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Steroids use and survival in patients with glioblastoma multiforme: a pooled analysis

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Abstract

Introduction

Steroids are commonly used for managing brain edema in patients with glioblastoma multiforme (GBM), treated with surgery and concomitant temozolomide-based chemoradiotherapy (CTRT). The adverse effects of glucocorticoids include lymphopenia, hyperglycemia, and risk of infection. We report the results of a meta-analysis evaluating the effects of steroids on outcome when associated with the treatment of GBM.

Methods

PubMed, the Cochrane Library, and Embase were searched from inception until September 2019 for observational or prospective studies reporting prognosis of adult patients with GBM and treated or not treated with steroids. Overall survival (OS) was the primary endpoint, and progression-free survival (PFS) was the secondary endpoint. The effect size was reported as hazard ratios (HRs) with a 95% confidence interval (CI), and an HR > 1 associated with the worst outcome in steroid users compared to non-users.

Results

Twenty-two publications were retrieved from studies selected for a total of 8,752 patients. In the primary analysis (n = 22 studies reporting data), OS was reduced in GBM patients taking steroids during treatment (HR = 1.54, 95% CI 1.37–1.75; p < 0.01). Similarly, PFS was inferior in steroid users in n = 9 studies with data available (HR = 1.28, 95% CI 1.1–1.49; p < 0.01).

Conclusions

In patients with GBM and treated with RT and/or CT, association with steroids significantly reduces survival and PFS. Use of the lowest dose of glucocorticoids for the shortest period needed to achieve the treatment goals and prevention of steroid-associated complications are essential aims of treatment of this disease.

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References

  1. Waljee AK, Rogers MAM, Lin P et al (2017) Short term use of oral corticosteroids and related harms among adults in the United States: population based cohort study. BMJ. https://doi.org/10.1136/bmj.j1415

    Article  PubMed  PubMed Central  Google Scholar 

  2. Moher D, Liberati A, Tetzlaff J, Altman D (2009) Preferred reporting items for systematic reviews and metaanalyses: the PRISMA statement. PLoS Med 6(6):e1000097. https://doi.org/10.1371/journal.pmed1.1000097

    Article  PubMed  PubMed Central  Google Scholar 

  3. Wells G, Shea B, O’Connell D, Peterson J (2000) The Newcastle–Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Hospital Research Institute, Ottawa

  4. Higgins JPT, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ Br Med J 327(7414):557–560. https://doi.org/10.1136/bmj.327.7414.557

    Article  Google Scholar 

  5. Adeberg S, Bernhardt D, Foerster R et al (2016) The influence of hyperglycemia during radiotherapy on survival in patients with primary glioblastoma. Acta Oncol (Madr) 55(2):201–207. https://doi.org/10.3109/0284186X.2015.1043397

    Article  Google Scholar 

  6. Bhavsar S, Hagan K, Arunkumar R et al (2016) Preoperative statin use is not associated with improvement in survival after glioblastoma surgery. J Clin Neurosci 31:176–180. https://doi.org/10.1016/j.jocn.2016.03.010

    Article  CAS  PubMed  Google Scholar 

  7. Carson KA, Grossman SA, Fisher JD, Shaw EG (2007) Prognostic factors for survival in adult patients with recurrent glioma enrolled onto the new approaches to brain tumor therapy CNS Consortium phase I and II clinical trials. J Clin Oncol. https://doi.org/10.1200/JCO.2006.08.1661

    Article  PubMed  Google Scholar 

  8. Colavolpe C, Chinot O, Metellus P et al (2012) FDG-PET predicts survival in recurrent high-grade gliomas treated with bevacizumab and irinotecan. Neuro Oncol 14(5):649–657. https://doi.org/10.1093/neuonc/nos012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Coleman N, Michalarea V, Alken S et al (2018) Safety, efficacy and survival of patients with primary malignant brain tumours (PMBT) in phase I (Ph1) trials: the 12-year royal Marsden experience. J Neurooncol 139(1):107–116. https://doi.org/10.1007/s11060-018-2847-z

    Article  PubMed  Google Scholar 

  10. Darlix A, Baumann C, Lorgis V et al (2013) Prolonged administration of adjuvant temozolomide improves survival in adult patients with glioblastoma. Anticancer Res 33(8):3467–3474

    CAS  PubMed  Google Scholar 

  11. Gorlia T, Stupp R, Brandes AA et al (2012) New prognostic factors and calculators for outcome prediction in patients with recurrent glioblastoma: a pooled analysis of EORTC Brain tumour Group phase i and II clinical trials. Eur J Cancer 48(8):1176–1184. https://doi.org/10.1016/j.ejca.2012.02.004

    Article  PubMed  Google Scholar 

  12. Gorlia T, van den Bent MJ, Hegi ME et al (2008) Nomograms for predicting survival of patients with newly diagnosed glioblastoma: prognostic factor analysis of EORTC and NCIC trial 26981–22981/CE3. Lancet Oncol 9(1):29–38. https://doi.org/10.1016/S1470-2045(07)70384-4

    Article  PubMed  Google Scholar 

  13. Grossman SA, Ye X, Lesser G et al (2011) Immunosuppression in patients with high-grade gliomas treated with radiation and temozolomide. Clin Cancer Res 17(16):5473–5480. https://doi.org/10.1158/1078-0432.CCR-11-0774

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Huang RY, Rahman R, Hamdan A et al (2013) Recurrent glioblastoma: volumetric assessment and stratification of patient survival with early posttreatment magnetic resonance imaging in patients treated with bevacizumab. Cancer 119(19):3479–3488. https://doi.org/10.1002/cncr.28210

    Article  CAS  PubMed  Google Scholar 

  15. Le Rhun E, Genbrugge E, Stupp R et al (2018) Associations of anticoagulant use with outcome in newly diagnosed glioblastoma. Eur J Cancer 101:95–104. https://doi.org/10.1016/j.ejca.2018.06.029

    Article  PubMed  Google Scholar 

  16. Michaelsen SR, Christensen IJ, Grunnet K et al (2013) Clinical variables serve as prognostic factors in a model for survival from glioblastoma multiforme: an observational study of a cohort of consecutive non-selected patients from a single institution. BMC Cancer. https://doi.org/10.1186/1471-2407-13-402

    Article  PubMed  PubMed Central  Google Scholar 

  17. Munck Rosenschold P, Law I, Engelholm S et al (2019) Influence of volumetric modulated arc therapy and FET-PET scanning on treatment outcomes for glioblastoma patients. Radiother Oncol. 130:149–155. https://doi.org/10.1016/j.radonc.2018.10.003

    Article  Google Scholar 

  18. Pitter KL, Tamagno I, Alikhanyan K et al (2016) Corticosteroids compromise survival in glioblastoma. Brain. https://doi.org/10.1093/brain/aww046

    Article  PubMed  PubMed Central  Google Scholar 

  19. Quillien V, Carpentier AF, Gey A et al (2019) Absolute numbers of regulatory T cells and neutrophils in corticosteroid-free patients are predictive for response to bevacizumab in recurrent glioblastoma patients. Cancer Immunol Immunother 68(6):871–882. https://doi.org/10.1007/s00262-019-02317-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Shields LBE, Shelton BJ, Shearer AJ et al (2015) Dexamethasone administration during definitive radiation and temozolomide renders a poor prognosis in a retrospective analysis of newly diagnosed glioblastoma patients. Radiat Oncol 10(1):4–11. https://doi.org/10.1186/s13014-015-0527-0

    Article  CAS  Google Scholar 

  21. Tabouret E, Barrie M, Thiebaut A et al (2013) Limited impact of prognostic factors in patients with recurrent glioblastoma multiforme treated with a bevacizumab-based regimen. J Neurooncol 114(2):191–198. https://doi.org/10.1007/s11060-013-1170-y

    Article  CAS  PubMed  Google Scholar 

  22. Urup T, Dahlrot RH, Grunnet K et al (2016) Development and validation of a prognostic model for recurrent glioblastoma patients treated with bevacizumab and irinotecan. Acta Oncol (Madr) 55(4):418–422. https://doi.org/10.3109/0284186X.2015.1114679

    Article  CAS  Google Scholar 

  23. van Linde ME, Brahm CG, de Witt Hamer PC et al (2017) Treatment outcome of patients with recurrent glioblastoma multiforme: a retrospective multicenter analysis. J Neurooncol 135(1):183–192. https://doi.org/10.1007/s11060-017-2564-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Welch MR, Grommes C (2013) Retrospective analysis of the effects of steroid therapy and antidiabetic medication on survival in diabetic glioblastoma patients. CNS Oncol 2(3):237–246. https://doi.org/10.2217/cns.13.12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wirsching HG, Tabatabai G, Roelcke U et al (2018) Bevacizumab plus hypofractionated radiotherapy versus radiotherapy alone in elderly patients with glioblastoma: the randomized, open-label, phase II ARTE trial. Ann Oncol 29(6):1423–1430. https://doi.org/10.1093/annonc/mdy120

    Article  PubMed  Google Scholar 

  26. Woo P, Ho J, Lam S et al (2018) A comparative analysis of the usefulness of survival prediction models for patients with glioblastoma in the temozolomide era: the importance of methylguanine methyltransferase promoter methylation, extent of resection, and subventricular zone location. World Neurosurg 115:e375–e385. https://doi.org/10.1016/j.wneu.2018.04.059

    Article  PubMed  Google Scholar 

  27. Ryken TC, McDermott M, Robinson PD et al (2010) The role of steroids in the management of brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol. https://doi.org/10.1007/s11060-009-0057-4

    Article  PubMed  PubMed Central  Google Scholar 

  28. Lu VM, Goyal A, Vaughan LS, McDonald KL (2018) The impact of hyperglycemia on survival in glioblastoma: a systematic review and meta-analysis. Clin Neurol Neurosurg. https://doi.org/10.1016/j.clineuro.2018.05.020

    Article  PubMed  Google Scholar 

  29. Chitadze G, Flüh C, Quabius ES et al (2017) In-depth immunophenotyping of patients with glioblastoma multiforme: impact of steroid treatment. Oncoimmunology. https://doi.org/10.1080/2162402X.2017.1358839

    Article  PubMed  PubMed Central  Google Scholar 

  30. Luedi MM, Singh SK, Mosley JC et al (2017) A dexamethasone-regulated gene signature is prognostic for poor survival in glioblastoma patients. J Neurosurg Anesthesiol. https://doi.org/10.1097/ANA.0000000000000368

    Article  PubMed  PubMed Central  Google Scholar 

  31. Kostopoulou ON, Mohammad AA, Bartek J et al (2018) Glucocorticoids promote a glioma stem cell-like phenotype and resistance to chemotherapy in human glioblastoma primary cells: biological and prognostic significance. Int J Cancer. https://doi.org/10.1002/ijc.31132

    Article  PubMed  Google Scholar 

  32. Dubinski D, Won SY, Gessler F et al (2018) Dexamethasone-induced leukocytosis is associated with poor survival in newly diagnosed glioblastoma. J Neurooncol. https://doi.org/10.1007/s11060-018-2761-4

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Oncology Unit, Medical Sciences Department, ASST Bergamo Ovest, Piazzale Ospedale 1, 24047, Treviglio, BG, Italy

    Fausto Petrelli

  2. Radiotherapy Unit, ASST Bergamo Ovest, Treviglio, BG, Italy

    Agostina De Stefani, Lorenza Bruschieri, Valentina Riboldi & Francesca Trevisan

  3. Oncology Unit, Casa Di Cura Igea, Milan, Italy

    Antonio Ghidini

  4. Oncology Unit, ASST Bergamo Est, Alzano Lombardo, BG, Italy

    Lorenzo Dottorini & Alessandro Iaculli

  5. Oncology Unit, Fondazione Poliambulanza, Brescia, Italy

    Alberto Zaniboni

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  1. Fausto Petrelli
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Correspondence to Fausto Petrelli.

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Petrelli, F., De Stefani, A., Ghidini, A. et al. Steroids use and survival in patients with glioblastoma multiforme: a pooled analysis. J Neurol 268, 440–447 (2021). https://doi.org/10.1007/s00415-020-09731-5

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  • DOI: https://doi.org/10.1007/s00415-020-09731-5

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