Tumor Treating Fields: A New Technology for Cancer Treatment


Introduction

A new cancer technique called tumor treating fields, sometimes referred to as Optune or TTFields, was developed to use electric fields to treat cancer. Utilizing a transportable, lightweight instrument, TTFields are administered. The machine's four adhesive patches are applied to the body part where the malignancy is located. The patches then apply alternating, low-intensity electric fields there. The electric fields prevent the division of cancerous cells. The TRIDENT clinical trial, which is scheduled to conclude in 2026, examines the potential survival advantage of utilizing tumor-treating fields in addition to radiation therapy and a chemotherapeutic agent.  

FDA approval was given to tumor treatment fields in 2019 for the treatment of mesothelioma. For individuals with rare or aggressive cancers like glioblastoma multiforme, the outcome of the most recent clinical trial using tumor-treating fields may determine how cancer will be treated in the future (GBM). The average patient survival time is 14 months, and GBM makes up 46% of primary brain malignancies. Using electrical fields in conjunction with conventional medicine, Tumor treating fields offer a fresh perspective on cancer treatment. Patients with brain tumors and mesothelioma live longer because of the technique, which also reduces drug toxicity.

Cancer still ranks as one of the primary causes of death despite significant therapeutic advancements. The tolerance and adherence of conventional medicines are also severely hampered by their toxicities. Alternating electric fields at particular frequencies and intensities are used in TTFields, a noninvasive anticancer therapy technique, to specifically disrupt mitosis in malignant cells. Apoptosis and the halt of mitosis are caused by TTFields' targeting of proteins essential to the cell cycle. An immune response that is anticancer is also supported by TTFields. GBM patients in clinical studies with TTFields have found it to be safe and effective, and it is FDA-approved for use in newly diagnosed and recurrent GBM. There are now active trials for various localized solid tumors.

The FDA has approved the use of TTFields for both newly diagnosed and recurrent illness due to its efficacy and tolerance profile in GBM. Given that TTFields' targets are widespread and largely tumor-type nonspecific, they might be helpful for several other localized malignancies other than GBM. Research is currently being done on TTFields in a number of additional solid tumours, such as malignant mesothelioma, ovarian, pancreatic, and NSCLC as well as brain metastases from these cancers.

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Tumor Treating Fields and Glioma

The primary malignant tumour of the central nervous system that occurs most frequently is a glioma (CNS). In particular, glioblastoma multiforme WHO° IV (GBM) exhibits aggressive behaviour with a concomitant negative result and thus a constrained life expectancy. The accepted standard of care entails six cycles of temozolomide (TMZ) monotherapy after a neurologically safe tumour resection, followed by adjuvant concurrent radiochemotherapy. The Stupp protocol is the name of this tactic. Nevertheless, there aren't many effective treatment options for recurrent or progressive sickness, and the illness is considered incurable.

As a result, there is still a big need for fresh ideas and focused treatment choices. A lot of research has been done in this area, but only a small number of potential therapeutic ideas have made it into clinical practice. One of them is the precise application of fields that treat tumours (TTFs). This approach relies on the local interference of electric fields with the tumor's mitotic activity. As the development of the mitotic spindle is interrupted in metaphase and anaphase, proliferating cells are prevented from continuing to divide or undergo apoptosis.

For the treatment of people with recently diagnosed GBM, TTFs have received FDA and EMA approval. In this situation, TTFs are ideally started concurrently with TMZ monotherapy and within six weeks of the conclusion of concurrent radiochemotherapy. To avoid the negative effects of systemic second-line chemotherapeutics in the case of recurrent GBM, TTF therapy is an alternative treatment option. However, there are still debates over the advantages of TTF.

Four gentle, non-invasive adhesive electrode arrays are practically applied on the patient's shaved head. The electrode arrays' poles, which are supplied via a wire, are where the electric field is produced. The pacemaker-equipped control device and the replaceable accumulator are put in a carry-on luggage or backpack. When the device was worn for at least 18 hours each day, there was therapeutic success, with benefits increasing with each additional hour. TTF therapy typically doesn't call for a second oncological follow-up visit or an overnight hospital stay. The manufacturer's service department offers technical support. However, daily assistance from a member of the patient's family is still required.

Since January 2016, this type of treatment for GBM has been a standard of care at our facility and is included in international clinical guidelines. In the years that followed, we developed practical expertise in TTF initiation, namely informed consent, compliance, and follow-up. As a result, we sought to discuss the state of the art today along with our extensive knowledge of TTF usage in daily life. Additionally, we assessed the present benefits, limitations, and TTF possibilities as well as continuing research.

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Tumor Treating Fields Treatment and Working

The portable TT fields treatment gadget may enable people to treat their cancer while carrying on with their regular activities. Small transducers are applied to the heads of patients receiving TT fields therapy using adhesive bandages. To utilize the gadget, hair must be shaven. The wires that the transducers are attached to are plugged into a battery that is roughly the size of a book. The batteries are contained in a bag that the user wears on their person, either as a messenger bag, a backpack, or across their body. The setup includes a charging station and several batteries. When new batteries are required, the user is informed. People have the option to unhook the gadget, but the therapy is ongoing.

Normal cells are unaffected by the TT fields' action on the rapidly dividing malignant tumor cells. Certain highly charged proteins in cells are affected by TT fields. These proteins are necessary for cell division, which aids in the growth and dissemination of malignancies. The proteins organize into chains that tear apart the copies of genetic material in the cell's nucleus when a cancer cell is ready to replicate itself. This process seems to be hampered by TT fields. The cancer cells self-destruct when the TT fields stop them from dividing properly. More tumor cells perish over the course of a few weeks or months, and the tumor gets smaller.

A small cohort of 10 patients participated in the first trial against GBM ever carried out with TTFields as monotherapy, which was started in 2007. A phase II experiment using TTFields following radiation and adjuvant temozolomide (TMZ) was conducted as a result of the study's positive safety findings, and the results showed a median overall survival (OS) of more than 39 months. 120 GBM patients receiving TTFields treatment in a randomized trial (EF-11) had comparable OS and responsiveness to 117 patients who received conventional systemic therapy. Based on these data, the FDA approved the first-generation TTFields device (NovoTTF-100A) as a treatment for recurrent GBM in 2011.

Conclusion

The development of TTFields as a promising therapeutic agent for the treatment of various solid tumours has advanced significantly from the initial laboratory observations to the implementation of multiple clinical trials. TTFields show potential as a novel, non-invasive anti-cancer therapeutic technique, most likely through inhibiting cell proliferation and tumour growth by limiting mitotic activity. Regarding precisely how TTFields affect cancer cells, there are still unanswered questions. According to mathematical modelling, TTFields instead cause changes in cell membrane potential that have negative downstream effects during cell separation at the cleavage furrow rather than producing severe anti-mitotic effects by disrupting microtubules.

Several additional unanswered mechanistic questions also need to be addressed. It is yet unknown how TTFields function during each cell cycle stage and how they relate to DNA repair pathways and mitotic catastrophe. Evaluating whether TTFields influence centrosome-mediated microtubule biology in a manner that preferentially affects tumour cells would be a fascinating topic of research. Gaining more knowledge about the workings of TTFields will undoubtedly open the door to more creative clinical trials. A deeper understanding of TTFields biology is essential to find novel vulnerabilities in particular malignancies that might be effectively targeted by TTFields, either as monotherapy or in combination with other therapeutics. To date, there have been six completed clinical trials and fourteen are currently ongoing at various stages.

Important Notes:

  • TT fields are low-intensity electrical pulses that pass through the scalp's skin and prevent cancer cells from proliferating.
  • This "field of interruption" might inhibit the growth and spread of a tumor.
  • The FDA approved a tumor-treating field device in 2011 for the treatment of a few cancers, including the most aggressive brain tumor, glioblastoma multiforme (GBM).
  • In one study, individuals with recurrent GBM who received TT fields treatment experienced an increase in survival that was on par with receiving further chemotherapy.
  • In contrast to chemotherapy and radiation, TT fields therapy does not result in the side effects of pain, nausea, exhaustion, or diarrhea.
  • The patient will put on an item that fits over their scalp while receiving TTF treatment. An electric field that cycles between positive and negative from 100,000 to 300,000 times per second is created via a network of wires and electrodes.
  • TTF prevents cancer cell proliferation because cancer cells include specific biological proteins that are both positive and negative, giving patients the option to extend survival.
  • The patient will use the TTF device for several hours every day while undergoing therapy, returning for checkups every one to two months. The patient will receive comprehensive TTF usage instructions from the patient care team.
  • TTF's electric fields don't heat up or activate tissue or cellular activity. The harm to healthy cells is minor. Mild to moderate skin irritation is the most frequent adverse reaction.
  • Adults with recurrent glioblastoma, one of the most challenging cancer types to treat, and mesothelioma are eligible for tumor-treating fields, according to the FDA.
  • TTF may also provide a novel therapeutic approach for a variety of solid tumors, including the most aggressive malignancies of the ovary, pancreas, non-small cell lung, and breast.

In the future, TTFields will keep expanding its application to incorporate fresh and little-known solid tumours. Breast, cervical, colorectal, gastric, hepatocellular, melanoma, renal, urinary transitional cell, and small-cell lung cancer preclinical research examining the utility of TTFields are currently being conducted. The success of using TTFields more frequently in cancer therapy in the future will be determined by the results of these preclinical investigations and the subsequent clinical trials. Designing new model kinds and applicators with the best functionality and usability when new tumours in other anatomical locations are taken into consideration will also present interesting challenges. Additionally, research will continue into how TTFields affect actively proliferating noncancerous cells in these many anatomical areas.

In order to improve the efficacy of TTFields in treating this and other malignancies, more study will be required because the majority of GBM patients who receive treatment with TTFields eventually die from tumour progression. Modifications to the applied frequency and intensity are two potential directions, as well as continued array arrangement optimization. The application of TTFields to tumours with less well defined boundaries or areas is another future idea. For example, TTFields has not yet been investigated in liquid malignancies. It would make a significant contribution to figure out how to apply alternating electric fields through a patient's circulatory system and to assess the effectiveness and safety profile of doing so.


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