Tumor Treating Fields Therapy Research Articles

PATH-26. MIDLINE INVOLVEMENT IS ASSOCIATED WITH ABERRANT RB1 SIGNALING IN PATIENTS WITH GRADE 4 IDH-MUTANT ASTROCYTOMA

Abstract BACKGROUND The prognostic factors impacting the survival of grade 4 IDH-mutant astrocytoma treated with standard radiation/temozolomide are not well-described. METHODS A retrospective cohort was generated of all patients diagnosed at Mayo Clinic with grade 4 IDH-mutant astrocytoma (2021 WHO Classification) on initial diagnosis between 2002-2023, and who received standard radiation/temozolomide. The impact of patient, tumor and molecular variables on overall survival (OS) and progression-free survival (PFS) was evaluated using survival analyses and Cox regression models. RESULTS Fifty-eight patients were identified. The median age was 36 years, 64% were male and 93% were white. The median follow up was 3.3 years. The median OS and PFS were 6.9 years and 2.4 years, respectively. CDKN2A/B homozygous deletion significantly reduced both OS (2.5 years vs NR, HR=3.9, p=0.0168) and PFS (1.4 vs 4.5 years, HR=4.2, p=0.0005). Midline involvement (brainstem, basal ganglia, thalamus, cerebellum or corpus callosum) also significantly reduced both OS (2.4 vs 12.8 years, HR=7.0, p=0.0014) and PFS (1.4 vs 4.5 years, HR=4.8, p=0.0002). MGMT promoter hypermethylation showed a trend toward significance for PFS (p=0.082) but did not impact OS. Age, sex, tumor size, ATRX immunohistochemistry and tumor-treating field therapy did not impact survival outcomes. Multivariable analyses revealed that PFS remained significantly impacted by both CDKN2A/B homozygous deletion (HR=3.5, p=0.0051) and midline involvement (HR=3.1, p=0.0125). A significant association between CDKN2A/B homozygous deletion and midline involvement was unexpectedly observed (53% if midline, 24% if non-midline; χ2=4.3, p=0.037). Exploratory analyses revealed that 15/15 (100%) of patients with midline involvement demonstrated aberration in RB1 signaling (CDKN2A/B homozygous deletion, n=8; CDKN2A/B hemizygous deletion or loss of heterozygosity, n=6; CDK4 amplification, n=1). CONCLUSION CDKN2A/B homozygous deletion and midline involvement independently impact PFS in patients with grade 4 IDH-mutant astrocytoma treated with standard radiation/temozolomide. Furthermore, midline involvement may be associated with aberrant RB1 signaling.

SURG-32. OPTIMIZING TUMOR TREATING FIELDS THERAPY FOR FIRST RECURRENT GLIOBLASTOMA WITH SKULL REMODELING SURGERY. FINAL RESULTS FROM OPTIMALTTF-2, A MULTI-CENTER, RANDOMIZED, CLINICAL TRIAL

Abstract Studies indicate that increasing the electric field intensity of Tumor Treating Fields therapy (TTFields) may prolong survival for glioblastoma (GBM) patients. Skull remodeling surgery (SR-surgery) aims to increase electric field intensity by 30-100% by removing the poorly conductive skull, and OptimalTTF-1 (pilot trial) concluded that SR-surgery was safe with a median overall survival (mOS) of 15.5 months for first recurrence GBM (rGBM). OptimalTTF-2 is a 1:1 randomized, comparative, multi-center, investigator-initiated, interventional clinical phase 2 trial investigating the efficacy and safety of TTFields and standard of care with or without SR-surgery for 84 rGBM subjects, with a planned interim analysis after enrollment of the first 52. Randomization is solely for SR-surgery and involves five burr holes of 15mm each in diameter, located in the skull between the tumor and the transducer arrays. The trial was nationwide in Denmark and active from 2020-2024. Major eligibility criteria include age ≥18 years, histopathological confirmed first recurrence of supratentorial GBM, and KPS ≥70. The primary endpoint is OS after 12 months (OS12), while secondary endpoints include PFS, QoL, ORR, QoL, KPS, steroid dose, and toxicity. The trial recruited 58 subjects and 52 had follow-up of 12-months or longer. Randomization was balanced and both arms had a median age of 59 years and no statistical difference in prognostic markers. Intent-to-treat analysis revealed the following for the intervention and control respectively, OS12 55% [95%CI 37-74%] vs. 45% [95%CI 27-64%](p=0.4), mOS 12.2 [7.9-19.1,95%CI] vs. 11 [6.5-17.1, 95%CI] months, and PFS 4.5 [3.4-9.5,95%CI] vs. 3.5 [3-6.4,95%CI] months. All the secondary outcomes were statistically insignificant. The trial was terminated early after interim analysis indicated no survival benefit from SR-surgery and a conditional power calculation that showed a low expected survival benefit for the planned cohort of 84 subjects. Post hoc analysis examining potential negative outcome modifiers is needed.

CTNI-41. LONG-TERM SURVIVAL AND PATTERNS OF PROGRESSION IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA TREATED WITH OR WITHOUT TUMOR TREATING FIELDS (TTFIELDS) IN A REAL-WORLD SETTING

Abstract BACKGROUND Tumor Treating Fields therapy (TTFields) is an FDA-approved locoregional treatment for patients with newly diagnosed glioblastoma (ndGBM). Previous trial data showed the addition of TTFields to standard TMZ-based therapy to significantly improve overall survival (OS), but real-world data is lacking, particularly with long follow-up duration. Here, we report real-world survival and patterns of progression for patients with ndGBM treated with or without TTFields. METHODS Patients diagnosed with GBM and treated with standard of care therapy at the Medical College of Wisconsin between March 2015–March 2023 were included. Progression-free survival (PFS) and OS outcomes were assessed, and compared across groups who received or did not receive TTFields therapy during maintenance treatment. Patterns of disease progression were analyzed via anatomic assessment. Patients were followed through March 1, 2024. RESULTS A total of 210 patients (TTFields: n=110/52.4%; No-TTFields: n=100/47.6%) were included for analysis. Median age was 60 and 63 years for the TTFields and No-TTFields groups, respectively, with each group 43% female. Other baseline characteristics were consistent across groups. Median TTFields duration was 6.8 months (range: 1–94). OS was significantly improved for the TTFields group vs No-TTFields group (median OS: 21.6 months [18.4–24.8] vs 17.7 months [15.0–20.8]; HR 0.73 [95% CI: 0.54–0.99, P=0.042]). Median PFS was 12.1 months (10.3–14.4) vs 9.6 months (8.5–12.8) with HR 0.77 (95% CI: 0.58–1.02; P=0.071). 5-year OS was 17% (10–28) for the TTFields group, and 11% (5–22) for No-TTFields group. Patients treated with TTFields exhibited a higher rate of non-local progression compared with the No-TTFields group (28% vs 15%, [P=0.044]). CONCLUSIONS Analysis of patients from a large institutional dataset reveals an association between TTFields use and long-term survival benefit. Higher incidence of non-local patterns of progression among TTFields users is consistent with pivotal trial findings.

Technical note: Computational study on thermal management schemes for tumor-treating fields therapy.

The study focuses on thermal management in tumor-treating fields (TTFields) therapy, crucial for patient compliance and therapeutic effectiveness. TTFields therapy, an established treatment for glioblastoma, involves applying alternating electric fields to the brain. However, managing the thermal effects generated by electrodes is a major challenge, impacting patient comfort and treatment efficiency. This research aims to explore methods for controlling temperature increases during TTFields therapy without reducing its duty cycle. The study emphasizes optimizing electrode configurations and array arrangements to mitigate temperature rise, thereby maintaining therapy effectiveness and patient compliance. Using a simplified multi-layer tissue model and finite element analysis, various electrode configurations and array shapes were tested in COMSOL Multiphysics v6.0. Adjustments included changing the electrode gel layer radius from 8 to 12mm, electrode spacing, and transitioning to a more uniform array arrangement, such as a square array or a circular array. The study revealed a strong correlation between high temperatures and edge current density distributions on electrodes. It was found that increasing the electrode gel layer's diameter, enlarging electrode spacing, and adopting a uniform array arrangement markedly mitigated temperature rises. By increasing the gel layer radius from the original 10 to 12mm, a reduction in the peak temperature increases of approximately 0.3°C was observed. Changing the layout from rectangular to circular with the same area further reduced the peak temperature rise by 0.5°C. Additionally, enlarging the spacing between electrodes also contributed to temperature control. By integrating these strategies, we designed a new circular electrode array with an electrode spacing of 45mm and a gel radius of 12mm, successfully reducing the peak temperature from 42.1°C to 40.8°C, effectively achieving temperature control. The research demonstrates that improving electrode and array configurations can effectively manage temperature in TTFields therapy without compromising treatment duration. This strategy is crucial as TTFields therapy relies on prolonged field exposure for effectiveness. The findings offer valuable insights into thermal management in electrode array design and could lead to enhanced patient compliance and treatment efficacy in TTFields therapy.

Cost-effectiveness Analysis of Tumor Treating Fields Therapy Combined With Immune Checkpoint Inhibitor in Metastatic Non-small-cell Lung Cancer

BackgroundThe LUNAR clinical trial revealed that incorporating Tumor Treating Fields (TTFields) therapy alongside immune checkpoint inhibitor (ICI) significantly prolonged the overall survival of patients with metastatic, platinum-resistant non-small-cell lung cancer (NSCLC). However, the cost of TTFields therapy is high and may further increase the financial burden for patients. Our research aims to evaluate the cost-effectiveness of TTFields therapy addition with ICI for metastatic NSCLC. MethodsWe constructed a Markov model to evaluate the healthcare costs associated with TTFields therapy combined with ICI for the treatment of advanced NSCLC. In this model, the clinical data utilized came from the LUNAR trial, while drug costs and health state utility values were extracted from public databases and relevant scholarly publications. The major outcomes incorporated costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). ResultsCompared with ICI therapy alone, ICI combination with TTFields therapy resulted in 0.42 QALYs at the cost of $167,329, with an ICER of $398,402.38 per year. The calculated ICER surpassed the generally accepted US willingness-to-pay (WTP) threshold of 150,000 per QALY. One-way sensitivity analyses demonstrated that the utility of progression disease is the most influential factor, followed by the cost of TTFields therapy, the utility of progression-free survival, the cost of ICI, and the cost of adverse events in TTFields therapy combined with ICI. Only when the cost of TTFields therapy is reduced by approximately 80.48%, it would be cost-effective within the commonly accepted WTP threshold of $150,000/QALY. ConclusionsAccording to the US WTP, the combination of TTFields therapy with ICI does not currently represent a cost-effective strategy for metastatic NSCLC followed progression on platinum-resistant therapy. Considering its promising clinical outcomes for metastatic NSCLC, it is necessary to control the expenses of this therapeutic strategy in future applications.

A theoretical study on evaluating brain tumor changes in tumor treating fields therapy by impedance detection.

TTFields is a novel FDA-approved technology utilized for treating glioblastoma multiforme (GBM) within the brain. Presently, the effectiveness of therapy is evaluated through MRI imaging at random two-month intervals. Electrical impedance is an important and effective parameter for reflecting changes in tissue properties. In TTFields treatment for brain tumors, electrodes attached to the scalp deliver electric field energy to the tumor region. We hypothesize that these electrodes can also serve as sensors to detect impedance changes caused by tumor alterations in real time, thus continuously assessing the effectiveness of the treatment. In this work, we propose and scrutinize this hypothesis by conducting an in silico study to confirm the potential feasibility of the proposed concept. Our results indicate that the impedance amplitude change measured between opposing TTFields electrode arrays utilizing voltage and frequency of 50 V and 200 kHz (typical TTFields treatment parameters), has enough resolution (> 1mm) and Signal-to-Noise Ratio (> 40 dB) to evaluate tumor size change in the head. The impedance detection technique may be a significant augmentation to TTFields cancer treatment, enabling the continuous evaluation of safety and efficacy throughout the procedure.

52683 Expert Guidance on the Prevention and Management of Dermatologic Adverse Events with Tumor Treating Fields Therapy in the Abdominal-Pelvic Region

52683 Expert Guidance on the Prevention and Management of Dermatologic Adverse Events with Tumor Treating Fields Therapy in the Abdominal-Pelvic Region

Letter to the Editor: "Imperative for Increased Research into Tumor Treating Fields Therapy for Enhancing Glioblastoma Outcomes"

Letter to the Editor: "Imperative for Increased Research into Tumor Treating Fields Therapy for Enhancing Glioblastoma Outcomes"

Abstract 7591: Tumor Treating Fields (TTFields) show efficacy in Triple-Negative breast cancer (TNBC) cells alone and in combination with PARP inhibitor Talazoparib

Abstract Breast cancer is the most common cancer in women worldwide, and the fifth leading cause of cancer-related deaths globally. Triple-negative breast cancer (TNBC), the most aggressive form of breast cancer, is usually treated with surgery, chemotherapy, and radiation. Tumor Treating Fields therapy are FDA-approved for the treatment of glioblastoma (GBM) and malignant pleural mesothelioma (MPM).TT Fields use alternating electric fields to inhibit tumor growth through mitotic disruption, cellular damage, integrated stress response activation, and immune mechanisms and inhibit cell proliferation, induce cell death, and cause cell cycle arrest.TT Fields can induce BRCAness and when combined with PARP inhibition, this combination may result in synthetic lethality. We explored the effect of TTFields on two TNBC cell lines MDA-MB436 (BRCA1-mutant, p53-null) and MDA-MB468 (BRCA1 wild-type, p53-mutant) treated with TTFields (150 kHz) for 24 hours. Western blot analysis showed elevation of p21 independent of p53 mutational status. We examined the combination of PARP inhibitor (Talazoparib) with TTFields in MDA-MB468 cells to determine the effect of the combination in BRCA wild-type cancer cells. Western blot analysis showed p21 upregulation after 24 hours in combination without an increase in p53. p21 acts as a G1-checkpoint protein and loss of p21 expression has been observed in a high percentage of human breast cancer cells. Our results suggest a rational and potentially effective therapy that could be further developed and used for the treatment of breast cancer. Our ongoing studies are exploring potential mechanisms of synergy between PARP inhibitor Talazoparib and TTFields using various TNBC models, and the effect of the combination on cell cycle arrest in cell culture and in vivo. Citation Format: Maryam Ghandali, Praveen Srinivasan, Yutong Xia, Eric T. Wong, Robert W. Sobol, Lanlan zhou, Benedito A. Carneiro, Stephanie L. Graff, Wafik S. El-Deiry. Tumor Treating Fields (TTFields) show efficacy in Triple-Negative breast cancer (TNBC) cells alone and in combination with PARP inhibitor Talazoparib [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7591.

Bevacizumab and gamma knife radiosurgery for first-recurrence glioblastoma

IntroductionGlioblastoma (GBM) is the most common central nervous system malignancy in adults. Despite decades of developments in surgical management, radiation treatment, chemotherapy, and tumor treating field therapy, GBM remains an ultimately fatal disease. There is currently no definitive standard of care for patients with recurrent glioblastoma (rGBM) following failure of initial management.ObjectiveIn this retrospective cohort study, we set out to examine the relative effects of bevacizumab and Gamma Knife radiosurgery on progression-free survival (PFS) and overall survival (OS) in patients with GBM at first-recurrence.MethodsWe conducted a retrospective review of all patients with rGBM who underwent treatment with bevacizumab and/or Gamma Knife radiosurgery at Roswell Park Comprehensive Cancer Center between 2012 and 2022. Mean PFS and OS were determined for each of our three treatment groups: Bevacizumab Only, Bevacizumab Plus Gamma Knife, and Gamma Knife Only.ResultsPatients in the combined treatment group demonstrated longer post-recurrence median PFS (7.7 months) and median OS (11.5 months) compared to glioblastoma patients previously reported in the literature, and showed improvements in total PFS (p=0.015), total OS (p=0.0050), post-recurrence PFS (p=0.018), and post-recurrence OS (p=0.0082) compared to patients who received either bevacizumab or Gamma Knife as monotherapy.ConclusionThis study demonstrates that the combined use of bevacizumab with concurrent stereotactic radiosurgery can have improve survival in patients with rGBM.

EE363 Cost-Effectiveness Analysis of Adding Tumor Treating Fields Therapy to Temozolomide Versus Temozolomide Only in Patients with Glioblastoma in France

EE363 Cost-Effectiveness Analysis of Adding Tumor Treating Fields Therapy to Temozolomide Versus Temozolomide Only in Patients with Glioblastoma in France

531P Tumor treating fields therapy for glioblastoma: Identifying needs and satisfaction of new and long-term users

531P Tumor treating fields therapy for glioblastoma: Identifying needs and satisfaction of new and long-term users

Tumor Treating Fields therapy with standard systemic therapy versus standard systemic therapy alone in metastatic non-small-cell lung cancer following progression on or after platinum-based therapy (LUNAR): a randomised, open-label, pivotal phase 3 study

Tumor Treating Fields (TTFields) are electric fields that disrupt processes critical for cancer cell survival, leading to immunogenic cell death and enhanced antitumour immune response. In preclinical models of non-small-cell lung cancer, TTFields amplified the effects of chemotherapy and immune checkpoint inhibitors. We report primary results from a pivotal study of TTFields therapy in metastatic non-small-cell lung cancer. This randomised, open-label, pivotal phase 3 study recruited patients at 130 sites in 19 countries. Participants were aged 22 years or older with metastatic non-small-cell lung cancer progressing on or after platinum-based therapy, with squamous or non-squamous histology and ECOG performance status of 2 or less. Previous platinum-based therapy was required, but no restriction was placed on the number or type of previous lines of systemic therapy. Participants were randomly assigned (1:1) to TTFields therapy and standard systemic therapy (investigator's choice of immune checkpoint inhibitor [nivolumab, pembrolizumab, or atezolizumab] or docetaxel) or standard therapy alone. Randomisation was performed centrally using variable blocked randomisation and an interactive voice-web response system, and was stratified by tumour histology, treatment, and region. Systemic therapies were dosed according to local practice guidelines. TTFields therapy (150 kHz) was delivered continuously to the thoracic region with the recommendation to achieve an average of at least 18 h/day device usage. The primary endpoint was overall survival in the intention-to-treat population. The safety population included all patients who received any study therapy and were analysed according to the actual treatment received. The study is registered with ClinicalTrials.gov, NCT02973789. Between Feb 13, 2017, and Nov 19, 2021, 276 patients were enrolled and randomly assigned to receive TTFields therapy with standard therapy (n=137) or standard therapy alone (n=139). The median age was 64 years (IQR 59-70), 178 (64%) were male and 98 (36%) were female, 156 (57%) had non-squamous non-small-cell lung cancer, and 87 (32%) had received a previous immune checkpoint inhibitor. Median follow-up was 10·6 months (IQR 6·1-33·7) for patients receiving TTFields therapy with standard therapy, and 9·5 months (0·1-32·1) for patients receiving standard therapy. Overall survival was significantly longer with TTFields therapy and standard therapy than with standard therapy alone (median 13·2 months [95% CI 10·3-15·5] vs 9·9 months [8·1-11·5]; hazard ratio [HR] 0·74 [95% CI 0·56-0·98]; p=0·035). In the safety population (n=267), serious adverse events of any cause were reported in 70 (53%) of 133 patients receiving TTFields therapy plus standard therapy and 51 (38%) of 134 patients receiving standard therapy alone. The most frequent grade 3-4 adverse events were leukopenia (37 [14%] of 267), pneumonia (28 [10%]), and anaemia (21 [8%]). TTFields therapy-related adverse events were reported in 95 (71%) of 133 patients; these were mostly (81 [85%]) grade 1-2 skin and subcutaneous tissue disorders. There were three deaths related to standard therapy (two due to infections and one due to pulmonary haemorrhage) and no deaths related to TTFields therapy. TTFields therapy added to standard therapy significantly improved overall survival compared with standard therapy alone in metastatic non-small-cell lung cancer after progression on platinum-based therapy without exacerbating systemic toxicities. These data suggest that TTFields therapy is efficacious in metastatic non-small-cell lung cancer and should be considered as a treatment option to manage the disease in this setting. Novocure.

Tumor Treating Fields therapy could potentiate immunotherapy in non-small-cell lung cancer

Tumor Treating Fields therapy could potentiate immunotherapy in non-small-cell lung cancer

Optimization of tumor-treating field therapy for triple-negative breast cancer cells in vitro via frequency modulation

PurposeCurrently, tumor-treating field (TTField) therapy utilizes a single “optimal” frequency of electric fields to achieve maximal cell death in a targeted population of cells. However, because of differences in cell size, shape, and ploidy during mitosis, optimal electric field characteristics for universal maximal cell death may not exist. This study investigated the anti-mitotic effects of modulating electric field frequency as opposed to utilizing uniform electric fields.MethodsWe developed and validated a custom device that delivers a wide variety of electric field and treatment parameters including frequency modulation. We investigated the efficacy of frequency modulating tumor-treating fields on triple-negative breast cancer cells compared to human breast epithelial cells.ResultsWe show that frequency-modulated (FM) TTFields are as selective at treating triple-negative breast cancer (TNBC) as uniform TTFields while having a greater efficacy for combating TNBC cell growth. TTField treatment at a mean frequency of 150 kHz with a frequency range of ± 10 kHz induced apoptosis in a greater number of TNBC cells after 24 h as compared to unmodulated treatment which led to further decreased cell viability after 48 h. Furthermore, all TNBC cells died after 72 h of FM treatment while cells that received unmodulated treatment were able to recover to cell number equivalent to the control.ConclusionTTFields were highly efficacious against TNBC growth, FM TTFields showed minimal effects on epithelial cells similar to unmodulated treatment.

Efficacy and selectivity of tumor-treating field therapy for triple-negative breast cancer cells via in-house delivery device

PurposeTriple-negative breast cancer continues to be one of the leading causes of death in women, making up 7% of all cancer deaths. Tumor-treating electric fields are low-energy, low-frequency oscillating electric fields that induce an anti-proliferative effect on mitotic cells in glioblastoma multiforme, non-small cell lung cancer, and ovarian cancer. Little is known about effects of tumor-treating fields on triple-negative breast cancer and known research for tumor-treating fields only utilizes low (< 3 V/cm) electric field intensities.MethodsWe have developed an in-house field delivery device capable of high levels of customization to explore a much wider variety of electric field and treatment parameters. Furthermore, we investigated the selectivity of tumor-treating field treatment between triple-negative breast cancer and human breast epithelial cells.ResultsTumor-treating fields show greatest efficacy against triple-negative breast cancer cell lines between 1 and 3 V/cm electric field intensities while having little effect on epithelial cells.ConclusionThese results provide a clear therapeutic window for tumor-treating field delivery to triple-negative breast cancer.

Effectiveness and safety of tumor-treating fields therapy for glioblastoma: A single-center study in a Chinese cohort.

Tumor-treating fields (TTFields) are a new therapeutic modality for patients with glioblastoma (GBM). However, studies on survival outcomes of TTFields are rarely reported in China. This study aimed to examine the clinical efficacy and safety of TTFields therapy for GBM in China. A total of 93 patients with newly diagnosed GBM (ndGBM) and recurrent GBM (rGBM) were included in our study retrospectively. They were divided into two groups based on whether they used TTFields. Progression-free survival (PFS), overall survival (OS), and toxicities were assessed. Among the patients with ndGBM, there were 13 cases with TTFields and 39 cases with no TTFields. The median PFS was 15.3 [95% confidence interval (CI): 6.5-24.1] months and 10.6 (95% CI: 5.4-15.8) months in the two groups, respectively, with P = 0.041. The median OS was 24.8 (95% CI: 6.8-42.8) months and 18.6 (95% CI: 11.4-25.8) months, respectively, with P = 0.368. Patients with subtotal resection (STR) who used TTFields had a better PFS than those who did not (P = 0.003). Among the patients with rGBM, there were 13 cases with TTFields and 28 cases with no TTFields. The median PFS in the two groups was 8.4 (95% CI: 1.7-15.2) months and 8.0 (95% CI: 5.8-10.2) months in the two groups, respectively, with P = 0.265. The median OS was 10.6 (95% CI: 4.8-16.4) months and 13.3 (95% CI: 11.0-15.6) months, respectively, with P = 0.655. A total of 21 patients (21/26, 80.8%) with TTFields developed dermatological adverse events (dAEs). All the dAEs could be resolved or controlled. TTFields therapy is a safe and effective treatment for ndGBM, especially in patients with STR. However, it may not improve survival in patients with rGBM.

A comment to improve tumor-treating fields therapy

&lt;abstract&gt; &lt;p&gt;Recent investigations have shown that special frequencies and intensities of electromagnetic waves could control the differentiations of some types of cells. Using this fact, tumor-treating fields (TTFields) therapy has been proposed as a technique which uses alternating electric fields of intermediate frequency (~100–500 kHz) and low intensity (1–3 V/cm) to disrupt the cell divisions of tumors. However, this technique may have harmful effects on ionic liquids around normal cells. For example, electrodes could induce an extra electrical current within blood vessels. To observe these effects, we connected electrodes to a slide that includes water and some extra ions and put them under a 1000× microscope. We found that some ions, microbes and cells move toward negative electrons and some go away. These attractions of cells by electrodes could cause the destruction of the brain. We also found some electrical currents within the liquid emerge which absorb or repel water molecules and induce some bubbles. If these types of bubbles arise within the blood vessels, they can exert a force on the membranes of normal cells and destroy them. To avoid these problems, we suggest that electrodes should be replaced by some electromagnetic sender/receiver which emits some special frequencies. These frequencies could be absorbed only by blood vessels around the tumors because these vessels may be created only to provide the needed food for tumor cells and thus have a different potential and electrical current as compared to vessels around normal cells. Thus, these tumor vessels could act as the antenna for TTFields.&lt;/p&gt; &lt;/abstract&gt;

Glioma stem cell signature predicts the prognosis and the response to tumor treating fields treatment.

Glioma stem cells (GSCs) play an important role in glioma recurrence and chemo-radiotherapy (CRT) resistance. Currently, there is a lack of efficient treatment approaches targeting GSCs. This study aimed to explore the potential personalized treatment of patients with GSC-enriched gliomas. Single-cell RNA sequencing (scRNA-seq) was used to identify the GSC-related genes. Then, machine learning methods were applied for clustering and validation. The least absolute shrinkage and selection operator (LASSO) and COX regression were used to construct the risk scores. Survival analysis was performed. Additionally, the incidence of chemo-radiotherapy resistance, immunotherapy status, and tumor treating field (TTF) therapy response were evaluated in high- and low-risk scores groups. Two GSC clusters exhibited significantly different stemness indices, immune microenvironments, and genomic alterations. Based on GSC clusters, 11-gene GSC risk scores were constructed, which exhibited a high predictive value for prognosis. In terms of therapy, patients with high GSC risk scores had a higher risk of resistance to chemotherapy. TTF therapy can comprehensively inhibit the malignant biological characteristics of the high GSC-risk-score gliomas. Our study constructed a GSC signature consisting of 11 GSC-specific genes and identified its prognostic value in gliomas. TTF is a promising therapeutic approach for patients with GSC-enriched glioma.

A comment to improve tumor treating fields therapy

A comment to improve tumor treating fields therapy