The Value of Tumor Treating Fields in Glioblastoma.
Ontology highlight
ABSTRACT:
SUBMITTER: Zhang C
PROVIDER: S-EPMC7671789 | biostudies-literature | 2020 Nov
REPOSITORIES: biostudies-literature
Publications
The Value of Tumor Treating Fields in Glioblastoma.
Zhang Chaochao C Du Jianyang J Xu Weidong W Huang Haiyan H Gao Li L
Journal of Korean Neurosurgical Society 20200508 6
Glioblastoma (GBM) is one of the most common tumors of the central nervous system, which is the most lethal brain cancer. GBM treatment is based primarily on surgical resection, combined with radiotherapy and chemotherapy. Despite the positive treatment, progression free survival and overall survival were not significantly prolonged because GBM almost always recurs. We are always looking forward to some new and effective treatments. In recent years, a novel treatment method called tumor treating ...[more]
Similar Datasets
Project description:BackgroundTumor Treating Fields (TTF) have entered clinical practice for newly diagnosed and recurrent glioblastoma (GGM). However, controversies remain unresolved with regard to appropriate usage. We sought to determine TTF usage in major academic neuro-oncology programs in New York City, USA and Heidelberg, Germany and understand current attitudes toward TTF usage among providers.MethodsWe retrospectively determined TTF usage among patients with GGM, before and since the publication of key clinical trial results and regulatory approvals. We also surveyed attendees of an educational session related to TTF during the 2019 American Society of Clinical Oncology annual meeting.ResultsTTF usage remains infrequent (3-12% of patients with newly diagnosed GBM, and 0-16% of patients with recurrent disease) in our practices, although it has increased over time. Among 30 survey respondents (77% of whom self-identified as neuro- or medical oncologists), 60% were convinced that TTF prolongs survival for newly diagnosed GGM despite published phase III data and regulatory approval, and only 30% viewed TTF as definitively part of the standard of care treatment. A majority (87%) opposed mandating TTF incorporation into the design of clinical trials.ConclusionsProviders continue to view TTF with some level of skepticism, with a lack of additional supportive data and logistical concerns representing continued barriers to uptake.
| S-EPMC7345837 | biostudies-literature
Project description:Glioblastoma is the most common yet most lethal of primary brain cancers with a one-year post-diagnosis survival rate of 65% and a five-year survival rate of barely 5%. Recently the U.S. Food and Drug Administration approved a novel fourth approach (in addition to surgery, radiation therapy, and chemotherapy) to treating glioblastoma; namely, tumor treating fields (TTFields). TTFields involves the delivery of alternating electric fields to the tumor but its mechanisms of action are not fully understood. Current theories involve TTFields disrupting mitosis due to interference with proper mitotic spindle assembly. We show that TTFields also alters cellular membrane structure thus rendering it more permeant to chemotherapeutics. Increased membrane permeability through the imposition of TTFields was shown by several approaches. For example, increased permeability was indicated through increased bioluminescence with TTFields exposure or with the increased binding and ingress of membrane-associating reagents such as Dextran-FITC or ethidium D or with the demonstration by scanning electron microscopy of augmented number and sizes of holes on the cellular membrane. Further investigations showed that increases in bioluminescence and membrane hole production with TTFields exposure disappeared by 24?h after cessation of alternating electric fields thus demonstrating that this phenomenom is reversible. Preliminary investigations showed that TTFields did not induce membrane holes in normal human fibroblasts thus suggesting that the phenomenom was specific to cancer cells. With TTFields, we present evidence showing augmented membrane accessibility by compounds such as 5-aminolevulinic acid, a reagent used intraoperatively to delineate tumor from normal tissue in glioblastoma patients. In addition, this mechanism helps to explain previous reports of additive and synergistic effects between TTFields and other chemotherapies. These findings have implications for the design of combination therapies in glioblastoma and other cancers and may significantly alter standard of care strategies for these diseases.
| S-EPMC6281619 | biostudies-literature
Project description:Alternating electric fields have been successfully applied to cancer cells in-vitro to disrupt malignant progression and this antimitotic therapy has now been proven to be efficacious in Phase II and Phase III randomized clinical trials of patients with glioblastoma. With additional clinical trials ongoing in a number of other malignancies, there is a crucial need for a better understanding of the radiographic predictors of response and standardization of surveillance imaging interpretation. However, many radiologists have yet to become familiarized with this emerging cancer therapy and there is little active investigation to develop prognostic or predictive imaging biomarkers. This article provides an overview of the pre-clinical data that elucidate the biologic mechanisms of alternating electric fields as a cancer therapy. Results from clinical trials in patients with glioblastoma are then reviewed while elaborating on the several limitations to adoption of this promising line of treatment. Finally, a proposal for the development of imaging markers as a means of overcoming some of these limitations is made, which may improve treatment utilization by augmenting patient selection not only in glioblastoma, but also other malignant conditions for which this therapy is currently being evaluated.
| S-EPMC6884888 | biostudies-literature
Project description:Glioblastoma is one of the most common malignant tumors in the central nervous system. Due to the high plasticity, heterogeneity and complexity of the tumor microenvironment, these tumors are resistant to almost all therapeutic strategies when they reach an advanced stage. Along with being a unique and effective way to kill cancer cells, tumor-treating fields (TTFields) has emerged as a breakthrough among glioblastoma therapies since the advent of temozolomide (TMZ), and the combination of these treatments has gradually been promoted and applied in the clinic. The combination of TTFields with other therapies is particularly suitable for this type of "cold" tumors and has attracted a large amount of attention from clinicians and researchers in the era of cancer cocktail therapy. Here, we introduced the current treatment regimen for glioblastoma, highlighting the unique advantages of TTFields in the treatment of glioblastoma. Then, we summarized current glioblastoma clinical trials that combine TTFields and other therapies. In addition, the main and potential mechanisms of TTFields were introduced to further understand the rationale for each combination therapy. Finally, we focused on the most advanced technologies applied in glioblastoma research and treatment and the prospect of their combination with TTFields. This review provides a unique overview of glioblastoma treatment.
| S-EPMC8085847 | biostudies-literature
Project description:BackgroundTo date, there has been no large-scale, real-world study of the health-related quality of life outcomes for patients using tumor treating fields (TTFields) therapy for glioblastoma (GBM) treatment.MethodsA survey was mailed to 2,815 patients actively using TTFields for treatment of GBM in the USA (n = 2,182) and Europe (n = 633). The survey included patient-reported demographic and clinical information, as well as EuroQol's EQ-5D-5L and visual analogue scale (EQ-VAS) overall health score.ResultsA total of 1,106 applicable patients responded to the survey (USA = 782 and Europe = 324), with a mean age of 58.6 years (SD = 12.3). The average time since diagnosis and time using TTFields were 21.5 months (SD = 25.1) and 13.5 months (SD = 13.2), respectively. Over 61% of patients had been diagnosed at least 1 year prior and 28.4% at least 2 years prior; 45 patients (4.2%) had been diagnosed at least 5 years prior. Progressed disease was reported in 307 patients, while 690 reported non-progressed disease. Regression analyses showed that GBM disease progression and older age had predictable negative associations (p < 0.001) with most EQ-5D-5L dimensions and the EQ-VAS. However, longer time since diagnosis was associated with improved self-care (p < 0.05), usual activities (p < 0.01), and EQ-VAS (p < 0.05) overall and in patients with progressed disease (p < 0.01, p < 0.05, and p < 0.01, respectively). Additionally, longer time using TTFields was associated with improved mobility (p < 0.05), self-care (p < 0.001), usual activities (p < 0.01), and EQ-VAS (p < 0.01) overall; with improved EQ-VAS in progression-free patients (p < 0.05); and with improved mobility (p < 0.05), self-care (p < 0.01), usual activities (p < 0.05), and EQ-VAS (p < 0.05) in patients with progressed disease.ConclusionThis is the largest real-world study of patient-reported quality of life in GBM and TTFields treatment to date. It shows unsurprising negative associations between quality of life and disease progression and older age, as well as more novel, positive associations between quality of life and longer time since diagnosis and time using TTFields therapy.
| S-EPMC8675863 | biostudies-literature
Project description:BackgroundThis review focuses on the recently published evidence on tumor treating fields (TTFields) administered alone or in combination with locoregional and systemic options for treating glioblastoma (GBM) in the past ten years. The aim is to critically summarize the novelty and results obtained with this innovative tool, which is becoming part of the armamentarium of neurosurgeons and neuro-oncologists.MethodsA comprehensive search and analysis were conducted on pivotal studies published in the past ten years. Furthermore, all completed clinical trials, whose results were published on clinicaltrials.gov, were examined and included in the present review, encompassing both recurrent (r) and newly diagnosed (n) GBM. Finally, an additional examination of the ongoing clinical trials was also conducted.ResultsRecent trials have shown promising results both in patients with nGBM and rGBM/progressive (rGBM), leading to Food and Drug Administration approval in selected patients and the Congress of Neurological Surgeons to include TTFields into current guidelines on the management of GBM (P100034/S001-029). Recently, different randomized trials have demonstrated promising results of TTFields in combination with standard treatment of n- and rGBM, especially when considering progression-free and overall survival, maintaining a low rate of mild to moderate adverse events.ConclusionOptimal outcomes were obtained in nGBM and progressive disease. A possible future refinement of TTFields could significantly impact the treatment of rGBM and the actual standard of care for GBM, given the better safety profile and survival effects.
| S-EPMC10695468 | biostudies-literature
Project description:BackgroundGlioblastoma, one of the common tumors of the central nervous system (CNS), is prone to recurrence even after standard treatment protocols. As an innovative physiotherapy method emerging in recent years, the tumor treating fields (TTFields) technique has been approved for the treatment of glioblastoma due to its non-invasive and portable features. The purpose of this study is to visualize and analyze the scientific results and research trends in TTFields therapy for glioblastoma.MethodsPublications related to TTFields therapy for glioblastoma were searched in the Web of Science Core Collection (WoSCC) database in September 2022. A bibliometric and visual analysis of publications in this field was performed mainly using CiteSpace and R software for country/region, author, journal, reference and keyword.ResultsA total of 618 publications in this field were retrieved, and 248 were finally obtained according to the search criteria, including 159 articles (64.11%) and 89 reviews (37.89%). The cumulative number of publications increased year by year, with an average growth rate (AGR) of 28.50%. The test results of Pearson correlation coefficient showed a high positive correlation between publications and citations (r=0.937, p<0.001). The USA had the largest number of publications (123, 49.60%), followed by Germany (32, 12.90%) and China (30, 12.10%). As for the country/region collaborations, the USA cooperated most closely with other countries/regions, followed by Germany and China. The degree of collaboration (DC) between countries/regions was 25.81%. The institutions with the largest number of publications were Tel Aviv Univ (10), Harvard Med Sch (10) and Novocure Ltd (10). Moreover, Wong E (18) possessed the greatest number of publications, followed by Weinberg U (11) and Kirson E (10). The DC between authors was 97.58%. STUPP R (236) was the most cited author followed by KIRSON ED (164) and GILADI M (104). JOURNAL OF NEURO-ONCOLOGY (22) was the journal with the largest number of published publications (75), followed by FRONTIERS IN ONCOLOGY (15) and CANCERS (13). The top 10 keywords that occurred frequently included glioblastoma (156), tumor treating field (152), temozolomide (134), randomized phase III (48), brain (46), survivor (46), cancer (44), trial (42), alternating electric field (42) and radiotherapy (36). Furthermore, cluster analysis was performed on the basis of keyword co-occurrence, and finally 15 clusters were formed to determine the current research status and future development trend of TTFields therapy for glioblastoma.ConclusionTTFields has been increasingly known as the fourth novel physical anti-tumor therapy in addition to surgery, radiotherapy and anti-tumor drugs. Cooperation and communication between countries/regions need to be enhanced in future research. Several studies have demonstrated the therapeutic potential of TTFields in glioma, and its application alone or in combination with other treatments has become a current research hotspot.
| S-EPMC9684468 | biostudies-literature
Project description:Glioblastoma (GBM) is the most common primary brain tumor. Despite aggressive treatment, GBM almost always recurs. The current standard-of-care for treatment of newly diagnosed GBM has remained relatively unchanged since 2005: maximal safe resection followed by concomitant chemoradiation (CRT) with temozolomide (TMZ), and subsequent adjuvant TMZ. In 2011, the first-generation tumor treating fields (TTF) device, known at the time as the NovoTTF-100A System (renamed Optune), was approved by the Food and Drug Administration (FDA) for treatment of recurrent GBM. The TTF device was subsequently approved as an adjuvant therapy for newly-diagnosed GBM in 2015. The following is a review of the TTF device, including evidence supporting its use and limitations.
| S-EPMC6406491 | biostudies-literature
Project description:IntroductionThe prognosis of glioblastoma remains unfavorable. TTFields utilize low intensity electric fields (frequency 150-300 kHz) that disrupt cellular processes critical for cancer cell viability and tumor progression. TTFields are delivered via transducer arrays placed on the patients' scalp. Methods: Between the years 2004 and 2022, 55 patients (20 female), aged 21.9-77.8 years (mean age 47.3±11.8 years; median 47.6 years) were treated with TTFields for newly-diagnosed GBM, and compared to 54 control patients (20 females), aged 27.0-76.7 years (mean age 51.4±12.2 years; median 51.7 years) (p=0.08). All patients underwent gross total or partial resection of GBM. One patient had biopsy only. When available, MGMT promoter methylation status and IDH mutation was detected.ResultsPatients on TTFields therapy demonstrated improvements in PFS and OS relative to controls (hazard ratio: 0.64, p=0.031; and 0.61, p=0.028 respectively). TTFields average time on therapy was 74.8% (median 82%): median PFS of these patients was 19.75 months. Seven patients with TTFields usage ≤60% (23-60%, mean 46.3%, median 53%) had a median PFS of 7.95 months (p=0.0356). Control patients with no TTFields exposure had a median PFS of 12.45 months. Median OS of TTF patients was 31.67 months compared to 24.80 months for controls.DiscussionThis is the most extensive study on newly-diagnosed GBM patients treated with TTFields, covering a period of 18 years at a single center and presenting not only data from clinical trials but also a group of 36 patients treated with TTFields as a part of routine clinical practice.
| S-EPMC9892904 | biostudies-literature
Project description:Tumor treating fields (TTFields) are approved for glioblastoma (GBM) therapy. TTFields disrupt cell division by inhibiting spindle fiber formation. Spindle assembly checkpoint (SAC) inhibition combined with antimitotic drugs synergistically decreases glioma cell growth in cell culture and mice. We hypothesized that SAC inhibition will increase TTFields efficacy. Human GBM cells (U-87 MG, GaMG) were treated with TTFields (200?kHz, 1.7?V/cm) and/or the SAC inhibitor MPS1-IN-3 (IN-3, 4?µM). Cells were counted after 24, 48, and 72?h of treatment and at 24 and 72?h after end of treatment (EOT). Flow cytometry, immunofluorescence microscopy, Annexin-V staining and TUNEL assay were used to detect alterations in cell cycle and apoptosis after 72?h of treatment. The TTFields/IN-3 combination decreased cell proliferation after 72?h compared to either treatment alone (-78.6% vs. TTFields, P?=?0.0337; -52.6% vs. IN-3, P?=?0.0205), and reduced the number of viable cells (62% less than seeded). There was a significant cell cycle shift from G1 to G2/M phase (P?<?0.0001). The apoptotic rate increased to 44% (TTFields 14%, P?=?0.0002; IN-3 4%, P?<?0.0001). Cell growth recovered 24?h after EOT with TTFields and IN-3 alone, but the combination led to further decrease by 92% at 72?h EOT if IN-3 treatment was continued (P?=?0.0288). The combination of TTFields and SAC inhibition led to earlier and prolonged effects that significantly augmented the efficacy of TTFields and highlights a potential new targeted multimodal treatment for GBM.
| S-EPMC6125382 | biostudies-literature