Policies & Guidelines

Asset Publisher

mp-536

Tumor-Treatment Fields Therapy for Glioblastoma

Policy Number: MP-536

Latest Review Date: July 2024

Category:Durable Medical Equipment (DME)

POLICY:

Tumor-treating fields (TTF) therapy may be considered medically necessary to treat histologically-confirmed Supratentorial Glioblastoma (known also as glioblastoma multiforme [GBM], Grade IV) as adjunctive therapy when used according to FDA labeled indications, contraindications, warnings and precautions, and when ALL the following criteria are met:

Initial treatment with debulking surgery or biopsy followed by chemoradiation with concomitant Temozolomide and radiotherapy have been completed; and
TTF is used in combination with Temozolomide* and
Individual has Karnofsky Performance Status (KPS) score of ≥60% (requires occasional assistance, but is able to care for most of their personal needs); and
Individual is age 22 or older and
Individual or caregiver has been trained and is willing and able to apply the device daily; and
Individual is willing to wear the device at least 18 hours daily.

*Recertification of TTF may be considered medically necessary after Temozolomide is completed if the member is receiving standard of care therapy in combination with TTF and all additional policy criteria is met.

Tumor-treating fields (TTF) therapy may be considered medically necessary to treat recurrence of previously histologically confirmed Supratentorial Glioblastoma (known also as glioblastoma multiforme [GBM], Grade IV) when used according to FDA labeled indications, contraindications, warnings and precautions, and when ALL the following criteria are met:

There is histologically or radiologically confirmed recurrence of supratentorial glioblastoma following treatment with surgery, chemotherapy, and/or radiation and
TTF is used as monotherapy, and
Individual has Karnofsky Performance Status (KPS) score of ≥60% (requires occasional assistance, but is able to care for most of their personal needs); and
Individual is age 22 or older and
Individual or caregiver has been trained and is willing and able to apply the device daily; and
Individual is willing to wear the device at least 18 hours daily.

Tumor Treatment Fields (TTF) therapy is considered investigational when the criteria above are not met and for all other indications, including but not limited to malignant pleural mesothelioma.

Computer software used for therapeutic radiology clinical treatment planning in conjunction with tumor treatment field (TTF) therapy is considered investigational.

DESCRIPTION OF PROCEDURE OR SERVICE:

Tumor treating fields (TTF) therapy is a noninvasive technology intended to treat glioblastoma and malignant pleural mesothelioma on an outpatient basis and at home using electrical fields. Glioblastoma multiforme (GBM) is the most common and deadly malignant brain tumor. It has a very poor prognosis and is associated with low quality of life during of treatment. Malignant pleural mesothelioma is an aggressive tumor with few treatment options that is associated with significant morbidity and mortality.

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 6.8 % 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 promotermethylation (See Medical Policy #582 on MGMT promotor methylation in malignant gliomas.)

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 (see the Supplemental Information section). 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 tolerances, re-radiation options for patients with recurrent GBM who have previously received initial external-beam RT are limited. There is no standard adjunctive 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, headache, 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.

The NovoTAL™ (transducer array layout) system is optional simulation software for use in clinical treatment planning with Optune therapy that may be leased from the manufacturer. Its purpose is to determine the optimal location of the transducer arrays based on the patient’s most recent magnetic resonance imaging (MRI) scan, head size, and tumor location.

KEY POINTS:

This evidence review has been updated regularly with searches of the PubMed database. The most recent literature update was through May 15, 2024.

Summary of Evidence:

For individuals who have newly diagnosed GBM on maintenance therapy after initial treatment who receive TTF therapy as an adjunct to standard maintenance therapy, the evidence includes an RCT. Relevant outcomes include overall survival, 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 and an increase of 4.9 months in overall survival 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, progression-free survival was assessed by blinded evaluators, and the placebo effects on the objective measure of overall survival 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. Relevant outcomes are overall survival, 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 (overall survival) compared with physicians’ 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 other 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.

For individuals who have unresectable, locally advanced or metastatic, malignant pleural mesothelioma who receive TTF therapy as an adjunct to standard maintenance therapy, the evidence includes one single-arm prospective study conducted in 80 patients and a retrospective study of 5 US patients. Relevant outcomes include overall survival, disease-specific survival, symptoms, functional outcomes, quality of life, and treatment-related morbidity. The study has not been published but is described in the FDA Summary associated with its Humanitarian Device Exemption designation. In patients who received TTF therapy in combination with pemetrexed and cisplatin or carboplatin, median overall survival was 18.2 months (95% CI 12.1 to 25.8 months). Because there was no comparison group, it is not possible to make conclusions about the effectiveness of the intervention compared to medical therapy alone. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

PRACTICE GUIDELINES AND POSITION STATEMENTS:

National Comprehensive Cancer Network

National Comprehensive Cancer Network guidelines on central nervous system cancers (v.1.2023) include recommendations for the treatment of glioblastoma (see Table 1). For the initial treatment of patients with glioblastoma with good performance status and either methylated or unmethylated or indeterminate O6-methylguanine-DNA methyltransferase promotor status, treatment with standard brain radiotherapy plus concurrent temozolomide and adjuvant temozolomide plus alternating electric field therapy is a category 1 recommendation. Alternating electric currents therapy is only an option for patients with supratentorial disease. Consideration of alternating electric field therapy for recurrent glioblastoma is a category 2B recommendation.

Table 1. Guidelines for Adjuvant Treatment of Glioblastoma, by Age and Performance Status

Age, y	KPS Score,%	Treatment Options	Category
≤70	≥60	Standard RT plus concurrent and adjuvant temozolomide plus TTF (preferred) Standard RT plus concurrent and adjuvant temozolomide	1
≤70	≥60	Standard RT alone (for unmethylated MGMT promoter status only)	2A
≤70	≥60	Standard RT plus concurrent and adjuvant lomustine and temozolomide(for methylated or indeterminate MGMT promoter status only)	2B
≤70	<60	Hypofractionated RT with/without concurrent or adjuvant temozolomide Temozolomide alone Palliative/best supportive care	2A
>70	≥60	Hypofractionated RT plus concurrent and adjuvant temozolomide(for methylated or indeterminate MGMT promoter status only)	1
>70	≥60	Standard RT plus concurrent and adjuvant temozolomide Temozolomide alone (for methylated or indeterminate MGMT promoter status only) Hypofractionated brain RT alone (for unmethylated MGMT promoter status only)	2A
>70	≥60	Hypofractionated brain RT alone (for methylated or indeterminate MGMT promoter status only)	2
>70	<60	Hypofractionated brain RT alone Temozolomide alone Palliative/best supportive care	2A

KPS: Karnofsky Performance Status; MGMT: O6-methylguanine-DNA-methyltransferase; RT: radiotherapy; TTF: tumor treating fields.

The National Comprehensive Cancer Network guidelines on malignant pleural mesothelioma (v.1.2024) do not address tumor treating fields as a treatment option for malignant pleural mesothelioma.

Congress of Neurological Surgeons

In 2022, the Congress of Neurological Surgeons released guidelines on role of cytotoxic chemotherapy and other cytotoxic therapies in the management of progressive glioblastoma. In regard to TTF use in adult patients with progressive glioblastoma, the Congress states that "the use of TTF with other chemotherapy may be considered when treating adult patients with progressive glioblastoma [pGBM]. There is insufficient evidence to recommend TTF to increase overall survival in adult patients with pGBM".

U.S. Preventive Services Task Force Recommendations

Not applicable.

KEY WORDS:

NovoTTF-100A, NovoTTF, Novocure, TTF, Glioblastoma, GBM, Optune, tumor-treating fields, NovoTAL, transducer array layout, Optune Lua, Optune Gio

APPROVED BY GOVERNING BODIES:

The NovoTTF-100A™ System (Novocure, Haifa, Israel; assigned the generic name of TTF) was approved by the FDA in April 2011 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.”

On September 28, 2014, FDA approved a request for Novocure to change its products name from NovoTTF-110A System to Optune™.

In October 5, 2015, FDA expanded the indication for Novocure’s use of Optune® in combination with temozolomide to include newly diagnosed GBM. The device was granted priority review status on May 8, 2015 because there was no legally marketed alternative device currently available for the treatment of newly diagnosed GBM that represents 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 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, 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."

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.

NovoTAL simulation software is not regulated by the FDA.

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.

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits. Group-specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply.

FEP: Special benefit consideration may apply. Refer to member’s benefit plan.

CURRENT CODING:

There are no specific codes for the initial application of this system or instruction on use. The patient reapplies the transducer arrays at home after the initial instruction.

CPT:

64999	Unlisted procedure, nervous system
77299	Unlisted procedure, therapeutic radiology clinical treatment planning

HCPCS Codes:

A4555	Electrode/transducer for use with electrical stimulation device used for cancer treatment, replacement only
E0766	Electrical stimulation device used for cancer treatment, includes all accessories, any type

REFERENCES:

Ceresoli GL, Aerts JG, Dziadziuszko R, et al. Tumour 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.
Chaudhry A, Benson L, Varshaver M, et al. NovoTTF™‐100A System (Tumor Treating Fields) transducer array layout planning for glioblastoma: a NovoTAL™ System user study. World J Surg Oncol. 2015;13:316.
Chien LN, Gittleman H, Ostrom QT, et al. Comparative brain and central nervous system tumor incidence and survival between the United States and Taiwan Based on Population-Based Registry. Front Public Health. Jul 21 2016;4:151.
Connelly J, Hormigo A, Mohilie N, et al. Planning TTFields treatment using the NovoTAL system-clinical case series beyond the use of MRI contrast enhancement. BMC Cancer. 2016 Nov 4;16(1):842.
Davies AM, Weinberg U, Palti Y. Tumor treating fields: a new frontier in cancer therapy. Ann N Y Acad Sci 2013.
De Bonis P, Doglietto F, Anile C et al. Electric fields for the treatment of glioblastoma. Expert Rev Neurother 2012; 12(10):1181-84.
Elzinga G, Wong ET. Resolution of cystic enhancement to add-on tumor treating electric fields for recurrent glioblastoma after incomplete response to bevacizumab. Case Rep Neurol. Jan 2014; 6(1):109-115.
Germano 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.
Hayes, Inc. Hayes Search & Summary. NovoTAL System (Novocure) for the treatment of glioblastoma. Lansdale, PA:Hayes, Inc.; April, 2017.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. 2014;41(suppl 6):S25-S34.
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:S25-34.
Kesari S, Ram Z, Investigators EFT. Tumor-treating fields plus chemotherapy versus chemotherapy alone for glioblastoma at first recurrence: a post hoc analysis of the EF-14 trial. CNS Oncol. Jul 2017; 6(3):185-193.
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). Apr16 2022; 14(8).
Mrugala MM, Engelhard HH, Dinh Tran D, et al. Clinical practice experience with NovoTTF-100A system for glioblastoma: The Patient Registry Dataset (PRiDe). Semin Oncol. Oct 2014; 41 Suppl 6:S4-S13.
National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Central Nervous System Cancers. Version 2.2021. https://www.nccn.org/professionals/physician_gls/pdf/cns.pdf.
National Cancer Institute (NCI). Adult Central Nervous System Tumors Treatment (PDQ)Health Professional Version. Updated January 18, 2022; https://www.cancer.gov/types/brain/hp/adult-brain-treatment-pdq#cit/section_1.1.
National Cancer Institute (NCI). Adult Central Nervous System Tumors Treatment (PDQ®)–Health Professional Version. 2017; www.cancer.gov/types/brain/hp/adult-brain-treatment-pdq#cit/section_1.1.
National Cancer Institute (NCI) - Adult Brain Tumors Treatment (PDQ®). Last modified May 14, 2013. Available online at: www.cancer.gov/cancertopics/pdq/treatment/adultbrain/HealthProfessional.
National Cancer Institute (NCI). Adult Central Nervous System Tumors Treatment (PDQ)Health Professional Version. 2018; https://www.cancer.gov/types/brain/hp/adult-brain-treatment-pdq#cit/section_1.1.
National Comprehensive Cancer Network (NCCN). Central nervous system cancers. NCCN Clinical Practice Guidelines in Oncology. Version 1.2016. For additional information visit the NCCN website at: www.nccn.org/index.asp.
National Comprehensive Cancer Network (NCCN). Anaplastic Gliomasª/Glioblastoma. NCCN Clinical Practice Guidelines in Oncology. Version 1.2016. For additional information visit the NCCN website at: www.nccn.org/index.asp.
National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Malignant Pleural Mesothelioma. Version 1.2020. https://www.nccn.org/professionals/physician_gls/pdf/mpm.pdf.
National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Central Nervous System Cancers. Version 2.2020. https://www.nccn.org/professionals/physician_gls/pdf/cns.pdf.
National Brain Tumor Society. Glioblastoma Facts & Figures. https://braintumor.org/take-action/about-gbm/.
Novocure. Novocure announces Optune Lua as the brand name for the NovoTTF-100L system. 2020; https://www.novocure.com/novocure-announces-optune-lua-as-the-brand-name-for-the-novottf-100l-system/.
Novocure Announces Presentations 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.
Pharma FW. FDA Grants Priority Review Status for Novocure's PMA Supplement Application of Optune in Newly Diagnosed Glioblastoma. 2015; www.firstwordpharma.com/node/1282764#axzz3bpYYLTNx, June 1, 2015.
Pless M, Weinberg U. Tumor treating fields: concept, evidence and future. Expert Opin Investig Drugs 2011; 20(8):1099-106.
Ram Z, Gutin PH. Subgroup and quality of life analyses of the phase III clinical trial of NovoTTF- 100A versus best standard chemotherapy for recurrent glioblastoma. Neuro-Oncology 2010; 12:iv48-iv49.
Ram Z, Wong ET, Gutin PH. Comparing the effect of novottf to bevacizumab in recurrent GBM: A post-HOC sub-analysis of the phase III trial data. Neuro-Oncology 2011; 13: iii52.
Regev O, Merkin V, Blumenthal DT, et al. Tumor-Treating Fields for the treatment of glioblastoma: a systematic review and meta-analysis. Neuro oncol Pract. Aug 2021; 8(4): 426-440.
Rulseh AM, Keller J, Klener J et al. Long-term survival of patients suffering from glioblastoma multiforme treated with tumor-treating fields. World J Surg Oncol 2012; 10:220.
Stupp R, Taillibert S, Kanner AA, et al. Maintenance therapy with tumor-treating fields plus temozolomide vs temozolomide alone for glioblastoma: a randomized clinical trial. JAMA. Dec 15 2015; 314(23):2535-2543.
Stupp R, Taillibert S, Kanner A, et al. Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma A Randomized Clinical Trial. JAMA. Dec 19 2017; 318(23):2306–2316. doi:10.1001/jama.2017.18718
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 2012; 48(14):2192-202.
Taphoorn MJB, Dirven L, Kanner AA, et al. Influence of treatment with tumor-treating fields on health-related quality of life of patients with newly diagnosed glioblastoma: a secondary analysis of a randomized clinical trial. JAMA Oncol. Apr 1 2018; 4(4):495-504.
Trusheim J, Dunbar E, Battiste J, et al. A state-of-the-art review and guidelines for tumor treating fields treatment planning and patient follow-up in glioblastoma. CNS Oncol. 2017 Jan;6(1):29-43. Epub 2016 Sep 15.
Turner SG, Gergel T, Wu H, et al. The effect of field strength on glioblastoma multiforme response in patients treated with the NovoTTF-100A system. World J Surg Oncol. 2014; 12(1):162.
U.S. Food and Drug Administration (FDA). Tumor treatment fields. NovoTTF-10A System. Summary of safety and effectiveness data (SSED). Premarket Approval Application (PMA) No. P100034. Premarket Notification Database. Rockville, MD: FDA; April 8, 2011. Available online at: www.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=19184.
U.S.Food and Drug Administration (FDA). Supplemental application for device name change. 2014; www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma_template.cfm?id=p100034s010
US Food and Drug Administration. NovoTTF 100L System: Summary of Safety and Probable Benefit. May 23, 2019. Available at: https://www.accessdata.fda.gov/cdrh_docs/pdf18/H180002B.pdf.
Villano JL, Williams LE, Watson KS et al. Delayed response and survival from NovoTTF-100A in recurrent GBM. Medical Oncology 2013; 30(1):1-3.
Wenger C, Salvador R, Basser PJ, et al. Improving tumor treating fields treatment efficacy in patients with glioblastoma using personalized array layouts [published online December 14, 2015]. Int J Radiat Oncol Biol Phys. 2015.
Wong ET, Lok E, Swanson KD, et al. Response assessment of NovoTTF-100A versus best physician's choice chemotherapy in recurrent glioblastoma. Cancer Med. Jun 2014; 3(3):592-602.
Zhu JJ, Goldlust SA, Kleinberg LR, et al. Tumor Treating Fields (TTFields) therapy vs physicians' choice standard-of-care treatment in patients with recurrent glioblastoma: a post-approval registry study (EF-19). Discov Oncol. Oct 14 2022; 13(1): 105.

POLICY HISTORY:

Medical Policy Panel, August 2013

Medical Policy Group, August 2013 (3): New policy; does not meet medical criteria for coverage and therefore considered investigational

Medical Policy Administration Committee, September 2013

Available for comment September 4 through October 19, 2013

Medical Policy Group, December 2013 (5): 2014 Coding Update- added new codes A4555 and E0766 to current coding effective 01/01/2014

Medical Policy Panel, August 2014

Medical Policy Group, August 2014 (5): Policy updated with literature review through June 26, 2014. Policy Description, Key Points, and References updated. Policy statement unchanged.

Medical Policy Panel, August 2015

Medical Policy Group, August 2015 (6): Updates to Description, Key Points, Approved by Governing Bodies and References; no change to policy statement

Medical Policy Group, May 2016 (6): Added Key Word “Optune”

Medical Policy Panel, August 2016

Medical Policy Group, August 2016 (6): Updates to Policy statement, Key Points, Practice Guidelines and Position Statements, Summary and References. No change in policy intent.

Medical Policy Group, September 2016 (6): Update to Practice Guidelines. No change to policy intent; remains investigational.

Medical Policy Panel, July 2017

Medical Policy Group, July 2017 (6): Updates to Description, Key Points, Practice Guidelines, Governing Bodies and References.

Medical Policy Group, April 2018 (6): Updates to Policy statement to allow coverage of TTF with criteria, Key Points, Practice Guidelines, Coding and References; full literature review to be completed with annual update.

Medical Policy Administration Committee May 2018

Available for comment May 4 through June 17, 2018

Medical Policy Panel, June 2018

Medical Policy Group, August 2018 (6): Updates to Description, Key Points, Added Key Word “tumor-treating fields”, Practice Guidelines, and References. No change to policy intent.

Medical Policy Group, August 2018 (6): Updates to include NovoTAL to Description, Key Points, Key Words (NovoTAL, transducer array layout), Governing Bodies, Coding (64999) and References.

Medical Policy Panel, July 2019

Medical Policy Group, July 2019 (6): Updates to Description, Key Points, and References. Clarification to Policy Statement-. Added "including but not limited to malignant pleural mesothelioma." No change in policy intent.

Medical Policy Group, May 2020 (6): Placed clarification statement for use of Temozolomide for initial glioblastoma in policy statement.

Medical Policy Panel, July 2020

Medical Policy Group, July 2020 (6): Updates to Key Points, Key Words (Optune Lua) Governing Bodies and References.

Medical Policy Panel, July 2021

Medical Policy Group, July 2021 (6): Updates to Key Points and Practice Guidelines.

Medical Policy Panel, July 2022

Medical Policy Group, July 2022 (6): Updates to Description, Key Points, Practice Guidelines and References.

Medical Policy Panel, July 2023

Medical Policy Group, July 2023 (6) Updates to Description, Key Points, Practice Guidelines, Benefit Application and References.

Medical Policy Panel, July 2024

Medical Policy Group, July 2024 (6): Updates to Key Points, Practice Guidelines, Governing Bodies, Key Words and References.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.