Tumour-treating Fields Research Articles

QLTI-04. UPDATE ON HIGH-GRADE GLIOMA PATIENTS TREATED WITH TTFIELDS FROM NANFANG HOSPITAL IN CHINA

Abstract OBJECTIVE Tumour-treating fields (TTFields) have changed the first-line clinical practice of glioblastoma worldwide due to their promising therapeutic efficacy. The aim of this study was to investigate the clinical efficacy of TTFields therapy for HGG in Nanfang Hospital, China. In 2023 ASNO we reported PFS.Now we reporte update about OS from our single center study. METHODS From January 2019 to December 2022, a total of 25 patients with newly diagnosed HGG (ndHGG) treated with TTFields were retrospectively included in our study. Among these patients, 9 patients received concurrent radiochemotherapy in combination with TTFields and 16 patients received non-concurrent chemoradiotherapy in combination with TTFields. The primary endpoint of the study was mPFS and mOS (Kaplan-Meier method used to estimate PFS and OS survival curves). Secondary endpoint was the influences about KPS score in PFS and OS. RESULTS The 25 ndHGG patients treated with TTFields included nine males and sixteen females with a mean age of 47.1 years (12-68). Gross total resection (GTR) was performed in eighteen patients. Twenty-one patients were IDH wild type, eleven patients showed methylation of the MGMT promoter. Followed up until January 2024, the median PFS was 13.3 months [95% CI: 11.33-15.2] with TTFields combined and 4.0 months (95% CI, 3.8-4.4) without TTFields treatment in EF-14.Median OS was 26.53 months [95% CI:19.47-33.57] with TTFields and 16.0 months (95% CI, 3.8-4.4) control in EF-14. In the KPS stratification, OS was 27.5 months (95% CI: 22.95-32.1) vs 4.3 months (95% CI: 0-11.2), p=0.0001. The OS of patients with concurrent chemoradiotherapy combined with TTFields vs. without concurrent chemoradiotherapy combined with TTFields was 26.5 months (95% CI: 24.33-28.7) vs 21.2 (95% CI: 3.1-39.3) months, p=0.59. CONCLUSIONS TTFields therapy is an effective treatment for HGG. In this study the addition of TTFields resulted in a statistically significant improvement in PFS and OS.

AB011. A propensity-score matched prospective study on the impact of tumour treating fields (TTF) on overall survival and quality of life in newly diagnosed WHO grade 4 astrocytoma patients.

World Health Organization (WHO) grade 4 astrocytoma is a high-grade brain tumour in adults. Tumour treating fields (TTF) has been shown to improve overall survival (OS). Few studies have explored quality-of-life (QoL) in these patients. This study aims to assess the QoL of TTF patients and OS. This was a prospective multicenter study of adult patients diagnosed with WHO grade 4 astrocytoma from 2018 to 2023 receiving TTF for >1 month after completing standard therapy. A propensity-score matched comparison with a 1:2 ratio with historical control was performed for OS analysis. The patients completed European Organisation for Research and Treatment of Cancer (EORTC) QLQ-30/BN20 questionnaires before TTF and at 3-month interval. Primary outcomes included OS, and secondary outcomes included QoL and TTF-associated adverse effects at 3 months. A total of 141 patients were reviewed, with TTF patients (n=47, 33%) and propensity-score matched controls (n=94). The mean duration of TTF use was 10±8 months. The mean age of the TTF group was 54±13 years, and for the control group 52±13 years. Sixty percent (n=28) were male, similar to the control group with 71% (n=67) (P=0.16). Seventy-two percent of TTF patients had preoperative Karnofsky Performance Scale (KPS) score ≥80, while controls had 70% (P=0.79). Five (11%) TTF patients and 8 (9%) controls were IDH1 mutant (P=0.70). Twenty (43%) TTF patients and 42 (45%) controls were O6-methylguanine-DNA methyltransferase promoter (pMGMT) methylated (P=0.81). Twenty-one (45%) of TTF patients and 55 (59%) of controls had gross total resection (P=0.72). After adjusting for independent predictors for OS, the median OS of the TTF group was 22.4 months [interquartile range (IQR): 18.6-26.5 months], significantly longer than the control group (17.2 months; IQR: 12.1-22.3 months) (log-rank test: P=0.01). Forty-seven TTF patients and 40 control patients completed EORTC questionnaires. There was no difference for EORTC functional and symptom scores between the TTF and control group [P=0.45, analysis of variance (ANOVA)] at 3 months. Thirty-two (67%) of TTF patients reported associated RTOG grade I scalp dermatitis. TTF for WHO grade 4 astrocytoma patients is an independent predictor for OS. QoL between the groups was similar, and overall QoL over time for TTF patients was not affected. TTF is a novel and effective outpatient treatment with minimal adverse effects.

Optune (NovoTTF-200A)

What Is the Indication Under Review?
 
 The indication under review is for the treatment of adults with newly diagnosed glioblastoma multiforme (ndGBM) following maximal debulking surgery and completion of radiotherapy together with and after standard of care maintenance chemotherapy. Glioblastoma is the development of cancer among glial cells in the central nervous system and is the most common form of brain cancer in Canada.
 
 What Is Optune?
 
 Optune is a medical device that produces alternating electrical fields called tumour-treating fields to target the growth of cancerous cells in addition to chemotherapy. Current treatment for glioblastoma consists of a combination of surgery, radiotherapy, and chemotherapy.
 
 How Did CADTH Evaluate This Device?
 
 To examine the value of Optune for the treatment of ndGBM, CADTH:
 
 reviewed and critically appraised the clinical and economic evidence submitted by the sponsor
 reviewed the literature to identify and describe ethical considerations relevant to the use of Optune, as well as to assess the validity of the sponsor’s modelling approaches, assumptions, and estimates regarding Optune
 sought input from patient and clinician groups and consulted an expert panel.
 
 
 
 What Did CADTH Find?
 Clinical Evidence
 
 This review included the EF-14 trial, a pivotal, multicentre, open-label randomized controlled trial that assessed the efficacy and safety of Optune plus temozolomide in adults with ndGBM following maximal debulking surgery and completion of radiotherapy, together with and after standard of care maintenance chemotherapy.
 Based on the single trial, there is evidence of low to moderate certainty that Optune plus temozolomide likely increases progression-free survival at 6 months of treatment and overall survival at 24 months of treatment compared to temozolomide alone. The treatment effect of Optune plus temozolomide on progression-free survival and overall survival may be dose-dependent, with at least 18 hours of daily use required for the most benefit.
 Overall, the evidence was of very low to moderate certainty due to concerns regarding selection bias and low generalizability of the results to real-world settings.
 
 Economic Evidence
 
 The submitted fee for Optune is $27,000 per month, which is added to the cost of temozolomide based on its public list price.
 The incremental cost-effectiveness ratio for Optune plus temozolomide versus temozolomide alone was $899,470 per quality-adjusted life-year (QALY) gained (incremental costs = $336,902; incremental QALYs = 0.37).
 Optune plus temozolomide was not considered cost-effective relative to temozolomide alone at conventional willingness-to pay thresholds (i.e., $50,000 per QALY gained and $100,000 per QALY gained). Consequently, a price reduction of between 91% and 97% would be required for Optune plus temozolomide to be considered cost-effective at a willingness-to-pay threshold between $50,000 and $100,000 per QALY gained.
 The budget impact of reimbursing Optune through the federal, provincial, and territorial public drug plans (excluding Quebec) is estimated to be $75,795,323 to cover 232 patients over the initial 3 years of funding.
 
 Ethical Considerations
 
 The extent to which Optune meets patients’ needs for an effective, accessible, and easily usable treatment may depend on an individual patient’s values and caregiver support network, especially as Optune requires managing an additional treatment modality and may require additional caregiver support.
 Further study on how — or if — factors such as functional status, race, sex, age, socioeconomic status, and availability of caregiver support have implications for device uptake and ability to adhere to treatment would be helpful to inform patient-centred and equitable use, given the diverse patient population in Canada.
 Careful attention must be paid to the quality of clinical consent conversations, including considerations of disease progression potentially impairing capacity to consent and requiring a substitute decision-maker.
 Equity-enhancing strategies for implementation will need to be explored to ensure that Optune is accessible in an equitable and effective manner for all eligible patients in Canada.

DNA damage response inhibitors enhance tumour treating fields (TTFields) potency in glioma stem-like cells

BackgroundHigh-grade gliomas are primary brain cancers with unacceptably low and persistent survival rates of 10–16 months for WHO grade 4 gliomas over the last 40 years, despite surgical resection and DNA-damaging chemo-radiotherapy. More recently, tumour-treating fields therapy (TTFields) has demonstrated modest survival benefit and been clinically approved in several countries. TTFields is thought to mediate anti-cancer activity by primarily disrupting mitosis. However, recent data suggest that TTFields may also attenuate DNA damage repair and replication fork dynamics, providing a potential platform for therapeutic combinations incorporating standard-of-care treatments and targeted DNA damage response inhibitors (DDRi).MethodsWe have used patient-derived, typically resistant, glioma stem-like cells (GSCs) in combination with the previously validated preclinical Inovitro™ TTFields system together with a number of therapeutic DDRi.ResultsWe show that TTFields robustly activates PARP- and ATR-mediated DNA repair (including PARylation and CHK1 phosphorylation, respectively), whilst combining TTFields with PARP1 or ATR inhibitor treatment leads to significantly reduced clonogenic survival. The potency of each of these strategies is further enhanced by radiation treatment, leading to increased amounts of DNA damage with profound delay in DNA damage resolution.ConclusionTo our knowledge, our findings represent the first report of TTFields applied with clinically approved or in-trial DDRi in GSC models and provides a basis for translational studies toward multimodal DDRi/TTFields-based therapeutic strategies for patients with these currently incurable tumours.

Tumour-treating fields for high-grade glioma

Tumour-treating fields for high-grade glioma

Novel therapeutic strategies in glioma targeting glutamatergic neurotransmission

High grade gliomas carry a poor prognosis despite aggressive surgical and adjuvant approaches including chemoradiotherapy. Recent studies have demonstrated a mitogenic association between neuronal electrical activity and glioma growth involving the PI3K-mTOR pathway. As the predominant excitatory neurotransmitter of the brain, glutamate signalling in particular has been shown to promote glioma invasion and growth. The concept of the neurogliomal synapse has been established whereby glutamatergic receptors on glioma cells have been shown to promote tumour propagation.Targeting glutamatergic signalling is therefore a potential treatment option in glioma. Antiepileptic medications decrease excess neuronal electrical activity and some may possess anti-glutamate effects. Although antiepileptic medications continue to be investigated for an anti-glioma effect, good quality randomised trial evidence is lacking. Other pharmacological strategies that downregulate glutamatergic signalling include riluzole, memantine and anaesthetic agents.Neuromodulatory interventions possessing potential anti-glutamate activity include deep brain stimulation and vagus nerve stimulation – this contributes to the anti-seizure efficacy of the latter and the possible neuroprotective effect of the former. A possible role of neuromodulation as a novel anti-glioma modality has previously been proposed and that hypothesis is extended to include these modalities. Similarly, the significant survival benefit in glioblastoma attributable to alternating electrical fields (Tumour Treating Fields) may be a result of disruption to neurogliomal signalling. Further studies exploring excitatory neurotransmission and glutamatergic signalling and their role in glioma origin, growth and propagation are therefore warranted.

Pulsed Electric Fields in Oncology: A Snapshot of Current Clinical Practices and Research Directions from the 4th World Congress of Electroporation.

The 4th World Congress of Electroporation (Copenhagen, 9-13 October 2022) provided a unique opportunity to convene leading experts in pulsed electric fields (PEF). PEF-based therapies harness electric fields to produce therapeutically useful effects on cancers and represent a valuable option for a variety of patients. As such, irreversible electroporation (IRE), gene electrotransfer (GET), electrochemotherapy (ECT), calcium electroporation (Ca-EP), and tumour-treating fields (TTF) are on the rise. Still, their full therapeutic potential remains underappreciated, and the field faces fragmentation, as shown by parallel maturation and differences in the stages of development and regulatory approval worldwide. This narrative review provides a glimpse of PEF-based techniques, including key mechanisms, clinical indications, and advances in therapy; finally, it offers insights into current research directions. By highlighting a common ground, the authors aim to break silos, strengthen cross-functional collaboration, and pave the way to novel possibilities for intervention. Intriguingly, beyond their peculiar mechanism of action, PEF-based therapies share technical interconnections and multifaceted biological effects (e.g., vascular, immunological) worth exploiting in combinatorial strategies.

Highlighted Advances in Therapies for Difficult-To-Treat Brain Tumours Such as Glioblastoma.

Glioblastoma multiforme (GBM) remains a challenging disease, as it is the most common and deadly brain tumour in adults and has no curative solution and an overall short survival time. This incurability and short survival time means that, despite its rarity (average incidence of 3.2 per 100,000 persons), there has been an increased effort to try to treat this disease. Standard of care in newly diagnosed glioblastoma is maximal tumour resection followed by initial concomitant radiotherapy and temozolomide (TMZ) and then further chemotherapy with TMZ. Imaging techniques are key not only to diagnose the extent of the affected tissue but also for surgery planning and even for intraoperative use. Eligible patients may combine TMZ with tumour treating fields (TTF) therapy, which delivers low-intensity and intermediate-frequency electric fields to arrest tumour growth. Nonetheless, the blood-brain barrier (BBB) and systemic side effects are obstacles to successful chemotherapy in GBM; thus, more targeted, custom therapies such as immunotherapy and nanotechnological drug delivery systems have been undergoing research with varying degrees of success. This review proposes an overview of the pathophysiology, possible treatments, and the most (not all) representative examples of the latest advancements.

Safety and efficacy of tumour-treating fields (TTFields) therapy for newly diagnosed glioblastoma in Japanese patients using the Novo-TTF System: a prospective post-approval study.

Tumour-treating fields therapy is a locoregional, anti-cancer treatment. Efficacy and safety of tumour-treating fields therapy in adults with newly diagnosed glioblastoma were demonstrated in the pivotal phase 3 EF-14 study (NCT00916409). Here, we report post-approval data of tumour-treating fields therapy in Japanese patients with newly diagnosed glioblastoma. Unsolicited post-marketing surveillance data from Japanese patients with newly diagnosed glioblastoma treated with tumour-treating fields therapy (December 2016-June 2020) were retrospectively analysed. The primary endpoints were skin, neurological and psychiatric adverse events. The secondary endpoints were 1- and 2-year overall survival rates, and the 6-month progression-free survival. adverse events were analysed using MedDRA v24.0. The overall survival and progression-free survival were assessed using the Kaplan-Meier survival analysis (log-rank testing). The Cox proportional hazard regression analyses were also performed. Forty patients with newly diagnosed glioblastoma were enrolled (62.5% male; median age 59years; median baseline Karnofsky Performance Scale score 90). The most common tumour-treating-fields-therapy-related adverse event was beneath-array local skin reaction (60% of patients). The adverse events were mostly mild to moderate in severity. Neurological disorders were observed in 2.5% patients (one patient reported dysesthesia). No psychiatric disorders were reported. The 1- and 2-year overall survival rates were 77.9% (95% CI 60.6-88.3) and 53.6% (35.5-68.7%), respectively. The 6-month progression-free survival was 77.5% (61.2-87.6%). These survival rates compare favourably with those in the EF-14 trial (1- and 2-year overall survival rates: 73% [69-77%] and 43% [39-48%], respectively; 6-month progression-free survival rate: 56% (51-61%). This post-approval, real-world evidence study revealed no new safety signals and suggests the safety and efficacy of tumour-treating fields therapy in Japanese patients with newly diagnosed glioblastoma.

The distinguishing electrical properties of cancer cells.

In recent decades, medical research has been primarily focused on the inherited aspect of cancers, despite the reality that only 5-10% of tumours discovered are derived from genetic causes. Cancer is a broad term, and therefore it is inaccurate to address it as a purely genetic disease. Understanding cancer cells' behaviour is the first step in countering them. Behind the scenes, there is a complicated network of environmental factors, DNA errors, metabolic shifts, and electrostatic alterations that build over time and lead to the illness's development. This latter aspect has been analyzed in previous studies, but how the different electrical changes integrate and affect each other is rarely examined. Every cell in the human body possesses electrical properties that are essential for proper behaviour both within and outside of the cell itself. It is not yet clear whether these changes correlate with cell mutation in cancer cells, or only with their subsequent development. Either way, these aspects merit further investigation, especially with regards to their causes and consequences. Trying to block changes at various levels of occurrence or assisting in their prevention could be the key to stopping cells from becoming cancerous. Therefore, a comprehensive understanding of the current knowledge regarding the electrical landscape of cells is much needed. We review four essential electrical characteristics of cells, providing a deep understanding of the electrostatic changes in cancer cells compared to their normal counterparts. In particular, we provide an overview of intracellular and extracellular pH modifications, differences in ionic concentrations in the cytoplasm, transmembrane potential variations, and changes within mitochondria. New therapies targeting or exploiting the electrical properties of cells are developed and tested every year, such as pH-dependent carriers and tumour-treating fields. A brief section regarding the state-of-the-art of these therapies can be found at the end of this review. Finally, we highlight how these alterations integrate and potentially yield indications of cells' malignancy or metastatic index.

Real-Time Monitoring of the Effect of Tumour-Treating Fields on Cell Division Using Live-Cell Imaging.

The effects of electric fields (EFs) on various cell types have been thoroughly studied, and exhibit a well-known regulatory effect on cell processes, implicating their usage in several medical applications. While the specific effect exerted on cells is highly parameter-dependent, the majority of past research has focused primarily on low-frequency alternating fields (<1 kHz) and high-frequency fields (in the order of MHz). However, in recent years, low-intensity (1–3 V/cm) alternating EFs with intermediate frequencies (100–500 kHz) have been of topical interest as clinical treatments for cancerous tumours through their disruption of cell division and the mitotic spindle, which can lead to cell death. These aptly named tumour-treating fields (TTFields) have been approved by the FDA as a treatment modality for several cancers, such as malignant pleural mesothelioma and glioblastoma multiforme, demonstrating remarkable efficacy and a high safety profile. In this work, we report the results of in vitro experiments with HeLa and MCF-10A cells exposed to TTFields for 18 h, imaged in real time using live-cell imaging. Both studied cell lines were exposed to 100 kHz TTFields with a 1-1 duty cycle, which resulted in significant mitotic and cytokinetic arrest. In the experiments with HeLa cells, the effects of the TTFields’ frequency (100 kHz vs. 200 kHz) and duty cycle (1-1 vs. 1-0) were also investigated. Notably, the anti-mitotic effect was stronger in the HeLa cells treated with 100 kHz TTFields. Additionally, it was found that single and two-directional TTFields (oriented orthogonally) exhibit a similar inhibitory effect on HeLa cell division. These results provide real-time evidence of the profound ability of TTFields to hinder the process of cell division by significantly delaying both the mitosis and cytokinesis phases of the cell cycle.

Tumour treating fields in glioblastoma: is the treatment tolerable, effective, and practical in UK patients?

Background Tumour Treating Fields (TTF) in combination with standard therapy, prolongs survival in patients with glioblastoma (GBM). The aim of the current study was to assess the feasibility of integrating TTF into a standard UK neuro-oncology service with a focus on patient tolerability, compliance, and treatment delivery. Methods A prospective study was performed of UK patients with IDH 1 Wild Type, MGMT Unmethylated GBM treated with TTF, in conjunction with conventional therapy. Patient compliance data, device-specific tolerability questions, and an evaluation of disease progression and survival were collected. Monthly quality of life (QoL) questionnaires (EORTC QLQ-C30 with BN-20) examined the trend of global health, psychosocial function, and symptom progression. Results Nine patients were enrolled with a median age of 47 (seven males; two females). Overall, compliance with TTF was 89% (range 16–97%). Only one patient failed to comply with treatment. Patients tolerated the device with minimal side effects. Eight patients described mild to moderate skin irritation, whilst all patients were keen to recommend the device to other patients (100%). Most patients found the weight and size of the device to be its biggest drawback (72%). Progression-free survival was 5.5 months and median overall survival was 14.9 months. Conclusions TTF was well-tolerated amongst a small cohort of UK patients, who were able to comply with treatment without any significant complication. QoL questionnaires showed no sustained deterioration in global health, physical and emotional function until the final months of life when the disease burden was greatest.

EXTH-34. ION CHANNELS AS A THERAPEUTIC TARGET IN PAEDIATRIC HIGH-GRADE GLIOMAS

Abstract Pediatric Glioblastoma Multiforme (GBM) is a leading cause of CNS cancer-related death in children. The scarcity of treatments for GBM has opened the field to new pathways in adults, such as tumour treating fields(TTF). Studies have identified the clinical benefit of electrotherapy in combination with chemotherapeutics, however the mechanistic action is unclear. Increasing evidence suggests that ion channels not only regulate electrical signalling of excitable cells, but are also crucial in the development/progression of brain tumours. Ion channels are essential in cell-cycle control, invasion and migration of cancer cells, therefore presenting as valuable therapeutic targets. Candidate ion channel genes(ICG) associated with high-grade glioma (HGG) were identified via analysis of inhouse and publicly available data sets. Expression patterns of selected ICGs were assessed along with clinician correlations.. Protein and RNA expression of target ICGs was assessed in pGBM cell lines/ TMAs. Finally, the Human ClariomTMS array was used for whole transcriptome gene expression analysis of paediatric GBM cell lines treated with tumour treating fields or low frequency electrical fields via deep brain stimulating electrodes. Paediatric brain tumour cells were exposed to genetic and pharmacological manipulation of CLIC1 and CLIC4 ion channels individually or in combination. We have shown that HGG exhibit increased expression of CLIC4 and CLIC1 at protein and RNA levels in both publically available data sets and inhouse cell lines / TMAs. Clinical correlation determined that high CLIC4 and CLIC1 expression was associated with poor overall survival. Further to this, DNA array analysis revealed a downregulation of CLIC1 and CLIC4 ion channels genes in KNS42 cells when treated with electrotherapy compared to untreated cells. Inhibition of CLIC1 and CLIC4 reduces Cl- flux across cell membranes and reduces cell proliferation. These data provide rationale that manipulation of ICGs will reduce the capacity of childhood brain tumours to proliferate and invade.

Electrotherapies for Glioblastoma.

Non‐thermal, intermediate frequency (100–500 kHz) electrotherapies present a unique therapeutic strategy to treat malignant neoplasms. Here, pulsed electric fields (PEFs) which induce reversible or irreversible electroporation (IRE) and tumour‐treating fields (TTFs) are reviewed highlighting the foundations, advances, and considerations of each method when applied to glioblastoma (GBM). Several biological aspects of GBM that contribute to treatment complexity (heterogeneity, recurrence, resistance, and blood‐brain barrier(BBB)) and electrophysiological traits which are suggested to promote glioma progression are described. Particularly, the biological responses at the cellular and molecular level to specific parameters of the electrical stimuli are discussed offering ways to compare these parameters despite the lack of a universally adopted physical description. Reviewing the literature, a disconnect is found between electrotherapy techniques and how they target the biological complexities of GBM that make treatment difficult in the first place. An attempt is made to bridge the interdisciplinary gap by mapping biological characteristics to different methods of electrotherapy, suggesting important future research topics and directions in both understanding and treating GBM. To the authors' knowledge, this is the first paper that attempts an in‐tandem assessment of the biological effects of different aspects of intermediate frequency electrotherapy methods, thus offering possible strategies toward GBM treatment.

Treatment options for progression or recurrence of glioblastoma: a network meta-analysis.

Treatment options for progression or recurrence of glioblastoma: a network meta-analysis.

A contemporary perspective on the diagnosis and treatment of diffuse gliomas in adults

Gliomas are intrinsic brain tumours, which are classified by the World Health Organization (WHO) into different grades of malignancy, with glioblastoma being the most frequent and most malignant subtype (WHO grade IV). Mutations in the isocitrate dehydrogenase (IDH) 1 or 2 genes are frequent in lower (WHO II/III) grade tumours but typically absent in classical glioblastoma. IDH mutations are associated with a better prognosis compared with IDH wild-type tumours of the same WHO grade. Following detection of a tumour mass by imaging, maximum safe surgery as feasible is commonly performed to reduce mass effect and to obtain tissue allowing histopathological diagnosis and molecular assessment. Radiotherapy has been the mainstay in the treatment of diffuse gliomas for several decades. It provides improved local control, but is not curative. Furthermore, several randomised trials have shown that the addition of alkylating chemotherapy, either temozolomide or nitrosourea-based regimens, to radiotherapy results in prolonged survival. Tumour-treating fields (TTFields) have emerged as an additional treatment option in combination with maintenance temozolomide treatment for patients with newly diagnosed glioblastoma. Treatment at recurrence is less standardised and depends on the patient&rsquo;s performance status, symptom burden and prior treatments. Bevacizumab prolongs progression-free survival in newly diagnosed and recurrent glioblastoma, but does not impact overall survival. However, in Switzerland and some other countries, it is still considered a valuable treatment option to reduce clinical symptom burden. Given the generally poor outcome for these patients, various novel treatment approaches are currently being explored within clinical trials including immunotherapeutic strategies such as immune checkpoint inhibition and the brain-penetrant proteasome inhibitor marizomib.

Treatment of newly diagnosed glioblastoma in the elderly: a network meta-analysis.

Treatment of newly diagnosed glioblastoma in the elderly: a network meta-analysis.

Barium Titanate Nanoparticles Sensitise Treatment-Resistant Breast Cancer Cells to the Antitumor Action of Tumour-Treating Fields

Although tumour-treating fields (TTFields) is a promising physical treatment modality based on disruption of dipole alignments and generation of dielectrophoretic forces during cytokinesis, not much is known about TTFields-responsive sensitisers. Here, we report a novel TTFields-responsive sensitiser, barium titanate nanoparticles (BTNPs), which exhibit cytocompatibility, with non-cytotoxic effects on breast cancer cells. BTNPs are characterised by high dielectric constant values and ferroelectric properties. Notably, we found that BTNPs sensitised TTFields-resistant breast cancer cells in response to TTFields. In addition, BTNPs accumulated in the cytoplasm of cancer cells in response to TTFields. Further, we showed that TTFields combined with BTNPs exhibited antitumor activity by modulating several cancer-related pathways in general, and the cell cycle-related apoptosis pathway in particular. Therefore, our data suggest that BTNPs increase the antitumor action of TTFields by an electric field-responsive cytosolic accumulation, establishing BTNP as a TTFields-responsive sensitiser.

The Glioma Elephant in The Room

Abstract Radiotherapy is the most effective treatment of glioblastoma, radical surgery and chemotherapy will help some patients. Tumour Treating Fields (TTF) is used in many countries in the developed world. Thousands of patients have been treated. Methods A survey at a neuro-oncology meeting of clinicians, scientists and charity members asking them about TTF. Results 1. 7 out of 8 clinicians did not discuss TTF with patients.: 2. The reasons being “not available”, “very expensive”, “don’t know enough”.: 3. Out of 17 non clinicians, 14 stated that TTF should be discussed with all patients.: 4. Out of 22 clinicians and non clinicians, 16 said they would consider trying to raise £200.000 for treatment from crowd funding. Discussion The report of the chief scientific officer of the department of health on brain tumours, the report of the Tessa Jowell funding, BNOS, do not discuss TTF.?why. NICE guidelines for NHS patients state “Do not offer TTF” but do not say “Do not discuss”. Conclusion Sadly, clinicians are not telling the patients about options for treatment. TTF is controversial and expensive and is now being used in several cancer treatments. The UK is one of the few developed countries that is not researching or discussing this treatment.

Wireless Bioelectronics Towards Treatment of Glioblastoma Multiforme

Abstract ‘Bioelectronic therapies’ are defined as treatments that provide therapy via electrical stimulation. As electrochemical signalling is a key communication pathway of the human body, learning and modulating these signals could allow us to regenerate lost functions and restore health where previously regarded impossible. Bioelectronics do not yet fully exploit this possibility as they lack resolution and plasticity to fully merge with biology. We aim to negate these problems by pioneering the development of wireless bioelectronics. One exciting area we hope this can be applied is that of tumour treating fields (TTFs). TTFs apply electric fields to a tumour region, providing a non-invasive anti-mitotic treatment modality. This anti-mitotic behaviour arises due to dipole alignment and di-electrophoresis. However, an understanding of the exact mode of action has not yet been reached. We aim to improve this knowledge by analysing how healthy astrocytes vs glioblastoma cells behave in various electrical systems: comparing ionic currents with electric fields. Furthermore, we hope to improve targeting of TTFs through the in-situ growth of conductive structures, via wireless electrochemistry. Proof of concept has been achieved by wirelessly growing silver micro-wires in the presence of U251 glioblastoma cells. Wire growth has been optimised without the presence of cells, allowing controlled growth direction via electrode geometry. Wires range from 2–9µm in diameter and have been shown to be conductive through the completion of a circuit lighting an LED. Such structures could ultimately be grown in the region of a tumour, therefore therapeutically targeting the electric field to that site.