Journal of Neuro-Oncology

, Volume 129, Issue 1, pp 15–22 | Cite as

Risk and survival outcomes of radiation-induced CNS tumors

  • Jessica W. Lee
  • A. Gabriella Wernicke
Topic Review


Patients treated with cranial radiation are at risk of developing secondary CNS tumors. Understanding the incidence, treatment, and long-term outcomes of radiation-induced CNS tumors plays a role in clinical decision-making and patient education. Additionally, as meningiomas and pituitary tumors have been detected at increasing rates across all ages and may potentially be treated with radiation, it is important to know and communicate the risk of secondary tumors in children and adults. After conducting an extensive literature search, we identified publications that report incidence and long-term outcomes of radiation-induced CNS tumors. We reviewed 14 studies in children, which reported that radiation confers a 7- to 10-fold increase in subsequent CNS tumors, with a 20-year cumulative incidence ranging from 1.03 to 28.9 %. The latency period for secondary tumors ranged from 5.5 to 30 years, with gliomas developing in 5–10 years and meningiomas developing around 15 years after radiation. We also reviewed seven studies in adults, where the two strongest studies showed no increased risk while the remaining studies found a higher risk compared to the general population. The latency period for secondary CNS tumors in adults ranged from 5 to 34 years. Treatment and long-term outcomes of radiation-induced CNS tumors have been documented in four case series, which did not conclusively demonstrate that secondary CNS tumors fared worse than primary CNS tumors. Radiation-induced CNS tumors remain a rare occurrence that should not by itself impede radiation treatment. Additional investigation is needed on the risk of radiation-induced tumors in adults and the long-term outcomes of these tumors.


Radiation-induced tumor Secondary tumor Brain tumor CNS tumor 


Compliance with ethical standards

Conflict of interest



  1. 1.
    Ostrom QT, Gittleman H, Liao P, Rouse C, Chen Y, Dowling J, Wolinsky Y, Kruchko C, Barnholtz-Sloan J (2012) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005–2009. Neuro Oncol 14(suppl 5):1–57CrossRefGoogle Scholar
  2. 2.
    CBTRUS (2009) 2009-2010 CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in eighteen states in 2002–2006Google Scholar
  3. 3.
    CBTRUS (2012) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the united states in 2004–2008 (March 23, 2012 Revision)Google Scholar
  4. 4.
    Petersen O (1954) Radiation Cancer. Acta Radiol 42:221–236CrossRefPubMedGoogle Scholar
  5. 5.
    Cahan WG, Woodard HQ, Higinbotham NL, Stewart FW, Coley BL (1998) Sarcoma arising in irradiated bone: report of eleven cases. 1948. Cancer 82:8–34CrossRefPubMedGoogle Scholar
  6. 6.
    Bowers DC, Nathan PC, Constine L, Woodman C, Bhatia S, Keller K, Bashore L (2013) Subsequent neoplasms of the CNS among survivors of childhood cancer: a systematic review. Lancet Oncol 14:e321–e328CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Ron E, Modan B, Boice JD, Alfandary E, Stovall M, Chetrit A, Katz L (1988) Tumors of the brain and nervous system after radiotherapy in childhood. N Engl J Med 319:1033–1039CrossRefPubMedGoogle Scholar
  8. 8.
    Walter AW, Hancock ML, Pui CH, Hudson MM, Ochs JS, Rivera GK, Pratt CB, Boyett JM, Kun LE (1998) Secondary brain tumors in children treated for acute lymphoblastic leukemia at St Jude Children’s Research Hospital. J Clin Oncol 16:3761–3767PubMedGoogle Scholar
  9. 9.
    Löning L, Zimmermann M, Reiter A, Kaatsch P, Henze G, Riehm H, Schrappe M (2000) Secondary neoplasms subsequent to Berlin-Frankfurt-Münster therapy of acute lymphoblastic leukemia in childhood: significantly lower risk without cranial radiotherapy. Blood 95:2770–2775PubMedGoogle Scholar
  10. 10.
    Bhatia S, Sather HN, Pabustan OB, Trigg ME, Gaynon PS, Robison LL (2002) Low incidence of second neoplasms among children diagnosed with acute lymphoblastic leukemia after 1983. Blood 99:4257–4264CrossRefPubMedGoogle Scholar
  11. 11.
    Hijiya N, Hudson MM, Lensing S et al (2007) Cumulative incidence of secondary neoplasms as a first event after childhood acute lymphoblastic leukemia. JAMA 297:1207–1215CrossRefPubMedGoogle Scholar
  12. 12.
    Armstrong GT, Liu Q, Yasui Y et al (2009) Long-term outcomes among adult survivors of childhood central nervous system malignancies in the childhood cancer survivor study. J Natl Cancer Inst 101:946–958CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Tsui K, Gajjar A, Li C et al (2014) Subsequent neoplasms in survivors of childhood central nervous system tumors: risk after modern multimodal therapy. Neuro Oncol 17:448–456PubMedPubMedCentralGoogle Scholar
  14. 14.
    Tsang RW, Laperriere NJ, Simpson WJ, Brierley J, Panzarella T, Smyth HS (1993) Glioma arising after radiation therapy for pituitary adenoma. A report of four patients and estimation of risk. Cancer 72:2227–2233CrossRefPubMedGoogle Scholar
  15. 15.
    Breen P, Flickinger JC, Kondziolka D, Martinez AJ (1998) Radiotherapy for nonfunctional pituitary adenoma: analysis of long-term tumor control. J Neurosurg 89:933–938CrossRefPubMedGoogle Scholar
  16. 16.
    Minniti G, Traish D, Ashley S, Gonsalves A, Brada M (2005) Risk of second brain tumor after conservative surgery and radiotherapy for pituitary adenoma: update after an additional 10 years. J Clin Endocrinol Metab 90:800–804CrossRefPubMedGoogle Scholar
  17. 17.
    Norberg L, Johansson R, Rasmuson T (2008) Pituitary adenomas in northern Sweden: a study on therapy choices and the risk of second primary tumours. Clin Endocrinol (Oxf) 68:780–785CrossRefGoogle Scholar
  18. 18.
    Norberg L, Johansson R, Rasmuson T (2010) Intracranial tumours after external fractionated radiotherapy for pituitary adenomas in northern Sweden. Acta Oncol 49:1276–1282CrossRefPubMedGoogle Scholar
  19. 19.
    van Varsseveld NC, van Bunderen CC, Ubachs DHH, Franken AAM, Koppeschaar HPF, van der Lely AJ, Drent ML (2015) Cerebrovascular events, secondary intracranial tumors, and mortality after radiotherapy for nonfunctioning pituitary adenomas: a subanalysis from the Dutch National Registry of Growth Hormone Treatment in Adults. J Clin Endocrinol Metab 100:1104–1112CrossRefPubMedGoogle Scholar
  20. 20.
    Gold DG, Neglia JP, Dusenbery KE (2003) Second neoplasms after megavoltage radiation for pediatric tumors. Cancer 97:2588–2596CrossRefPubMedGoogle Scholar
  21. 21.
    Neglia JP, Robison LL, Stovall M et al (2006) New primary neoplasms of the central nervous system in survivors of childhood cancer: a report from the childhood cancer survivor study. J Natl Cancer Inst 98:1528–1537CrossRefPubMedGoogle Scholar
  22. 22.
    Sharif S, Ferner R, Birch JM, Gillespie JE, Gattamaneni HR, Baser ME, Evans DGR (2006) Second primary tumors in neurofibromatosis 1 patients treated for optic glioma: substantial risks after radiotherapy. J Clin Oncol 24:2570–2575CrossRefPubMedGoogle Scholar
  23. 23.
    Cardous-Ubbink MC, Heinen RC, Bakker PJM, van den Berg H, Oldenburger F, Caron HN, Voûte PA, van Leeuwen FE (2007) Risk of second malignancies in long-term survivors of childhood cancer. Eur J Cancer 43:351–362CrossRefPubMedGoogle Scholar
  24. 24.
    Goshen Y, Stark B, Kornreich L, Michowiz S, Feinmesser M, Yaniv I (2007) High incidence of meningioma in cranial irradiated survivors of childhood acute lymphoblastic leukemia. Pediatr Blood Cancer 49:294–297CrossRefPubMedGoogle Scholar
  25. 25.
    Taylor AJ, Little MP, Winter DL et al (2010) Population-based risks of CNS tumors in survivors of childhood cancer: the British childhood cancer survivor study. J Clin Oncol 28:5287–5293CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Vinchon M, Leblond P, Caron S, Delestret I, Baroncini M, Coche B (2011) Radiation-induced tumors in children irradiated for brain tumor: a longitudinal study. Childs Nerv Syst 27:445–453CrossRefPubMedGoogle Scholar
  27. 27.
    You SH, Lyu CJ, Kim D-S, Suh C-O (2013) Second primary brain tumors following cranial irradiation for pediatric solid brain tumors. Childs Nerv Syst 29:1865–1870CrossRefPubMedGoogle Scholar
  28. 28.
    De Gonzalez AB, Curtis RE, Kry SF, Gilbert E, Lamart S, Berg CD, Stovall M, Ron E (2011) Proportion of second cancers attributable to radiotherapy treatment in adults: a cohort study in the US SEER cancer registries. Lancet Oncol 12:353–360CrossRefPubMedCentralGoogle Scholar
  29. 29.
    Kutsenko A, Berrington de Gonzalez A, Curtis RE, Rajaraman P (2014) Risk of second benign brain tumors among cancer survivors in the surveillance, epidemiology, and end results program. Cancer Causes Control 25:659–668CrossRefPubMedGoogle Scholar
  30. 30.
    Shapiro S, Mealey J, Sartorius C (1989) Radiation-induced intracranial malignant gliomas. J Neurosurg 71:77–82CrossRefPubMedGoogle Scholar
  31. 31.
    Carret AS, Tabori U, Crooks B, Hukin J, Odame I, Johnston DL, Keene DL, Freeman C, Bouffet E (2006) Outcome of secondary high-grade glioma in children previously treated for a malignant condition: a study of the Canadian Pediatric Brain Tumour Consortium. Radiother Oncol 81:33–38CrossRefPubMedGoogle Scholar
  32. 32.
    Kleinschmidt-Demasters BK, Kang JS, Lillehei KO (2006) The burden of radiation-induced central nervous system tumors: a single institution s experience. J Neuropathol Exp Neurol 65:204–216CrossRefPubMedGoogle Scholar
  33. 33.
    Galloway TJ, Indelicato DJ, Amdur RJ, Swanson EL, Morris CG, Marcus RB (2011) Favorable outcomes of pediatric patients treated with radiotherapy to the central nervous system who develop radiation-induced meningiomas. Int J Radiat Oncol Biol Phys 79:117–120CrossRefPubMedGoogle Scholar
  34. 34.
    Baker KS (2003) New malignancies after blood or marrow stem-cell transplantation in children and adults: incidence and risk factors. J Clin Oncol 21:1352–1358CrossRefPubMedGoogle Scholar
  35. 35.
    Ng AK, Kenney LB, Gilbert ES, Travis LB (2010) Secondary malignancies across the age spectrum. Semin Radiat Oncol 20:67–78CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Stich Radiation OncologyWeill Cornell Medical College/New York-Presbyterian HospitalNew YorkUSA
  3. 3.Department of NeurosurgeryWeill Cornell Medical College/New York-Presbyterian HospitalNew YorkUSA

Personalised recommendations