Abstract
Medulloblastoma is the most common form of brain malignancy of childhood. The mainstay of epidemiological data regarding childhood medulloblastoma is derived from case series, hence population-based studies are warranted to improve the accuracy of survival estimates. To utilize a big-data approach to update survival estimates in a contemporary cohort of children with medulloblastoma. We performed a population-based retrospective observational cohort study utilizing the Surveillance, Epidemiology, and End Results Program database that captures all children, less than 20 years of age, between 1973 and 2012 in 18 geographical regions representing 28% of the US population. We included all participants with a presumed or histologically diagnosis of medulloblastoma. The main outcome of interest is survivors at 1, 5 and 10 years following diagnosis. A cohort of 1735 children with a median (interquartile range) age at diagnosis of 7 (4–11) years, with a diagnosis of medulloblastoma were identified. The incidence and prevalence of pediatric medulloblastoma has remained stable over the past 4 decades. There is a critical time point at 1990 when the overall survival has drastically improved. In the contemporary cohort (1990 onwards), the percentage of participants alive was 86, 70 and 63% at 1, 5 and 10 years, respectively. Multivariate Cox-Regression model demonstrated Radiation (HR 0.37; 95% CI 0.30–0.46, p < 0.001) and Surgery (HR 0.42; 95% CI 0.30–0.58, p < 0.001) independently predict survival. The probability of mortality from a neurological cause is <5% in patients who are alive 8 years following diagnosis. The SEER cohort analysis demonstrates significant improvements in pediatric medulloblastoma survival. In contrast to previous reports, the majority of patients survive in the modern era, and those alive 8 years following initial diagnosis are likely a long-term survivor. The importance of minimizing treatment-related toxicity is increasingly apparent given the likelihood of long-term survival.
Similar content being viewed by others
References
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109. doi:10.1007/s00401-007-0243-4
Ostrom QT, Gittleman H, Liao P, Rouse C, Chen Y, Dowling J, Wolinsky Y, Kruchko C, Barnholtz-Sloan J (2014) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007–2011. Neuro Oncol 16(Suppl 4):iv1–i63. doi:10.1093/neuonc/nou223
McNeil DE, Cote TR, Clegg L, Rorke LB (2002) Incidence and trends in pediatric malignancies medulloblastoma/primitive neuroectodermal tumor: a SEER update. Surveillance Epidemiology and End Results. Med Pediatr Oncol 39:190–194. doi:10.1002/mpo.10121
Fallah A (2015) Moving beyond evidence-based medicine: Incorporating patient values and preferences. Epilepsy Behav 53:209–210. doi:10.1016/j.yebeh.2015.10.006
Remke M, Ramaswamy V, Taylor MD (2013) Medulloblastoma molecular dissection: the way toward targeted therapy. Curr Opin Oncol 25:674–681. doi:10.1097/CCO.0000000000000008
von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP, Strobe Initiative (2007) The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 370:1453–1457. doi:10.1016/S0140-6736(07)61602-X
Institute NC (2016) Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/registries/index.html
Hankinson TC, Fields EC, Torok MR, Beaty BL, Handler MH, Foreman NK, O’Neill BR, Liu AK (2012) Limited utility despite accuracy of the national SEER dataset for the study of craniopharyngioma. J Neurooncol 110:271–278. doi:10.1007/s11060-012-0966-5
Noorbakhsh A, Tang JA, Marcus LP, McCutcheon B, Gonda DD, Schallhorn CS, Talamini MA, Chang DC, Carter BS, Chen CC (2014) Gross-total resection outcomes in an elderly population with glioblastoma: a SEER-based analysis. J Neurosurg 120:31–39. doi:10.3171/2013.9.JNS13877
Johnston DL, Keene D, Kostova M, Lafay-Cousin L, Fryer C, Scheinemann K, Carret AS, Fleming A, Percy V, Afzal S, Wilson B, Bowes L, Zelcer S, Mpofu C, Silva M, Larouche V, Brossard J, Strother D, Bouffet E (2015) Survival of children with medulloblastoma in Canada diagnosed between 1990 and 2009 inclusive. J Neurooncol 124:247–253. doi:10.1007/s11060-015-1831-0
Tulla M, Berthold F, Graf N, Rutkowski S, von Schweinitz D, Spix C, Kaatsch P (2015) Incidence, trends, and survival of children with embryonal tumors. Pediatrics 136:e623–e632. doi:10.1542/peds.2015-0224
Fairley L, Picton SV, McNally RJ, Bailey S, McCabe MG, Feltbower RG (2016) Incidence and survival of children and young people with central nervous system embryonal tumours in the North of England, 1990–2013. Eur J Cancer 61:36–43. doi:10.1016/j.ejca.2016.03.083
Ning MS, Perkins SM, Dewees T, Shinohara ET (2015) Evidence of high mortality in long term survivors of childhood medulloblastoma. J Neurooncol 122:321–327. doi:10.1007/s11060-014-1712-y
Judkins AR, Mauger J, Ht A, Rorke LB, Biegel JA (2004) Immunohistochemical analysis of hSNF5/INI1 in pediatric CNS neoplasms. Am J Surg Pathol 28:644–650
Rutkowski S, Bode U, Deinlein F, Ottensmeier H, Warmuth-Metz M, Soerensen N, Graf N, Emser A, Pietsch T, Wolff JE, Kortmann RD, Kuehl J (2005) Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med 352:978–986. doi:10.1056/NEJMoa042176
Gajjar A, Chintagumpala M, Ashley D, Kellie S, Kun LE, Merchant TE, Woo S, Wheeler G, Ahern V, Krasin MJ, Fouladi M, Broniscer A, Krance R, Hale GA, Stewart CF, Dauser R, Sanford RA, Fuller C, Lau C, Boyett JM, Wallace D, Gilbertson RJ (2006) Risk-adapted craniospinal radiotherapy followed by high-dose 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. doi:10.1016/S1470-2045(06)70867-1
Rutkowski S (2006) Current treatment approaches to early childhood medulloblastoma. Expert Rev Neurother 6:1211–1221. doi:10.1586/14737175.6.8.1211
von Bueren AO, von Hoff K, Pietsch T, Gerber NU, Warmuth-Metz M, Deinlein F, Zwiener I, Faldum A, Fleischhack G, Benesch M, Krauss J, Kuehl J, Kortmann RD, Rutkowski S (2011) Treatment of young children with localized medulloblastoma by chemotherapy alone: results of the prospective, multicenter trial HIT 2000 confirming the prognostic impact of histology. Neuro Oncol 13:669–679. doi:10.1093/neuonc/nor025
Wong TT, Liu YL, Ho DM, Chang KP, Liang ML, Chen HH, Lee YY, Chang FC, Lin SC, Hsu TR, Chen KW, Kwang WK, Hou WY, Wang CY, Yen SH, Guo WY, Chen YW (2015) Factors affecting survival of medulloblastoma in children: the changing concept of management. Childs Nerv Syst 31:1687–1698. doi:10.1007/s00381-015-2884-2
Samkari A, White JC, Packer RJ (2015) Medulloblastoma: toward biologically based management. Semin Pediatr Neurol 22:6–13. doi:10.1016/j.spen.2014.12.010
Evans AE, Jenkin RD, Sposto R, Ortega JA, Wilson CB, Wara W, Ertel IJ, Kramer S, Chang CH, Leikin SL et al (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. doi:10.3171/jns.1990.72.4.0572
Albright AL, Wisoff JH, Zeltzer PM, Boyett JM, Rorke LB, Stanley P (1996) Effects of medulloblastoma resections on outcome in children: a report from the Children’s Cancer Group. Neurosurgery 38:265–271
Thompson EM, Hielscher T, Bouffet E, Remke M, Luu B, Gururangan S, McLendon RE, Bigner DD, Lipp ES, Perreault S, Cho YJ, Grant G, Kim SK, Lee JY, Rao AA, Giannini C, Li KK, Ng HK, Yao Y, Kumabe T, Tominaga T, Grajkowska WA, Perek-Polnik M, Low DC, Seow WT, Chang KT, Mora J, Pollack IF, Hamilton RL, Leary S, Moore AS, Ingram WJ, Hallahan AR, Jouvet A, Fevre-Montange M, Vasiljevic A, Faure-Conter C, Shofuda T, Kagawa N, Hashimoto N, Jabado N, Weil AG, Gayden T, Wataya T, Shalaby T, Grotzer M, Zitterbart K, Sterba J, Kren L, Hortobagyi T, Klekner A, Laszlo B, Pocza T, Hauser P, Schuller U, Jung S, Jang WY, French PJ, Kros JM, van Veelen ML, Massimi L, Leonard JR, Rubin JB, Vibhakar R, Chambless LB, Cooper MK, Thompson RC, Faria CC, Carvalho A, Nunes S, Pimentel J, Fan X, Muraszko KM, Lopez-Aguilar E, Lyden D, Garzia L, Shih DJ, Kijima N, Schneider C, Adamski J, Northcott PA, Kool M, Jones DT, Chan JA, Nikolic A, Garre ML, Van Meir EG, Osuka S, Olson JJ, Jahangiri A, Castro BA, Gupta N, Weiss WA, Moxon-Emre I, Mabbott DJ, Lassaletta A, Hawkins CE, Tabori U, Drake J, Kulkarni A, Dirks P, Rutka JT, Korshunov A, Pfister SM, Packer RJ, Ramaswamy V, Taylor MD (2016) Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis. Lancet Oncol 17:484–495. doi:10.1016/S1470-2045(15)00581-1
Landberg TG, Lindgren ML, Cavallin-Stahl EK, Svahn-Tapper GO, Sundbarg G, Garwicz S, Lagergren JA, Gunnesson VL, Brun AE, Cronqvist SE (1980) Improvements in the radiotherapy of medulloblastoma, 1946–1975. Cancer 45:670–678
Roberts RO, Lynch CF, Jones MP, Hart MN (1991) Medulloblastoma: a population-based study of 532 cases. J Neuropathol Exp Neurol 50:134–144
Halberg FE, Wara WM, Fippin LF, Edwards MS, Levin VA, Davis RL, Prados MB, Wilson CB (1991) Low-dose craniospinal radiation therapy for medulloblastoma. Int J Radiat Oncol Biol Phys 20:651–654
Packer RJ, Sutton LN, Elterman R, Lange B, Goldwein J, Nicholson HS, Mulne L, Boyett J, D’Angio G, Wechsler-Jentzsch K et al (1994) Outcome for children with medulloblastoma treated with radiation and cisplatin, CCNU, and vincristine chemotherapy. J Neurosurg 81:690–698. doi:10.3171/jns.1994.81.5.0690
Packer RJ (1990) Chemotherapy for medulloblastoma/primitive neuroectodermal tumors of the posterior fossa. Ann Neurol 28:823–828. doi:10.1002/ana.410280615
Packer RJ, Sutton LN, Goldwein JW, Perilongo G, Bunin G, Ryan J, Cohen BH, D’Angio G, Kramer ED, Zimmerman RA et al (1991) Improved survival with the use of adjuvant chemotherapy in the treatment of medulloblastoma. J Neurosurg 74:433–440. doi:10.3171/jns.1991.74.3.0433
Tait DM, Thornton-Jones H, Bloom HJ, 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
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 24:4202–4208. doi:10.1200/JCO.2006.06.4980
Dhall G, Grodman H, Ji L, Sands S, Gardner S, Dunkel IJ, McCowage GB, Diez B, Allen JC, Gopalan A, Cornelius AS, Termuhlen A, Abromowitch M, Sposto R, Finlay JL (2008) Outcome of children less than three years old at diagnosis with non-metastatic medulloblastoma treated with chemotherapy on the “Head Start” I and II protocols. Pediatr Blood Cancer 50:1169–1175. doi:10.1002/pbc.21525
Parsons DW, Li M, Zhang X, Jones S, Leary RJ, Lin JC, Boca SM, Carter H, Samayoa J, Bettegowda C, Gallia GL, Jallo GI, Binder ZA, Nikolsky Y, Hartigan J, Smith DR, Gerhard DS, Fults DW, VandenBerg S, Berger MS, Marie SK, Shinjo SM, Clara C, Phillips PC, Minturn JE, Biegel JA, Judkins AR, Resnick AC, Storm PB, Curran T, He Y, Rasheed BA, Friedman HS, Keir ST, McLendon R, Northcott PA, Taylor MD, Burger PC, Riggins GJ, Karchin R, Parmigiani G, Bigner DD, Yan H, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE (2011) The genetic landscape of the childhood cancer medulloblastoma. Science 331:435–439. doi:10.1126/science.1198056
Northcott PA, Shih DJ, Peacock J, Garzia L, Morrissy AS, Zichner T, Stutz AM, Korshunov A, Reimand J, Schumacher SE, Beroukhim R, Ellison DW, Marshall CR, Lionel AC, Mack S, Dubuc A, Yao Y, Ramaswamy V, Luu B, Rolider A, Cavalli FM, Wang X, Remke M, Wu X, Chiu RY, Chu A, Chuah E, Corbett RD, Hoad GR, Jackman SD, Li Y, Lo A, Mungall KL, Nip KM, Qian JQ, Raymond AG, Thiessen NT, Varhol RJ, Birol I, Moore RA, Mungall AJ, Holt R, Kawauchi D, Roussel MF, Kool M, Jones DT, Witt H, Fernandez LA, Kenney AM, Wechsler-Reya RJ, Dirks P, Aviv T, Grajkowska WA, Perek-Polnik M, Haberler CC, Delattre O, Reynaud SS, Doz FF, Pernet-Fattet SS, Cho BK, Kim SK, Wang KC, Scheurlen W, Eberhart CG, Fevre-Montange M, Jouvet A, Pollack IF, Fan X, Muraszko KM, Gillespie GY, Di Rocco C, Massimi L, Michiels EM, Kloosterhof NK, French PJ, Kros JM, Olson JM, Ellenbogen RG, Zitterbart K, Kren L, Thompson RC, Cooper MK, Lach B, McLendon RE, Bigner DD, Fontebasso A, Albrecht S, Jabado N, Lindsey JC, Bailey S, Gupta N, Weiss WA, Bognar L, Klekner A, Van Meter TE, Kumabe T, Tominaga T, Elbabaa SK, Leonard JR, Rubin JB, Liau LM, Van Meir EG, Fouladi M, Nakamura H, Cinalli G, Garami M, Hauser P, Saad AG, Iolascon A, Jung S, Carlotti CG, Vibhakar R, Ra YS, Robinson S, Zollo M, Faria CC, Chan JA, Levy ML, Sorensen PH, Meyerson M, Pomeroy SL, Cho YJ, Bader GD, Tabori U, Hawkins CE, Bouffet E, Scherer SW, Rutka JT, Malkin D, Clifford SC, Jones SJ, Korbel JO, Pfister SM, Marra MA, Taylor MD (2012) Subgroup-specific structural variation across 1,000 medulloblastoma genomes. Nature 488:49–56. doi:10.1038/nature11327
Clinicaltrials.gov (2016) International Society of Paediatric Oncology (SIOP) PNET 5 Medulloblastoma. https://clinicaltrials.gov/ct2/show/NCT02066220. Accessed 9 Oct 2016
Clinicaltrials.gov (2016) A Clinical and Molecular Risk-Directed Therapy for Newly Diagnosed Medulloblastoma. https://clinicaltrials.gov/ct2/show/NCT01878617. Accessed 9 Oct 2016
Sampson JH, Lad SP, Herndon JE 2nd, Starke RM, Kondziolka D (2014) SEER insights. J Neurosurg 120:297–298. doi:10.3171/2013.6.JNS13993
Mathew RK, O’Kane R, Parslow R, Stiller C, Kenny T, Picton S, Chumas PD (2014) Comparison of survival between the UK and US after surgery for most common pediatric CNS tumors. Neuro Oncol 16:1137–1145. doi:10.1093/neuonc/nou056
Ris MD, Packer R, Goldwein J, Jones-Wallace D, Boyett JM (2001) Intellectual outcome after reduced-dose radiation therapy plus adjuvant chemotherapy for medulloblastoma: a Children’s Cancer Group study. J Clin Oncol 19:3470–3476
Author contributions
Conception and design: AGW, AF. Acquisition of data: HJW, RTA, AF. Analysis and interpretation of data: AGW, AF, C-hT. Drafting the article: AGW, HJW, ACW, GMI, AF. Critically revising the article: AGW, GMI, ACW, LC, SP, TD, AF. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: AGW, AF. Statistical analysis: C-hT, AF. Study supervision: AGW, AF.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Weil, A.G., Wang, A.C., Westwick, H.J. et al. Survival in pediatric medulloblastoma: a population-based observational study to improve prognostication. J Neurooncol 132, 99–107 (2017). https://doi.org/10.1007/s11060-016-2341-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11060-016-2341-4