Malignant Brain Tumors

  • Akanksha SharmaEmail author
  • Lynne P. Taylor


The brain tumor patient presents as a complex challenge to the care provider, demanding a knowledge of their cancer, its treatment and complications, and the neurological impact of the tumor. Brain tumors may range from primary to metastatic, from surgically curable to highly malignant. Each type of tumor has its own unique impact, and the management, prognosis and long-term outcomes differ for each patient. It is outside the scope of this chapter to review all of these trajectories individually. Instead, we aim to make certain generalizations on the presentation, management and course of primary and metastatic brain tumors as a group. We present some of the most common symptoms experienced by this patient group and make suggestions on management. We also focus on the important subject of advanced care and end of life planning in this population, as well as discuss how the clinician can help prepare the patient and caregivers for the end of life.


Neuro-oncology Brain neoplasms Seizures Tumors Glioblastoma Metastases Leptomeningeal 


  1. 1.
    Barnholtz-Sloan JS, Sloan AE, Davis FG, Vigneau FD, Lai P, Sawaya RE. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol. 2004;22(14):2865–72.PubMedGoogle Scholar
  2. 2.
    Maher EA, McKee AC. Neoplasms of the central nervous system. In: Skarin AT, Canellos GP, editors. Atlas of diagnostic oncology. 3rd ed. London: Elsevier Science Ltd.; 2003.Google Scholar
  3. 3.
    Ostrom QT, Gittleman H, Xu J, Kromer C, Wolinsky Y, Kruchko C, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2009–2013. Neuro-Oncology. 2016;18(Suppl_5):v1–75.PubMedGoogle Scholar
  4. 4.
    Porter KR, McCarthy BJ, Freels S, Kim Y, Davis FG. Prevalence estimates for primary brain tumors in the United States by age, gender, behavior, and histology. Neuro-Oncology. 2010;12(6):520–7.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Frankel S, German W. Glioblastoma multiforme; review of 219 cases with regard to natural history, pathology, diagnostic methods, and treatment. J Neurosurg. 1958;15(5):489–503.PubMedGoogle Scholar
  6. 6.
    Roth JG, Elvidge AR. Glioblastoma multiforme: a clinical survey. J Neurosurg. 1960;17:736–50.PubMedGoogle Scholar
  7. 7.
    Nelson S, Taylor LP. Headaches in brain tumor patients: primary or secondary? Headache. 2014;54(4):776–85.PubMedGoogle Scholar
  8. 8.
    Taylor LP. Mechanism of brain tumor headache. Headache. 2014;54(4):772–5.PubMedGoogle Scholar
  9. 9.
    Chandana SR, Movva S, Arora M, Singh T. Primary brain tumors in adults. Am Fam Physician. 2008;77(10):1423–30.PubMedGoogle Scholar
  10. 10.
    Jacobs AH, Kracht LW, Gossmann A, Rüger MA, Thomas AV, Thiel A, et al. Imaging in neurooncology. NeuroRx. 2005;2(2):333–47.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Trifiletti DM, Alonso C, Grover S, Fadul CE, Sheehan JP, Showalter TN. Prognostic implications of extent of resection in glioblastoma: analysis from a large database. World Neurosurg. 2017;103:330–40.PubMedGoogle Scholar
  12. 12.
    Mehta MP, Rodrigus P, Terhaard CH, Rao A, Suh J, Roa W, et al. Survival and neurologic outcomes in a randomized trial of motexafin gadolinium and whole-brain radiation therapy in brain metastases. J Clin Oncol. 2003;21(13):2529–36.PubMedGoogle Scholar
  13. 13.
    Mehta MP, Ahluwalia MS. Whole-brain radiotherapy and stereotactic radiosurgery in brain metastases: what is the evidence? Am Soc Clin Oncol Educ Book. 2015:e99–104. doi:10.14694/EdBook_AM.2015.35.e99.Google Scholar
  14. 14.
    Brown PD, Pugh S, Laack NN, Wefel JS, Khuntia D, Meyers C, et al. Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Neuro-Oncology. 2013;15(10):1429–37.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96.Google Scholar
  16. 16.
    Cloughesy TF, Prados MD, Wen PY, Mikkelsen T, Abrey LE, Schiff D, et al. A phase II, randomized, non-comparative clinical trial of the effect of bevacizumab (BV) alone or in combination with irinotecan (CPT) on 6-month progression free survival (PFS6) in recurrent, treatment-refractory glioblastoma (GBM). J Clin Oncol. 2008;26(15_suppl):2010b-b.Google Scholar
  17. 17.
    Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014;370(8):699–708.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Norden AD, Bartolomeo J, Tanaka S, Drappatz J, Ciampa AS, Doherty LM, et al. Safety of concurrent bevacizumab therapy and anticoagulation in glioma patients. J Neuro-Oncol. 2012;106(1):121–5.Google Scholar
  19. 19.
    Fraum TJ, Kreisl TN, Sul J, Fine HA, Iwamoto FM. Ischemic stroke and intracranial hemorrhage in glioma patients on antiangiogenic therapy. J Neuro-Oncol. 2011;105(2):281–9.Google Scholar
  20. 20.
    Sharma K, Marcus JR. Bevacizumab and wound-healing complications: mechanisms of action, clinical evidence, and management recommendations for the plastic surgeon. Ann Plast Surg. 2013;71(4):434–40.PubMedGoogle Scholar
  21. 21.
    Tlemsani C, Mir O, Boudou-Rouquette P, Huillard O, Maley K, Ropert S, et al. Posterior reversible encephalopathy syndrome induced by anti-VEGF agents. Target Oncol. 2011;6(4):253–8.PubMedGoogle Scholar
  22. 22.
    Schouten LJ, Rutten J, Huveneers HA, Twijnstra A. Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer. 2002;94(10):2698–705.PubMedGoogle Scholar
  23. 23.
    Clarke JL, Perez HR, Jacks LM, Panageas KS, Deangelis LM. Leptomeningeal metastases in the MRI era. Neurology. 2010;74(18):1449–54.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Waki F, Ando M, Takashima A, Yonemori K, Nokihara H, Miyake M, et al. Prognostic factors and clinical outcomes in patients with leptomeningeal metastasis from solid tumors. J Neuro-Oncol. 2009;93(2):205–12.Google Scholar
  25. 25.
    Wasserstrom WR, Glass JP, Posner JB. Diagnosis and treatment of leptomeningeal metastases from solid tumors: experience with 90 patients. Cancer. 1982;49(4):759–72.PubMedGoogle Scholar
  26. 26.
    Grossman SA, Moynihan TJ. Neoplastic meningitis. Neurol Clin. 1991;9(4):843–56.PubMedGoogle Scholar
  27. 27.
    Freilich RJ, Krol G, DeAngelis LM. Neuroimaging and cerebrospinal fluid cytology in the diagnosis of leptomeningeal metastasis. Ann Neurol. 1995;38(1):51–7.PubMedGoogle Scholar
  28. 28.
    Collie DA, Brush JP, Lammie GA, Grant R, Kunkler I, Leonard R, et al. Imaging features of leptomeningeal metastases. Clin Radiol. 1999;54(11):765–71.PubMedGoogle Scholar
  29. 29.
    Minniti G, Paolini S, D’Andrea G, Lanzetta G, Cicone F, Confaloni V, et al. Outcomes of postoperative stereotactic radiosurgery to the resection cavity versus stereotactic radiosurgery alone for melanoma brain metastases. J Neuro-Oncol. 2017;132(3):455–62.PubMedGoogle Scholar
  30. 30.
    Minniti G, Esposito V, Clarke E, Scaringi C, Lanzetta G, Salvati M, et al. Multidose stereotactic radiosurgery (9 Gy × 3) of the postoperative resection cavity for treatment of large brain metastases. Int J Radiat Oncol Biol Phys. 2013;86(4):623–9.PubMedGoogle Scholar
  31. 31.
    Brennan C, Yang TJ, Hilden P, Zhang Z, Chan K, Yamada Y, et al. A phase 2 trial of stereotactic radiosurgery boost after surgical resection for brain metastases. Int J Radiat Oncol Biol Phys. 2014;88(1):130–6.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Patchell RA, Regine WF, Loeffler JS, Sawaya R, Andrews DW, Chin LS. Radiosurgery plus whole-brain radiation therapy for brain metastases. JAMA. 2006;296(17):2089–90; author reply 2090–1.PubMedGoogle Scholar
  33. 33.
    Vecht CJ. Clinical management of brain metastasis. J Neurol. 1998;245(3):127–31.PubMedGoogle Scholar
  34. 34.
    Brown PD, Ballman KV, Cerhan JH, Anderson SK, Carrero XW, Whitton AC, et al. Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial. Lancet Oncol. 2017;18:1049.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Houillier C, Wang X, Kaloshi G, Mokhtari K, Guillevin R, Laffaire J, et al. IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas. Neurology. 2010;75(17):1560–6.PubMedGoogle Scholar
  36. 36.
    Borgelt B, Gelber R, Kramer S, Brady LW, Chang CH, Davis LW, et al. The palliation of brain metastases: final results of the first two studies by the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys. 1980;6(1):1–9.PubMedGoogle Scholar
  37. 37.
    DeAngelis LM, Boutros D. Leptomeningeal metastasis. Cancer Investig. 2005;23(2):145–54.Google Scholar
  38. 38.
    Halkett GK, Lobb EA, Oldham L, Nowak AK. The information and support needs of patients diagnosed with High Grade Glioma. Patient Educ Couns. 2010;79(1):112–9.PubMedGoogle Scholar
  39. 39.
    Gould SJ. The median isn’t the message. Virtual Mentor. 2013;15(1):77–81.PubMedGoogle Scholar
  40. 40.
    Fritz L, Dirven L, Reijneveld JC, Koekkoek JA, Stiggelbout AM, Pasman HR, et al. Advance care planning in glioblastoma patients. Cancers (Basel). 2016;8(11):102.Google Scholar
  41. 41.
    Von Roenn JH, von Gunten CF. Setting goals to maintain hope. J Clin Oncol. 2003;21(3):570–4.Google Scholar
  42. 42.
    Taillibert S, Laigle-Donadey F, Sanson M. Palliative care in patients with primary brain tumors. Curr Opin Oncol. 2004;16(6):587–92.PubMedGoogle Scholar
  43. 43.
    Daly FN, Schiff D. Supportive management of patients with brain tumors. Expert Rev Neurother. 2007;7(10):1327–36.PubMedGoogle Scholar
  44. 44.
    Pace A, Di Lorenzo C, Lorenzo CD, Guariglia L, Jandolo B, Carapella CM, et al. End of life issues in brain tumor patients. J Neuro-Oncol. 2009;91(1):39–43.Google Scholar
  45. 45.
    Thier K, Calabek B, Tinchon A, Grisold W, Oberndorfer S. The last 10 days of patients with glioblastoma: assessment of clinical signs and symptoms as well as treatment. Am J Hosp Palliat Care. 2015;33(10):985–8.Google Scholar
  46. 46.
    Sizoo EM, Pasman HR, Buttolo J, Heimans JJ, Klein M, Deliens L, et al. Decision-making in the end-of-life phase of high-grade glioma patients. Eur J Cancer. 2012;48(2):226–32.PubMedGoogle Scholar
  47. 47.
    Diamond EL, Russell D, Kryza-Lacombe M, Bowles KH, Applebaum AJ, Dennis J, et al. Rates and risks for late referral to hospice in patients with primary malignant brain tumors. Neuro-Oncology. 2016;18(1):78–86.PubMedGoogle Scholar
  48. 48.
    Teno JM, Gruneir A, Schwartz Z, Nanda A, Wetle T. Association between advance directives and quality of end-of-life care: a national study. J Am Geriatr Soc. 2007;55(2):189–94.PubMedGoogle Scholar
  49. 49.
    Song K. Advance care planning in patients with brain tumours: a prospective cohort study. J Cancer Res Ther. 2015;7(3):85–91.Google Scholar
  50. 50.
    Song K, Amatya B, Voutier C, Khan F. Advance care planning in patients with primary malignant brain tumors: a systematic review. Front Oncol. 2016;6:223.PubMedPubMedCentralGoogle Scholar
  51. 51.
    Péus D, Newcomb N, Hofer S. Appraisal of the karnofsky performance status and proposal of a simple algorithmic system for its evaluation. BMC Med Inform Decis Mak. 2013;13:72.PubMedPubMedCentralGoogle Scholar
  52. 52.
    Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6):649–55.PubMedGoogle Scholar
  53. 53.
    Bergo E, Lombardi G, Guglieri I, Capovilla E, Pambuku A, Zagonel V. Neurocognitive functions and health-related quality of life in glioblastoma patients: a concise review of the literature. Eur J Cancer Care (Engl). 2015; Scholar
  54. 54.
    Gehrke AK, Baisley MC, Sonck AL, Wronski SL, Feuerstein M. Neurocognitive deficits following primary brain tumor treatment: systematic review of a decade of comparative studies. J Neuro-Oncol. 2013;115(2):135–42.Google Scholar
  55. 55.
    Davidson PS, Gao FQ, Mason WP, Winocur G, Anderson ND. Verbal fluency, trail making, and Wisconsin Card Sorting Test performance following right frontal lobe tumor resection. J Clin Exp Neuropsychol. 2008;30(1):18–32.PubMedGoogle Scholar
  56. 56.
    Rapp SR, Case LD, Peiffer A, Naughton MM, Chan MD, Stieber VW, et al. Donepezil for irradiated brain tumor survivors: a phase III randomized placebo-controlled clinical trial. J Clin Oncol. 2015;33(15):1653–9.PubMedPubMedCentralGoogle Scholar
  57. 57.
    Hulshof MC, Stark NM, van der Kleij A, Sminia P, Smeding HM, Gonzalez GD. Hyperbaric oxygen therapy for cognitive disorders after irradiation of the brain. Strahlenther Onkol. 2002;178(4):192–8.PubMedGoogle Scholar
  58. 58.
    Zucchella C, Capone A, Codella V, De Nunzio AM, Vecchione C, Sandrini G, et al. Cognitive rehabilitation for early post-surgery inpatients affected by primary brain tumor: a randomized, controlled trial. J Neuro-Oncol. 2013;114(1):93–100.Google Scholar
  59. 59.
    Catt S, Chalmers A, Fallowfield L. Psychosocial and supportive-care needs in high-grade glioma. Lancet Oncol. 2008;9(9):884–91.PubMedGoogle Scholar
  60. 60.
    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.Google Scholar
  61. 61.
    Hickmann AK, Nadji-Ohl M, Haug M, Hopf NJ, Ganslandt O, Giese A, et al. Suicidal ideation, depression, and health-related quality of life in patients with benign and malignant brain tumors: a prospective observational study in 83 patients. Acta Neurochir. 2016;158(9):1669–82.PubMedGoogle Scholar
  62. 62.
    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; discussion 366–7.PubMedGoogle Scholar
  63. 63.
    Rooney A, Grant R. Pharmacological treatment of depression in patients with a primary brain tumour. Cochrane Database Syst Rev. 2013;(5):CD006932.Google Scholar
  64. 64.
    Wen PY, Schiff D, Kesari S, Drappatz J, Gigas DC, Doherty L. Medical management of patients with brain tumors. J Neuro-Oncol. 2006;80(3):313–32.Google Scholar
  65. 65.
    Johannessen Landmark C, Henning O, Johannessen SI. Proconvulsant effects of antidepressants – What is the current evidence? Epilepsy Behav. 2016;61:287–91.PubMedGoogle Scholar
  66. 66.
    Verrotti A, Prezioso G, Di Sabatino F, Franco V, Chiarelli F, Zaccara G. The adverse event profile of levetiracetam: a meta-analysis on children and adults. Seizure. 2015;31:49–55.PubMedGoogle Scholar
  67. 67.
    Molassiotis A, Wilson B, Brunton L, Chaudhary H, Gattamaneni R, McBain C. Symptom experience in patients with primary brain tumours: a longitudinal exploratory study. Eur J Oncol Nurs. 2010;14(5):410–6.PubMedGoogle Scholar
  68. 68.
    Faithfull S, Brada M. Somnolence syndrome in adults following cranial irradiation for primary brain tumours. Clin Oncol (R Coll Radiol). 1998;10(4):250–4.Google Scholar
  69. 69.
    Lovely MP, Miaskowski C, Dodd M. Relationship between fatigue and quality of life in patients with glioblastoma multiformae. Oncol Nurs Forum. 1999;26(5):921–5.PubMedGoogle Scholar
  70. 70.
    Day J, Yust-Katz S, Cachia D, Wefel J, Katz LH, Tremont I, et al. Interventions for the management of fatigue in adults with a primary brain tumour. Cochrane Database Syst Rev. 2016;(4):CD011376.Google Scholar
  71. 71.
    Adelbratt S, Strang P. Death anxiety in brain tumour patients and their spouses. Palliat Med. 2000;14(6):499–507.PubMedGoogle Scholar
  72. 72.
    Strang S, Strang P, Ternestedt BM. Existential support in brain tumour patients and their spouses. Support Care Cancer. 2001;9(8):625–33.PubMedGoogle Scholar
  73. 73.
    van Breemen MS, Wilms EB, Vecht CJ. Epilepsy in patients with brain tumours: epidemiology, mechanisms, and management. Lancet Neurol. 2007;6(5):421–30.PubMedGoogle Scholar
  74. 74.
    Glantz MJ, Cole BF, Forsyth PA, Recht LD, Wen PY, Chamberlain MC, et al. Practice parameter: anticonvulsant prophylaxis in patients with newly diagnosed brain tumors. Report of the quality standards subcommittee of the American Academy of Neurology. Neurology. 2000;54(10):1886–93.PubMedGoogle Scholar
  75. 75.
    Mikkelsen T, Paleologos NA, Robinson PD, Ammirati M, Andrews DW, Asher AL, et al. The role of prophylactic anticonvulsants in the management of brain metastases: a systematic review and evidence-based clinical practice guideline. J Neuro-Oncol. 2010;96(1):97–102.Google Scholar
  76. 76.
    Perucca E. Optimizing antiepileptic drug treatment in tumoral epilepsy. Epilepsia. 2013;54(Suppl 9):97–104.PubMedGoogle Scholar
  77. 77.
    Delattre JY, Safai B, Posner JB. Erythema multiforme and Stevens-Johnson syndrome in patients receiving cranial irradiation and phenytoin. Neurology. 1988;38(2):194–8.PubMedGoogle Scholar
  78. 78.
    Hoang-Xuan K, Delattre JY, Poisson M. Stevens-Johnson syndrome in a patient receiving cranial irradiation and carbamazepine. Neurology. 1990;40(7):1144–5.PubMedGoogle Scholar
  79. 79.
    Lawson LA, Blouin RA, Smith RB, Rapp RP, Young AB. Phenytoin-dexamethasone interaction: a previously unreported observation. Surg Neurol. 1981;16(1):23–4.PubMedGoogle Scholar
  80. 80.
    Schiff D, Lee EQ, Nayak L, Norden AD, Reardon DA, Wen PY. Medical management of brain tumors and the sequelae of treatment. Neuro-Oncology. 2015;17(4):488–504.PubMedGoogle Scholar
  81. 81.
    Rossetti AO, Jeckelmann S, Novy J, Roth P, Weller M, Stupp R. Levetiracetam and pregabalin for antiepileptic monotherapy in patients with primary brain tumors. A phase II randomized study. Neuro-Oncology. 2014;16(4):584–8.PubMedGoogle Scholar
  82. 82.
    Usery JB, Michael LM, Sills AK, Finch CK. A prospective evaluation and literature review of levetiracetam use in patients with brain tumors and seizures. J Neuro-Oncol. 2010;99(2):251–60.Google Scholar
  83. 83.
    Brodie MJ, Besag F, Ettinger AB, Mula M, Gobbi G, Comai S, et al. Epilepsy, antiepileptic drugs, and aggression: an evidence-based review. Pharmacol Rev. 2016;68(3):563–602.PubMedPubMedCentralGoogle Scholar
  84. 84.
    Weller M, Gorlia T, Cairncross JG, van den Bent MJ, Mason W, Belanger K, et al. Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma. Neurology. 2011;77(12):1156–64.PubMedPubMedCentralGoogle Scholar
  85. 85.
    Kerkhof M, Dielemans JC, van Breemen MS, Zwinkels H, Walchenbach R, Taphoorn MJ, et al. Effect of valproic acid on seizure control and on survival in patients with glioblastoma multiforme. Neuro-Oncology. 2013;15(7):961–7.PubMedPubMedCentralGoogle Scholar
  86. 86.
    Kerkhof M, Vecht CJ. Seizure characteristics and prognostic factors of gliomas. Epilepsia. 2013;54(Suppl 9):12–7.PubMedGoogle Scholar
  87. 87.
    Chaichana KL, Parker SL, Olivi A, Quiñones-Hinojosa A. Long-term seizure outcomes in adult patients undergoing primary resection of malignant brain astrocytomas. Clin Artic J Neurosurg. 2009;111(2):282–92.Google Scholar
  88. 88.
    Flechl B, Ackerl M, Sax C, Oberndorfer S, Calabek B, Sizoo E, et al. The caregivers’ perspective on the end-of-life phase of glioblastoma patients. J Neuro-Oncol. 2013;112(3):403–11.Google Scholar
  89. 89.
    Ly KI, Wen PY. Clinical relevance of steroid use in neuro-oncology. Curr Neurol Neurosci Rep. 2017;17(1):5.PubMedGoogle Scholar
  90. 90.
    Hempen C, Weiss E, Hess CF. Dexamethasone treatment in patients with brain metastases and primary brain tumors: do the benefits outweigh the side-effects? Support Care Cancer. 2002;10(4):322–8.PubMedGoogle Scholar
  91. 91.
    Liu R, Page M, Solheim K, Fox S, Chang SM. Quality of life in adults with brain tumors: current knowledge and future directions. Neuro-Oncology. 2009;11(3):330–9.PubMedPubMedCentralGoogle Scholar
  92. 92.
    Russo M, Villani V, Taga A, Genovese A, Terrenato I, Manzoni GC, et al. Headache as a presenting symptom of glioma: a cross-sectional study. Cephalalgia. 2017;38(4):730–5.PubMedGoogle Scholar
  93. 93.
    Walbert T, Khan M. End-of-life symptoms and care in patients with primary malignant brain tumors: a systematic literature review. J Neuro-Oncol. 2014;117(2):217–24.Google Scholar
  94. 94.
    Bausewein C, Hau P, Borasio GD, Voltz R. How do patients with primary brain tumours die? Palliat Med. 2003;17(6):558–9.PubMedGoogle Scholar
  95. 95.
    Sherwood PR, Given BA, Doorenbos AZ, Given CW. Forgotten voices: lessons from bereaved caregivers of persons with a brain tumour. Int J Palliat Nurs. 2004;10(2):67–75; discussion.PubMedGoogle Scholar
  96. 96.
    Janda M, Steginga S, Dunn J, Langbecker D, Walker D, Eakin E. Unmet supportive care needs and interest in services among patients with a brain tumour and their carers. Patient Educ Couns. 2008;71(2):251–8.PubMedGoogle Scholar
  97. 97.
    Sizoo EM, Braam L, Postma TJ, Pasman HR, Heimans JJ, Klein M, et al. Symptoms and problems in the end-of-life phase of high-grade glioma patients. Neuro-Oncology. 2010;12(11):1162–6.PubMedPubMedCentralGoogle Scholar
  98. 98.
    Anderson GD, Saneto RP. Current oral and non-oral routes of antiepileptic drug delivery. Adv Drug Deliv Rev. 2012;64(10):911–8.PubMedGoogle Scholar
  99. 99.
    August DA, Huhmann MB, the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Board of Directors. A.S.P.E.N Clinical Guidelines: Nutrition Support Therapy During Adult Anticancer Treatment and in Hematopoietic Cell Transplantation. Journal of Parenteral and Enteral Nutrition 2009;33(5):472–500.PubMedGoogle Scholar
  100. 100.
    Mummudi N, Jalali R. Palliative care and quality of life in neuro-oncology. F1000Prime Rep. 2014;6:71.PubMedPubMedCentralGoogle Scholar
  101. 101.
    Koekkoek JA, Dirven L, Reijneveld JC, Sizoo EM, Pasman HR, Postma TJ, et al. End of life care in high-grade glioma patients in three European countries: a comparative study. J Neuro-Oncol. 2014;120(2):303–10.Google Scholar
  102. 102.
    Janssens R, van Delden JJ, Widdershoven GA. Palliative sedation: not just normal medical practice. Ethical reflections on the Royal Dutch Medical Association’s guideline on palliative sedation. J Med Ethics. 2012;38(11):664–8.PubMedGoogle Scholar
  103. 103.
    Walbert T. Integration of palliative care into the neuro-oncology practice: patterns in the United States. Neurooncol Pract. 2014;1(1):3–7.PubMedPubMedCentralGoogle Scholar
  104. 104.
    Walbert T, Chasteen K. Palliative and supportive care for glioma patients. Cancer Treat Res. 2015;163:171–84.PubMedGoogle Scholar
  105. 105.
    Walbert T, Pace A. End-of-life care in patients with primary malignant brain tumors: early is better. Neuro-Oncology. 2016;18:7–8.PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Neuro-OncologyMayo Clinic ArizonaPhoenixUSA
  2. 2.Department of NeurologyAlvord Brain Tumor CenterSeattleUSA

Personalised recommendations