Advertisement

Acta Neurochirurgica

, Volume 160, Issue 6, pp 1167–1174 | Cite as

Tumor-treating fields as a fourth treating modality for glioblastoma: a meta-analysis

  • Dimitrios E. Magouliotis
  • Eftihia K. Asprodini
  • Konstantina A. Svokos
  • Vasiliki S. Tasiopoulou
  • Alexis A. Svokos
  • Steven A. Toms
Original Article - Brain Tumors

Abstract

Background

We aim to review the available literature on patients suffering from glioblastoma treated with tumor-treating fields (TTFields) plus radio chemotherapy or conventional radio chemotherapy alone, to compare the efficacy and safety of the two methods.

Methods

A systematic literature search was performed in PubMed, Cochrane library, and Scopus databases, in accordance with the PRISMA guidelines. Six studies met the inclusion criteria incorporating 1806 patients for the qualitative analysis and 1769 for the quantitative analysis.

Results

This study reveals increased median overall survival (weighted mean difference (WMD) 3.29 [95% confidence interval (CI) 2.37, 4.21]; p < 0.00001), survival at 1 year (odds ratio (OR) 1.81 [95% CI 1.41, 2.32]; p < 0.00001) and 2 years (OR 2.33 [95% CI 1.73, 3.14]; p < 0.00001), and median progression-free survival (WMD 2.35 [95% CI 1.76, 2.93]; p < 0.00001) along with progression-free survival at 6 months (WMD 6.86 [95% CI 5.91, 7.81]; p < 0.00001) for the patients treated with TTFields. Survival at 3 years was comparable between the two groups. TTFields were associated with fewer adverse events compared to chemotherapy along with similar incidence of skin irritation.

Conclusions

TTFields are a safe and efficient novel treatment modality. More randomized controlled studies, with longer follow-up, are necessary to further assess the clinical outcomes of TTFields.

Keywords

Glioblastoma Tumor-treating fields TTFields Alternating electric fields Meta-analysis 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

Does not apply.

Supplementary material

701_2018_3536_MOESM1_ESM.docx (65 kb)
Table S1 (DOCX 64 kb)
701_2018_3536_MOESM2_ESM.docx (100 kb)
Table S2 (DOCX 100 kb)
701_2018_3536_MOESM3_ESM.docx (485 kb)
Fig. S1 (DOCX 484 kb)
701_2018_3536_MOESM4_ESM.docx (98 kb)
Fig. S2 (DOCX 97 kb)
701_2018_3536_MOESM5_ESM.docx (65 kb)
Fig. S3 (DOCX 65 kb)
701_2018_3536_MOESM6_ESM.docx (102 kb)
Fig. S4 (DOCX 102 kb)
701_2018_3536_MOESM7_ESM.doc (63 kb)
ESM 1 (DOC 63 kb)

References

  1. 1.
    Borensteina M, Hedgesb LV, JPT H, Rothstein HR (2010) A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods 1:97–111.  https://doi.org/10.1002/jrsm.12 CrossRefGoogle Scholar
  2. 2.
    Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, Hoang-Xuan K, Kavan P, Cernea D, Brandes AA, Hilton M, Abrey L, Cloughesy T (2014) Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med 370(8):709–722CrossRefPubMedGoogle Scholar
  3. 3.
    Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, Chakravarti A, Pugh S, Won M, Jeraj R, Brown PD, Jaeckle KA, Schiff D, Stieber VW, Brachman DG, Werner-Wasik M, Tremont-Lukats IW, Sulman EP, Aldape KD, Curran WJ Jr, Mehta MP (2014) A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med 370(8):699–708CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    GSE HJ (2011) Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]Google Scholar
  6. 6.
    Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352(10):997–1003CrossRefPubMedGoogle Scholar
  7. 7.
    Higgins JPT, Green S (2011) Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. The Cochrane Collaboration. Available from www.cochrane-handbook.org
  8. 8.
    Kanner AA, Wong ET, Villano JL, Ram Z, EF-11 Investigators (2014) Post hoc analyses of intention-to-treat population in phase III comparison of NovoTTF-100A™ system versus best physician’s choice chemotherapy. Semin Oncol 41(Suppl 6):S25–S34CrossRefPubMedGoogle Scholar
  9. 9.
    Kirson ED, Dbaly V, Tovaryš F, Vymazal J, Soustiel JF, Itzhaki A, Mordechovich D, Steinberg-Shapira S, Gurvich Z, Schneiderman R, Wasserman Y, Salzberg M, Ryffel B, Goldsher D, Dekel E, Paltiet Y (2007) Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors. PNAS www.pnas.org/cgi/doi/10.1073/pnas.0702916104
  10. 10.
    Kirson ED, Schneiderman RS, Dbalý V, Tovarys F, Vymazal J, Itzhaki A, Mordechovich D, Gurvich Z, Shmueli E, Goldsher D, Wasserman Y, Palti Y (2009) Chemotherapeutic treatment efficacy and sensitivity are increased by adjuvant alternating electric fields (TTFields). BMC Med Phys.  https://doi.org/10.1186/1756-6649-9-1
  11. 11.
    Lacouture ME, Davis ME, Elzinga G, Butowski N, Tran D, Villano JL, DiMeglio L, Davies AM, Wong ET (2014) Characterization and management of dermatologic adverse events with the NovoTTF-100A system, a novel anti-mitotic electric field device for the treatment of recurrent glioblastoma. Semin Oncol 41(No 3, Suppl 4): S1–S14.  https://doi.org/10.1053/j.seminoncol.2014.03.011
  12. 12.
    Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med 6:e1000100CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Marko NF, Weil RJ, Schroeder JL, Lang FF, Suki D, Sawaya RE (2014) Extent of resection of glioblastoma revisited: personalized survival modeling facilitates more accurate survival prediction and supports a maximum-safe-resection approach to surgery. J Clin Oncol 32(8):774–782CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Mrugala MM, Engelhard HH, Tran DD, Kew Y, Cavaliere R, Villano JL, Annenelie Bota D, Rudnick J, Love Sumrall A, Zhu JJ, Butowski (2014) Clinical practice experience with NovoTTF-100A™ system for glioblastoma: the Patient Registry Dataset (PRiDe). Semin Oncol.  https://doi.org/10.1053/j.seminoncol.2014.09.010
  15. 15.
    Ostrom QT, Gittleman H, Fulop J, Liu M, Blanda R, Kromer C, Wolinsky Y, Kruchko C, Barnholtz-Sloan JS (2015) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2008–2012. Neuro-Oncology 17(Suppl. 4):iv1–iv62.  https://doi.org/10.1093/neuonc/nov189 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Ram Z, Gutin PH, Stupp R: NO-55 (2010) Subgroup and quality of life analyses of the phase III clinical trial of NovoTTF-100A versus best standard chemotherapy for recurrent glioblastoma. Neuro-Oncology 12(Suppl 4):iv48–iv49Google Scholar
  17. 17.
    Ram Z, Wong ET, Gutin PH: NO-50 (2011) Comparing the effect of NovoTTF to bevacizumab in recurrent GBM: a post-hoc subanalysis of the phase III trial data. Neuro-Oncology 13(Suppl 3):iii52Google Scholar
  18. 18.
    Schneiderman RS, Voloshin T, Giladi M, Porat Y, Muster M, Blat T, Sherbo S, Kirson ED, Weinberg U, Palti Y (2015) p53 status dependence of tumor treating fields (TTFields) efficacy against glioma cancer cells. Neuro-Oncology 17:v23.  https://doi.org/10.1093/neuonc/nov204.25 CrossRefPubMedCentralGoogle Scholar
  19. 19.
    Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25:603–605CrossRefPubMedGoogle Scholar
  20. 20.
    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, European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996CrossRefPubMedGoogle Scholar
  21. 21.
    Stupp R, Wong ET, Kanner AA, Steinberg D, Engelhard H, Heidecke V, Kirson ED, Taillibert S, Liebermann F, Dbalý V, Ram Z, Villano JL, Rainov N, Weinberg U, Schiff D, Kunschner L, Raizer J, Honnorat J, Sloan A, Malkin M, Landolfi JC, Payer F, Mehdorn M, Weil RJ, Pannullo SC, Westphal M, Smrcka M, Chin L, Kostron H, Hofer S, Bruce J, Cosgrove R, Paleologous N, Palti Y, Gutin PH (2012) NovoTTF-100A versus physician’s choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer 48:2192–2202.  https://doi.org/10.1016/j.ejca.2012.04.011 CrossRefPubMedGoogle Scholar
  22. 22.
    Stupp R, Taillibert S, Kanner AA, Read W, Steinberg DM, Lhermitte B, Toms S, Idbaih A, Ahluwalia MS, Fink K, Di Meco F, Lieberman F, Zhu JJ, Stragliotto G, Tran DD, Brem S, Hottinger AF, Kirson ED, Lavy-Shahaf G, Weinberg U, Kim CY, Paek SH, Nicholas G, Burna J, Hirte H, Weller M, Palti Y, Hegi ME, Ram Z (2017) Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma a randomized clinical trial. JAMA 19 318(23):2306–2316.  https://doi.org/10.1001/jama.2017.18718 CrossRefPubMedGoogle Scholar
  23. 23.
    Wong ET, Ram Z, Gutin PH, Stupp R, OT-09 (2011) Updated survival data of the phase III clinical trial of NovoTTF-100A versus best standard chemotherapy for recurrent glioblastoma. Neuro-Oncology 13(Suppl 3):iii87Google Scholar
  24. 24.
    Wong ET, Lok E, Swanson KD (2015) Clinical benefit in recurrent glioblastoma from adjuvant NovoTTF-100A and TCCC after temozolomide and bevacizumab failure: a preliminary observation. Cancer Med 4(3):383–391.  https://doi.org/10.1002/cam4.421 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Yan W, Zhang W, You G, Bao Z, Wang Y, Liu Y, Kang C, You Y, Wang L, Jiang T (2012) Correlation of IDH1 mutation with clinicopathologic factors and prognosis in primary glioblastoma: a report of 118 patients from China. PLoS One 7(1):e30339.  https://doi.org/10.1371/journal.pone.0030339 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Zhu P, Du XL, Lu G, Zhu JJ (2017) Survival benefit of glioblastoma patients after FDA approval of temozolomide concomitant with radiation and bevacizumab: a population-based study. Oncotarget 8:44015–44031.  https://doi.org/10.18632/oncotarget.17054 PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of SurgeryUniversity Hospital of LarissaLarissaGreece
  2. 2.Laboratory of Pharmacology, School of MedicineUniversity of ThessalyLarissaGreece
  3. 3.Department of Neurosurgery, The Warren Alpert Medical SchoolBrown UniversityProvidenceUSA
  4. 4.Faculty of MedicineUniversity of ThessalyLarissaGreece
  5. 5.Riverside Regional Medical CenterNewport NewsUSA

Personalised recommendations