scholarly journals Noninvasive Application of Alternating Electric Fields in Glioblastoma: A Fourth Cancer Treatment Modality

2012 ◽  
pp. 126-131 ◽  
Author(s):  
Philip H. Gutin ◽  
Eric T. Wong
Keyword(s):  
Cancer Treatment ◽  
Electric Fields ◽  
Treatment Modality ◽  
Skin Surface ◽  
Recurrent Glioblastoma ◽  
Treatment Modalities ◽  
Future Research ◽  
Clinical Safety ◽  
Tumor Treating Fields ◽  
Radiation Treatments

Overview: Tumor treating fields (TTF) therapy is a novel antimitotic, electric field–based treatment for cancer. This nonchemical, nonablative treatment is unlike any of the established cancer treatment modalities, such as surgery, radiation, and chemotherapy. Recently, it has entered clinical use after a decade of intensive translational research. TTF therapy is delivered to patients by a portable, battery-operated, medical device using noninvasive transducer arrays placed on the skin surface surrounding the treated tumor. TTF therapy is now a U.S. Food and Drug Administration (FDA)–approved treatment for patients with recurrent glioblastoma (GBM) who have exhausted surgical and radiation treatments. This article will introduce the basic science behind TTF therapy, its mechanism of action, the preclinical findings that led to its clinical testing, and the clinical safety and efficacy data available to date, as well as offer future research directions on this novel treatment modality for cancer.

scholarly journals INNV-20. A SYSTEMATIC REVIEW OF TUMOR TREATING FIELDS THERAPY FOR PRIMARY FOR RECURRENT AND GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi134-vi135
Author(s):  
Pavan Shah ◽  
Taija White ◽  
Carrie Price ◽  
Debraj Mukherjee
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Electric Fields ◽  
Treatment Modality ◽  
Randomized Clinical Trials ◽  
Treatment Options ◽  
Recurrent Glioblastoma ◽  
Skin Reactions ◽  
Tumor Treating Fields ◽  
Novel Treatment

Abstract BACKGROUND Glioblastoma is an aggressive primary central nervous system malignancy with poor prognosis and limited treatment options. Tumor treating fields (TTFs) are a novel treatment modality utilizing alternating electric fields that have demonstrated promise in randomized clinical trials for primary and recurrent glioblastomas. In addition to these studies, a multitude of smaller investigations have been performed examining their efficacy in a variety of combination therapies. This systematic review of available literature aims to summarize and evaluate the efficacy and safety of TTFs for primary and recurrent glioblastoma patients. METHODS A systematic review of the literature was performed according to PRISMA guidelines from database inception through 2/27/2019. Databases queried include PubMed, Embase, Cochrane, Scopus, Web of Science, and ClinicalTrials.gov. 856 unique studies were initially identified in this search, 9 of which met final inclusion criteria. 2 authors independently performed the screening and data extraction of the studies. RESULTS Excluding historical controls, 1569 patients were identified in these studies, 1191 of which received TTFs therapy. TTFs were evaluated in single-arm clinical trials (n = 2), randomized clinical trials (n = 2), and retrospective studies (n = 5). These 9 studies are presented based on treatments provided, baseline patient characteristics, and patient outcomes. No adverse events appear to be associated with TTFs other than adverse skin reactions. Given the heterogeneity in the presented studies, a quantitative meta-analysis was not performed. CONCLUSIONS TTFs are a novel treatment modality that have demonstrated safety and efficacy in a number of settings and study designs. However, further investigation is needed to continue characterizing treatment outcomes and assessing TTFs interactions with various drug regimens.

P14.77 Efficacy and safety of Tumor-Treating Fields associated with Depatux M and metronomic temozolomide for recurrent glioblastoma: a case-report

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii52-ii53
Author(s):  
A Pellerino ◽  
F Bruno ◽  
E Muscolino ◽  
R Rudà ◽  
R Soffietti
Keyword(s):  
Electric Fields ◽  
Tumor Size ◽  
Brain Mri ◽  
Combined Treatment ◽  
Recurrent Glioblastoma ◽  
Treatment Modalities ◽  
Blurred Vision ◽  
Extensive Resection ◽  
Local Progression ◽  
First Recurrence

Abstract BACKGROUND Patients with glioblastoma (GBM) have a poor prognosis following an extensive resection, radiotherapy (RT) and concomitant/adjuvant temozolomide (TMZ). Once GBM progresses after SOC, lomustine is the standard second-line treatment, while rechallenge with TMZ may be employed in selected patients with methylated promoter of MGMT, and bevacizumab is reserved for patients with extensive edema and need for steroids. New treatment modalities have been investigated at first recurrence, including alternating electric fields (TTFields) or antibody direct against epidermal growth factor receptor (EGFR), such as depatuximab mafodontin (ABT-414, Depatux-M), that have shown some activity in terms of disease control and progression-free survival (PFS). CLINICAL PRESENTATION In September 2018, a 38 year-old man developed reduced strength in left upper limb and daily focal seizures. MRI showed an enhancing right fronto-temporal lesion which was subtotally removed with a diagnosis of glioblastoma (IDH 1/2 wild type, MGMT methylated - 40%, EGFR amplified, EGFRvIII positive). As the patient had a poor KPS (50), in October 2018 a hypofractionated RT (DFT 40 Gy/15 fractions) with concomitant TMZ (140 mg/day) was performed, followed by adjuvant standard TMZ (340 mg/day); however, chemotherapy was stopped after 3 cycles due to local progression on MRI coupled with strength worsening, increased seizure frequency, and need for steroids. Pseudoprogression was ruled out due to tumor growth out of the field of RT. Based on the high level of methylation of the MGMT promoter and EGFR amplification, a combined treatment with metronomic TMZ (100 mg/day continuously) plus Depatux-M (1.25 mg/kg every 2 weeks) was started (February 2019), but a brain MRI performed after 3 months of treatment displayed no significant changes on both MRI and neurological status. At this time point (May 2019) TTFields treatment was added. An initial decrease of tumor size was observed on MRI after 5 months, while a reduction of tumor size more than 90% has been progressively achieved after 1 year of treatment (April 2020). Moreover, a seizure-free status was observed without changing the antiepileptic medication. The patient developed a grade 3 ocular side effect (CTCAE version 5.0) with photophobia, blurred vision, foreign body sensation in the eyes after 6 months of treatment, which improved after dose delays and dose reduction of Depatux-M. The patient is still alive, and free of progression after 30 months and 25 months from diagnosis and first recurrence, respectively. CONCLUSION To our knowledge, this is the first report of a recurrent GBM with a significant and long-lasting neuroradiological response following a combined treatment with TTFields, Depatux-M, and intensified schedule of TMZ. A synergistic effect of TTFields with compounds interfering with the microtubular system should be further investigated.

scholarly journals Case Series, Systematic Review, and Meta-Analysis of Basilar Bifurcation Aneurysms Treated Between 2001 and 2017

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Charlotte Dandurand ◽  
Swetha Prakash ◽  
Amir A Sepehry ◽  
Katherine Tourigny ◽  
Charles Haw ◽  
...  
Keyword(s):  
Treatment Modality ◽  
Meta Analysis ◽  
Case Series ◽  
Treatment Decision ◽  
Post Treatment ◽  
Treatment Modalities ◽  
Future Research ◽  
Bias Analysis ◽  
Complete Occlusion ◽  
Bifurcation Aneurysm

Abstract INTRODUCTION A lower rate of aneurysmal recanalization in stent assisted coiling vs coiling alone has been observed. This study aims to stratify and compare degree of occlusion outcomes by treatment modalities for basilar bifurcation aneurysms. Secondarily, this study aims to stratify and compare postoperative adverse events. METHODS Medical literature including MEDLINE and EMBASE database was searched. We performed metaregressions, bias analysis, and fail-safe N. We controlled for the quality of the studies. RESULTS Eligible studies (N = 12) and study center patients (n = 117) data were pooled for a total of 396 nonduplicated patients. Patients were separated into 4 groups: microsurgical, stent-assisted coiling, coiling, stent only. Stent-assisted coiling had a lower rate of retreatment (17% vs 24%) and higher rate of post-treatment haemorrhage (5% vs 3%) compared to coiling. Stent-assisted coiling had a higher rate of complete occlusion (55% vs 45%) and lower rate of residual aneurysm (15% vs 23%) compared to coiling. Comparative analyses were performed. Microsurgical technique remained the most morbid treatment modality with the best rate of complete occlusion (93%) and lowest rehemorrhage (2%) and retreatment rate (5%). CONCLUSION This is the first and largest meta-analysis focusing on patients treated for basilar bifurcation aneurysm. This is the first study to stratify and compare degree of occlusion and clinical outcomes per treatment modality. This is the first study to report higher rates of post-treatment hemorrhage with stent-assisted coiling. This study provides benchmark data to guide clinicians in future treatment decision-making and encourages future research to stratify outcomes.

scholarly journals In Vivo Safety of Tumor Treating Fields (TTFields) Applied to the Torso

2021 ◽  
Vol 11 ◽  
Author(s):  
Roni Blatt ◽  
Shiri Davidi ◽  
Mijal Munster ◽  
Anna Shteingauz ◽  
Shay Cahal ◽  
...  
Keyword(s):  
Electric Fields ◽  
Cellular Proliferation ◽  
Complete Blood Count ◽  
Malignant Tumors ◽  
Neurological Status ◽  
Recurrent Glioblastoma ◽  
Activity Level ◽  
Internal Organs ◽  
Tumor Treating Fields

BackgroundTumor Treating Fields (TTFields) therapy is a non-invasive, loco-regional, anti-mitotic treatment modality that targets rapidly dividing cancerous cells, utilizing low intensity, alternating electric fields at cancer-cell-type specific frequencies. TTFields therapy is approved for the treatment of newly diagnosed and recurrent glioblastoma (GBM) in the US, Europe, Israel, Japan, and China. The favorable safety profile of TTFields in patients with GBM is partially attributed to the low rate of mitotic events in normal, quiescent brain cells. However, specific safety evaluations are warranted at locations with known high rates of cellular proliferation, such as the torso, which is a primary site of several of the most aggressive malignant tumors.MethodsThe safety of delivering TTFields to the torso of healthy rats at 150 or 200 kHz, which were previously identified as optimal frequencies for treating multiple torso cancers, was investigated. Throughout 2 weeks of TTFields application, animals underwent daily clinical examinations, and at treatment cessation blood samples and internal organs were examined. Computer simulations were performed to verify that the targeted internal organs of the torso were receiving TTFields at therapeutic intensities (≥ 1 V/cm root mean square, RMS).ResultsNo treatment-related mortality was observed. Furthermore, no significant differences were observed between the TTFields-treated and control animals for all examined safety parameters: activity level, food and water intake, stools, motor neurological status, respiration, weight, complete blood count, blood biochemistry, and pathological findings of internal organs. TTFields intensities of 1 to 2.5 V/cm RMS were confirmed for internal organs within the target region.ConclusionsThis research demonstrates the safety of therapeutic level TTFields at frequencies of 150 and 200 kHz when applied as monotherapy to the torso of healthy rats.

A Review of Chemotherapy and Photodynamic Therapy for Lung Cancer Treatment

2020 ◽  
Vol 21 (2) ◽  
pp. 149-161 ◽  
Author(s):  
Ahmed El-Hussein ◽  
Sello L. Manoto ◽  
Saturnin Ombinda-Lemboumba ◽  
Ziya A. Alrowaili ◽  
Patience Mthunzi-Kufa
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Photodynamic Therapy ◽  
Cancer Treatment ◽  
Treatment Modality ◽  
Treatment Modalities ◽  
Fatal Disease ◽  
Mortality And Morbidity ◽  
Lung Cancer Treatment ◽  
Different Types

: Cancer is among the leading causes of mortality and morbidity worldwide. Among the different types of cancers, lung cancer is considered to be the leading cause of death related to cancer and the most commonly diagnosed form of such disease. Chemotherapy remains a dominant treatment modality for many types of cancers at different stages. However, in many cases, cancer cells develop drug resistance and become nonresponsive to chemotherapy, thus, necessitating the exploration of alternative and /or complementary treatment modalities. Photodynamic Therapy (PDT) has emerged as an effective treatment modality for various malignant neoplasia and tumors. In PDT, the photochemical interaction of light, Photosensitizer (PS) and molecular oxygen produces Reactive Oxygen Species (ROS), which induces cell death. Combination therapy, by using PDT and chemotherapy, can promote synergistic effect against this fatal disease with the elimination of drug resistance, and enhancement of the efficacy of cancer eradication. In this review, we give an overview of chemotherapeutic modalities, PDT, and the different types of drugs associated with each therapy. Furthermore, we also explored the combined use of chemotherapy and PDT in the course of lung cancer treatment and how this approach could be the last resort for thousands of patients that have been diagnosed by this fatal disease.

Tumor Treating Fields – Behind and Beyond Inhibiting the Cancer Cell Cycle

2020 ◽  
Vol 19 (8) ◽  
pp. 599-610 ◽  
Author(s):  
Cédric Kissling ◽  
Stefano Di Santo
Keyword(s):  
Cancer Cell ◽  
Electric Fields ◽  
Unmet Need ◽  
Mechanisms Of Action ◽  
Treatment Modalities ◽  
Tumor Treating Fields ◽  
Precise Knowledge ◽  
Alternating Electric Fields ◽  
State Of Research ◽  
New Treatment

The unmet need for a safe treatment that significantly improves the overall survival, as well as the quality of life of patients with brain tumors, has urged researchers to work out new treatment modalities. About 15 years ago, it was shown that alternating electric fields significantly impair the growth of cancer cells. Recently, this potentially revolutionary approach called Tumor Treating Fields (TTFs) has been FDA-approved for the treatment of glioblastoma as well as mesothelioma. However, despite the promising reports on the potential of TTFs, the precise knowledge of the mechanisms of action is still lacking. The purpose of this review is, thus, to present the current state of research and to highlight the variety of ultrastructural effects of TTFs. Moreover, the aim is to bring to the foreground less discussed mechanisms of action of TTFs, which might develop into novel therapeutic approaches. Therefore, a systematic literature search in Ovid Medline and Embase was performed on clinical and preclinical data concerning TTFs. The alternating electric fields force cellular components to aberrant dynamics, among which the most evident is the inhibition of the mitotic spindle assembly leading to impaired cancer cell division and cell death. However, a variety of other microstructural events induced by TTFs, such as inhibition of DNA repair and cell migration, as well as an enhancement of anti- tumor immune response and membrane permeability, have been reported. In addition, apart from a suggested interference with angiogenesis, no TTF-induced effects on normal cells have been described so far.

scholarly journals SS-3 Tumor Treating Fields: from the Petri dish to the patient

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii1-ii2
Author(s):  
Moshe Giladi
Keyword(s):  
Cell Death ◽  
Treatment Outcomes ◽  
Electric Fields ◽  
Recurrent Glioblastoma ◽  
Preclinical Research ◽  
Tumor Treating Fields ◽  
Research Activities ◽  
New Findings

Abstract Tumor Treating Fields (TTFields) are a non-invasive, loco-regional, antineoplastic treatment modality targeting rapidly dividing cancer cells using low intensity, alternating electric fields at cell-type-specific intermediate frequencies (100–500 kHz). TTFields therapy is approved for the treatment of newly-diagnosed and recurrent glioblastoma as well as malignant pleural mesothelioma, following clinical trials demonstrating efficacy and a favorable safety profile. Using novel in vitro and in vivo systems for TTFields application, research activities are being conducted to extend the understanding of the underlying mechanisms of action (MoA) and to assess additional means to improve treatment outcomes. The demonstrated antimitotic effects of TTFields discerned the positive combinatorial potential of TTFields with other agents targeting the division process. Subsequent to elucidation of anti-mitotic effects, other downstream effects of TTFields include induction of endoplasmic reticulum stress, up-regulation of autophagy and cell death, thus driving immunogenic cell death. Indeed, in several preclinical models, combining TTFields with immunotherapeutics demonstrated enhanced efficacy. Recently, additional novel effects of TTFields were characterized, including inhibition of DNA damage repair responses and induction of transient and reversible permeabilization of the blood brain barrier (BBB). These new findings offer potentially innovative means to optimize treatment outcomes by combining TTFields with radiation therapy and DNA damaging agents, as well as improved delivery of impermeant agents across the BBB. These scientific findings were instrumental in advancing the clinical pipeline of TTFields, which includes conduct of ongoing trials combining TTFields with a variety of modalities, in approved indications and in other solid malignant tumor types. The aim of this talk is to describe TTFields’ preclinical research activities and tools, and to specify how these study outcomes have defined and advanced the clinical pipeline.

Sign in / Sign up

Export Citation Format

Share Document