Cancers: Application of tumor treatment electric field in glioblastoma

In 2011, the first generation of tumor treatment electric field (Tumor-Treating Fields, TTFields), then known as the NovoTField-100A system (now renamed Optune), was approved by the U.SFood and Drug Administration (FDA) for the treatment of recurrent GBMAuxiliary treatment for newly diagnosed GBM was approved in 2015Denise Fabian et alof Ohio State University's Department of Radiation Oncology recently systematically reviewed TTFields's therapeutic effects on gliomas, and the results were published online in Cancers in February 2019- From the article chapter
(Ref: Fabian D, et alCancers) 2019 Feb 2;11 (2)Pii: E174doi: 10.3390/cancer11020174glioblastoma (glioblastfor multime, GBM) is the most common primary brain tumorDespite active treatment, GBM almost always recursSince 2005, the standard treatment for newly diagnosed GBM has included maximum surgical excision, postoperative radiotherapy combined with TMZ synchronous assisted chemotherapy, but clinical results remain limitedIn 2011, the first generation of tumor treatment electric field (Tumor-Treating Fields, TTFields), then known as the NovoTField-100A system (now renamed Optune), was approved by the U.SFood and Drug Administration (FDA) for the treatment of recurrent GBMAuxiliary treatment for newly diagnosed GBM was approved in 2015Denise Fabian et al of Ohio State University's Department of Radiation Oncology recently systematically reviewed TTFields's therapeutic effects on gliomas, and the results were published online in Cancers in February 2019 TTFields device consists of four sensor arrays, each consisting of nine insulated electrodes, acting on the patient's scalp, providing a low-intensity, medium-frequency (100-300 kHz) alternating electric field Principles of action: (1) to destroy the direction of microtubule proteins, interfere with the composition of microtubules (2) interfere with cell filament division; But the effects of TTFields on cell-to-cell interactions are still unknown and may be more complex than initially thought; Therefore, further research is needed from tumor cell and animal models EF-11 and EF-14 trials have shown that TTFields therapy can be an effective alternative to chemotherapy in patients with recurrent GBM and an effective complementary treatment for newly diagnosed GBM patients Excitingly, the EF-14 trial reported a median survival of 20.9 months for newly diagnosed GBM patients in the TTFields-TMZ group, compared with 16.0 months in the TMZ group See table 1 for details Table 1 Clinical trials of TTF treatment of GBM Although EF-14 has very convincing clinical research data and the FDA has approved TTFields for clinical treatment, many neuro-oncologists have questioned this, and commercial health insurance companies agree that the treatment is still in the experimental stage and that TTFields devices have not yet been included in the payment The current questions about TTFields in the academic community are mainly focused on the following points: on the one hand, the mechanism of TTFields cell level is unclear, especially when combined with other treatments is unclear; , on the other hand, the current clinical study does not use a "double-blind" design, i.e no group of "fake hat" control group patients to rule out the potential placebo effect However, from the point of view of experimental ethics, it is unethical for the control group to shave their heads and wear "fake hats" for more than 18 hours/day, so the study of "double-blind" design is very difficult; , on the other hand, the EF-14 study design is randomized 2 months after GBM diagnosis, there may be selective bias, only including potential prognosis patients finally, most of the preclinical research data that led the TTFields trial was obtained by the Novocure Scientists Institute, such as Dr Eilon Kirson, while the EF-11 and EF-14 trials were sponsored by Novocure and lacked independent data from more other units These causes some neurosurgery/neuro-oncologists to have concerns about the clinical application of TTFields As of December 2018, there have been eight TTFields-related clinical studies initiated and are expected to provide more objective and effective clinical evidence for TTFields's therapeutic outcomes in the coming years TTFields devices need to be worn as continuously as possible, and recent analysis shows a correlation between dependency and OS: 90 percent of patients showed 29.3 percent of 5-year OS Although the EF-14 trial has shown increased patient survival, patients may still be reluctant to wear TTF devices for social or cultural reasons TTFields has striking advantages of minimalcreativity and low systemic side effects Especially for relapsed patients, they have undergone surgery, chemotherapy and other treatment, can not bear a heavier mental and physical burden In the EF-11 trial, no typical systemic side effects were observed In the EF-14 trial, there was no significant difference in systemic side effects from TMZ alone (48% VS 44%) In a recent Phase I clinical trial, TTFields was treated with TTFields-assisted radiotherapy in 10 GBM patients, and the results showed a tTFields-associated skin toxicity incidence (40%) similar to the EF-14 trial For patients with 6 months in the TTFields group, there was a slight improvement in health-related quality of life (health-quality of life, HRQOL), and at 9 months and 12 months, HRQOL showed no significant difference The good news is that there was no significant difference in HRQOL results between the majority of patients using TTFields and those who did not receive TTFields TTFields are therefore safe and reliable without compromising patient quality of life, functional state, and cognitive function the device is currently not covered by Medicare or other health insurance reimbursements Technical costs associated with treatment can be reimbursed from Medicare's AmbuledDI Classification; Health care provider spending is reimbursed from Medicare's Physician Fee Even so, the total cost of treatment is still as high as about $21,000 per month, which some patients cannot afford The cost of treatment varies widely in different countries and regions, and in many medical centers it is not a conventional treatment For some uninsured patients, Novocure uses free hardware to help them get treatment finally, the authors believe that long-term, objective clinical data are still needed to promote the rational use of TTFields by clinicians If TTFields is effective in treating diseases other than GBM, it will help to increase the acceptance and widespread use of TTFields The authors also believe that by finding markers that can predict the effectiveness of TTFields treatment, TTFields can also help screen suitable patients At the same time, further improvements to the equipment to make it more adaptable to everyday life and less invasive have helped to improve patient compliance, such as the second-generation TTFields device, which is lighter in weight The most important thing is to identify the benefits and potential risks of TTFields in combination with chemotherapy through a wider range of RCT clinical trials.