Medical Policy: 06.01.34
Original Effective Date: November 2014
Reviewed: October 2017
Revised: October 2017
Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.
This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.
The mechanism of action as described by the manufacturer: Tumor treating fields (TTF)/Electric tumor treatment fields (ETTF) or TTFields therapy is a locally or regionally delivered treatment that produces electric fields within the human body to disrupt the rapid cell division exhibited by cancer cells. TTFields therapy works by creating alternating, “wave-like” electric fields that travel across their region of usage in different directions. Because structures within dividing cells have an electric charge, they interact with these electric fields.
To apply TTF therapy, four insulated transducer arrays are placed on the patient’s shaved scalp according to the tumor’s location. The transducer arrays connect to the portable generator, which noninvasively delivers TTF therapy by generating 200 kHz electric fields within the brain in two perpendicular directions (operated sequentially). Novocure presets the exact treatment parameters; no electrical output adjustments are available to the patient. The patient or caregiver must re-shave the scalp area and replace transducer arrays once or twice a week (every four to seven days) and learn how to change and recharge depleted batteries and connect to an external power supply.
The patient can receive TTF therapy outside the hospital on a continuous basis (between 20 to 24 hours per day) for the treatment’s duration, which can be several months.To shower, patients must disconnect the transducer arrays from the generator. The patient can place a shower cap over the existing transducer arrays on the scalp to keep them dry or remove them to shower and replace them with a new pair.
The system used for the therapy consists of the Optune Treatment Kit (Novocure, Ltd.) and INE Transducer Arrays. The kit includes the Electric Field Generator (NovoTTF-100A device), power supply, portable battery, battery rack, battery charger, connection cable, and carrying case. The arrays are packaged with a gel layer, padding, medical tape, and overlapping liner. The device is used continuously, so patients carry the six-pound portable generator in an over-the-shoulder bag or backpack during daily activities, with transducer arrays placed on their head and connected to the generator.
The primary treatment for glioblastoma multiforme is debulking surgery to remove as much of the tumor as possible. At that time, some patients may undergo implantation of the tumor cavity with a carmustine (bis chloroethylnitrosourea [BCNU]) - impregnated wafer. Depending on the patient’s physical condition, adjuvant radiation therapy, chemotherapy (typically temozolomide), or a combination of the 2 are sometimes given. After adjuvant therapy, some patients may undergo maintenance therapy with temozolomide. In patients with disease that recurs after these initial therapies, additional debulking surgery may be used if recurrence is localized. Treatment options for recurrent disease include various forms of systemic medications such as bevacizumab, bevacizumab plus chemotherapy (eg, irinotecan, BCNU/chloroethylnitrosourea [CCNU], temozolomide), temozolomide, nitrosourea, PCV (procarbazine, CCNU, vincristine), cyclophosphamide, and platinum-based agents.
Electric tumor treating fields technology is also being studied as a treatment for other solid tumors (e.g., melanoma and non-small cell lung cancer). However, there is a lack of published evidence from randomized controlled trials examining the long-term safety and effectiveness of ETTF as a treatment of tumors.
A major limitation of the RCT was the lack of a sham device in the control arm, raising the possibility that differences in supportive care or health-promoting behaviors could have contributed to improved outcomes in the device arm. In addition, quality of life data have not yet been presented. A previous open-label randomized trial of TTFields in 237 patients with recurrent glioblastoma showed no improvement in survival compared with physician’s choice chemotherapy.
Clinical Practice Guidelines in Oncology/Central Nervous System Cancers. Version 1.2017. This guideline includes alternating electric field therapy (Optune Treatment Kit) as a treatment option for the recurrent disease pathway (GLIO-4), for local, multiple, or diffuse glioblastoma. According to this guideline, “patients with recurring glioblastoma may also consider alternating electric field therapy” (category 2B). The guideline elaborates by stating that “due to lack of efficacy, not all panelists recommend the treatment.” The National Comprehensive Cancer Network’s central nervous system tumors guidelines (v.1.2016)2 have updated the recommendation for the treatment of glioblastoma (GBM). For the treatment of patients with GBM with good performance status and either methylated or unmethylated or indeterminate MGMT promotor status, a 2A recommendation was added for a treatment option for standard brain radiotherapy, with concurrent temozolomide and adjuvant temozolomide and alternating electric currents therapy. Currently the recommendation is within the same algorithm stem as clinical trials, based on consensus and lower-level evidence.
EANO Guideline on the Diagnosis and Treatment of Anaplastic Gliomas and Glioblastoma. 2014. This guideline states: “new approaches of glioma therapy… device based therapies such as tumor-treating fields should only be administered in the context of clinical trials.”
High-grade Glioma: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-up. 2014. This guideline states: “Applying alternating electric fields—tumor-treating fields—using a battery powered device connected to electrodes placed on the patient’s scalp—was compared with physicians’ choice of chemotherapy in a randomized trial in recurrent disease. TTF failed to prolong survival compared with second-line chemotherapy [I, A].” This guideline defines Level of Evidence I as “evidence from at least one large randomized, controlled trial of good methodological quality (low potential for bias) or meta-analyses of well-conducted randomized trials without heterogeneity.” This guideline defines Grade of Recommendation A as “strong evidence for efficacy with a substantial clinical benefit, strongly recommended.
Some clinical researchers assert that TTF "could be further evaluated in combination with chemotherapy, as a maintenance treatment, or as a salvage therapy if radiotherapy or surgery is not possible." Clinical studies are ongoing to determine the safety and efficacy of TTF therapy as part of combination therapy for treating recurrent GBM. TTF therapy is under investigation as a combination therapy with chemotherapy plus bevacizumab and as a combination therapy with chemotherapy after irradiation therapy for treating recurrent GBM.
The use of electrical tumor treatment fields (TTF) is considered investigational for all indications including, but not limited to, treatment of glioblastoma multiforme, and the reoccurrence of glioblastoma multiforme, due to a lack of evidence demonstrating an impact on improved health outcomes, including but not limited to disease survival. This includes in combination with chemotherapy or as stand-alone therapy.
The use of tumor treatment fields for all other cancers including, but not limited to non-small cell lung cancer, advanced pancreatic adenocarcinoma (together with gemcitabine), recurrent ovarian cancer,recurrent atypical anaplastic meningioma, and malignant mesothelioma. is considered investigational.
Data is limited regarding the effectiveness of electric tumor treatment fields (TTF) for the treatment of recurrent glioblastoma or any indication. Evidence in the published, peer-reviewed scientific literature consists of several small case studies and a single randomized controlled trial (RCT). Results from the RCT did not demonstrate improved progression free survival or overall survival with this intervention compared with chemotherapy. In addition, differences in response rates, progression-free survival at 6 months, and reduction in risk of death were not statistically significant.
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