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Currentblue cross blue shield - south dakotaPolicy 06.01.34

Tumor Treatment Fields Therapy

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This policy governs coverage and medical necessity criteria for tumor treating fields (TTF) therapy (e.g., Optune®) for glioblastoma, malignant pleural mesothelioma, and non-small cell lung cancer for Wellmark Blue Cross Blue Shield - South Dakota members.

Policy Summary

Payerblue cross blue shield - south dakota

PolicyTumor Treatment Fields Therapy

Policy CodePolicy 06.01.34

Change TypeNo material change

Effective DateNov 1, 2014

Last ReviewSep 1, 2025

Next Review DateSep 1, 2025

Key ActionObtain prior authorization documenting histologically confirmed GBM, performance status, prior therapies, device model, and intended daily TTF use (≥18 hours/day) and minimum duration (≥1 month).

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

Prior approval requiredPrior approval required

Age ≥ 18Minimum age

KPS ≥ 60%KPS threshold

+4.9 moNewly diagnosed GBM OS benefit

≥18 h/dayDaily use recommendation

22%EF-11 discontinuation

Coverage and Medical Necessity Criteria

Initial Therapy — Newly diagnosed GBM

Covered when ALL of the following are met

Newly diagnosed GBM coverage criteria: Individuals ≥ 18 years of ageage >= 18

Newly diagnosed GBM coverage criteria: Supratentorial tumor

See Policy Guidelines for supratentorial definition

Newly diagnosed GBM coverage criteria: Karnofsky Performance Status (KPS) score ≥ 60%KPS >= 60%

Policy Summary

Payerblue cross blue shield - south dakota

PolicyTumor Treatment Fields Therapy

Policy CodePolicy 06.01.34

Change TypeNo material change

Effective DateNov 1, 2014

Last ReviewSep 1, 2025

Next Review DateSep 1, 2025

SourceLink

On This Page

Newly diagnosed GBM coverage criteria:

The individual understands device use and will comply with the FDA label (including shaved head and device management)

TTF used as adjunct to standard maintenance temozolomide following initial surgery, radiotherapy and/or chemotherapy

Initial Therapy — Recurrent GBM

Covered when ALL of the following are met (Choose A or B):

Recurrent GBM coverage criteria: Criteria previously met for newly diagnosed GBM (see Initial Therapy criteria)

Per policy, recurrent GBM is considered when the newly diagnosed criteria have been previously met

Recurrent GBM coverage criteria: Recurrent supratentorial GBM following histologic or radiologic confirmation after prior chemotherapy/surgery/radiation

FDA-labeled recurrent indication applies to adults >=22 years per device labeling

Continuation Therapy — Diagnosed GBM

Covered when ALL of the following are met

Continuation criteria: Initial applicable review criteria for newly diagnosed or recurrent GBM have been met

Continuation criteria: No evidence of disease progression within 90 days of the continuation request90 days

See Policy Guidelines for imaging and assessment

Continuation criteria: The individual continues to understand device use (including requirement for a shaved head) and remains willing to comply with the FDA label

Continuation contingent on stability and ongoing compliance

Mesothelioma (HDE)

Mesothelioma HDE coverage: TTF may be considered medically necessary for malignant pleural mesothelioma in accordance with the FDA Humanitarian Device Exemption (HDE) specifications

See Humanitarian Use Devices policy 10.01.14 and Optune Lua (NovoTTF-100L) labeling

Investigational / Not Covered

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

Investigational indications: Not meeting the above criteria for initial or recurrent GBM

Investigational indications: As an adjunct to standard medical therapy for progressive GBM (e.g., with bevacizumab or other chemotherapy)

Investigational indications: As an adjunct to maintenance therapy other than temozolomide

Investigational indications: As an alternative to standard medical therapy for initial, progressive, or recurrent GBM

Investigational indications: For brain metastases or cancers outside the brain

Investigational indications: As an adjunct to standard medical therapy (pemetrexed + platinum) for malignant pleural mesothelioma (outside HDE specifications)

Investigational indications: As an adjunct to standard medical therapy for non-small cell lung cancer (NSCLC) outside of trial contexts or FDA-labeled indications

All Category III codes will be considered investigational unless explicitly covered

Indications aligned with FDA labeling (newly diagnosed and recurrent supratentorial GBM)

Covered when ALL of the following are met:

FDA-indicated population: Adult patient (≥22 years) with histologically confirmed glioblastoma involving the supratentorial regionage >=22

FDA-labeled indication per device labeling

Disease status: For newly diagnosed GBM: following maximal debulking surgery and completion of radiation therapy with concomitant temozolomide; For recurrent GBM: histologic or radiologic confirmation of supratentorial recurrence after chemotherapy and when surgical/radiation options have been exhausted

Per FDA-approved indications

Performance status: Patient has adequate performance status (e.g., KPS generally >=60; pivotal trial median KPS 90)KPS >= 60

KPS influences candidacy

Treatment plan: Documented plan for device use (minimum 18 hours/day and at least 1 month of therapy) and follow-up monitoring>=18 hours/day; >=1 month

Device-specific usage requirements per FDA label and trial protocols

Newly diagnosed glioblastoma — adjunctive TTF with maintenance temozolomide

Covered when ALL of the following are met

Eligibility for adjunctive TTF in newly diagnosed GBM: Newly diagnosed supratentorial glioblastoma; completed standard initial therapy (biopsy or surgical resection followed by radiotherapy and concomitant temozolomide); treatment intended as maintenance therapy in combination with temozolomide

EF-14 trial required KPS >=70 and targeted device use >18 hours/day; trial showed PFS +2.7 months and OS +4.9 months with TTF+TMZ

Performance and adherence: Karnofsky Performance Status (KPS) >= 70 as required in pivotal trial; expectation of device adherence (target >18 hours/day)KPS >=70; device use >18 h/day expected

Document planned daily wear-time and willingness to comply

Recurrent/progressive glioblastoma — TTF monotherapy

Considered when ALL of the following are met (evidence summary and practical considerations)

Eligibility for TTF in recurrent GBM: Recurrent or progressive supratentorial glioblastoma after failure of conventional treatments (radiotherapy, surgery, prior chemotherapy); KPS >=70; TTF may be used as monotherapy or as an alternative to physician's choice chemotherapyKPS >=70

EF-11 RCT did not show improved overall survival versus physician's choice therapy; evidence limited by trial design and high discontinuation rates

Practical considerations: Document prior treatments, performance status, ability to manage device, and expected adherence; note TTF associated with fewer systemic toxicities but risk of device discontinuation

High noncompliance (22%) observed in EF-11; longitudinal QoL data limited

Evidence-based coverage considerations

Evidence summary considerations

Recurrent/Progressive Glioblastoma: Single RCT (EF-11) found similar survival between TTF and physician's choice chemotherapy but trial limitations (not designed as noninferiority, high loss to follow-up, lack of blinding) prevent definitive efficacy conclusions

TTF associated with fewer systemic chemo toxicities; common AE: scalp contact dermatitis (mostly grade 1-2)

Malignant Pleural Mesothelioma: STELLAR single-arm study (n=80) reported median OS 18.2 months and median PFS 7.6 months with TTF plus pemetrexed and platinum, but absence of a control group limits comparative conclusions

Skin reactions were the primary TTF-associated adverse event; no QoL data reported

Supportive Nonrandomized Evidence: Registry and post hoc analyses (eg, PRiDe, Zhu et al) suggest possible survival benefit in some analyses but are observational and hypothesis-generating

Selection and confounding may influence findings

Use of TTF for unresectable, previously untreated malignant pleural mesothelioma (STELLAR evidence)

Evidence available from a single prospective single-arm study and small retrospective series; coverage decisions hinge on limitations of comparative evidence.

STELLAR enrollment and treatment: Patient has unresectable, previously untreated malignant pleural mesothelioma and received TTF (NovoTTF-100L/Optune Lua) concurrently with pemetrexed and cisplatin or carboplatin as in the STELLAR studyN=80 in study

STELLAR was single-arm; no randomized comparator

Outcomes observed: Median OS 18.2 months; median PFS 7.6 months; 40% partial response among those with follow-up imaging

72 of 80 had at least one follow-up CT; skin reactions mostly mild-moderate

Evidence limitations: No control group and small sample size limit conclusions about effectiveness compared to standard care

May influence noncoverage or conditional coverage decisions

Use of TTF for metastatic NSCLC after progression on platinum-based therapy (LUNAR RCT evidence)

Randomized evidence exists from the LUNAR phase 3 trial evaluating TTF plus standard therapy versus standard therapy alone.

Trial population and intervention: Adults with metastatic NSCLC who progressed on or after platinum-based therapy; intervention arm received TTF (target average >=18 h/day) plus immune checkpoint inhibitor or docetaxeln=276; active n=137; comparator n=139

Open-label phase 3 RCT (LUNAR)

Primary and key outcomes: TTF + standard therapy demonstrated a 3.3-month median OS improvement (median OS 13.2 vs 9.9 months; HR 0.74; p=0.035); PFS and overall response rate were not significantly different; serious adverse events were more frequent with TTFMedian OS TTF 13.2 vs standard 9.9 months

Lack of sham control and evolving standard of care are trial limitations

Evidence limitations: Open-label design without sham control, some patients did not receive current standard baseline testing, and the original planned sample size was reduced at interim analysisoriginal N 534 reduced to 276

These factors may affect applicability and coverage decisions

Guideline and Expert Input

Supplemental guidance and guideline context for TTF use

Guideline support: NCCN v5.2024 lists alternating electric field therapy (TTF) plus adjuvant temozolomide as a category 1 recommendation for initial glioblastoma in patients with good performance status and supratentorial disease; recurrent glioblastoma consideration is category 2B

See NCCN guideline tables

Professional input: 2016 clinician input showed majority but not consensus support for TTF as adjunct to maintenance after initial therapy for glioblastoma and mixed support for use as an alternative to chemotherapy in recurrent disease

Input from specialty societies and an academic medical center

Guideline caution for progressive disease: Congress of Neurological Surgeons (2022) states insufficient evidence to recommend TTF to increase overall survival in adult patients with progressive glioblastoma, though TTF with chemotherapy may be considered

May affect coverage for progressive disease

TTF therapy is considered investigational and not covered for indications that do not meet the policy’s specified criteria for newly diagnosed or recurrent glioblastoma. Examples include use as an adjunct to standard medical therapy (such as bevacizumab or other chemotherapies) for progressive GBM, use as an adjunct to maintenance regimens other than temozolomide, use as an alternative to standard medical therapy for initial, progressive, or recurrent GBM, treatment of brain metastases, cancers outside the brain, and adjunctive use for malignant pleural mesothelioma or non-small cell lung cancer. All Category III codes will be considered investigational unless explicitly addressed as covered in a Wellmark policy.

Patients with FDA-labeled contraindications are excluded from TTF therapy and may be denied coverage. Contraindications listed by the FDA include the presence of bullet fragment(s), an unrepaired skull defect (missing bone without replacement), or an active implanted medical device such as an implantable defibrillator, deep brain stimulator, pacemaker, programmable shunt, spinal cord stimulator, or vagus nerve stimulator.

Clinical trials of TTF lacked sham-controlled blinding and reported substantial practical limitations. The EF-11 and EF-14 trial reports note there was no sham control and treatment assignment was not blinded, and high rates of discontinuation or loss to follow-up were observed. Patients who are unable to tolerate the device or who demonstrate high noncompliance (for example, inability to manage the device or early discontinuation) represent practical exclusions from effective use and may affect coverage decisions.

There is no randomized controlled trial evidence demonstrating TTF plus chemotherapy is superior to chemotherapy alone for malignant pleural mesothelioma (MPM). The STELLAR study was a single-arm prospective trial of TTF plus pemetrexed and platinum chemotherapy and therefore lacked a randomized comparator; because of this absence of direct comparative evidence, TTF used as adjunctive therapy for MPM is considered investigational.

The document sections reviewed do not list additional explicit exclusions beyond contraindications and investigational indications; however, limitations in the evidence base—such as lack of randomized comparators, small sample sizes, and incomplete reporting of outcomes including quality-of-life measures—are identified as reasons that certain uses may be excluded or denied coverage.

Guideline sources do not currently endorse TTF for mesothelioma or NSCLC. The NCCN malignant pleural mesothelioma guideline (v.1.2024) and the NCCN NSCLC guideline (v.3.2025) do not address TTF as a treatment option, which limits guideline support for coverage in these indications.

No additional explicit clinical coverage criteria or exclusions are provided in the coded sections cited here; the policy includes coding and billing instructions (e.g., CPT 1025T; HCPCS E0766, A4555) but specific medical necessity rules and exclusions are located elsewhere in the full policy document.

Use of TTF as an adjunct to standard medical therapy for malignant pleural mesothelioma and for non-small cell lung cancer is considered investigational (not medically necessary) under this policy because supporting evidence consists primarily of single-arm data for MPM (STELLAR) and limited or evolving trial data for NSCLC; randomized, controlled comparative evidence demonstrating net clinical benefit is lacking or limited.

TTF use outside FDA-aligned indications or study-like clinical contexts is not supported by the evidence summarized here. Examples include application for non‑supratentorial GBM, patients who have not completed recommended prior therapies (surgery, radiotherapy, and, where indicated, temozolomide), or other clinical contexts that do not match the trial or FDA-labeled populations.

TTF monotherapy did not demonstrate superiority for overall survival in the EF-11 randomized trial of recurrent GBM. The RCT reported similar survival between TTF and physician’s choice chemotherapy, with fewer systemic toxicities but important trial limitations; absence of demonstrated survival benefit should be considered when evaluating TTF as a replacement for standard chemotherapy.

The EF-11 trial was not designed as a noninferiority study and had substantial limitations (lack of blinding, high loss to follow-up, and discontinuations), therefore noninferiority of TTF compared with chemotherapy cannot be inferred from the available data.

Several potential indications are supported only by single‑arm, uncontrolled data (for example, the STELLAR study for unresectable MPM). Because these studies lack randomized comparators and have design limitations (small sample size, no quality-of-life reporting, losses to follow-up), these indications are considered investigational and lack evidence of benefit compared with standard care.

Expert guidance and society statements reflect uncertainty for TTF in progressive disease. The Congress of Neurological Surgeons (2022) concluded there is insufficient evidence to recommend TTF to increase overall survival in adults with progressive glioblastoma, although TTF combined with chemotherapy may be considered in select cases; this supports conservative coverage decisions for progressive disease.

No specific not‑medically‑necessary conditions are enumerated in the chunks cited beyond the investigational lists above; any additional NMN specifications appear elsewhere in the full policy. Providers should consult the policy’s full text for complete NMN language.

Billing and Procedure Codes

Investigational / Category IIImixedNot Covered

Category III codes

All Category III codes will be considered investigational unless explicitly addressed as covered

Coding referencesmixed

Not specified in this section

No explicit CPT/HCPCS/ICD-10 codes are listed within these document chunks.

Referenced CPT CodesCPT

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.

Referenced HCPCS Codes / DMEHCPCS

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.

Daily device use — ≥ 18 hours daily

Daily device use (FDA label)>= 18 hours daily (Optune should be used for at least 18 hours/day to get best response)

Device worn duration (device instructions)Device may be worn up to 24 hours/day except brief hygiene breaks and 2–3 days/month for maintenance

Shaved head requirementIndividuals will maintain a shaved head per FDA labeling

Minimum therapy duration — At least 4 full weeks of therapy

Minimum continuous therapy duration (FDA label)Finish at least 4 full weeks of therapy to get the best response; stopping before 4 weeks lowers chances of response

Maximum reported use periodTTF therapy has been used up to 24 months or less

Implication for prior authorizationDocumentation should show planned minimum 4-week course per labeling

Minimum daily wear time — >= 18 hours/day

Policy/device minimum daily wear time>= 18 hours/day (minimum daily treatment for glioblastoma)

Device operational daily maximumDevice may be worn up to 24 hours/day except brief periods for hygiene and maintenance

NSCLC reported minimum (for comparison)NSCLC minimum daily treatment reported as 12 hours/day in some protocols

Minimum treatment duration — >= 1 month

Minimum treatment duration (policy/device)>= 1 month (minimum duration of treatment; continuation available until recurrence)

FDA recommended minimum effective courseAt least 4 full weeks per FDA label to optimize chance of response

Continuation conditionContinuation requires no evidence of progression within 90 days of the continuation request (per policy)

Minimum daily TTF usage reported — NSCLC: 12 hours/day minimum; STELLAR MPM protocol reported ≥18 hours/day

NSCLC minimum reported daily usage12 hours/day minimum reported for NSCLC (policy notes minimum for NSCLC)

STELLAR (MPM) reported daily usageSTELLAR MPM protocol reported >= 18 hours/day in some reports

FDA/Optune GBM recommendationOptune/TTF recommended >= 18 hours/day for GBM per FDA label

Prior Authorization, Documentation, and Operational Guidance

Prior Authorization

PRIOR APPROVAL

Prior approval is required.

Prior Authorization

Diagnosed Glioblastoma (GBM)

Diagnosed Glioblastoma (GBM) Tumor treatment fields (TTF) therapy to treat histologically confirmed glioblastoma multiforme (GBM) as an adjunctive treatment to standard maintenance therapy with Temodar® (temozolomide) is considered medically necessary following initial treatment with surgery, radiotherapy and/or chemotherapy when one of the following are met (Choose A or B): - A. In newly diagnosed GBM when all the following criteria are met - Individuals ≥ 18 years of age; - Supratentorial tumor (see Policy Guidelines); - Karnofsky Performance Status (KPS) score ≥ 60%; - The individual understands device use and will comply with the criteria according to the Food and Drug Administration (FDA) label (see Policy Guidelines). - B. In recurrent GBM when all of criteria have been previously met for a newly diagnosed GBM.

Prior Authorization

Continuation for Diagnosed Glioblastoma (GBM)

Continuation for Diagnosed Glioblastoma (GBM) Tumor treatment field (TTF) therapy (e.g., Optune®) for continued use to treat a diagnosed glioblastoma (GBM) is considered medically necessary when all of the following conditions are met: - The initial review for the applicable clinical scenario for a newly diagnosed glioblastoma (GBM) or recurrent glioblastoma (GBM) medical review criteria above have been met; and - No evidence of disease progression within 90 days of the continuation request (see Policy Guidelines); and - The individual continues to understand device use, including the requirement of a shaved head and is still willing to comply with the use criteria according to the Food and Drug Administration (FDA) label (see Policy Guidelines).

Denial Risk

Tumor Treatment Field (TTF) Therapy: Investigational

Tumor Treatment Field (TTF) Therapy: Investigational Tumor treatment field (TTF) therapy is considered investigational in all other conditions including, but not limited to the following, because the evidence is insufficient in determining the technology results in improved net health outcomes: - Not meeting the above criteria for initial and recurrent glioblastoma (GBM); or - As an adjunct to standard medical therapy (e.g., bevacizumab, chemotherapy) for individuals with progressive glioblastoma (GBM); or - As an adjunct to maintenance therapy other than temozolomide (Temodar®); or - As an alternative to standard medical therapy for individuals with initial , progressive or recurrent glioblastoma (GBM) or - For brain metastases; or - For cancer in areas other than the brain; or - 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). - ALL Category III codes will be considered investigational unless the code is explicitly addressed as a covered service in a Wellmark BlueCross BlueShield Medical Coverage Policy.

Documentation Required

U.S. Food and Drug Administration Label

U.S. Food and Drug Administration Label The U.S. Food and Drug Administration label includes the following notices: - Individuals will maintain a shaved head - Individuals should use Optune® for at least 18 hours daily 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. - Tumor treating fields (TTF) therapy has been used 24 months or less.

Documentation Required

Documentation Requirements

Required clinical documentation should include: histologically confirmed GBM, patient age ≥18 years, supratentorial tumor site, Karnofsky Performance Status ≥60%, documentation of prior standard treatments (surgery, radiotherapy, chemotherapy), device model (Optune product), intended concurrent systemic therapy (temozolomide for newly diagnosed GBM), evidence of understanding and willingness to comply with device use (including shaved head and minimum daily usage), and for continuation requests documentation of no evidence of progression within 90 days of the request.

Note

Provider Guidance and Evidence Summary

Clinical guidance and evidence context: - The National Comprehensive Cancer Network (NCCN) includes alternating electric field therapy (TTF) plus temozolomide as a Category 1 recommendation for initial (newly diagnosed), supratentorial glioblastoma maintenance therapy in eligible patients (KPS ≥60%, appropriate age and postoperative status). Recurrent glioblastoma consideration is a Category 2B recommendation. - Clinical practice guidance indicates TTF may be considered as an adjunct to maintenance temozolomide for newly diagnosed GBM or as an alternative/adjunct for recurrent GBM after standard surgical and radiation options have been exhausted; providers should document prior standard therapies and the intended treatment plan when requesting prior authorization. - Other guidance (Congress of Neurological Surgeons) states there is insufficient evidence to recommend TTF to increase overall survival in adult patients with progressive (recurrent) GBM; this limitation may influence coverage for progressive disease and requires documentation supporting the intended use and rationale.

Document the Optune product and clinical indication (newly diagnosed supratentorial GBM with temozolomide maintenance, or recurrent supratentorial GBM following prior standard therapies).
Prior authorization requests must verify FDA-labeled indications (adult patients ≥22 years per FDA label for some versions) and that clinical criteria mirror study-like inclusion criteria (supratentorial GBM, performance status, prior completion of RT/chemotherapy).
Continuation requests require that initial criteria were met and no evidence of progression within 90 days of the continuation request.

Denial Risk

Contraindications and Denial Risks

Contraindications and denial risks - Presence of FDA-labeled contraindications (e.g., retained bullet fragments, skull defect without replacement, active implanted medical devices such as pacemakers, defibrillators, deep brain stimulators, programmable shunts, spinal cord stimulators, vagus nerve stimulators) should be identified and may lead to denial of coverage. - Insufficient evidence for indications outside those specified (including adjunctive use with chemotherapies other than temozolomide, for brain metastases, for MPM or NSCLC outside specified study contexts) may lead to denial. High discontinuation/noncompliance rates and incomplete follow-up in trials may prompt requests for additional documentation.

Billing Rule

Billing and Coding

Billing and coding To report provider services, use appropriate CPT, HCPCS, Revenue, and ICD diagnosis codes. Relevant codes include CPT 1025T (diagnostic imaging for dosimetry), HCPCS E0766 (electrical stimulation device used for cancer treatment) and A4555 (electrode/transducer replacement). Claims may be denied if submitted without appropriate CPT, HCPCS, Revenue, and/or ICD diagnosis codes as instructed in the policy.

CPT: 1025T
HCPCS: E0766, A4555
Type of Service: Durable Medical Equipment
Place of Service: Outpatient/Physician's Office

Technology and Evidence Overview

Tumor treating fields (TTF) is a noninvasive outpatient/home therapy that delivers alternating electric fields via transducer arrays (trade names: Optune, NovoTTF) to treat certain solid tumors. The technology has been evaluated as adjunctive therapy with temozolomide for newly diagnosed supratentorial glioblastoma, as monotherapy or alternative therapy in recurrent GBM, and as adjunctive therapy to platinum/pemetrexed chemotherapy in malignant pleural mesothelioma (STELLAR). Evidence and regulatory status vary by indication.

Key Terms and Abbreviations

Tumor treating fields (TTF) therapy — A noninvasive technology delivering electric fields intended to treat various solid tumors on an outpatient basis and at home.

DefinitionTumor treating fields (TTF) therapy is a noninvasive technology delivering electric fields intended to treat solid tumors on an outpatient basis and at home

Delivery methodAlternating electric fields are delivered via transducer arrays connected to a portable, battery-powered device carried in a bag or backpack

Typical application sitesFor GBM: four disposable transducer arrays applied to the shaved head; for MPM/NSCLC: arrays applied to the chest/back

Karnofsky Performance Status (KPS) — A scale that classifies functional impairment; lower scores indicate worse survival and greater need for assistance.

PurposeKPS classifies functional impairment and prognosis; lower scores indicate worse survival and greater need for assistance

Use in trials/guidelinesPivotal trials required higher KPS (median baseline KPS 90 in EF-14); NCCN recommends KPS >= 60% for consideration

Scale interpretationKPS scores range 0–100; e.g., 100 = normal, 70 = unable to work but cares for self, 60 = requires occasional assistance

Supratentorial region — The area of the brain located above the tentorium cerebelli that contains the cerebrum; TTF therapy is recommended only for supratentoria...

Anatomic definitionSupratentorial region: area of the brain above the tentorium cerebelli that contains the cerebrum

Policy relevanceTTF therapy is recommended only for supratentorial disease (not infratentorial) per policy and trials

Clinical implicationTumors below the tentorium (cerebellum/brainstem) are not appropriate for TTF per policy guidance

Karnofsky Performance Status (KPS) — A scale to classify functional impairment and prognosis; lower scores indicate worse survival. NCCN recommends KPS ≥60 for consideration;...

Scale purpose and prognostic useKPS classifies functional impairment and prognosis; lower scores indicate worse survival

Coverage thresholdNCCN recommends KPS >= 60% for consideration for TTF; pivotal trials often required KPS >= 70%

DocumentationPolicy requires documenting KPS (studies required KPS >=70 to ensure independence in ADLs) when authorizing TTF

Progressive disease (EF-14 / MacDonald criteria) — Tumor growth >25% compared with the smallest tumor area measured in the trial or appearance of one or more new brain tumors diagnosed rad...

Progressive disease definition (EF-14 / MacDonald)Tumor growth >25% compared with the smallest tumor area measured during the trial or appearance of one or more new brain tumors diagnosed radiologically as GBM

Use in eligibility/continuationProgression per these criteria informs eligibility for continuation or classification as recurrent/progressive disease

Source trialDefinition used in EF-14 trial and documented in policy materials

TTF (Tumor Treating Fields) — A therapy delivering alternating electric fields via transducer arrays (device example: Optune/NovoTTF) used as adjunctive therapy with t...

Therapy descriptionTTF delivers alternating electric fields via transducer arrays (example devices: Optune/NovoTTF) used as adjunctive therapy with temozolomide in newly diagnosed GBM or as monotherapy/alternative in recurrent GBM

Typical componentsPortable battery-powered generator, transducer arrays with insulated electrodes, layout determined by specialized software

Patient applicationArrays are applied to a shaved treatment site (head or chest) and replaced regularly (e.g., twice weekly for GBM)

KPS — Karnofsky Performance Status; clinical trials required KPS ≥70 to ensure independence in activities of daily living.

KPS requirement in trialsClinical trials commonly required KPS >= 70 to ensure independence in activities of daily living

Policy vs trial thresholdsPolicy documents and NCCN note KPS >=60 for consideration while trials often enrolled patients with KPS >=70 (median KPS 90 in EF-14)

Documentation expectationKPS should be recorded in authorization documentation to confirm eligibility

TTF delivery system for MPM; disposable transducer arrays applied to chest and back — Optune Lua / NovoTTF-100L System

Device for MPMOptune Lua / NovoTTF-100L System (disposable transducer arrays applied to chest and back)

ApplicationArrays applied to shaved chest and back for treatment of malignant pleural mesothelioma

Regulatory noteNovoTTF-100L has FDA Humanitarian Device Exemption (HDE) documentation referenced in policy

physician's choice chemotherapy (comparator in EF-11 and registries) — PCC

Comparator termPhysician's choice chemotherapy (PCC) used as comparator in EF-11 and registries

ContextPCC included various standard chemotherapies and targeted agents (eg, bevacizumab) in recurrent GBM trials

ImplicationTTF was compared to PCC in EF-11 trial (recurrent GBM) with no OS improvement shown

TTF (Tumor Treating Fields) — Alternating electrical field therapy delivered by the Optune/NovoTTF system using transducer arrays applied to the chest; reported daily ...

Chest-applied TTFAlternating electrical field therapy delivered by Optune/NovoTTF system using transducer arrays applied to the chest; daily usage thresholds vary by study (eg, NSCLC 12 h/day, MPM reports >=18 h/day)

Device portabilityPortable, battery-powered device carried in a bag while performing activities of daily living

Array layoutTransducer array layout determined by specialized software for optimal field delivery

STELLAR — Prospective, single-arm multicenter study (NCT02397928) of TTF plus pemetrexed and platinum chemotherapy in unresectable, previously untr...

Study designSTELLAR: prospective, single-arm multicenter study (NCT02397928) of TTF plus pemetrexed and platinum chemotherapy in unresectable, previously untreated MPM (N=80)

Outcomes reportedMedian OS 18.2 months; median PFS 7.6 months; 40% partial response among those with follow-up imaging

LimitationNo randomized control group; small sample size limits comparative effectiveness conclusions

LUNAR — Randomized, open-label phase 3 trial (NCT02973789) evaluating TTF plus standard therapy (immune checkpoint inhibitor or docetaxel) versus...

Trial designLUNAR: randomized, open-label phase 3 trial (NCT02973789) evaluating TTF plus standard therapy (immune checkpoint inhibitor or docetaxel) versus standard therapy alone in metastatic NSCLC

PopulationAdults with metastatic NSCLC after progression on/after platinum-based therapy; target average TTF >=18 h/day

Sample sizeApproximately 276 patients (137 active vs 139 comparator)

KPS — Karnofsky Performance Status, used in NCCN recommendation tables to stratify treatment options.

Use in guidelinesKPS is used in NCCN recommendation tables to stratify treatment options for glioblastoma

NCCN coverage thresholdNCCN recommends adjuvant TTF plus temozolomide as category 1 for initial GBM in patients with good performance status (supratentorial disease)

Documentation relevanceKPS and other clinical factors (eg, MGMT status) should be documented when considering TTF

MGMT — O6-methylguanine-DNA-methyltransferase promoter methylation status, referenced as a factor in selecting adjuvant therapy.

Biomarker referencedMGMT (O6-methylguanine-DNA-methyltransferase) promoter methylation status is referenced as a factor in selecting adjuvant therapy

Role in decision-makingMGMT methylation status influences selection of adjuvant temozolomide and related considerations when using TTF

DocumentationPolicy suggests documenting MGMT status where relevant for initial glioblastoma management

NovoTTF/Optune — Trade names for TTFields delivery systems; FDA premarket and PMA/SSED documentation for these devices are cited.

Device trade namesNovoTTF and Optune are trade names for TTFields delivery systems referenced in FDA materials

Regulatory documentationFDA premarket and PMA/SSED documentation for these devices are cited in the policy references

Market statusOptune branded products are the only legally marketed TTF delivery systems in the U.S.

Humanitarian Device Exemption (HDE) — An FDA regulatory pathway noted in the document for the NovoTTF-100L system (H180002).

Regulatory pathwayHumanitarian Device Exemption (HDE) noted for the NovoTTF-100L system (H180002)

Indication contextHDE used in policy discussion for malignant pleural mesothelioma treatment with NovoTTF-100L

ReferenceFDA HDE summary (May 23, 2019) cited in policy references