Acceptance and compliance of TTFields treatment among high grade glioma patients

  • Julia Onken
  • Franziska Staub-Bartelt
  • Peter Vajkoczy
  • Martin Misch
Clinical Study

Abstract

Background

Tumor treating fields (TTFields) significantly prolong both progression-free and overall survival in patients with newly diagnosed glioblastoma (GBM). TTFields are delivered to the brain tumor via skin transducer arrays and should be applied for a minimum of 18 h per day (≥ 75% compliance). This may cause limited acceptance by patients because of obstacles in daily routine. So far, there are limited data on factors influencing therapy acceptance and compliance.

Methods

In this retrospective study, fourty-one patients with primary GBM or recurrent high grade glioma (rHGG) have been treated with TTFields in our department. Compliance reports were generated at the monthly routine check of the device. We investigated demographic data, stage of disease and therapy duration in regard to treatment compliance.

Results

Thirty percent of patients with primary diagnosis of GBM were informed about TTFields. Acceptance rate among these patients was 36%. In this study, TTFields were prescribed in newly diagnosed GBM patients (57%) and in rHGG. Mean treatment compliance was 87% in the total population independent of age, sex and stage of disease. Compliance was not negatively correlated with time on treatment.

Conclusion

TTFields are effective in newly diagnosed GBM, therefore acceptance and compliance is important for GBM treatment. We experienced moderate acceptance rate for TTFields, which is influenced by factors such as social support, comorbidities and independence in daily life. Overall therapy compliance lies above 75% and is not influenced by age, sex, stage of disease or duration of therapy. Improved patient consultation strategies will increase acceptance and compliance for better outcome.

Keywords

Glioblastoma TTFields treatment OPTUNE® Acceptance Compliance 

Notes

Acknowledgements

J. Mansfeld from Novocure provided compliance reports of all patients during therapy and helped preparing this manuscript.

References

  1. 1.
    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 (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. New Engl J Med 352:987–996.  https://doi.org/10.1056/NEJMoa043330 CrossRefPubMedGoogle Scholar
  2. 2.
    Schaub C, Schafer N, Mack F, Stuplich M, Kebir S, Niessen M, Tzaridis T, Banat M, Vatter H, Waha A, Herrlinger U, Glas M (2016) The earlier the better? Bevacizumab in the treatment of recurrent MGMT-non-methylated glioblastoma. J Cancer Res Clin Oncol 142:1825–1829.  https://doi.org/10.1007/s00432-016-2187-3 CrossRefPubMedGoogle Scholar
  3. 3.
    Szopa W, Burley TA, Kramer-Marek G, Kaspera W (2017) Diagnostic and therapeutic biomarkers in glioblastoma: current status and future perspectives. Biomed Res Int 2017:8013575.  https://doi.org/10.1155/2017/8013575 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Hottinger AF, Pacheco P, Stupp R (2016) Tumor treating fields: a novel treatment modality and its use in brain tumors. Neuro-Oncology 18:1338–1349.  https://doi.org/10.1093/neuonc/now182 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Clark PA, Gaal JT, Strebe JK, Pasch CA, Deming DA, Kuo JS, Robins HI (2017) The effects of tumor treating fields and temozolomide in MGMT expressing and non-expressing patient-derived glioblastoma cells. J Clin Neurosci 36:120–124.  https://doi.org/10.1016/j.jocn.2016.10.042 CrossRefPubMedGoogle Scholar
  6. 6.
    Stupp R, Taillibert S, Kanner AA, Kesari S, Steinberg DM, Toms SA, Taylor LP, Lieberman F, Silvani A, Fink KL, Barnett GH, Zhu JJ, Henson JW, Engelhard HH, Chen TC, Tran DD, Sroubek J, Tran ND, Hottinger AF, Landolfi J, Desai R, Caroli M, Kew Y, Honnorat J, Idbaih A, Kirson ED, Weinberg U, Palti Y, Hegi ME, Ram Z (2015) Maintenance therapy with tumor-treating fields plus temozolomide vs temozolomide alone for glioblastoma: a randomized clinical trial. JAMA 314:2535–2543.  https://doi.org/10.1001/jama.2015.16669 CrossRefPubMedGoogle Scholar
  7. 7.
    Arvold ND, Reardon DA (2014) Treatment options and outcomes for glioblastoma in the elderly patient. Clin Interv Aging 9:357–367.  https://doi.org/10.2147/cia.s44259 PubMedPubMedCentralGoogle Scholar
  8. 8.
    Malmstrom A, Gronberg BH, Marosi C, Stupp R, Frappaz D, Schultz H, Abacioglu U, Tavelin B, Lhermitte B, Hegi ME, Rosell J, Henriksson R (2012) Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial. Lancet Oncol 13:916–926.  https://doi.org/10.1016/s1470-2045(12)70265-6 CrossRefPubMedGoogle Scholar
  9. 9.
    Wick W, Platten M, Meisner C, Felsberg J, Tabatabai G, Simon M, Nikkhah G, Papsdorf K, Steinbach JP, Sabel M, Combs SE, Vesper J, Braun C, Meixensberger J, Ketter R, Mayer-Steinacker R, Reifenberger G, Weller M (2012) Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial. Lancet Oncol 13:707–715.  https://doi.org/10.1016/s1470-2045(12)70164-x CrossRefPubMedGoogle Scholar
  10. 10.
    Zarnett OJ, Sahgal A, Gosio J, Perry J, Berger MS, Chang S, Das S (2015) Treatment of elderly patients with glioblastoma: a systematic evidence-based analysis. JAMA Neurol 72:589–596.  https://doi.org/10.1001/jamaneurol.2014.3739 CrossRefPubMedGoogle Scholar
  11. 11.
    Kesari S, Ram Z (2017) Tumor-treating fields plus chemotherapy versus chemotherapy alone for glioblastoma at first recurrence: a post hoc analysis of the EF-14 trial. CNS Oncol.  https://doi.org/10.2217/cns-2016-0049 Google Scholar
  12. 12.
    Chaudhry A, Benson L, Varshaver M, Farber O, Weinberg U, Kirson E, Palti Y (2015) NovoTTF-100A system (tumor treating fields) transducer array layout planning for glioblastoma: a NovoTAL system user study. World J Surg Oncol 13:316.  https://doi.org/10.1186/s12957-015-0722-3 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, Degroot J, Wick W, Gilbert MR, Lassman AB, Tsien C, Mikkelsen T, Wong ET, Chamberlain MC, Stupp R, Lamborn KR, Vogelbaum MA, van den Bent MJ, Chang SM (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28:1963–1972.  https://doi.org/10.1200/jco.2009.26.3541 CrossRefPubMedGoogle Scholar
  14. 14.
    Kanner AA, Wong ET, Villano JL, Ram Z (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–S34.  https://doi.org/10.1053/j.seminoncol.2014.09.008 CrossRefPubMedGoogle Scholar
  15. 15.
    Mrugala MM, Engelhard HH, Dinh Tran D, Kew Y, Cavaliere R, Villano JL, Annenelie Bota D, Rudnick J, Love Sumrall A, Zhu JJ, Butowski N (2014) Clinical practice experience with NovoTTF-100A system for glioblastoma: the Patient Registry Dataset (PRiDe). Semin Oncol 41(Suppl 6):S4–Ss13.  https://doi.org/10.1053/j.seminoncol.2014.09.010 CrossRefPubMedGoogle Scholar
  16. 16.
    Ram Z, Kim C-Y, Nicholas GA, Toms S (2017) ACTR-27. Compliance and treatment duration predict survival in a phase 3 ef-14 trial of tumor treating fields with temozolomide in patients with newly diagnosed glioblastomA. Neuro-Oncology 19:vi6–vi7.  https://doi.org/10.1093/neuonc/nox168.022 CrossRefGoogle Scholar
  17. 17.
    Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW (2016) The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131:803–820.  https://doi.org/10.1007/s00401-016-1545-1 CrossRefPubMedGoogle Scholar
  18. 18.
    Korshoej AR, Hansen FL, Thielscher A, von Oettingen GB, Sorensen JCH (2017) Impact of tumor position, conductivity distribution and tissue homogeneity on the distribution of tumor treating fields in a human brain: a computer modeling study. PLoS ONE 12:e0179214.  https://doi.org/10.1371/journal.pone.0179214 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Saria MG, Kesari S (2016) Efficacy and Safety of treating glioblastoma with tumor-treating fields therapy. Clin J Oncol Nurs 20:S9–S13.  https://doi.org/10.1188/16.cjon.s1.9-13 CrossRefPubMedGoogle Scholar
  20. 20.
    Proescholdt M, Onken J, Hau P, Doenitz C, Misch M (2017) Hout-06. TTfields for newly diagnosed glioblastoma: impact of consultation strategy. Neuro-Oncology 19:vi107.  https://doi.org/10.1093/neuonc/nox168.439 CrossRefGoogle Scholar
  21. 21.
    Macedo M, Wenger C, Salvador R, Fernandes SR, Miranda PC (2016) I. Investigating an alternative ring design of transducer arrays for tumor treating fields (TTFields). In: Engineering in medicine and biology society (EMBC), 2016 IEEE Annual International Conference of the 2016 (pp. 5168-5171). IEEE.Google Scholar
  22. 22.
    Trusheim J, Dunbar E, Battiste J, Iwamoto F, Mohile N, Damek D, Bota DA, Connelly J (2017) A state-of-the-art review and guidelines for tumor treating fields treatment planning and patient follow-up in glioblastoma. CNS Oncol 6:29–43.  https://doi.org/10.2217/cns-2016-0032 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of NeurosurgeryUniversitätsmedizin Charité BerlinBerlinGermany
  2. 2.Berlin School of Integrative Oncology (BSIO)BerlinGermany

Personalised recommendations