Long-term Survivors of Childhood Brain Tumors: Impact on General Health and Quality of Life

Abstract

Purpose of Review

We review and summarize the key issues affecting general health and quality of life (QOL) of pediatric long-term survivors of brain tumors.

Recent Findings

Long-term survivors of brain tumors are at risk of considerable late morbidity and mortality. Lengthening survival in brain tumors has highlighted the deep impact of tumor and its treatment on the physical, psychological, functional, and social health and QOL of these survivors. Evolution in tumor therapy including surgery, radiotherapy, and systemic therapies, etc., has the potential to mitigate this impact to some extent.

Summary

Sensitization of health staff, policy makers, and the primary designers of clinical trials towards integration of QOL end points while measuring survival in brain tumor patients is the need of the hour. New developments in tumor therapeutics must not only provide quantitative gain but also improve the quality of survival in these long-term survivors. While majority of the issues presented pertain to survivorship in pediatric brain tumor population, similar challenges are likely to exist in young adults surviving brain tumors as well.

This is a preview of subscription content, log in to check access.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.

    Papathoma P, Thomopoulos TP, Karalexi MA, Ryzhov A, Zborovskaya A, Dimitrova N, et al. Childhood central nervous system tumours: incidence and time trends in 13 Southern and Eastern European cancer registries. Eur J Cancer. 2015;51(11):1444–55.

    PubMed  Article  Google Scholar 

  2. 2.

    Ullrich NJ, Embry L. Neurocognitive dysfunction in survivors of childhood brain tumors. Semin Pediatr Neurol. 2012;19(1):35–42.

    PubMed  Article  Google Scholar 

  3. 3.

    •• Armstrong GT, Chen Y, Yasui Y, Leisenring W, Gibson TM, Mertens AC, et al. Reduction in late mortality among 5-year survivors of childhood cancer. N Engl J Med. 2016;374(9):833–42. CCSS group studied late mortality in > 34,000 childhood cancer survivors including > 6,000 CNS patients, showing that 40% of deaths are due to health-related causes. Evolution in treatment over two decades directly reduced late mortality by lowering the therapeutic exposure.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  4. 4.

    Labussière M, Boisselier B, Mokhtari K, Di Stefano A-L, Rahimian A, Rossetto M, et al. Combined analysis of TERT, EGFR, and IDH status defines distinct prognostic glioblastoma classes. Neurology. 2014;83(13):1200–6.

    PubMed  Article  Google Scholar 

  5. 5.

    Cairncross G, Wang M, Shaw E, Jenkins R, Brachman D, Buckner J, et al. Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol. 2013;31(3):337–43.

    CAS  PubMed  Article  Google Scholar 

  6. 6.

    Bloom HJ, Wallace EN, Henk JM. The treatment and prognosis of medulloblastoma in children. A study of 82 verified cases. Am J Roentgenol Radium Therapy, Nucl Med. 1969;105(1):43–62.

    CAS  Article  Google Scholar 

  7. 7.

    Mostow EN, Byrne J, Connelly RR, Mulvihill JJ. Quality of life in long-term survivors of CNS tumors of childhood and adolescence. J Clin Oncol. 1991;9(4):592–9.

    CAS  PubMed  Article  Google Scholar 

  8. 8.

    Frange P, Alapetite C, Gaboriaud G, Bours D, Zucker JM, Zerah M, et al. From childhood to adulthood: long-term outcome of medulloblastoma patients. The Institut Curie experience (1980–2000). J Neuro-Oncol. 2009;95(2):271–9.

    CAS  Article  Google Scholar 

  9. 9.

    Hudson MM, Mertens AC, Yasui Y, Hobbie W, Chen H, Gurney JG, et al. Health status of adult long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. JAMA. 2003;290(12):1583–92.

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    Robinson KE, Kuttesch JF, Champion JE, Andreotti CF, Hipp DW, Bettis A, et al. A quantitative meta-analysis of neurocognitive sequelae in survivors of pediatric brain tumors. Pediatr Blood Cancer. 2010;55(3):525–31.

    PubMed  Article  Google Scholar 

  11. 11.

    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.

    CAS  PubMed  Article  Google Scholar 

  12. 12.

    Grill J, Renaux VK, Bulteau C, Viguier D, Levy-Piebois C, Sainte-Rose C, et al. Long-term intellectual outcome in children with posterior fossa tumors according to radiation doses and volumes. Int J Radiat Oncol Biol Phys. 1999;45(1):137–45.

    CAS  PubMed  Article  Google Scholar 

  13. 13.

    Ellenberg L, Liu Q, Gioia G, Yasui Y, Packer RJ, Mertens A, et al. Neurocognitive status in long-term survivors of childhood CNS malignancies: a report from the Childhood Cancer Survivor Study. Neuropsychology. 2009;23(6):705–17.

    PubMed  PubMed Central  Article  Google Scholar 

  14. 14.

    Duffner PK. Risk factors for cognitive decline in children treated for brain tumors. Eur J Paediatr Neurol. 2010;14(2):106–15.

    PubMed  Article  Google Scholar 

  15. 15.

    Butler RW, Fairclough DL, Katz ER, Kazak AE, Noll RB, Thompson RD, et al. Intellectual functioning and multi-dimensional attentional processes in long-term survivors of a central nervous system related pediatric malignancy. Life Sci. 2013;93(17):611–6.

    CAS  PubMed  Article  Google Scholar 

  16. 16.

    Limond JA, Bull KS, Calaminus G, Kennedy CR, Spoudeas HA, Chevignard MP. Quality of survival assessment in European childhood brain tumour trials, for children aged 5 years and over. Eur J Paediatr Neurol. 2015;19(2):202–10.

    PubMed  Article  Google Scholar 

  17. 17.

    Chemaitilly W, Li Z, Huang S, Ness KK, Clark KL, Green DM, et al. Anterior hypopituitarism in adult survivors of childhood cancers treated with cranial radiotherapy: a report from the St Jude Lifetime Cohort Study. J Clin Oncol. 2015;33(5):492–500.

    PubMed  PubMed Central  Article  Google Scholar 

  18. 18.

    Merchant TE, Goloubeva O, Pritchard DL, Gaber MW, Xiong X, Danish RK, et al. Radiation dose-volume effects on growth hormone secretion. Int J Radiat Oncol Biol Phys. 2002;52(5):1264–70.

    CAS  PubMed  Article  Google Scholar 

  19. 19.

    Merchant TE, Rose SR, Bosley C, Wu S, Xiong X, Lustig RH. Growth hormone secretion after conformal radiation therapy in pediatric patients with localized brain tumors. J Clin Oncol. 2011;29(36):4776–80.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  20. 20.

    • Gunn ME, Lähdesmäki T, Malila N, Arola M, Grönroos M, Matomäki J, et al. Late morbidity in long-term survivors of childhood brain tumors: a nationwide registry-based study in Finland. Neuro-Oncology. 2015;17(5):747–56. The authors showed that risk of development of endocrinopathies, cognitive deficits, developmental disorders, and neurological diseases at > 5 years from cancer diagnosis is many times higher in childhood BTLS as compared to that in siblings.

    PubMed  Article  Google Scholar 

  21. 21.

    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.

    PubMed  Article  Google Scholar 

  22. 22.

    Orgel E, Jain S, Ji L, Pollick L, Si S, Finlay J, et al. Hearing loss among survivors of childhood brain tumors treated with an irradiation-sparing approach. Pediatr Blood Cancer. 2012;58(6):953–8.

    PubMed  Article  Google Scholar 

  23. 23.

    • Brinkman TM, Bass JK, Li Z, Ness KK, Gajjar A, Pappo AS, et al. Treatment-induced hearing loss and adult social outcomes in survivors of childhood CNS and non-CNS solid tumors: results from the St. Jude Lifetime Cohort Study. Cancer. 2015;121(22):4053–61. Serious therapy-related hearing loss is seen in a third of childhood BTLS, with significant adverse impact on their education, employment, and independent living.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  24. 24.

    Oeffinger KC, Mertens AC, Sklar CA, Kawashima T, Hudson MM, Meadows AT, et al. Chronic health conditions in adult survivors of childhood cancer. N Engl J Med. 2006;355(15):1572–82.

    CAS  PubMed  Article  Google Scholar 

  25. 25.

    Bowers DC, Liu Y, Leisenring W, McNeil E, Stovall M, Gurney JG, et al. Late-occurring stroke among long-term survivors of childhood leukemia and brain tumors: a report from the Childhood Cancer Survivor Study. J Clin Oncol. 2006;24(33):5277–82.

    PubMed  Article  Google Scholar 

  26. 26.

    • Sterkenburg AS, Hoffmann A, Gebhardt U, Warmuth-Metz M, Daubenbüchel AMM, Müller HL. Survival, hypothalamic obesity, and neuropsychological/psychosocial status after childhood-onset craniopharyngioma: newly reported long-term outcomes. Neuro-Oncology. 2015;17(7):1029–38. Hypothalamic involvement in craniopharyngioma may cause severe long-term obesity, reduced 20-year OS, and worse long-term QOL in survivors.

    PubMed  PubMed Central  Article  Google Scholar 

  27. 27.

    Nolan VG, Gapstur R, Gross CR, Desain LA, Neglia JP, Gajjar A, et al. Sleep disturbances in adult survivors of childhood brain tumors. Qual Life Res. 2013;22(4):781–9.

    PubMed  Article  Google Scholar 

  28. 28.

    Oeffinger KC, Mertens AC, Sklar CA, Yasui Y, Fears T, Stovall M, 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):1359–65.

    PubMed  Article  Google Scholar 

  29. 29.

    Ross L, Johansen C, Dalton SO, Mellemkjaer L, Thomassen LH, Mortensen PB, et al. Psychiatric hospitalizations among survivors of cancer in childhood or adolescence. N Engl J Med. 2003;349(7):650–7.

    PubMed  Article  Google Scholar 

  30. 30.

    Litofsky SN, Resnick AG. The relationships between depression and brain tumors. J Neuro-Oncol. 2009;94(2):153–61.

    Article  Google Scholar 

  31. 31.

    Litofsky NS, Farace E, Anderson F, Meyers CA, Huang W, Laws ER, et al. Depression in patients with high-grade glioma: results of the Glioma Outcomes Project. Neurosurgery. 2004;54(2):358–66-7.

    PubMed  Article  Google Scholar 

  32. 32.

    Pelletier G, Verhoef MJ, Khatri N, Hagen N. Quality of life in brain tumor patients: the relative contributions of depression, fatigue, emotional distress, and existential issues. J Neuro-Oncol. 2002;57(1):41–9.

    Article  Google Scholar 

  33. 33.

    Fox SW, Lyon D, Farace E. Symptom clusters in patients with high-grade glioma. J Nurs Scholarsh an Off Publ Sigma Theta Tau Int Honor Soc Nurs. 2007;39(1):61–7.

    Google Scholar 

  34. 34.

    Hahn CA, Dunn RH, Logue PE, King JH, Edwards CL, Halperin EC. Prospective study of neuropsychologic testing and quality-of-life assessment of adults with primary malignant brain tumors. Int J Radiat Oncol Biol Phys. 2003;55(4):992–9.

    CAS  PubMed  Article  Google Scholar 

  35. 35.

    Brown PD, Maurer MJ, Rummans TA, Pollock BE, Ballman KV, Sloan JA, et al. A prospective study of quality of life in adults with newly diagnosed high-grade gliomas: the impact of the extent of resection on quality of life and survival. Neurosurgery. 2005;57(3):495–504.

    PubMed  Article  Google Scholar 

  36. 36.

    • Brinkman TM, Liptak CC, Delaney BL, Chordas CA, Muriel AC, Manley PE. Suicide ideation in pediatric and adult survivors of childhood brain tumors. J Neuro-Oncol. 2013;113(3):425–32. Nearly 12% of BTLS reported suicide ideation, especially those with previous history of seizures or depression

    Article  Google Scholar 

  37. 37.

    Rueegg CS, Michel G, Wengenroth L, von der Weid NX, Bergstraesser E, Kuehni CE, et al. Physical performance limitations in adolescent and adult survivors of childhood cancer and their siblings. PLoS One. 2012;7(10):e47944.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  38. 38.

    •• Hobbie WL, Ogle S, Reilly M, Barakat L, Lucas MS, Ginsberg JP, et al. Adolescent and young adult survivors of childhood brain tumors: life after treatment in their own words. Cancer Nurs. 2017;39(2):134–43. The authors provide a unique perspective of life after brain tumor treatment in the survivors’ own words, highlighting the long-term impact of therapy-related morbidity.

    Article  Google Scholar 

  39. 39.

    French AE, Tsangaris E, Barrera M, Guger S, Brown R, Urbach S, et al. School attendance in childhood cancer survivors and their siblings. J Pediatr. 2013;162(1):160–5.

    PubMed  Article  Google Scholar 

  40. 40.

    Yağci-Küpeli B, Yalçin B, Küpeli S, Varan A, Akyüz C, Kutluk T, et al. Educational achievement, employment, smoking, marital, and insurance statuses in long-term survivors of childhood malignant solid tumors. J Pediatr Hematol Oncol. 2013;35(2):129–33.

    PubMed  Article  Google Scholar 

  41. 41.

    Lancashire ER, Frobisher C, Reulen RC, Winter DL, Glaser A, Hawkins MM. Educational attainment among adult survivors of childhood cancer in Great Britain: a population-based cohort study. J Natl Cancer Inst. 2010;102(4):254–70.

    CAS  PubMed  Article  Google Scholar 

  42. 42.

    Bonneau J, Lebreton J, Taque S, Chappe C, Bayart S, Edan C, et al. School performance of childhood cancer survivors: mind the teenagers! J Pediatr. 2011;158(1):135–41.

    PubMed  Article  Google Scholar 

  43. 43.

    Lorenzi M, McMillan AJ, Siegel LS, Zumbo BD, Glickman V, Spinelli JJ, et al. Educational outcomes among survivors of childhood cancer in British Columbia, Canada: report of the Childhood/Adolescent/Young Adult Cancer Survivors (CAYACS) Program. Cancer. 2009;115(10):2234–45.

    PubMed  Article  Google Scholar 

  44. 44.

    Gurney JG, Krull KR, Kadan-Lottick N, Nicholson HS, Nathan PC, Zebrack B, et al. Social outcomes in the childhood cancer survivor study cohort. J Clin Oncol. 2009;27(14):2390–5.

    PubMed  PubMed Central  Article  Google Scholar 

  45. 45.

    Green DM, Zevon MA, Hall B. Achievement of life goals by adult survivors of modern treatment for childhood cancer. Cancer. 1991;67(1):206–13.

    CAS  PubMed  Article  Google Scholar 

  46. 46.

    de Boer AGEM, Verbeek JHAM, van Dijk FJH. Adult survivors of childhood cancer and unemployment. Cancer 2006;107(1):1–11.

  47. 47.

    Armstrong GT, Liu Q, Yasui Y, Huang S, Ness KK, Leisenring W, et al. Long-term outcomes among adult survivors of childhood central nervous system malignancies in the Childhood Cancer Survivor Study. J Natl Cancer Inst. 2009;101(13):946–58.

    PubMed  PubMed Central  Article  Google Scholar 

  48. 48.

    Pang JWY, Friedman DL, Whitton JA, Stovall M, Mertens AC, Robison LL, et al. Employment status among adult survivors in the Childhood Cancer Survivor Study. Pediatr Blood Cancer. 2008;50(1):104–10.

    PubMed  Article  Google Scholar 

  49. 49.

    Koch SV, Kejs AMT, Engholm G, Møller H, Johansen C, Schmiegelow K. Leaving home after cancer in childhood: a measure of social independence in early adulthood. Pediatr Blood Cancer. 2006;47(1):61–70.

    PubMed  Article  Google Scholar 

  50. 50.

    Bhat SR, Goodwin TL, Burwinkle TM, Lansdale MF, Dahl GV, Huhn SL, et al. Profile of daily life in children with brain tumors: an assessment of health-related quality of life. J Clin Oncol. 2005;23(24):5493–500.

    PubMed  Article  Google Scholar 

  51. 51.

    • Chevignard M, Câmara-costa H, Doz F, Dellatolas G. Core deficits and quality of survival after childhood medulloblastoma: a review. Neuro-Oncology Pract. 2017;4(2):82–97. An insightful review of the long-term dysfunction and its causative factors in childhood medulloblastoma survivors

    Google Scholar 

  52. 52.

    Fuemmeler BF, Elkin TD, Mullins LL. Survivors of childhood brain tumors: behavioral, emotional, and social adjustment. Clin Psychol Rev. 2002;22(4):547–85.

    PubMed  Article  Google Scholar 

  53. 53.

    Mattsson E, Lindgren B, Von Essen L. Are there any positive consequences of childhood cancer? A review of the literature. Acta Oncol (Madr). 2008;47(2):199–206.

    CAS  Article  Google Scholar 

  54. 54.

    Stam H, Grootenhuis MA, Last BF. The course of life of survivors of childhood cancer. Psychooncology. 2005;14(3):227–38.

    CAS  PubMed  Article  Google Scholar 

  55. 55.

    van Dijk EM, van Dulmen-den Broeder E, Kaspers GJL, van Dam EWCM, Braam KI, Huisman J. Psychosexual functioning of childhood cancer survivors. Psychooncology 2008;17(5):506–511.

  56. 56.

    Koch SV, Mette A, Kejs T, Engholm G, Mller H, Johansen C, et al. Marriage and divorce among childhood cancer survivors. J Pediatr Hematol Oncol. 2011;33(7):500–5.

    PubMed  Article  Google Scholar 

  57. 57.

    Pivetta E, Maule MM, Pisani P, Zugna D, Haupt R, Jankovic M, et al. Marriage and parenthood among childhood cancer survivors: a report from the Italian AIEOP Off-Therapy Registry. Haematologica. 2011;96(5):744–51.

    PubMed  PubMed Central  Article  Google Scholar 

  58. 58.

    Janson C, Leisenring W, Cox C, Termuhlen AM, Mertens AC, Whitton JA, et al. Predictors of marriage and divorce in adult survivors of childhood cancers: a report from the Childhood Cancer Survivor Study. Cancer Epidemiol Biomark Prev. 2009;18(10):2626–35.

    Article  Google Scholar 

  59. 59.

    Frobisher C, Lancashire ER, Winter DL, Taylor AJ, Reulen RC, Hawkins MM, et al. Long-term population-based divorce rates among adult survivors of childhood cancer in Britain. Pediatr Blood Cancer. 2010;54(1):116–22.

    PubMed  Article  Google Scholar 

  60. 60.

    Armstrong GT. Long-term survivors of childhood central nervous system malignancies: the experience of the Childhood Cancer Survivor Study. Eur J Paediatr Neurol. 2010;14(4):298–303.

    PubMed  PubMed Central  Article  Google Scholar 

  61. 61.

    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.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  62. 62.

    Krex D, Klink B, Hartmann C, von Deimling A, Pietsch T, Simon M, et al. Long-term survival with glioblastoma multiforme. Brain. 2007;130(Pt 10):2596–606.

    PubMed  Article  Google Scholar 

  63. 63.

    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.

  64. 64.

    •• Tallen G, Resch A, Calaminus G, Wiener A, Leiss U, Pletschko T, et al. Strategies to improve the quality of survival for childhood brain tumour survivors. Eur J Paediatr Neurol. 2015;19(6):619–39. The authors have studied the QOL issues in European childhood BTLS in detail and provided recommendations covering all the aspects of treatment to improve long-term QOL of survivors.

    PubMed  Article  Google Scholar 

  65. 65.

    Armstrong GT, Sklar CA, Hudson MM, Robison LL. Long-term health status among survivors of childhood cancer: does sex matter? J Clin Oncol. 2007;25(28):4477–89.

    PubMed  Article  Google Scholar 

  66. 66.

    Butler RW, Copeland DR, Fairclough DL, Mulhern RK, Katz ER, Kazak AE, et al. A multicenter, randomized clinical trial of a cognitive remediation program for childhood survivors of a pediatric malignancy. J Consult Clin Psychol. 2008;76(3):367–78.

    PubMed  PubMed Central  Article  Google Scholar 

  67. 67.

    Butler RW, Copeland DR. Attentional processes and their remediation in children treated for cancer: a literature review and the development of a therapeutic approach. J Int Neuropsychol Soc. 2002;8(1):115–24.

    PubMed  Article  Google Scholar 

  68. 68.

    Patel SK, Katz ER, Richardson R, Rimmer M, Kilian S. Cognitive and problem solving training in children with cancer: a pilot project. J Pediatr Hematol Oncol. 2009;31(9):670–7.

    PubMed  Article  Google Scholar 

  69. 69.

    Hardy KK, Willard VW, Bonner MJ. Computerized cognitive training in survivors of childhood cancer: a pilot study. J Pediatr Oncol Nurs. 2011;28(1):27–33.

    PubMed  Article  Google Scholar 

  70. 70.

    Thompson SJ, Leigh L, Christensen R, Xiong X, Kun LE, Heideman RL, et al. Immediate neurocognitive effects of methylphenidate on learning-impaired survivors of childhood cancer. J Clin Oncol. 2001;19(6):1802–8.

    CAS  PubMed  Article  Google Scholar 

  71. 71.

    Conklin HM, Reddick WE, Ashford J, Ogg S, Howard SC, Morris EB, et al. Long-term efficacy of methylphenidate in enhancing attention regulation, social skills, and academic abilities of childhood cancer survivors. J Clin Oncol. 2010;28(29):4465–72.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  72. 72.

    Gehring K, Patwardhan SY, Collins R, Groves MD, Etzel CJ, Meyers CA, et al. A randomized trial on the efficacy of methylphenidate and modafinil for improving cognitive functioning and symptoms in patients with a primary brain tumor. J Neuro-Oncol. 2012;107(1):165–74.

    CAS  Article  Google Scholar 

  73. 73.

    Shaw EG, Rosdhal R, D’Agostino RB, Lovato J, Naughton MJ, Robbins ME, et al. Phase II study of donepezil in irradiated brain tumor patients: effect on cognitive function, mood, and quality of life. J Clin Oncol. 2006;24(9):1415–20.

    CAS  PubMed  Article  Google Scholar 

  74. 74.

    Castellino SM, Tooze JA, Flowers L, Hill DF, McMullen KP, Shaw EG, et al. Toxicity and efficacy of the acetylcholinesterase (AChe) inhibitor donepezil in childhood brain tumor survivors: a pilot study. Pediatr Blood Cancer. 2012;59(3):540–7.

    PubMed  PubMed Central  Article  Google Scholar 

  75. 75.

    Radcliffe J, Bennett DS, Kazan AE, Foley B, Phillip PC. Adjustment in childhood brain tumor survival: child, mother, and teacher report. J Pediatr Psychol. 1996;21(4):529–39.

    CAS  PubMed  Article  Google Scholar 

  76. 76.

    Carlson-Green B, Morris RD, Krawiecki N. Family and illness predictors of outcome in pediatric brain tumors. J Pediatr Psychol. 1995;20(6):769–84.

    CAS  PubMed  Article  Google Scholar 

  77. 77.

    Hocking MC, Hobbie WL, Deatrick JA, Hardie TL, Barakat LP. Family functioning mediates the association between neurocognitive functioning and health-related quality of life in young adult survivors of childhood brain tumors. J Adolesc Young Adult Oncol. 2015;4(1):18–25.

    PubMed  PubMed Central  Article  Google Scholar 

  78. 78.

    Ness KK, Hudson MM, Ginsberg JP, Nagarajan R, Kaste SC, Marina N, et al. Physical performance limitations in the Childhood Cancer Survivor Study cohort. J Clin Oncol. 2009;27(14):2382–9.

    PubMed  PubMed Central  Article  Google Scholar 

  79. 79.

    Peterson CC, Drotar D. Family impact of neurodevelopmental late effects in survivors of pediatric cancer: review of research, clinical evidence, and future directions. Clin Child Psychol Psychiatry. 2006;11(3):349–66.

    PubMed  Article  Google Scholar 

  80. 80.

    Hocking MC, Hobbie WL, Deatrick JA, Lucas MS, Szabo MM, Volpe EM, et al. Neurocognitive and family functioning and quality of life among young adult survivors of childhood brain tumors. Clin Neuropsychol. 2011;25(6):942–62.

    PubMed  PubMed Central  Article  Google Scholar 

  81. 81.

    Georgiadi M, Kourkoutas EE. Supporting pupils with cancer on their return to school: a case study report of a reintegration program. Procedia - Soc Behav Sci. 2010;5(2):1273–7.

    Google Scholar 

  82. 82.

    Mulhern RK, Merchant TE, Gajjar A, Reddick WE, Kun LE. Late neurocognitive sequelae in survivors of brain tumours in childhood. Lancet Oncol. 2004;5(7):399–408.

    PubMed  Article  Google Scholar 

  83. 83.

    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 Biomark Prev. 2009;18(4):1033–40.

    Article  Google Scholar 

  84. 84.

    Kuhnt D, Ganslandt O, Schlaffer S-M, Buchfelder M, Nimsky C. Quantification of glioma removal by intraoperative high-field magnetic resonance imaging: an update. Neurosurgery. 2011;69(4):852–63.

    PubMed  Article  Google Scholar 

  85. 85.

    Ulrich NH, Burkhardt J-K, Serra C, Bernays R-L, Bozinov O. Resection of pediatric intracerebral tumors with the aid of intraoperative real-time 3-D ultrasound. Childs Nerv Syst. 2012;28(1):101–9.

    PubMed  Article  Google Scholar 

  86. 86.

    Ahmad F, Sandberg DI. Endoscopic management of intraventricular brain tumors in pediatric patients: a review of indications, techniques, and outcomes. J Child Neurol. 2010;25(3):359–67.

    PubMed  Article  Google Scholar 

  87. 87.

    • Jalali R, Gupta T, Goda JS, Goswami S, Shah N, Dutta D, et al. Efficacy of stereotactic conformal radiotherapy vs conventional radiotherapy on benign and low-grade brain tumors: a randomized clinical trial. JAMA Oncol. 2017;3(10):1368–76. Level 1 evidence has been generated with this RCT for benefit of modern high-precision conformal RT over conventional RT to preserve neurocognitive and endocrine functions in pediatric benign/low-grade CNS tumors.

    PubMed  Article  Google Scholar 

  88. 88.

    Doger de Speville E, Robert C, Perez-Guevara M, Grigis A, Bolle S, Pinaud C, et al. Relationships between regional radiation doses and cognitive decline in children treated with cranio-spinal irradiation for posterior fossa tumors. Front Oncol. 2017;7:166.

    PubMed  PubMed Central  Article  Google Scholar 

  89. 89.

    Moxon-Emre I, Bouffet E, Taylor MD, Laperriere N, Scantlebury N, Law N, et al. Impact of craniospinal dose, boost volume, and neurologic complications on intellectual outcome in patients with medulloblastoma. J Clin Oncol. 2014;32(17):1760–8.

    PubMed  Article  Google Scholar 

  90. 90.

    Carrie C, Grill J, Figarella-Branger D, Bernier V, Padovani L, Habrand JL, et al. Online quality control, hyperfractionated radiotherapy alone and reduced boost volume for standard risk medulloblastoma: long-term results of MSFOP 98. J Clin Oncol. 2009;27(11):1879–83.

    PubMed  Article  Google Scholar 

  91. 91.

    Merchant TE, Hua C, Shukla H, Ying X, Nill S, Oelfke U. Proton versus photon radiotherapy for common pediatric brain tumors: comparison of models of dose characteristics and their relationship to cognitive function. Pediatr Blood Cancer. 2008;51(1):110–7.

    PubMed  Article  Google Scholar 

  92. 92.

    Yock TI, Bhat S, Szymonifka J, Yeap BY, Delahaye J, Donaldson SS, et al. Quality of life outcomes in proton and photon treated pediatric brain tumor survivors. Radiother Oncol. 2014;113(1):89–94.

    PubMed  PubMed Central  Article  Google Scholar 

  93. 93.

    • Gondi V, Yock TI, Mehta MP. Proton therapy for paediatric CNS tumours - improving treatment-related outcomes. Nat Rev Neurol. 2016;12(6):334–45. The authors have provided a balanced review of all the evidence of the use of proton therapy in childhood CNS tumors, its benefit in limiting toxicities justifying the high costs.

    CAS  PubMed  Article  Google Scholar 

  94. 94.

    Koga T, Shin M, Maruyama K, Kamada K, Ota T, Itoh D, et al. Integration of corticospinal tractography reduces motor complications after radiosurgery. Int J Radiat Oncol. 2012;83(1):129–33.

    Article  Google Scholar 

  95. 95.

    Pantelis E, Papadakis N, Verigos K, Stathochristopoulou I, Antypas C, Lekas L, et al. Integration of functional MRI and white matter tractography in stereotactic radiosurgery clinical practice. Int J Radiat Oncol. 2010;78(1):257–67.

    Article  Google Scholar 

  96. 96.

    Igaki H, Sakumi A, Mukasa A, Saito K, Kunimatsu A, Masutani Y, et al. Corticospinal tract-sparing intensity-modulated radiotherapy treatment planning. Reports Pract Oncol Radiother J Gt Cancer Cent Pozn Polish Soc Radiat Oncol. 2014;19(5):310–6.

    Google Scholar 

  97. 97.

    • Ramaswamy V, Remke M, Bouffet E, Bailey S, Clifford SC, Doz F, et al. Risk stratification of childhood medulloblastoma in the molecular era: the current consensus. Acta Neuropathol. 2016;131(6):821–31. Molecular-based risk stratification in medulloblastoma is the foundation of therapy de-escalation and personalized treatment for these patients

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  98. 98.

    Thompson EM, Hielscher T, Bouffet E, Remke M, Luu B, Gururangan S, et al. Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis. Lancet Oncol. 2016;17(4):484–95.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  99. 99.

    Moxon-Emre I, Taylor MD, Bouffet E, Hardy K, Campen CJ, Malkin D, et al. Intellectual outcome in molecular subgroups of medulloblastoma. J Clin Oncol. 2016;34(34):4161–70.

    PubMed  Article  Google Scholar 

  100. 100.

    Archer TC, Mahoney EL, Pomeroy SL. Medulloblastoma: molecular classification-based personal therapeutics. Neurotherapeutics. 2017;14(2):265–73.

    CAS  PubMed  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Rakesh Jalali.

Ethics declarations

Conflict of Interest

Priyamvada Gupta and Rakesh Jalali each declare no potential conflicts of interest.

Human and Animal Rights and Informed Consent

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki Declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

Additional information

This article is part of the Topical Collection on Neuro-Oncology

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Gupta, P., Jalali, R. Long-term Survivors of Childhood Brain Tumors: Impact on General Health and Quality of Life. Curr Neurol Neurosci Rep 17, 99 (2017). https://doi.org/10.1007/s11910-017-0808-0

Download citation

Keywords

  • Brain tumors
  • Long-term survivors
  • Cancer survivors
  • Childhood brain tumors