Skip to main content

Advertisement

SpringerLink
Log in

Long-term outcomes of adult medulloblastoma patients treated with radiotherapy

  • Clinical Study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Medulloblastoma (MB) is rare in adults and treatment guidelines are consequently not well-established. Few modern series have reported long-term follow-up and treatment sequelae. We examined long-term outcomes of adult MB patients at one institution. Records of 29 consecutive patients (18 male, 11 female) aged ≥ 18 years who received radiotherapy (RT) for primary MB from 1990 to 2016 were reviewed. Median age at diagnosis was 28 years (range 18–72 years). Seventeen patients were standard risk and 12 were high risk. Nineteen patients had gross total resection, seven had subtotal resection, and three had biopsy only. Median craniospinal irradiation and boost doses were 36 Gy (range 23.4–39.6 Gy) and 55.8 Gy (range 54–59.4 Gy), respectively. Of 24 patients receiving chemotherapy, 20 received concurrent + adjuvant and 4 received adjuvant only. At median follow-up of 9.0 years (range 1.1–20.5 years), five patients recurred: four in the posterior fossa and one in both the posterior fossa and above the tentorium. Five patients died: two of disease progression and three after possible treatment complications (seizure, lobar pneumonia, and multifactorial sepsis). At last follow-up, 23 patients were alive with no evidence of disease. Long-term effects include executive dysfunction (n = 17), weakness/ataxia (n = 16), and depression/anxiety (n = 13). Kaplan–Meier estimates of 10-year overall survival and failure-free survival are 83% (95% confidence interval [CI] 59–93%) and 79% (CI 55–91%), respectively. Despite encouraging disease control in this cohort, long-term sequelae may limit quality of life. Multimodality pediatric regimens using lower RT doses may be considered to reduce treatment-related morbidity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Lai R (2008) Survival of patients with adult medulloblastoma: a population-based study. Cancer 112(7):1568–1574. doi:10.1002/cncr.23329

    Article  PubMed  Google Scholar 

  2. Ostrom QT, Gittleman H, Xu J, Kromer C, Wolinsky Y, Kruchko C, Barnholtz-Sloan JS (2016) CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2009–2013. Neuro-oncol. doi:10.1093/neuonc/now207

    Google Scholar 

  3. Giordana MT, Cavalla P, Dutto A, Borsotti L, Chio A, Schiffer D (1997) Is medulloblastoma the same tumor in children and adults? J Neurooncol 35(2):169–176

    Article  CAS  PubMed  Google Scholar 

  4. Douglas JG, Barker JL, Ellenbogen RG, Geyer JR (2004) Concurrent chemotherapy and reduced-dose cranial spinal irradiation followed by conformal posterior fossa tumor bed boost for average-risk medulloblastoma: efficacy and patterns of failure. Int J Radiat Oncol Biol Phys 58(4):1161–1164. doi:10.1016/j.ijrobp.2003.09.010

    Article  PubMed  Google Scholar 

  5. Brandes AA, Franceschi E, Tosoni A, Blatt V, Ermani M (2007) Long-term results of a prospective study on the treatment of medulloblastoma in adults. Cancer 110(9):2035–2041. doi:10.1002/cncr.23003

    Article  PubMed  Google Scholar 

  6. Brandes AA, Bartolotti M, Marucci G, Ghimenton C, Agati R, Fioravanti A, Mascarin M, Volpin L, Ammannati F, Masotto B, Gardiman MP, De Biase D, Tallini G, Crisi G, Bartolini S, Franceschi E (2015) New perspectives in the treatment of adult medulloblastoma in the era of molecular oncology. Crit Rev Oncol Hematol 94(3):348–359. doi:10.1016/j.critrevonc.2014.12.016

    Article  PubMed  Google Scholar 

  7. Brandes AA, Franceschi E (2014) Shedding light on adult medulloblastoma: current management and opportunities for advances. Am Soc Clin Oncol Educ Book. doi:10.14694/EdBook_AM.2014.34.e82

    PubMed  Google Scholar 

  8. Vigneron C, Entz-Werle N, Lutz P, Spiegel A, Jannier S, Helfre S, Alapetite C, Coca A, Kehrli P, Noel G (2015) Evolution of the management of pediatric and adult medulloblastoma. Cancer Radiother 19(5):347–357. doi:10.1016/j.canrad.2015.03.010 (quiz 358–349, 362)

    Article  CAS  PubMed  Google Scholar 

  9. Prados MD, Warnick RE, Wara WM, Larson DA, Lamborn K, Wilson CB (1995) Medulloblastoma in adults. Int J Radiat Oncol Biol Phys 32(4):1145–1152

    Article  CAS  PubMed  Google Scholar 

  10. Frost PJ, Laperriere NJ, Wong CS, Milosevic MF, Simpson WJ, Pintilie M (1995) Medulloblastoma in adults. Int J Radiat Oncol Biol Phys 32(4):951–957

    Article  CAS  PubMed  Google Scholar 

  11. Carrie C, Lasset C, Alapetite C, Haie-Meder C, Hoffstetter S, Demaille MC, Kerr C, Wagner JP, Lagrange JL, Maire JP et al (1994) Multivariate analysis of prognostic factors in adult patients with medulloblastoma: retrospective study of 156 patients. Cancer 74(8):2352–2360

    Article  CAS  PubMed  Google Scholar 

  12. Abacioglu U, Uzel O, Sengoz M, Turkan S, Ober A (2002) Medulloblastoma in adults: treatment results and prognostic factors. Int J Radiat Oncol Biol Phys 54(3):855–860

    Article  PubMed  Google Scholar 

  13. Padovani L, Sunyach MP, Perol D, Mercier C, Alapetite C, Haie-Meder C, Hoffstetter S, Muracciole X, Kerr C, Wagner JP, Lagrange JL, Maire JP, Cowen D, Frappaz D, Carrie C (2007) Common strategy for adult and pediatric medulloblastoma: a multicenter series of 253 adults. Int J Radiat Oncol Biol Phys 68(2):433–440. doi:10.1016/j.ijrobp.2006.12.030

    Article  PubMed  Google Scholar 

  14. Selek U, Zorlu F, Hurmuz P, Cengiz M, Turker A, Soylemezoglu F, Gurkaynak M (2007) Craniospinal radiotherapy in adult medulloblastoma. Strahlentherapie Onkologie : Organ der Deutschen Rontgengesellschaft [et al] 183(5):236–240. doi:10.1007/s00066-007-1563-y

    Article  Google Scholar 

  15. Ang C, Hauerstock D, Guiot MC, Kasymjanova G, Roberge D, Kavan P, Muanza T (2008) Characteristics and outcomes of medulloblastoma in adults. Pediatr Blood Cancer 51(5):603–607. doi:10.1002/pbc.21588

    Article  PubMed  Google Scholar 

  16. Ertas G, Ucer AR, Altundag MB, Durmus S, Calikoglu T, Ozbagi K, Abanuz H, Altundag K, Demirkasimoglu A (2008) Medulloblastoma/primitive neuroectodermal tumor in adults: prognostic factors and treatment results: a single-center experience from Turkey. Medical oncology 25(1):69–72. doi:10.1007/s12032-007-0044-6

    Article  PubMed  Google Scholar 

  17. Menon G, Krishnakumar K, Nair S (2008) Adult medulloblastoma: clinical profile and treatment results of 18 patients. J Clin Neurosci 15(2):122–126. doi:10.1016/j.jocn.2007.06.007

    Article  PubMed  Google Scholar 

  18. Smee RI, Williams JR (2008) Medulloblastomas-primitive neuroectodermal tumours in the adult population. J Med Imaging Radiat Oncol 52(1):72–76. doi:10.1111/j.1440-1673.2007.01915.x

    Article  CAS  PubMed  Google Scholar 

  19. Brandes AA, Ermani M, Amista P, Basso U, Vastola F, Gardiman M, Iuzzolino P, Turazzi S, Rotilio A, Volpin L, Mazza C, Sainati L, Ammannati F, Berti F (2003) The treatment of adults with medulloblastoma: a prospective study. Int J Radiat Oncol Biol Phys 57(3):755–761

    Article  PubMed  Google Scholar 

  20. Moots PL, O’Neill A, Londer H, Mehta M, Blumenthal DT, Barger GR, Grunnet ML, Grossman S, Gilbert MR, Schiff D (2016) Preradiation chemotherapy for adult high-risk medulloblastoma: a trial of the ECOG-ACRIN cancer research group (E4397). Am J Clin Oncol. doi:10.1097/coc.0000000000000326

    PubMed  Google Scholar 

  21. Chang CH, Housepian EM, Herbert C Jr (1969) An operative staging system and a megavoltage radiotherapeutic technic for cerebellar medulloblastomas. Radiology 93(6):1351–1359. doi:10.1148/93.6.1351

    Article  CAS  PubMed  Google Scholar 

  22. Cheng DT, Mitchell TN, Zehir A, Shah RH, Benayed R, Syed A, Chandramohan R, Liu ZY, Won HH, Scott SN, Brannon AR, O’Reilly C, Sadowska J, Casanova J, Yannes A, Hechtman JF, Yao J, Song W, Ross DS, Oultache A, Dogan S, Borsu L, Hameed M, Nafa K, Arcila ME, Ladanyi M, Berger MF (2015) Memorial sloan kettering-integrated mutation profiling of actionable cancer targets (MSK-IMPACT): a hybridization capture-based next-generation sequencing clinical assay for solid tumor molecular oncology. J Mol Diagn 17(3):251–264. doi:10.1016/j.jmoldx.2014.12.006

    Article  CAS  PubMed  Google Scholar 

  23. Brock PR, Knight KR, Freyer DR, Campbell KCM, Steyger PS, Blakley BW, Rassekh SR, Chang KW, Fligor BJ, Rajput K, Sullivan M, Neuwelt EA (2012) Platinum-induced ototoxicity in children: a consensus review on mechanisms, predisposition, and protection, including a new international society of pediatric oncology boston ototoxicity scale. J Clin Oncol 30(19):2408–2417. doi:10.1200/jco.2011.39.1110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Silvani A, Gaviani P, Lamperti E, Botturi A, DiMeco F, Franzini A, Ferroli P, Fariselli L, Milanesi I, Erbetta A, Pollo B, Salmaggi A (2012) Adult medulloblastoma: multiagent chemotherapy with cisplatinum and etoposide: a single institutional experience. J Neurooncol 106(3):595–600. doi:10.1007/s11060-011-0696-0

    Article  CAS  PubMed  Google Scholar 

  25. Riffaud L, Saikali S, Leray E, Hamlat A, Haegelen C, Vauleon E, Thierry Lesimple (2009) Survival and prognostic factors in a series of adults with medulloblastomas. J Neurosurg 111(3):478–487. doi:10.3171/2009.1.jns081004

    Article  PubMed  Google Scholar 

  26. Chan AW, Tarbell NJ, Black PM, Louis DN, Frosch MP, Ancukiewicz M, Chapman P, Loeffler JS (2000) Adult medulloblastoma: prognostic factors and patterns of relapse. Neurosurgery 47(3):623–631 (discussion 631–622)

    CAS  PubMed  Google Scholar 

  27. Kann BH, Lester-Coll NH, Park HS, Yeboa DN, Kelly JR, Baehring JM, Becker KP, Yu JB, Bindra RS, Roberts KB (2016) Adjuvant chemotherapy and overall survival in adult medulloblastoma. Neuro-oncol. doi:10.1093/neuonc/now150

    PubMed Central  Google Scholar 

  28. Packer RJ, Zhou T, Holmes E, Vezina G, Gajjar A (2013) Survival and secondary tumors in children with medulloblastoma receiving radiotherapy and adjuvant chemotherapy: results of Children’s Oncology Group trial A9961. Neuro-oncol 15(1):97–103. doi:10.1093/neuonc/nos267

    Article  CAS  PubMed  Google Scholar 

  29. 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. doi:10.1200/jco.1999.17.3.832

    Article  CAS  PubMed  Google Scholar 

  30. Hubbard JL, Scheithauer BW, Kispert DB, Carpenter SM, Wick MR, Laws ER Jr (1989) Adult cerebellar medulloblastomas: the pathological, radiographic, and clinical disease spectrum. J Neurosurg 70(4):536–544. doi:10.3171/jns.1989.70.4.0536

    Article  CAS  PubMed  Google Scholar 

  31. 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. doi:10.3171/jns.1981.55.1.0043

    Article  CAS  PubMed  Google Scholar 

  32. 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. doi:10.1200/jco.2006.06.4980

    Article  CAS  PubMed  Google Scholar 

  33. Kortmann RD, Kuhl 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, Sorensen 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(2):269–279

    Article  CAS  PubMed  Google Scholar 

  34. 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(4):1184–1193. doi:10.1016/j.ijrobp.2003.08.010

    Article  PubMed  Google Scholar 

  35. 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 (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. doi:10.1200/jco.2003.05.116

    Article  CAS  PubMed  Google Scholar 

  36. Brown AP, Barney CL, Grosshans DR, McAleer MF, de Groot JF, Puduvalli VK, Tucker SL, Crawford CN, Khan M, Khatua S, Gilbert MR, Brown PD, Mahajan A (2013) Proton beam craniospinal irradiation reduces acute toxicity for adults with medulloblastoma. Int J Radiat Oncol Biol Phys 86(2):277–284. doi:10.1016/j.ijrobp.2013.01.014

    Article  PubMed  PubMed Central  Google Scholar 

  37. Barney CL, Brown AP, Grosshans DR, McAleer MF, de Groot JF, Puduvalli V, Tucker SL, Crawford CN, Gilbert MR, Brown PD, Mahajan A (2014) Technique, outcomes, and acute toxicities in adults treated with proton beam craniospinal irradiation. Neuro-oncol 16(2):303–309. doi:10.1093/neuonc/not155

    Article  CAS  PubMed  Google Scholar 

  38. Merchant TE, Kun LE, Krasin MJ, Wallace D, Chintagumpala MM, Woo SY, Ashley DM, Sexton M, Kellie SJ, Ahern V, Gajjar A (2008) Multi-institution prospective trial of reduced-dose craniospinal irradiation (23.4 Gy) followed by conformal posterior fossa (36 Gy) and primary site irradiation (55.8 Gy) and dose-intensive chemotherapy for average-risk medulloblastoma. Int J Radiat Oncol Biol Phys 70(3):782–787. doi:10.1016/j.ijrobp.2007.07.2342

    Article  PubMed  Google Scholar 

  39. Huang E, Teh BS, Strother DR, Davis QG, Chiu JK, Lu HH, Carpenter LS, Mai WY, Chintagumpala MM, South M, Grant WH 3rd, Butler EB, Woo SY (2002) Intensity-modulated radiation therapy for pediatric medulloblastoma: early report on the reduction of ototoxicity. Int J Radiat Oncol Biol Phys 52(3):599–605

    Article  PubMed  Google Scholar 

  40. Ricardi U, Corrias A, Einaudi S, Genitori L, Sandri A, di Montezemolo LC, Besenzon L, Madon E, Urgesi A (2001) Thyroid dysfunction as a late effect in childhood medulloblastoma: a comparison of hyperfractionated versus conventionally fractionated craniospinal radiotherapy. Int J Radiat Oncol Biol Phys 50(5):1287–1294

    Article  CAS  PubMed  Google Scholar 

  41. Paulino AC (2002) Hypothyroidism in children with medulloblastoma: a comparison of 3600 and 2340 cGy craniospinal radiotherapy. Int J Radiat Oncol Biol Phys 53(3):543–547

    Article  PubMed  Google Scholar 

  42. 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. doi:10.1007/s00401-011-0922-z

    Article  CAS  Google Scholar 

  43. Remke M, Hielscher T, Northcott PA, Witt H, Ryzhova M, Wittmann A, Benner A, von Deimling A, Scheurlen W, Perry A, Croul S, Kulozik AE, Lichter P, Taylor MD, Pfister SM, Korshunov A (2011) Adult medulloblastoma comprises three major molecular variants. J Clin Oncol 29(19):2717–2723. doi:10.1200/jco.2011.34.9373

    Article  PubMed  Google Scholar 

  44. Lou E, Schomaker M, Wilson JD, Ahrens M, Dolan M, Nelson AC (2016) Complete and sustained response of adult medulloblastoma to first-line sonic hedgehog inhibition with vismodegib. Cancer Biol Ther 17(10):1010–1016. doi:10.1080/15384047.2016.1220453

    Article  CAS  PubMed Central  Google Scholar 

Download references

Acknowledgements

Funding was provided by the National Institutes of Health/National Cancer Institute Cancer Center Support Grant (P30 CA008748). This work is also supported by a gift from Jack and Susan Rudin.

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Brian De, Kathryn Beal, Suchit H. Patel & Suzanne L. Wolden

  2. Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Kevin C. De Braganca, Ira J. Dunkel, Yasmin Khakoo & Stephen W. Gilheeney

  3. Department of Pediatrics, Weill Cornell Medical College, New York, NY, USA

    Ira J. Dunkel & Yasmin Khakoo

  4. Department of Neurosurgery, Memorial Sloan Kettering Cancer Center & Weill Cornell Medical College, New York, NY, USA

    Mark M. Souweidane

  5. Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Kevin C. De Braganca, Yasmin Khakoo & Lisa M. DeAngelis

  6. Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA, USA

    Paul Menzel

Authors
  1. Brian De
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kathryn Beal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kevin C. De Braganca
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mark M. Souweidane
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ira J. Dunkel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yasmin Khakoo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Stephen W. Gilheeney
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lisa M. DeAngelis
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Paul Menzel
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Suchit H. Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Suzanne L. Wolden
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Suzanne L. Wolden.

Ethics declarations

Conflict of interest

M.M.S. reports personal fees from Aesculap, Sanofi, and Baxter. I.J.D. reports personal fees from Bayer, Bristol-Myers Squibb, Ipsen, Eisai, and Pfizer, and grants from Genentech and Parexel (GSK, Novartis). L.M.D reports personal fees from Novartis, GlaxoSmithKline, and Celgene. All payments are outside the submitted work. Other authors declare no conflicts.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and the 1964 Helsinki declaration and its later amendments.

Formal consent

For this type of study formal consent is not required.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

De, B., Beal, K., De Braganca, K.C. et al. Long-term outcomes of adult medulloblastoma patients treated with radiotherapy. J Neurooncol 136, 95–104 (2018). https://doi.org/10.1007/s11060-017-2627-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-017-2627-1

Keywords

Search

Navigation