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Side Effects of Therapies for Brain Tumours

  • Robin GrantEmail author
Chapter

Abstract

Initial symptomatic management aimed at reducing oedema and treating seizures in brain tumour patients, at an appropriate dose and for an appropriate duration, will produce more benefits than harms.

Surgery can be associated with immediate or occasionally delayed complications in about a third of cases, but slow recovery then occurs in two thirds of these patients. Radiotherapy may produce early toxicity, related to temporary worsening of oedema or demyelination in one-third of patients. In survivors from brain tumour, “late” side effects from radiotherapy are inevitable; these start from 6 months after radiotherapy but increase in frequency and severity with duration of survival and are related to vascular or degenerative pathologies.

Chemotherapy produces immediate dose-related temporary side effects and gradually cumulative late toxicities with increasing numbers of courses. Multi-system cytotoxicity involves the bone marrow, muco-cutaneous system, liver and kidney, and occasionally peripheral nerves and lungs. Immunotherapy, whether cell-based or antibody-based, has a more systemic autoimmune profile associated with elevated levels of pro-inflammatory cytokines. Care must be taken to predict the risk and prevent or minimise the extent of acute and late toxicities, as these may not only result in lifelong disability, but also occasionally in death.

Late side effects (e.g., fatigue, cognitive difficulties, personality change and mood problems) are often multifactorial. Identifying acceptable levels of risk, withdrawal of a causative drug, replacement of a deficient hormone, and management of treatable factors, seizures, anxiety, depression, sleep, drowsiness, cognition and fatigue will all help. Neuro-rehabilitation and neuro-cognitive rehabilitation should be established as early as possible after treatment.

References

  1. 1.
    Scales DC, Fischer HD, Li P, et al. Unintentional continuation of medications intended for acute illness after hospital discharge: a population-based cohort study. J Gen Intern Med. 2016;31:196.CrossRefGoogle Scholar
  2. 2.
    Kerrigan S, Erridge SE, Liaquat I, et al. Mental incapacity in patients undergoing neuro-oncologic treatment: a cross-sectional study. Neurology. 2014;83(6):537–41.CrossRefGoogle Scholar
  3. 3.
    Brell M, Ibanez J, Caral L, Ferrer E. Factors influencing surgical complications of intra-axial brain tumours. Acta Neurochir (Wein). 2000;142:739–50.CrossRefGoogle Scholar
  4. 4.
    Gudrunardottir T, Sehested A, Juhler M, Schmiegelow K. Cerebellar mutism: review of the literature. Childs Nerv Syst. 2011;27(3):355–63.CrossRefGoogle Scholar
  5. 5.
    Potgieser ARE, de Jong BM, Wagemakers M, Hoving EW, Groen RJM. Insights from the supplementary motor area syndrome in balancing movement initiation and inhibition. Front Hum Neurosci. 2014;8:960.CrossRefGoogle Scholar
  6. 6.
    Armstrong TS, Cron SG, Bolanos EV, et al. Risk factors for fatigue severity in primary brain tumor patients. Cancer. 2010;116(11):2707–15.PubMedGoogle Scholar
  7. 7.
    Day J, Yust-Katz S, Cachia D, et al. Interventions for the management of fatigue in adults with a primary brain tumour. Cochrane Database Syst Rev. 2016;(4):CD011376.  https://doi.org/10.1002/14651858.CD011376.pub2.
  8. 8.
    Boele FW, Douw L, de Groot M, et al. The effect of modafinil on fatigue, cognitive functioning, and mood in primary brain tumor patients: a multicenter randomized controlled trial. Neuro-Oncology. 2013;15(10):1420–8.CrossRefGoogle Scholar
  9. 9.
    Robbins ME, Zhao W. Chronic oxidative stress and radiation-induced late normal tissue injury: a review. Int J Radiat Biol. 2004;80:251–9.CrossRefGoogle Scholar
  10. 10.
    Wilson CM, Gaber MW, Sabek OM, Zawaski JA, Merchant TE. Radiation-induced astrogliosis and blood–brain barrier damage can be abrogated using anti-TNF treatment. Int J Radiat Oncol Biol Phys. 2009;74:934–41.CrossRefGoogle Scholar
  11. 11.
    Lee WH, Sonntag WE, Mitschelen M, Yan H, Lee YW. Irradiation induces regionally specific alterations in pro-inflammatory environments in rat brain. Int J Radiat Biol. 2010;86:132–44.CrossRefGoogle Scholar
  12. 12.
    Brown WR, Blair RM, Moody DM, Thore CR, Ahmed S, Robbins ME, Wheeler KT. Capillary loss precedes the cognitive impairment induced by fractionated whole-brain irradiation: a potential rat model of vascular dementia. J Neurol Sci. 2007;257:67–71.CrossRefGoogle Scholar
  13. 13.
    Meyers CA, Brown PD. Role and relevance of neurocognitive assessment in clinical trials of patients with CNS tumors. J Clin Oncol. 2006;24:1305–9.CrossRefGoogle Scholar
  14. 14.
    Nieder C, Leicht A, Motaref B, Nestle U, Niewald M, Schnabel K. Late radiation toxicity after whole brain radiotherapy: the influence of antiepileptic drugs. Am J Clin Oncol. 1999;22:573–9.CrossRefGoogle Scholar
  15. 15.
    Chung C, Brown PD. Interventions for the treatment of brain radionecrosis after radiotherapy or radiosurgery. Cochrane Database Syst Rev. 2015;(1):CD011492.  https://doi.org/10.1002/14651858.CD011492.
  16. 16.
    Shaw E, Arusell R, Scheithauer B, et al. A prospective randomized trial of low- versus high-dose radiation therapy in adults with supratentorial low-grade glioma: initial report of a NCCTG-RTOG-ECOG Study. J Clin Oncol. 2002;20:2267–76.CrossRefGoogle Scholar
  17. 17.
    Kerklaan JP, Lycklama A Nijeholt GJ, Wiggenraad RG, Berghuis B, Postma TJ, Taphoorn MJ. SMART syndrome: a late reversible complication after radiation therapy for brain tumours. J Neurol. 2011;258(6):1098–104.CrossRefGoogle Scholar
  18. 18.
    Bradshaw J, Chen L, Saling M, Fitt G, Hughes A, Dowd A. Neurocognitive recovery in SMART syndrome: a case report. Cephalalgia. 2011;31:372–6.CrossRefGoogle Scholar
  19. 19.
    Larson JJ, Ball WS, Bove KE, et al. Formation of intracerebral cavernous malformations after radiation treatment for central nervous system neoplasia in children. J Neurosurg. 1998;88:51–6.CrossRefGoogle Scholar
  20. 20.
    Heckl S, Aschoff A, Kunze S. Radiation-induced cavernous hemangiomas of the brain: a late effect predominantly in children. Cancer. 2002;94:3285–91.CrossRefGoogle Scholar
  21. 21.
    Darzy KH, Shalet SM. Hypopituitarism following radiotherapy revisited. Endocr Dev. 2009;15:1–24.CrossRefGoogle Scholar
  22. 22.
    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;349:640–9.CrossRefGoogle Scholar
  23. 23.
    Chamberlain M. Temozolomide: therapeutic limitations in the treatment of adult high grade gliomas. Expert Rev Neurother. 2010;10(10):1537–44.CrossRefGoogle Scholar
  24. 24.
    Kaehler KC, Piel S, Livingstone E, Schilling B, Hauschild A, Schadendorf D. Update on immunologic therapy with anti-CTLA-4 antibodies in melanoma: identification of clinical and biological response patterns, immune-related adverse events, and their management. Semin Oncol. 2010;37(5):485–98.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Edinburgh Centre for Neuro-OncologyWestern General HospitalEdinburghUK

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