Glioblastoma (GBM) is the most aggressive and most common form of primary brain tumor in the U.S. Close to 10,000 patients in the U.S. are diagnosed with GBM every year. It is still unknown what causes GBM. Historically, based on literature, the median overall survival time from initial diagnosis is 15 months with optimal treatment, and median survival from the time of tumor recurrence is only 3-5 months without additional effective treatment. The disease is widely recognized as one of the deadliest forms of cancer.
The three main options of treating GBM are operation, radiation and chemotherapy. But it is no secret that radiation therapy and cancer drugs may allow patients to live longer than if they had no treatment, they do have side effects. These side effects include hair loss, skin irritation, possible hearing problems, nausea, vomiting, loss of appetite, effects related to the brain, and tiredness.
A novel cancer treatment modality delivering Tumor Treating Fields (TTFields) therapy was just tested against chemotherapy in patients with recurrent glioblastoma (GBM) and the results of this study were published in the European Journal of Cancer (Stupp R. et al., NovoTTF-100A versus physician’s choice chemotherapy in recurrent glioblastoma: A randomized phase III trial of a novel treatment modality, Eur J Cancer(2012), http://dx.doi.org/10.1016/j.ejca.2012.04.011). The study showed that NovoTTFTM therapy was comparable to active chemotherapy in extending overall survival, with minimal side effects and far better quality of life.
NovocureTM, a commercial stage private oncology company, manufactures the device, NovoTTFTM-100A, a wearable device weighing around 6 pounds that can fit into a shoulder bag for easy handling. Using non-invasive, insulated transducer arrays that are placed directly on the skin in the region surrounding the tumor, TTF therapy is unlike previous applications of electricity in medicine. Specifically, TTF therapy does not deliver any electric current to the tissue. TTF therapy does not stimulate nerves or muscles or heat tissue. TTF therapy creates an artificial, alternating electric field within the tumor that attracts and repels the charged components of the cells during mitosis. The forces that the alternating electric fields exert on the cellular components are shown to inhibit mitosis and induce cell death prior to division in preclinical models.
What is Brain Cancer?
In simple terms, brain cancer is a growth of cells that form a tumor in the brain. Just like any other form of cancer, brain tumors can spread to other parts of the brain. They do not usually spread outside of the brain. Even before the brain cancer grows and spreads, the tumor could cause problems inside the brain. The brain controls the functions of the body. Any problem in the brain will affect normal functioning. Therefore, symptoms of brain cancer depend on where and how big the tumor is.
Thanks to Dr. Eilon Kirson, Chief Medical Officer at Novocure, I was treated to a detailed description of TTF Therapy and it’s applications to GBM which I humbly try to share with you here.
An electric field is a field of potential forces. It is similar to a gravitational field. An electric field is based on voltage or potential so if you have an electric potential, electric charges (electrons, protons), around the charged body will be an electric field. If you take a charged element and put it in the electric field, it will move. In an electric field we have positive and negative charges. Electric field can exert a force on an element around it. Ancient history from the 1820s tells us that opposite charges attract while similar charges repel. This is the basis for all the modern electric appliances we use.
You can generate an electric field within the body by using two plates. We call them arrays. Anything within the body that is charged will move according to the electric field. If you take this electric field and two plates with the charge that is being generated between them, one with negative, one with positive. Over time you can change the voltage on the two plates, you can make the plus go to minus. You can flip it back and forth. The rate at which you flip the field is called the field frequency. We know that many medical devices use low frequencies–pacemakers, muscle stimulators are all based on low frequency electric fields. These frequencies change directions less than 1 kilohertz (1000 times a second). If you go to very high frequencies (millions of times or even trillions of times a second), these frequencies heat the tissue. These are used in surgery for cauterizing, and they are the basis of how a microwave oven works.
The intermediate range of frequencies are the tumor treating fields. How do they inhibit the division process of cancer cells? We know that cells divide into two through a process called mitosis. What happens initially is the cell actually has within it the nuclear content, DNA content. When they replicate, chromosomes form a nice line in the middle of the cell, one set goes to right, one to the left. This structure is called a microtubule spindle. Threads grow and pull them apart. Apparently those threads are formed out of many little building blocks. Each block has a positive charge on one end, and negative charge on the other. They are polar structures. If they sit within an electric field they will flip in the direction of the electric field. If they do that, they can’t latch onto the strings and the strings stop growing and will never reach the chromosomes to pull them apart. The target of TTF therapy is that building block of the mechanical machinery that pulls apart the chromosomes. By flipping these building blocks around it acts to stop the mitotic process. Cells that stop the division process follow their own program to death which is called apoptosis. They commit suicide. By stopping the process of spindle formation, we lead these cells to a suicide pathway.
Dr. Kirson also described the benefits of TTF Therapy as compared to chemotherapy and others. TTF is a regional therapy that treats a certain part of the body. It’s not hitting the rest of the body which lowers the side effects. Chemotherapy isn’t targeted so the effects of the drug can spread to many areas. This is one of its big downfalls which scientists are addressing all the time. In addition to that even if there are cells within the region being treated with TTF that are dividing, normal cells that aren’t cancerous, TTF can be tuned to a frequency which works on a specific cell type. Cancer cells tend to be much smaller than other dividing cells. TTF can be tuned to that size and normal cells aren’t being damaged.
GBM can come back even with operations and the treatments described above. In these cases, some of the above treatments (operation, radiation, cancer drugs) may still work to treat the cancer. However, in some cases, operations and radiation will no longer work for the patient. In those cases, doctors may use a systemic cancer drug treatment, or, alternatively once a patient has had treatment with a cancer drug, the NovoTTF-100A System.
For more information on Novocure and TTF Therapy visit their website at http://www.novottftherapy.com/.