Journal of Neuro-Oncology

, Volume 103, Issue 3, pp 705–711

Recurrence in childhood medulloblastoma

  • Monika Warmuth-Metz
  • Sophia Blashofer
  • André O. von Bueren
  • Katja von Hoff
  • Brigitte Bison
  • Fabian Pohl
  • Rolf-Dieter Kortmann
  • Torsten Pietsch
  • Stefan Rutkowski
Clinical Study – Patient Study
  • 284 Downloads

Abstract

Thirty-eight consecutive children treated according to the HIT2000 and HIT91 studies for medulloblastoma who suffered 40 recurrence events were identified from a neuroradiological database. Relapse was associated with younger median age compared with all children treated on HIT2000. Eight patients relapsed with isolated local recurrence. There was no correlation with incomplete surgical removal or violation of the respective treatment protocol. Four patients were younger than 4 years at time of initial presentation and thus were not treated primarily with radiotherapy, suggesting that delayed radiotherapy might be a contributing factor. Meningeal dissemination was present in 32 events; 16 were located in the frontal region, 8 of which were isolated nodular frontal and frontobasal meningeal disease. Circumscribed meningeal recurrences were associated with better overall survival (OS) compared with diffuse, widespread recurrences. Isolated frontobasal meningeal relapses are a well-known phenomenon in medulloblastomas even years after treatment and have been correlated to an underdose of radiation in many literature reports. However, in our patients there was no correlation to possible treatment violations, indicating that inadequate radiation dose to the frontobasal region was unlikely to be a causative factor. Surgical technique varied due to the multicentric nature of our study, so position during surgery was not recognized as a predisposing factor for frontobasal recurrence.

Keywords

Medulloblastoma Relapse Meningeal dissemination 

References

  1. 1.
    Kaatsch P, Rickert CH, Kühl J, Schüz J, Michaelis J (2001) Population-based epidemiologic data on brain tumours in German children. Cancer 92:3155–3164PubMedCrossRefGoogle Scholar
  2. 2.
    Packer RJ, Rood BR, MacDonald TJ (2003) Medulloblastoma: present concepts of stratification into risk groups. Pediatr Neurosurg 39:60–67PubMedCrossRefGoogle Scholar
  3. 3.
    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 17:832–845PubMedGoogle Scholar
  4. 4.
    Kortmann RD, Kühl J, Timmermann B, Mittler U, Urban C, Budach V, Richter E, Willich N, Flentje M, Berthold F, Slavc I, Wolff J, Meisner C, Wiestler O, Soerensen 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 46:269–279PubMedCrossRefGoogle Scholar
  5. 5.
    Inakoshi H, Kayamori R, Tsuchida E, Sakai K, Shibamoto Y, Wakushima H, Ogawa J, Kobayashi M, Obara T (2003) Multivariate analysis of dissemination relapse of medulloblastoma and estimation of its time parameter for craniospinal irradiation. Radiat Med 2:37–45Google Scholar
  6. 6.
    Bouffet E, Doz F, Demaille MC, Tron P, Roche H, Plantaz D, Thyss A, Stephan JL, Lejars O, Sariban E, Buclon M, Zücker JM, Brunat-Mentigny M, Bernard JL, Gentet JC (1998) Improving survival in recurrent medulloblastoma: earlier detection, better treatment or still an impasse? Br J Cancer 77:1321–1326PubMedCrossRefGoogle Scholar
  7. 7.
    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 136:117–126CrossRefGoogle Scholar
  8. 8.
    Rutkowski S, von Bueren AO, Warmuth-Metz M, Soerensen N, Deinlein F, Schlegel PG, Kühl J, Benesch M, Zwiener I, Faldum A, Pietsch T, Kortmann RD (2010) Treatment of children and adolescents with metastatic medulloblastoma by conventional chemotherapy and hyperfractionated radiotherapy. Preliminary results of the prospective GPOH-trial HIT 2000 (MET HIT 2000 AB4). Neuro Oncol 12:ii5 (abstr)Google Scholar
  9. 9.
    Von Hoff K, Hinkes B, Gerber N, Deinlein F, Mittler U, Urban C, Benesch M, Warmuth-Metz M, Soerensen N, Zwiener I, Goette H, Schlegel PG, Pietsch T, Kortmann RD, Kuehl J, Rutkowski S (2009) Long-term outcome and clinical prognostic factors in children with medulloblastomas treated in the prospective randomised multicentre trial HIT’91. Eur J Cancer 45:1209–1217CrossRefGoogle Scholar
  10. 10.
    Lannering B, Rutkowski S, Doz F, Pizer B, Gustafson G, Navajas A, Massimino M, Faldum A, Clifford S, Pietsch T, Kortmann R-D (2010) HIT-SIOP PNET4. A randomised multicentre study of hyperfractionated (HFRT) versus standard radiotherapy (StRT) in children with standard risk medulloblastoma. Neuro Oncol 12:ii5 (abstr)Google Scholar
  11. 11.
    Von Bueren AO, Pietsch T, Warmuth-Metz M, Soerensen N, Deinlein F, Schlegel PG, Kühl J, Benesch M, Zwiener I, Faldum A, Kortmann RD, Rutkowski S (2010) Treatment of young children (<4 years) with medulloblastoma by chemotherapy alone. Interim results of the prospective multicenter GPOH-trial HIT 2000 (HIT 2000 BIS4) confirming the prognostic impact of histology. Neuro Oncol 12:ii7 (abstr)Google Scholar
  12. 12.
    Rutkowski S, Bode U, Deinlein F, Ottensmeier H, Warmuth-Metz M, Soerensen N, Graf N, Emser A, Pietsch T, Wolff JE, Kortmann RD, Kühl J (2005) Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med 352:978–986PubMedCrossRefGoogle Scholar
  13. 13.
    Di Rocco C, Iannelli A, Tancredi A (1995) Patterns of failure in surgical therapy of medulloblastomas. J Neurosurg Sci 39:1–6PubMedGoogle Scholar
  14. 14.
    Jenkin D, Shabanah MA, Shail EA, Gray A, Hassounah M, Khafaga Y, Kofide A, Mustafa M, Schultz H (2000) Prognostic factors for medulloblastoma. Int J Radiat Oncol Biol Phys 47:573–584PubMedCrossRefGoogle Scholar
  15. 15.
    Evans AE, Jenkin RD, Sposto R, Ortega JA, Wilson CB, Wara W, Ertel IJ, Kramer S, Chang CH, Leikin SL (1990) The treatment of medulloblastoma. Results of a prospective randomized trial of radiation therapy with and without CCNU, vincristine, and prednisone. J Neurosurg 72:572–582PubMedCrossRefGoogle Scholar
  16. 16.
    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 19:73–77PubMedCrossRefGoogle Scholar
  17. 17.
    Karlsson U, Kirby T, Orrison W, Lionberger M (1995) Ocular globe topography in radiotherapy. Int J Radiat Oncol Biol Phys 33:705–712PubMedCrossRefGoogle Scholar
  18. 18.
    Miralbell R, Bleher A, Huguenin P, Ries G, Kann R, Mirimanoff RO, Notter M, Nouet P, Bieri S, Thum P, Toussi H (1997) Pediatric medulloblastoma: radiation treatment technique and patterns of failure. Int J Radiat Oncol Biol Phys 37:523–529PubMedCrossRefGoogle Scholar
  19. 19.
    Halperin EC (1996) Impact of radiation technique upon the outcome of treatment for medulloblastoma. Int J Radiat Oncol Biol Phys 36:233–239PubMedCrossRefGoogle Scholar
  20. 20.
    Hardy DG, Hope-Stone HF, McKenzie CG, Scholtz CL (1978) Recurrence of medulloblastoma after homogeneous field radiotherapy. Report of three cases. J Neurosurg 49:434–440PubMedCrossRefGoogle Scholar
  21. 21.
    Carrie C, Hofstetter S, Gomez F, Moncho V, Doz F, Alapetite C, Murraciole X, Maire JP, Benhassel M, Chapet S, Quentin P, Kolodie H, Lagrange JL, Cuillere JC, Habrand JL (1999) Impact of targeting deviations on outcome in medulloblastoma: study of the French Society of Pediatric Oncology (SFOP). Int J Radiat Oncol Biol Phys 45:435–439PubMedGoogle Scholar
  22. 22.
    Carrie C, Muracciole X, Gomez F, Habrand J-L, Benhassel M, Mege M, Mahe M, Quetin P, Maire JP, Soum F, Baron MH, Clavere P, Chapet S, Gaci Z, Kolodie H, Maingon P, Vie B, Bernier V, Alapetite C, Hoffstetter S, Grill J, Lafay F (2005) Conformal radiotherapy, reduced boost volume, hyperfractionated radiotherapy, and online quality control in standard risk medulloblastoma without chemotherapy: results of the French M-SFOP 98 protocol. Int J Radiat Oncol Biol Phys 63:711–716PubMedCrossRefGoogle Scholar
  23. 23.
    Sun L-M, Yeh S-A, Wang C-J, Huang E-Y, Chen H-C, Hsu H-C, Lee SP (2002) Postoperative radiation therapy for medulloblastoma—high recurrence rate in the subfrontal region. J Neurooncol 58:77–85PubMedCrossRefGoogle Scholar
  24. 24.
    Taylor RE, Bailey CC, Robinson KJ, Weston CL, Ellison D, Ironside J, Lucraft H, Gilbertson R, Tait DM, Saran F, Walker DA, Pizer BL, Lashford LS (2004) Impact of radiotherapy parameters on outcome in the International Society of Paediatric Oncology/United Kingdom Children’s Cancer Study Group PNET-3 study of preradiotherapy chemotherapy for M0–M1 medulloblastoma. Int J Radiat Oncol Biol Phys 58:1184–1193PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Monika Warmuth-Metz
    • 1
  • Sophia Blashofer
    • 1
  • André O. von Bueren
    • 5
  • Katja von Hoff
    • 5
  • Brigitte Bison
    • 1
  • Fabian Pohl
    • 2
  • Rolf-Dieter Kortmann
    • 3
  • Torsten Pietsch
    • 4
  • Stefan Rutkowski
    • 5
  1. 1.Department of Neuroradiology, Reference Center for NeuroradiologyUniversity of WürzburgWürzburgGermany
  2. 2.Department for RadiooncologyUniversity of WürzburgWürzburgGermany
  3. 3.Department of Radiooncology, Reference Center for RadiooncologyUniversity of LeipzigLeipzigGermany
  4. 4.Department of Neuropathology, National Brain Tumor Reference CenterUniversity of BonnBonnGermany
  5. 5.Department of Pediatric Hematology and Oncology, HIT2000 Study CenterUniversity Medical Center Hamburg-EppendorfHamburgGermany

Personalised recommendations