MUSELLA FOUNDATION

Patient Decision Aid

For the TTFields Device

REV 8/22/26

This Patient Decision Aid (PDA) is intended to provide glioblastoma patients information about a treatment device they can discuss with their physician and determine if using this device is right for them.

The device is the Optune Gio Tumor Treatment Fields ("TTFields").

This PDA consists of two modules and a physician interface:

1) Educational Module: Comprehensive, evidence-based information.

2) Decision Readiness Check Module: This is a short, True/False check to see if a patient understands the information and is able to decide use of the TTFields consistent with their lifestyle and values. Any misunderstandings can be corrected in a discussion with the physician.

EDUCATION MODULE

Section 1

Understanding Glioblastoma (GBM)

What is GBM? It is the most common and aggressive form of adult brain cancer. It consists of highly abnormal cells that grow into a lump with tendrils that infiltrate nearby healthy brain tissue. Because of its infiltration, glioblastoma is essentially a whole brain disease causing the surgical removal of all the cancerous cells to be virtually impossible.

Why is recurrence common? Glioblastoma remains one of the most treatment-resistant malignancies in medicine. Despite advances in surgery, radiation and chemotherapy recurrence is nearly universal, because microscopic populations of tumor cells survive treatment through a combination of treatment resistance, genetic diversity, its hostile microenvironment, and the ability to infiltrate surrounding brain tissue.

What treatments are FDA approved for GBM Following surgery and/or radiation, FDA-approved treatments used for newly diagnosed and/or recurrent glioblastoma include temozolomide (Temodar), Tumor Treating Fields (TTFields), Gliadel (carmustine) wafers, Lomustine (CCNU), and Avastin (bevacizumab). GammaTile is FDA-cleared for use in brain tumors generally, including malignant and recurrent brain tumors, as a surgically implanted radiation treatment.

Of these FDA-approved treatments, only temozolomide and TTFields have demonstrated a significant improvement in overall survival for newly diagnosed glioblastoma in randomized phase III trials.

The National Comprehensive Cancer Network (NCCN) gives TTFields its highest level of recommendation for newly diagnosed glioblastoma patients and includes TTFields as an option for recurrent glioblastoma.

Why are multiple treatments often combined? To defeat GBM many researchers and doctors are concluding that a combination of treatments is needed to manage the disease. TTFields is an approved candidate for contributing to a combination strategy.

Section 2

Understanding TTFields

What it is. TTFields (Optune Gio) is a novel system developed for cancer therapy. The system consists of a portable field-generating device (with a bag), arrays, batteries, battery charger, and plug-in power supply. The device is worn on the head like a cap.

Mechanism of action: Unlike chemotherapy or radiation, TTFields act as a biophysical treatment rather than a chemical or radiological one. TTFields consists of a cap with transducers that deliver low intensity (1-3 V/cm), intermediate-frequency (100-300 kHz) electrical pulses through the skin of the scalp and will slow or stop cancer cells' ability to divide. These pulses are tuned to specific frequencies to target cancer cells.

How it works: Normally, all the cells of our body grow and divide. To do that, the DNA in a cell replicates itself and lines up in the center of the cell. Fibers called microtubules form and pull half of the DNA to opposite ends of the cell, and the cell develops an hour-glass like shape and eventually breaks into two cells. But when cells are cancerous they divide more rapidly and uncontrollably, forming lumps called tumors.

TTFields emits low intensity, alternating, wave-like electrical pulses; it does not emit ionizing radiation. These electrical pulses interfere with cancer cell division at two points in the process:

Microtubule Interference. Microtubules rely on their electrical charges to be able to pull the halves of the DNA away from each other. In the presence of the TTFields pulses, the microtubules of cancer cells struggle to form properly and cannot complete their task of pulling the DNA to opposite ends of the cell.

Structural Damage to Cancer Cells. When a dividing cancer cell develops the hourglass like shape and tries to pinch into two, the TTFields pulse pushes cell parts back to the center potentially causing structural damage to those cells. These interferences lead to a slowing or a stopping of GBM cells ability to grow and spread, but they will not eliminate the cancer.

TTFields is targeted to act on the rapidly dividing cancer cells. Normal adult brain cells divide slowly, if at all, so are thought not to be affected by TTFields.

When is it used: For those with newly diagnosed GBM, TTFields is used with temozolomide following surgery and radiation. For those with recurrent GBM, TTFields can be used alone when options like surgery and radiation have been exhausted or may be used in clinical trials with other treatments.

Dose-Dependent Response: Clinical data shows that the TTFields therapy requires a minimum number of hours of use to be effective, because the electric fields must be active during the unpredictable window when cancer cells attempt to divide. There is no particular time when tumor cells multiply. Higher daily use of the device (18 hours or more per day) directly correlates with significantly prolonged progression-free and overall survival rates.

The benefit scales upward with increased use. Patients able to achieve an adherence rate above 90% achieved the highest long-term survival metrics in post-hoc analyses. Conversely, when the device is not in use, cancer cells can divide unchecked. If the system is disconnected for extended intervals, the therapeutic effect drops sharply because the physical forces are only present when the device is active.

Approvals: TTFields is approved for newly diagnosed GBM (concomitant with maintenance temozolomide chemotherapy) and for recurrent GBM (as a monotherapy), in the United States (by the US Food and Drug Administration) Canada, China, Israel, Japan, Australia, and several countries in Europe. The device is Conformite Europeenne [CE]-marked by the European Union.

Section 3

Evidenced-Based Benefits

Overview: Tumor-Treating Fields (TTFields) therapy provides evidence-based survival extensions, improved disease control, and a favorable systemic safety profile for newly diagnosed glioblastoma patients. When added to standard maintenance chemotherapy, it significantly improves patient outcomes without adding systemic toxicities.

EF-14 Benchmark Trial: Between July 2009 and November 2014, researchers conducted a global, randomized, Phase 3 clinical trial (referred to as "EF-14") with 695 glioblastoma patients recruited from 83 sites in North America, Europe, Korea and Israel.

The EF-14 clinical trial results for newly diagnosed glioblastoma patients are summarized in this table:

	TTFields + Temozolomide	Temozolomide Only	Relative Improvement with TTFields
Median Progression-Free Survival (PFS)	6.7 months	4 months	67.5%
Median Overall Survival (OS)	20.9 months	16 months	30.6%
5 Year Survival with high usage	29.3%	4.5%	551%*

* Results are based on a post-hoc, nonrandomized comparison from the EF-14 trial based on achieved, high usage. It demonstrates a strong association between high usage and survival while it may not prove that usage alone caused the entire difference.

Long-term survivors. The EF-14 trial tracked survival rates over several years to measure long-term impact. Approximately 13% of patients using TTFields were alive at 5 years, compared to only 5% of patients who received chemotherapy alone.

The EF-14 trial's final analysis was published in the Dec. 19, 2017, issue of the Journal of the American Medical Association.

Recurrent Patients' OS Extended: In one study, patients with recurrent GBM who used TTFields treatment saw improvement in survival comparable to that of a second round of chemotherapy.

Median Benefit Explained: The findings reported above are "median" results, which means the exact middle value in a set of numbers arranged from smallest to largest. Half of the data points fall below this number, and half fall above it. Therefore, "median PFS" is the exact length of time at which half of the patients in a trial see their disease worsen, while the other half remain stable or cancer-free.

Additional Therapeutic Effects: Although TTFields were initially found to inhibit tumor growth by interfering with cancer cell growth, by 2020 it had become increasingly clear that TTFields disrupts a multitude of cancer's biological processes, including DNA repair, cell permeability and immunological responses, which may elicit therapeutic effects. These effects were reported in the November 4, 2020, issue of the British Journal of Cancer.

Expansion of the Technology: In addition to glioblastoma, the FDA has also authorized TTFields products for unresectable locally advanced/metastatic malignant pleural mesothelioma (Optune Lua), metastatic NSCLC after platinum therapy (Optune Lua), and, as of February 2026, locally advanced pancreatic cancer (Optune Pax).

Section 4

Practical Advantages

Safe; Non-invasive. TTFields therapy is not invasive, so it does not cause side effects like pain, nausea, fatigue, diarrhea or blood , all of which are typical of chemotherapy and radiation. Because TTFields lack the systemic toxicities of traditional chemotherapy, patients can remain more emotionally present and interactive in their relationships.

Work. Many patients are able to safely maintain employment while using TTFields. However, continuing to work depends on the physical demands of the job, the underlying cancer symptoms, and how the patient adapts to the TTFields device. Jobs requiring intense manual labor, heavy sweating, or helmets may not be compatible with TTFields, because sweat can loosen the adhesive patches on the skin.

Suitable for desk jobs. The system can be plugged into a standard wall outlet, making desk jobs well-suited for using this treatment.

No radiation or hazard to co-workers. The alternating electric fields are completely contained within the patient's body; there is zero radiation exposure or electrical hazard to nearby colleagues.

Shared Family Mission. Clinical qualitative data indicates that actively managing TTFields gives families a tangible task, fostering a sense of control and a shared mission against the disease.

Relationship Communication Needs. The presence of physical wires, sticky arrays, and a continuous device connection requires open communication and mechanical adjustments regarding physical intimacy and sleeping arrangements.

Relationship Formation. Using the device connects patients to specialized technical support teams, device specialists and other users. Patients and families frequently report forming tight bonds with these external support networks.

Travel. Because the TTFields is portable, lightweight, and battery-powered, it is specifically designed to allow the user to maintain their daily routine, take vacations, and travel by plane, train, or car.

Section 5

Lifestyle Challenges

Overview. TTFields is designed to provide those diagnosed with GBM the best possible survival outcome. Like other medical devices, it does, however, present certain lifestyle challenges to be considered in your decision.

Wearing the Device. TTFields are delivered through four transducer arrays -- adhesive patches containing insulated electrodes -- that are placed directly on the skin of the scalp and positioned according to the tumor's location; the arrays are connected by cables to the battery-powered device. The device weighs about 3 pounds and can be carried in a dedicated bag (backpack, shoulder bag, or waistpack).

Head Shaving. The head must be carefully shaved in order to use the device. The shaving must be performed every few days, which can be emotionally difficult for some.

Power Source. The system comes with multiple, rechargeable batteries and a charging station; it can also be plugged into a standard wall outlet. The batteries do require periodic changing and the user is alerted to that.

Usage. Higher average daily use of TTFields has been associated with longer progression-free and overall survival. Although patients are generally encouraged to use the device for at least 18 hours per day, the most favorable outcomes in an EF-14 subgroup analysis were observed among patients who averaged more than 90% usage--equivalent to more than 21.6 hours per day. This is because, unlike a drug, the effects of TTF on glioblastoma cells are only expected to occur when treatment is active. The total length of treatment will be determined by the doctor. Users are able to unplug the device for short times (e.g., to shower).

Scalp Issues. The most common side effect of TTFields is skin irritation where the adhesive arrays contact the scalp. This is very common: about half of patients experience redness, scaling, itching, or contact dermatitis. These symptoms are usually manageable and reversible, but patients should expect that regular scalp care and adjustments to the arrays will be needed.

Sleep. Sleeping while connected to the device is a primary way patients reach their daily hourly target. Managing sleep routines may require some adjustments to stay comfortable and ensure the therapy runs smoothly through the night. Patients usually plug the device into a wall outlet and route the connection cables behind their pillows or over the headboard to allow freedom of movement without tangling.

Heat. The transducer arrays generate a small amount of heat. As a safety precaution, the device will alarm and temporarily stop treatment if one or more arrays becomes too hot. The device may also alarm and turn off in direct sunlight. Patients may need to use cooling strategies, such as lightweight head coverings, umbrellas, and shade to stay comfortable and avoid overheating.

Precautions. TTFields is generally very safe, but there are some practical precautions that can improve both safety and treatment effectiveness. The most recommended are:

Shaving the scalp carefully with an electric clipper every few days to maintain good array contact while minimizing cuts.

Changing arrays on a consistent schedule (typically every 2-4 days, or sooner if adhesion is poor).

Using a mirror or having a caregiver help inspect the scalp during each array change to catch irritation early.

Keeping extra supplies, batteries, and chargers available in case of travel delays or equipment problems.

Planning battery changes before leaving home so the device continues running during outings.

Appearances. The need for continuous wearing means that the user's medical condition becomes evident to others. Looking like a cancer patient in public can cause some to feel self-conscious. Patients will often wear loose, breathable hats, beanies, or scarves over the arrays. This conceals the bandages and wires while protecting the scalp from direct sunlight. Some patients and their families choose to embrace the look by drawing designs on the mesh arrays or adding decorative stickers, turning the medical device into a form of personal expression.

Relationships. The use of the TTFields changes one's relationships. The transducer arrays require regular changing, skin care, and re-shaving of the treatment area (e.g., the scalp for glioblastoma) every few days. Patients may need a spouse, partner, or family member to assist with this process. This increases a patient's dependence on family members' assistance.

Section 6

Financial Consideration (Applicable in the U.S.)

Retail Cost. The retail cost of TTFields therapy can be very high if paid entirely out-of-pocket. However, the vast majority of patients are able to cover the high cost with insurance coverage and manufacturer assistance programs. The Musella Foundation has an assistance program which may help patients with $5,000 per year and can be applied to a patient's insurance out-of-pocket maximum, if applicable. A person's ultimate economic impact depends on several factors:

Insurance Coverage

Medicare: Covers TTFields therapy for newly diagnosed glioblastoma patients who meet certain medical criteria. Please note that Medicare coverage for newly diagnosed GBM patients requires that TTFields therapy be initiated within 7 weeks from the last dose of concomitant chemotherapy or radiotherapy, whichever is later.

Private Insurance: Most major private insurance providers offer coverage, though it often requires a prior authorization process handled by the clinical team.

Out-of-Pocket Cap: Patients with coverage generally only pay their standard deductible, co-insurance, or maximum out-of-pocket limits defined by their specific health plan.

Financial Assistance

MyNovocure Support: The device manufacturer, Novocure, operates a dedicated patient support network called MyNovocure. This support network automatically screens for internal financial aid programs or external charitable grants to help cover remaining co-pays.

Direct Negotiation: Novocure has a program to assist patients appealing an adverse response from their insurance company. Novocure assigns coordinators to talk directly with insurance companies to minimize patient out-of-pocket expenses.

Hardship Programs: Novocure provides financial assistance or zero-cost options for eligible underinsured or uninsured patients based on financial need.

Indirect Costs

Medical Supplies: There are costs for shaving supplies and specialized skin care products required to maintain a clean scalp for optimal electrode contact.

Adverse Events: Clinical data indicates potential treatment management costs for device-related side effects, such as localized skin dermatitis, which can occasionally be expensive for separate dermatological care, if severe. Coverage of such costs would be defined by the patient's health insurance.

Electricity: There may be increased household utility bills from continuously recharging the portable battery packs and/or increased use of air conditioning.

Section 7

What experts still disagree about

Researchers generally agree that TTFields improves outcomes on average. However, legitimate discussions continue around certain scientific uncertainties.

Questions About Optimal Patient Selection. Experts continue to debate whether TTFields should be viewed as a broadly applicable adjunct to standard therapy or whether future use should become increasingly personalized through biomarker-guided patient selection.

Questions About Mechanism(s) of Action. There is also ongoing discussion about the biological mechanisms responsible for TTFields' antitumor activity. Preclinical studies indicate that alternating electric fields interfere with mitotic spindle formation, cytokinesis, and chromosome segregation, while additional work suggests broader effects on DNA damage repair, cell membrane permeability, immune activation, autophagy, and the tumor microenvironment.

However, the relative importance of these mechanisms in patients remains uncertain, and it is not yet established which are primarily responsible for the clinical benefit observed in randomized trials.

Questions About Predictors of Response. Similarly, questions persist regarding trial methodology and interpretation of the evidence. Because TTFields require continuous device use, sham-controlled studies are challenging, raising concerns about potential biases related to treatment adherence, patient selection, and open-label trial design, even though overall survival is generally considered a robust endpoint.

Questions About Integration Into Multimodal Treatment Strategies. Looking ahead, many investigators believe that the greatest advances may come from rational combination strategies rather than TTFields alone. Ongoing studies are evaluating combinations with immunotherapy, targeted therapies, DNA damage response inhibitors, and novel radiotherapy or chemotherapy approaches, based on the hypothesis that TTFields may sensitize tumors to other treatments. Whether these combinations will produce additive or synergistic benefits, and in which biological subsets of patients, remains an active area of investigation.

Section 8

Values Clarification

These questions are intended to help you clarify your priorities. There are no right or wrong answers.

How do I think about time versus quality of life?

If treatment gives me a chance at living longer, how much day-to-day inconvenience am I willing to tolerate?

Would I regret not trying this treatment with evidence of benefit, even if the benefit is uncertain for me personally?

Or, would I regret spending too much of my remaining time focused on treatment?

How important is maximizing survival?

Is "doing everything possible" an important value for me?

Or is maintaining as much normalcy as possible more important?

How much treatment burden am I comfortable accepting? (TTFields has very few side effects, but it is demanding. )

How would I feel about wearing a device most of the day?

Would I feel self-conscious in public wearing or carrying it?

How much would shaving my head bother me?

Would frequent array changes become emotionally or physically draining?

What activities matter most to me?

Which activities define a good day for me?

Would the device interfere with those?

Could I realistically adapt and continue doing what I enjoy?

How do I make decisions under uncertainty? (TTFields improves outcomes on average across groups of patients, but no one knows whether any individual person will benefit. )

Am I comfortable accepting burdens for a chance of benefit?

Or, do I generally prefer treatments when the personal benefit feels more certain?

What role must my family and loved ones play in this if I choose to proceed?

Would using the device reassure my family that we've pursued the available options?

Would managing the device place significant burdens on my caregiver?

Am I comfortable asking others to help with maintenance if needed?

What matters more to me emotionally?

Some people say: "If I don't try it, I'll always wonder." Others say: "I don't want my life to revolve around cancer treatment."

Which statement feels more like me?

Which choice would leave me with fewer regrets?

How do I feel about visible reminders of illness?

Would wearing the device help me feel proactive against my cancer?

Or, would it be a constant reminder I have cancer and make it harder to feel like myself?

What are my practical limits? (Sometimes practical realities are just as important as medical considerations. )

What about:

Travel

Work

Financial impact (including insurance coverage and indirect costs)

Access to support

Energy for learning and maintaining the device

Have my goals changed? (People's priorities often shift during treatment.)

What am I hoping for now?

If my priorities change later, would I feel comfortable stopping the device?

Am I giving myself permission to reassess rather than treating today's decision as irreversible?

A useful exercise (Some people find it helpful to rank these values from most to least important: )

Living as long as possible.

Preserving independence.

Preserving privacy.

Maintaining quality of life day to day.

Avoiding regret.

Spending meaningful time with loved ones.

Minimizing treatment burden.

Maximizing the fight against the disease.

Staying active and mobile.

Feeling in control of treatment decisions.

(There is no "correct" ranking, but seeing which values rise to the top can make the decision clearer. )

Questions to discuss with your neuro-oncologist

Based on my age, tumor characteristics, and overall health, how much benefit do you think TTFields is likely to provide for me specifically?

What side effects do your patients most commonly experience?

If I try it and decide it's not consistent with my goals, can I stop without affecting my other treatments?

What have patients with priorities similar to mine found most helpful or most challenging?

Decision Making.

Your decision should align with your definition of living well while facing glioblastoma. A choice that is clearly right for you may not be the right choice for another, even when both of you have very similar medical situations.

Section 9

For More Reading (Optional)

To learn more about the Optune Gio: please go to https://www.optunegio.com

Scientific articles:

Report of the benchmark EF-14 study by 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. 2017;318(23):2306-2316. doi:10.1001/jama.2017.18718

Article by Simon Khagi, Rupesh Kotecha, Na Tosha N Gatson, Suriya Jeyapalan, Huda Ismail Abdullah, Nicholas G Avgeropoulos, Eleni T Batzianouli, Moshe Giladi, Leonardo Lustgarten, Samuel A Goldlust, Recent advances in Tumor Treating Fields (TTFields) therapy for glioblastoma, The Oncologist, Volume 30, Issue 2, February 2025, oyae227, https://doi.org/10.1093/oncolo/oyae227

Ballo MT, Conlon P, Lavy-Shahaf G, Kinzel A, Vymazal J, Rulseh AM. Association of Tumor Treating Fields (TTFields) therapy with survival in newly diagnosed glioblastoma: a systematic review and meta-analysis. J Neurooncol. 2023 Aug;164(1):1-9. doi: 10.1007/s11060-023-04348-w. Epub 2023 Jul 26. PMID: 37493865; PMCID: PMC10462574.

Mehta M, Wen P, Nishikawa R, Reardon D, Peters K. Critical review of the addition of tumor treating fields (TTFields) to the existing standard of care for newly diagnosed glioblastoma patients. Crit Rev Oncol/Hematol 2017;111:60-5. https://doi.org/10.1016/j.critrevonc.2017.01.005.

Lassman AB, Joanta-Gomez AE, Pan PC, Wick W. Current usage of tumor treating fields for glioblastoma. Neurooncol Adv 2020 2(1):vdaa069. https://doi.org/10.1093/noajnl/vdaa069.

Glas M, Ballo MT, Bomzon Z, Urman N, Levi S, Lavy-Shahaf G, et al. The impact of Tumor Treating Fields on glioblastoma progression patterns. Int J Radiat Oncol Biol Phys 2022; 112(5):1269-78. https://doi:10.1016/j.ijrobp.2021.12.152.

Chen D, Le SB, Hutchinson TE, Calinescu AA, Sebastian M, Jin D, et al. Tumor Treating Fields dually activate STING and AIM2 inflammasomes to induce adjuvant immunity in glioblastoma. J Clin Invest 2022; 132(8):e149258. https://doi:org/10.1172/JCI149258.

Wainer-Katsir K, Haber A, Fishman H, Ding L, Story MD, Du R, et al. The transcriptomic fingerprint of cancer response to Tumor Treating Fields (TTFields). Cell Death Discov 2025;11(1): 319. https://doi.org/10.1038/s41420-025-02615-5.

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