Abstract
Between 1985 and 1989, 38 children with newly diagnosed medulloblastoma entered our therapeutic protocol. After surgery and postoperative staging assessments, patients were assigned to risk groups. Eleven with “standard-risk” (SR) tumors were treated with radiation therapy alone, while 27 with “high-risk” (HR) tumors received radiation therapy plus adjuvant chemotherapy with vincristine, methotrexate, VM-26, and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). After a minimum follow-up of 5 years (range 5–9 years) 21/38 children had developed a recurrence or progression of their disease and 19/38 patients had died. Five-year event-free survival rates and 5-year total survival rates for all 38 patients were 47.4% and 50% respectively. The event-free survival rates at 5 years for SR and HR patients separately were 27.3% and 55.6%, respectively. The corresponding 5-year total survival rates were 27.3% and 59.3%. The differences were not statistically significant. Univariate analysis showed age at diagnosis to be the most important prognostic factor. Infants aged 5 years or less had a significantly shorter event-free survival time than older patients (P=0.00897). Similar effects were found when total survival time was considered. There were significant differences in outcome in patients receiving different doses of radiation, suggesting a dose-response relationship. A Cox stepwise multivariate analysis showed age at diagnosis as the only independent prognostic factor. Variables relating to treatment entered the model, suggesting that chemotherapy could play an important role in determining outcome.
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Allen JC, Bloom J, Ertel I, Evans A, Hammond D, Jones H, Levin V, Jenkin D, Sposto R, Wara W (1986) Brain tumors in children: current cooperation and institutional chemotherapy trials in newly diagnosed and recurrent disease. Semin Oncol 13:110–122
Belza MG, Donaldson SS, Steinberg GK, Cox RS, Cogen PH (1991) Medulloblastoma: freedom from relapse longer than 8 years — a therapeutic cure? J Neurosurg 75:575–582
Berry MP, Jenkin RDT, Keen CW, Nair BD, Simpson WJ (1981) Radiation treatment for medulloblastoma. A 21-year review. J Neurosurg 55:43–51
Bloom HJG (1981) SIOP medulloblastoma and high grade ependymoma therapeutic clinical trial: preliminary results. Proceedings of the XIII Meeting of the International Society of Paediatric Oncology, Marseilles
Bloom HJG, Wallace ENK, Henk JM (1969) The treatment and prognosis of medulloblastoma in children. A study of 82 verified cases. Am J Roentgenol Radium Ther Nucl Med 105:43–62
Chang CH, Housepian EM, Herbert C Jr (1969) An operative staging system and a megavoltage radiotherapeutic technic for cerebellar medulloblastomas. Radiology 93:1351–1359
Chin HW, Maruyama Y (1982) Prognostic factors in medulloblastoma. Am J Clin Oncol 5:359–369
Cox DR (1972) Regression models and life-tables (with discussion). J R Stat Soc [B] 34:187–220
Evans AE, Anderson J, Chang C, Jenkin RTD, Kramer S, Schoenfeld D, Wilson CB (1979) Adjuvant chemotherapy for medulloblastoma and ependymoma. In: Paoletti P, Walker MD, Butti G, Knerich R (eds) Multidisciplinary aspects of brain tumor therapy. Elsevier/North-Holland Biomedical Press, Amsterdam, pp 219–222
Evans AE, Jenkin RD, Sposto R, Ortega JA, Wilson CB, Wara W, Ertel IJ, Kramer S, Chang CH, Leikin SL, Hammond GD (1990) The treatment of medulloblastoma. Results of a prospective randomized trial of radiation therapy with and without CCNU, vincristine, and prednisone. J Neurosurg 72:572–582
Harisiadis L, Chang CH (1977) Medulloblastoma in children: a correlation between staging and results of treatment. Int J Radiat Oncol Biol Phys 2:833–841
Hershatter BW, Halpen EC, Cox EB (1986) Medulloblastoma: the Duke University Medical Center experience. Int J Radiat Oncol Biol Phys 12:1771–1777
Jenkin D, Goddard K, Armstrong D, Becker L, Berry M, Chan H, Doherty M, Greenberg M, Hendrick B, Hoffman H, Humphreys R, Soley M, Weizman S, Zipursky A (1990) Posterior fossa medulloblastoma in chidhood: treatment results and a proposal for a new staging system. Int J Radiat Oncol Biol Phys 19:265–274
Kanev PM, Berger MS, Lefebvre JF, Mauseth RS (1991) Growth hormone deficiency following radiation therapy of primary brain tumors in children. J Neurosurg 74:743–748
Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481
Knerich R, Adinolfi D, Buoncristiani P, Butti G, Calculli G, Cordero di Montezemolo L, Madon E, Mazza C, Tanghetti B, Tarenzi L (1979) Combined therapy for malignant brain tumors in children. J Neurosurg Sci 23:273–278
Krischer JP, Ragab AH, Kun L, Kim TH, Laurent JP, Boyett JM, Cornell CJ, Link M, Ridolfi Luthy A, Camitta B (1991) Nitrogen mustard, vincristine, procarbazine, and prednisone as adjuvant chemotherapy in the treatment of medulloblastoma. A Pediatric Oncology Group study. J Neurosurg 74:905–909
Levin VA, Rodriguez LA, Edwards MSB, Wara W, Liu HC, Fulton D, Davis RL, Wilson CB, Silver P (1988) Treatment of medulloblastoma with procarbazine, hydroxyurea, and reduced radiation doses to whole brain and spine. J Neurosurg 68:383–387
McIntosh S, Chen M, Sartain PA, Duncan C, Fishburn R, Klatskin EH, Schwartz AD, Venes JL (1985) Adjuvant chemotherapy for medulloblastoma. Cancer 56:1316–1319
Miller AB, Hoogstraten B, Staquet M, Winkler A (1981) Reporting results of cancer treatment. Cancer 47:207–214
Mulhern RK, Hancock J, Fairclough D, Kun L (1992) Neuropsychological status of children treated for brain tumors. A critical review and integrative analysis. Med Pediatr Oncol 20:181–191
Neidhardt MK, Bailey CC (1987) Prospective randomized cooperative medulloblastoma trial (MED 84) of the International Society of Paediatric Oncology (SIOP) and of the German Society of Paediatric Oncology (GPO). Child's Nerv Syst 3:70–73
Oberfield S, Allen J, Pollack J, New MI, Levine LS (1986) Long-term endocrine sequelae after treatment of medulloblastoma: prospective studies on growth and thyroid function. J Pediatr 108:219–223
Packer RJ, Siegel KR, Sutton LN, Evans AE, D'Angio G, Rorke LB, Bunin GR, Schut L (1988) Efficacy of adjuvant chemotherapy for patients with poor risk medulloblastoma: a preliminary report. Ann Neurol 24:503–508
Packer RJ, Sutton LN, Golwein JW, Perilongo G, Bunin G, Rayan J, Cohen BH, D'Angio G, Kramer ED, Zimmerman RA, Rorke LB, Evans AE, Schut L (1991) Improved survival with the use of adjuvant chemotherapy in the treatment of medulloblastoma. J Neurosurg 74:433–440
Park TS, Hoffmann HJ, Hendrick EB, Humphreys RB, Becker LE (1983) Medulloblastoma: clinical presentation and management-experience at the Hospital for Sick Children, Toronto 1950–1980. J Neurosurg 58:543–552
Peto R, Pike MC, Amitage P, Breslow NE, Cox DR, Howard SV, Mantel N, McPerson K, Peto J, Smith PG (1977) Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. Analysis and examples. Br J Cancer 35:1–39
Raimondi AJ, Tomita T (1979) Medulloblastoma in childhood. Acta Neurochir 50:127–138
Rivera-Luna R, Rueda-Franco F, Lanche-Guevara MT, Martinez-Guerra G (1987) Multidisciplinary treatment of medulloblastoma in childhood. Child's Nerv Syst 3:228–231
Silverman CL, Simpson JR (1982) Cerebellar medulloblastoma: the importance of posterior fossa dose to survival and patterns of failure. Int J Radiat Oncol Biol Phys 8:1869–1876
Tait DM, Thorton-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
Zeltzer PM (1986) Chemotherapy for medulloblastoma: a review of treatment in recurrent and de novo tumors. In: Zeltzer PM, Pochedly C (eds) Medulloblastomas in children: new concepts in tumor biology, diagnosis and treatment. Praeger, New York, pp 182–199
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Pezzotta, S., Cordero di Montezemolo, L., Knerich, R. et al. CNS-85 trial: a cooperative pediatric CNS tumor study — results of treatment of medulloblastoma patients. Child's Nerv Syst 12, 87–96 (1996). https://doi.org/10.1007/BF00819502
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DOI: https://doi.org/10.1007/BF00819502