Second Neoplasms After Successful Treatment for Pediatric Central Nervous System Tumors

  • Mark J. Amsbaugh
  • Shiao Y. WooEmail author


As survival rates following treatment for pediatric central nervous system tumors continue to improve, it is now clear that survivors of childhood cancer are at risk for a wide range of health, neurocognitive, social, and psychiatric issues. Perhaps the most significant and damaging complication facing survivors of childhood cancers is diagnosis of a second neoplasm. The development of a second neoplasm is a multifactorial process that is influenced by cancer histology, genetics, treatment technique and intensity, and environmental factors. These are a group of histologically diverse cancers that can occur at any location in the body with varied latency times. Many secondary malignant neoplasms have an extremely poor prognosis. While radiotherapy dose and field design been associated with second neoplasm development, new treatment strategies and technologies such as proton therapy have the potential to significantly reduce this devastating complication of treatment. As our ability to understand and quantify the factors that influence risk improve, models accurately predicting individual risk may be incorporated into treatment selection.


  1. Albrecht S, Goodman JC, Rajagopolan S, Levy M, Cech DA, Cooley LD (1994) Malignant meningioma in Gorlin’s syndrome: cytogenetic and p53 gene analysis. Case report. J Neurosurg 81(3):466–471. doi: 10.3171/jns.1994.81.3.0466 PubMedCrossRefGoogle Scholar
  2. Amirjamshidi A, Abbassioun K (2000) Radiation-induced tumors of the central nervous system occurring in childhood and adolescence. Four unusual lesions in three patients and a review of the literature. Childs Nerv Syst 16(7):390–397PubMedCrossRefGoogle Scholar
  3. Amsbaugh MJ, Grosshans DR, McAleer MF, Zhu R, Wages C, Crawford CN, Palmer M, De Gracia B, Woo S, Mahajan A (2012) Proton therapy for spinal ependymomas: planning, acute toxicities, and preliminary outcomes. Int J Radiat Oncol Biol Phys 83(5):1419–1424. doi: 10.1016/j.ijrobp.2011.10.034 PubMedCrossRefGoogle Scholar
  4. Armstrong GT (2010) Long-term survivors of childhood central nervous system malignancies: the experience of the Childhood Cancer Survivor Study. Eur J Paediatr Neurol 14(4):298–303. doi: 10.1016/j.ejpn.2009.12.006 PubMedPubMedCentralCrossRefGoogle Scholar
  5. Armstrong GT, Liu Q, Yasui Y, Huang S, Ness KK, Leisenring W, Hudson MM, Donaldson SS, King AA, Stovall M, Krull KR, Robison LL, Packer RJ (2009) Long-term outcomes among adult survivors of childhood central nervous system malignancies in the Childhood Cancer Survivor Study. J Natl Cancer Inst 101(13):946–958. doi: 10.1093/jnci/djp148 PubMedPubMedCentralCrossRefGoogle Scholar
  6. 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(12):4257–4264PubMedCrossRefGoogle Scholar
  7. 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(8):e321–e328. doi: 10.1016/s1470-2045(13)70107-4 PubMedPubMedCentralCrossRefGoogle Scholar
  8. Broniscer A, Ke W, Fuller CE, Wu J, Gajjar A, Kun LE (2004) Second neoplasms in pediatric patients with primary central nervous system tumors: the St. Jude Children’s Research Hospital experience. Cancer 100(10):2246–2252. doi: 10.1002/cncr.20253 PubMedCrossRefGoogle Scholar
  9. Burn S, Gunny R, Phipps K, Gaze M, Hayward R (2007) Incidence of cavernoma development in children after radiotherapy for brain tumors. J Neurosurg 106(5 Suppl):379–383. doi: 10.3171/ped.2007.106.5.379 PubMedGoogle Scholar
  10. Cardous-Ubbink MC, Heinen RC, Bakker PJ, van den Berg H, Oldenburger F, Caron HN, Voute PA, van Leeuwen FE (2007) Risk of second malignancies in long-term survivors of childhood cancer. Eur J Cancer (Oxford, England: 1990) 43(2):351–362. doi: 10.1016/j.ejca.2006.10.004 CrossRefGoogle Scholar
  11. 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(1):33–38. doi: 10.1016/j.radonc.2006.08.005 PubMedCrossRefGoogle Scholar
  12. Casey DL, Friedman DN, Moskowitz CS, Hilden PD, Sklar CA, Wexler LH, Wolden SL (2014) Second cancer risk in childhood cancer survivors treated with intensity-modulated radiation therapy (IMRT). Pediatr Blood Cancer. doi: 10.1002/pbc.25285 PubMedCentralGoogle Scholar
  13. Chojnacka M, Pedziwiatr K, Skowronska-Gardas A, Perek-Polnik M, Perek D, Olasek P (2014) Second brain tumors following central nervous system radiotherapy in childhood. Br J Radiol 87(1041):20140211. doi: 10.1259/bjr.20140211 PubMedPubMedCentralCrossRefGoogle Scholar
  14. Chung CS, Yock TI, Nelson K, Xu Y, Keating NL, Tarbell NJ (2013) Incidence of second malignancies among patients treated with proton versus photon radiation. Int J Radiat Oncol Biol Phys 87(1):46–52. doi: 10.1016/j.ijrobp.2013.04.030 PubMedCrossRefGoogle Scholar
  15. Darby SC, Doll R, Gill SK, Smith PG (1987) Long term mortality after a single treatment course with X-rays in patients treated for ankylosing spondylitis. Br J Cancer 55(2):179–190PubMedPubMedCentralCrossRefGoogle Scholar
  16. de Vathaire F, Hawkins M, Campbell S, Oberlin O, Raquin MA, Schlienger JY, Shamsaldin A, Diallo I, Bell J, Grimaud E, Hardiman C, Lagrange JL, Daly-Schveitzer N, Panis X, Zucker JM, Sancho-Garnier H, Eschwege F, Chavaudra J, Lemerle J (1999) Second malignant neoplasms after a first cancer in childhood: temporal pattern of risk according to type of treatment. Br J Cancer 79(11–12):1884–1893. doi: 10.1038/sj.bjc.6690300 PubMedPubMedCentralCrossRefGoogle Scholar
  17. Devarahally SR, Severson RK, Chuba P, Thomas R, Bhambhani K, Hamre MR (2003) Second malignant neoplasms after primary central nervous system malignancies of childhood and adolescence. Pediatr Hematol Oncol 20(8):617–625PubMedCrossRefGoogle Scholar
  18. Diallo I, Haddy N, Adjadj E, Samand A, Quiniou E, Chavaudra J, Alziar I, Perret N, Guerin S, Lefkopoulos D, de Vathaire F (2009) Frequency distribution of second solid cancer locations in relation to the irradiated volume among 115 patients treated for childhood cancer. Int J Radiat Oncol Biol Phys 74(3):876–883. doi: 10.1016/j.ijrobp.2009.01.040 PubMedCrossRefGoogle Scholar
  19. Duffner PK, Krischer JP, Horowitz ME, Cohen ME, Burger PC, Friedman HS, Kun LE (1998) Second malignancies in young children with primary brain tumors following treatment with prolonged postoperative chemotherapy and delayed irradiation: a Pediatric Oncology Group study. Ann Neurol 44(3):313–316. doi: 10.1002/ana.410440305 PubMedCrossRefGoogle Scholar
  20. Duhem R, Vinchon M, Leblond P, Soto-Ares G, Dhellemmes P (2005) Cavernous malformations after cerebral irradiation during childhood: report of nine cases. Childs Nerv Syst 21(10):922–925. doi: 10.1007/s00381-004-1120-2 PubMedCrossRefGoogle Scholar
  21. Elsamadicy AA, Babu R, Kirkpatrick JP, Adamson DC (2015) Radiation-induced malignant gliomas: a current review. World Neurosurg 83(4):530–542. doi: 10.1016/j.wneu.2014.12.009 PubMedCrossRefGoogle Scholar
  22. Flint-Richter P, Sadetzki S (2007) Genetic predisposition for the development of radiation-associated meningioma: an epidemiological study. Lancet Oncol 8(5):403–410. doi: 10.1016/s1470-2045(07)70107-9 PubMedCrossRefGoogle Scholar
  23. Friedman JM, Birch P (1997) An association between optic glioma and other tumours of the central nervous system in neurofibromatosis type 1. Neuropediatrics 28(2):131–132. doi: 10.1055/s-2007-973687 PubMedCrossRefGoogle Scholar
  24. Friedman DL, Kadan-Lottick NS, Whitton J, Mertens AC, Yasui Y, Liu Y, Meadows AT, Robison LL, Strong LC (2005) Increased risk of cancer among siblings of long-term childhood cancer survivors: a report from the childhood cancer survivor study. Cancer Epidemiol Biomark Prev 14(8):1922–1927. doi: 10.1158/1055-9965.EPI-05-0066 CrossRefGoogle Scholar
  25. Friedman DL, Whitton J, Leisenring W, Mertens AC, Hammond S, Stovall M, Donaldson SS, Meadows AT, Robison LL, Neglia JP (2010) Subsequent neoplasms in 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study. J Natl Cancer Inst 102(14):1083–1095. doi: 10.1093/jnci/djq238 PubMedPubMedCentralCrossRefGoogle Scholar
  26. Garwicz S, Anderson H, Olsen JH, Dollner H, Hertz H, Jonmundsson G, Langmark F, Lanning M, Moller T, Sankila R, Tulinius H (2000) Second malignant neoplasms after cancer in childhood and adolescence: a population-based case-control study in the 5 Nordic countries. The Nordic Society for Pediatric Hematology and Oncology. The Association of the Nordic Cancer Registries. Int J Cancer 88(4):672–678PubMedCrossRefGoogle Scholar
  27. Ghim TT, Seo JJ, O’Brien M, Meacham L, Crocker I, Krawiecki N (1993) Childhood intracranial meningiomas after high-dose irradiation. Cancer 71(12):4091–4095PubMedCrossRefGoogle Scholar
  28. Gold DG, Neglia JP, Dusenbery KE (2003) Second neoplasms after megavoltage radiation for pediatric tumors. Cancer 97(10):2588–2596. doi: 10.1002/cncr.11356 PubMedCrossRefGoogle Scholar
  29. 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(3):294–297. doi: 10.1002/pbc.21153 PubMedCrossRefGoogle Scholar
  30. Guerin S, Guibout C, Shamsaldin A, Dondon MG, Diallo I, Hawkins M, Oberlin O, Hartmann O, Michon J, Le Deley MC, de Vathaire F (2007) Concomitant chemo-radiotherapy and local dose of radiation as risk factors for second malignant neoplasms after solid cancer in childhood: a case-control study. Int J Cancer 120(1):96–102. doi: 10.1002/ijc.22197 PubMedCrossRefGoogle Scholar
  31. Hall EJ (2006) Intensity-modulated radiation therapy, protons, and the risk of second cancers. Int J Radiat Oncol Biol Phys 65(1):1–7. doi: 10.1016/j.ijrobp.2006.01.027 PubMedCrossRefGoogle Scholar
  32. Hammal DM, Bell CL, Craft AW, Parker L (2005) Second primary tumors in children and young adults in the North of England (1968–99). Pediatr Blood Cancer 45(2):155–161. doi: 10.1002/pbc.20448 PubMedCrossRefGoogle Scholar
  33. Heckl S, Aschoff A, Kunze S (2002) Radiation-induced cavernous hemangiomas of the brain: a late effect predominantly in children. Cancer 94(12):3285–3291. doi: 10.1002/cncr.10596 PubMedCrossRefGoogle Scholar
  34. Hijiya N, Hudson MM, Lensing S, Zacher M, Onciu M, Behm FG, Razzouk BI, Ribeiro RC, Rubnitz JE, Sandlund JT, Rivera GK, Evans WE, Relling MV, Pui CH (2007) Cumulative incidence of secondary neoplasms as a first event after childhood acute lymphoblastic leukemia. JAMA 297(11):1207–1215. doi: 10.1001/jama.297.11.1207 PubMedCrossRefGoogle Scholar
  35. Inskip PD, Curtis RE (2007) New malignancies following childhood cancer in the United States, 1973–2002. Int J Cancer 121(10):2233–2240. doi: 10.1002/ijc.22827 PubMedCrossRefGoogle Scholar
  36. Jazbec J, Ecimovic P, Jereb B (2004) Second neoplasms after treatment of childhood cancer in Slovenia. Pediatr Blood Cancer 42(7):574–581. doi: 10.1002/pbc.20025 PubMedCrossRefGoogle Scholar
  37. Jenkinson H, Hawkins M (1999) Secondary brain tumours in children with ALL. Lancet 354(9184):1126. doi: 10.1016/s0140-6736(05)76922-1 PubMedCrossRefGoogle Scholar
  38. Jenkinson HC, Hawkins MM, Stiller CA, Winter DL, Marsden HB, Stevens MC (2004) Long-term population-based risks of second malignant neoplasms after childhood cancer in Britain. Br J Cancer 91(11):1905–1910. doi: 10.1038/sj.bjc.6602226 PubMedPubMedCentralCrossRefGoogle Scholar
  39. Kantar M, Cetingul N, Kansoy S, Anacak Y, Demirtas E, Ersahin Y, Mutluer S (2004) Radiotherapy-induced secondary cranial neoplasms in children. Childs Nerv Syst 20(1):46–49. doi: 10.1007/s00381-003-0798-x PubMedCrossRefGoogle Scholar
  40. Kingston JE, Hawkins MM, Draper GJ, Marsden HB, Kinnier Wilson LM (1987) Patterns of multiple primary tumours in patients treated for cancer during childhood. Br J Cancer 56(3):331–338PubMedPubMedCentralCrossRefGoogle Scholar
  41. Klein G, Michaelis J, Spix C, Wibbing R, Eggers G, Ritter J, Kaatsch P (2003) Second malignant neoplasms after treatment of childhood cancer. Eur J Cancer (Oxford, England: 1990) 39(6):808–817CrossRefGoogle Scholar
  42. Klein EE, Maserang B, Wood R, Mansur D (2006) Peripheral doses from pediatric IMRT. Med Phys 33(7):2525–2531PubMedCrossRefGoogle Scholar
  43. Kony SJ, de Vathaire F, Chompret A, Shamsaldim A, Grimaud E, Raquin MA, Oberlin O, Brugieres L, Feunteun J, Eschwege F, Chavaudra J, Lemerle J, Bonaiti-Pellie C (1997) Radiation and genetic factors in the risk of second malignant neoplasms after a first cancer in childhood. Lancet 350(9071):91–95. doi: 10.1016/s0140-6736(97)01116-1 PubMedCrossRefGoogle Scholar
  44. Korones DN, Padowski J, Factor BA, Constine LS (2003) Do children with optic pathway tumors have an increased frequency of other central nervous system tumors? Neuro-Oncology 5(2):116–120. doi: 10.1215/s1522-8517-02-00030-3 PubMedPubMedCentralCrossRefGoogle Scholar
  45. Kry SF, Salehpour M, Followill DS, Stovall M, Kuban DA, White RA, Rosen II (2005) The calculated risk of fatal secondary malignancies from intensity-modulated radiation therapy. Int J Radiat Oncol Biol Phys 62(4):1195–1203. doi: 10.1016/j.ijrobp.2005.03.053 PubMedCrossRefGoogle Scholar
  46. Kuenzle C, Weissert M, Roulet E, Bode H, Schefer S, Huisman T, Landau K, Boltshauser E (1994) Follow-up of optic pathway gliomas in children with neurofibromatosis type 1. Neuropediatrics 25(6):295–300. doi: 10.1055/s-2008-1073043 PubMedCrossRefGoogle Scholar
  47. Lew SM, Morgan JN, Psaty E, Lefton DR, Allen JC, Abbott R (2006) Cumulative incidence of radiation-induced cavernomas in long-term survivors of medulloblastoma. J Neurosurg 104(2 Suppl):103–107. doi: 10.3171/ped.2006.104.2.103 PubMedGoogle Scholar
  48. Little MP, de Vathaire F, Shamsaldin A, Oberlin O, Campbell S, Grimaud E, Chavaudra J, Haylock RG, Muirhead CR (1998) Risks of brain tumour following treatment for cancer in childhood: modification by genetic factors, radiotherapy and chemotherapy. Int J Cancer 78(3):269–275. doi: 10.1002/(sici)1097-0215(19981029)78:3<269::aid-ijc1>;2-t PubMedCrossRefGoogle Scholar
  49. Loning L, Zimmermann M, Reiter A, Kaatsch P, Henze G, Riehm H, Schrappe M (2000) Secondary neoplasms subsequent to Berlin-Frankfurt-Munster therapy of acute lymphoblastic leukemia in childhood: significantly lower risk without cranial radiotherapy. Blood 95(9):2770–2775PubMedGoogle Scholar
  50. Lonser RR, Walbridge S, Vortmeyer AO, Pack SD, Nguyen TT, Gogate N, Olson JJ, Akbasak A, Bobo RH, Goffman T, Zhuang Z, Oldfield EH (2002) Induction of glioblastoma multiforme in nonhuman primates after therapeutic doses of fractionated whole-brain radiation therapy. J Neurosurg 97(6):1378–1389. doi: 10.3171/jns.2002.97.6.1378 PubMedCrossRefGoogle Scholar
  51. MacArthur AC, Spinelli JJ, Rogers PC, Goddard KJ, Phillips N, McBride ML (2007) Risk of a second malignant neoplasm among 5-year survivors of cancer in childhood and adolescence in British Columbia, Canada. Pediatr Blood Cancer 48(4):453–459. doi: 10.1002/pbc.20921 PubMedCrossRefGoogle Scholar
  52. Makidono A, Kobayashi N, Saida Y, Manabe A, Kawamori J, Suzuki K (2009) Metachronous gliomas following cranial irradiation for mixed germ cell tumors. Childs Nerv Syst 25(6):713–718. doi: 10.1007/s00381-009-0829-3 PubMedCrossRefGoogle Scholar
  53. Mann I, Yates PC, Ainslie JP (1953) Unusual case of double primary orbital tumour. Br J Ophthalmol 37(12):758–762PubMedPubMedCentralCrossRefGoogle Scholar
  54. Mathews JD, Forsythe AV, Brady Z, Butler MW, Goergen SK, Byrnes GB, Giles GG, Wallace AB, Anderson PR, Guiver TA, McGale P, Cain TM, Dowty JG, Bickerstaffe AC, Darby SC (2013) Cancer risk in 680,000 people exposed to computed tomography scans in childhood or adolescence: data linkage study of 11 million Australians. BMJ 346:f2360. doi: 10.1136/bmj.f2360 PubMedPubMedCentralCrossRefGoogle Scholar
  55. Maule M, Scelo G, Pastore G, Brennan P, Hemminki K, Pukkala E, Weiderpass E, Olsen JH, Tracey E, McBride ML, Brewster DH, Pompe-Kirn V, Tonita JM, Kliewer EV, Chia KS, Jonasson JG, Martos C, Magnani C, Boffetta P (2008) Risk of second malignant neoplasms after childhood central nervous system malignant tumours: an international study. Eur J Cancer (Oxford, England: 1990) 44(6):830–839. doi: 10.1016/j.ejca.2008.02.012 CrossRefGoogle Scholar
  56. Meadows AT, Baum E, Fossati-Bellani F, Green D, Jenkin RD, Marsden B, Nesbit M, Newton W, Oberlin O, Sallan SG et al (1985) Second malignant neoplasms in children: an update from the Late Effects Study Group. J Clin Oncol 3(4):532–538PubMedCrossRefGoogle Scholar
  57. Meadows AT, Friedman DL, Neglia JP, Mertens AC, Donaldson SS, Stovall M, Hammond S, Yasui Y, Inskip PD (2009) Second neoplasms in survivors of childhood cancer: findings from the Childhood Cancer Survivor Study cohort. J Clin Oncol 27(14):2356–2362. doi: 10.1200/jco.2008.21.1920 PubMedPubMedCentralCrossRefGoogle Scholar
  58. Miralbell R, Lomax A, Cella L, Schneider U (2002) Potential reduction of the incidence of radiation-induced second cancers by using proton beams in the treatment of pediatric tumors. Int J Radiat Oncol Biol Phys 54(3):824–829PubMedCrossRefGoogle Scholar
  59. Moteabbed M, Yock TI, Paganetti H (2014) The risk of radiation-induced second cancers in the high to medium dose region: a comparison between passive and scanned proton therapy, IMRT and VMAT for pediatric patients with brain tumors. Phys Med Biol 59(12):2883–2899. doi: 10.1088/0031-9155/59/12/2883 PubMedCrossRefGoogle Scholar
  60. Mu X, Bjork-Eriksson T, Nill S, Oelfke U, Johansson KA, Gagliardi G, Johansson L, Karlsson M, Zackrisson DB (2005) Does electron and proton therapy reduce the risk of radiation induced cancer after spinal irradiation for childhood medulloblastoma? A comparative treatment planning study. Acta Oncol (Stockholm, Sweden) 44(6):554–562. doi: 10.1080/02841860500218819 CrossRefGoogle Scholar
  61. Neglia JP, Meadows AT, Robison LL, Kim TH, Newton WA, Ruymann FB, Sather HN, Hammond GD (1991) Second neoplasms after acute lymphoblastic leukemia in childhood. N Engl J Med 325(19):1330–1336. doi: 10.1056/nejm199111073251902 PubMedCrossRefGoogle Scholar
  62. Neglia JP, Robison LL, Stovall M, Liu Y, Packer RJ, Hammond S, Yasui Y, Kasper CE, Mertens AC, Donaldson SS, Meadows AT, Inskip PD (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(21):1528–1537. doi: 10.1093/jnci/djj411 PubMedCrossRefGoogle Scholar
  63. Newhauser WD, Fontenot JD, Mahajan A, Kornguth D, Stovall M, Zheng Y, Taddei PJ, Mirkovic D, Mohan R, Cox JD, Woo S (2009) The risk of developing a second cancer after receiving craniospinal proton irradiation. Phys Med Biol 54(8):2277–2291. doi: 10.1088/0031-9155/54/8/002 PubMedPubMedCentralCrossRefGoogle Scholar
  64. Nguyen F, Rubino C, Guerin S, Diallo I, Samand A, Hawkins M, Oberlin O, Lefkopoulos D, De Vathaire F (2008) Risk of a second malignant neoplasm after cancer in childhood treated with radiotherapy: correlation with the integral dose restricted to the irradiated fields. Int J Radiat Oncol Biol Phys 70(3):908–915. doi: 10.1016/j.ijrobp.2007.10.034 PubMedCrossRefGoogle Scholar
  65. Nygaard R, Garwicz S, Haldorsen T, Hertz H, Jonmundsson GK, Lanning M, Moe PJ (1991) Second malignant neoplasms in patients treated for childhood leukemia. A population-based cohort study from the Nordic countries. The Nordic Society of Pediatric Oncology and Hematology (NOPHO). Acta Paediatr Scand 80(12):1220–1228PubMedCrossRefGoogle Scholar
  66. Oeffinger KC, Mertens AC, Sklar CA, Kawashima T, Hudson MM, Meadows AT, Friedman DL, Marina N, Hobbie W, Kadan-Lottick NS, Schwartz CL, Leisenring W, Robison LL (2006) Chronic health conditions in adult survivors of childhood cancer. N Engl J Med 355(15):1572–1582. doi: 10.1056/NEJMsa060185 PubMedCrossRefGoogle Scholar
  67. Olsen JH, Boice JD Jr, Seersholm N, Bautz A, Fraumeni JF Jr (1995) Cancer in the parents of children with cancer. N Engl J Med 333(24):1594–1599. doi: 10.1056/nejm199512143332403 PubMedCrossRefGoogle Scholar
  68. Olsen JH, Moller T, Anderson H, Langmark F, Sankila R, Tryggvadottir L, Winther JF, Rechnitzer C, Jonmundsson G, Christensen J, Garwicz S (2009) Lifelong cancer incidence in 47,697 patients treated for childhood cancer in the Nordic countries. J Natl Cancer Inst 101(11):806–813. doi: 10.1093/jnci/djp104 PubMedCrossRefGoogle Scholar
  69. Packer RJ, Zhou T, Holmes E, Vezina G, Gajjar A (2013) Survival and secondary tumors in children with medulloblastoma receiving radiotherapy and adjuvant chemotherapy: results of Children’s Oncology Group trial A9961. Neuro-Oncology 15(1):97–103. doi: 10.1093/neuonc/nos267 PubMedCrossRefGoogle Scholar
  70. Pan E, Prados MD (2003) Familial tumors syndromes of the central nervous system. In: Pollock RE, Weichselbaum RR (eds) Holland-Frei cancer medicine. BC Decker, Hamilton (ON)Google Scholar
  71. Paulino AC, Mai WY, Chintagumpala M, Taher A, Teh BS (2008) Radiation-induced malignant gliomas: is there a role for reirradiation? Int J Radiat Oncol Biol Phys 71(5):1381–1387. doi: 10.1016/j.ijrobp.2007.12.018 PubMedCrossRefGoogle Scholar
  72. Paulino AC, Ahmed IM, Mai WY, Teh BS (2009) The influence of pretreatment characteristics and radiotherapy parameters on time interval to development of radiation-associated meningioma. Int J Radiat Oncol Biol Phys 75(5):1408–1414. doi: 10.1016/j.ijrobp.2009.01.052 PubMedCrossRefGoogle Scholar
  73. Pearce MS, Salotti JA, Little MP, McHugh K, Lee C, Kim KP, Howe NL, Ronckers CM, Rajaraman P, Craft AW, Parker L, Berrington de González A (2012) Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study. Lancet 380(9840):499–505. doi: 10.1016/s0140-6736(12)60815-0 PubMedPubMedCentralCrossRefGoogle Scholar
  74. Perkins SM, Dewees T, Shinohara ET, Reddy MM, Frangoul H (2013) Risk of subsequent malignancies in survivors of childhood leukemia. J Cancer Surviv 7(4):544–550. doi: 10.1007/s11764-013-0292-8 PubMedCrossRefGoogle Scholar
  75. Peterson KM, Shao C, McCarter R, MacDonald TJ, Byrne J (2006) An analysis of SEER data of increasing risk of secondary malignant neoplasms among long-term survivors of childhood brain tumors. Pediatr Blood Cancer 47(1):83–88. doi: 10.1002/pbc.20690 PubMedCrossRefGoogle Scholar
  76. Pettorini BL, Narducci A, de Carlo A, Abet F, Caldarelli M, Massimi L, Tamburrini G, Di Rocco C (2009) Thyroid neoplasm after central nervous system irradiation for medulloblastoma in childhood: report of two cases. Childs Nerv Syst 25(5):631–634. doi: 10.1007/s00381-009-0814-x PubMedCrossRefGoogle Scholar
  77. Relling MV, Rubnitz JE, Rivera GK, Boyett JM, Hancock ML, Felix CA, Kun LE, Walter AW, Evans WE, Pui CH (1999) High incidence of secondary brain tumours after radiotherapy and antimetabolites. Lancet 354(9172):34–39. doi: 10.1016/s0140-6736(98)11079-6 PubMedCrossRefGoogle Scholar
  78. Reulen RC, Frobisher C, Winter DL, Kelly J, Lancashire ER, Stiller CA, Pritchard-Jones K, Jenkinson HC, Hawkins MM (2011) Long-term risks of subsequent primary neoplasms among survivors of childhood cancer. JAMA 305(22):2311–2319. doi: 10.1001/jama.2011.747 PubMedCrossRefGoogle Scholar
  79. Romeike BF, Kim YJ, Steudel WI, Graf N (2007) Diffuse high-grade gliomas as second malignant neoplasms after radio-chemotherapy for pediatric malignancies. Childs Nerv Syst 23(2):185–193. doi: 10.1007/s00381-006-0199-z PubMedCrossRefGoogle Scholar
  80. Rosso P, Terracini B, Fears TR, Jankovic M, Fossati Bellani F, Arrighini A, Carli M, Cordero di Montezemolo L, Garre ML, Guazzelli C et al (1994) Second malignant tumors after elective end of therapy for a first cancer in childhood: a multicenter study in Italy. Int J Cancer 59(4):451–456PubMedCrossRefGoogle Scholar
  81. Sadetzki S, Chetrit A, Freedman L, Stovall M, Modan B, Novikov I (2005) Long-term follow-up for brain tumor development after childhood exposure to ionizing radiation for tinea capitis. Radiat Res 163(4):424–432PubMedCrossRefGoogle Scholar
  82. Salminen E, Pukkala E, Teppo L (1999) Second cancers in patients with brain tumours—impact of treatment. Eur J Cancer (Oxford, England: 1990) 35(1):102–105CrossRefGoogle Scholar
  83. Salvati M, D’Elia A, Melone GA, Brogna C, Frati A, Raco A, Delfini R (2008) Radio-induced gliomas: 20-year experience and critical review of the pathology. J Neuro-Oncol 89(2):169–177. doi: 10.1007/s11060-008-9565-x CrossRefGoogle Scholar
  84. Sankila R, Olsen JH, Anderson H, Garwicz S, Glattre E, Hertz H, Langmark F, Lanning M, Moller T, Tulinius H (1998) Risk of cancer among offspring of childhood-cancer survivors. Association of the Nordic Cancer Registries and the Nordic Society of Paediatric Haematology and Oncology. N Engl J Med 338(19):1339–1344. doi: 10.1056/nejm199805073381902 PubMedCrossRefGoogle Scholar
  85. Sharif S, Ferner R, Birch JM, Gillespie JE, Gattamaneni HR, Baser ME, Evans DG (2006) Second primary tumors in neurofibromatosis 1 patients treated for optic glioma: substantial risks after radiotherapy. J Clin Oncol 24(16):2570–2575. doi: 10.1200/jco.2005.03.8349 PubMedCrossRefGoogle Scholar
  86. Shore RE, Moseson M, Harley N, Pasternack BS (2003) Tumors and other diseases following childhood x-ray treatment for ringworm of the scalp (Tinea capitis). Health Phys 85(4):404–408PubMedCrossRefGoogle Scholar
  87. Shore-Freedman E, Abrahams C, Recant W, Schneider AB (1983) Neurilemomas and salivary gland tumors of the head and neck following childhood irradiation. Cancer 51(12):2159–2163PubMedCrossRefGoogle Scholar
  88. Smith MA, Seibel NL, Altekruse SF, Ries LA, Melbert DL, O’Leary M, Smith FO, Reaman GH (2010) Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28(15):2625–2634. doi: 10.1200/jco.2009.27.0421 PubMedPubMedCentralCrossRefGoogle Scholar
  89. Soffer D, Gomori JM, Siegal T, Shalit MN (1989) Intracranial meningiomas after high-dose irradiation. Cancer 63(8):1514–1519PubMedCrossRefGoogle Scholar
  90. Stavrou T, Bromley CM, Nicholson HS, Byrne J, Packer RJ, Goldstein AM, Reaman GH (2001) Prognostic factors and secondary malignancies in childhood medulloblastoma. J Pediatr Hematol Oncol 23(7):431–436PubMedCrossRefGoogle Scholar
  91. Strenger V, Sovinz P, Lackner H, Dornbusch HJ, Lingitz H, Eder HG, Moser A, Urban C (2008) Intracerebral cavernous hemangioma after cranial irradiation in childhood. Incidence and risk factors. Strahlenther Onkol 184(5):276–280. doi: 10.1007/s00066-008-1817-3 PubMedCrossRefGoogle Scholar
  92. Strojan P, Popovic M, Jereb B (2000) Secondary intracranial meningiomas after high-dose cranial irradiation: report of five cases and review of the literature. Int J Radiat Oncol Biol Phys 48(1):65–73PubMedCrossRefGoogle Scholar
  93. Sugden E, Taylor A, Pretorius P, Kennedy C, Bhangoo R (2014) Meningiomas occurring during long-term survival after treatment for childhood cancer. JRSM Open 5(4):2054270414524567. doi: 10.1177/2054270414524567 PubMedPubMedCentralCrossRefGoogle Scholar
  94. Svahn-Tapper G, Garwicz S, Anderson H, Shamsaldin A, De Vathaire F, Olsen JH, Dollner H, Hertz H, Jonmundsson G, Langmark F, Lanning M, Sankila R, Tulinius H, Moller T (2006) Radiation dose and relapse are predictors for development of second malignant solid tumors after cancer in childhood and adolescence: a population-based case-control study in the five Nordic countries. Acta Oncol (Stockholm, Sweden) 45(4):438–448. doi: 10.1080/02841860600658633 CrossRefGoogle Scholar
  95. Taylor AJ, Frobisher C, Ellison DW, Reulen RC, Winter DL, Taylor RE, Stiller CA, Lancashire ER, Tudor EC, Baggott C, May S, Hawkins MM (2009) Survival after second primary neoplasms of the brain or spinal cord in survivors of childhood cancer: results from the British Childhood Cancer Survivor Study. J Clin Oncol 27(34):5781–5787. doi: 10.1200/jco.2009.22.4386 PubMedCrossRefGoogle Scholar
  96. Taylor AJ, Little MP, Winter DL, Sugden E, Ellison DW, Stiller CA, Stovall M, Frobisher C, Lancashire ER, Reulen RC, Hawkins MM (2010) Population-based risks of CNS tumors in survivors of childhood cancer: the British Childhood Cancer Survivor Study. J Clin Oncol 28(36):5287–5293. doi: 10.1200/jco.2009.27.0090 PubMedPubMedCentralCrossRefGoogle Scholar
  97. Thompson DE, Mabuchi K, Ron E, Soda M, Tokunaga M, Ochikubo S, Sugimoto S, Ikeda T, Terasaki M, Izumi S et al (1994) Cancer incidence in atomic bomb survivors. Part II: solid tumors, 1958–1987. Radiat Res 137(2 Suppl):S17–S67PubMedCrossRefGoogle Scholar
  98. Torres CF, Korones DN, Pilcher W (1997) Multiple ependymomas in a patient with Turcot’s syndrome. Med Pediatr Oncol 28(1):59–61PubMedCrossRefGoogle Scholar
  99. Travis LB, Ng AK, Allan JM, Pui CH, Kennedy AR, Xu XG, Purdy JA, Applegate K, Yahalom J, Constine LS, Gilbert ES, Boice JD Jr (2012) Second malignant neoplasms and cardiovascular disease following radiotherapy. J Natl Cancer Inst 104(5):357–370. doi: 10.1093/jnci/djr533 PubMedPubMedCentralCrossRefGoogle Scholar
  100. Tsui K, Gajjar A, Li C, Srivastava D, Broniscer A, Wetmore C, Kun LE, Merchant TE, Ellison DW, Orr BA, Boop FA, Klimo P, Ross J, Robison LL, Armstrong GT (2015) Subsequent neoplasms in survivors of childhood central nervous system tumors: risk after modern multimodal therapy. Neuro-Oncology 17(3):448–456. doi: 10.1093/neuonc/nou279 PubMedCrossRefGoogle Scholar
  101. Tubiana M (2009) Can we reduce the incidence of second primary malignancies occurring after radiotherapy? A critical review. Radiother Oncol 91(1):4–15. ; discussion 11–13. doi: 10.1016/j.radonc.2008.12.016 PubMedCrossRefGoogle Scholar
  102. 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(3):445–453. doi: 10.1007/s00381-011-1390-4 PubMedCrossRefGoogle Scholar
  103. von Hoff K, Hinkes B, Gerber NU, Deinlein F, Mittler U, Urban C, Benesch M, Warmuth-Metz M, Soerensen N, Zwiener I, Goette H, Schlegel PG, Pietsch T, Kortmann RD, Kuehl J, Rutkowski S (2009) Long-term outcome and clinical prognostic factors in children with medulloblastoma treated in the prospective randomised multicentre trial HIT’91. Eur J Cancer (Oxford, England: 1990) 45(7):1209–1217. doi: 10.1016/j.ejca.2009.01.015 CrossRefGoogle Scholar
  104. 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(12):3761–3767PubMedCrossRefGoogle Scholar
  105. Winther JF, Sankila R, Boice JD, Tulinius H, Bautz A, Barlow L, Glattre E, Langmark F, Moller TR, Mulvihill JJ, Olafsdottir GH, Ritvanen A, Olsen JH (2001) Cancer in siblings of children with cancer in the Nordic countries: a population-based cohort study. Lancet 358(9283):711–717. doi: 10.1016/s0140-6736(01)05838-x PubMedCrossRefGoogle Scholar
  106. You SH, Lyu CJ, Kim DS, Suh CO (2013) Second primary brain tumors following cranial irradiation for pediatric solid brain tumors. Childs Nerv Syst 29(10):1865–1870. doi: 10.1007/s00381-013-2098-4 PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Radiation OncologyThe University of LouisvilleLouisvilleUSA

Personalised recommendations