Tumor Treating Fields show safety & efficiency for Glioblastoma



Tumor treating fields (TTFields) therapy for cancer treatment is a new, noninvasive, regional anti-mitotic intervention modality. (See Exhibit A, below). It has been approved for the treatment of recurrent glioblastoma by the U.S. FDA. (1) It also benefits from the CE European Seal. Given its non-invasiveness and interesting mechanisms of action that promotes cancer cell apoptosis, this therapy is part of the ACR Institute’s scope of inquiry, notwithstanding its high costs. (2)


TTFields therapy delivers via electrodes  low-intensity (1-3 V/cm), intermediate-frequency (100-300 kHz), alternating electric fields ( 3) to the tumor using transducer arrays ( 4) placed on the skin around the region of the body containing the tumor. (5)

TTFields therapy affects metaphase, by disrupting mitotic spindle formation, and anaphase, by dielectrophoretic dislocation of intracellular constituents, resulting in apoptosis. (See the ACT Institute’s Education Videos). According to the manufacturer:

“Tumor Treating Fields, or TTFields, are low intensity, alternating electric fields within the intermediate frequency range. TTFields disrupt cell division through physical interactions with key molecules during mitosis. This non-invasive treatment targets solid tumors. There are two well established physical processes that TTFields use to disrupt dividing cells, dipole alignment and dielectrophoresis.” (6)


The antimitotic effect of TTFields therapy has been demonstrated in multiple cell lines when the appropriate frequency was utilized. A phase III trial of TTFields monotherapy compared to active chemotherapy in recurrent glioblastoma patients established that TTFields therapy is associated with minimal toxicity, better quality of life, and comparable efficacy to chemotherapy. (7)

The preliminary results of a Novocure-sponsored randomized clinical trial of TTF in patients with newly diagnosed glioblastoma were reported at a meeting of the Society for Neuro-Oncology in November, 2014 wherein it was showed that a statistically significant benefit in median survival for patients treated with TTF plus conventional therapy (temozolomide, radiation, and surgery) versus patients treated with conventional therapy alone, a result which led the trial’s independent data monitoring committee to recommended early study termination. (8) On the basis of these results, the FDA approved a modification of the trial protocol, allowing all patients on the trial to be offered TTF. (9) A recent peer reviewed study wrote:

“ Intra-rater reliability was very high, indicating reproducible performance”. (10)


TTFields therapy is presently a novel noninvasive low frequency therapeutic option for recurrent GBM. Ongoing and future trials are set to evaluate TTFields beyond neuro-oncology, in particular with nonsmall cell lung cancer, ovarian and pancreatic cancers. (11 )

Even though “hard-evidence” via additional clinical trials are still ongoing and inconclusive, the ACR Institute recommends this new standard of care in conjunction with integrative and holistic healing modalities, including, but not limited to other techniques in energy medicine, from electro-acupuncture, to pmef, meditation and other frequency-based modalities that can positively impact the cellular tissues.

One of the important drawbacks of this technique is its price, 20k per month. The Institute will therefore be vigilant to see if there are other less costly integrative and holistic techniques that can also selectively disrupt cancer cells’ mitotic spindle formation, in particular the dipole alignment and dielectrophoresis processes. For more information about this field, see the Institute’s workshops and reports in energy medicine and the Institute’s education video section.

Pr. Joubert (ACR Institute)


Alternating current (green curve). The horizontal axis measures time; the vertical, current or voltage.


(1). http://www.accessdata.fda.gov/cdrh_docs/pdf10/P100034b.pdf. See also http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm251669.htm.

(2) As of December 2014, treatment with the Optune device cost $21,000 per month. Kotz, Deborah (December 27, 2014). “Scalp device might help patients with brain tumors”. Boston Globe. Retrieved 30 November 2015 (Source)

( 3) Alternating current (AC), is an electric current in which the flow of electric charge periodically reverses direction, whereas in direct current (DC, also dc), the flow of electric charge is only in one direction.

(4) A transducer is a device that converts one form of energy to another. Usually a transducer converts a signal in one form of energy to a signal in another.

(5) Davies AM1, Weinberg U, Palti Y.Tumor treating fields: a new frontier in cancer therapy. Ann N Y Acad Sci. 2013 Jul;1291:86-95.

(6)  Source  http://www.novocure.com/our-therapy/mechanism-of-action.aspx

(7) Op cit.,  Davies

(8). Stupp, Roger; Wong, Eric; Scott, Charles; Taillibert, Sophie; Kanner, Andrew; Kesari, Santosh; Ram, Zvi. “Interim Analysis of the EF-14 Trial: A Prospective, Multi-center Trial of NovoTTF-100A Together With Temozolomide Compared to Temozolomide Alone in Patients with Newly Diagnosed GBM (Abstract)” (PDF). Neuro-Oncology 16 (suppl 5): v167.

(9). “Novocure Announces FDA Approval of an IDE Supplement Allowing All Control Patients in its Phase III Trial in Newly Diagnosed GBM to Cross Over to Receive Tumor Treating Fields” (PDF) (Source) Retrieved Nov 30, 2015.

(10). Chaudhry A1, Benson L2, Varshaver M3, Farber O4, Weinberg U5, Kirson E6, Palti Y7. NovoTTF(™)-100A System (Tumor Treating Fields) transducer array layout planning for glioblastoma: a NovoTAL(™) system user study. World J Surg Oncol. 2015 Nov 11;13(1):316.  (Source)

(11). Op cit., Davies.


World J Surg Oncol. 2015 Nov 11;13(1):316.

NovoTTF(™)-100A System (Tumor Treating Fields) transducer array layout planning for glioblastoma: a NovoTAL(™) system user study.

Chaudhry A1, Benson L2, Varshaver M3, Farber O4, Weinberg U5, Kirson E6, Palti Y7.


Optune™, previously known as the NovoTTF-100A System™, generates Tumor Treating Fields (TTFields), an effective anti-mitotic therapy for glioblastoma. The system delivers intermediate frequency, alternating electric fields to the supratentorial brain. Patient therapy is personalized by configuring transducer array layout placement on the scalp to the tumor site using MRI measurements and the NovoTAL System. Transducer array layout mapping optimizes therapy by maximizing electric field intensity to the tumor site. This study evaluated physician performance in conducting transducer array layout mapping using the NovoTAL System compared with mapping performed by the Novocure in-house clinical team.


Fourteen physicians (7 neuro-oncologists, 4 medical oncologists, and 3 neurosurgeons) evaluated five blinded cases of recurrent glioblastoma and performed head size and tumor location measurements using a standard Digital Imaging and Communications in Medicine reader. Concordance with Novocure measurement and intra- and inter-rater reliability were assessed using relevant correlation coefficients. The study criterion for success was a concordance correlation coefficient (CCC) >0.80.


CCC for each physician versus Novocure on 20 MRI measurements was 0.96 (standard deviation, SD±0.03, range 0.90-1.00), indicating very high agreement between the two groups. Intra- and inter-rater reliability correlation coefficients were similarly high: 0.83 (SD ±0.15, range 0.54-1.00) and 0.80 (SD ±0.18, range 0.48-1.00), respectively.


This user study demonstrated an excellent level of concordance between prescribing physicians and Novocure in-house clinical teams in performing transducer array layout planning. Intra-rater reliability was very high, indicating reproducible performance. Physicians prescribing TTFields, when trained on the NovoTAL System, can independently perform transducer array layout mapping required for the initiation and maintenance of patients on TTFields therapy. (Source)


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