Abstract
To reduce the sequelae of craniospinal irradiation (CSI) in children under 10 (≥3) years old and to improve the prognosis for high-risk medulloblastoma in adolescents, we adjusted postoperative chemotherapy and CSI doses to patients’ stage and age. From 1986 to 1995, 73 patients entered the study. Children under 10 and adolescents with metastases, residual disease (RD) or stage >T3 received postoperative IV vincristine and high-dose (HD) ± intrathecal (IT) methotrexate, while standard-risk adolescents were given IV vincristine and IT methotrexate. Chemotherapy was followed by CSI (19.8 Gy for children <10; 36 Gy for adolescents), with a 54-Gy posterior fossa boost. Maintenance chemotherapy with lomustine and vincristine was administered for a year afterwards. A total of 39 children were under 10 of whom 20 had metastases. Response to chemotherapy was recorded in 70%, but 5-year EFS and OS were only 48 and 56%, respectively. Results were significantly worse for metastatic cases, patients under 10, those with RD, and those staged without MRI (unavailable early in the study). Efforts to preserve survivors’ quality of life did not pay off, and most patients over 30 still depended on their parents’ income and had severe cognitive/endocrine disabilities. In conclusion, despite a very high response rate with this preradiation HD methotrexate schedule, the outcome for high-risk medulloblastoma patients did not improve (especially when lower CSI doses were used) and patients still developed severe morbidities.
Similar content being viewed by others
References
Duffner PK, Cohen ME, Thomas PR et al (1985) The long-term effects of cranial irradiation on the central nervous system. Cancer 56:1841–1846
Walter AW, Mulhern RK, Gajjar A et al (1999) Survival and neurodevelopmental outcome of young children with medulloblastoma at St Jude Children’s Hospital. J Clin Oncol 17:3720–3728
Chang CH, Houseplan EM, Herbert C (1969) An operative staging system for a megavoltage radiotherapeutic technique for cerebellar medulloblastoma. Radiology 93:1351–1359
Butler RW, Hill JM, Steinherz PG, Meyers PA, Finlay JL (1994) Neuropsychologic effects of cranial irradiation, intrathecal methotrexate, and systemic methotrexate in childhood cancer. J Clin Oncol 12:2621–2629
Gnekow AK (1995) Recommendations of the brain tumor subcommittee for the reporting of trials. SIOP brain tumor subcommittee. international society of pediatric oncology. Med Pediatr Oncol 24:104–108
Kaplan ES, Meier P (1958) Non-parametric estimations from incomplete observations. J Am Stat Assoc 53:457–482
Riva D, Giorgi C, Nichelli F et al (2002) Intrathecal methotrexate affects cognitive function in children with medulloblastoma. Neurology 59:48–53
Gajjar A, Chintagumpala M, Ashley D et al (2006) Risk-adapted craniospinal radiotherapy followed by HD 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 7:813–820
Gandola L, Massimino M, Cefalo G et al (2009) Hyperfractionated accelerated radiotherapy in the Milan strategy for metastatic medulloblastoma. J Clin Oncol 27:566–571
Goldwein JW, Radcliffe J, Johnson J et al (1996) Updated results of a pilot study of low-dose craniospinal irradiation plus chemotherapy for children under five with cerebellar primitive neuroectodermal tumors (medulloblastoma). Int J Radiat Oncol Biol Phys 34:899–904
Jakacki RI, Feldman H, Jamison C, Boaz JC, Luerssen TG, Timmerman R (2004) A pilot study of preirradiation chemotherapy and 1,800 cGy craniospinal irradiation in young children with medulloblastoma. Int J Radiat Oncol Biol Phys 60:531–536
Deutsch M, Thomas PRM, Kirscher J et al (1996) Results of a prospective randomized trial comparing standard dose neuraxis irradiation (3,600 cGY/20) with reduced neuraxis irradiation (2,340 cGY/13) in patients with low-stage medulloblastoma. Pediatr Neurosurg 24:167–177
Mulhern RK, Kepner JL, Thomas PR et al (1998) Neuropsychologic functioning of survivors of childhood medulloblastoma randomized to receive conventional or reduced-dose craniospinal irradiation: A Pediatric Oncology Group study. J Clin Oncol 16:1723–1728
Thomas PR, Deutsch M, Kepner JL et al (2000) Low-stage medulloblastoma: final analysis of trial comparing standard-dose with reduced-dose neuraxis irradiation. J Clin Oncol 18:3004–3011
Packer RJ, Gajjar A, Vezina G et al (2006) Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol 24:4202–4208
Rosen G, Ghavimi F, Nirenberg A et al (1977) High-dose methotrexate with citrovorum factor rescue for the treatment of central nervous system tumors in children. Cancer Treat Rep 61:681–690
Kortmann RD, Kuhl J, Timmermann B et al (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 46:269–279
Evans AE, Jenkin RDT, Sposto R et al (1990) The treatment of medulloblastoma. J Neurosurg 72:572–582
Bailey CC, Gnekow A, Wellek S et al (1995) Prospective randomised trial of chemotherapy given before radiotherapy in childhood medulloblastoma. International Society of Paediatric Oncology (SIOP) and the (German) Society of Paediatric Oncology (GPO): SIOP II. Med Pediatr Oncol 25:166–178
Taylor RE, Bailey CC, Robinson K et al (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 21:1581–1591
Rutkowski S, Bode U, Deinlein F et al (2005) Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med 352:978–986
Langer T, Martus P, Ottensmeier H, Hertzberg H, Beck JD, Meier W (2002) CNS late-effects after ALL therapy in childhood. Part III. Neuropsychological performance in long-term survivors of childhood all: impairments of concentration, attention, and memory. Med Pediatr Oncol 38:320–328
Kellie SJ, Chaku J, Lockwood LR, O’Regan P, Waters KD, Wong CKF (2005) Late magnetic resonance imaging features of leukoencephalopathy in children with central nervous system tumours following high-dose methotrexate and neuraxis radiation therapy. Eur J Cancer 41:1588–1596
Acknowledgments
This work was partially supported by Associazione Bianca Garavaglia onlus, Busto Arsizio, Italy, provided resident scholarships
Conflict of interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Massimino, M., Cefalo, G., Riva, D. et al. Long-term results of combined preradiation chemotherapy and age-tailored radiotherapy doses for childhood medulloblastoma. J Neurooncol 108, 163–171 (2012). https://doi.org/10.1007/s11060-012-0822-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11060-012-0822-7