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Radiotherapy-related outcomes in pediatric patients with atypical teratoid thabdoid tumor of the central nervous system

  • Original Research
  • Published:
Journal of Radiation Oncology

Abstract

Objective

Atypical teratoid/rhabdoid tumor (ATRT) of the central nervous system (CNS) is a rare, highly malignant tumor of early childhood. Current protocols favor multimodality treatment, but practice guidelines differ with regard to radiotherapy. The aim of this study was to evaluate outcomes and prognostic factors in pediatric ATRT receiving multimodality treatment including postoperative radiation.

Methods

Pediatric subjects with CNS ATRT treated at our institution between 2000 and 2014 were retrospectively evaluated. Kaplan-Meier method was used to estimate progression free survival (PFS) and overall survival (OS) over time. Log-rank tests were used to examine associations of demographic and treatment factors with PFS and OS.

Results

Twenty pediatric subjects (median age 23.5 months; range 4–99 months) were eligible for analysis. All underwent surgical resection, adjuvant radiotherapy, and intensive multi-agent chemotherapy. PFS at 1 year was 63.3 % (95 % CI, 38.1–80.6 %) and 2 years was 46.1 % (95 % CI, 22.9–66.5 %). OS at both 1 and 2 years was 73.0 % (95 % CI, 46.7–87.8 %). Infratentorial disease, localized disease at diagnosis, and gross total tumor resection were identified as beneficial prognostic factors in PFS and OS. Progressive disease after radiation was identified as a poor prognostic factor in OS. Radiation modality (proton versus x-ray) did not affect disease-related outcomes.

Conclusion

Modern treatment for ATRT with intensive multimodality therapy including radiotherapy results in a significant portion of subjects with long-term disease control. Initial evidence demonstrates that focal proton therapy in very young subjects is feasible with limited toxicities. Prognosis appears to be improved in localized, completely resected disease.

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References

  1. Lefkowitz IB, Rorke LB, Packer RJ et al (1987) Atypical teratoid tumor of infancy: definition of an entity. Ann Neurol 22:448–449 (abstr. 133)

    Google Scholar 

  2. Packer RJ, Biegel JA, Blaney S et al (2002) Atypical teratoid/rhabdoid tumor of the central nervous system: report on workshop. J Pediatr Hematol Oncol 24(5):337–342

    Article  PubMed  Google Scholar 

  3. 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(1):56–65. doi:10.3171/jns.1996.85.1.0056

    Article  CAS  PubMed  Google Scholar 

  4. Biegel JA, Kalpana G, Knudsen ES et al (2002) The role of INI1 and the SWI/SNF complex in the development of rhabdoid tumors: meeting summary from the workshop on childhood atypical teratoid/rhabdoid tumors. Cancer Res 62(1):323–328

    CAS  PubMed  Google Scholar 

  5. Woehrer A, Slavc I, Waldhoer T et al (2010) Incidence of atypical teratoid/rhabdoid tumors in children: a population-based study by the Austrian Brain Tumor Registry, 1996-2006. Cancer 116(24):5725–5732. doi:10.1002/cncr.25540

    Article  PubMed  Google Scholar 

  6. Chi SN, Zimmerman MA, Yao X et al (2009) Intensive multimodality treatment for children with newly diagnosed CNS atypical teratoid rhabdoid tumor. J Clin Oncol 27(3):385–389. doi:10.1200/JCO.2008.18.7724

    Article  PubMed Central  PubMed  Google Scholar 

  7. Duffner PK, Horowitz ME, Krischer JP et al (1993) Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med 328(24):1725–1731. doi:10.1056/NEJM199306173282401

    Article  CAS  PubMed  Google Scholar 

  8. Hilden JM, Meerbaum S, Burger P et al (2004) Central nervous system atypical teratoid/rhabdoid tumor: results of therapy in children enrolled in a registry. J Clin Oncol 22(14):2877–2884. doi:10.1200/JCO.2004.07.073

    Article  PubMed  Google Scholar 

  9. Tekautz TM, Fuller CE, Blaney S et al (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(7):1491–1499. doi:10.1200/JCO.2005.05.187

    Article  CAS  PubMed  Google Scholar 

  10. Chen Y-W, Wong T-T, Ho DM-T et al (2006) Impact of radiotherapy for pediatric CNS atypical teratoid/rhabdoid tumor (single institute experience). Int J Radiat Oncol Biol Phys 64(4):1038–1043. doi:10.1016/j.ijrobp.2005.10.001

    Article  PubMed  Google Scholar 

  11. 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(9):651–663. doi:10.1097/MPH.0b013e3181b258a9

    Article  PubMed  Google Scholar 

  12. 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(17):4212–4219. doi:10.1002/cncr.27373

    Article  PubMed  Google Scholar 

  13. Pai Panandiker AS, Merchant TE, Beltran C et al (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(5):1756–1763. doi:10.1016/j.ijrobp.2011.02.059

    Article  PubMed  Google Scholar 

  14. Chang CH, Housepian EM, Herbert C (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 

  15. Children’s Oncology Group (2011) ACNS0333 Treatment of Atypical Teratoid/Rhabdoid Tumors (ATRT) of the Central Nervous System with Surgery, Intensive Chemotherapy, and 3-D Conformal Radiation: A Phase II Group-Wide Study. https://members.childrensoncologygroup.org/Prot/ACNS0333/ACNS0333DOC.pdf

  16. Blaney SM, Kocak M, Gajjar A et al (2012) Pilot study of systemic and intrathecal mafosfamide followed by conformal radiation for infants with intracranial central nervous system tumors: a pediatric brain tumor consortium study (PBTC-001). J Neurooncol 109(3):565–571. doi:10.1007/s11060-012-0929-x

    Article  PubMed Central  PubMed  Google Scholar 

  17. Crist W, Gehan EA, Ragab AH et al (1995) The Third Intergroup Rhabdomyosarcoma Study. J Clin Oncol 3(3):610–630

    Article  Google Scholar 

  18. Burger PC, Yu IT, Tihan T et al (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(9):1083–1092

    Article  CAS  PubMed  Google Scholar 

  19. Reinhardt D, Behnke-Mursch J, Weiss E et al (2000) Rhabdoid tumors of the central nervous system. Childs Nerv Syst 16(4):228–234

    Article  CAS  PubMed  Google Scholar 

  20. McGovern SL, Okcu MF, Munsell MF et al (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(5):1143–1152. doi:10.1016/j.ijrobp.2014.08.354

    Article  PubMed Central  PubMed  Google Scholar 

  21. Weber DC, Ares C, Malyapa R et al (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 Neurooncol 121(2):389–397. doi:10.1007/s11060-014-1648-2

    Article  PubMed  Google Scholar 

  22. De Amorim BK, Sethi R, Trofimov A et al (2013) Early clinical outcomes using proton radiation for children with central nervous system atypical teratoid rhabdoid tumors. Int J Radiat Oncol Biol Phys 86(1):114–120. doi:10.1016/j.ijrobp.2012.12.004

    Article  Google Scholar 

  23. Merchant TE, Hua C-H, Shukla H et al (2008) Proton versus photon radiotherapy for common pediatric brain tumors: comparison of models of dose characteristics and their relationship to cognitive function. Pediatr Blood Cancer 51(1):110–117. doi:10.1002/pbc.21530

    Article  PubMed  Google Scholar 

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Acknowledgments

This project was made possible by funding from Alex’s Lemonade Stand Foundation.

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Authors and Affiliations

  1. Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd, 2nd Floor West, Philadelphia, PA, 19104, USA

    Melissa Frick, Jane E. Minturn, Yimei Li & Christine Hill-Kayser

  2. Division of Oncology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Jane E. Minturn, Yimei Li & Christine Hill-Kayser

  3. Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA

    Yimei Li

  4. Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA

    Christine Hill-Kayser

Authors
  1. Melissa Frick
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  2. Jane E. Minturn
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  3. Yimei Li
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  4. Christine Hill-Kayser
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Corresponding author

Correspondence to Christine Hill-Kayser.

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Funding

The work was supported by a grant from the Alex’s Lemonade Stand Foundation, as well as the Department of Radiation Oncology at the University of Pennsylvania, Philadelphia, PA, and the Division of Oncology, Department of Pediatrics, at the Children’s Hospital of Philadelphia, Philadelphia, PA.

Conflict of Interest

Melissa Frick declares that she has no conflict of interest. Yimei Li declares that she has no conflict of interest. Jane Minturn declares that she has no conflict of interest. Christine Hill-Kayser declares that she has no conflict of interest.

Ethical approval

All procedures performed were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

For this type of study, formal consent is not required, and a waiver of informed consent was obtained from the Institutional Review Board.

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Frick, M., Minturn, J.E., Li, Y. et al. Radiotherapy-related outcomes in pediatric patients with atypical teratoid thabdoid tumor of the central nervous system. J Radiat Oncol 6, 153–160 (2017). https://doi.org/10.1007/s13566-016-0271-6

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  • DOI: https://doi.org/10.1007/s13566-016-0271-6

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