Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Overall Survival of Primary Intracranial Atypical Teratoid Rhabdoid Tumor Following Multimodal Treatment: A Pooled Analysis of Individual Patient Data

  • 178 Accesses

  • 1 Citations


No standard treatment protocol to guide the management of the primary central nervous system atypical teratoid rhabdoid tumors (ATRTs). To evaluate the efficacy of GTR (gross total resection), RT (radiotherapy), CCMT (conventional chemotherapy), or intensified chemotherapy (ICMT) and verify the optimal treatment strategy. A total of 501 cases (18 cases from our center and 483 cases from published literature) were eligible for analysis. Clinical characteristics were reviewed, and overall survival (OS) of each combined treatment modality was compared. These prior publication data were processed according to PRISMA guidelines. This study included 265 (52.9%) males and 216 (43.1%) females. The median age of the cohort was 2.2 years with 295 (58.9%) cases younger than 3 years. GTR was achieved in 217 (43.3%) patients. Initial adjuvant CCMT, CCMT plus intrathecal chemotherapy (ITCMT), CCMT plus high-dose chemotherapy (HDCMT), and CCMT plus ITCMT and HDCMT were administered in 228 (45.5%), 78 (15.6%), 55 (11.0%), and 24 (4.8%) patients, respectively. Radiotherapy (RT) was prescribed in 266 (53.1%) patients. Fewer patients younger than 3 years old received RT (21.9% vs 33.0%, p < 0.001, chi-square test). The OS of the entire cohort at 1, 3, and 5 years were 56.6, 35.9, and 30.8%, respectively. After adjusting for age and sex, GTR (HR 0.630; p < 0.001), RT (HR = 0.295; p < 0.001), CCMT (HR = 0.382; p < 0.001), and ICMT (HR = 0.209; p < 0.001) were independent prognostic factors. The 3-year OS of surgery alone, surgery plus CCMT, surgery plus RT, surgery plus ICMT, surgery plus CCMT and RT, and surgery plus ICMT and RT were 8.9, 13.4, 23.7, 37.4, 48.3, and 68.5%, respectively. When taking into consideration the extent of tumor resection (n = 462), GTR followed by RT, CCMT, intrathecal chemotherapy, and high-dose chemotherapy provided the best OS (5-year OS 88.2%). In younger children, adjuvant ICMT had a greater 3-year OS than adjuvant RT alone (34.0% vs 0%, p = .001). This study identified independent favorable predictors for OS of ATRTs and distinguished significantly different OS following various treatment modalities. If tolerable, intensive treatment with GTR followed by adjuvant RT and ICMT is recommended. Intensified CCMT could be an alternative to avoid radiological radiotoxicity for younger children CRD42018098841.

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

Fig. 1
Fig. 2
Fig. 3


  1. 1.

    Athale UH, Duckworth J, Odame I, Barr R (2009) Childhood atypical teratoid rhabdoid tumor of the central nervous system: a meta-analysis of observational studies. J Pediatr Hematol Oncol 31:651–663. https://doi.org/10.1097/MPH.0b013e3181b258a9

  2. 2.

    Benesch M, Bartelheim K, Fleischhack G, Gruhn B, Schlegel PG, Witt O, Stachel KD, Hauch H, Urban C, Quehenberger F, Massimino M, Pietsch T, Hasselblatt M, Giangaspero F, Kordes U, Schneppenheim R, Hauser P, Klingebiel T, Fruhwald MC (2014) High-dose chemotherapy (HDCT) with auto-SCT in children with atypical teratoid/rhabdoid tumors (AT/RT): a report from the European Rhabdoid Registry (EU-RHAB). Bone Marrow Transplant 49:370–375. https://doi.org/10.1038/bmt.2013.208

  3. 3.

    Biswas A, Julka PK, Bakhshi S, Suri A, Rath GK (2015) Intracranial atypical teratoid rhabdoid tumor: current management and a single institute experience of 15 patients from North India. Acta Neurochir 157:589–596. https://doi.org/10.1007/s00701-015-2355-2

  4. 4.

    Burger PC, Yu IT, Tihan T, Friedman HS, Strother DR, Kepner JL, Duffner PK, Kun LE, Perlman EJ (1998) Atypical teratoid/rhabdoid tumor of the central nervous system: a highly malignant tumor of infancy and childhood frequently mistaken for medulloblastoma: a pediatric oncology group study. Am J Surg Pathol 22:1083–1092. https://doi.org/10.1097/00000478-199809000-00007

  5. 5.

    Buscariollo DL, Park HS, Roberts KB, Yu JB (2012) Survival outcomes in atypical teratoid rhabdoid tumor for patients undergoing radiotherapy in a surveillance, epidemiology, and end results analysis. Cancer 118:4212–4219. https://doi.org/10.1002/cncr.27373

  6. 6.

    Chen YW, Wong TT, Ho DM, Huang PI, Chang KP, Shiau CY, Yen SH (2006) Impact of radiotherapy for pediatric CNS atypical teratoid/rhabdoid tumor (single institute experience). Int J Radiat Oncol Biol Phys 64:1038–1043. https://doi.org/10.1016/j.ijrobp.2005.10.001

  7. 7.

    Chi SN, Zimmerman MA, Yao X, Cohen KJ, Burger P, Biegel JA, Rorke-Adams LB, Fisher MJ, Janss A, Mazewski C, Goldman S, Manley PE, Bowers DC, Bendel A, Rubin J, Turner CD, Marcus KJ, Goumnerova L, Ullrich NJ, Kieran MW (2009) Intensive multimodality treatment for children with newly diagnosed CNS atypical teratoid rhabdoid tumor. J Clin Oncol 27:385–389. https://doi.org/10.1200/JCO.2008.18.7724

  8. 8.

    De Amorim Bernstein K, Sethi R, Trofimov A, Zeng C, Fullerton B, Yeap BY, Ebb D, Tarbell NJ, Yock TI, MacDonald SM (2013) Early clinical outcomes using proton radiation for children with central nervous system atypical teratoid rhabdoid tumors. Int J Radiat Oncol Biol Phys 86:114–120. https://doi.org/10.1016/j.ijrobp.2012.12.004

  9. 9.

    de Leon-Bojorge B, Rueda-Franco F, Anaya-Jara M (2008) Central nervous system atypical teratoid rhabdoid tumor: experience at the National Institute of Pediatrics, Mexico City. Childs Nerv Syst 24:307–312. https://doi.org/10.1007/s00381-007-0464-9

  10. 10.

    Dufour C, Beaugrand A, Le Deley MC, Bourdeaut F, Andre N, Leblond P, Bertozzi AI, Frappaz D, Rialland X, Fouyssac F, Edan C, Grill J, Quidot M, Varlet P (2012) Clinicopathologic prognostic factors in childhood atypical teratoid and rhabdoid tumor of the central nervous system: a multicenter study. Cancer 118:3812–3821. https://doi.org/10.1002/cncr.26684

  11. 11.

    Fidani P, De Ioris MA, Serra A, De Sio L, Ilari I, Cozza R, Boldrini R, Milano GM, Garre ML, Donfrancesco A (2009) A multimodal strategy based on surgery, radiotherapy, ICE regimen and high dose chemotherapy in atypical teratoid/rhabdoid tumours: a single institution experience. J Neuro-Oncol 92:177–183. https://doi.org/10.1007/s11060-008-9750-y

  12. 12.

    Finkelstein-Shechter T, Gassas A, Mabbott D, Huang A, Bartels U, Tabori U, Janzen L, Hawkins C, Taylor M, Bouffet E (2010) Atypical teratoid or rhabdoid tumors: improved outcome with high-dose chemotherapy. J Pediatr Hematol Oncol 32:e182–e186. https://doi.org/10.1097/MPH.0b013e3181dce1a2

  13. 13.

    Fischer-Valuck BW, Chen I, Srivastava AJ, PhD JMFM, Yuan JR, PhD AAKM, Shinohara ET, Perkins SM (2017) Assessment of the treatment approach and survival outcomes in a modern cohort of patients with atypical teratoid rhabdoid tumors using the National Cancer Database. Cancer 123:682–687

  14. 14.

    Gardner SL, Asgharzadeh S, Green A, Horn B, McCowage G, Finlay J (2008) Intensive induction chemotherapy followed by high dose chemotherapy with autologous hematopoietic progenitor cell rescue in young children newly diagnosed with central nervous system atypical teratoid rhabdoid tumors. Pediatr Blood Cancer 51:235–240. https://doi.org/10.1002/pbc.21578

  15. 15.

    Ginn KF, Gajjar A (2012) Atypical teratoid rhabdoid tumor: current therapy and future directions. Front Oncol 2:114. https://doi.org/10.3389/fonc.2012.00114

  16. 16.

    Haberler C, Laggner U, Slavc I, Czech T, Ambros IM, Ambros PF, Budka H, Hainfellner JA (2006) Immunohistochemical analysis of INI1 protein in malignant pediatric CNS tumors: lack of INI1 in atypical teratoid/rhabdoid tumors and in a fraction of primitive neuroectodermal tumors without rhabdoid phenotype. Am J Surg Pathol 30:1462–1468. https://doi.org/10.1097/01.pas.0000213329.71745.ef

  17. 17.

    Hilden JM, Meerbaum S, Burger P, Finlay J, Janss A, Scheithauer BW, Walter AW, Rorke LB, Biegel JA (2004) Central nervous system atypical teratoid/rhabdoid tumor: results of therapy in children enrolled in a registry. J Clin Oncol 22:2877–2884. https://doi.org/10.1200/JCO.2004.07.073

  18. 18.

    Kuhl J, Muller HL, Berthold F, Kortmann RD, Deinlein F, Maass E, Graf N, Gnekow A, Scheurlen W, Gobel U, Wolff JE, Bamberg M, Kaatsch P, Kleihues P, Rating D, Sorensen N, Wiestler OD (1998) Preradiation chemotherapy of children and young adults with malignant brain tumors: results of the German pilot trial HIT’88/’89. Klin Padiatr 210:227–233. https://doi.org/10.1055/s-2008-1043883

  19. 19.

    Lafay-Cousin L, Hawkins C, Carret AS, Johnston D, Zelcer S, Wilson B, Jabado N, Scheinemann K, Eisenstat D, Fryer C, Fleming A, Mpofu C, Larouche V, Strother D, Bouffet E, Huang A (2012) Central nervous system atypical teratoid rhabdoid tumours: the Canadian Paediatric Brain Tumour Consortium experience. Eur J Cancer 48:353–359. https://doi.org/10.1016/j.ejca.2011.09.005

  20. 20.

    Lee JY, Kim IK, Phi JH, Wang KC, Cho BK, Park SH, Ahn HS, Kim IH, Kim SK (2012) Atypical teratoid/rhabdoid tumors: the need for more active therapeutic measures in younger patients. J Neuro-Oncol 107:413–419. https://doi.org/10.1007/s11060-011-0769-0

  21. 21.

    Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW (2016) The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131:803–820. https://doi.org/10.1007/s00401-016-1545-1

  22. 22.

    McGovern SL, Okcu MF, Munsell MF, Kumbalasseriyil N, Grosshans DR, McAleer MF, Chintagumpala M, Khatua S, Mahajan A (2014) Outcomes and acute toxicities of proton therapy for pediatric atypical teratoid/rhabdoid tumor of the central nervous system. Int J Radiat Oncol Biol Phys 90:1143–1152. https://doi.org/10.1016/j.ijrobp.2014.08.354

  23. 23.

    Merchant TE, Beltran C, Wu S, Sharma S, Boop FA, Jenkins JJ, Helton KJ, Wright KD, Broniscer A (2012) Sequencing of local therapy affects the pattern of treatment failure and survival in children with atypical teratoid rhabdoid tumors of the central nervous system. Int J Radiat Oncol Biol Phys 82:1756–1763

  24. 24.

    Nicolaides T, Tihan T, Horn B, Biegel J, Prados M, Banerjee A (2010) High-dose chemotherapy and autologous stem cell rescue for atypical teratoid/rhabdoid tumor of the central nervous system. J Neuro-Oncol 98:117–123. https://doi.org/10.1007/s11060-009-0071-6

  25. 25.

    Oka H, Scheithauer BW (1999) Clinicopathological characteristics of atypical teratoid/rhabdoid tumor. Neurol Med Chir (Tokyo) 39:510–517; discussion 517-518. https://doi.org/10.2176/nmc.39.510

  26. 26.

    Olson TA, Bayar E, Kosnik E, Hamoudi AB, Klopfenstein KJ, Pieters RS, Ruymann FB (1995) Successful treatment of disseminated central nervous system malignant rhabdoid tumor. J Pediatr Hematol Oncol 17:71–75. https://doi.org/10.1097/00043426-199502000-00013

  27. 27.

    Ostrom QT, Chen Y, MdB P, Ondracek A, Farah P, Gittleman H, Wolinsky Y, Kruchko C, Cohen ML, Brat DJ, Barnholtz-Sloan JS (2014) The descriptive epidemiology of atypical teratoid/rhabdoid tumors in the United States, 2001-2010. Neuro-Oncology 16:1392–1399. https://doi.org/10.1093/neuonc/nou090

  28. 28.

    Park ES, Sung KW, Baek HJ, Park KD, Park HJ, Won SC, Lim DH, Kim HS (2012) Tandem high-dose chemotherapy and autologous stem cell transplantation in young children with atypical teratoid/rhabdoid tumor of the central nervous system. J Korean Med Sci 27:135–140. https://doi.org/10.3346/jkms.2012.27.2.135

  29. 29.

    Ren YM, Wu X, You C, Zhang YK, Li Q, Ju Y (2017) Multimodal treatments combined with gamma knife surgery for primary atypical teratoid/rhabdoid tumor of the central nervous system: a single-institute experience of 18 patients. Childs Nerv Syst 34:627–638. https://doi.org/10.1007/s00381-017-3688-3

  30. 30.

    Rorke LB, Packer RJ, Biegel JA (1996) Central nervous system atypical teratoid/rhabdoid tumors of infancy and childhood: definition of an entity. J Neurosurg 85:56–65. https://doi.org/10.3171/jns.1996.85.1.0056

  31. 31.

    Schrey D, Carceller Lechon F, Malietzis G, Moreno L, Dufour C, Chi S, Lafay-Cousin L, von Hoff K, Athanasiou T, Marshall LV, Zacharoulis S (2016) Multimodal therapy in children and adolescents with newly diagnosed atypical teratoid rhabdoid tumor: individual pooled data analysis and review of the literature. J Neuro-Oncol 126:81–90. https://doi.org/10.1007/s11060-015-1904-0

  32. 32.

    Slavc I, Chocholous M, Leiss U, Haberler C, Peyrl A, Azizi AA, Dieckmann K, Woehrer A, Peters C, Widhalm G, Dorfer C, Czech T (2014) Atypical teratoid rhabdoid tumor: improved long-term survival with an intensive multimodal therapy and delayed radiotherapy. The Medical University of Vienna Experience 1992-2012. Cancer Med 3:91–100. https://doi.org/10.1002/cam4.161

  33. 33.

    Sultan I, Qaddoumi I, Rodriguez-Galindo C, Nassan AA, Ghandour K, Al-Hussaini M (2010) Age, stage, and radiotherapy, but not primary tumor site, affects the outcome of patients with malignant rhabdoid tumors. Pediatr Blood Cancer 54:35–40. https://doi.org/10.1002/pbc.22285

  34. 34.

    Tonning Olsson I, Perrin S, Lundgren J, Hjorth L, Johanson A (2014) Long-term cognitive sequelae after pediatric brain tumor related to medical risk factors, age, and sex. Pediatr Neurol 51:515–521. https://doi.org/10.1016/j.pediatrneurol.2014.06.011

  35. 35.

    Von HK, Hinkes B, Dannenmannstern E, von Bueren AO, Warmuthmetz M, Soerensen N, Emser A, Zwiener I, Schlegel PG, Kuehl J (2011) Frequency, risk-factors and survival of children with atypical teratoid rhabdoid tumors (AT/RT) of the CNS diagnosed between 1988 and 2004, and registered to the German HIT database. Pediatr Blood Cancer 57:978–985

  36. 36.

    Wang RF, Guan WB, Yan Y, Jiang B, Ma J, Jiang MW, Wang LF (2016) Atypical teratoid/rhabdoid tumours: clinicopathological characteristics, prognostic factors and outcomes of 22 children from 2010 to 2015 in China. Pathology 48:555–563. https://doi.org/10.1016/j.pathol.2016.05.010

  37. 37.

    Weber DC, Ares C, Malyapa R, Albertini F, Calaminus G, Kliebsch U, Mikroutsikos L, Morach P, Bolsi A, Lomax T, Schneider R (2015) Tumor control and QoL outcomes of very young children with atypical teratoid/rhabdoid tumor treated with focal only chemo-radiation therapy using pencil beam scanning proton therapy. J Neuro-Oncol 121:389–397. https://doi.org/10.1007/s11060-014-1648-2

  38. 38.

    Woehrer A, Slavc I, Waldhoer T, Heinzl H, Zielonke N, Czech T, Benesch M, Hainfellner JA, Haberler C, Austrian Brain Tumor R (2010) Incidence of atypical teratoid/rhabdoid tumors in children: a population-based study by the Austrian Brain Tumor Registry, 1996-2006. Cancer 116:5725–5732. https://doi.org/10.1002/cncr.25540

  39. 39.

    Zaky W, Dhall G, Ji L, Haley K, Allen J, Atlas M, Bertolone S, Cornelius A, Gardner S, Patel R (2014) Intensive induction chemotherapy followed by myeloablative chemotherapy with autologous hematopoietic progenitor cell rescue for young children newly-diagnosed with central nervous system atypical teratoid/rhabdoid tumors: the head start III experience. Pediatr Blood Cancer 61:95–101. https://doi.org/10.1002/pbc.24648

Download references

Author information

Correspondence to Da Li or Zhen Wu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The experimental protocol and informed consent were approved by the Institutional Review Board.

Informed consent

All subjects were provided with informed consents.



Additional information

Note: No portion of the paper this paper has been presented previously or published elsewhere.

Electronic supplementary material


(DOCX 646 kb)


(DOCX 36 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ma, X., Li, D., Wang, L. et al. Overall Survival of Primary Intracranial Atypical Teratoid Rhabdoid Tumor Following Multimodal Treatment: A Pooled Analysis of Individual Patient Data. Neurosurg Rev 43, 281–292 (2020). https://doi.org/10.1007/s10143-018-1055-9

Download citation


  • Atypical teratoid rhabdoid tumors
  • Central nervous system
  • Chemotherapy
  • Multimodal treatment
  • Radiotherapy