Organ Dysfunction, Second Malignant Neoplasms, and Survival

  • Robert T. RussellEmail author
  • Anna T. Meadows


Childhood cancer survival rates have continued to increase during the past four decades, so now the expectation is that the approximately 80 % will be cured. For some, this improved survival has been achieved at the expense of long-term complications of surgery, chemotherapy, and radiation. These late effects include neurocognitive deficits, cardiovascular and pulmonary morbidity, endocrine dysfunction, auditory impairment, and reduced fertility, and will be detailed in this chapter. Second malignant neoplasms are another late complication for survivors. The need for long-term follow-up of childhood cancer survivors is necessary in order to identify these late effects and provide survivors with appropriate care and surveillance. Research is also needed in order to learn more about late effects of therapy as childhood cancer survivors’ age, and to identify and further characterize second malignant neoplasms. This information is critical in refining treatment algorithms that are designed to reduce late effects, and to continue to improve survival.


Childhood cancer Organ dysfunction Treatment effects Second malignancies Survival after childhood cancer 


  1. 1.
    Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60(5):277–300.PubMedCrossRefGoogle Scholar
  2. 2.
    Ries L, Melbert D, Krapcho M. SEER cancer statistics review, 1975–2005. Bethesda: National Cancer Institute; 2007.Google Scholar
  3. 3.
    Horner M, Ries L, Krapcho M. SEER cancers statistics review, 1975–2006. Bethesda: National Cancer Institute; 2009.Google Scholar
  4. 4.
    Mariotto AB, Rowland JH, Yabroff KR, Scoppa S, Hachey M, Ries L, et al. Long-term survivors of childhood cancers in the United States. Cancer Epidemiol Biomarkers Prev. 2009;18(4):1033–40.PubMedCrossRefGoogle Scholar
  5. 5.
    Campbell LK, Scaduto M, Sharp W, Dufton L, Van Slyke D, Whitlock JA, et al. A meta-analysis of the neurocognitive sequelae of treatment for childhood acute lymphocytic leukemia. Pediatr Blood Cancer. 2007;49(1):65–73.PubMedCrossRefGoogle Scholar
  6. 6.
    Reimers TS, Ehrenfels S, Mortensen EL, Schmiegelow M, Sonderkaer S, Carstensen H, et al. Cognitive deficits in long-term survivors of childhood brain tumors: identification of predictive factors. Med Pediatr Oncol. 2003;40(1):26–34.PubMedCrossRefGoogle Scholar
  7. 7.
    Walter AW, Mulhern RK, Gajjar A, Heideman RL, Reardon D, Sanford RA, et al. Survival and neurodevelopmental outcome of young children with medulloblastoma at St Jude Children’s Research Hospital. J Clin Oncol. 1999;17(12):3720–8.PubMedGoogle Scholar
  8. 8.
    Palmer SL, Gajjar A, Reddick WE, Glass JO, Kun LE, Wu S, et al. Predicting intellectual outcome among children treated with 35–40 Gy craniospinal irradiation for medulloblastoma. Neuropsychology. 2003;17(4):548–55.PubMedCrossRefGoogle Scholar
  9. 9.
    Duffner PK. Long-term effects of radiation therapy on cognitive and endocrine function in children with leukemia and brain tumors. Neurologist. 2004;10(6):293–310.PubMedCrossRefGoogle Scholar
  10. 10.
    Ris MD, Packer R, Goldwein J, Jones-Wallace D, Boyett JM. Intellectual outcome after reduced-dose radiation therapy plus adjuvant chemotherapy for medulloblastoma: a Children’s Cancer Group study. J Clin Oncol. 2001;19(15):3470–6.PubMedGoogle Scholar
  11. 11.
    Radcliffe J, Packer RJ, Atkins TE, Bunin GR, Schut L, Goldwein JW, et al. Three- and four-year cognitive outcome in children with noncortical brain tumors treated with whole-brain radiotherapy. Ann Neurol. 1992;32(4):551–4.PubMedCrossRefGoogle Scholar
  12. 12.
    Silber JH, Radcliffe J, Peckham V, Perilongo G, Kishnani P, Fridman M, et al. Whole-brain irradiation and decline in intelligence: the influence of dose and age on IQ score. J Clin Oncol. 1992;10(9):1390–6.PubMedGoogle Scholar
  13. 13.
    Landier W, Bhatia S, Eshelman DA. Development of risk-based guidelines for pediatric cancer survivors: the Children’s Oncology Group Long-Term Follow-up Guidelines from the Children’s Oncology Group Late Effects Committee and Nursing Discipline. J Clin Oncol. 2004;22:4979–90.PubMedCrossRefGoogle Scholar
  14. 14.
    Buizer AI, de Sonneville LM, Veerman AJ. Effects of chemotherapy on neurocognitive function in children with acute lymphoblastic leukemia: a critical review of the literature. Pediatr Blood Cancer. 2009;52(4):447–54.PubMedCrossRefGoogle Scholar
  15. 15.
    Jansen NC, Kingma A, Schuitema A, Bouma A, Veerman AJ, Kamps WA. Neuropsychological outcome in chemotherapy-only-treated children with acute lymphoblastic leukemia. J Clin Oncol. 2008;26(18):3025–30.PubMedCrossRefGoogle Scholar
  16. 16.
    Silverman LB, Gelber RD, Dalton VK, Asselin BL, Barr RD, Clavell LA, et al. Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber consortium protocol 91-01. Blood. 2001;97(5):1211–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Bostrom BC, Sensel MR, Sather HN, Gaynon PS, La MK, Johnston K, et al. Dexamethasone versus prednisone and daily oral versus weekly intravenous mercaptopurine for patients with standard-risk acute lymphoblastic leukemia: a report from the Children’s Cancer Group. Blood. 2003;101(10):3809–17.PubMedCrossRefGoogle Scholar
  18. 18.
    Mitchell CD, Richards SM, Kinsey SE, Lilleyman J, Vora A, Eden TO. Benefit of dexamethasone compared with prednisolone for childhood acute lymphoblastic leukaemia: results of the UK Medical Research Council ALL97 randomized trial. Br J Haematol. 2005;129(6):734–45.PubMedCrossRefGoogle Scholar
  19. 19.
    Abid SH, Malhotra V, Perry MC. Radiation-induced and chemotherapy-induced pulmonary injury. Curr Opin Oncol. 2001;13(4):242–8.PubMedCrossRefGoogle Scholar
  20. 20.
    Meyer S, Reinhard H, Gottschling S, Nunold H, Graf N. Pulmonary dysfunction in pediatric oncology patients. Pediatr Hematol Oncol. 2004;21(2):175–95.PubMedCrossRefGoogle Scholar
  21. 21.
    Jakacki RI, Schramm CM, Donahue BR, Haas F, Allen JC. Restrictive lung disease following treatment for malignant brain tumors: a potential late effect of craniospinal irradiation. J Clin Oncol. 1995;13(6):1478–85.PubMedGoogle Scholar
  22. 22.
    Benoist MR, Lemerle J, Jean R, Rufin P, Scheinmann P, Paupe J. Effects of pulmonary function of whole lung irradiation for Wilm’s tumour in children. Thorax. 1982;37(3):175–80.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Villani F, Viviani S, Bonfante V, De Maria P, Soncini F, Laffranchi A. Late pulmonary effects in favorable stage I and IIA Hodgkin’s disease treated with radiotherapy alone. Am J Clin Oncol. 2000;23(1):18–21.PubMedCrossRefGoogle Scholar
  24. 24.
    Ginsberg SJ, Comis RL. The pulmonary toxicity of antineoplastic agents. Semin Oncol. 1982;9(1):34–51.PubMedGoogle Scholar
  25. 25.
    Eigen H, Wyszomierski D. Bleomycin lung injury in children. Pathophysiology and guidelines for management. Am J Pediatr Hematol Oncol. 1985;7(1):71–8.PubMedGoogle Scholar
  26. 26.
    O’Driscoll BR, Hasleton PS, Taylor PM, Poulter LW, Gattameneni HR, Woodcock AA. Active lung fibrosis up to 17 years after chemotherapy with carmustine (BCNU) in childhood. N Engl J Med. 1990;323(6):378–82.PubMedCrossRefGoogle Scholar
  27. 27.
    Lipshultz SE, Alvarez JA, Scully RE. Anthracycline associated cardiotoxicity in survivors of childhood cancer. Heart. 2008;94(4):525–33.PubMedCrossRefGoogle Scholar
  28. 28.
    Adams M, Lipshultz SE. Pathophysiology of anthracycline- and radiation-associated cardiomyopathies: implications for screening and prevention. Pediatr Blood Cancer. 2005;44:600–6.PubMedCrossRefGoogle Scholar
  29. 29.
    Lipshultz SE, Colan SD. Cardiovascular trials in long-term survivors of childhood cancer. J Clin Oncol. 2004;22(5):769–73.PubMedCrossRefGoogle Scholar
  30. 30.
    Krischer JP, Epstein S, Cuthbertson DD, Goorin AM, Epstein ML, Lipshultz SE. Clinical cardiotoxicity following anthracycline treatment for childhood cancer: the Pediatric Oncology Group experience. J Clin Oncol. 1997;15(4):1544–52.PubMedGoogle Scholar
  31. 31.
    Kremer LC, van Dalen E, Offringa M. Frequency and risk factors of anthracycline-induced clinical heart failure in children: a systematic review. Ann Oncol. 2002;13:503–12.PubMedCrossRefGoogle Scholar
  32. 32.
    Giantris A, Abdurrahman L, Hinkle A, Asselin B, Lipshultz SE. Anthracycline-induced cardiotoxicity in children and young adults. Crit Rev Oncol Hematol. 1998;27(1):53–68.PubMedCrossRefGoogle Scholar
  33. 33.
    Lipshultz SE, Giantris AL, Lipsitz SR, Kimball Dalton V, Asselin BL, Barr RD, et al. Doxorubicin administration by continuous infusion is not cardioprotective: the Dana-Farber 91-01 Acute Lymphoblastic Leukemia protocol. J Clin Oncol. 2002;20(6):1677–82.PubMedCrossRefGoogle Scholar
  34. 34.
    Lipshultz SE, Rifai N, Dalton VM, Levy DE, Silverman LB, Lipsitz SR, et al. The effect of dexrazoxane on myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia. N Engl J Med. 2004;351(2):145–53.PubMedCrossRefGoogle Scholar
  35. 35.
    Silber JH, Cnaan A, Clark BJ, Paridon SM, Chin AJ, Rychik J, et al. Enalapril to prevent cardiac function decline in long-term survivors of pediatric cancer exposed to anthracyclines. J Clin Oncol. 2004;22(5):820–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Glanzmann C, Kaufmann P, Jenni R, Hess OM, Huguenin P. Cardiac risk after mediastinal irradiation for Hodgkin’s disease. Radiother Oncol. 1998;46(1):51–62.PubMedCrossRefGoogle Scholar
  37. 37.
    Lipshultz SE, Sallan SE. Cardiovascular abnormalities in long-term survivors of childhood malignancy. J Clin Oncol. 1993;11(7):1199–203.PubMedGoogle Scholar
  38. 38.
    Adams MJ, Lipshultz SE, Schwartz C, Fajardo LF, Coen V, Constine LS. Radiation-associated cardiovascular disease: manifestations and management. Semin Radiat Oncol. 2003;13(3):346–56.PubMedCrossRefGoogle Scholar
  39. 39.
    Adams MJ, Hardenbergh PH, Constine LS, Lipshultz SE. Radiation-associated cardiovascular disease. Crit Rev Oncol Hematol. 2003;45(1):55–75.PubMedCrossRefGoogle Scholar
  40. 40.
    Jurado J, Thompson PD. Prevention of coronary artery disease in cancer patients. Pediatr Blood Cancer. 2005;44(7):620–4.PubMedCrossRefGoogle Scholar
  41. 41.
    Heyn R, Raney Jr RB, Hays DM, Tefft M, Gehan E, Webber B, et al. Late effects of therapy in patients with paratesticular rhabdomyosarcoma. Intergroup Rhabdomyosarcoma Study Committee. J Clin Oncol. 1992;10(4):614–23.PubMedGoogle Scholar
  42. 42.
    Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991;21(1):109–22.PubMedCrossRefGoogle Scholar
  43. 43.
    Mahboubi S, Silber JH. Radiation-induced esophageal strictures in children with cancer. Eur Radiol. 1997;7(1):119–22.PubMedCrossRefGoogle Scholar
  44. 44.
    Donaldson SS, Jundt S, Ricour C, Sarrazin D, Lemerle J, Schweisguth O. Radiation enteritis in children. A retrospective review, clinicopathologic correlation, and dietary management. Cancer. 1975;35(4):1167–78.PubMedCrossRefGoogle Scholar
  45. 45.
    Lawrence TS, Robertson JM, Anscher MS, Jirtle RL, Ensminger WD, Fajardo LF. Hepatic toxicity resulting from cancer treatment. Int J Radiat Oncol Biol Phys. 1995;31(5):1237–48.PubMedCrossRefGoogle Scholar
  46. 46.
    Corbacioglu S, Cesaro S, Faraci M, Valteau-Couanet D, Gruhn B, Rovelli A, et al. Defibrotide for prophylaxis of hepatic veno-occlusive disease in paediatric haemopoietic stem-cell transplantation: an open-label, phase 3, randomised controlled trial. Lancet. 2012;379(9823):1301–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Locasciulli A, Testa M, Pontisso P, Benvegnu L, Fraschini D, Corbetta A, et al. Prevalence and natural history of hepatitis C infection in patients cured of childhood leukemia. Blood. 1997;90(11):4628–33.PubMedGoogle Scholar
  48. 48.
    Jones DP, Chesney RW. Renal toxicity of cancer chemotherapeutic agents in children: ifosfamide and cisplatin. Curr Opin Pediatr. 1995;7(2):208–13.PubMedCrossRefGoogle Scholar
  49. 49.
    Jones DP, Spunt SL, Green D, Springate JE. Renal late effects in patients treated for cancer in childhood: a report from the Children’s Oncology Group. Pediatr Blood Cancer. 2008;51(6):724–31.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Marina NM, Poquette CA, Cain AM, Jones D, Pratt CB, Meyer WH. Comparative renal tubular toxicity of chemotherapy regimens including ifosfamide in patients with newly diagnosed sarcomas. J Pediatr Hematol Oncol. 2000;22(2):112–8.PubMedCrossRefGoogle Scholar
  51. 51.
    Skinner R. Chronic ifosfamide nephrotoxicity in children. Med Pediatr Oncol. 2003;41(3):190–7.PubMedCrossRefGoogle Scholar
  52. 52.
    Cohen EP, Robbins ME. Radiation nephropathy. Semin Nephrol. 2003;23(5):486–99.PubMedCrossRefGoogle Scholar
  53. 53.
    Paulino AC, Wen BC, Brown CK, Tannous R, Mayr NA, Zhen WK, et al. Late effects in children treated with radiation therapy for Wilms’ tumor. Int J Radiat Oncol Biol Phys. 2000;46(5):1239–46.PubMedCrossRefGoogle Scholar
  54. 54.
    Sasso G, Greco N, Murino P, Sasso FS. Late toxicity in Wilms tumor patients treated with radiotherapy at 15 years of median follow-up. J Pediatr Hematol Oncol. 2010;32(7):e264–7.PubMedCrossRefGoogle Scholar
  55. 55.
    Breslow NE, Collins AJ, Ritchey ML, Grigoriev YA, Peterson SM, Green DM. End stage renal disease in patients with Wilms tumor: results from the National Wilms Tumor Study Group and the United States Renal Data System. J Urol. 2005;174(5):1972–5.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Bardi E, Olah AV, Bartyik K, Endreffy E, Jenei C, Kappelmayer J, et al. Late effects on renal glomerular and tubular function in childhood cancer survivors. Pediatr Blood Cancer. 2004;43(6):668–73.PubMedCrossRefGoogle Scholar
  57. 57.
    Schell MJ, McHaney VA, Green AA, Kun LE, Hayes FA, Horowitz M, et al. Hearing loss in children and young adults receiving cisplatin with or without prior cranial irradiation. J Clin Oncol. 1989;7(6):754–60.PubMedGoogle Scholar
  58. 58.
    Rybak LP, Whitworth CA, Mukherjea D, Ramkumar V. Mechanisms of cisplatin-induced ototoxicity and prevention. Hear Res. 2007;226(1-2):157–67.PubMedCrossRefGoogle Scholar
  59. 59.
    Knight KR, Kraemer DF, Neuwelt EA. Ototoxicity in children receiving platinum chemotherapy: underestimating a commonly occurring toxicity that may influence academic and social development. J Clin Oncol. 2005;23(34):8588–96.PubMedCrossRefGoogle Scholar
  60. 60.
    Hua C, Bass JK, Khan R, Kun LE, Merchant TE. Hearing loss after radiotherapy for pediatric brain tumors: effect of cochlear dose. Int J Radiat Oncol Biol Phys. 2008;72(3):892–9.PubMedCrossRefGoogle Scholar
  61. 61.
    Bess FH, Dodd-Murphy J, Parker RA. Children with minimal sensorineural hearing loss: prevalence, educational performance, and functional status. Ear Hear. 1998;19(5):339–54.PubMedCrossRefGoogle Scholar
  62. 62.
    Gleeson HK, Shalet SM. Endocrine complications of neoplastic diseases in children and adolescents. Curr Opin Pediatr. 2001;13(4):346–51.PubMedCrossRefGoogle Scholar
  63. 63.
    Nandagopal R, Laverdiere C, Mulrooney D, Hudson MM, Meacham L. Endocrine late effects of childhood cancer therapy: a report from the Children’s Oncology Group. Horm Res. 2008;69(2):65–74.PubMedCrossRefGoogle Scholar
  64. 64.
    Costin G. Effects of low-dose cranial radiation on growth hormone secretory dynamics and hypothalamic-pituitary function. Am J Dis Child. 1988;142(8):847–52.PubMedGoogle Scholar
  65. 65.
    Brownstein CM, Mertens AC, Mitby PA, Stovall M, Qin J, Heller G, et al. Factors that affect final height and change in height standard deviation scores in survivors of childhood cancer treated with growth hormone: a report from the childhood cancer survivor study. J Clin Endocrinol Metab. 2004;89(9):4422–7.PubMedCrossRefGoogle Scholar
  66. 66.
    Gleeson HK, Shalet SM. The impact of cancer therapy on the endocrine system in survivors of childhood brain tumours. Endocr Relat Cancer. 2004;11(4):589–602.PubMedCrossRefGoogle Scholar
  67. 67.
    Gurney JG, Ness KK, Stovall M, Wolden S, Punyko JA, Neglia JP, et al. Final height and body mass index among adult survivors of childhood brain cancer: childhood cancer survivor study. J Clin Endocrinol Metab. 2003;88(10):4731–9.PubMedCrossRefGoogle Scholar
  68. 68.
    Chow EJ, Friedman DL, Yasui Y, Whitton JA, Stovall M, Robison LL, et al. Decreased adult height in survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. J Pediatr. 2007;150(4):370–5. 5.e1.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Sklar C, Wolden S. Therapy for pediatric brain tumors and the risk of growth hormone deficiency. J Clin Oncol. 2011;29(36):4743–4.PubMedCrossRefGoogle Scholar
  70. 70.
    Oberfield SE, Soranno D, Nirenberg A, Heller G, Allen JC, David R, et al. Age at onset of puberty following high-dose central nervous system radiation therapy. Arch Pediatr Adolesc Med. 1996;150(6):589–92.PubMedCrossRefGoogle Scholar
  71. 71.
    Mills JL, Fears TR, Robison LL, Nicholson HS, Sklar CA, Byrne J. Menarche in a cohort of 188 long-term survivors of acute lymphoblastic leukemia. J Pediatr. 1997;131(4):598–602.PubMedCrossRefGoogle Scholar
  72. 72.
    Sigurdson AJ, Ronckers CM, Mertens AC, Stovall M, Smith SA, Liu Y, et al. Primary thyroid cancer after a first tumour in childhood (the Childhood Cancer Survivor Study): a nested case-control study. Lancet. 2005;365(9476):2014–23.PubMedCrossRefGoogle Scholar
  73. 73.
    Green DM, Sklar CA, Boice Jr JD, Mulvihill JJ, Whitton JA, Stovall M, et al. Ovarian failure and reproductive outcomes after childhood cancer treatment: results from the Childhood Cancer Survivor Study. J Clin Oncol. 2009;27(14):2374–81.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Chemaitilly W, Mertens AC, Mitby P, Whitton J, Stovall M, Yasui Y, et al. Acute ovarian failure in the childhood cancer survivor study. J Clin Endocrinol Metab. 2006;91(5):1723–8.PubMedCrossRefGoogle Scholar
  75. 75.
    Julie B. Pregnancy outcome following anticancer therapy. In: Bern MM, Frigoletto FD, editors. Hematologic disorders in maternal-fetal medicine. New York: Alan R. Liss; 1990. p. 569.Google Scholar
  76. 76.
    Kalapurakal JA, Peterson S, Peabody EM, Thomas PR, Green DM, D’Angio GJ, et al. Pregnancy outcomes after abdominal irradiation that included or excluded the pelvis in childhood Wilms tumor survivors: a report from the National Wilms Tumor Study. Int J Radiat Oncol Biol Phys. 2004;58(5):1364–8.PubMedCrossRefGoogle Scholar
  77. 77.
    Green DM, Kawashima T, Stovall M, Leisenring W, Sklar CA, Mertens AC, et al. Fertility of male survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol. 2010;28(2):332–9.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Clifton DK, Bremner WJ. The effect of testicular x-irradiation on spermatogenesis in man. A comparison with the mouse. J Androl. 1983;4(6):387–92.PubMedCrossRefGoogle Scholar
  79. 79.
    Whitehead E, Shalet SM, Jones PH, Beardwell CG, Deakin DP. Gonadal function after combination chemotherapy for Hodgkin’s disease in childhood. Arch Dis Child. 1982;57(4):287–91.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Viviani S, Santoro A, Ragni G, Bonfante V, Bestetti O, Bonadonna G. Gonadal toxicity after combination chemotherapy for Hodgkin’s disease. Comparative results of MOPP vs ABVD. Eur J Cancer Clin Oncol. 1985;21(5):601–5.PubMedCrossRefGoogle Scholar
  81. 81.
    Rivkees SA, Crawford JD. The relationship of gonadal activity and chemotherapy-induced gonadal damage. JAMA. 1988;259(14):2123–5.PubMedCrossRefGoogle Scholar
  82. 82.
    Sklar C. Reproductive physiology and treatment-related loss of sex hormone production. Med Pediatr Oncol. 1999;33(1):2–8.PubMedCrossRefGoogle Scholar
  83. 83.
    Meistrich ML. Male gonadal toxicity. Pediatr Blood Cancer. 2009;53(2):261–6.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Sherins RJ, Olweny CL, Ziegler JL. Gynecomastia and gonadal dysfunction in adolescent boys treated with combination chemotherapy for Hodgkin’s disease. N Engl J Med. 1978;299(1):12–6.PubMedCrossRefGoogle Scholar
  85. 85.
    Inskip PD, Curtis RE. New malignancies following childhood cancer in the United States, 1973–2002. Int J Cancer. 2007;121(10):2233–40.PubMedCrossRefGoogle Scholar
  86. 86.
    Friedman DL, Whitton J, Leisenring W, Mertens AC, Hammond S, Stovall M, et al. Subsequent neoplasms in 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study. J Natl Cancer Inst. 2010;102(14):1083–95.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Reulen RC, Taylor AJ, Winter DL, Stiller CA, Frobisher C, Lancashire ER, et al. Long-term population-based risks of breast cancer after childhood cancer. Int J Cancer. 2008;123(9):2156–63.PubMedCrossRefGoogle Scholar
  88. 88.
    Bhatia S, Robison LL, Oberlin O, Greenberg M, Bunin G, Fossati-Bellani F, et al. Breast cancer and other second neoplasms after childhood Hodgkin’s disease. N Engl J Med. 1996;334(12):745–51.PubMedCrossRefGoogle Scholar
  89. 89.
    Neglia JP, Friedman DL, Yasui Y, Mertens AC, Hammond S, Stovall M, et al. Second malignant neoplasms in five-year survivors of childhood cancer: childhood cancer survivor study. J Natl Cancer Inst. 2001;93(8):618–29.PubMedCrossRefGoogle Scholar
  90. 90.
    Kenney LB, Yasui Y, Inskip PD, Hammond S, Neglia JP, Mertens AC, et al. Breast cancer after childhood cancer: a report from the Childhood Cancer Survivor Study. Ann Intern Med. 2004;141(8):590–7.PubMedCrossRefGoogle Scholar
  91. 91.
    Ron E, Lubin JH, Shore RE, Mabuchi K, Modan B, Pottern LM, et al. Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies. Radiat Res. 1995;141(3):259–77.PubMedCrossRefGoogle Scholar
  92. 92.
    Sklar C, Whitton J, Mertens A, Stovall M, Green D, Marina N, et al. Abnormalities of the thyroid in survivors of Hodgkin’s disease: data from the Childhood Cancer Survivor Study. J Clin Endocrinol Metab. 2000;85(9):3227–32.PubMedGoogle Scholar
  93. 93.
    Ronckers CM, Sigurdson AJ, Stovall M, Smith SA, Mertens AC, Liu Y, et al. Thyroid cancer in childhood cancer survivors: a detailed evaluation of radiation dose response and its modifiers. Radiat Res. 2006;166(4):618–28.PubMedCrossRefGoogle Scholar
  94. 94.
    Bhatti P, Veiga LH, Ronckers CM, Sigurdson AJ, Stovall M, Smith SA, et al. Risk of second primary thyroid cancer after radiotherapy for a childhood cancer in a large cohort study: an update from the childhood cancer survivor study. Radiat Res. 2010;174(6):741–52.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Veiga LH, Bhatti P, Ronckers CM, Sigurdson AJ, Stovall M, Smith SA, et al. Chemotherapy and thyroid cancer risk: a report from the childhood cancer survivor study. Cancer Epidemiol Biomarkers Prev. 2012;21(1):92–101.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Henderson TO, Rajaraman P, Stovall M, Constine LS, Olive A, Smith SA, et al. Risk factors associated with secondary sarcomas in childhood cancer survivors: a report from the childhood cancer survivor study. Int J Radiat Oncol Biol Phys. 2012;84(1):224–30.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Tucker MA, D’Angio GJ, Boice Jr JD, Strong LC, Li FP, Stovall M, et al. Bone sarcomas linked to radiotherapy and chemotherapy in children. N Engl J Med. 1987;317(10):588–93.PubMedCrossRefGoogle Scholar
  98. 98.
    Hawkins MM, Wilson LM, Burton HS, Potok MH, Winter DL, Marsden HB, et al. Radiotherapy, alkylating agents, and risk of bone cancer after childhood cancer. J Natl Cancer Inst. 1996;88(5):270–8.PubMedCrossRefGoogle Scholar
  99. 99.
    Reulen RC, Frobisher C, Winter DL, Kelly J, Lancashire ER, Stiller CA, et al. Long-term risks of subsequent primary neoplasms among survivors of childhood cancer. JAMA. 2011;305(22):2311–9.PubMedCrossRefGoogle Scholar
  100. 100.
    Wong FL, Boice Jr JD, Abramson DH, Tarone RE, Kleinerman RA, Stovall M, et al. Cancer incidence after retinoblastoma. Radiation dose and sarcoma risk. JAMA. 1997;278(15):1262–7.PubMedCrossRefGoogle Scholar
  101. 101.
    Fletcher O, Easton D, Anderson K, Gilham C, Jay M, Peto J. Lifetime risks of common cancers among retinoblastoma survivors. J Natl Cancer Inst. 2004;96(5):357–63.PubMedCrossRefGoogle Scholar
  102. 102.
    Kleinerman RA, Tucker MA, Tarone RE, Abramson DH, Seddon JM, Stovall M, et al. Risk of new cancers after radiotherapy in long-term survivors of retinoblastoma: an extended follow-up. J Clin Oncol. 2005;23(10):2272–9.PubMedCrossRefGoogle Scholar
  103. 103.
    Henderson TO, Oeffinger KC, Whitton J, Leisenring W, Neglia J, Meadows A, et al. Secondary gastrointestinal cancer in childhood cancer survivors: a cohort study. Ann Intern Med. 2012;156(11):757–66. W-260.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Frobisher C, Gurung PM, Leiper A, Reulen RC, Winter DL, Taylor AJ, et al. Risk of bladder tumours after childhood cancer: the British Childhood Cancer Survivor Study. BJU Int. 2010;106(7):1060–9.PubMedCrossRefGoogle Scholar
  105. 105.
    Bhatia S, Yasui Y, Robison LL, Birch JM, Bogue MK, Diller L, et al. High risk of subsequent neoplasms continues with extended follow-up of childhood Hodgkin’s disease: report from the Late Effects Study Group. J Clin Oncol. 2003;21(23):4386–94.PubMedCrossRefGoogle Scholar
  106. 106.
    Leung W, Sandlund JT, Hudson MM, Zhou Y, Hancock ML, Zhu Y, et al. Second malignancy after treatment of childhood non-Hodgkin lymphoma. Cancer. 2001;92(7):1959–66.PubMedCrossRefGoogle Scholar
  107. 107.
    Bielorai B, Meyer C, Trakhtenbrot L, Golan H, Rozner E, Amariglio N, et al. Therapy-related acute myeloid leukemia with t(2;11)(q37;q23) after treatment for osteosarcoma. Cancer Genet Cytogenet. 2010;203(2):288–91.PubMedCrossRefGoogle Scholar
  108. 108.
    Pratt CB, Meyer WH, Luo X, Cain AM, Kaste SC, Pappo AS, et al. Second malignant neoplasms occurring in survivors of osteosarcoma. Cancer. 1997;80(5):960–5.PubMedCrossRefGoogle Scholar
  109. 109.
    Nottage K, Lanctot J, Li Z, Neglia JP, Bhatia S, Hammond S, et al. Long-term risk for subsequent leukemia after treatment for childhood cancer: a report from the Childhood Cancer Survivor Study. Blood. 2011;117(23):6315–8.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Pui CH, Behm FG, Raimondi SC, Dodge RK, George SL, Rivera GK, et al. Secondary acute myeloid leukemia in children treated for acute lymphoid leukemia. N Engl J Med. 1989;321(3):136–42.PubMedCrossRefGoogle Scholar
  111. 111.
    Armstrong GT, Liu Q, Yasui Y, Neglia JP, Leisenring W, Robison LL, et al. Late mortality among 5-year survivors of childhood cancer: a summary from the Childhood Cancer Survivor Study. J Clin Oncol. 2009;27(14):2328–38.PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Wasilewski-Masker K, Liu Q, Yasui Y, Leisenring W, Meacham LR, Hammond S, et al. Late recurrence in pediatric cancer: a report from the Childhood Cancer Survivor Study. J Natl Cancer Inst. 2009;101(24):1709–20.PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Steliarova-Foucher E, Stiller C, Lacour B, Kaatsch P. International classification of childhood cancer, third edition. Cancer. 2005;103(7):1457–67.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Division of Pediatric Surgery, Department of SurgeryUniversity of Alabama at Birmingham, Children’s of AlabamaBirminghamUSA
  2. 2.Department of PediatricsPe e, University of PennsylvaniaPhiladelphiaUSA

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