Abstract
The novel anti-mitotic based tumor treating fields (TTFields) is FDA approved for recurrent glioblastoma. Recently the phase III upfront trial combining the Novo TTF-100A device, called Optune, with temozolomide following concurrent radiation therapy and chemotherapy, demonstrated improvement in survival. Wider use of this novel therapy is expected. The most common adverse event is dermatologic, which dominates compared to the next most frequently observed adverse event of headaches, the incidence of which was even in both arms in the phase III registration trial for recurrent glioblastoma. Our case review outlines the presentation, treatment, and outcome of representative patients using TTFields. In summary, preventative strategies to inform and educate patients and operators can prevent many of these dermatological events. Skin toxicity in the setting of concurrent use of TTFields with other therapies such as bevacizumab is an unknown and will need to be closely followed.
Similar content being viewed by others
References
Davies AM, Weinberg U, Palti Y (2013) Tumor treating fields: a new frontier in cancer therapy. Ann N Y Acad Sci 1291:86–95. doi:10.1111/nyas.12112
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. doi:10.1001/jama.2015.16669
Stupp R, Wong ET, Kanner AA, Steinberg D, Engelhard H, Heidecke V, Kirson ED, Taillibert S, Liebermann F, Dbaly 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. doi:10.1016/j.ejca.2012.04.011
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-S13. doi:10.1053/j.seminoncol.2014.09.010
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
Westbury C, Hines F, Hawkes E, Ashley S, Brada M (2000) Advice on hair and scalp care during cranial radiotherapy: a prospective randomized trial. Radiother Oncol 54:109–116
NovoTTF-100A With Bevacizumab (Avastin) in Patients with recurrent glioblastoma.ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01894061?term=bevacizumab+and+novocure&rank=3. Accessed 21 May 2017
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(Suppl 4): S1–S14 doi:10.1053/j.seminoncol.2014.03.011
NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0. http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf
Chen AP, Setser A, Anadkat MJ, Cotliar J, Olsen EA, Garden BC, Lacouture ME (2012) Grading dermatologic adverse events of cancer treatments: the common terminology criteria for adverse events version 4.0. J Am Acad Dermatol 67:1025–1039. doi:10.1016/j.jaad.2012.02.010
Grice EA, Segre JA (2011) The skin microbiome. Nat Rev Microbiol 9:244–253. doi:10.1038/nrmicro2537
Post-approval Study of NovoTTF-100A in Recurrent GBM patients. ClinicalTrials.gov.https://clinicaltrials.gov/ct2/show/NCT01756729?term=ef+19&rank=1. Accessed May 21, 2017
Voegeli D (2013) Moisture-associated skin damage: an overview for community nurses. Br J Community Nurs 18(6):10–12. doi:10.12968/bjcn.2013.18.Sup9.S6
Christopherson KM, Rotondo RL, Bradley JA, Pincus DW, Wynn TT, Fort JA, Morris CG, Mendenhall NP, Marcus RB Jr, Indelicato DJ (2014) Late toxicity following craniospinal radiation for early-stage medulloblastoma. Acta Oncol 53:471–480. doi:10.3109/0284186X.2013.862596
Rudolph R, Utley J, Woodward M, Hurn I (1981) The ultrastructure of chronic radiation damage in rat skin. Surg Gynecol Obstet 152:171–178
Kirson ED, Schneiderman RS, Dbaly 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 9:1. doi:10.1186/1756-6649-9-1
Salzberg M, Kirson E, Palti Y, Rochlitz C (2008) A pilot study with very low-intensity, intermediate-frequency electric fields in patients with locally advanced and/or metastatic solid tumors. Onkologie 31:362–365. doi:10.1159/000137713
Pless M, Droege C, von Moos R, Salzberg M, Betticher D (2013) A phase I/II trial of Tumor Treating Fields (TTFields) therapy in combination with pemetrexed for advanced non-small cell lung cancer. Lung Cancer 81:445–450. doi:10.1016/j.lungcan.2013.06.025
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
This article does not contain studies with human participants performed by any of the authors.
Rights and permissions
About this article
Cite this article
Lukas, R.V., Ratermann, K.L., Wong, E.T. et al. Skin toxicities associated with tumor treating fields: case based review. J Neurooncol 135, 593–599 (2017). https://doi.org/10.1007/s11060-017-2612-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11060-017-2612-8