CurrentBlue Cross Blue Shield - IowaPolicy N/A

Tumor Treating Fields (TTF) Therapy

Wellmark Blue Cross Blue Shield Iowa policy on medical necessity, prior approval, indications, continuation, investigational exclusions, and regulatory/contextual background for Tumor Treating Fields (TTF) therapy (Optune®) for glioblastoma multiforme (GBM), malignant pleural mesothelioma (MPM), and non-small cell lung cancer (NSCLC). This part (1 of 3) contains evidence summaries, FDA indications, medical necessity criteria for GBM and mesothelioma HDE, continuation criteria, investigational conditions, contraindications, and related background.

Policy Summary

PayerBlue Cross Blue Shield - Iowa

PolicyTumor Treating Fields (TTF) Therapy

Policy CodePolicy N/A

Change TypeRevised (September 2025 review)

Effective DateN/A

Next Review Date2025-09

Key ActionObtain prior approval before initiating TTF therapy and document histologic GBM confirmation, supratentorial location, age ≥18, KPS ≥60%, and patient understanding/ability to comply with device use.

SourceLink

POLICY UPDATE CHANGES

Document updated with review date and revised September 2025 (no explicit clinical policy statement changes indicated in this part).

Policy Revised during Annual Review (September 2025).

1Covered Indication: Newly diagnosed supratentorial GBM (adjunct to temozolomide)

1Covered Indication: Recurrent GBM (if prior criteria met)

1Mesothelioma per FDA HDE

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Investigational: Other cancers/uses (including NSCLC adjunct, progressive GBM adjunct)

4Indications reviewed

1Key RCT (EF-14) shows OS benefit

Coverage Summary

This Wellmark Blue Cross Blue Shield - Iowa policy (06.01.34) addresses Tumor Treating Fields (TTF) therapy (Optune® family) with a mixed coverage stance. Prior approval is required. The policy specifies medically necessary coverage for TTF as an adjunct to maintenance temozolomide for histologically confirmed, supratentorial glioblastoma in adults meeting eligibility criteria (e.g., age ≥18, KPS ≥60%) and continuation criteria; TTF for other indications is generally investigational except for mesothelioma when consistent with the FDA HDE. The policy was last reviewed and revised in September 2025 with the next review listed as September 2025.

Key Eligibility & Thresholds

Age / PerformanceAdults ≥18 years; KPS ≥60% required

Supratentorial tumorRequired for GBM indication

Minimum daily use>= 18 hours/day (FDA label; LUNAR targeted average ≥18 h/day)

NSCLC minimum daily useMinimum 12 hours/day for NSCLC (FDA/labeling)

Minimum initial duration>= 4 weeks (finish at least 4 full weeks)

Continuation criterionNo evidence of progression within 90 days of continuation request

Maximum cumulative useUsed 24 months or less (≤24 months) per FDA labeling

Medical-Necessity Criteria

Prior Approval

Prior approval is required.

Prior approval obtained before initiation of TTF therapy

Mesothelioma (HDE Indication)

TTF may be considered medically necessary for mesothelioma when consistent with FDA Humanitarian Device Exemption (HDE) specifications.

Unresectable, locally advanced or metastatic malignant pleural mesothelioma treated per HDE/Optune Lua labeling concurrently with pemetrexed and platinum-based chemotherapy as specified by FDA HDE

See FDA HDE (NovoTTF-100L / Optune Lua) and policy 10.01.14 Humanitarian Use Devices for operational details

Investigational / Not Medically Necessary

TTF therapy is considered investigational (not medically necessary) for all other conditions including, but not limited to:

Evidence & Guideline Summaries

Tumor Treating Fields (TTF) is a noninvasive alternating electric field therapy (Optune® and Optune Lua™ systems) intended to inhibit tumor cell division and potentially augment chemotherapy; the device is portable and delivered via transducer arrays applied to a shaved head or chest depending on indication. FDA approvals include recurrent supratentorial GBM (PMA 2011) and expanded approval for newly diagnosed GBM in combination with temozolomide (2015), an Optune Lua HDE for malignant pleural mesothelioma (2019), and more recent approvals for specific NSCLC indications. Key evidence includes the EF-14 randomized trial in newly diagnosed supratentorial GBM showing improved PFS by 2.7 months (6.7 vs 4.0 months) and OS by 4.9 months (20.9 vs 16.0 months) when TTF was added to maintenance temozolomide, as well as the EF-11 RCT in recurrent GBM which did not demonstrate a statistically significant survival benefit versus physician's-choice chemotherapy. Additional trials include the STELLAR single-arm study in mesothelioma and the LUNAR open-label RCT in metastatic NSCLC (TTF + checkpoint inhibitor or docetaxel showed a 3.3-month OS benefit but no PFS or ORR benefit; trial limitations include lack of sham control and evolving standards of care).

Evidence summaries by indication

Findings and conclusions from clinical trials and studies by indication:

EF-14 (Newly diagnosed GBM): Addition of TTF to maintenance temozolomide increased PFS by 2.7 months and OS by 4.9 months versus temozolomide alone; no sham control; PFS assessed by blinded evaluators; adverse events mainly scalp dermatitis.

Stupp et al. EF-14 results

Coding

Covered HCPCS / Device Codes referencedHCPCSCovered

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

Referenced CPT (Therapy planning / reporting)CPT

1025T

Diagnostic imaging for computed tomography and magnetic resonance imaging simulation imported into the therapy treatment-planning system may be reported in addition to the alternating electric fields dosimetry.

Investigational - Category III codesCPTExperimental

Category III codes

All Category III codes will be considered investigational unless explicitly addressed as covered in a Wellmark Medical Coverage Policy

Place/Type of Servicemixed

Durable Medical Equipment	Type of Service
Outpatient/Physician's Office	Place of Service

Provider Actions & Billing Guidance

Prior Authorization

Prior approval required

Obtain prior approval before initiating TTF therapy; prior approval is required per policy.

Documentation Required

Document eligibility criteria for GBM

Document histologic confirmation of GBM, supratentorial location, age >=18, KPS >=60%, and patient understanding/consent to comply with FDA label (including shaved head).

Documentation Required

Continuation documentation

For continuation requests, document no evidence of progression within 90 days and ongoing adherence/ability to comply.

Definitions

Term	Definition
Supratentorial
Area of the brain located above the tentorium cerebelli containing the cerebrum; TTF recommended only for supratentorial disease.
Progressive Disease (EF-14 definition)
Tumor growth >25% compared with smallest tumor area measured during the trial or appearance of one or more new tumors in the brain radiologically diagnosed as GBM (MacDonald criteria).
Recurrent Disease
Cancer that has recurred after a period during which it could not be detected; may recur at the original site or elsewhere.
Karnofsky Performance Status (KPS)
Scale to classify functional impairment; policy requires KPS >= 60% for coverage eligibility.
TTF
Tumor Treating Fields therapy; alternating electric field therapy delivered via Optune/Optune Lua devices.
OS
Overall survival
PFS
Progression-free survival
KPS (duplicate)
Karnofsky Performance Status, used to assess functional status and stratify treatment options.
MGMT
O6-methylguanine-DNA-methyltransferase; promoter methylation status influences temozolomide benefit.

Medicare Determinations

Device / Submission	Number	Effective / Year(s)
NovoTTF-100A / Optune
P100034 / P100034/S013
PMA approval April 2011; PMA supplement Oct 2015 (expanded indication for newly diagnosed GBM)
Optune Lua / NovoTTF-100L
H180002 / P230042
HDE May 2019 (Optune Lua for malignant pleural mesothelioma); P230042 referenced for later submissions (2023/2024 approvals)

Revision History

September 2025revisedLatest

Document updated with review date and revised September 2025 (no explicit clinical policy statement changes indicated in this part).

September 2025revisedLatest

Policy Revised during Annual Review (September 2025).

September 2024

Policy Summary

PayerBlue Cross Blue Shield - Iowa

PolicyTumor Treating Fields (TTF) Therapy

Policy CodePolicy N/A

Change TypeRevised (September 2025 review)

Effective DateN/A

Next Review Date2025-09

SourceLink

On This Page

Not meeting the above criteria for initial and recurrent glioblastoma (GBM)

As an adjunct to standard medical therapy (e.g., bevacizumab, chemotherapy) for individuals with progressive GBM

As an adjunct to maintenance therapy other than temozolomide (Temodar®)

As an alternative to standard medical therapy for individuals with initial, progressive or recurrent GBM

For brain metastases

For cancer in areas other than the brain (other solid tumors) except when covered by explicit FDA HDE/approval

As an adjunct to standard medical therapy (pemetrexed and platinum-based chemotherapy) for individuals with malignant pleural mesothelioma (except per HDE)

As an adjunct to standard medical therapy for individuals with non-small cell lung cancer (NSCLC)

ALL Category III codes will be considered investigational unless explicitly addressed as covered in a Wellmark policy

Age Criterion

Age eligibility per trials and labeling

Per pivotal trials and FDA labeling, individuals must be ≥ 18 years of age (trial enrollment and median age details: median ~56, range 19-83)>= 18 years

Median age ~56 (range 19-83) per trials

FDA Labeled Contraindications

Contraindications per FDA label (include but not limited to):

Presence of bullet fragment(s)

Skull defect (missing bone with no replacement)

Active implanted medical device including but not limited to defibrillators, deep brain stimulators, pacemakers, programmable shunts, spinal cord stimulators, vagus nerve stimulators

EF-11 (Recurrent GBM): EF-11 RCT comparing TTF monotherapy to physician's choice chemotherapy in relapsed GBM (n=237) did not show statistically significant survival benefit; registry and observational data (PRiDe, Zhu 2022, Kesari post hoc) report variable median OS (pooled median OS ~10.3 months, PFS ~5.7 months); limitations include lack of blinding and high loss to follow-up.

Stupp 2012 and systematic review

STELLAR (Mesothelioma): Prospective single-arm study (N=80) with TTF plus pemetrexed and platinum showed median OS 18.2 months, median PFS 7.6 months; no control group; skin reactions common; conclusions limited by single-arm design and small sample.

STELLAR trial results

LUNAR (NSCLC): Randomized, open-label phase 3 (n=276) adding TTF to immune checkpoint inhibitor or docetaxel after platinum progression showed median OS 13.2 vs 9.9 months (HR 0.74; p=0.035); PFS and response rates not significantly different; increased serious AEs with TTF; limitations include lack of sham control and some patients not treated per current SOC.

LUNAR trial results

NCCN/Guideline-derived Recommendations for Glioblastoma

Guideline summaries for adjuvant treatment of glioblastoma by age and Karnofsky Performance Status (KPS):

Age ≤ 70 AND KPS ≥ 60: Standard RT plus concurrent and adjuvant temozolomide plus TTF (preferred) -- Category 1; Standard RT plus concurrent and adjuvant temozolomide -- Category 1

NCCN recommendations

Age ≤ 70 AND KPS ≥ 60 (MGMT unmethylated): Standard RT alone (for unmethylated MGMT promoter status only) -- Category 2A

Age ≤ 70 AND KPS ≥ 60 (MGMT methylated or indeterminate): Standard RT plus concurrent and adjuvant lomustine and temozolomide -- Category 2B

Age ≤ 70 AND KPS < 60: Hypofractionated RT with/without concurrent or adjuvant temozolomide -- Category 2A; Temozolomide alone -- Category 2A; Palliative/best supportive care -- Category 2A

Age > 70 AND KPS ≥ 60: Hypofractionated RT plus concurrent and adjuvant temozolomide (for methylated or indeterminate MGMT promoter status only) -- Category 1; alternate options include standard RT plus concurrent and adjuvant temozolomide plus TTF; standard RT plus concurrent and adjuvant temozolomide; temozolomide alone (for methylated or indeterminate MGMT) -- see NCCN

Age > 70 AND KPS ≥ 60 (alternate NCCN options): Standard RT plus concurrent and adjuvant temozolomide plus TTF; Standard RT plus concurrent and adjuvant temozolomide; Temozolomide alone (for methylated or indeterminate MGMT promoter status only); Hypofractionated RT alone (for unmethylated MGMT promoter status only) -- various categories per NCCN

Age > 70 AND KPS < 60: Hypofractionated brain RT alone -- Category 2A; Temozolomide alone -- Category 2A; Palliative/best supportive care -- Category 2A

Recurrent Glioblastoma

Guideline statement:

Consideration of alternating electric field therapy (TTF) for recurrent glioblastoma is a category 2B recommendation.

NCCN category 2B

Other Tumor Types

Guideline statements about TTF in other cancers:

Malignant pleural mesothelioma: NCCN v.1.2024 do not address TTF as a treatment option.

Non-small cell lung cancer (NSCLC): NCCN v.3.2025 do not address TTF as a treatment option.

EF-14 (Stupp et al., newly diagnosed GBM)TTF+temozolomide: PFS +2.7 mo (6.7 vs 4.0), OS +4.9 mo (20.9 vs 16.0)

EF-11 (Stupp et al., recurrent GBM)TTF monotherapy vs physician's choice: median OS 6.6 vs 6.0 mo; not statistically significant

STELLAR (MPM, single-arm)TTF+pemetrexed+platinum: median OS 18.2 mo; median PFS 7.6 mo (no control)

LUNAR (NSCLC RCT)TTF+ICI/docetaxel: median OS 13.2 vs 9.9 mo (HR 0.74; p=0.035); no PFS/ORR benefit; increased serious AEs

Systematic review / pooled (newly diagnosed GBM)Pooled median OS 21.7 mo; pooled median PFS 7.2 mo

Systematic review / pooled (recurrent GBM)Pooled median OS ~10.3 mo; PFS ~5.7 mo

Documentation Required

Document MGMT promoter methylation status and KPS

Document MGMT promoter methylation status and KPS to determine guideline-recommended options.

Documentation Required

Device usage expectations

Document daily device usage hours and caregiver ability; report skin adverse events.

Minimum daily use: >=18 h/day typical; NSCLC minimum 12 h/day (LUNAR)

Billing Rule

Category III code treatment

All Category III CPT codes are considered investigational unless explicitly covered; claims using Category III codes may be denied.

Billing Rule

Report therapy planning CPT when applicable

Diagnostic imaging for CT/MR simulation imported into therapy planning may be reported with CPT 1025T in addition to alternating electric fields dosimetry.

1025T

Billing Rule

Report device and accessory HCPCS

Use HCPCS E0766 for the electrical stimulation device and A4555 for replacement electrode/transducer.

E0766
A4555

Denial Risk

Evidence limitations

Note key study limitations (lack of sham controls, single-arm designs, high loss to follow-up) that may affect medical necessity determinations.

Policy Revised during Annual Review (September 2024).

September 2023revised

Policy Revised during Annual Review (September 2023).

October 2022revised

Policy Revised during Annual Review (October 2022).

March 2022revised

Policy Revised during Interim Review (March 2022).

October 2021revised

Policy Revised during Annual Review (October 2021).

November 2020revised

Policy Revised during Annual Review (November 2020).

March 2020revised

Policy Revised during Interim Review (March 2020).

November 2019revised

Policy Revised during Annual Review (November 2019).

June 2019revised

Policy Revised during Interim Review (June 2019).

October 2018revised

Policy Revised during Annual Review (October 2018).

October 2017revised

Policy Revised during Annual Review (October 2017).

October 2016revised

Policy Revised during Annual Review (October 2016).

October 2015revised

Policy Revised during Annual Review (October 2015).

November 2014original_effective

Original effective date of the policy (November 2014).