Childhood pineoblastoma: experiences from the prospective multicenter trials HIT-SKK87, HIT-SKK92 and HIT91
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To analyze the outcome of children with pineoblastoma (PB), treated within the prospective multicenter trials HIT-SKK87, HIT-SKK92 and HIT91 of German-speaking countries.
We report on 11 children suffering from PB. Five children younger than 3 years of age received chemotherapy after surgery until eligible for radiotherapy (HIT-SKK87 and HIT-SKK92). Five of six children older than 3 years were treated after surgery with immediate chemotherapy and craniospinal irradiation, and one child received maintenance chemotherapy after postoperative radiotherapy (HIT91).
Five of the six older children are still alive in continuous complete remission (CCR) with a median overall survival (OS) and progression free survival (PFS) of 7.9 years. Five of these six HIT91 patients responded to postoperative chemotherapy and radiotherapy. The only patient with tumor progression during initial chemotherapy achieved complete remission with radiotherapy and is alive. In contrast, all five young children died of tumor progression after a median OS of 0.9 years (PFS 0.6 years). They had either metastatic disease (M1) and/or postoperative residual tumor. Response to postoperative chemotherapy was lower than in the older age group, and only one of these children received radiotherapy.
Combined chemotherapy and radiotherapy were feasible and effective in the older age group, leading to prolonged remissions in five of six children. Tumor biology may be more aggressive in younger children with PB, who presented more frequently with high-risk features at diagnosis and had poorer response rates to neoadjuvant postoperative chemotherapy. More intensified treatment regimens may be needed for young children with PB.
KeywordsPineoblastoma PNET Supratentorial PNET Young children Chemotherapy Radiotherapy Trial
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- 1.Kleihues P, Cavenee WK (eds) (2000) World Health Organisation classification of tumors: Pathology and genetics of tumors of the nervous system. IARC Press, Lyon, pp 141–144Google Scholar
- 2.Kleihues P, Louis DN, Scheithauer BW, Rorke LB, Reifenberger G, Burger PC, Cavenee WK (2002) The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol 61(3):215–225; discussion 226–229Google Scholar
- 4.Raffel C, Jenkins RB, Frederick L et al (1997) Sporadic medulloblastomas contain PTCH mutations. Cancer Res 57:842–845Google Scholar
- 11.Jakacki RI, Zeltzer PM, Boyett JM, Albright AL, Allen JC, Geyer JR, Rorke LB, Stanley P, Stevens KR, Wisoff J et al (1995) Survival and prognostic factors following radiation and/or chemotherapy for primitive neuroectodermal tumors of the pineal region in infants and children: a report of the Childrens Cancer Group. J Clin Oncol Jun;13(6):1377–1383Google Scholar
- 12.Kuehl J, Mueller HL, Berthold F, Kortmann RD, Deinlein F, Maass F, Graf N, Gnekow A, Scheurlen W, Goebel U, Wolf JEA, Bamberg M, Kaatsch P, Kleihues P, Rating D, Soerensen N, Wiestler OD (1998) Pre-irradiation chemotherapy of children and young adults with malignant brain tumors: results of the German pilot trial HIT88/89. Klin Paediatr 210:227–233CrossRefGoogle Scholar
- 14.Cohen BH, Zeltzer PM, Boyett JM, Geyer JR, Allen JC, Finlay JL, McGuire-Cullen P, Milstein JM, Rorke LB, Stanley P et al (1995) Prognostic factors and treatment results for supratentorial primitive neuroectodermal tumors in children using radiation and chemotherapy: a childrens cancer group randomized trial. J Clin Oncol 13(7):1687–1696PubMedGoogle Scholar
- 15.Prados MD, Wara WM, Edwards MHB, Cogen PH (1993) Hyperfractionated craniospinal radiation for primitive neuroectodermal tumors; early results of a pilot study. Int J Radiat Oncol Biol Phys 28:431–438Google Scholar
- 18.Kortmann RD, Kuehl J, Timmermann B, Mittler U, Urban C, Burdach V, Richter E, Willich N, Flentje M, Berthold F, Slavc I, Wolff J, Meisner C, Wiestler O, Sorense N, Warmuth-Metz M, Bamberg M (2000) Postoperative neoadjuvant chemotherapy before radiotherapy as compared to immediate radiotherapy followed by maintenance chemotherapy in the treatment of medulloblastoma in childhood: results of the German prospective randomized trial HIT ‘91. Int J Radiat Oncol Biol Phys Jan 15, 46(2):269–279Google Scholar
- 20.Kuehl J, Beck J, Bode U et al (1995) Delayed radiation therapy after postoperative chemotherapy in children less than 3 years of age with medulloblatoma: results of the trial HIT-SKK’87 and preliminary results of the pilot trial HIT-SKK’92. Med Pediatr Oncol 25(Suppl):250Google Scholar
- 22.Timmermann B, Kortmann RD, Kuehl J, Rutkowski S, Meisner C, Pietsch T, Deinlein F, Urban C, Warmuth-Metz M, Bamberg M (2006) Role of radiotherapy in supratentorial primitive neuroectodermal tumor in young children: results of the German HIT-SKK87 and HIT-SKK92 trials. J Clin Oncol 24(10):1554–1560PubMedCrossRefGoogle Scholar
- 23.Seegenschmied MH (1998) Nebenwirkungen in der Onkologie. Springer-Verlag, Berlin, HeidelbergGoogle Scholar
- 25.Timmermann B, Kortmann RD, Kuehl J, Meisner C, Dieckmann K, Pietsch T, Bamberg M (2002) Role of Radiotherapy in the treatment of supratentorial primitive neuroectodermal tumors in childhood: results of the prospective German brain tumor trials HIT 88/89 and 91. J Clin Oncol 20(3):842–849PubMedCrossRefGoogle Scholar
- 26.Geyer JR, Zeltzer PM, Boyett JM, Rorke LB, Stanley P, Albright AL, Wisoff JH, Milstein JM, Allen JC, Finlay JL et al (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 Children’s Cancer Group. J Clin Oncol 12(8):1607–1615PubMedGoogle Scholar
- 27.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 (2005) Children’s cancer group: multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the Children’s Cancer Group. J Clin Oncol 23(30):7621–7631PubMedCrossRefGoogle Scholar
- 28.Broniscer A, Nicolaides TP, Dunkel IJ, Gardner SL, Johnson J Jr, Allen JC, Sposto R, Finlay JL (2004) High-dose chemotherapy with autologous stem-cell rescue in the treatment of patients with recurrent non-cerebellar primitive neuroectodermal tumors. Pediatr Blood Cancer 42(3):261–267PubMedCrossRefGoogle Scholar