When I was a PhD student in the United States, my supervisor was an oncologist who specialized in treating brain tumors. But he later came to see fewer and fewer patients, but instead spent a lot of time doing scientific research, and his income dropped significantly. I asked him why? He said: "Because the main people who come are malignant gliomas, there are so few ways to do it, and almost every patient who comes, I know that he is likely to die within a year." I don't know how to give them hope. ”
Indeed, malignant gliomas (glioblastomas), which have traditionally been one of the worst tumor types, have a high recurrence rate, with a 5-year survival rate of only about 5%.
From patients to families to doctors to scientists, everyone is asking, where is the hope?
At the beginning of 2014, Steve, a 55-year-old middle-aged man in the United States, was unfortunately recruited. He was very healthy himself, but suddenly one day his left leg could not move. When he went to the hospital, he got bad news: he had a malignant glioma; and the doctor told him very directly that this cancer was incurable.
At this time, he has two choices: one is to do nothing, and the other is to start standard treatment (surgery + radiation therapy + chemotherapy).
Knowing that there is no cure, is it still not curable? This is not an easy question to answer. But for Steve, the answer is simple, that is, it must be cured! An important reason is that Steve's wife, who has been married for 30 years, has been diagnosed with skin cancer twice and successfully defeated twice, so they once again chose to fight and hope.
Surgery, radiation, chemotherapy, one harder than the other, but Steve survived.
The good news was that the vast majority of the cancer cells had been removed, and his left leg was again at the mercy of the call. But the bad news is that there are still many residual cancer cells in the head, and they are almost doomed to relapse in the future.
What to do?
He still did not give up and began to seek clinical trials. At this time, someone recommended a clinical trial and a therapy that he had never heard of: tumor electric field therapy.
The doctor opened the slide and began to introduce a special hat, saying that this hat is a new technology, after powering up, can produce a special electric field locally to control tumor cell growth. Early clinical trials have shown that it, in conjunction with chemotherapy, can improve patient median survival by several months. It may not seem like much, but for patients with advanced brain tumors, a few months is already a luxury hope.
Using an electric field to treat a tumor? It feels very mysterious!
Steve was skeptical, but since there was no better way, he chose to join the clinical trial.
Luckily, Steve is still alive today, wearing that special hat every day and living a regular life.
At this time, it had been exactly 8 years since he was diagnosed with an "incurable" brain tumor.
Like many people, when I first heard about tumor electric field treatment, I was very skeptical. Because from childhood to adulthood, I have heard too many masters who are known as "electric fields and aura" to treat various diseases, including some qigong fools.
But after research, I found that this time I was wrong, and the electric field treatment of this tumor in the United States is really different.
It's called Tumblr Treating Fields, or TTFields for short, and it's a new approach that's already on the market. A wearable device developed by Israeli biotech company Novokure, approved by the FDA in 2011 for the treatment of malignant gliomas, it has recently begun to expand to other tumor treatments.
Looks like this, it's like this.
Its inventor is the Israeli scientist Dr. Yarmam Palti, at the beginning of its existence, due to the special mechanism, it was indeed questioned, until clinical trials proved its efficacy, was approved by the US FDA for the treatment of glioma, began to be widely accepted.
In the United States, tumor electric field therapy is approved for the treatment of malignant gliomas and malignant pleural mesotheliomas.
In clinical trials for patients with recurrence, tumor electric field therapy alone is similar to chemotherapy, but the side effects are significantly smaller. Among patients receiving chemotherapy, 16% had serious adverse reactions, including headaches, hypothrombocytopenia, nausea, diarrhea and other adverse reactions, while in patients treated with tumor electric fields, common side effects were dermatitis, headache, etc., and the proportion of serious adverse reactions was only 6%.
The real breakthrough came from first-line adjuvant therapy for newly diagnosed patients, and the data was published in the Journal of the American Medical Association in 2017.
In an international Phase III controlled clinical trial code-named EF-14, nearly 700 patients with glioma who completed radiotherapy and chemotherapy received temozolomide (chemotherapy) in one group and a combination of tumor electric field therapy + temozolomide.
The results showed that after adding tumor electric field treatment, the progression-free survival rate and overall survival rate were significantly improved.
Median progression-free survival increased from 4 months to 6.7 months, while median overall survival increased from 15.6 months to 20.9 months. The five-year survival rate has also increased from 5% to 13%.
Studies have also shown that the longer you wear it, the better. For patients who exceeded 22 hours a day, the median survival was extended to 25 months, approaching 30% for five years! For such a challenging disease, such data is encouraging.
In addition, tumor electric field therapy with standard therapy does not increase significant toxic side effects, so in 2015, it was successfully approved by the FDA for marketing and was also written into the international NCCN guidelines. China's guidelines have also been updated, explicitly stating in the Code of Diagnosis and Treatment of Gliomas (2018 Edition):
"Current studies have shown that electric field therapy is safe and effective, and is recommended for treatment of both new GBM (level 1 evidence) and recurrent high-grade gliomas (level 2 evidence)."
Success in brain tumors is important because it proves that tumor electric field therapy is not pseudoscience. This gave the researchers a shot in the arm and opened up a broader world. From the original point of view of tumor electric field treatment, tumor electric field treatment combined with chemotherapy and other means can not only treat brain tumors, but also may be used for other tumors.
In May 2019, the U.S. FDA approved an electric field treatment for tumors combined with pemetrexed and platinum chemotherapy regimens for the first-line treatment of unresectable locally advanced or metastatic malignant pleural mesothelioma (MPM). In the malignant mesothelioma study code-named STELLAR, the median overall survival of tumor electric field therapy combined with chemotherapy reached 18.2 months, while historical data showed that chemotherapy alone was only 12.1 months.
As a research hotspot, combination therapy has also repeatedly spread good news. This time last year, a LUNAR study of TTFields plus immunotherapy or docetaxel for advanced non-small cell lung cancer was asked to shorten follow-up time and sample size after being evaluated by the Monitoring Board. This is seen as a good signal to look forward to the final data release. In addition, a phase 2 clinical study called 2-THE-TOP showed a median overall survival of 25.2 months in glioblastoma patients treated with TTFields plus K drug and temozolomide, compared with 15.9 months in patients with historical pairing EF-14.
In addition, it has a number of clinical trials in the fields of tumor brain metastasis, pancreatic cancer, ovarian cancer, stomach cancer, liver cancer and other fields.
After talking about so much data, everyone must ask, how does tumor electric field treatment work?
Simply put, it uses an electric field to interfere with cell division and make it wrong, thereby inducing the death of rapidly dividing cells ( such as cancer cells ) .
Just as every car has many parts, there are many complex components in every cell, including protein molecules, DNA molecules, and so on. For a car to run, it needs every part to fit closely together, and so do the cells. Various molecules in the cell need to appear in the right place at the right time to ensure cell function.
For example, the division of cancer cells (the term is "mitosis") requires many cellular parts to work together to ensure the replication and separation of DNA, so that one cancer cell becomes two cancer cells.
One of the most important parts of this splitting process is the microtubules (the green part of the figure below).
The image above shows a cell that is dividing, with a blue chromosome (DNA) in the middle, pulled by microtubules, preparing to split in two. As you can see, the correct arrangement of microtubules in cells is extremely important for chromosomal replication and isolation, and for the smooth division of cells, and cancer cells are no exception.
Each microtubule is made up of a large number of tubulin proteins (green and blue globules in the figure below) built according to a fixed structure. It's like Lego bricks, piled up one by one.
Figure: Microtubules built of tubulin
What does this have to do with electric field therapy?
It has a lot to do because tubulin is polar! If it is continuously disturbed by external electric fields, tubulin may run around, and it will not be possible to build useful microtubules smoothly. In this way, the whole cell division cannot proceed smoothly.
Tubulin is just one example, there are many core proteins in cancer cell division, including Septins, which are polar and may be affected by electric fields.
The essence of tumor electric field treatment is to use a suitable electric field (such as an intermediate frequency low-intensity alternating electric field) to continuously act locally (such as the brain), thereby affecting the arrangement of many polar molecules such as tubulin and blocking the division of cancer cells.
The following figures show the cancer cells that are disturbed by the electric field and cannot divide normally. It can be intuitively seen that their microtubule structure has been disordered.
It must be pointed out that not all electric fields can treat tumors, optune electric field treatment is currently the only approved tumor electric field treatment system. It is very complex in itself, from the electric field strength, frequency, distance, etc. there are many exquisite, by no means easy to get it done.
Just like after the success of PD-1 immunotherapy, a bunch of big flashes in the name of immunotherapy suddenly appeared in society. I reckon that its success will also spawn a batch of magical "XX field therapies". Everyone must polish their eyes.
The success of electric field therapy on cancer is a particularly inspiring story.
On the one hand, it helps many brain tumor patients survive for a long time and return to normal life. On the other hand, it has caused many skeptics to change their minds.
Dr. Palti himself is an expert in biophysics and electrophysiology, not a drug, and the concept of tumor electric field therapy is not understood, valued, or even accepted in the field of anti-cancer scientific research based on the development of drugs. So it has always been a non-mainstream presence. In 2000, the first laboratory to start research on the treatment of tumor electric fields was the basement of Dr. Palti's house.
Why did it succeed?
Or rely on clinical trials and objective data!
Good scientists like to question, but also keep an open mind. From the publication of the first research paper in 2004, to the opening of the Phase 3 clinical trial in 2006, and then to the second Phase 3 clinical trial in 2009, scientists and companies have published a large number of peer-reviewed data around this project. With the success of clinical trials of tumor electric field therapy, more and more scientists and doctors are beginning to embrace this new treatment.
At the end of 2018, the tumor electric field treatment has been listed in Hong Kong, and the first patient has already used it. In May 2020, tumor electric field therapy was launched in mainland China.
I hope that this therapy can benefit more patients, and I hope that more "non-mainstream" anti-cancer therapies can withstand the test of science! Anyway, no matter the black cat or the white cat, the mouse can be caught is a good cat!
The following is a group of popular science students who use their spare time to do popular science videos during their freshman year, hoping to help everyone understand this therapy more vividly.
bibliography
[1] NovoTTF-100A versus physician's choicechemotherapy in recurrentglioblastoma: a randomised phase III trial of a noveltreatment modality. Eur J Cancer, 2012. 48(14): p.2192-202.
[2] Effect of Tumor-TreatingFields PlusMaintenance Temozolomide vs Maintenance Temozolomide Alone onSurvival inPatients With Glioblastoma: A Randomized Clinical Trial. JAMA,2017. 318(23): p.2306-2316.
*This article aims to popularize the science behind new cancer drugs, not drug promotional materials, let alone treatment plan recommendations. For guidance on treatment options, visit a regular hospital.