Tumor Treating Fields (TTFields) induce homologous recombination deficiency in ovarian cancer cells, thus mitigating drug resistance.

Background: Ovarian cancer is the leading cause of mortality among gynecological malignancies. Carboplatin and poly (ADP-ribose) polymerase inhibitors (PARPi) are often implemented in the treatment of ovarian cancer. Homologous recombination deficient (HRD) tumors demonstrate increased sensitivity to these treatments; however, many ovarian cancer patients are homologous recombination proficient (HRP). TTFields are non-invasive electric fields that induce an HRD-like phenotype in various cancer types. The current study aimed to investigate the impact of TTFields applied together with carboplatin or PARPi (olaparib or niraparib) in preclinical ovarian cancer models. Methods: A2780 (HRP), OVCAR3 (HRD), and A2780cis (platinum-resistant) human ovarian cancer cells were treated in vitro with TTFields (1 V/cm RMS, 200 kHz, 72 h), alone or with various drug concentrations. Treated cells were measured for cell count, colony formation, apoptosis, DNA damage, expression of DNA repair proteins, and cell cycle. In vivo, ID8-fLuc (HRP) ovarian cancer cells were inoculated intraperitoneally to C57BL/6 mice, which were then treated with either sham, TTFields (200 kHz), olaparib (50 mg/kg), or TTFields plus olaparib; over a period of four weeks. Tumor growth was analyzed using bioluminescent imaging at treatment cessation; and survival analysis was performed. Results: The nature of TTFields-drug interaction was dependent on the drug's underlying mechanism of action and on the genetic background of the cells, with synergistic interactions between TTFields and carboplatin or PARPi seen in HRP and resistant cells. Treated cells demonstrated elevated levels of DNA damage, accompanied by G2/M arrest, and induction of an HRD-like phenotype. In the tumor-bearing mice, TTFields and olaparib co-treatment resulted in reduced tumor volume and a survival benefit relative to olaparib monotherapy and to control. Conclusion: By inducing an HRD-like phenotype, TTFields sensitize HRP and resistant ovarian cancer cells to treatment with carboplatin or PARPi, potentially mitigating a-priori and de novo drug resistance, a major limitation in ovarian cancer treatment.

Revisiting the standards of cancer detection and therapy alongside their comparison to modern methods.

In accordance with the World Health Organization data, cancer remains at the forefront of fatal diseases. An upward trend in cancer incidence and mortality has been observed globally, emphasizing that efforts in developing detection and treatment methods should continue. The diagnostic path typically begins with learning the medical history of a patient; this is followed by basic blood tests and imaging tests to indicate where cancer may be located to schedule a needle biopsy. Prompt initiation of diagnosis is crucial since delayed cancer detection entails higher costs of treatment and hospitalization. Thus, there is a need for novel cancer detection methods such as liquid biopsy, elastography, synthetic biosensors, fluorescence imaging, and reflectance confocal microscopy. Conventional therapeutic methods, although still common in clinical practice, pose many limitations and are unsatisfactory. Nowadays, there is a dynamic advancement of clinical research and the development of more precise and effective methods such as oncolytic virotherapy, exosome-based therapy, nanotechnology, dendritic cells, chimeric antigen receptors, immune checkpoint inhibitors, natural product-based therapy, tumor-treating fields, and photodynamic therapy. The present paper compares available data on conventional and modern methods of cancer detection and therapy to facilitate an understanding of this rapidly advancing field and its future directions. As evidenced, modern methods are not without drawbacks; there is still a need to develop new detection strategies and therapeutic approaches to improve sensitivity, specificity, safety, and efficacy. Nevertheless, an appropriate route has been taken, as confirmed by the approval of some modern methods by the Food and Drug Administration.

Global post­marketing safety surveillance of Tumor Treating Fields (TTFields) therapy in over 25,000 patients with CNS malignancies treated between 2011-2022.

BACKGROUND: Tumor Treating Fields (TTFields) are alternating electric fields that disrupt cancer cell processes. TTFields therapy is approved for recurrent glioblastoma (rGBM), and newly-diagnosed (nd) GBM (with concomitant temozolomide for ndGBM; US), and for grade IV glioma (EU). We present an updated global, post-marketing surveillance safety analysis of patients with CNS malignancies treated with TTFields therapy. METHODS: Safety data were collected from routine post-marketing activities for patients in North America, Europe, Israel, and Japan (October 2011-October 2022). Adverse events (AEs) were stratified by age, sex, and diagnosis. RESULTS: Overall, 25,898 patients were included (diagnoses: ndGBM [68%], rGBM [26%], anaplastic astrocytoma/oligodendroglioma [4%], other CNS malignancies [2%]). Median (range) age was 59 (3-103) years; 66% patients were male. Most (69%) patients were 18-65 years; 0.4% were < 18 years; 30% were > 65 years. All-cause and TTFields-related AEs occurred in 18,798 (73%) and 14,599 (56%) patients, respectively. Most common treatment-related AEs were beneath-array skin reactions (43%), electric sensation (tingling; 14%), and heat sensation (warmth; 12%). Treatment-related skin reactions were comparable in pediatric (39%), adult (42%), and elderly (45%) groups, and in males (41%) and females (46%); and similar across diagnostic subgroups (ndGBM, 46%; rGBM, 34%; anaplastic astrocytoma/oligodendroglioma, 42%; other, 40%). No TTFields-related systemic AEs were reported. CONCLUSIONS: This long-term, real-world analysis of > 25,000 patients demonstrated good tolerability of TTFields in patients with CNS malignancies. Most therapy-related AEs were manageable localized, non-serious skin events. The TTFields therapy safety profile remained consistent across subgroups (age, sex, and diagnosis), indicative of its broad applicability.

Tumor-treating fields in cancer therapy: advances of cellular and molecular mechanisms.

Tumor-Treating Fields (TTFields) use intermediate-frequency and low-intensity electric fields to inhibit tumor cells. However, their mechanisms are still not well understood. This article reviews their key antitumor mechanisms at the cellular and molecular levels, including inhibition of proliferation, induction of death, disturbance of migration, and activation of the immune system. The multifaceted biological effects in combination with other cancer treatments are also summarized. The deep insight into their mechanism will help develop more potential antitumor treatments.

Current status and research progress of minimally invasive treatment of glioma.

Glioma has a high malignant degree and poor prognosis, which seriously affects the prognosis of patients. Traditional treatment methods mainly include craniotomy tumor resection, postoperative radiotherapy and chemotherapy. Although above methods have achieved remarkable curative effect, they still have certain limitations and adverse reactions. With the introduction of the concept of minimally invasive surgery and its clinical application as well as the development and progress of imaging technology, minimally invasive treatment of glioma has become a research hotspot in the field of neuromedicine, including photothermal treatment, photodynamic therapy, laser-induced thermal theraphy and TT-Fields of tumor. These therapeutic methods possess the advantages of precision, minimally invasive, quick recovery and significant curative effect, and have been widely used in clinical practice. The purpose of this review is to introduce the progress of minimally invasive treatment of glioma in recent years and the achievements and prospects for the future.

Tumor treating fields for newly diagnosed high-grade glioma based on the criteria of 2021 WHO CNS5: A retrospective analysis of Chinese patients in a single center.

BACKGROUND AND OBJECTIVE: High-grade glioma (HGG) is known to be characterized by a high degree of malignancy and a worse prognosis. The classical treatment is safe resection supplemented by radiotherapy and chemotherapy. Tumor treating fields (TTFields), an emerging physiotherapeutic modality that targets malignant solid tumors using medium-frequency, low-intensity, alternating electric fields to interfere with cell division, have been used for the treatment of new diagnosis of glioblastoma, however, their administration in HGG requires further clinical evidence. The efficacy and safety of TTFields in Chinese patients with HGG were retrospectively evaluated by us in a single center. METHODS: We enrolled and analyzed 52 patients with newly diagnosed HGG undergoing surgery and standard chemoradiotherapy regimens from December 2019 to June 2022, and followed them until June 2023. Based on whether they used TTFields, they were divided into a TTFields group and a non-TTFields group. Progression-free survival (PFS) and overall survival (OS) were compared between the two groups. RESULTS: There were 26 cases in the TTFields group and 26 cases in the non-TTFields group. In the TTFields group, the median PFS was 14.2 months (95% CI: 9.50-18.90), the median OS was 19.7 months (95% CI: 14.95-24.25) , the median interval from surgery to the start of treatment with TTFields was 2.47 months (95% CI: 1.47-4.13), and the median duration of treatment with TTFields was 10.6 months (95% CI: 9.57-11.63). 15 (57.69%) patients experienced an adverse event and no serious adverse event was reported. In the non-TTFields group, the median PFS was 9.57 months (95% CI: 6.23-12.91) and the median OS was 16.07 months (95% CI: 12.90-19.24). There was a statistically significant difference in PFS (p = 0.005) and OS (p = 0.007) between the two groups. CONCLUSIONS: In this retrospective analysis, TTFields were observed to improve newly diagnosed HGG patients' median PFS and OS. Compliance was much higher than reported in clinical trials and safety remained good.

Biophysical phenotyping of single-cell based on impedance and application for individualized precision medicine.

Single-cell biophysical characterization based on impedance measurement is an advantageous approach due to its label-free, high-efficiency, cost-effective and real-time capability. Biophysical phenotyping can yield timely and rich information on physiological and pathological state of cells for disease diagnosis, drug screening, precision medicine, etc. However, precise measurement on single-cell impedance is challenging, particularly hard to figure out the detailed biophysical parameters of single cell due to coupling and complexity of impedance model. Here, we propose an analytic determination method to decode single-cell electrophysiological parameters (including cell-substrate interface capacitance, cell membrane capacitance, cell membrane conductivity, and cytoplasm conductivity) from the impedances measured at optimized frequencies by using analytic solution rather than spectrum fitting. With this simple and fast analytic solution method, the physiological parameters of single cell in natural adhesion state can be accurately determined in real time. We validate this cell parameter determination method in monitoring the change of cell adhesion under hydraulic effects and exploring electrophysiological differences among MCF-7, HeLa, Huh7, and MDA-MB-231 cell lines. Particularly, we apply the approach to optimize tumor treating fields (TTFields) therapy, realizing individualized precision medicine. Our work provides an accurate and efficient approach for characterizing single-cell biophysical properties with real-time, in-situ, label-free, and less invasive advantages.

Tumor treating fields in glioblastoma: long-term treatment and high compliance as favorable prognostic factors.

Introduction: Tumor treating fields (TTFields) have earned substantial attention in recent years as a novel therapeutic approach with the potential to improve the prognosis of glioblastoma (GBM) patients. However, the impact of TTFields remains a subject of ongoing debate. This study aimed to offer real-world evidence on TTFields therapy for GBM, and to investigate the clinical determinants affecting its efficacy. Methods: We have reported a retrospective analysis of 81 newly diagnosed Chinese GBM patients who received TTFields/Stupp treatment in the Second Affiliated Hospital of Zhejiang University. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier method. Cox regression models with time-dependent covariates were utilized to address non-proportional hazards and to assess the influence of clinical variables on PFS and OS. Results: The median PFS and OS following TTFields/STUPP treatment was 12.6 months (95% CI 11.0-14.1) and 21.3 months (95% CI 10.0-32.6) respectively. Long-term TTFields treatment (>2 months) exhibits significant improvements in PFS and OS compared to the short-term treatment group (≤2 months). Time-dependent covariate COX analysis revealed that longer TTFields treatment was correlated with enhanced PFS and OS for up to 12 and 13 months, respectively. Higher compliance to TTFields (≥ 0.8) significantly reduced the death risk (HR=0.297, 95%CI 0.108-0.819). Complete surgical resection and MGMT promoter methylation were associated with significantly lower risk of progression (HR=0.337, 95% CI 0.176-0.643; HR=0.156, 95% CI 0.065-0.378) and death (HR=0.276, 95% CI 0.105-0.727; HR=0.249, 95% CI 0.087-0.710). Conclusion: The TTFields/Stupp treatment may prolong median OS and PFS in GBM patients, with long-term TTFields treatment, higher TTFields compliance, complete surgical resection, and MGMT promoter methylation significantly improving prognosis.

A qualitative evaluation of factors influencing Tumor Treating fields (TTFields) therapy decision making among brain tumor patients and physicians.

BACKGROUND: Tumor Treating Fields (TTFields) Therapy is an FDA-approved therapy in the first line and recurrent setting for glioblastoma. Despite Phase 3 evidence showing improved survival with TTFields, it is not uniformly utilized. We aimed to examine patient and clinician views of TTFields and factors shaping utilization of TTFields through a unique research partnership with medical neuro oncology and medical social sciences. METHODS: Adult glioblastoma patients who were offered TTFields at a tertiary care academic hospital were invited to participate in a semi-structured interview about their decision to use or not use TTFields. Clinicians who prescribe TTFields were invited to participate in a semi-structured interview about TTFields. RESULTS: Interviews were completed with 40 patients with a mean age of 53 years; 92.5% were white and 60% were male. Participants who decided against TTFields stated that head shaving, appearing sick, and inconvenience of wearing/carrying the device most influenced their decision. The most influential factors for use of TTFields were the efficacy of the device and their clinician's opinion. Clinicians (N = 9) stated that TTFields was a good option for glioblastoma patients, but some noted that their patients should consider the burdens and benefits of TTFields as it may not be the desired choice for all patients. CONCLUSIONS: This is the first study to examine patient decision making for TTFields. Findings suggest that clinician support and efficacy data are among the key decision-making factors. Properly understanding the path to patients' decision making is crucial in optimizing the use of TTFields and other therapeutic decisions for glioblastoma patients.

Tumor-treating fields dosimetry in glioblastoma: Insights into treatment planning, optimization, and dose-response relationships.

Tumor-treating fields (TTFields) are currently a Category 1A treatment recommendation by the US National Comprehensive Cancer Center for patients with newly diagnosed glioblastoma. Although the mechanism of action of TTFields has been partly elucidated, tangible and standardized metrics are lacking to assess antitumor dose and effects of the treatment. This paper outlines and evaluates the current standards and methodologies in the estimation of the TTFields distribution and dose measurement in the brain and highlights the most important principles governing TTFields dosimetry. The focus is on clinical utility to facilitate a practical understanding of these principles and how they can be used to guide treatment. The current evidence for a correlation between TTFields dose, tumor growth, and clinical outcome will be presented and discussed. Furthermore, we will provide perspectives and updated insights into the planning and optimization of TTFields therapy for glioblastoma by reviewing how the dose and thermal effects of TTFields are affected by factors such as tumor location and morphology, peritumoral edema, electrode array position, treatment duration (compliance), array "edge effect," electrical duty cycle, and skull-remodeling surgery. Finally, perspectives are provided on how to optimize the efficacy of future TTFields therapy.

[Simulation model of tumor-treating fields].

Tumor-treating fields (TTFields) is a novel treatment modality for malignant solid tumors, often employing electric field simulations to analyze the distribution of electric fields on the tumor under different parameters of TTFields. Due to the present difficulties and high costs associated with reproducing or implementing the simulation model construction techniques, this study used readily available open-source software tools to construct a highly accurate, easily implementable finite element simulation model for TTFields. The accuracy of the model is at a level of 1 mm 3. Using this simulation model, the study carried out analyses of different factors, such as tissue electrical parameters and electrode configurations. The results show that factors influncing the distribution of the internal electric field of the tumor include changes in scalp and skull conductivity (with a maximum variation of 21.0% in the treatment field of the tumor), changes in tumor conductivity (with a maximum variation of 157.8% in the treatment field of the tumor), and different electrode positions and combinations (with a maximum variation of 74.2% in the treatment field of the tumor). In summary, the results of this study validate the feasibility and effectiveness of the proposed modeling method, which can provide an important reference for future simulation analyses of TTFields and clinical applications.

Aurora kinase A inhibition plus Tumor Treating Fields suppress glioma cell proliferation in a cilium-independent manner.

Tumor Treating Fields (TTFields) extend the survival of glioblastoma (GBM) patients by interfering with a broad range of tumor cellular processes. Among these, TTFields disrupt primary cilia stability on GBM cells. Here we asked if concomitant treatment of TTFields with other agents that interfere with GBM ciliogenesis further suppress GBM cell proliferation in vitro. Aurora kinase A (AURKA) promotes both cilia disassembly and GBM growth. Inhibitors of AURKA, such as Alisertib, inhibit cilia disassembly and increase ciliary frequency in various cell types. However, we found that Alisertib treatment significantly reduced GBM cilia frequency in gliomaspheres across multiple patient derived cell lines, and in patient biopsies treated ex vivo. This effect appeared glioma cell-specific as it did not reduce normal neuronal or glial cilia frequencies. Alisertib-mediated depletion of glioma cilia appears specific to AURKA and not AURKB inhibition, and attributable in part to autophagy pathway activation. Treatment of two different GBM patient-derived cell lines with TTFields and Alisertib resulted in a significant reduction in cell proliferation compared to either treatment alone. However, this effect was not cilia-dependent as the combined treatment reduced proliferation in cilia-depleted cell lines lacking, ARL13B, or U87MG cells which are naturally devoid of ARL13B+ cilia. Thus, Alisertib-mediated effects on glioma cilia may be a useful biomarker of drug efficacy within tumor tissue. Considering Alisertib can cross the blood brain barrier and inhibit intracranial growth, our data warrant future studies to explore whether concomitant Alisertib and TTFields exposure prolongs survival of brain tumor-bearing animals in vivo.

Real-world cost- effectiveness analysis: Tumor Treating Fields for newly diagnosed glioblastoma in China.

BACKGROUND: Glioblastoma (GBM) stands as the most aggressive and prevalent primary brain malignancy. Tumor Treating Fields (TTFields), an innovative therapy complementing chemotherapy for GBM treatment, which can significantly enhance overall survival, disease progression-free survival, and patient's quality of life. However, there is a dearth of health economics evaluation on TTFields therapy both domestically and internationally. OBJECTIVE: The study aims to assess the cost-effectiveness of TTFields + temozolomide (TMZ) in comparison to TMZ alone for newly diagnosed GBM patients. The intent is to provide robust economic evidence to serve as a foundation for policymaking and decision-making processes in GBM treatment. METHODS: We estimated outcomes for newly diagnosed GBM patients over a lifetime horizon using a partitioned survival model with three states: Progression-Free Survival, Progression Disease, and Death. The survival model was derived from a real-world study in China, with long-term survival data drawn from GBM epidemiology literature. Adverse event rates were sourced from the EF-14 trial data. Cost data, validated by expert consultation, was obtained from public literature and databases. Utility values were extracted from published literature. Using Microsoft Excel, we calculated expected costs and quality-adjusted life years (QALYs) over 15 years from a health system perspective. The willingness-to-pay threshold was set at three times the Chinese per capita Gross Domestic Product (GDP) in 2022, amounting to CN¥242,928 (US$37,655) /QALY. A 5% discount rate was applied to costs and utilities. Results underwent analysis through single factor and probability sensitivity analyses. RESULTS: TTFields + TMZ demonstrated a mean increase in cost by CN¥389,326 (US$57,859) and an increase of 2.46 QALYs compared to TMZ alone. The incremental cost-effectiveness ratio (ICER) was CN¥157,979 (US$23,474) per QALY gained. The model exhibited heightened sensitivity to changes in the discount rate. Probability sensitivity analysis indicates that, under the existing threshold, the probability of TTFields + TMZ being economical is 95.60%. CONCLUSIONS: This cost-effectiveness analysis affirms that incorporating TTFields into TMZ treatment proves to be cost-effective, given a threshold three times the Chinese per capita GDP.

"Tumor Treating Fields" delivered via electromagnetic induction have varied effects across glioma cell lines and electric field amplitudes.

Previous studies reported that alternating electric fields (EFs) in the intermediate frequency (100-300 kHz) and low intensity (1-3 V/cm) regime - termed "Tumor Treating Fields" (TTFields) - have a specific, anti-proliferative effect on glioblastoma multiforme (GBM) cells. However, the mechanism(s) of action remain(s) incompletely understood, hindering the clinical adoption of treatments based on TTFields. To advance the study of such treatment in vitro, we developed an inductive device to deliver EFs to cell cultures which improves thermal and osmolar regulation compared to prior devices. Using this inductive device, we applied continuous, 200 kHz electromagnetic fields (EMFs) with a radial EF amplitude profile spanning 0-6.5 V/cm to cultures of primary rat astrocytes and several human GBM cell lines - U87, U118, GSC827, and GSC923 - for a duration of 72 hours. Cell density was assessed via segmented pixel densities from GFP expression (U87, U118) or from staining (astrocytes, GSC827, GSC923). Further RNA-Seq analyses were performed on GSC827 and GSC923 cells. Treated cultures of all cell lines exhibited little to no change in proliferation at lower EF amplitudes (0-3 V/cm). At higher amplitudes (> 4 V/cm), different effects were observed. Apparent cell densities increased (U87), decreased (GSC827, GSC923), or showed little change (U118, astrocytes). RNA-Seq analyses on treated and untreated GSC827 and GSC923 cells revealed differentially expressed gene sets of interest, such as those related to cell cycle control. Up- and down-regulation, however, was not consistent across cell lines nor EF amplitudes. Our results indicate no consistent, anti-proliferative effect of 200 kHz EMFs across GBM cell lines and thus contradict previous in vitro findings. Rather, effects varied across different cell lines and EF amplitude regimes, highlighting the need to assess the effect(s) of TTFields and similar treatments on a per cell line basis.

Theory and application of TTFields in newly diagnosed glioblastoma.

BACKGROUND: Glioblastoma is the most common primary malignant brain tumor in adults. TTFields is a therapy that use intermediate-frequency and low-intensity alternating electric fields to treat tumors. For patients with ndGBM, the addition of TTFields after the concurrent chemoradiotherapy phase of the Stupp regimen can improve prognosis. However, TTFields still has the potential to further prolong the survival of ndGBM patients. AIM: By summarizing the mechanism and application status of TTFields in the treatment of ndGBM, the application prospect of TTFields in ndbm treatment is prospected. METHODS: We review the recent literature and included 76 articles to summarize the mechanism of TTfields in the treatment of ndGBM. The current clinical application status and potential health benefits of TTFields in the treatment of ndGBM are also discussed. RESULTS: TTFields can interfere with tumor cell mitosis, lead to tumor cell apoptosis and increased autophagy, hinder DNA damage repair, induce ICD, activate tumor immune microenvironment, reduce cancer cell metastasis and invasion, and increase BBB permeability. TTFields combines with chemoradiotherapy has made progress, its optimal application time is being explored and the problems that need to be considered when retaining the electrode patches for radiotherapy are further discussed. TTFields shows potential in combination with immunotherapy, antimitotic agents, and PARP inhibitors, as well as in patients with subtentorial gliomas. CONCLUSION: This review summarizes mechanisms of TTFields in the treatment of ndGBM, and describes the current clinical application of TTFields in ndGBM. Through the understanding of its principle and application status, we believe that TTFields still has the potential to further prolong the survival of ndGBM patients. Thus,research is still needed to explore new ways to combine TTFields with other therapies and optimize the use of TTFields to realize its full potential in ndGBM patients.

Corrigendum: Establishment of tumor treating fields combined with mild hyperthermia as novel supporting therapy for pancreatic cancer.

[This corrects the article DOI: 10.3389/fonc.2021.738801.].

Cost-effectiveness of tumor-treating fields plus standard therapy for advanced non-small cell lung cancer progressed after platinum-based therapy in the United States.

Background: Tumor treating fields (TTF) was first approved for treatment of glioblastoma. Recently, the LUNAR study demonstrated that TTF + standard therapy (ST) extended survival in patients with advanced non-small cell lung cancer (NSCLC). This primary objective of this study is to analyze the cost-effectiveness of this treatment from the United States healthcare payers' perspective. Methods: A 3-health-state Markov model was established to compare the cost-effectiveness of TTF + ST and that of ST alone. Clinical data were extracted from the LUNAR study, supplemented by additional cost and utility data obtained from publications or online sources. One-way sensitivity analysis, probabilistic sensitivity analysis, and scenario analysis were conducted. The willingness-to-pay (WTP) threshold per quality-adjusted life-years (QALYs) gained was set to $150,000. The main results include total costs, QALYs, incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit (INMB). Subgroup analyses were conducted for two types of ST, including immune checkpoint inhibitor, and docetaxel. Results: During a 10-year time horizon, the costs of TTF + ST and ST alone were $431,207.0 and $128,125.9, and the QALYs were 1.809 and 1.124, respectively. The ICER of TTF + ST compared to ST was $442,732.7 per QALY, and the INMB was -$200,395.7 at the WTP threshold. The cost of TTF per month was the most influential factor in cost-effectiveness, and TTF + ST had a 0% probability of being cost-effective at the WTP threshold compared with ST alone. Conclusion: TTF + ST is not a cost-effective treatment for advanced NSCLC patients who progressed after platinum-based therapy from the perspective of the United States healthcare payers.

Impact of glioma peritumoral edema, tumor size, and tumor location on alternating electric fields (AEF) therapy in realistic 3D rat glioma models: a computational study.

Objective.Alternating electric fields (AEF) therapy is a treatment modality for patients with glioblastoma. Tumor characteristics such as size, location, and extent of peritumoral edema may affect the AEF strength and distribution. We evaluated the sensitivity of the AEFs in a realistic 3D rat glioma model with respect to these properties.Approach.The electric properties of the peritumoral edema were varied based on calculated and literature-reported values. Models with different tumor composition, size, and location were created. The resulting AEFs were evaluated in 3D rat glioma models.Main results.In all cases, a pair of 5 mm diameter electrodes induced an average field strength >1 V cm-1. The simulation results showed that a negative relationship between edema conductivity and field strength was found. As the tumor core size was increased, the average field strength increased while the fraction of the shell achieving >1.5 V cm-1decreased. Increasing peritumoral edema thickness decreased the shell's mean field strength. Compared to rostrally/caudally, shifting the tumor location laterally/medially and ventrally (with respect to the electrodes) caused higher deviation in field strength.Significance.This study identifies tumor properties that are key drivers influencing AEF strength and distribution. The findings might be potential preclinical implications.

Breaking Barriers in Neuro-Oncology: A Scoping Literature Review on Invasive and Non-Invasive Techniques for Blood-Brain Barrier Disruption.

The blood-brain barrier (BBB) poses a significant challenge to drug delivery for brain tumors, with most chemotherapeutics having limited permeability into non-malignant brain tissue and only restricted access to primary and metastatic brain cancers. Consequently, due to the drug's inability to effectively penetrate the BBB, outcomes following brain chemotherapy continue to be suboptimal. Several methods to open the BBB and obtain higher drug concentrations in tumors have been proposed, with the selection of the optimal method depending on the size of the targeted tumor volume, the chosen therapeutic agent, and individual patient characteristics. Herein, we aim to comprehensively describe osmotic disruption with intra-arterial drug administration, intrathecal/intraventricular administration, laser interstitial thermal therapy, convection-enhanced delivery, and ultrasound methods, including high-intensity focused and low-intensity ultrasound as well as tumor-treating fields. We explain the scientific concept behind each method, preclinical/clinical research, advantages and disadvantages, indications, and potential avenues for improvement. Given that each method has its limitations, it is unlikely that the future of BBB disruption will rely on a single method but rather on a synergistic effect of a combined approach. Disruption of the BBB with osmotic infusion or high-intensity focused ultrasound, followed by the intra-arterial delivery of drugs, is a promising approach. Real-time monitoring of drug delivery will be necessary for optimal results.