Pediatric Drugs

, Volume 8, Issue 2, pp 71–84 | Cite as

Surviving Childhood Cancer

The Impact on Life
  • Robert E. Goldsby
  • Denah R. Taggart
  • Arthur R. Ablin
Leading Article


With modern therapies, most children diagnosed with cancer are expected to reach adulthood. Therefore, there are large and ever-increasing numbers of children and young adults in our population who are survivors of childhood cancer. Many of the therapies responsible for improved cancer survival rates can also damage normal cells and tissues. As more children survive cancer, the physical and emotional costs of enduring cancer therapy become increasingly important. Although most childhood cancer survivors are now expected to survive, they remain at risk for relapse, second malignant neoplasms, organ dysfunction, and a negative psychologic impact. Individual risk is quite variable and is dependent on multiple factors including the type and site of cancer, the therapy utilized, and the individual’s constitution. The risks are likely to change as we learn more about the specific long-term effects of cancer therapy, develop more refined and targeted therapies, and develop and apply more effective preventative strategies or therapeutic interventions. Guidelines for long-term follow-up have been established and are available to help facilitate appropriate monitoring of and care for potential late effects.


  1. 1.
    Ries L, Eisner M, Kosary C, et al. SEER cancer statistics review 1975–2002. Bethesda (MD): National Cancer Institute, 2003. Also available online from URL: [Accessed 2005]Google Scholar
  2. 2.
    Bhatia S, Meadows A. Long-term follow-up of childhood cancer survivors: future directions for clinical care and research. Pediatr Blood Cancer 2006; 46(2): 143–8PubMedGoogle Scholar
  3. 3.
    Hewitt M, Wiener S, Si Mone JV, editors. Childhood cancer survivorship: improving care and quality of life. National Cancer Policy Board. Washington, DC: National Academics Press, 2003Google Scholar
  4. 4.
    Ablin AR. Supportive care of children with cancer: current therapy and guidelines from the Children’s Cancer Group. 2nd ed. Baltimore (MD): The Johns Hopkins University Press, 1997Google Scholar
  5. 5.
    Pizzo PA, Poplack DG. Principles and practice of pediatric oncology. 4th ed. Philadelphia (PA): Lippincott Williams and Wilkins, 2002Google Scholar
  6. 6.
    Kubota M, Lin YW, Hamahata K, et al. Cancer chemotherapy and somatic cell mutation. Mutat Res 2000; 470(2): 93–102PubMedGoogle Scholar
  7. 7.
    Dempsey JL, Seshadri RS, Morley AA. Increased mutation frequency following treatment with cancer chemotherapy. Cancer Res 1985; 45(6): 2873–7PubMedGoogle Scholar
  8. 8.
    Loeb LA, Loeb KR, Anderson JP. Multiple mutations and cancer. Proc Natl Acad Sci U S A 2003; 100(3): 776–81PubMedGoogle Scholar
  9. 9.
    Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100(1): 57–70PubMedGoogle Scholar
  10. 10.
    Langeveld NE, Ubbink MC, Last BF, et al. Educational achievement, employment and living situation in long-term young adult survivors of childhood cancer in the Netherlands. Psychooncology 2003; 12(3): 213–25PubMedGoogle Scholar
  11. 11.
    Pui CH, Cheng C, Leung W, et al. Extended follow-up of long-term survivors of childhood acute lymphoblastic leukemia. N Engl J Med 2003; 349(7): 640–9PubMedGoogle Scholar
  12. 12.
    Garre ML, Gandus S, Cesana B, et al. Health status of long-term survivors after cancer in childhood: results of an uniinstitutional study in Italy. Am J Pediatr Hematol Oncol 1994; 16(2): 143–52PubMedGoogle Scholar
  13. 13.
    Hudson MM, Mertens AC, Yasui Y, et al. Health status of adult long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. JAMA 2003; 290(12): 1583–92PubMedGoogle Scholar
  14. 14.
    Lackner H, Benesch M, Schagerl S, et al. Prospective evaluation of late effects after childhood cancer therapy with a follow-up over 9 years. Eur J Pediatr 2000; 159(10): 750–8PubMedGoogle Scholar
  15. 15.
    Humpl T, Fritsche M, Bartels U, et al. Survivors of childhood cancer for more than twenty years. Acta Oncol 2001; 40(1): 44–9PubMedGoogle Scholar
  16. 16.
    Pastore G, Mosso ML, Magnani C, et al. Physical impairment and social life goals among adult long-term survivors of childhood cancer: a population-based study from the childhood cancer registry of Piedmont, Italy. Tumori 2001; 87(6): 372–8PubMedGoogle Scholar
  17. 17.
    Mertens AC, Yasui Y, Neglia JP, et al. Late mortality experience in five-year survivors of childhood and adolescent cancer: the Childhood Cancer Survivor Study. J Clin Oncol 2001; 19(13): 3163–72PubMedGoogle Scholar
  18. 18.
    Frei III E, Karon M, Levin RH, et al. The effectiveness of combinations of antileukemic agents in inducing and maintaining remission in children with acute leukemia. Blood 1965; 26(5): 642–56PubMedGoogle Scholar
  19. 19.
    Hudson MM, Jones D, Boyett J, et al. Late mortality of long-term survivors of childhood cancer. J Clin Oncol 1997; 15(6): 2205–13PubMedGoogle Scholar
  20. 20.
    Moller TR, Garwicz S, Barlow L, et al. Decreasing late mortality among five-year survivors of cancer in childhood and adolescence: a population-based study in the Nordic countries. J Clin Oncol 2001; 19(13): 3173–81PubMedGoogle Scholar
  21. 21.
    Robertson CM, Hawkins MM, Kingston JE. Late deaths and survival after childhood cancer: implications for cure. BMJ 1994; 309(6948): 162–6PubMedGoogle Scholar
  22. 22.
    Jazbec J, Ecimovic P, Jereb B. Second neoplasms after treatment of childhood cancer in Slovenia. Pediatr Blood Cancer 2004; 42(7): 574–81PubMedGoogle Scholar
  23. 23.
    Robison LL, Mertens A. Second tumors after treatment of childhood malignancies. Hematol Oncol Clin North Am 1993; 7(2): 401–15PubMedGoogle Scholar
  24. 24.
    Neglia JP, Friedman DL, Yasui Y, et al. Second malignant neoplasms in five-year survivors of childhood cancer: childhood cancer survivor study. J Natl Cancer Inst 2001; 93(8): 618–29PubMedGoogle Scholar
  25. 25.
    Wong FL, Boice Jr JD, Abramson DH, et al. Cancer incidence after retinoblastoma: radiation dose and sarcoma risk. JAMA 1997; 278(15): 1262–7PubMedGoogle Scholar
  26. 26.
    Moll AC, Imhof SM, Schouten-Van Meeteren AY, et al. Second primary tumors in hereditary retinoblastoma: a register-based study, 1945–1997: is there an age effect on radiation-related risk? Ophthalmology 2001; 108(6): 1109–14PubMedGoogle Scholar
  27. 27.
    Garwicz S, Anderson H, Olsen JH, et al. 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 2000; 88(4): 672–8PubMedGoogle Scholar
  28. 28.
    Bhatia S, Yasui Y, Robison LL, 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): 4386–94PubMedGoogle Scholar
  29. 29.
    Bhatia S, Robison LL, Oberlin O, et al. Breast cancer and other second neoplasms after childhood Hodgkin’s disease. N Engl J Med 1996; 334(12): 745–51PubMedGoogle Scholar
  30. 30.
    Wahner-Roedler DL, Nelson DF, Croghan IT, et al. Risk of breast cancer and breast cancer characteristics in women treated with supradiaphragmatic radiation for Hodgkin lymphoma: Mayo Clinic experience. Mayo Clin Proc 2003; 78(6): 708–15PubMedGoogle Scholar
  31. 31.
    Clemons M, Loijens L, Goss P. Breast cancer risk following irradiation for Hodgkin’s disease. Cancer Treat Rev 2000; 26(4): 291–302PubMedGoogle Scholar
  32. 32.
    Sklar C, Whitton J, Mertens A, 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): 3227–32PubMedGoogle Scholar
  33. 33.
    Inskip PD. Thyroid cancer after radiotherapy for childhood cancer. Med Pediatr Oncol 2001; 36(5): 568–73PubMedGoogle Scholar
  34. 34.
    Felix CA. Leukemias related to treatment with DNA topoisomerase II inhibitors. Med Pediatr Oncol 2001; 36(5): 525–35PubMedGoogle Scholar
  35. 35.
    Green DM, Zevon MA, Reese PA, et al. Second malignant tumors following treatment during childhood and adolescence for cancer. Med Pediatr Oncol 1994; 22(1): 1–10PubMedGoogle Scholar
  36. 36.
    Klein G, Michaelis J, Spix C, et al. Second malignant neoplasms after treatment of childhood cancer. Eur J Cancer 2003; 39(6): 808–17PubMedGoogle Scholar
  37. 37.
    Le Deley MC, Leblanc T, Shamsaldin A, et al. Risk of secondary leukemia after a solid tumor in childhood according to the dose of epipodophyllotoxins and anthracyclines: a case-control study by the Societe Francaise d’Oncologie Pediatrique. J Clin Oncol 2003; 21(6): 1074–81PubMedGoogle Scholar
  38. 38.
    Smith MA, Rubinstein L, Anderson JR, et al. Secondary leukemia or myelodys-plastic syndrome after treatment with epipodophyllotoxins. J Clin Oncol 1999; 17(2): 569–77PubMedGoogle Scholar
  39. 39.
    Swerdlow AJ, Schoemaker MJ, Allerton R, et al. Lung cancer after Hodgkin’s disease: a nested case-control study of the relation to treatment. J Clin Oncol 2001; 19(6): 1610–8PubMedGoogle Scholar
  40. 40.
    Swerdlow AJ, Barber JA, Hudson GV, et al. Risk of second malignancy after Hodgkin’s disease in a collaborative British cohort: the relation to age at treatment. J Clin Oncol 2000; 18(3): 498–509PubMedGoogle Scholar
  41. 41.
    van Leeuwen FE, Klokman WJ, Veer MB, et al. Long-term risk of second malignancy in survivors of Hodgkin’s disease treated during adolescence or young adulthood. J Clin Oncol 2000; 18(3): 487–97PubMedGoogle Scholar
  42. 42.
    Metayer C, Lynch CF, Clarke EA, et al. Second cancers among long-term survivors of Hodgkin’s disease diagnosed in childhood and adolescence. J Clin Oncol 2000; 18(12): 2435–43PubMedGoogle Scholar
  43. 43.
    de Vathaire F, Hawkins M, Campbell S, et al. Second malignant neoplasms after a first cancer in childhood: temporal pattern of risk according to type of treatment. Br J Cancer 1999; 79(11–12): 1884–93PubMedGoogle Scholar
  44. 44.
    van Leeuwen FE, Klokman WJ, Stovall M, et al. Roles of radiotherapy and smoking in lung cancer following Hodgkin’s disease. J Natl Cancer Inst 1995; 87(20): 1530–7PubMedGoogle Scholar
  45. 45.
    Giovannucci E. Alcohol, one-carbon metabolism, and colorectal cancer: recent insights from molecular studies. J Nutr 2004; 134(9): 2475S–81SPubMedGoogle Scholar
  46. 46.
    Cutuli B, Borel C, Dhermain F, et al. Breast cancer occurred after treatment for Hodgkin’s disease: analysis of 133 cases. Radiother Oncol 2001; 59(3): 247–55PubMedGoogle Scholar
  47. 47.
    Diller L, Medeiros Nancarrow C, Shaffer K, et al. Breast cancer screening in women previously treated for Hodgkin’s disease: a prospective cohort study. J Clin Oncol 2002; 20(8): 2085–91PubMedGoogle Scholar
  48. 48.
    Wolden SL, Hancock SL, Carlson RW, et al. Management of breast cancer after Hodgkin’s disease. J Clin Oncol 2000; 18(4): 765–72PubMedGoogle Scholar
  49. 49.
    Gow KW, Lensing S, Hill DA, et al. Thyroid carcinoma presenting in childhood or after treatment of childhood malignancies: an institutional experience and review of the literature. J Pediatr Surg 2003; 38(11): 1574–80PubMedGoogle Scholar
  50. 50.
    Packer RJ, Gurney JG, Punyko JA, et al. Long-term neurologic and neurosensory sequelae in adult survivors of a childhood brain tumor: childhood cancer survivor study. J Clin Oncol 2003; 21(17): 3255–61PubMedGoogle Scholar
  51. 51.
    Sonderkaer S, Schmiegelow M, Carstensen H, et al. Long-term neurological outcome of childhood brain tumors treated by surgery only. J Clin Oncol 2003; 21(7): 1347–51PubMedGoogle Scholar
  52. 52.
    Syndikus I, Tait D, Ashley S, et al. Long-term follow-up of young children with brain tumors after irradiation. Int J Radiat Oncol Biol Phys 1994; 30(4): 781–7PubMedGoogle Scholar
  53. 53.
    Gurney JG, Kadan-Lottick NS, Packer RJ, et al. Endocrine and cardiovascular late effects among adult survivors of childhood brain tumors: Childhood Cancer Survivor Study. Cancer 2003; 97(3): 663–73PubMedGoogle Scholar
  54. 54.
    Ross L, Johansen C, Dalton SO, et al. Psychiatric hospitalizations among survivors of cancer in childhood or adolescence. N Engl J Med 2003; 349(7): 650–7PubMedGoogle Scholar
  55. 55.
    Butler RW, Copeland DR. Neuropsychological effects of central nervous system prophylactic treatment in childhood leukemia: methodological considerations. J Pediatr Psychol 1993; 18(3): 319–38PubMedGoogle Scholar
  56. 56.
    Meadows AT, Gordon J, Massari DJ, et al. Declines in IQ scores and cognitive dysfunctions in children with acute lymphocytic leukaemia treated with cranial irradiation. Lancet 1981; II(8254): 1015–8Google Scholar
  57. 57.
    Hill JM, Kornblith AB, Jones D, et al. A comparative study of the long term psychosocial functioning of childhood acute lymphoblastic leukemia survivors treated by intrathecal methotrexate with or without cranial radiation. Cancer 1998; 82(1): 208–18PubMedGoogle Scholar
  58. 58.
    Waber DP, Shapiro BL, Carpentieri SC, et al. Excellent therapeutic efficacy and minimal late neurotoxicity in children treated with 18 grays of cranial radiation therapy for high-risk acute lymphoblastic leukemia: a 7-year follow-up study of the Dana-Farber Cancer Institute Consortium Protocol 87–01. Cancer 2001; 92(1): 15–22PubMedGoogle Scholar
  59. 59.
    Smibert E, Anderson V, Godber T, et al. Risk factors for intellectual and educational sequelae of cranial irradiation in childhood acute lymphoblastic leukaemia. Br J Cancer 1996; 73(6): 825–30PubMedGoogle Scholar
  60. 60.
    Waber DP, Tarbell NJ, Fairclough D, et al. Cognitive sequelae of treatment in childhood acute lymphoblastic leukemia: cranial radiation requires an accomplice. J Clin Oncol 1995; 13(10): 2490–6PubMedGoogle Scholar
  61. 61.
    Jankovic M, Brouwers P, Valsecchi MG, et al. Association of 1800 cGy cranial irradiation with intellectual function in children with acute lymphoblastic leukaemia: ISPACC. International Study Group on Psychosocial Aspects of Childhood Cancer. Lancet 1994; 344(8917): 224–7PubMedGoogle Scholar
  62. 62.
    Moore IM, Kramer JH, Wara W, et al. Cognitive function in children with leukemia: effect of radiation dose and time since irradiation. Cancer 1991; 68(9): 1913–7PubMedGoogle Scholar
  63. 63.
    Clarke M, Gaynon P, Hann I, et al. CNS-directed therapy for childhood acute lymphoblastic leukemia: Childhood ALL Collaborative Group overview of 43 randomized trials. J Clin Oncol 2003; 21(9): 1798–809PubMedGoogle Scholar
  64. 64.
    Kingma A, van Dommelen RI, Mooyaart EL, et al. Slight cognitive impairment and magnetic resonance imaging abnormalities but normal school levels in children treated for acute lymphoblastic leukemia with chemotherapy only. J Pediatr 2001; 139(3): 413–20PubMedGoogle Scholar
  65. 65.
    Kingma A, Van Dommelen RI, Mooyaart EL, et al. No major cognitive impairment in young children with acute lymphoblastic leukemia using chemotherapy only: a prospective longitudinal study. J Pediatr Hematol Oncol 2002; 24(2): 106–14PubMedGoogle Scholar
  66. 66.
    Vilmer E, Suciu S, Ferster A, et al. Long-term results of three randomized trials (58831, 58832, 58881) in childhood acute lymphoblastic leukemia: a CLCG-EORTC report. Children Leukemia Cooperative Group. Leukemia 2000; 14(12): 2257–66PubMedGoogle Scholar
  67. 67.
    Hill FG, Richards S, Gibson B, et al. Successful treatment without cranial radiotherapy of children receiving intensified chemotherapy for acute lymphoblastic leukaemia: results of the risk-stratified randomized central nervous system treatment trial MRC UKALL XI (ISRC TN 16757172). Br J Haematol 2004; 124(1): 33–46PubMedGoogle Scholar
  68. 68.
    Noll RB, Gartstein MA, Vannatta K, et al. Social, emotional, and behavioral functioning of children with cancer. Pediatrics 1999; 103(1): 71–8PubMedGoogle Scholar
  69. 69.
    Glover DA, Byrne J, Mills JL, et al. Impact of CNS treatment on mood in adult survivors of childhood leukemia: a report from the Children’s Cancer Group. J Clin Oncol 2003; 21(23): 4395–401PubMedGoogle Scholar
  70. 70.
    Langeveld N, Ubbink M, Smets E. ‘I don’t have any energy’: the experience of fatigue in young adult survivors of childhood cancer. Eur J Oncol Nurs 2000; 4(1): 20–8PubMedGoogle Scholar
  71. 71.
    Langeveld NE, Grootenhuis MA, Voute PA, et al. No excess fatigue in young adult survivors of childhood cancer. Eur J Cancer 2003; 39(2): 204–14PubMedGoogle Scholar
  72. 72.
    Noorda EM, Somers R, van Leeuwen FE, et al. Adult height and age at menarche in childhood cancer survivors. Eur J Cancer 2001; 37(5): 605–12PubMedGoogle Scholar
  73. 73.
    Probert JC, Parker BR. The effects of radiation therapy on bone growth. Radiology 1975; 114(1): 155–62PubMedGoogle Scholar
  74. 74.
    Gurney JG, Ness KK, Stovall M, 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): 4731–9PubMedGoogle Scholar
  75. 75.
    Howard SC, Pui CH. Endocrine complications in pediatric patients with acute lymphoblastic leukemia. Blood Rev 2002; 16(4): 225–43PubMedGoogle Scholar
  76. 76.
    Shalet SM, Brennan BM. Growth and growth hormone status following treatment for childhood leukaemia. Horm Res 1998; 50(1): 1–10PubMedGoogle Scholar
  77. 77.
    Birkebaek NH, Clausen N. Height and weight pattern up to 20 years after treatment for acute lymphoblastic leukaemia. Arch Dis Child 1998; 79(2): 161–4PubMedGoogle Scholar
  78. 78.
    Holm K, Nysom K, Hertz H, et al. Normal final height after treatment for acute lymphoblastic leukemia without irradiation. Acta Paediatr 1994; 83(12): 1287–90PubMedGoogle Scholar
  79. 79.
    Dalton VK, Rue M, Silverman LB, et al. Height and weight in children treated for acute lymphoblastic leukemia: relationship to CNS treatment. J Clin Oncol 2003; 21(15): 2953–60PubMedGoogle Scholar
  80. 80.
    Robison LL, Bhatia S. Late-effects among survivors of leukaemia and lymphoma during childhood and adolescence. Br J Haematol 2003; 122(3): 345–59PubMedGoogle Scholar
  81. 81.
    Sklar C, Mertens A, Walter A, et al. Final height after treatment for childhood acute lymphoblastic leukemia: comparison of no cranial irradiation with 1800 and 2400 centigrays of cranial irradiation. J Pediatr 1993; 123(1): 59–64PubMedGoogle Scholar
  82. 82.
    Cicognani A, Cacciari E, Rosito P, et al. Longitudinal growth and final height in long-term survivors of childhood leukaemia. Eur J Pediatr 1994; 153(10): 726–30PubMedGoogle Scholar
  83. 83.
    Rose SR, Schreiber RE, Kearney NS, et al. Hypothalamic dysfunction after chemotherapy. J Pediatr Endocrinol Metab 2004; 17(1): 55–66PubMedGoogle Scholar
  84. 84.
    Cohen LE. Endocrine late effects of cancer treatment. Endo Metab Clin North Am 2005; 34(3): 769–80Google Scholar
  85. 85.
    Gleeson HK, Stoeter R, Ogilvy-Stuart AL, et al. Improvements in final height over 25 years in growth hormone (GH)-deficient childhood survivors of brain tumors receiving GH replacement. J Clin Endocrinol Metab 2003; 88(8): 3682–9PubMedGoogle Scholar
  86. 86.
    Gleeson HK, Shalet SM. Endocrine complications of neoplastic diseases in children and adolescents. Curr Opin Pediatr 2001; 13(4): 346–51PubMedGoogle Scholar
  87. 87.
    Murray RD, Darzy KH, Gleeson HK, et al. GH-deficient survivors of childhood cancer: GH replacement during adult life. J Clin Endocrinol Metab 2002; 87(1): 129–35PubMedGoogle Scholar
  88. 88.
    Leung W, Rose SR, Zhou Y, et al. Outcomes of growth hormone replacement therapy in survivors of childhood acute lymphoblastic leukemia. J Clin Oncol 2002; 20(13): 2959–64PubMedGoogle Scholar
  89. 89.
    Swerdlow AJ, Reddingius RE, Higgins CD, et al. Growth hormone treatment of children with brain tumors and risk of tumor recurrence. J Clin Endocrinol Metab 2000; 85(12): 4444–9PubMedGoogle Scholar
  90. 90.
    Sklar CA, Mertens AC, Mitby P, et al. Risk of disease recurrence and second neoplasms in survivors of childhood cancer treated with growth hormone: a report from the Childhood Cancer Survivor Study. J Clin Endocrinol Metab 2002; 87(7): 3136–41PubMedGoogle Scholar
  91. 91.
    Packer RJ, Boyett JM, Janss AJ, et al. Growth hormone replacement therapy in children with medulloblastoma: use and effect on tumor control. J Clin Oncol 2001; 19(2): 480–7PubMedGoogle Scholar
  92. 92.
    Lustig RH, Post SR, Srivannaboon K, et al. Risk factors for the development of obesity in children surviving brain tumors. J Clin Endocrinol Metab 2003; 88(2): 611–6PubMedGoogle Scholar
  93. 93.
    Oeffinger KC, Mertens AC, Sklar CA, et al. Obesity in adult survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. J Clin Oncol 2003; 21(7): 1359–65PubMedGoogle Scholar
  94. 94.
    Didi M, Didcock E, Davies HA, et al. High incidence of obesity in young adults after treatment of acute lymphoblastic leukemia in childhood. J Pediatr 1995; 127(1): 63–7PubMedGoogle Scholar
  95. 95.
    Warner JT, Evans WD, Webb DK, et al. Body composition of long-term survivors of acute lymphoblastic leukaemia. Med Pediatr Oncol 2002; 38(3): 165–72PubMedGoogle Scholar
  96. 96.
    Lustig RH, Hinds PS, Ringwald-Smith K, et al. Octreotide therapy of pediatric hypothalamic obesity: a double-blind, placebo-controlled trial. J Clin Endocrinol Metab 2003; 88(6): 2586–92PubMedGoogle Scholar
  97. 97.
    Reilly JJ, Ventham JC, Ralston JM, et al. Reduced energy expenditure in preobese children treated for acute lymphoblastic leukemia. Pediatr Res 1998; 44(4): 557–62PubMedGoogle Scholar
  98. 98.
    Reilly JJ, Kelly A, Ness P, et al. Premature adiposity rebound in children treated for acute lymphoblastic leukemia. J Clin Endocrinol Metab 2001; 86(6): 2775–8PubMedGoogle Scholar
  99. 99.
    van Santen HM, Vulsma T, Dijkgraaf MG, et al. No damaging effect of chemotherapy in addition to radiotherapy on the thyroid axis in young adult survivors of childhood cancer. J Clin Endocrinol Metab 2003; 88(8): 3657–63PubMedGoogle Scholar
  100. 100.
    Schmiegelow M, Feldt-Rasmussen U, Rasmussen AK, et al. Assessment of the hypothalamo-pituitary-adrenal axis in patients treated with radiotherapy and chemotherapy for childhood brain tumor. J Clin Endocrinol Metab 2003; 88(7): 3149–54PubMedGoogle Scholar
  101. 101.
    Cicognani A, Pasini A, Pession A, et al. Gonadal function and pubertal development after treatment of a childhood malignancy. J Pediatr Endocrinol Metab 2003; 16Suppl. 2: 321–6PubMedGoogle Scholar
  102. 102.
    Muller J. Disturbance of pubertal development after cancer treatment. Best Pract Res Clin Endocrinol Metab 2002; 16(1): 91–103PubMedGoogle Scholar
  103. 103.
    Chiarelli AM, Marrett LD, Darlington G. Early menopause and infertility in females after treatment for childhood cancer diagnosed in 1964–1988 in Ontario, Canada. Am J Epidemiol 1999; 150(3): 245–54PubMedGoogle Scholar
  104. 104.
    Larsen EC, Muller J, Schmiegelow K, et al. Reduced ovarian function in long-term survivors of radiation- and chemotherapy-treated childhood cancer. J Clin Endocrinol Metab 2003; 88(11): 5307–14PubMedGoogle Scholar
  105. 105.
    Byrne J, Mulvihill JJ, Myers MH, et al. Effects of treatment on fertility in long-term survivors of childhood or adolescent cancer. N Engl J Med 1987; 317(21): 1315–21PubMedGoogle Scholar
  106. 106.
    Stillman RJ, Schinfeld JS, Schiff I, et al. Ovarian failure in long-term survivors of childhood malignancy. Am J Obstet Gynecol 1981; 139(1): 62–6PubMedGoogle Scholar
  107. 107.
    Teinturier C, Hartmann O, Valteau-Couanet D, et al. Ovarian function after autologous bone marrow transplantation in childhood: high-dose busulfan is a major cause of ovarian failure. Bone Marrow Transplant 1998; 22(10): 989–94PubMedGoogle Scholar
  108. 108.
    Thibaud E, Rodriguez-Macias K, Trivin C, et al. Ovarian function after bone marrow transplantation during childhood. Bone Marrow Transplant 1998; 21(3): 287–90PubMedGoogle Scholar
  109. 109.
    Blatt J. Pregnancy outcome in long-term survivors of childhood cancer. Med Pediatr Oncol 1999; 33(1): 29–33PubMedGoogle Scholar
  110. 110.
    Green DM, Whitton JA, Stovall M, et al. Pregnancy outcome of female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Am J Obstet Gynecol 2002; 187(4): 1070–80PubMedGoogle Scholar
  111. 111.
    Green DM, Zevon MA, Lowrie G, et al. Congenital anomalies in children of patients who received chemotherapy for cancer in childhood and adolescence. N Engl J Med 1991; 325(3): 141–6PubMedGoogle Scholar
  112. 112.
    Green DM, Fiorello A, Zevon MA, et al. Birth defects and childhood cancer in offspring of survivors of childhood cancer. Arch Pediatr Adolesc Med 1997; 151(4): 379–83PubMedGoogle Scholar
  113. 113.
    Mustieles C, Munoz A, Alonso M, et al. Male gonadal function after chemotherapy in survivors of childhood malignancy. Med Pediatr Oncol 1995; 24(6): 347–51PubMedGoogle Scholar
  114. 114.
    Colpi GM, Contalbi GF, Nerva F, et al. Testicular function following chemoradiotherapy. Eur J Obstet Gynecol Reprod Biol 2004; 113Suppl. 1: S2–6PubMedGoogle Scholar
  115. 115.
    Green DM, Whitton JA, Stovall M, et al. Pregnancy outcome of partners of male survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 2003; 21(4): 716–21PubMedGoogle Scholar
  116. 116.
    Kenney LB, Laufer MR, Grant FD, et al. High risk of infertility and long term gonadal damage in males treated with high dose cyclophosphamide for sarcoma during childhood. Cancer 2001; 91(3): 613–21PubMedGoogle Scholar
  117. 117.
    Heikens J, Behrendt H, Adriaanse R, et al. Irreversible gonadal damage in male survivors of pediatric Hodgkin’s disease. Cancer 1996; 78(9): 2020–4PubMedGoogle Scholar
  118. 118.
    Ogilvy-Stuart AL, Shalet SM. Effect of radiation on the human reproductive system. Environ Health Perspect 1993; 101Suppl. 2: 109–16PubMedGoogle Scholar
  119. 119.
    Byrne J, Fears TR, Mills JL, et al. Fertility of long-term male survivors of acute lymphoblastic leukemia diagnosed during childhood. Pediatr Blood Cancer 2004; 42(7): 589–97PubMedGoogle Scholar
  120. 120.
    Lefrak EA, Pitha J, Rosenheim S, et al. A clinicopathologic analysis of adriamycin cardiotoxicity. Cancer 1973; 32(2): 302–14PubMedGoogle Scholar
  121. 121.
    Bristow MR, Billingham ME, Mason JW, et al. Clinical spectrum of anthracycline antibiotic cardiotoxicity. Cancer Treat Rep 1978; 62(6): 873–9PubMedGoogle Scholar
  122. 122.
    Nysom K, Holm K, Lipsitz SR, et al. Relationship between cumulative anthra-cycline dose and late cardiotoxicity in childhood acute lymphoblastic leukemia. J Clin Oncol 1998; 16(2): 545–50PubMedGoogle Scholar
  123. 123.
    Ewer MS, Jaffe N, Ried H, et al. Doxorubicin cardiotoxicity in children: comparison of a consecutive divided daily dose administration schedule with single dose (rapid) infusion administration. Med Pediatr Oncol 1998; 31(6): 512–5PubMedGoogle Scholar
  124. 124.
    Steinherz LJ, Steinherz PG, Tan CT, et al. Cardiac toxicity 4 to 20 years after completing anthracycline therapy. JAMA 1991; 266(12): 1672–7PubMedGoogle Scholar
  125. 125.
    Sorensen K, Levitt GA, Bull C, et al. Late anthracycline cardiotoxicity after childhood cancer: a prospective longitudinal study. Cancer 2003; 97(8): 1991–8PubMedGoogle Scholar
  126. 126.
    Von Hoff DD, Layard MW, Basa P, et al. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med 1979; 91(5): 710–7Google Scholar
  127. 127.
    Kremer LC, van Dalen EC, Offringa M, et al. Anthracycline-induced clinical heart failure in a cohort of 607 children: long-term follow-up study. J Clin Oncol 2001; 19(1): 191–6PubMedGoogle Scholar
  128. 128.
    Poutanen T, Tikanoja T, Riikonen P, et al. Long-term prospective follow-up study of cardiac function after cardiotoxic therapy for malignancy in children. J Clin Oncol 2003; 21(12): 2349–56PubMedGoogle Scholar
  129. 129.
    Minow RA, Benjamin RS, Lee ET, et al. Adriamycin cardiomyopathy: risk factors. Cancer 1977; 39(4): 1397–402PubMedGoogle Scholar
  130. 130.
    Billingham ME, Bristow MR, Glatstein E, et al. Adriamycin cardiotoxicity: endo-myocardial biopsy evidence of enhancement by irradiation. Am J Surg Pathol 1977; 1(1): 17–23PubMedGoogle Scholar
  131. 131.
    Bar J, Davidi O, Goshen Y, et al. Pregnancy outcome in women treated with doxorubicin for childhood cancer. Am J Obstet Gynecol 2003; 189(3): 853–7PubMedGoogle Scholar
  132. 132.
    Lipshultz SE, Lipsitz SR, Sallan SE, et al. Long-term enalapril therapy for left ventricular dysfunction in doxorubicin-treated survivors of childhood cancer. J Clin Oncol 2002; 20(23): 4517–22PubMedGoogle Scholar
  133. 133.
    Gupta M, Steinherz PG, Cheung NK, et al. Late cardiotoxicity after bolus versus infusion anthracycline therapy for childhood cancers. Med Pediatr Oncol 2003; 40(6): 343–7PubMedGoogle Scholar
  134. 134.
    Safra T. Cardiac safety of liposomal anthracyclines. Oncologist 2003; 8Suppl. 2: 17–24PubMedGoogle Scholar
  135. 135.
    Wexler LH. Ameliorating anthracycline cardiotoxicity in children with cancer: clinical trials with dexrazoxane. Semin Oncol 1998; 25 (4 Suppl. 10): 86–92PubMedGoogle Scholar
  136. 136.
    Wexler LH, Andrich MP, Venzon D, et al. Randomized trial of the cardioprotective agent ICRF-187 in pediatric sarcoma patients treated with doxorubicin. J Clin Oncol 1996; 14(2): 362–72PubMedGoogle Scholar
  137. 137.
    Arsenian MA. Cardiovascular sequelae of therapeutic thoracic radiation. Prog Cardiovasc Dis 1991; 33(5): 299–311PubMedGoogle Scholar
  138. 138.
    Hull MC, Morris CG, Pepine CJ, et al. Valvular dysfunction and carotid, subclavian, and coronary artery disease in survivors of Hodgkin lymphoma treated with radiation therapy. JAMA 2003; 290(21): 2831–7PubMedGoogle Scholar
  139. 139.
    Adams MJ, Lipshultz SE, Schwartz C, et al. Radiation-associated cardiovascular disease: manifestations and management. Semin Radiat Oncol 2003; 13(3): 346–56PubMedGoogle Scholar
  140. 140.
    Constine LS, Schwartz RG, Savage DE, et al. Cardiac function, perfusion, and morbidity in irradiated long-term survivors of Hodgkin’s disease. Int J Radiat Oncol Biol Phys 1997; 39(4): 897–906PubMedGoogle Scholar
  141. 141.
    Silber JH, Cnaan A, Clark BJ, et al. Enalapril to prevent cardiac function decline in long-term survivors of pediatric cancer exposed to anthracyclines. J Clin Oncol 2004; 22(5): 820–8PubMedGoogle Scholar
  142. 142.
    Steinherz LJ, Graham T, Hurwitz R, et al. Guidelines for cardiac monitoring of children during and after anthracycline therapy: report of the Cardiology Committee of the Childrens Cancer Study Group. Pediatrics 1992; 89 (5 Pt 1): 942–9PubMedGoogle Scholar
  143. 143.
    Abid SH, Malhotra V, Perry MC. Radiation-induced and chemotherapy-induced pulmonary injury. Curr Opin Oncol 2001; 13(4): 242–8PubMedGoogle Scholar
  144. 144.
    Mertens AC, Yasui Y, Liu Y, et al. Pulmonary complications in survivors of childhood and adolescent cancer: a report from the Childhood Cancer Survivor Study. Cancer 2002; 95(11): 2431–41PubMedGoogle Scholar
  145. 145.
    Nysom K, Holm K, Olsen JH, et al. Pulmonary function after treatment for acute lymphoblastic leukaemia in childhood. Br J Cancer 1998; 78(1): 21–7PubMedGoogle Scholar
  146. 146.
    Fulgoni P, Zoia MC, Corsico A, et al. Lung function in survivors of childhood acute lymphoblastic leukemia. Chest 1999; 116(5): 1163–7PubMedGoogle Scholar
  147. 147.
    Ellis ER, Marcus Jr RB, Cicale MJ, et al. Pulmonary function tests after whole-lung irradiation and doxorubicin in patients with osteogenic sarcoma. J Clin Oncol 1992; 10(3): 459–63PubMedGoogle Scholar
  148. 148.
    Kaplan E, Sklar C, Wilmott R, et al. Pulmonary function in children treated for rhabdomyosarcoma. Med Pediatr Oncol 1996; 27(2): 79–84PubMedGoogle Scholar
  149. 149.
    Kharasch VS, Lipsitz S, Santis W, et al. Long-term pulmonary toxicity of multi-agent chemotherapy including bleomycin and cyclophosphamide in osteosarcoma survivors. Med Pediatr Oncol 1996; 27(2): 85–91PubMedGoogle Scholar
  150. 150.
    Lund MB, Kongerud J, Nome O, et al. Lung function impairment in long-term survivors of Hodgkin’s disease. Ann Oncol 1995; 6(5): 495–501PubMedGoogle Scholar
  151. 151.
    Bossi G, Cerveri I, Volpini E, et al. Long-term pulmonary sequelae after treatment of childhood Hodgkin’s disease. Ann Oncol 1997; 8Suppl. 1: 19–24PubMedGoogle Scholar
  152. 152.
    Cerveri I, Zoia MC, Fulgoni P, et al. Late pulmonary sequelae after childhood bone marrow transplantation. Thorax 1999; 54(2): 131–5PubMedGoogle Scholar
  153. 153.
    Cerveri I, Fulgoni P, Giorgiani G, et al. Lung function abnormalities after bone marrow transplantation in children: has the trend recently changed? Chest 2001; 120(6): 1900–6PubMedGoogle Scholar
  154. 154.
    Neve V, Foot AB, Michon J, et al. Longitudinal clinical and functional pulmonary follow-up after megatherapy, fractionated total body irradiation, and autologous bone marrow transplantation for metastatic neuroblastoma. Med Pediatr Oncol 1999; 32(3): 170–6PubMedGoogle Scholar
  155. 155.
    Nenadov Beck M, Meresse V, Hartmann O, et al. Long-term pulmonary sequelae after autologous bone marrow transplantation in children without total body irradiation. Bone Marrow Transplant 1995; 16(6): 771–5PubMedGoogle Scholar
  156. 156.
    Movsas B, Raffin TA, Epstein AH, et al. Pulmonary radiation injury. Chest 1997; 111(4): 1061–76PubMedGoogle Scholar
  157. 157.
    Hansen SW, Groth S, Sorensen PG, et al. Enhanced pulmonary toxicity in smokers with germ-cell cancer treated with cis-platinum, vinblastine and bleomycin: a long-term follow-up. Eur J Cancer Clin Oncol 1989; 25(4): 733–6PubMedGoogle Scholar
  158. 158.
    Kakihara T, Imai C, Hotta H, et al. Impaired tubular excretory function as a late renal side effect of chemotherapy in children. J Pediatr Hematol Oncol 2003; 25(3): 209–14PubMedGoogle Scholar
  159. 159.
    Suarez A, McDowell H, Niaudet P, et al. Long-term follow-up of ifosfamide renal toxicity in children treated for malignant mesenchymal tumors: an International Society of Pediatric Oncology report. J Clin Oncol 1991; 9(12): 2177–82PubMedGoogle Scholar
  160. 160.
    Ho PT, Zimmerman K, Wexler LH, et al. A prospective evaluation of ifosfamide-related nephrotoxicity in children and young adults. Cancer 1995; 76(12): 2557–64PubMedGoogle Scholar
  161. 161.
    Loebstein R, Atanackovic G, Bishai R, et al. Risk factors for long-term outcome of ifosfamide-induced nephrotoxicity in children. J Clin Pharmacol 1999; 39(5): 454–61PubMedGoogle Scholar
  162. 162.
    Skinner R. Chronic ifosfamide nephrotoxicity in children. Med Pediatr Oncol 2003; 41(3): 190–7PubMedGoogle Scholar
  163. 163.
    Liesner RJ, Leiper AD, Hann IM, et al. Late effects of intensive treatment for acute myeloid leukemia and myelodysplasia in childhood. J Clin Oncol 1994; 12(5): 916–24PubMedGoogle Scholar
  164. 164.
    Ritchey ML, Green DM, Thomas PR, et al. Renal failure in Wilms’ tumor patients: a report from the National Wilms’ Tumor Study Group. Med Pediatr Oncol 1996; 26(2): 75–80PubMedGoogle Scholar
  165. 165.
    Miser JS, Kinsella TJ, Triche TJ, et al. Ifosfamide with mesna uroprotection and etoposide: an effective regimen in the treatment of recurrent sarcomas and other tumors of children and young adults. J Clin Oncol 1987; 5(8): 1191–8PubMedGoogle Scholar
  166. 166.
    Vogelzang NJ. Nephrotoxicity from chemotherapy: prevention and management. Oncology (Huntingt) 1991; 5(10): 97–102, 105Google Scholar
  167. 167.
    Antman KH, Elias A, Ryan L. Ifosfamide and mesna: response and toxicity at standard- and high-dose schedules. Semin Oncol 1990; 17 (2 Suppl. 4): 68–73PubMedGoogle Scholar
  168. 168.
    Halonen P, Mattila J, Ruuska T, et al. Liver histology after current intensified therapy for childhood acute lymphoblastic leukemia: microvesicular fatty change and siderosis are the main findings. Med Pediatr Oncol 2003; 40(3): 148–54PubMedGoogle Scholar
  169. 169.
    Strasser SI, Sullivan KM, Myerson D, et al. Cirrhosis of the liver in long-term marrow transplant survivors. Blood 1999; 93(10): 3259–66PubMedGoogle Scholar
  170. 170.
    Leonard MB. Assessment of bone health in children and adolescents with cancer: promises and pitfalls of current techniques. Med Pediatr Oncol 2003; 41(3): 198–207PubMedGoogle Scholar
  171. 171.
    Henderson RC, Madsen CD, Davis C, et al. Bone density in survivors of childhood malignancies. J Pediatr Hematol Oncol 1996; 18(4): 367–71PubMedGoogle Scholar
  172. 172.
    Kadan-Lottick N, Marshall JA, Baron AE, et al. Normal bone mineral density after treatment for childhood acute lymphoblastic leukemia diagnosed between 1991 and 1998. J Pediatr 2001; 138(6): 898–904PubMedGoogle Scholar
  173. 173.
    Aisenberg J, Hsieh K, Kalaitzoglou G, et al. Bone mineral density in young adult survivors of childhood cancer. J Pediatr Hematol Oncol 1998; 20(3): 241–5PubMedGoogle Scholar
  174. 174.
    Kaste SC, Jones-Wallace D, Rose SR, et al. Bone mineral decrements in survivors of childhood acute lymphoblastic leukemia: frequency of occurrence and risk factors for their development. Leukemia 2001; 15(5): 728–34PubMedGoogle Scholar
  175. 175.
    Hosalkar HS, Dormans JP. Limb sparing surgery for pediatric musculoskeletal tumors. Pediatr Blood Cancer 2004; 42(4): 295–310PubMedGoogle Scholar
  176. 176.
    Tomita K, Tsuchiya H. Intermediate results and functional evaluation of limb-salvage surgery for osteosarcoma: an intergroup study in Japan. J Surg Oncol 1989; 41(2): 71–6PubMedGoogle Scholar
  177. 177.
    Nagarajan R, Neglia JP, Clohisy DR, et al. Limb salvage and amputation in survivors of pediatric lower-extremity bone tumors: what are the long-term implications? J Clin Oncol 2002; 20(22): 4493–501PubMedGoogle Scholar
  178. 178.
    Refaat Y, Gunnoe J, Hornicek FJ, et al. Comparison of quality of life after amputation or limb salvage. Clin Orthop Relat Res 2002 Apr; (397): 298–305Google Scholar
  179. 179.
    Rougraff BT, Simon MA, Kneisl JS, et al. Limb salvage compared with amputation for osteosarcoma of the distal end of the femur: a long-term oncological, functional, and quality-of-life study. J Bone Joint Surg Am 1994; 76(5): 649–56PubMedGoogle Scholar
  180. 180.
    Hudson MM, Tyc VL, Cremer LK, et al. Patient satisfaction after limb-sparing surgery and amputation for pediatric malignant bone tumors. J Pediatr Oncol Nurs 1998; 15(2): 60–9PubMedGoogle Scholar
  181. 181.
    Postma A, Kingma A, De Ruiter JH, et al. Quality of life in bone tumor patients comparing limb salvage and amputation of the lower extremity. J Surg Oncol 1992; 51(1): 47–51PubMedGoogle Scholar
  182. 182.
    Ham SJ, Schraffordt Koops H, Veth RP, et al. Limb salvage surgery for primary bone sarcoma of the lower extremities: long-term consequences of endopros-thetic reconstructions. Ann Surg Oncol 1998; 5(5): 423–36PubMedGoogle Scholar
  183. 183.
    Grimer RJ, Carter SR, Pynsent PB. The cost-effectiveness of limb salvage for bone tumours. J Bone Joint Surg Br 1997; 79(4): 558–61PubMedGoogle Scholar
  184. 184.
    Hopewell JW. Radiation-therapy effects on bone density. Med Pediatr Oncol 2003; 41(3): 208–11PubMedGoogle Scholar
  185. 185.
    Maguire A, Craft AW, Evans RG, et al. The long-term effects of treatment on the dental condition of children surviving malignant disease. Cancer 1987; 60(10): 2570–5PubMedGoogle Scholar
  186. 186.
    Duggal MS, Curzon ME, Bailey CC, et al. Dental parameters in the long-term survivors of childhood cancer compared with siblings. Oral Oncol 1997; 33(5): 348–53PubMedGoogle Scholar
  187. 187.
    Kaste SC, Hopkins KP, Jones D, et al. Dental abnormalities in children treated for acute lymphoblastic leukemia. Leukemia 1997; 11(6): 792–6PubMedGoogle Scholar
  188. 188.
    Nasman M, Forsberg CM, Dahllof G. Long-term dental development in children after treatment for malignant disease. Eur J Orthod 1997; 19(2): 151–9PubMedGoogle Scholar
  189. 189.
    Duggal MS. Root surface areas in long-term survivors of childhood cancer. Oral Oncol 2003; 39(2): 178–83PubMedGoogle Scholar
  190. 190.
    Jaffe N, Toth BB, Hoar RE, et al. Dental and maxillofacial abnormalities in long-term survivors of childhood cancer: effects of treatment with chemotherapy and radiation to the head and neck. Pediatrics 1984; 73(6): 816–23PubMedGoogle Scholar
  191. 191.
    van Kempen-Harteveld ML, Struikmans H, Kal HB, et al. Cataract after total body irradiation and bone marrow transplantation: degree of visual impairment. Int J Radiat Oncol Biol Phys 2002; 52(5): 1375–80PubMedGoogle Scholar
  192. 192.
    Wilde G, Sjostrand J. A clinical study of radiation cataract formation in adult life following gamma irradiation of the lens in early childhood. Br J Ophthalmol 1997; 81(4): 261–6PubMedGoogle Scholar
  193. 193.
    Raney RB, Anderson JR, Kollath J, et al. Late effects of therapy in 94 patients with localized rhabdomyosarcoma of the orbit: Report from the Intergroup Rhabdo-myosarcoma Study (IRS)-III, 1984–1991. Med Pediatr Oncol 2000; 34(6): 413–20PubMedGoogle Scholar
  194. 194.
    Miettinen S, Laurikainen E, Johansson R, et al. Radiotherapy enhanced ototoxicity of cisplatin in children. Acta Otolaryngol Suppl 1997; 529: 90–4PubMedGoogle Scholar
  195. 195.
    Weatherly RA, Owens JJ, Catlin FI, et al. cis-platinum ototoxicity in children. Laryngoscope 1991; 101(9): 917–24PubMedGoogle Scholar
  196. 196.
    Johannesen TB, Rasmussen K, Winther FO, et al. Late radiation effects on hearing, vestibular function, and taste in brain tumor patients. Int J Radiat Oncol Biol Phys 2002; 53(1): 86–90PubMedGoogle Scholar
  197. 197.
    Notteghem P, Soler C, Dellatolas G, et al. Neuropsychological outcome in long-term survivors of a childhood extracranial solid tumor who have undergone autologous bone marrow transplantation. Bone Marrow Transplant 2003; 31(7): 599–606PubMedGoogle Scholar
  198. 198.
    Goldsby RE, Ablin AR. Surviving childhood cancer; now what? Controversies regarding long-term follow-up. Pediatr Blood Cancer 2004; 43(3): 211–4PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  • Robert E. Goldsby
    • 1
  • Denah R. Taggart
    • 1
  • Arthur R. Ablin
    • 1
  1. 1.Division of Pediatric Hematology/OncologyUniversity of CaliforniaSan FranciscoUSA

Personalised recommendations