Tumour treating fields: OPTUNE
What is it?
Optune is a physical therapy. It is a portable, non-invasive medical device designed for continuous use by patients. Unlike healthy cells, cancer cells divide quickly, in an uncontrolled way (mitosis). As they divide, they form a mass or tumour. Optune is a non-invasive regional therapy that targets dividing cancer cells in the brain and generally does not harm healthy cells. It works by creating alternating, “wave-like” electric fields called Tumour Treating Fields (TTFields). TTFields travel across the upper part of the brain in different directions to help slow or stop recurrent glioblastoma cancer cells from dividing.
Optune is delivered through 4 transducer arrays that are placed directly on the scalp to target the tumour. The transducer array placement is determined based on each patient’s MRI results to maximize the therapy’s effect on the tumour.
Optune has received marketing approval in the U.S. under the brand name Optune™ for recurrent GBM. The NovoTTF-100A System is a CE Marked device cleared for sale in the European Union, Switzerland, Australia and Israel.
How is it used?
Studies have shown that treatment is more effective if used for more than 18 hours a day. It is worn from first diagnosis until death and is used with the standard treatment protocol of radiotherapy and chemotherapy (temozolomide).
To work effectively, the transducer arrays must be placed directly on the scalp, so the head has to be shaved throughout treatment. The transducer arrays need to be replaced one to two times per week (every 4 to 7 days), depending on factors like how much the patient sweats and how quickly hair grows. Patients can shower without taking off the transducer arrays but they have to wear a shower cap.
The patient must learn to change and recharge depleted device batteries and to connect to an external power supply overnight. In addition, the transducer arrays need to be replaced once to twice a week and the scalp re-shaved in order to maintain optimal contact. Patients carry the device in an over-the-shoulder bag or backpack and receive continuous treatment without changing their daily routine. This is heavy – about 7kgs. Second generation systems weigh much less (1.3kgs)
Optune commonly causes skin irritation beneath the transducer arrays and in rare cases can lead to headaches, falls, fatigue, muscle twitching or skin ulcers. 45% of patients had skin irritation (2% severe).
A randomized phase III trial was conducted in newly diagnosed patients. The primary endpoint was progression free survival (PFS). The pre-specified, interim analysis of EF-14 trial data was conducted on the first 315 patients, representing approximately 50 percent of the targeted study population. The trial was stopped early due to the success.
The data shows that:
- Patients treated with TTFields together with temozolomide demonstrated a significant increase in progression free survival compared to temozolomide alone (median PFS of 7.1 months compared to 4.0 months, hazard ratio=0.63, p=0.001).
- Patients treated with TTFields together with temozolomide demonstrated a significant increase in overall survival compared to temozolomide alone (median OS of 19.6 months compared to 16.6 months, hazard ratio=0.75, p=0.034).
- The percentage of patients alive at 2 years in the TTFields together with temozolomide arm was 43% compared to 29% in the temozolomide alone arm.
In summary you are looking at an average of an extra 12 weeks for both PFS and OS).
“These results are spectacular – a lot better and much more convincing than we ever would have dreamt of,” said Dr. Roger Stupp, M.D., Director of the University Hospital Cancer Center at the University of Zurich, Zurich, Switzerland and EF-14 Principal Investigator. “A new standard of care for patients suffering from glioblastoma is born.”
- Actively participating in another clinical treatment trial
- Within 4 weeks from surgery for recurrence
- Within 4 weeks from any prior chemotherapy
- Within 4 weeks from radiation therapy
- Significant co-morbidities within 4 weeks prior to enrollment
- Implanted pacemaker, defibrillator or deep brain stimulator, or documented clinically significant arrhythmias
- Infra-tentorial tumor
- Evidence of increased intracranial pressure (midline shift > 5mm, clinically significant papilledema, vomiting and nausea or reduced
1) Significant liver function impairment—AST or ALT > 3 times the upper limit of normal
2) Total bilirubin > upper limit of normal
3) Significant renal impairment (serum creatinine > 1.7 mg/dL)
4) Coagulopathy (as evidenced by PT or APTT >1.5 times control in subjects not undergoing anticoagulation)
5) Thrombocytopenia (platelet count < 100 x 103/μL)
6) Neutropenia (absolute neutrophil count < 1 x 103/μL)
7) Anemia (Hb < 10 g/L)
8) Severe acute infection
The U.S. FDA has approved Optune for use as a treatment for adult patients (22 years of age or older) with histologically-confirmed GBM, following histologically – or radiologically-confirmed recurrence in the supra-tentorial region of the brain after receiving chemotherapy. The device is intended to be used as monotherapy, and is intended as an alternative to standard medical therapy for GBM after surgical and radiation options have been exhausted.
Benefits and risks
- Optune works as well as chemotherapy.
- There are minimal side effects. Optune delivers treatment to the region where the tumor is located and does not cause many of the side effects of chemotherapy, including infections, nausea, vomiting, diarrhoea, and blood toxicities.
- Better quality of life. Patients using Optune reported a better quality of life with improved cognitive and emotional functioning compared to patients treated with chemotherapy.
Skin irritation is often seen under the transducer arrays when using Optune. The irritation can be treated with steroid cream or by moving the transducer arrays. If it isn’t treated, the skin irritation could become more serious. This may lead to open sores, infections, pain and blisters.
Headaches, weakness, convulsions, and thinking changes were seen in the clinical study of Optune. In the device group. 18 out of 116 patients had headaches, 10 out of 116 patients had weakness, 10 out of 116 patients had convulsions, and 6 out of 116 patients had thinking changes. These events are also seen in patients with recurrent GBM who do not use Optune. However, there was a higher rate of these problems overall in Optune patients (43.1%) compared to patients on cancer drugs (36.3%). Only skin redness and open sores are related to Optune treatment itself.
You can read more information about Optune here.
It seems to only be effective on patients with smaller GBMs in the supratentorial region.
It appears to provide an extra 12 weeks PFS and OS.
It costs $20,000 per month.
The clinical community is skeptical of this treatment.
Tumor Treating Fields (TTF-Optune)
Unexpected results – only phase 3 trial that has met primary end points. Overall survival extended by about 12 – 16 weeks.
Not adopted widely because:
- lack of experience
- science is not explained
- interim data set is not representative
- patients don’t all accept the device
- cost (£20k per month)
- shift needed from molecular physics to biophysics
- Impractical, unwieldy and unsightly
There is a huge marketing machine behind Novocure. They said if this had been a drug it would have been accepted. What has thrown them is that Roger Stupp was the principle investigator who sat on the independent panel. He is very highly regarded and was behind the current standard protocol.
It will be very many years before this is approved by NICE for use in England. In the meantime patients will need to source and finance this for themselves.
Questions you should ask yourself:
- How would I feel having to wear this round the clock for the rest of my life?
- How will I feel having to shave my head twice a week?
- How will I feel having to carry a 7KG battery around all of the time?
- This will mark me as different when I’m are out and about. How do I feel about this?
- What is important to me? e.g. some people may have a reason for wanting the extra time. For others their identity may be more important.
- How will I fund this treatment?
Did this information make you feel more resourced, more confident or more in control?
Date published: 17-05-2009
Last edited: 28-02-2018
Due for review: 28-02-2021