BlueCross BlueShield of Tennessee Medical Policy Manual

Tumor-Treatment Fields Therapy for Glioblastoma


Tumor-treatment fields (TTF) therapy is a noninvasive technology intended to treat glioblastoma on an outpatient basis using electric fields.  TTF therapy exposes cancer cells to alternating electric fields of low intensity and intermediate frequency, which are purported to both selectively inhibit tumor growth and reduce tumor angiogenesis.   Tumor treatment fields are proposed to inhibit rapidly dividing tumor cells by two mechanisms: arrest of cell proliferation and destruction of cells while undergoing division.

The NovoTTF-100A™ System (assigned the generic name of TTF) received FDA marketing approval in 2011 to deliver tumor treatment field therapy to adults with confirmed glioblastoma multiforme (GBM), following confirmed recurrence in the upper region of the brain after receiving chemotherapy.  The device is intended as an alternative to standard medical therapy for recurrent GBM after surgical and radiation options have been exhausted.  In 2014, the system’s name was changed to Optune™.  In October 2015, FDA expanded the indication for use of Optune in combination with temozolomide to include newly diagnosed GBM.  The battery-powered portable device generates the electrical fields via disposable electrodes that are noninvasively attached to the individual’s shaved scalp over the site of the tumor.  The device is used by the individual at home on a continuous basis (20 - 24 hours per day) for the duration of treatment which can last for several months.

Glioblastomas are a type of astrocytoma and the most common form of malignant primary brain tumor in adults. They comprise approximately 15 percent of all brain and central nervous system tumors and over 50 percent of all tumors that arise from glial cells. The supratentorial glioblastomas is above the tentorium, in the cerebrum, and mostly found in adults (70%). The infratentorial glioblastomas is below the tentorium, in the cerebellum, and mostly found in children (70%). GBMs are further classified as high-grade or grade IV astrocytomas, which are the most deadly type of glial cell tumor and are often resistant to standard chemotherapy. The primary treatment for GBM is debulking, or surgical reduction in size, to remove as much of the tumor as possible. Depending on the individuals physical condition, adjuvant radiation therapy, chemotherapy or a combination of the two are sometimes given. For individuals with recurring disease after the initial therapies, additional debulking surgery may be used if recurrence is localized.





Based on the small amount of published evidence and the lack of demonstrated treatment benefit to date, further evidence from high-quality trials is needed to assess the efficacy of electrical fields therapy for the treatment of recurrent glioblastoma.


BlueCross BlueShield Association. Medical Policy Reference Manual. (7:2017). Tumor treatment fields therapy for glioblastoma (1.01.29). Retrieved September 18, 2017 from BlueWeb. (13 articles and/or guidelines reviewed)

CGS Administrators, LLC. Local Coverage Article. (2017, January). Tumor treatment field therapy (TTFT) (L34823).  Retrieved September 18, 2017 from

ECRI Institute. Emerging Technology Evidence Report. (2016, July). Tumor treating fields therapy (Optune) for recurrent glioblastoma. Retrieved August 31, 2016 from ECRI Institute. (69 articles and/or guidelines reviewed)

National Comprehensive Cancer Network. (2017, August). NCCN Clinical Practice Guidelines in Oncology. (NCCN Guidelines®). Central nervous system cancers (V.1.2017). Retrieved September 18, 2017 from

Rulseh, A. M., Keller, J., Klener, J., Šroubek, J., Dbalý, V., Syrůček, M., et al. (2012). Long-term survival of patients suffering from glioblastoma multiforme treated with tumor-treating fields. World Journal of Surgical Oncology, 10 (220). (Level 4 evidence)

Stupp, R., Taillibert, S., Kanner, A., Kesari, S., Steinberg, D., Toms, S., et al. (2015). Maintenance therapy with tumor-treating fields plus temozolomide vs temozolomide alone for glioblastoma [ a randomized clinical trial. Journal of the American Medical Association, 314 (23), 2536-2545.  (Level 2 evidence)

Stupp, R., Wong, E. T., Kanner, A. A., Steinberg, D., Engelhard, H., Heidecke, V., et al. (2012). NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: A randomised phase III trial of a novel treatment modality. European Journal of Cancer, 48 (14), 2192-2202. (Level 4 evidence)

U. S. Food and Drug Administration. (2015, October). Center for Devices and Radiological Health. Pre-market approval decisions for October 2015.  P100034/S013. Retrieved August 31, 2016 from

Winifred S. Hayes, Inc. Medical Technology Directory. (2016, March). Novocure (tumor treating fields). Retrieved June 3, 2016 from (37 articles and/or guidelines reviewed)

Wong, E., Lok, E., & Swanson, K. (2015) An evidence-based review of alternating electric fields therapy for malignant gliomas. Current Treatment Options in Oncology, 2015, 16 (40), 1-11. (Level 4 evidence)

Zhu, P. and Zhu J. (2017, August) Tumor treating fields: a novel and effective therapy for glioblastoma: mechanism, efficacy, safety and future perspectives. Chinese Clinical Oncology, 6 (4), 41. Abstract retrieved September 18, from PubMed database.




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