Medical policy: Tumor Treating Fields Therapy

Policy number: MP 6.054

Effective date: 2/1/2026

Policy

Tumor treating fields therapy to treat glioblastoma multiforme (GBM) is considered medically necessary as an adjunct to standard maintenance therapy with temozolomide in individuals with newly diagnosed GBM following initial treatment with surgery, radiotherapy, and/or chemotherapy under the following conditions:

• Individuals ≥18 years of age;
• Supratentorial tumor;
• Karnofsky Performance Status score ≥70%;
• Individual understands device use, including the requirement for a shaved head, and is willing to comply with use criteria according to the U.S. Food and Drug Administration label (see Policy Guidelines).

Tumor treating fields therapy is considered investigational in all other conditions, including but not limited to the following situations:

• As an adjunct to standard medical therapy (e.g., bevacizumab, chemotherapy) for individuals with progressive or recurrent GBM;
• As an alternative to standard medical therapy for individuals with progressive or recurrent GBM;
• For brain metastases;
• For cancer in areas other than the brain;
• As an adjunct to standard medical therapy (pemetrexed and platinum-based chemotherapy) for individuals with malignant pleural mesothelioma;
• As an adjunct to standard medical therapy for individuals with non-small cell lung cancer (NSCLC).

Policy guidelines

Progression was defined in the EF-14 trial (Stupp et al [2015, 2017]) according to the MacDonald criteria (tumor growth >25% compared with the smallest tumor area measured in the individual during the trial or appearance of 1 or more new tumors in the brain that are diagnosed radiologically as glioblastoma multiforme).

Per the pivotal trial, individuals ≥18 years of age were eligible for enrollment. The median age was about 56 years with a range of 19 to 83 years; subgroup analyses for younger age groups were not provided.

The recommended Karnofsky Performance Status (KPS) varies from the NCCN guideline (score ≥60). In the pivotal trial the median KPS score at baseline was 90.0, with a range from 60 to 100. Subgroup analyses for individuals with score 60 to 70 were not provided.

The U.S. Food and Drug Administration label includes the following notices:

• Individuals should use Optune for at least 18 hours a day to get the best response to treatment.
• Individuals should finish at least 4 full weeks of therapy to get the best response to treatment. Stopping treatment before 4 weeks lowers the chances of a response to treatment.

Product variations

This policy is only applicable to certain programs and products administered by Capital Blue Cross and subject to benefit variations. Please see additional information below.

FEP PPO - Refer to FEP Medical Policy Manual.

Description/Background

Glioblastoma multiforme

Glioblastomas, also known as glioblastoma multiforme (GBM), are the most common form of malignant primary brain tumor in adults. Glioblastomas are grade IV astrocytomas, a rapidly progressing and deadly type of glial cell tumor that is often resistant to standard medical therapy (e.g., bevacizumab, chemotherapy). Together, anaplastic astrocytomas and glioblastomas comprise approximately 49.1% of all primary malignant brain tumors. Mean age at GBM diagnosis is 65 years. Glioblastomas have the lowest survival rate of any central nervous system tumor; the 5-year survival rate and average length of survival is estimated at 6.9% and 8 months, respectively.

Treatment of newly diagnosed glioblastoma multiforme

The primary treatment for patients newly diagnosed with GBM is to resect the tumor to confirm a diagnosis while debulking the tumor to relieve symptoms of increased intracranial pressure or compression. If total resection is not feasible, subtotal resection and open biopsy are options. During surgery, some patients may undergo implantation of the tumor cavity with a carmustine (bis-chloroethylnitrosourea) impregnated wafer. Due to the poor efficacy of local treatment, postsurgical treatment with adjuvant radiotherapy (RT), chemotherapy (typically temozolomide), or a combination of these 2 therapies is recommended. After adjuvant therapy, patients may undergo maintenance therapy with temozolomide. Maintenance temozolomide is given for 5 days of every 28-day cycle for 6 cycles. Response and overall survival rates with temozolomide are higher in patients who have O⁶-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation.

Prognostic factors for therapy success are age, histology, performance status or physical condition of the patient, and extent of resection. National Comprehensive Cancer Network recommendations include patient age and Karnofsky Performance Status score as important determinants of postsurgical treatment choice. For patients with good performance status, the most aggressive treatment (standard RT plus temozolomide) is recommended. For patients with poor performance status, only single treatment cycles or even palliative or supportive care are recommended. Hypofractionated RT is indicated for patients with poor performance status because it is better tolerated, and more patients are able to complete RT.

Treatment of GBM is rarely curative, and tumors will recur in essentially all patients.

Treatment of recurrent glioblastoma multiforme

When disease recurs, additional debulking surgery may be used if the recurrence is localized. Due to radiation tolerance, re-radiation options for patients with recurrent GBM who have previously received initial external-beam RT are limited. There is no standard adjuvant treatment for recurrent GBM. Treatment options for recurrent disease include various forms of systemic medications such as the antivascular endothelial growth factor drug bevacizumab, alkylating agents such as nitrosoureas (e.g., lomustine, carmustine), or retreatment with temozolomide. Medical therapy is associated with side effects that include hematologic toxicity, headaches, loss of appetite, nausea, vomiting, and fatigue. Response rates in recurrent disease are less than 10%, and the progression-free survival rate at 6 months is less than 20%. There is a need for new treatments that can improve survival in patients with recurrent GBM or reduce the side effects of treatment while retaining survival benefits.

Malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is an aggressive tumor that is associated with significant morbidity and mortality. It is associated with asbestos exposure and has a latency period of about 40 years after asbestos exposure. Recommendations for treatment are mainly chemotherapy as first line with pemetrexed plus platinum. Surgical cytoreduction is also recommended in selected patients with early-stage disease. Adjuvant radiation can be offered for patients who have resection of intervention tracts found to be histologically positive or for palliation of symptomatic patients.

Non-small cell lung cancer

Lung cancer, including non-small cell lung cancer (NSCLC), is the leading cause of cancer-related death in the United States. There are numerous treatment options for NSCLC which have improved survival rates. Patients eligible for targeted or immunotherapies now have 5-year survival rates up to 62.5%. Tumor treating fields have been studied in combination with immune checkpoint inhibitors (i.e., PD-1/PD-L1 inhibitors) or docetaxel in patients with metastatic NSCLC who progressed with platinum-based therapy.

Regulatory status

In April 2011, the NovoTTF-100A™ System (Novocure; assigned the generic name of TTF) was approved by the U.S. Food and Drug Administration (FDA) through the premarket approval process. The FDA approved label reads as follows: “The NovoTTF-100A System is intended as a treatment for adult patients (22 years of age or older) with confirmed GBM, following confirmed recurrence in an upper region of the brain (supratentorial) after receiving chemotherapy. The device is intended to be used as a stand-alone treatment and is intended as an alternative to standard medical therapy for recurrent GBM after surgical and radiation options have been exhausted.”

In September 2014, FDA approved Novocure’s request for a product name change from NovoTTF-110A System to Optune®.

In October 2015, FDA expanded the indication for Optune in combination with temozolomide to include newly diagnosed GBM. The device was granted priority review status in May 2015 because there was no legally marketed alternative device available for the treatment of newly diagnosed GBM, a life-threatening condition. In July 2016, a smaller, lighter version of the Optune device, called the Optune System (NovoTTF-200A System), received FDA approval.

The FDA-approved label for newly diagnosed GBM reads as follows: “This device is indicated as treatment for adult patients (22 years of age or older) with histologically confirmed glioblastoma multiforme (GBM). Optune with temozolomide is indicated for the treatment of adult patients with newly diagnosed, supratentorial glioblastoma following maximal debulking surgery and completion of radiation therapy together with concomitant standard of care chemotherapy.”

In May 2019, the FDA approved a modified version of the Optune System (NovoTTF-100A System), which is now called the Optune Lua™ System (NovoTTF™-100L System), for treatment of adult patients with unresectable, locally advanced or metastatic malignant pleural mesothelioma (MPM) to be used concurrently with pemetrexed and platinum-based chemotherapy. The indication was modified from that granted for the Humanitarian Device Exemption designation to more clearly identify the patient population the device is intended to treat and in which the safety and probable benefit of the device is supported by the available clinical data.

In September 2021, the FDA granted breakthrough designation to the NovoTTF-200T System for use together with atezolizumab and bevacizumab for the first-line treatment of patients with unresectable or metastatic liver cancer.

To date, all of the existing tumor treating fields products fall under the brand name Optune. In March 2020, the manufacturer of Optune products announced a plan to include a suffix after the brand name for newly approved indications to further delineate specific indications for individual products (e.g., Optune Lua). Optune was renamed Optune Gio™ in 2023.

Rationale

Summary of evidence

For individuals who have newly diagnosed glioblastoma multiforme (GBM) on maintenance therapy after initial treatment who receive tumor treating fields (TTF) therapy as an adjunct to standard maintenance therapy, the evidence includes a randomized controlled trial (RCT) and a systematic review. Relevant outcomes include overall survival (OS), disease-specific survival, symptoms, functional outcomes, quality of life, and treatment-related morbidity. The EF-14 trial found a significant increase of 2.7 months in progression-free survival (PFS) and an increase of 4.9 months in OS with the addition of TTF therapy to standard maintenance therapy (i.e., temozolomide) in patients with newly diagnosed GBM. Although patients were not blinded to treatment assignment, PFS was assessed by blinded evaluators, and the placebo effects on objective measures of OS are expected to be minimal. In a systematic review that included the EF-14 trial, along with other observational studies, the pooled median OS and PFS in newly diagnosed patients who received TTF therapy was 21.7 months and 7.2 months, respectively. This technology represents a clinically significant option in the treatment of patients with GBM, for whom options are limited. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have progressive or recurrent GBM who receive TTF therapy as an adjunct or alternative to standard medical therapy, the evidence includes an RCT, nonrandomized comparative studies, and a systematic review of these data. Relevant outcomes are OS, disease-specific survival, quality of life, and treatment-related morbidity. The single RCT evaluating TTF therapy for recurrent GBM did not show superiority of TTF therapy for the primary outcome (OS) compared with physician’s choice chemotherapy. Because no serious adverse effects have been identified with TTF therapy, this raises the possibility that treatment with TTF might reduce the toxicity associated with treatment for recurrent GBM. A reduction in chemotherapy-associated toxicity without loss of efficacy would be considered a net health benefit. However, this RCT is not sufficient to permit conclusions on the efficacy of the device. Because the trial was not designed as a noninferiority trial, no inferences of noninferiority compared with chemotherapy can be made. Also, quality of life assessment was measured in an insufficient number of patients to reach firm conclusions on differences in quality of life between TTF therapy and medical treatment. The highest quality study of TTF combined with medical treatment for recurrent GBM is a post hoc analysis of the EF-14 trial. Two registry studies also evaluated real-world outcomes in patients enrolled in the PRiDe registry compared to patients in the EF-11 study. In a systematic review that included the RCT and post hoc analysis of the EF-14 trial, along with observational studies, the pooled median OS and PFS in patients with recurrent GBM who received TTF therapy was 10.3 months and 5.7 months, respectively. A high-quality, prospective RCT is needed. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have unresectable, locally advanced or metastatic malignant pleural mesothelioma (MPM) who receive TTF therapy as an adjunct to standard maintenance therapy, the evidence includes a single-arm prospective study conducted in 80 patients and a retrospective study of 5 US patients. Relevant outcomes include OS, disease-specific survival, symptoms, functional outcomes, quality of life, and treatment-related morbidity. In patients who received TTF therapy in combination with pemetrexed and cisplatin or carboplatin, median OS was 18.2 months (95% confidence interval [CI], 12.1 to 25.8 months). Because there was no comparison group, it is not possible to draw conclusions about the effectiveness of the intervention compared to medical therapy alone. The retrospective study is the first publication of real-world implementation of TTF for MPM. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have metastatic non-small cell lung cancer (NSCLC) who receive TTF with concurrent standard care including an immune checkpoint inhibitor or docetaxel and who have progressed on or after platinum-based therapy, the evidence includes an open-label RCT conducted in 276 patients. Relevant outcomes include OS, disease-specific survival, symptoms, functional outcomes, quality of life, and treatment-related morbidity. The LUNAR trial found a significant increase of 3.3 months in OS with TTF in combination with an immune checkpoint inhibitor or docetaxel, but there was no significant improvement in PFS or overall response rate. The trial is limited by the lack of a sham comparator, a lack of baseline mental health testing, and changes in standard of care. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Definitions

Karnofsky Performance Status is a standard way of measuring the ability of individuals to perform ordinary tasks. The Karnofsky Performance Status scores range from 0 to 100. A higher score means the patient is better able to carry out daily activities. Karnofsky Performance Status may be used to determine a patient’s prognosis, to measure changes in a patient’s ability to function, or to decide if a patient could be included in a clinical trial. Also called KPS.

Disclaimer

Capital Blue Cross’ medical policies are used to determine coverage for specific medical technologies, procedures, equipment, and services. These medical policies do not constitute medical advice and are subject to change as required by law or applicable clinical evidence from independent treatment guidelines. Treating providers are solely responsible for medical advice and treatment of members. These policies are not a guarantee of coverage or payment. Payment of claims is subject to a determination regarding the member’s benefit program and eligibility on the date of service, and a determination that the services are medically necessary and appropriate. Final processing of a claim is based upon the terms of contract that applies to the members’ benefit program, including benefit limitations and exclusions. If a provider or a member has a question concerning this medical policy, please contact Capital Blue Cross’ Provider Services or Member Services.

Coding information

Note: This list of codes may not be all-inclusive, and codes are subject to change at any time. The identification of a code in this section does not denote coverage as coverage is determined by the terms of member benefit information. In addition, not all covered services are eligible for separate reimbursement.

May be considered medically necessary: When used for tumor treating fields therapy for newly diagnosed glioblastoma

ICD-10-CM diagnosis codes

References

1. National Cancer Institute (NCI). Adult central nervous system tumors treatment (PDQ) health professional version. Updated March 28, 2025. https://www.cancer.gov/types/brain/hp/adult-brain-treatment-pdq#section_1.1
2. National Brain Tumor Society. Glioblastoma facts and figures. https://braintumor.org/take-action/about-gbm/
3. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Central nervous system cancers. Version 5.2024.
4. Stupp R, Wong ET, Kanner AA, et al. NovoTTF-100A versus physician’s choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer. Sep 2012; 48(14): 2192-2202. PMID 22608262
5. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Non-small cell lung cancer. Version 3.2025.
6. U.S. Food and Drug Administration. Optune Lua. Premarket approval.
7. U.S. Food and Drug Administration (FDA). Tumor treating fields. NovoTTF-10A System. Summary of safety and effectiveness data (SSED). Premarket approval. Application (PMA) No. P100034. 2011; http://www.accessdata.fda.gov/cdrh_docs/pdf10/P100034b.pdf
8. U.S. Food and Drug Administration (FDA). Supplemental application for device name change. 2014.
9. U.S. Food and Drug Administration (FDA). Summary of safety and effectiveness data (SSED): Optune™ (formerly NovoTTF-100ATM System). 2015. https://www.accessdata.fda.gov/cdrh_docs/pdf10/P100034S013B.pdf
10. U.S. Food and Drug Administration (FDA). NovoTTF-100L System: Summary of safety and probable benefit. May 23, 2019. https://www.accessdata.fda.gov/cdrh_docs/pdf18/H180002B.pdf
11. FDA grants breakthrough device designation to the NovoTTF-200T System for advanced liver cancer. September 9, 2021. https://www.novocure.com/fda-grants-breakthrough-device-designation-to-the-novottf-200t-system-for-advanced-liver-cancer/
12. Novocure. Novocure announces Optune Lua as the brand name for the NovoTTF-100L system. March 19, 2020. https://www.novocure.com/novocure-announces-optune-lua-as-the-brand-name-for-the-novottf-100l-system/
13. Novocure announces presentation on tumor treating fields therapy, including new clinical data and real-world evidence, at 2023 Society for Neuro-Oncology Annual Meeting. Novocure. Published November 10, 2023. https://www.novocure.com/novocure-announces-presentation-on-tumor-treating-fields-therapy-including-new-clinical-data-and-real-world-evidence-at-2023-society-for-neuro-oncology-annual-meeting/
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23. Kanner AA, Wong ET, Villano JL, et al. Post hoc analyses of intention-to-treat population in phase III comparison of NovoTTF-100A™ system versus best physician’s choice chemotherapy. Semin Oncol. Oct 2014; 41 Suppl 6: S25-S34. PMID 25213871
24. Ceresoli GL, Aerts JG, Dziadziuszko R, et al. Tumor treating fields in combination with pemetrexed and cisplatin or carboplatin as first-line treatment for unresectable malignant pleural mesothelioma (STELLAR): a multicentre, single-arm phase 2 trial. Lancet Oncol. Dec 2019; 20(12): 1702-1709. PMID 31628016
25. Kutuk T, Appel H, Avendano MC, et al. Feasibility of tumor treating fields with pemetrexed and platinum-based chemotherapy for unresectable malignant pleural mesothelioma: single-center, real-world data. Cancers (Basel). Apr 16 2022; 14(8). PMID 35454925
26. Leal T, Kotecha R, Ramlau R, et al. Tumor treating fields therapy with standard systemic therapy versus standard systemic therapy alone in metastatic non-small-cell lung cancer following progression on or after platinum-based therapy (LUNAR): a randomized, open-label, pivotal phase 3 study. Lancet Oncol. Sep 2023; 24(9): 1002-1017. PMID 37657460
27. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Mesothelioma: Pleural. Version 2.2025.
28. Germain IM, Ziu M, Wen P, et al. Congress of Neurological Surgeons systematic review and evidence-based guidelines update on the role of cytotoxic chemotherapy and other cytotoxic therapies in the management of progressive glioblastoma in adults. J Neurooncol. Jun 2022; 158(2): 225-253. PMID 35195819