Quality-adjusted life years in glioma patients: a systematic review on currently available data and the lack of evidence-based utilities

  • Vicki Marie Butenschoen
  • Anna Kelm
  • Bernhard Meyer
  • Sandro M. KriegEmail author
Topic Review



Cost-effectiveness studies gain importance in the context of rising health care expenses and treatment options. Especially in the neuro-oncological context, surgical therapy may increase overall survival, but restrain the patient by postoperative disability. Quality-adjusted life years, express treatment effects and are based on health utilities. In our study, we analyze the current evidence on health economic evaluations in glioma patients.

Material and methods

We performed a systematic database search including Medline and Cochrane Library. Studies were critically appraised for statistical analyzes including glioma patients, health economic modeling and detailed health outcome. Study evidence was classified according to levels of evidence for therapeutic studies from the Centre for Evidence-Based Medicine (Oxford).


37 studies (1995–2018) were identified, 29 matched our inclusion criteria. Studies addressed surgical cost-efficiency and/or the standard treatment, postoperative chemotherapy (n = 6) and 5-ALA (n = 3). Only 16 studies used QALY as the outcome measure, most used overall survival or life years gained (LYG). Utilities were either based on one single study (Garside et al. in Health Technol Assess 11:iii–iv, ix-221) or derived from visual analogue scale (VAS). None assessed quality of life values for specific health statuses or utilities. Incremental cost-effectiveness ratios varied from 8325€ per QALY (5-ALA) to 518,342€ per LYG (tumor treating fields).


Only one study generated utility values to conduct cost-effectiveness analysis (CEA); most studies used indirect outcomes such as LYG or based their model on previously published data. Health economic evaluations lack specific utilities, further investigations are necessary to conduct reliable CEA in the neurosurgical context.


Quality of life Glioma Cost-effectiveness 


Author contributions

VB, AK and SK made substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data; SK and VB have been involved in drafting the manuscript or revising it critically for important intellectual content; SK and BM given final approval of the version to be published. VB and SK agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.


This work was financed by the Department of Neurosurgery, Technische Universität München, Klinikum rechts der Isar.

Compliance with ethical standards

Conflict of interest

SK is a consultant for Spineart Deutschland GmbH (Frankfurt, Germany) and Nexstim Plc (Helsinki, Finland) and received honoraria from Medtronic (Meerbusch, Germany) and Carl Zeiss Meditec (Oberkochen, Germany). SK and BM received research grants from and are consultants for Brainlab AG (Munich, Germany). BM received honoraria, consulting fees, and research grants from Medtronic (Meerbusch, Germany), icotec ag (Altstätten, Switzerland), and Relievant Medsystemy Inc. (Sunnyvale, CA, USA), honoraria and research grants from Ulrich Medical (Ulm, Germany), honoraria and consulting fees from Spineart Deutschland GmbH (Frankfurt, Germany) and DePuy Synthes (West Chester, PA, USA), and royalties from Spineart Deutschland GmbH (Frankfurt, Germany). Yet, all authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this publication.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The data used was based on previously published data, there was no need for ethics approval.

Informed consent

Informed consent for publication was obtained.


  1. 1.
    Duffau H (2015) Preserving quality of life is not incompatible with increasing overall survival in diffuse low-grade glioma patients. Acta Neurochir 157:165–167. CrossRefGoogle Scholar
  2. 2.
    Soffietti R, Baumert BG, Bello L, von Deimling A, Duffau H, Frénay M, Grisold W, Grant R, Graus F, Hoang-Xuan K, Klein M, Melin B, Rees J, Siegal T, Smits A, Stupp R, Wick W, Societies EFoN (2010) Guidelines on management of low-grade gliomas: report of an EFNS-EANO Task Force. Eur J Neurol 17:1124–1133. CrossRefGoogle Scholar
  3. 3.
    Hickmann AK, Hechtner M, Nadji-Ohl M, Janko M, Reuter AK, Kohlmann K, Haug M, Grüninger S, Deininger M, Ganslandt O, König J, Wirtz CR, Coburger J, Renovanz M (2017) Evaluating patients for psychosocial distress and supportive care needs based on health-related quality of life in primary brain tumors: a prospective multicenter analysis of patients with gliomas in an outpatient setting. J Neurooncol 131:135–151. CrossRefGoogle Scholar
  4. 4.
    Jakola AS, Unsgård G, Solheim O (2011) Quality of life in patients with intracranial gliomas: the impact of modern image-guided surgery. J Neurosurg 114:1622–1630. CrossRefGoogle Scholar
  5. 5.
    Jakola AS, Sagberg LM, Gulati S, Solheim O (2015) Perioperative quality of life in functionally dependent glioblastoma patients: a prospective study. Br J Neurosurg 29:843–849. CrossRefGoogle Scholar
  6. 6.
    Fountain DM, Allen D, Joannides AJ, Nandi D, Santarius T, Chari A (2016) Reporting of patient-reported health-related quality of life in adults with diffuse low-grade glioma: a systematic review. Neuro Oncol 18:1475–1486. CrossRefGoogle Scholar
  7. 7.
    Armstrong TS, Gilbert MR (2014) Patient reported endpoints for measuring clinical benefit in (high grade glioma) primary brain tumor patients. Curr Treat Options Oncol 15:519–528. CrossRefGoogle Scholar
  8. 8.
    Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO, Groups EOfRaToCBTaR, Group NCIoCCT (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996. CrossRefGoogle Scholar
  9. 9.
    Claxton K, Martin S, Soares M, Rice N, Spackman E, Hinde S, Devlin N, Smith PC, Sculpher M (2015) Methods for the estimation of the National Institute for Health and Care Excellence cost-effectiveness threshold. Health Technol Assess 19:1–503, v–vi. CrossRefGoogle Scholar
  10. 10.
    Cheng JX, Zhang X, Liu BL (2009) Health-related quality of life in patients with high-grade glioma. Neuro Oncol 11:41–50. CrossRefGoogle Scholar
  11. 11.
    Taphoorn MJ, Sizoo EM, Bottomley A (2010) Review on quality of life issues in patients with primary brain tumors. Oncologist 15:618–626. CrossRefGoogle Scholar
  12. 12.
    Sagberg LM, Jakola AS, Solheim O (2014) Quality of life assessed with EQ-5D in patients undergoing glioma surgery: what is the responsiveness and minimal clinically important difference? Qual Life Res 23:1427–1434. CrossRefGoogle Scholar
  13. 13.
    Boele FW, Douw L, Reijneveld JC, Robben R, Taphoorn MJ, Aaronson NK, Heimans JJ, Klein M (2015) Health-related quality of life in stable, long-term survivors of low-grade glioma. J Clin Oncol 33:1023–1029. CrossRefGoogle Scholar
  14. 14.
    Muacevic A, Kreth FW (2003) Quality-adjusted survival after tumor resection and/or radiation therapy for elderly patients with glioblastoma multiforme. J Neurol 250:561–568. CrossRefGoogle Scholar
  15. 15.
    Murray KJ, Nelson DF, Scott C, Fischbach AJ, Porter A, Farnan N, Curran WJ (1995) Quality-adjusted survival analysis of malignant glioma. Patients treated with twice-daily radiation (RT) and carmustine: a report of Radiation Therapy Oncology Group (RTOG) 83–02. Int J Radiat Oncol Biol Phys 31:453–459. CrossRefGoogle Scholar
  16. 16.
    Scott CB (1997) Quality-adjusted survival analysis of malignant glioma patients. Control Clin Trials 18:277–285CrossRefGoogle Scholar
  17. 17.
    Howick J, Iain Chalmers PG, Greenhalgh T, Heneghan C, Liberati A, Moschetti I, Phillips B, Thornton H (2011) The 2011 Oxford CEBM levels of evidence (Introductory document). Oxford University Press, OxfordGoogle Scholar
  18. 18.
    Edejer TT (2006) Improving the use of research evidence in guideline development: 11. Incorporating considerations of cost-effectiveness, affordability and resource implications. Health Res Policy Syst 4:23. CrossRefGoogle Scholar
  19. 19.
    Raizer JJ, Fitzner KA, Jacobs DI, Bennett CL, Liebling DB, Luu TH, Trifilio SM, Grimm SA, Fisher MJ, Haleem MS, Ray PS, McKoy JM, DeBoer R, Tulas KM, Deeb M (2015) Economics of malignant gliomas: a critical review. J Oncol Pract 11:e59–65. CrossRefGoogle Scholar
  20. 20.
    Ray S, Bonafede MM, Mohile NA (2014) Treatment patterns, survival, and healthcare costs of patients with malignant gliomas in a large us commercially insured population. Am Health Drug Benefits 7:140–149Google Scholar
  21. 21.
    Jakola AS, Unsgard G, Myrmel KS, Kloster R, Torp SH, Lindal S, Solheim O (2012) Low grade gliomas in eloquent locations: implications for surgical strategy, survival and long term quality of life. PLoS ONE 7:e51450. CrossRefGoogle Scholar
  22. 22.
    Butenschon VM, Ille S, Sollmann N, Meyer B, Krieg SM (2018) Cost-effectiveness of preoperative motor mapping with navigated transcranial magnetic brain stimulation in patients with high-grade glioma. Neurosurg Focus 44:e18. CrossRefGoogle Scholar
  23. 23.
    Ghosh S, Baker S, de Castro DG, Kepka L, Kumar N, Sinaika V, Matiello J, Lomidze D, Dyttus-Cebulok K, Rosenblatt E, Fidarova E, Roa W (2018) Improved cost-effectiveness of short-course radiotherapy in elderly and/or frail patients with glioblastoma. Radiother Oncol 127:114–120. CrossRefGoogle Scholar
  24. 24.
    Bernard-Arnoux F, Lamure M, Ducray F, Aulagner G, Honnorat J, Armoiry X (2016) The cost-effectiveness of tumor-treating fields therapy in patients with newly diagnosed glioblastoma. Neuro Oncol 18:1129–1136. CrossRefGoogle Scholar
  25. 25.
    Diebold G, Ducray F, Henaine AM, Frappaz D, Guyotat J, Cartalat-Carel S, Breant V, Fouquet A, Aulagner G, Honnorat J, Armoiry X (2014) Management of glioblastoma: comparison of clinical practices and cost-effectiveness in two cohorts of patients (2008 versus 2004) diagnosed in a French University Hospital. J Clin Pharm Ther 39:642–648. CrossRefGoogle Scholar
  26. 26.
    Lamers LM, Stupp R, van den Bent MJ, Al MJ, Gorlia T, Wasserfallen JB, Mittmann N, Jin Seung S, Crott R, Uyl-de Groot CA, Study EN-CCI (2008) Cost-effectiveness of temozolomide for the treatment of newly diagnosed glioblastoma multiforme: a report from the EORTC 26981/22981 NCI-C CE3 Intergroup Study. Cancer 112:1337–1344. CrossRefGoogle Scholar
  27. 27.
    Uyl-de Groot CA, Stupp R, van der Bent M (2009) Cost-effectiveness of temozolomide for the treatment of newly diagnosed glioblastoma multiforme. Expert Rev Pharmacoecon Outcomes Res 9:235–241. CrossRefGoogle Scholar
  28. 28.
    Johannesen TB, Norum J, Lote K, Scheie D, Hirschberg H (2002) A cost-minimising analysis of standard radiotherapy and two experimental therapies in glioblastoma. Radiother Oncol 62:227–231CrossRefGoogle Scholar
  29. 29.
    Latif AZ, Signorini D, Gregor A, Whittle IR (1998) The costs of managing patients with malignant glioma at a neuro-oncology clinic. Br J Neurosurg 12:118–122CrossRefGoogle Scholar
  30. 30.
    Martino J, Gomez E, Bilbao JL, Dueñas JC, Vázquez-Barquero A (2013) Cost-utility of maximal safe resection of WHO grade II gliomas within eloquent areas. Acta Neurochir 155:41–50. CrossRefGoogle Scholar
  31. 31.
    Martikainen JA, Kivioja A, Hallinen T, Vihinen P (2005) Economic evaluation of temozolomide in the treatment of recurrent glioblastoma multiforme. Pharmacoeconomics 23:803–815. CrossRefGoogle Scholar
  32. 32.
    Briggs A, Sculpher M, Claxton K (2006) Decision modelling for health economic evaluation. Oxford University Press, OxfordGoogle Scholar
  33. 33.
    Garside R, Pitt M, Anderson R, Rogers G, Dyer M, Mealing S, Somerville M, Price A, Stein K (2007) The effectiveness and cost-effectiveness of carmustine implants and temozolomide for the treatment of newly diagnosed high-grade glioma: a systematic review and economic evaluation. Health Technol Assess 11:3–4Google Scholar
  34. 34.
    Rogers G, Garside R, Mealing S, Pitt M, Anderson R, Dyer M, Stein K, Somerville M (2008) Carmustine implants for the treatment of newly diagnosed high-grade gliomas: a cost-utility analysis. Pharmacoeconomics 26:33–44CrossRefGoogle Scholar
  35. 35.
    Esteves S, Alves M, Castel-Branco M, Stummer W (2015) A pilot cost-effectiveness analysis of treatments in newly diagnosed high-grade gliomas: the example of 5-aminolevulinic Acid compared with white-light surgery. Neurosurgery 76:552–562; discussion 562. CrossRefGoogle Scholar
  36. 36.
    Slof J, Díez Valle R, Galván J (2015) Cost-effectiveness of 5-aminolevulinic acid-induced fluorescence in malignant glioma surgery. Neurologia 30:163–168. CrossRefGoogle Scholar
  37. 37.
    Haagsma JA, Maertens de Noordhout C, Polinder S, Vos T, Havelaar AH, Cassini A, Devleesschauwer B, Kretzschmar ME, Speybroeck N, Salomon JA (2015) Assessing disability weights based on the responses of 30660 people from four European countries. Popul Health Metr 13:10. CrossRefGoogle Scholar
  38. 38.
    Paquette B, Vernerey D, Chauffert B, Dabakuyo S, Feuvret L, Taillandier L, Frappaz D, Taillia H, Schott R, Ducray F, Fabbro M, Tennevet I, Ghiringhelli F, Guillamo JS, Durando X, Castera D, Frenay M, Campello C, Dalban C, Skrzypski J, Chinot O, Anota A, Bonnetain F (2016) Prognostic value of health-related quality of life for death risk stratification in patients with unresectable glioblastoma. Cancer Med 5:1753–1764. CrossRefGoogle Scholar
  39. 39.
    Guzauskas GF, Pollom EL, Stieber VW, Wang BCM, Garrison LP Jr (2019) Tumor treating fields and maintenance temozolomide for newly-diagnosed glioblastoma: a cost-effectiveness study. J Med Econ. Google Scholar
  40. 40.
    Wichmann AB, Adang EM, Stalmeier PF, Kristanti S, Van den Block L, Vernooij-Dassen MJ, Engels Y, PACE (2017) The use of quality-adjusted life years in cost-effectiveness analyses in palliative care: mapping the debate through an integrative review. Palliat Med 31:306–322. CrossRefGoogle Scholar
  41. 41.
    Walker M, Brown J, Brown K, Gregor A, Whittle IR, Grant R (2003) Practical problems with the collection and interpretation of serial quality of life assessments in patients with malignant glioma. J Neurooncol 63:179–186CrossRefGoogle Scholar
  42. 42.
    Jakola AS, Solheim O, Gulati S, Sagberg LM (2017) Is there a response shift in generic health-related quality of life 6 months after glioma surgery? Acta Neurochir 159:377–384. CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Neurosurgery, Klinikum Rechts Der IsarTechnische Universität MünchenMunichGermany

Personalised recommendations