Role of early and aggressive post-operative radiation therapy in improving outcome for pediatric central nervous system atypical teratoid/rhabdoid tumor
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The purpose of the study is to evaluate possible prognostic factors and optimal management for pediatric atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system (CNS).
Twenty-eight pediatric patients with CNS AT/RT who were treated with radiation therapy (RT) as part of multimodality treatment regimens at a single institution (1996–2015) were reviewed. Survival outcomes were analyzed in relation to possible prognostic factors.
The 28 patients analyzed were followed up for a median 48-month period. Median progression-free survival (PFS) was 11 months, and overall survival (OS) was 57 months. Patients < 3 years old had RT delayed for a longer period after surgery (p = 0.04), and the mean RT dose to tumor bed was lower (p < 0.01) than in patients ≥ 3 years old. In multivariate analysis, a higher primary tumor bed RT dose was identified as a favorable prognostic factor for both PFS (hazard ratio [HR] = 0.85 per gray, p < 0.01) and OS (HR = 0.92 per gray, p = 0.02). In addition, an interval between surgery and RT initiation > 2 months, with disease progression observed before RT, as compared with an interval ≤ 2 months without disease progression prior to RT, was associated with worse PFS (HR = 8.50, p < 0.01) and OS (HR = 5.27, p < 0.01).
Early and aggressive RT after surgery is critical for successful disease control in AT/RT patients. Conversely, a delay in RT until disease progression is observed that leads to unfavorable outcomes.
KeywordsHigh-dose chemotherapy Radiation dose Radiation therapy Time interval
We would like to thank Taipei Veterans General Hospital pediatric CNS tumor group for assistance in this study.
No funding was received for this study.
Compliance with ethical standards
The study was conducted in accordance with the Declaration of Helsinki.
The data of this study was extracted from database of pediatric brain tumors in Taipei Veterans General Hospital, and the study protocol was approved by the Institutional Review Board of the Taipei Veterans General Hospital. The IRB number is 97-07-05A.
Conflict of interest
The authors declare that they have no conflict of interest.
Informed consent to this study was obtained from the parents of all participants.
- 2.Bartelheim K, Nemes K, Seeringer A, Kerl K, Buechner J, Boos J, Graf N, Durken M, Gerss J, Hasselblatt M, Kortmann RD, Teichert von Luettichau I, Nagel I, Nygaard R, Oyen F, Quiroga E, Schlegel PG, Schmid I, Schneppenheim R, Siebert R, Solano-Paez P, Timmermann B, Warmuth-Metz M, Fruhwald MC (2016) Improved 6-year overall survival in AT/RTS—results of the registry study Rhabdoid 2007. Cancer Med 5:1765–1775. https://doi.org/10.1002/cam4.741 CrossRefGoogle Scholar
- 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 22:1083–1092CrossRefGoogle Scholar
- 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 CrossRefGoogle Scholar
- 8.Christopherson KM, Rotondo RL, Bradley JA, Pincus DW, Wynn TT, Fort JA, Morris CG, Mendenhall NP, Marcus RB Jr, Indelicato DJ (2014) Late toxicity following craniospinal radiation for early-stage medulloblastoma. Acta Oncol (Stockh) 53:471–480. https://doi.org/10.3109/0284186x.2013.862596 CrossRefGoogle Scholar
- 10.Fossey M, Li H, Afzal S, Carret AS, Eisenstat DD, Fleming A, Hukin J, Hawkins C, Jabado N, Johnston D, Brown T, Larouche V, Scheinemann K, Strother D, Wilson B, Zelcer S, Huang A, Bouffet E, Lafay-Cousin L (2017) Atypical teratoid rhabdoid tumor in the first year of life: the Canadian ATRT registry experience and review of the literature. J Neuro-Oncol 132:155–162. https://doi.org/10.1007/s11060-016-2353-0 CrossRefGoogle Scholar
- 11.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 CrossRefGoogle Scholar
- 12.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 CrossRefGoogle Scholar
- 14.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 CrossRefGoogle Scholar
- 15.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 CrossRefGoogle Scholar
- 16.Pai Panandiker AS, Merchant TE, Beltran C, Wu S, Sharma S, Boop FA, Jenkins JJ, Helton KJ, Wright KD, Broniscer A, Kun LE, Gajjar 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. https://doi.org/10.1016/j.ijrobp.2011.02.059 CrossRefGoogle Scholar
- 17.Perez-Martinez A, Lassaletta A, Gonzalez-Vicent M, Sevilla J, Diaz MA, Madero L (2005) High-dose chemotherapy with autologous stem cell rescue for children with high risk and recurrent medulloblastoma and supratentorial primitive neuroectodermal tumors. J Neuro-Oncol 71:33–38. https://doi.org/10.1007/s11060-004-4527-4 CrossRefGoogle Scholar
- 18.Reddickaij WE, Russell JM, Glass JO, Xiong X, Mulhern RK, Langston JW, Merchant TE, Kun LE, Gajjar A (2000) Subtle white matter volume differences in children treated for medulloblastoma with conventional or reduced dose craniospinal irradiation. Magn Reson Imaging 18:787–793. https://doi.org/10.1016/S0730-725X(00)00182-X CrossRefGoogle Scholar
- 19.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 CrossRefGoogle Scholar
- 20.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 CrossRefGoogle Scholar
- 23.Tekautz TM, Fuller CE, Blaney S, Fouladi M, Broniscer A, Merchant TE, Krasin M, Dalton J, Hale G, Kun LE, Wallace D, Gilbertson RJ, Gajjar A (2005) Atypical teratoid/rhabdoid tumors (ATRT): improved survival in children 3 years of age and older with radiation therapy and high-dose alkylator-based chemotherapy. J Clin Oncol 23:1491–1499. https://doi.org/10.1200/jco.2005.05.187 CrossRefGoogle Scholar
- 25.von Hoff K, Hinkes B, Dannenmann-Stern E, von Bueren AO, Warmuth-Metz M, Soerensen N, Emser A, Zwiener I, Schlegel PG, Kuehl J, Fruhwald MC, Kortmann RD, Pietsch T, Rutkowski S (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. https://doi.org/10.1002/pbc.23236 CrossRefGoogle Scholar
- 26.Zaky W, Dhall G, Ji L, Haley K, Allen J, Atlas M, Bertolone S, Cornelius A, Gardner S, Patel R, Pradhan K, Shen V, Thompson S, Torkildson J, Sposto R, Finlay JL (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 CrossRefGoogle Scholar