J, Sposto R, Finlay JL (2014) Intensive induction chemotherapy followed by myeloablative chemotherapy with autologous hematopoietic progenitor cell rescue for young children newly-diagnosed with central nervous system atypical teratoid/rhabdoid tumors: the head start III experience. Pediatr Blood Cancer 61(1):95–101PubMedGoogle Scholar
  15. 15.
    Wong KK, All S, Waxer J, Olch AJ, Venkatramani R, Dhall G, Davidson TB, Zaky W, Finlay JL (2017) Radiotherapy after high-dose chemotherapy with autologous hematopoietic cell rescue: quality assessment of Head Start III. Pediatr Blood Cancer 64(10):e26529Google Scholar
  16. 16.
    Capper D, Jones DTW, Sill M, Hovestadt V, Schrimpf D, Sturm D, Koelsche C, Sahm F, Chavez L, Reuss DE, Kratz A, Wefers AK, Huang K, Pajtler KW, Schweizer L, Stichel D, Olar A, Engel NW, Lindenberg K, Harter PN, Braczynski AK, Plate KH, Dohmen H, Garvalov BK, Coras R, Hölsken A, Hewer E, Bewerunge-Hudler M, Schick M, Fischer R, Beschorner R, Schittenhelm J, Staszewski O, Wani K, Varlet P, Pages M, Temming P, Lohmann D, Selt F, Witt H, Milde T, Witt O, Aronica E, Giangaspero F, Rushing E, Scheurlen W, Geisenberger C, Rodriguez FJ, Becker A, Preusser M, Haberler C, Bjerkvig R, Cryan J, Farrell M, Deckert M, Hench J, Frank S, Serrano J, Kannan K, Tsirigos A, Brück W, Hofer S, Brehmer S, Seiz-Rosenhagen M, Hänggi D, Hans V, Rozsnoki S, Hansford JR, Kohlhof P, Kristensen BW, Lechner M, Lopes B, Mawrin C, Ketter R, Kulozik A, Khatib Z, Heppner F, Koch A, Jouvet A, Keohane C, Mühleisen H, Mueller W, Pohl U, Prinz M, Benner A, Zapatka M, Gottardo NG, Driever PH, Kramm CM, Müller HL, Rutkowski S, von Hoff K, Frühwald MC, Gnekow A, Fleischhack G, Tippelt S, Calaminus G, Monoranu CM, Perry A, Jones C, Jacques TS, Radlwimmer B, Gessi M, Pietsch T, Schramm J, Schackert G, Westphal M, Reifenberger G, Wesseling P, Weller M, Collins VP, Blümcke I, Bendszus M, Debus J, Huang A, Jabado N, Northcott PA, Paulus W, Gajjar A, Robinson GW, Taylor MD, Jaunmuktane Z, Ryzhova M, Platten M, Unterberg A, Wick W, Karajannis MA, Mittelbronn M, Acker T, Hartmann C, Aldape K, Schüller U, Buslei R, Lichter P, Kool M, Herold-Mende C, Ellison DW, Hasselblatt M, Snuderl M, Brandner S, Korshunov A, von Deimling A, Pfister SM (2018) DNA methylation-based classification of central nervous system tumours. Nature. 555(7697):469–474PubMedPubMedCentralGoogle Scholar
  17. 17.
    Assenov Y, Müller F, Lutsik P, Walter J, Lengauer T, Bock C (2014) Comprehensive analysis of DNA methylation data with RnBeads. Nat Methods 11(11):1138–1140PubMedPubMedCentralGoogle Scholar
  18. 18.
    Triche TJ, Weisenberger DJ, Van Den Berg D, Laird PW, Siegmund KD (2013) Low-level processing of Illumina Infinium DNA Methylation BeadArrays. Nucleic Acids Res 41(7):e90–e90PubMedPubMedCentralGoogle Scholar
  19. 19.
    Teschendorff AE, Marabita F, Lechner M, Bartlett T, Tegner J, Gomez-Cabrero D, Beck S (2013) A beta-mixture quantile normalization method for correcting probe design bias in Illumina Infinium 450 k DNA methylation data. Bioinformatics. 29(2):189–196PubMedGoogle Scholar
  20. 20.
    Hubner JM, Kool M, Pfister SM, Pajtler KW (2018) Epidemiology, molecular classification and WHO grading of ependymoma. J Neurosurg Sci 62(1):46–50PubMedGoogle Scholar
  21. 21.
    Pajtler KW, Witt H, Sill M, Jones DTW, Hovestadt V, Kratochwil F, Wani K, Tatevossian R, Punchihewa C, Johann P, Reimand J, Warnatz HJ, Ryzhova M, Mack S, Ramaswamy V, Capper D, Schweizer L, Sieber L, Wittmann A, Huang Z, van Sluis P, Volckmann R, Koster J, Versteeg R, Fults D, Toledano H, Avigad S, Hoffman LM, Donson AM, Foreman N, Hewer E, Zitterbart K, Gilbert M, Armstrong TS, Gupta N, Allen JC, Karajannis MA, Zagzag D, Hasselblatt M, Kulozik AE, Witt O, Collins VP, von Hoff K, Rutkowski S, Pietsch T, Bader G, Yaspo ML, von Deimling A, Lichter P, Taylor MD, Gilbertson R, Ellison DW, Aldape K, Korshunov A, Kool M, Pfister SM (2015) Molecular classification of ependymal tumors across all CNS compartments, histopathological grades, and age groups. Cancer Cell 27(5):728–743PubMedPubMedCentralGoogle Scholar
  22. 22.
    Wang X, Dubuc AM, Ramaswamy V, Mack S, Gendoo DMA, Remke M, Wu X, Garzia L, Luu B, Cavalli F, Peacock J, López B, Skowron P, Zagzag D, Lyden D, Hoffman C, Cho YJ, Eberhart C, MacDonald T, Li XN, van Meter T, Northcott PA, Haibe-Kains B, Hawkins C, Rutka JT, Bouffet E, Pfister SM, Korshunov A, Taylor MD (2015) Medulloblastoma subgroups remain stable across primary and metastatic compartments. Acta Neuropathol 129(3):449–457PubMedPubMedCentralGoogle Scholar
  23. 23.
    Hovestadt V, Remke M, Kool M, Pietsch T, Northcott PA, Fischer R, Cavalli FMG, Ramaswamy V, Zapatka M, Reifenberger G, Rutkowski S, Schick M, Bewerunge-Hudler M, Korshunov A, Lichter P, Taylor MD, Pfister SM, Jones DTW (2013) Robust molecular subgrouping and copy-number profiling of medulloblastoma from small amounts of archival tumour material using high-density DNA methylation arrays. Acta Neuropathol 125(6):913–916PubMedPubMedCentralGoogle Scholar
  24. 24.
    Sturm D, Witt H, Hovestadt V, Khuong-Quang D-A, Jones DTW, Konermann C, Pfaff E, Tönjes M, Sill M, Bender S, Kool M, Zapatka M, Becker N, Zucknick M, Hielscher T, Liu XY, Fontebasso AM, Ryzhova M, Albrecht S, Jacob K, Wolter M, Ebinger M, Schuhmann MU, van Meter T, Frühwald MC, Hauch H, Pekrun A, Radlwimmer B, Niehues T, von Komorowski G, Dürken M, Kulozik AE, Madden J, Donson A, Foreman NK, Drissi R, Fouladi M, Scheurlen W, von Deimling A, Monoranu C, Roggendorf W, Herold-Mende C, Unterberg A, Kramm CM, Felsberg J, Hartmann C, Wiestler B, Wick W, Milde T, Witt O, Lindroth AM, Schwartzentruber J, Faury D, Fleming A, Zakrzewska M, Liberski PP, Zakrzewski K, Hauser P, Garami M, Klekner A, Bognar L, Morrissy S, Cavalli F, Taylor MD, van Sluis P, Koster J, Versteeg R, Volckmann R, Mikkelsen T, Aldape K, Reifenberger G, Collins VP, Majewski J, Korshunov A, Lichter P, Plass C, Jabado N, Pfister SM (2012) Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell 22(4):425–437PubMedGoogle Scholar
  25. 25.
    Sturm D, Orr BA, Toprak UH, Hovestadt V, Jones DTW, Capper D, Sill M, Buchhalter I, Northcott PA, Leis I, Ryzhova M, Koelsche C, Pfaff E, Allen SJ, Balasubramanian G, Worst BC, Pajtler KW, Brabetz S, Johann PD, Sahm F, Reimand J, Mackay A, Carvalho DM, Remke M, Phillips JJ, Perry A, Cowdrey C, Drissi R, Fouladi M, Giangaspero F, Łastowska M, Grajkowska W, Scheurlen W, Pietsch T, Hagel C, Gojo J, Lötsch D, Berger W, Slavc I, Haberler C, Jouvet A, Holm S, Hofer S, Prinz M, Keohane C, Fried I, Mawrin C, Scheie D, Mobley BC, Schniederjan MJ, Santi M, Buccoliero AM, Dahiya S, Kramm CM, von Bueren AO, von Hoff K, Rutkowski S, Herold-Mende C, Frühwald MC, Milde T, Hasselblatt M, Wesseling P, Rößler J, Schüller U, Ebinger M, Schittenhelm J, Frank S, Grobholz R, Vajtai I, Hans V, Schneppenheim R, Zitterbart K, Collins VP, Aronica E, Varlet P, Puget S, Dufour C, Grill J, Figarella-Branger D, Wolter M, Schuhmann MU, Shalaby T, Grotzer M, van Meter T, Monoranu CM, Felsberg J, Reifenberger G, Snuderl M, Forrester LA, Koster J, Versteeg R, Volckmann R, van Sluis P, Wolf S, Mikkelsen T, Gajjar A, Aldape K, Moore AS, Taylor MD, Jones C, Jabado N, Karajannis MA, Eils R, Schlesner M, Lichter P, von Deimling A, Pfister SM, Ellison DW, Korshunov A, Kool M (2016) New brain tumor entities emerge from molecular classification of CNS-PNETs. Cell. 164(5):1060–1072PubMedPubMedCentralGoogle Scholar
  26. 26.
    Johann PD, Erkek S, Zapatka M, Kerl K, Buchhalter I, Hovestadt V, Jones DTW, Sturm D, Hermann C, Segura Wang M, Korshunov A, Rhyzova M, Gröbner S, Brabetz S, Chavez L, Bens S, Gröschel S, Kratochwil F, Wittmann A, Sieber L, Geörg C, Wolf S, Beck K, Oyen F, Capper D, van Sluis P, Volckmann R, Koster J, Versteeg R, von Deimling A, Milde T, Witt O, Kulozik AE, Ebinger M, Shalaby T, Grotzer M, Sumerauer D, Zamecnik J, Mora J, Jabado N, Taylor MD, Huang A, Aronica E, Bertoni A, Radlwimmer B, Pietsch T, Schüller U, Schneppenheim R, Northcott PA, Korbel JO, Siebert R, Frühwald MC, Lichter P, Eils R, Gajjar A, Hasselblatt M, Pfister SM, Kool M (2016) Atypical teratoid/rhabdoid tumors are comprised of three epigenetic subgroups with distinct enhancer landscapes. Cancer Cell 29(3):379–393PubMedGoogle Scholar
  27. 27.
    Duffner PK, Cohen ME, Myers MH, Heise HW (1986) Survival of children with brain tumors: SEER program, 1973-1980. Neurology. 36(5):597–601PubMedGoogle Scholar
  28. 28.
    Farwell JR, Dohrmann GJ, Flannery JT (1978) Intracranial neoplasms in infants. Arch Neurol 35(8):533–537PubMedGoogle Scholar
  29. 29.
    Evans AE, Jenkin RD, Sposto R, Ortega JA, Wilson CB, Wara W et al (1990) The treatment of medulloblastoma. Results of a prospective randomized trial of radiation therapy with and without CCNU, vincristine, and prednisone. J Neurosurg 72(4):572–582PubMedGoogle Scholar
  30. 30.
    Lafay-Cousin L, Smith A, Chi SN, Wells E, Madden J, Margol A et al (2016) Clinical, pathological, and molecular characterization of infant medulloblastomas treated with sequential high-dose chemotherapy. Pediatr Blood Cancer 14(5):1526–1531Google Scholar
  31. 31.
    Robinson GW, Rudneva VA, Buchhalter I, Billups CA, Waszak SM, Smith KS, Bowers DC, Bendel A, Fisher PG, Partap S, Crawford JR, Hassall T, Indelicato DJ, Boop F, Klimo P, Sabin ND, Patay Z, Merchant TE, Stewart CF, Orr BA, Korbel JO, Jones DTW, Sharma T, Lichter P, Kool M, Korshunov A, Pfister SM, Gilbertson RJ, Sanders RP, Onar-Thomas A, Ellison DW, Gajjar A, Northcott PA (2018) Risk-adapted therapy for young children with medulloblastoma (SJYC07): therapeutic and molecular outcomes from a multicentre, phase 2 trial. Lancet Oncol. 19(6):768–784PubMedPubMedCentralGoogle Scholar
  32. 32.
    Packer RJ, Gajjar A, Vezina G, Rorke-Adams L, Burger PC, Robertson PL, Bayer L, LaFond D, Donahue BR, Marymont MAH, Muraszko K, Langston J, Sposto R (2006) Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol 24(25):4202–4208PubMedGoogle Scholar
  33. 33.
    Packer RJ, Zhou T, Holmes E, Vezina G, Gajjar A (2013) Survival and secondary tumors in children with medulloblastoma receiving radiotherapy and adjuvant chemotherapy: results of Children’s Oncology Group trial A9961. Neuro-Oncology 15(1):97–103PubMedGoogle Scholar
  34. 34.
    Gajjar AJ, Robinson GW (2014) Medulloblastoma—translating discoveries from the bench to the bedside. Nat Rev Clin Oncol 11(12):714–722PubMedGoogle Scholar
  35. 35.
    Ramaswamy V, Remke M, Bouffet E, Bailey S, Clifford SC, Doz F et al (2016) Risk stratification of childhood medulloblastoma in the molecular era: the current consensus. Acta Neuropathol. Springer Berlin Heidelberg 131(6):821–831PubMedPubMedCentralGoogle Scholar
  36. 36.
    Zacharoulis S, Levy A, Chi SN, Gardner S, Rosenblum M, Miller DC, Dunkel I, Diez B, Sposto R, Ji L, Asgharzadeh S, Hukin J, Belasco J, Dubowy R, Kellie S, Termuhlen A, Finlay J (2007) Outcome for young children newly diagnosed with ependymoma, treated with intensive induction chemotherapy followed by myeloablative chemotherapy and autologous stem cell rescue. Pediatr Blood Cancer 49(1):34–40PubMedGoogle Scholar
  37. 37.
    Massimino M, Miceli R, Giangaspero F, Boschetti L, Modena P, Antonelli M, Ferroli P, Bertin D, Pecori E, Valentini L, Biassoni V, Garrè ML, Schiavello E, Sardi I, Cama A, Viscardi E, Scarzello G, Scoccianti S, Mascarin M, Quaglietta L, Cinalli G, Diletto B, Genitori L, Peretta P, Mussano A, Buccoliero A, Calareso G, Barra S, Mastronuzzi A, Giussani C, Marras CE, Balter R, Bertolini P, Giombelli E, la Spina M, Buttarelli FR, Pollo B, Gandola L (2016) Final results of the second prospective AIEOP protocol for pediatric intracranial ependymoma. Neuro-Oncology 18(10):1451–1460PubMedPubMedCentralGoogle Scholar
  38. 38.
    Merchant TE, Li C, Xiong X, Kun LE, Boop FA, Sanford RA (2009) Conformal radiotherapy after surgery for paediatric ependymoma: a prospective study. Lancet Oncol. 10(3):258–266PubMedPubMedCentralGoogle Scholar
  39. 39.
    MacDonald SM, Sethi R, Lavally B, Yeap BY, Marcus KJ, Caruso P et al (2013) Proton radiotherapy for pediatric central nervous system ependymoma: clinical outcomes for 70 patients. Neuro-Oncology 15(11):1552–1559PubMedPubMedCentralGoogle Scholar
  40. 40.
    Ramaswamy V, Hielscher T, Mack SC, Lassaletta A, Lin T, Pajtler KW, Jones DTW, Luu B, Cavalli FMG, Aldape K, Remke M, Mynarek M, Rutkowski S, Gururangan S, McLendon RE, Lipp ES, Dunham C, Hukin J, Eisenstat DD, Fulton D, van Landeghem FKH, Santi M, van Veelen MLC, van Meir EG, Osuka S, Fan X, Muraszko KM, Tirapelli DPC, Oba-Shinjo SM, Marie SKN, Carlotti CG, Lee JY, Rao AAN, Giannini C, Faria CC, Nunes S, Mora J, Hamilton RL, Hauser P, Jabado N, Petrecca K, Jung S, Massimi L, Zollo M, Cinalli G, Bognár L, Klekner A, Hortobágyi T, Leary S, Ermoian RP, Olson JM, Leonard JR, Gardner C, Grajkowska WA, Chambless LB, Cain J, Eberhart CG, Ahsan S, Massimino M, Giangaspero F, Buttarelli FR, Packer RJ, Emery L, Yong WH, Soto H, Liau LM, Everson R, Grossbach A, Shalaby T, Grotzer M, Karajannis MA, Zagzag D, Wheeler H, von Hoff K, Alonso MM, Tuñon T, Schüller U, Zitterbart K, Sterba J, Chan JA, Guzman M, Elbabaa SK, Colman H, Dhall G, Fisher PG, Fouladi M, Gajjar A, Goldman S, Hwang E, Kool M, Ladha H, Vera-Bolanos E, Wani K, Lieberman F, Mikkelsen T, Omuro AM, Pollack IF, Prados M, Robins HI, Soffietti R, Wu J, Metellus P, Tabori U, Bartels U, Bouffet E, Hawkins CE, Rutka JT, Dirks P, Pfister SM, Merchant TE, Gilbert MR, Armstrong TS, Korshunov A, Ellison DW, Taylor MD (2016) Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: a retrospective multicohort analysis. J Clin Oncol 34(21):2468–2477PubMedPubMedCentralGoogle Scholar
  41. 41.
    Moore BD, Ater JL, Copeland DR (1992) Improved neuropsychological outcome in children with brain tumors diagnosed during infancy and treated without cranial irradiation. J Child Neurol 7(3):281–290PubMedGoogle Scholar
  42. 42.
    Saha A, Salley CG, Saigal P, Rolnitzky L, Goldberg J, Scott S, Olshefski R, Hukin J, Sands SA, Finlay J, Gardner SL (2014) Late effects in survivors of childhood CNS tumors treated on head start I and II protocols. Pediatr Blood Cancer 61(9):1644–1672PubMedPubMedCentralGoogle Scholar
  43. 43.
    Sands SA, Pasichow KP, Weiss R, Garvin J, Gardner S, Dunkel IJ, Finlay JL (2011) Quality of life and behavioral follow-up study of Head Start I pediatric brain tumor survivors. J Neuro-Oncol 101(2):287–295Google Scholar
  44. 44.
    Zebrack BJ, Gurney JG, Oeffinger K, Whitton J, Packer RJ, Mertens A, Turk N, Castleberry R, Dreyer ZA, Robison LL, Zeltzer LK (2004) Psychological outcomes in long-term survivors of childhood brain cancer: a report from the childhood cancer survivor study. J Clin Oncol 22(6):999–1006PubMedGoogle Scholar
  45. 45.
    Cohen ME, Duffner PK (1984) Long term clinical effects of radiation and chemotherapy in brain tumors in children. Raven Press, New York, pp 308–323Google Scholar
  46. 46.
    Chin HW, Maruyama Y (1984) Age at treatment and long-term performance results in medulloblastoma. Cancer. 53(9):1952–1958PubMedGoogle Scholar
  47. 47.
    Packer RJ, Sutton LN, Atkins TE, Radcliffe J, Bunin GR, D’Angio G et al (1989) A prospective study of cognitive function in children receiving whole-brain radiotherapy and chemotherapy: 2-year results. J Neurosurg 70(5):707–713PubMedGoogle Scholar
  48. 48.
    Torchia J, Golbourn B, Feng S, Ho KC, Sin-Chan P, Vasiljevic A et al (2016) Integrated (epi)-genomic analyses identify subgroup-specific therapeutic targets in CNS rhabdoid tumors. Cancer Cell 30(6):891–908PubMedPubMedCentralGoogle Scholar
  49. 49.
    Korshunov A, Ryzhova M, Hovestadt V, Bender S, Sturm D, Capper D, Meyer J, Schrimpf D, Kool M, Northcott PA, Zheludkova O, Milde T, Witt O, Kulozik AE, Reifenberger G, Jabado N, Perry A, Lichter P, von Deimling A, Pfister SM, Jones DTW (2015) Integrated analysis of pediatric glioblastoma reveals a subset of biologically favorable tumors with associated molecular prognostic markers. Acta Neuropathol 129(5):669–678PubMedGoogle Scholar
  50. 50.
    Castelo-Branco P, Choufani S, Mack S, Gallagher D, Zhang C, Lipman T, Zhukova N, Walker EJ, Martin D, Merino D, Wasserman JD, Elizabeth C, Alon N, Zhang L, Hovestadt V, Kool M, Jones DTW, Zadeh G, Croul S, Hawkins C, Hitzler J, Wang JCY, Baruchel S, Dirks PB, Malkin D, Pfister S, Taylor MD, Weksberg R, Tabori U (2013) Methylation of the TERT promoter and risk stratification of childhood brain tumours: an integrative genomic and molecular study. Lancet Oncol 14(6):534–542PubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Pediatric Neurosurgery, Department of Neurosurgery, Hassenfeld Children’s HospitalNYU Langone HealthNew YorkUSA
  2. 2.Department of PathologyNYU Langone HealthNew YorkUSA
  3. 3.Pediatric Neuro-Oncology, Department of Pediatrics, Hassenfeld Children’s HospitalNYU Langone HealthNew YorkUSA
  4. 4.Pediatric Neuro-Oncology Service, Department of PediatricsMemorial Sloan Kettering Cancer Center (MSKCC)New YorkUSA

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