Advertisement

Journal of Neuro-Oncology

, Volume 139, Issue 3, pp 523–539 | Cite as

The clinical importance of medulloblastoma extent of resection: a systematic review

  • Eric M. ThompsonEmail author
  • Alexa Bramall
  • James E. HerndonII
  • Michael D. Taylor
  • Vijay Ramaswamy
Topic Review

Abstract

Background

Although the majority of current medulloblastoma adjuvant therapy protocols treat patients with ≥ 1.5 cm2 residual tumor as high risk with increased craniospinal irradiation, the true prognostic significance of extent of resection (EOR) in medulloblastoma is unknown.

Objectives

We sought to synthesize the body of literature on EOR and survival to determine if a definitive association exists.

Data sources/eligibility criteria

A PubMed search was conducted for the terms “medulloblastoma” combined with “extent of resection,” “overall survival,” “progression free survival,” “gross total resection,” “near total resection,” “partial resection,” or “subtotal resection.” Studies that performed a statistical analysis of EOR and survival were included.

Results

Sixteen articles including 1489 patients found a statistically significant association between EOR and survival, 20 articles including 2335 patients did not find a significant association between EOR and survival, and 14 articles including 2950 patients had mixed results. The three articles that accounted for molecular subgroup found varying associations between EOR and progression free survival, while no association was found between EOR and overall survival.

Limitations

This review is limited by inconsistent definitions of EOR, the retrospective nature of the articles analyzed, and infrequent use of multivariate statistical analyses.

Conclusions

The prognostic importance of EOR for medulloblastoma is unclear and warrants re-evaluation, particularly in the context of molecular subgrouping.

Keywords

Medulloblastoma Extent of resection Residual Subgroup Surgery Survival 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare no potential conflicts of interest.

Supplementary material

11060_2018_2906_MOESM1_ESM.docx (19 kb)
Supplementary material 1 (DOCX 19 KB)

References

  1. 1.
    Cavalli FMG, Remke M, Rampasek L, Peacock J, Shih DJH, Luu B, Garzia L, Torchia J, Nor C, Morrissy AS, Agnihotri S, Thompson YY, Kuzan-Fischer CM, Farooq H, Isaev K, Daniels C, Cho BK, Kim SK, Wang KC, Lee JY, Grajkowska WA, Perek-Polnik M, Vasiljevic A, Faure-Conter C, Jouvet A, Giannini C, Nageswara Rao AA, Li KKW, Ng HK, Eberhart CG, Pollack IF, Hamilton RL, Gillespie GY, Olson JM, Leary S, Weiss WA, Lach B, Chambless LB, Thompson RC, Cooper MK, Vibhakar R, Hauser P, van Veelen MC, Kros JM, French PJ, Ra YS, Kumabe T, Lopez-Aguilar E, Zitterbart K, Sterba J, Finocchiaro G, Massimino M, Van Meir EG, Osuka S, Shofuda T, Klekner A, Zollo M, Leonard JR, Rubin JB, Jabado N, Albrecht S, Mora J, Van Meter TE, Jung S, Moore AS, Hallahan AR, Chan JA, Tirapelli DPC, Carlotti CG, Fouladi M, Pimentel J, Faria CC, Saad AG, Massimi L, Liau LM, Wheeler H, Nakamura H, Elbabaa SK, Perezpena-Diazconti M, de Leon FCP, Robinson S, Zapotocky M, Lassaletta A, Huang A, Hawkins CE, Tabori U, Bouffet E, Bartels U, Dirks PB, Rutka JT, Bader GD, Reimand J, Goldenberg A, Ramaswamy V, Taylor MD (2017) Intertumoral heterogeneity within medulloblastoma subgroups. Cancer Cell 31(6):737–754.  https://doi.org/10.1016/j.ccell.2017.05.005 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Taylor MD, Northcott PA, Korshunov A, Remke M, Cho YJ, Clifford SC, Eberhart CG, Parsons DW, Rutkowski S, Gajjar A, Ellison DW, Lichter P, Gilbertson RJ, Pomeroy SL, Kool M, Pfister SM (2012) Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol 123(4):465–472.  https://doi.org/10.1007/s00401-011-0922-z CrossRefPubMedGoogle Scholar
  3. 3.
    Thompson EM, Keir ST, Venkatraman T, Lascola C, Yeom KW, Nixon AB, Liu Y, Picard D, Remke M, Bigner DD, Ramaswamy V, Taylor MD (2017) The role of angiogenesis in Group 3 medulloblastoma pathogenesis and survival. Neuro Oncol 19(9):1217–1227.  https://doi.org/10.1093/neuonc/nox033 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Perreault S, Ramaswamy V, Achrol AS, Chao K, Liu TT, Shih D, Remke M, Schubert S, Bouffet E, Fisher PG, Partap S, Vogel H, Taylor MD, Cho YJ, Yeom KW (2014) MRI surrogates for molecular subgroups of medulloblastoma. AJNR Am J Neuroradiol 35(7):1263–1269.  https://doi.org/10.3174/ajnr.A3990 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Thompson EM, Hielscher T, Bouffet E, Remke M, Luu B, Gururangan S, McLendon RE, Bigner DD, Lipp ES, Perreault S, Cho YJ, Grant G, Kim SK, Lee JY, Rao AA, Giannini C, Li KK, Ng HK, Yao Y, Kumabe T, Tominaga T, Grajkowska WA, Perek-Polnik M, Low DC, Seow WT, Chang KT, Mora J, Pollack IF, Hamilton RL, Leary S, Moore AS, Ingram WJ, Hallahan AR, Jouvet A, Fevre-Montange M, Vasiljevic A, Faure-Conter C, Shofuda T, Kagawa N, Hashimoto N, Jabado N, Weil AG, Gayden T, Wataya T, Shalaby T, Grotzer M, Zitterbart K, Sterba J, Kren L, Hortobagyi T, Klekner A, Laszlo B, Pocza T, Hauser P, Schuller U, Jung S, Jang WY, French PJ, Kros JM, van Veelen ML, Massimi L, Leonard JR, Rubin JB, Vibhakar R, Chambless LB, Cooper MK, Thompson RC, Faria CC, Carvalho A, Nunes S, Pimentel J, Fan X, Muraszko KM, Lopez-Aguilar E, Lyden D, Garzia L, Shih DJ, Kijima N, Schneider C, Adamski J, Northcott PA, Kool M, Jones DT, Chan JA, Nikolic A, Garre ML, Van Meir EG, Osuka S, Olson JJ, Jahangiri A, Castro BA, Gupta N, Weiss WA, Moxon-Emre I, Mabbott DJ, Lassaletta A, Hawkins CE, Tabori U, Drake J, Kulkarni A, Dirks P, Rutka JT, Korshunov A, Pfister SM, Packer RJ, Ramaswamy V, Taylor MD (2016) Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis. Lancet Oncol 17(4):484–495.  https://doi.org/10.1016/S1470-2045(15)00581-1 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Ramaswamy V, Remke M, Bouffet E, Bailey S, Clifford SC, Doz F, Kool M, Dufour C, Vassal G, Milde T, Witt O, von Hoff K, Pietsch T, Northcott PA, Gajjar A, Robinson GW, Padovani L, Andre N, Massimino M, Pizer B, Packer R, Rutkowski S, Pfister SM, Taylor MD, Pomeroy SL (2016) Risk stratification of childhood medulloblastoma in the molecular era: the current consensus. Acta Neuropathol 31(6):821–831.  https://doi.org/10.1007/s00401-016-1569-6 CrossRefGoogle Scholar
  7. 7.
    Albright AL, Sposto R, Holmes E, Zeltzer PM, Finlay JL, Wisoff JH, Berger MS, Packer RJ, Pollack IF (2000) Correlation of neurosurgical subspecialization with outcomes in children with malignant brain tumors. Neurosurgery 47(4):879–885 (discussion 885–877)CrossRefPubMedGoogle Scholar
  8. 8.
    Cochrane DD, Gustavsson B, Poskitt KP, Steinbok P, Kestle JR (1994) The surgical and natural morbidity of aggressive resection for posterior fossa tumors in childhood. Pediatr Neurosurg 20(1):19–29CrossRefPubMedGoogle Scholar
  9. 9.
    Korah MP, Esiashvili N, Mazewski CM, Hudgins RJ, Tighiouart M, Janss AJ, Schwaibold FP, Crocker IR, Curran WJ Jr, Marcus RB Jr (2010) Incidence, risks, and sequelae of posterior fossa syndrome in pediatric medulloblastoma. Int J Radiat Oncol Biol Phys 77(1):106–112.  https://doi.org/10.1016/j.ijrobp.2009.04.058 CrossRefPubMedGoogle Scholar
  10. 10.
    Gajjar A, Sanford RA, Bhargava R, Heideman R, Walter A, Li Y, Langston JW, Jenkins JJ, Muhlbauer M, Boyett J, Kun LE (1996) Medulloblastoma with brain stem involvement: the impact of gross total resection on outcome. Pediatr Neurosurg 25(4):182–187.  https://doi.org/10.1159/000121121 CrossRefPubMedGoogle Scholar
  11. 11.
    Pollack IF, Polinko P, Albright AL, Towbin R, Fitz C (1995) Mutism and pseudobulbar symptoms after resection of posterior fossa tumors in children: incidence and pathophysiology. Neurosurgery 37(5):885–893CrossRefPubMedGoogle Scholar
  12. 12.
    Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339:b2700.  https://doi.org/10.1136/bmj.b2700 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Higgins JPT, Green S (2011) Cochrane handbook for systematic reviews of interventions, Version 5.1.0. http://www.handbook.cochrane.org
  14. 14.
    Berry MP, Jenkin RD, Keen CW, Nair BD, Simpson WJ (1981) Radiation treatment for medulloblastoma. A 21-year review. J Neurosurg 55(1):43–51.  https://doi.org/10.3171/jns.1981.55.1.0043 CrossRefPubMedGoogle Scholar
  15. 15.
    Bourne JP, Geyer R, Berger M, Griffin B, Milstein J (1992) The prognostic significance of postoperative residual contrast enhancement on CT scan in pediatric patients with medulloblastoma. J Neurooncol 14(3):263–270CrossRefPubMedGoogle Scholar
  16. 16.
    Buglione M, Ghirardelli P, Triggiani L, Pedretti S, Pasinetti N, De Bari B, Tonoli S, Borghetti P, Spiazzi L, Magrini SM (2015) Radiotherapy for adult medulloblastoma: long term result from a single institution. A review of prognostic factors and why we do need a multi-institutional cooperative program. Rep Pract Oncol Radiother 20(4):284–291.  https://doi.org/10.1016/j.rpor.2015.03.003 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Giralt J, Sanchez de Toledo J, Moraga F, Poch JM, Gallego S, Rosello J, Maldonado X, Prats J (1996) Improving survival of medulloblastoma: results in two groups of patients. Oncology 53(1):38–42CrossRefPubMedGoogle Scholar
  18. 18.
    Hughes EN, Shillito J, Sallan SE, Loeffler JS, Cassady JR, Tarbell NJ (1988) Medulloblastoma at the joint center for radiation therapy between 1968 and 1984. The influence of radiation dose on the patterns of failure and survival. Cancer 61(10):1992–1998CrossRefPubMedGoogle Scholar
  19. 19.
    Jenkin D, Goddard K, Armstrong D, Becker L, Berry M, Chan H, Doherty M, Greenberg M, Hendrick B, Hoffman H et al (1990) Posterior fossa medulloblastoma in childhood: treatment results and a proposal for a new staging system. Int J Radiat Oncol Biol Phys 19(2):265–274CrossRefPubMedGoogle Scholar
  20. 20.
    Lannering B, Rutkowski S, Doz F, Pizer B, Gustafsson G, Navajas A, Massimino M, Reddingius R, Benesch M, Carrie C, Taylor R, Gandola L, Bjork-Eriksson T, Giralt J, Oldenburger F, Pietsch T, Figarella-Branger D, Robson K, Forni M, Clifford SC, Warmuth-Metz M, von Hoff K, Faldum A, Mosseri V, Kortmann R (2012) Hyperfractionated versus conventional radiotherapy followed by chemotherapy in standard-risk medulloblastoma: results from the randomized multicenter HIT-SIOP PNET 4 trial. J Clin Oncol 30(26):3187–3193.  https://doi.org/10.1200/jco.2011.39.8719 CrossRefPubMedGoogle Scholar
  21. 21.
    Park TS, Hoffman HJ, Hendrick EB, Humphreys RP, Becker LE (1983) Medulloblastoma: clinical presentation and management. Experience at the hospital for sick children, toronto, 1950–1980. J Neurosurg 58(4):543–552.  https://doi.org/10.3171/jns.1983.58.4.0543 CrossRefPubMedGoogle Scholar
  22. 22.
    Rieken S, Mohr A, Habermehl D, Welzel T, Lindel K, Witt O, Kulozik AE, Wick W, Debus J, Combs SE (2011) Outcome and prognostic factors of radiation therapy for medulloblastoma. Int J Radiat Oncol Biol Phys 81(3):e7–e13.  https://doi.org/10.1016/j.ijrobp.2010.12.042 CrossRefGoogle Scholar
  23. 23.
    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. New Engl J Med 352(10):978–986.  https://doi.org/10.1056/NEJMoa042176 CrossRefPubMedGoogle Scholar
  24. 24.
    Stavrou T, Bromley CM, Nicholson HS, Byrne J, Packer RJ, Goldstein AM, Reaman GH (2001) Prognostic factors and secondary malignancies in childhood medulloblastoma. J Pediatr Hematol Oncol 23(7):431–436CrossRefPubMedGoogle Scholar
  25. 25.
    Sure U, Bertalanffy H, Isenmann S, Brandner S, Berghorn WJ, Seeger W, Aguzzi A (1995) Secondary manifestation of medulloblastoma: metastases and local recurrences in 66 patients. Acta Neurochir 136(3–4):117–126CrossRefPubMedGoogle Scholar
  26. 26.
    Tait DM, Thornton-Jones H, Bloom HJ, 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(4):464–469CrossRefPubMedGoogle Scholar
  27. 27.
    Tomita T, Yasue M, Engelhard HH, McLone DG, Gonzalez-Crussi F, Bauer KD (1988) Flow cytometric DNA analysis of medulloblastoma. Prognostic implication of aneuploidy. Cancer 61(4):744–749CrossRefPubMedGoogle Scholar
  28. 28.
    Zhang N, Ouyang T, Kang H, Long W, Thomas B, Zhu S (2015) Adult medulloblastoma: clinical characters, prognostic factors, outcomes and patterns of relapse. J Neurooncol 124(2):255–264.  https://doi.org/10.1007/s11060-015-1833-y CrossRefPubMedGoogle Scholar
  29. 29.
    Srikantha U, Balasubramaniam A, Santosh V, Somanna S, Bhagavatula ID, Ashwathnarayana CB (2010) Recurrence in medulloblastoma—influence of clinical, histological and immunohistochemical factors. Br J Neurosurg 24(3):280–288.  https://doi.org/10.3109/02688691003660558 CrossRefPubMedGoogle Scholar
  30. 30.
    Harisiadis L, Chang CH (1977) Medulloblastoma in children: a correlation between staging and results of treatment. Int J Radiat Oncol Biol Phys 2(9–10):833–841CrossRefPubMedGoogle Scholar
  31. 31.
    Akyuz C, Varan A, Kupeli S, Akalan N, Soylemezoglu F, Zorlu F, Kutluk T, Buyukpamukcu M (2008) Medulloblastoma in children: a 32-year experience from a single institution. J Neurooncol 90(1):99–103.  https://doi.org/10.1007/s11060-008-9638-x CrossRefPubMedGoogle Scholar
  32. 32.
    Caputy AJ, McCullough DC, Manz HJ, Patterson K, Hammock MK (1987) A review of the factors influencing the prognosis of medulloblastoma. The importance of cell differentiation. J Neurosurg 66(1):80–87.  https://doi.org/10.3171/jns.1987.66.1.0080 CrossRefPubMedGoogle Scholar
  33. 33.
    Christopherson KM, Bradley JA, Rotondo RL, Pincus DW, Fort JA, Morris CG, Mendenhall NP, Marcus RB Jr, Indelicato DJ (2014) Local control in non-metastatic medulloblastoma. Acta Oncol 53(9):1151–1157.  https://doi.org/10.3109/0284186x.2014.932434 CrossRefPubMedGoogle Scholar
  34. 34.
    David KM, Casey AT, Hayward RD, Harkness WF, Phipps K, Wade AM (1997) Medulloblastoma: is the 5-year survival rate improving? A review of 80 cases from a single institution. J Neurosurg 86(1):13–21.  https://doi.org/10.3171/jns.1997.86.1.0013 CrossRefPubMedGoogle Scholar
  35. 35.
    Evans AE, Jenkin RD, Sposto R, Ortega JA, Wilson CB, Wara W, Ertel IJ, Kramer S, Chang CH, Leikin SL 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):572–582.  https://doi.org/10.3171/jns.1990.72.4.0572 CrossRefPubMedGoogle Scholar
  36. 36.
    Garre ML, Cama A, Bagnasco F, Morana G, Giangaspero F, Brisigotti M, Gambini C, Forni M, Rossi A, Haupt R, Nozza P, Barra S, Piatelli G, Viglizzo G, Capra V, Bruno W, Pastorino L, Massimino M, Tumolo M, Fidani P, Dallorso S, Schumacher RF, Milanaccio C, Pietsch T (2009) Medulloblastoma variants: age-dependent occurrence and relation to Gorlin syndrome–a new clinical perspective. Clin Cancer Res 15(7):2463–2471.  https://doi.org/10.1158/1078-0432.CCR-08-2023 CrossRefPubMedGoogle Scholar
  37. 37.
    Grabenbauer GG, Beck JD, Erhardt J, Seegenschmiedt MH, Seyer H, Thierauf P, Sauer R (1996) Postoperative radiotherapy of medulloblastoma. Impact of radiation quality on treatment outcome. Am J Clin Oncol 19(1):73–77CrossRefPubMedGoogle Scholar
  38. 38.
    Herms J, Neidt I, Luscher B, Sommer A, Schurmann P, Schroder T, Bergmann M, Wilken B, Probst-Cousin S, Hernaiz-Driever P, Behnke J, Hanefeld F, Pietsch T, Kretzschmar HA (2000) C-MYC expression in medulloblastoma and its prognostic value. Int J Cancer 89(5):395–402CrossRefPubMedGoogle Scholar
  39. 39.
    Johnston DL, Keene D, Bartels U, Carret AS, Crooks B, Eisenstat DD, Fryer C, Lafay-Cousin L, Larouche V, Moghrabi A, Wilson B, Zelcer S, Silva M, Brossard J, Bouffet E (2009) Medulloblastoma in children under the age of three years: a retrospective Canadian review. J Neurooncol 94(1):51–56.  https://doi.org/10.1007/s11060-009-9799-2 CrossRefPubMedGoogle Scholar
  40. 40.
    Kann BH, Lester-Coll NH, Park HS, Yeboa DN, Kelly JR, Baehring JM, Becker KP, Yu JB, Bindra RS, Roberts KB (2017) Adjuvant chemotherapy and overall survival in adult medulloblastoma. Neuro Oncol 19(2):259–269.  https://doi.org/10.1093/neuonc/now150 PubMedCrossRefGoogle Scholar
  41. 41.
    Kumar LP, Deepa SF, Moinca I, Suresh P, Naidu KV (2015) Medulloblastoma: a common pediatric tumor: prognostic factors and predictors of outcome. Asian J Neurosurg 10(1):50.  https://doi.org/10.4103/1793-5482.151516 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Lal P, Nagar YS, Kumar S, Singh S, Maria Das KJ, Narayan SL, Kumar R, Jain VK, Ayyagari S (2002) Medulloblastomas: clinical profile, treatment techniques and outcome—an institutional experience. Indian J Cancer 39(3):97–105PubMedGoogle Scholar
  43. 43.
    Mealey J Jr, Hall PV (1977) Medulloblastoma in children. Survival and treatment. J Neurosurg 46(1):56–64.  https://doi.org/10.3171/jns.1977.46.1.0056 CrossRefPubMedGoogle Scholar
  44. 44.
    Modha A, Vassilyadi M, George A, Kuehn S, Hsu E, Ventureyra EC (2000) Medulloblastoma in children–the Ottawa experience. Child’s Nerv Syst 16(6):341–350.  https://doi.org/10.1007/s003810050529 CrossRefGoogle Scholar
  45. 45.
    Nasr A, Al-Ghamdy H (2004) The prognostic impact of additional chemotherapy to radiation therapy for postoperative management of pediatric medulloblastoma. J Egypt Natl Cancer Inst 16(4):195–201Google Scholar
  46. 46.
    Taylor RE, Bailey CC, Robinson K, Weston CL, Ellison D, Ironside J, Lucraft H, Gilbertson R, Tait DM, Walker DA, Pizer BL, Imeson J, Lashford LS, International Society of Paediatric O, United Kingdom Children’s Cancer Study G (2003) Results of a randomized study of preradiation chemotherapy versus radiotherapy alone for nonmetastatic medulloblastoma: the International Society of Paediatric Oncology/United Kingdom Children’s Cancer Study Group PNET-3 Study. J Clin Oncol 21(8):1581–1591.  https://doi.org/10.1200/JCO.2003.05.116 CrossRefPubMedGoogle Scholar
  47. 47.
    Woodburn RT, Azzarelli B, Montebello JF, Goss IE (2001) Intense p53 staining is a valuable prognostic indicator for poor prognosis in medulloblastoma/central nervous system primitive neuroectodermal tumors. J Neurooncol 52(1):57–62CrossRefPubMedGoogle Scholar
  48. 48.
    Pietsch T, Schmidt R, Remke M, Korshunov A, Hovestadt V, Jones DT, Felsberg J, Kaulich K, Goschzik T, Kool M, Northcott PA, von Hoff K, von Bueren AO, Friedrich C, Mynarek M, Skladny H, Fleischhack G, Taylor MD, Cremer F, Lichter P, Faldum A, Reifenberger G, Rutkowski S, Pfister SM (2014) Prognostic significance of clinical, histopathological, and molecular characteristics of medulloblastomas in the prospective HIT2000 multicenter clinical trial cohort. Acta Neuropathol 128(1):137–149.  https://doi.org/10.1007/s00401-014-1276-0 CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    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):1169–1175.  https://doi.org/10.1002/pbc.21525 CrossRefPubMedGoogle Scholar
  50. 50.
    Albright AL, Wisoff JH, Zeltzer PM, Boyett JM, Rorke LB, Stanley P (1996) Effects of medulloblastoma resections on outcome in children: a report from the Children’s Cancer Group. Neurosurgery 38(2):265–271CrossRefPubMedGoogle Scholar
  51. 51.
    Brasme JF, Grill J, Doz F, Lacour B, Valteau-Couanet D, Gaillard S, Delalande O, Aghakhani N, Puget S, Chalumeau M (2012) Long time to diagnosis of medulloblastoma in children is not associated with decreased survival or with worse neurological outcome. PLoS ONE 7(4):e33415.  https://doi.org/10.1371/journal.pone.0033415 CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Call JA, Naik M, Rodriguez FJ, Giannini C, Wu W, Buckner JC, Parney IF, Laack NN (2014) Long-term outcomes and role of chemotherapy in adults with newly diagnosed medulloblastoma. Am J Clin Oncol 37(1):1–7.  https://doi.org/10.1097/COC.0b013e31826b9cf0 CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Danjoux CE, Jenkin RD, McLaughlin J, Grimard L, Gaspar LE, Dar AR, Fisher B, Whitton AC, Kraus V, Springer CD, et al. (1996) Childhood medulloblastoma in Ontario, 1977–1987: population-based results. Med Pediatr Oncol 26 (1):1–9CrossRefPubMedGoogle Scholar
  54. 54.
    Grill J, Sainte-Rose C, Jouvet A, Gentet JC, Lejars O, Frappaz D, Doz F, Rialland X, Pichon F, Bertozzi AI, Chastagner P, Couanet D, Habrand JL, Raquin MA, Le Deley MC, Kalifa C, French Society of Paediatric O (2005) Treatment of medulloblastoma with postoperative chemotherapy alone: an SFOP prospective trial in young children. Lancet Oncol 6(8):573–580.  https://doi.org/10.1016/S1470-2045(05)70252-7 CrossRefPubMedGoogle Scholar
  55. 55.
    Hershatter BW, Halperin EC, Cox EB (1986) Medulloblastoma: the Duke University Medical Center experience. Int J Radiat Oncol Biol Phys 12(10):1771–1777CrossRefPubMedGoogle Scholar
  56. 56.
    Khafaga Y, Kandil AE, Jamshed A, Hassounah M, DeVol E, Gray AJ (1996) Treatment results for 149 medulloblastoma patients from one institution. Int J Radiat Oncol Biol Phys 35(3):501–506CrossRefPubMedGoogle Scholar
  57. 57.
    Michiels EM, Heikens J, Jansen MJ, Oldenburger F, Voute T (2000) Are clinical parameters valuable prognostic factors in childhood primitive neuroectodermal tumors? A multivariate analysis of 105 cases. Radiother Oncol Oncology 54(3):229–238CrossRefGoogle Scholar
  58. 58.
    Packer RJ, Boyett JM, Janss AJ, Stavrou T, Kun L, Wisoff J, Russo C, Geyer R, Phillips P, Kieran M, Greenberg M, Goldman S, Hyder D, Heideman R, Jones-Wallace D, August GP, Smith SH, Moshang T (2001) Growth hormone replacement therapy in children with medulloblastoma: use and effect on tumor control. J Clin Oncol 19(2):480–487.  https://doi.org/10.1200/jco.2001.19.2.480 CrossRefPubMedGoogle Scholar
  59. 59.
    Schwalbe EC, Lindsey JC, Nakjang S, Crosier S, Smith AJ, Hicks D, Rafiee G, Hill RM, Iliasova A, Stone T, Pizer B, Michalski A, Joshi A, Wharton SB, Jacques TS, Bailey S, Williamson D, Clifford SC (2017) Novel molecular subgroups for clinical classification and outcome prediction in childhood medulloblastoma: a cohort study. Lancet Oncol.  https://doi.org/10.1016/S1470-2045(17)30243-7 PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Wang C, Yuan XJ, Jiang MW, Wang LF (2016) Clinical characteristics and abandonment and outcome of treatment in 67 Chinese children with medulloblastoma. J Neurosurg Pediatr 17(1):49–56.  https://doi.org/10.3171/2015.5.peds1573 CrossRefPubMedGoogle Scholar
  61. 61.
    Weil MD, Lamborn K, Edwards MS, Wara WM (1998) Influence of a child’s sex on medulloblastoma outcome. JAMA 279(18):1474–1476CrossRefPubMedGoogle Scholar
  62. 62.
    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(3):832–845.  https://doi.org/10.1200/jco.1999.17.3.832 CrossRefPubMedGoogle Scholar
  63. 63.
    Esbenshade AJ, Kocak M, Hershon L, Rousseau P, Decarie JC, Shaw S, Burger P, Friedman HS, Gajjar A, Moghrabi A (2017) A Phase II feasibility study of oral etoposide given concurrently with radiotherapy followed by dose intensive adjuvant chemotherapy for children with newly diagnosed high-risk medulloblastoma (protocol POG 9631): A report from the Children’s Oncology Group. Pediatr Blood Cancer.  https://doi.org/10.1002/pbc.26373 CrossRefPubMedGoogle Scholar
  64. 64.
    Packer RJ, Gajjar A, Vezina G, Rorke-Adams L, Burger PC, Robertson PL, Bayer L, LaFond D, Donahue BR, Marymont MH, 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):4202–4208.  https://doi.org/10.1200/jco.2006.06.4980 CrossRefPubMedGoogle Scholar
  65. 65.
    Gajjar A, Chintagumpala M, Ashley D, Kellie S, Kun LE, Merchant TE, Woo S, Wheeler G, Ahern V, Krasin MJ, Fouladi M, Broniscer A, Krance R, Hale GA, Stewart CF, Dauser R, Sanford RA, Fuller C, Lau C, Boyett JM, Wallace D, Gilbertson RJ (2006) Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial. Lancet Oncol 7(10):813–820.  https://doi.org/10.1016/s1470-2045(06)70867-1 CrossRefPubMedGoogle Scholar
  66. 66.
    Xu H, Robinson GW, Huang J, Lim JY, Zhang H, Bass JK, Broniscer A, Chintagumpala M, Bartels U, Gururangan S, Hassall T, Fisher M, Cohn R, Yamashita T, Teitz T, Zuo J, Onar-Thomas A, Gajjar A, Stewart CF, Yang JJ (2015) Common variants in ACYP2 influence susceptibility to cisplatin-induced hearing loss. Nat Genet 47(3):263–266.  https://doi.org/10.1038/ng.3217 CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Paulino AC, Lobo M, Teh BS, Okcu MF, South M, Butler EB, Su J, Chintagumpala M (2010) Ototoxicity after intensity-modulated radiation therapy and cisplatin-based chemotherapy in children with medulloblastoma. Int J Radiat Oncol Biol Phys 78(5):1445–1450.  https://doi.org/10.1016/j.ijrobp.2009.09.031 CrossRefPubMedGoogle Scholar
  68. 68.
    Yock TI, Yeap BY, Ebb DH, Weyman E, Eaton BR, Sherry NA, Jones RM, MacDonald SM, Pulsifer MB, Lavally B, Abrams AN, Huang MS, Marcus KJ, Tarbell NJ (2016) Long-term toxic effects of proton radiotherapy for paediatric medulloblastoma: a phase 2 single-arm study. Lancet Oncol 17(3):287–298.  https://doi.org/10.1016/S1470-2045(15)00167-9 CrossRefPubMedGoogle Scholar
  69. 69.
    Mulhern RK, Palmer SL, Merchant TE, Wallace D, Kocak M, Brouwers P, Krull K, Chintagumpala M, Stargatt R, Ashley DM, Tyc VL, Kun L, Boyett J, Gajjar A (2005) Neurocognitive consequences of risk-adapted therapy for childhood medulloblastoma. J Clin Oncol 23(24):5511–5519.  https://doi.org/10.1200/JCO.2005.00.703 CrossRefPubMedGoogle Scholar
  70. 70.
    Christopherson KM, Rotondo RL, Bradley JA, Pincus DW, Wynn TT, Fort JA, Morris CG, Mendenhall NP, Marcus RB Jr, Indelicato DJ (2014) Late toxicity following craniospinal radiation for early-stage medulloblastoma. Acta Oncol 53(4):471–480.  https://doi.org/10.3109/0284186X.2013.862596 CrossRefPubMedGoogle Scholar
  71. 71.
    Albert FK, Forsting M, Sartor K, Adams HP, Kunze S (1994) Early postoperative magnetic resonance imaging after resection of malignant glioma: objective evaluation of residual tumor and its influence on regrowth and prognosis. Neurosurgery 34(1):45–60. (discussion 60–41)PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Eric M. Thompson
    • 1
    • 2
    • 7
    Email author
  • Alexa Bramall
    • 1
  • James E. HerndonII
    • 3
  • Michael D. Taylor
    • 4
    • 5
  • Vijay Ramaswamy
    • 6
  1. 1.Department of NeurosurgeryDuke UniversityDurhamUSA
  2. 2.Preston Robert Tisch Brain Tumor CenterDuke UniversityDurhamUSA
  3. 3.Department of Biostatistics and BioinformaticsDuke UniversityDurhamUSA
  4. 4.Division of Neurosurgery, The Arthur and Sonia Labatt Brain Tumour Research Centre, Developmental & Stem Cell Biology ProgramThe Hospital for Sick ChildrenTorontoCanada
  5. 5.Department of Laboratory Medicine and PathobiologyUniversity of TorontoTorontoCanada
  6. 6.Division of Haematology/Oncology, The Arthur and Sonia Labatt Brain Tumour Research Centre, Programme in Neuroscience and Mental HealthThe Hospital for Sick ChildrenTorontoCanada
  7. 7.Duke University Medical CenterDurhamUSA

Personalised recommendations