Efficacy of Bortezomib for Treating Anti-Interferon-Gamma Autoantibody-Associated Adult-Onset Immunodeficiency Syndrome.

BACKGROUND: Currently, there is no effective treatment for adult-onset immunodeficiency (AOID) syndrome with anti-interferon-gamma autoantibodies (anti-IFN-γ-auto-Abs). This study aimed to investigate the effectiveness of bortezomib (BTZ) for decreasing anti-IFN-γ-auto-Abs. METHODS: A pre- and post-intervention study was conducted from February 2017 through June 2019 at Siriraj Hospital (Bangkok, Thailand). Five patients were invited to receive once-weekly BTZ (1.3 mg/m2 body surface area) subcutaneously for 8 weeks followed by oral cyclophosphamide (1 mg/kg/d) for 4 months. The primary outcomes were the difference in antibody level at 8 and 48 weeks compared with baseline and the incidence of serious adverse events (AEs). The secondary outcome was the occurrence of opportunistic infections (OIs) during the 72 weeks after starting BTZ. RESULTS: The median patient age was 46 years (range, 34-53). All patients had 3-5 OIs prior to enrollment. All patients were receiving antimycobacterial agents for treatment of nontuberculous mycobacterial infection at enrollment. There was no significant difference in the mean optical density of auto-Abs at 8 weeks (3.73 ± 0.72) or 48 weeks (3.74 ± 0.53) compared with baseline (3.84 ± 0.49; P = .336 and P = .555, respectively). However, after serum dilution, the antibody titer nonsignificantly decreased 8-16 weeks after BTZ initiation (P = .345). Ten OIs were observed 24-72 weeks after BTZ initiation. CONCLUSIONS: Treatment with BTZ followed by cyclophosphamide yielded no significant decrease in antibody titer levels, and 10 OIs were observed during 24-72 weeks of BTZ treatment. No serious AEs were observed. Combining rituximab with BTZ is likely necessary to prevent generation of new autoantibody-producing plasma cells. Clinical Trials Registration. NCT03103555.

Recent advances in Tumor Treating Fields (TTFields) therapy for glioblastoma.

Tumor Treating Fields (TTFields) therapy is a locoregional, anticancer treatment consisting of a noninvasive, portable device that delivers alternating electric fields to tumors through arrays placed on the skin. Based on efficacy and safety data from global pivotal (randomized phase III) clinical studies, TTFields therapy (Optune Gio) is US Food and Drug Administration-approved for newly diagnosed (nd) and recurrent glioblastoma (GBM) and Conformité Européenne-marked for grade 4 glioma. Here we review data on the multimodal TTFields mechanism of action that includes disruption of cancer cell mitosis, inhibition of DNA replication and damage response, interference with cell motility, and enhancement of systemic antitumor immunity (adaptive immunity). We describe new data showing that TTFields therapy has efficacy in a broad range of patients, with a tolerable safety profile extending to high-risk subpopulations. New analyses of clinical study data also confirmed that overall and progression-free survival positively correlated with increased usage of the device and dose of TTFields at the tumor site. Additionally, pilot/early phase clinical studies evaluating TTFields therapy in ndGBM concomitant with immunotherapy as well as radiotherapy have shown promise, and new pivotal studies will explore TTFields therapy in these settings. Finally, we review recent and ongoing studies in patients in pediatric care, other central nervous system tumors and brain metastases, as well as other advanced-stage solid tumors (ie, lung, ovarian, pancreatic, gastric, and hepatic cancers), that highlight the broad potential of TTFields therapy as an adjuvant treatment in oncology.

Triple-regulated conditionally replicating adenovirus for effective and safer treatment of peritoneal carcinomatosis.

There is no effective therapy for peritoneal carcinomatosis derived from gastric cancer. An ideal conditionally replicating adenovirus (CRA) that selectively replicates in and kills cancer cells has not been developed for gastric cancer-derived peritoneal carcinomatosis. Using our platform technology of CRA regulated and treating tumors with multiple factors (m-CRA), we generated two types of survivin-responsive m-CRAs, Surv.m-CRA-CMVp and Surv.m-CRA-CEAp, consisting of E1A downstream of the survivin promoter, and the mutated E1B gene downstream of the human cytomegalovirus immediate early gene enhancer/promoter and carcinoembryonic antigen promoter, respectively. Survivin mRNA was expressed at high and undetectable levels in two gastric cancer cells and eleven normal cells, respectively. Carcinoembryonic antigen was expressed at high and very low levels in MKN-45 gastric cancer and normal PrEC cells, respectively, and was not detected in other cell types. While both Surv.m-CRA-CEAp and Surv.m-CRA-CMVp exhibited potent cytotoxic effects on MKN-45 cells in vitro, Surv.m-CRA-CEAp significantly reduced cytotoxicity to normal cells compared to Surv.m-CRA-CMVp. Control mice that received an intraperitoneal injection of MKN-45 cells gradually lost body weight and died of peritoneal carcinomatosis within 98 days. In contrast, all mice receiving Surv.m-CRA-CEAp or Surv.m-CRA-CMVp-infected MKN-45 cells increased their body weight and survived 120 days. In conclusion, the triple-regulated Surv.m-CRA-CEAp enhances cancer specificity (i.e., safety) without reducing the potent therapeutic effect for carcinoembryonic antigen-positive gastric cancer-derived peritoneal carcinomatosis. The modified E1B promoter strategy of CRA facilitates the development of novel CRAs for the effective and safe treatment of a variety of refractory cancers.

A guided single session intervention to reduce intrusive memories of work-related trauma: a randomised controlled trial with healthcare workers in the COVID-19 pandemic.

BACKGROUND: Intrusive memories of psychologically traumatic events bring distress both sub-clinically and clinically. This parallel-group, two-arm randomised controlled trial evaluated the effect of a brief behavioural intervention on reducing intrusive memories in frontline healthcare workers exposed to traumatic events during the COVID-19 pandemic. METHODS: Participants with at least two intrusive memories of work-related trauma in the week before recruitment were randomised 1:1 to an imagery-competing task intervention (n = 73) or attention-based control task (n = 71). The number of intrusive memories was assessed at baseline and 5 weeks after the guided session (primary endpoint). RESULTS: The intervention significantly reduced intrusive memory frequency compared with control [intervention Mdn = 1.0 (IQR = 0-3), control Mdn = 5.0 (IQR = 1-17); p < 0.0001, IRR = 0.30; 95% CI = 0.17-0.53] and led to fewer post-traumatic stress-related symptoms at 1, 3 and 6 month follow-ups (secondary endpoints). Participants and statisticians were blinded to allocation. Adverse events data were acquired throughout the trial, demonstrating safety. There was high adherence and low attrition. CONCLUSIONS: This brief, single-symptom, repeatable digital intervention for subclinical-to-clinical samples after trauma allows scalability, taking a preventing-to-treating approach after trauma. TRIAL REGISTRATION: 2020-07-06, ClinicalTrials.gov identifier: NCT04460014.

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.

Comparative effectiveness of treating prenatal depression with counseling versus antidepressants in relation to preterm delivery.

BACKGROUND: Maternal depression during pregnancy is prevalent and has been associated with increased risk of preterm delivery. However, comparative effectiveness of 2 commonly used treatment options, mental health counseling and use of antidepressants, in mitigating the risk of preterm delivery associated with maternal depression remains uncertain. Although antidepressant use has been associated with increased risk of preterm delivery in many previous studies, a direct head-to-head comparison between these 2 treatment options has not been investigated. Thus, the comparative risk-benefit profiles of those 2 treatment options remain unclear. OBJECTIVE: To determine the comparative effectiveness of 2 commonly used options for treating prenatal depression in limiting the risk of preterm delivery associated with maternal depression. STUDY DESIGN: A large prospective cohort study was conducted among 82,170 pregnant women at Kaiser Permanente Northern California, an integrated health care delivery system. Clinically diagnosed depression and its treatments (use of antidepressants and mental health counseling) were identified from the Kaiser Permanente Northern California electronic health record system. Gestational age was also recorded for all deliveries and captured by electronic health records for determining preterm delivery. RESULTS: Using Cox proportional hazards regression incorporating propensity score methodology to ensure comparability between comparison cohorts, relative to those without depression, pregnant women with untreated depression had 41% increased risk of preterm delivery: adjusted hazard ratio=1.41, 95% confidence interval=1.24 to 1.60, confirming increased risk of preterm delivery associated underlying maternal depression. Relative to untreated depression, any mental health counseling was associated with an 18% of reduced risk of preterm delivery: adjusted hazard ratio=0.82 (0.71-0.96). The inverse association showed a dose-response pattern: increased number of counseling visits was associated with greater reduction in preterm delivery risk with 43% reduction in preterm delivery risk associated with 4 or more visits (adjusted hazard ratio=0.57, 95% confidence interval=0.45-0.73). In contrast, use of antidepressants during pregnancy was associated with an additional 31% increased risk of preterm delivery independent of underlying depression: adjusted hazard ratio=1.31, 95% confidence interval=1.06 to 1.61. This positive association also showed a dose-response relationship: a longer duration of use was associated with an even higher risk. CONCLUSION: This study provides much needed evidence regarding the comparative effectiveness of 2 common treatment options for prenatal depression in the context of preterm delivery risk. The results indicate that, to reduce preterm delivery risk due to maternal depression, mental health counseling is more effective. Use of antidepressants may add additional risk of preterm delivery, independent of the underlying depression. The findings provide data for clinicians and pregnant women to make informed and evidence-based treatment decisions that take into account the risks and benefits to both maternal and fetal health.

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.

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.

Voltage-Gated K+ Channel Modulation by Marine Toxins: Pharmacological Innovations and Therapeutic Opportunities.

Bioactive compounds are abundant in animals originating from marine ecosystems. Ion channels, which include sodium, potassium, calcium, and chloride, together with their numerous variants and subtypes, are the primary molecular targets of the latter. Based on their cellular targets, these venom compounds show a range of potencies and selectivity and may have some therapeutic properties. Due to their potential as medications to treat a range of (human) diseases, including pain, autoimmune disorders, and neurological diseases, marine molecules have been the focus of several studies over the last ten years. The aim of this review is on the various facets of marine (or marine-derived) molecules, ranging from structural characterization and discovery to pharmacology, culminating in the development of some "novel" candidate chemotherapeutic drugs that target potassium channels.

[Research progress in raw and processed Raphani Semen and prediction of quality markers].

Raphani Semen, with both edible and medicinal values, is a typical Chinese herbal medicine with different effects before and after processing. The raw helps ascending and the cooked helps descending. This paper comprehensively summarizes the differences in chemical constituents and pharmacological effects between raw and processed Raphani Semen that are reported in recent years. Based on the principle of quality markers(Q-markers) of traditional Chinese medicines, the chemical constituent sources, chemical constituent detection techniques, and correlation between bidirectional regulatory efficacy and chemical constituents are compared between raw and processed Raphani Semen. The results suggest that sulforaphene and glucoraphanin could be used as candidate Q-markers of raw and processed Raphani Semen, respectively. This review is expected to provide a reference for further research on the processing, new drug development, and improvement of safety and effectiveness of Raphani Semen in clinical application.

[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.

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

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

Association of Tumor Treating Fields (TTFields) therapy with survival in newly diagnosed glioblastoma: a systematic review and meta-analysis.

PURPOSE: Tumor Treating Fields (TTFields) therapy, an electric field-based cancer treatment, became FDA-approved for patients with newly diagnosed glioblastoma (GBM) in 2015 based on the randomized controlled EF-14 study. Subsequent approvals worldwide and increased adoption over time have raised the question of whether a consistent survival benefit has been observed in the real-world setting, and whether device usage has played a role. METHODS: We conducted a literature search to identify clinical studies evaluating overall survival (OS) in TTFields-treated patients. Comparative and single-cohort studies were analyzed. Survival curves were pooled using a distribution-free random-effects method. RESULTS: Among nine studies, seven (N = 1430 patients) compared the addition of TTFields therapy to standard of care (SOC) chemoradiotherapy versus SOC alone and were included in a pooled analysis for OS. Meta-analysis of comparative studies indicated a significant improvement in OS for patients receiving TTFields and SOC versus SOC alone (HR: 0.63; 95% CI 0.53-0.75; p < 0.001). Among real-world post-approval studies, the pooled median OS was 22.6 months (95% CI 17.6-41.2) for TTFields-treated patients, and 17.4 months (95% CI 14.4-21.6) for those not receiving TTFields. Rates of gross total resection were generally higher in the real-world setting, irrespective of TTFields use. Furthermore, for patients included in studies reporting data on device usage (N = 1015), an average usage rate of ≥ 75% was consistently associated with prolonged survival (p < 0.001). CONCLUSIONS: Meta-analysis of comparative TTFields studies suggests survival may be improved with the addition of TTFields to SOC for patients with newly diagnosed GBM.

Tumor Treating Fields (TTFields) increase the effectiveness of temozolomide and lomustine in glioblastoma cell lines.

PURPOSE: Tumor Treating Fields (TTFields) are electric fields that disrupt cellular processes critical for cancer cell viability and tumor progression, ultimately leading to cell death. TTFields therapy is approved for treatment of newly-diagnosed glioblastoma (GBM) concurrent with maintenance temozolomide (TMZ). Recently, the benefit of TMZ in combination with lomustine (CCNU) was demonstrated in patients with O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. The addition of adjuvant TTFields to TMZ plus CCNU further improved patient outcomes, leading to a CE mark for this regimen. The current in vitro study aimed to elucidate the mechanism underlying the benefit of this treatment protocol. METHODS: Human GBM cell lines with different MGMT promoter methylation statuses were treated with TTFields, TMZ, and CCNU, and effectiveness was tested by cell count, apoptosis, colony formation, and DNA damage measurements. Expression levels of relevant DNA-repair proteins were examined by western blot analysis. RESULTS: TTFields concomitant with TMZ displayed an additive effect, irrespective of MGMT expression levels. TTFields concomitant with CCNU or with CCNU plus TMZ was additive in MGMT-expressing cells and synergistic in MGMT-non-expressing cells. TTFields downregulated the FA-BRCA pathway and increased DNA damage induced by the chemotherapy combination. CONCLUSIONS: The results support the clinical benefit demonstrated for TTFields concomitant with TMZ plus CCNU. Since the FA-BRCA pathway is required for repair of DNA cross-links induced by CCNU in the absence of MGMT, the synergy demonstrated in MGMT promoter methylated cells when TTFields and CCNU were co-applied may be attributed to the BRCAness state induced by TTFields.

Availability and affordability of anticancer medicines at cancer treating hospitals in Rwanda.

BACKGROUND: Availability and accessibility of anti-cancer medicines is the pillar of cancer management, and it is one of the main concerns in low-income countries including Rwanda. The objective of this study was to assess the availability and affordability of anticancer medicines at cancer-treating hospitals in Rwanda. METHODOLOGY: A descriptive cross-sectional study was conducted at 5 cancer-treating hospitals in Rwanda. Quantitative data were collected from stock cards and software that manage medicines and included the availability of anti-cancer medicines at the time of data collection, their stock status within the last two years, and the selling price. RESULTS: The study found the availability of anti-cancer medicines at 41% in public hospitals at the time of data collection, and 45% within the last two years. We found the availability of anti-cancer medicines at 45% in private hospitals at the time of data collection, and 61% within the last two years. 80% of anti-cancer medicines in private hospitals were unaffordable while 20% were affordable. The public hospital that had most of the anti-cancer medicines in the public sector provided free services to the patients, and no cost was applied to the anti-cancer medicines. CONCLUSION: The availability of anti-cancer medicines in cancer-treating hospitals is low in Rwanda, and most of them are unaffordable. There is a need to design strategies that can increase the availability and affordability of anti-cancer medicines, for the patients to get recommended cancer treatment options.

The safety profile of Tumor Treating Fields (TTFields) therapy in glioblastoma patients with ventriculoperitoneal shunts.

INTRODUCTION: Tumor Treating Fields (TTFields, 200 kHz) therapy is a noninvasive, locoregional cancer treatment approved for use in newly diagnosed glioblastoma (GBM), recurrent GBM, and malignant pleural mesothelioma. GBM patients with hydrocephalus may require implantation of a ventriculoperitoneal (VP) shunt, however, the current TTFields therapy label does not include the use of VP shunts in GBM patients due to insufficient safety data. This analysis evaluates the safety of TTFields therapy use in this population. METHODS: Unsolicited post-marketing global surveillance data from patients with GBM and a VP shunt (programmable/non-programmable) who received TTFields therapy between November 2012-April 2021 were retrospectively analyzed. Adverse events (AEs) were assessed using the Medical Dictionary for Regulatory Activities version 24.0. RESULTS: Overall, 156 patients with VP shunts were identified and included in this analysis. In total, 77% reported ≥ 1 AE; the most common TTFields therapy-related AEs were non-serious and localized, beneath-array skin AEs (43%). The incidence and categories of AEs were comparable between patients with or without VP shunts. Six patients with VP shunts experienced seven serious TTFields therapy-related AEs: skin erosion at the shunt site (n = 3); wound dehiscence at the shunt site (n = 2) and at the resection scar (n = 2). No shunt malfunctions were deemed related to TTFields therapy. CONCLUSIONS: In the real-world setting, TTFields therapy in GBM patients with VP shunts demonstrated good tolerability and a favorable safety profile. There was no evidence that TTFields therapy disrupted VP shunt effectiveness. These results suggest TTFields therapy may be safely used in patients with VP shunts.

Newly Diagnosed Glioblastoma in Elderly Patients.

PURPOSE OF REVIEW: Elderly patients with newly diagnosed glioblastoma (eGBM) carry a worse prognosis compared with their younger counterparts. eGBM garners special attention due to the unique challenges, including increased treatment-associated toxicity, less relative benefit from aggressive therapy, medical comorbidities, and immunosuppression. The pivotal GBM trials excluded patients > 70 years old and the optimal treatment approach remains unsettled for eGBM. In this review, we analyze the historical evidence-based data for treating eGBM and discuss the future direction for managing this vulnerable population. RECENT FINDINGS: Treatment for eGBM continues to evolve. Therapy choice is guided by performance status and presence of O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation. For eGBM with good performance status, combinatorial hypofractionated radiation therapy (hRT) and temozolomide should be recommended. For those with poor performance status, further stratification based on MGMT promoter methylation test result is recommended. Single-agent temozolomide is a viable treatment option for MGMT methylated tumors (mMGMT); in particular, those classified with receptor tyrosine kinase II methylation. hRT alone can be considered in MGMT unmethylated (uMGMT) eGBM patients. As precision oncology continues to advance, effective targeted and immunotherapy may emerge as new treatment options for eGBM. Management of elderly patients with newly diagnosed GBM carries a unique set of challenges. Progress has been made in defining the optimal therapeutic approach for these patients, but many questions remain to be answered.

Perception of clinical research among patients and healthy volunteers of clinical trials.

PURPOSE: Clinical research relies on data from patients and volunteers, yet the target sample size is often not achieved. Here, we assessed the perception of clinical research among clinical trial participants to improve the recruitment process for future studies. METHODS: We conducted a single-center descriptive and exploratory study of 300 current or former participants in various phase I-III clinical trials. Questionnaires were either distributed to current clinical trial participants or emailed to former subjects. RESULTS: Subjects strongly agreed or agreed that contributing to improving medical care (> 81%), contributing to scientific research (> 79%), and trusting their treating physicians (> 77%) were motives for study participation. Among healthy volunteers, financial motives positively correlated with the number of clinical trials they had participated in (p < 0.05). Higher age positively correlated with expectation of best available treatment during study participation among patients (p < 0.05). Less than 8% of all subjects expressed "great concern" about the potential risks of sharing their personal information as part of the study. Subjects displayed "great trust" or "trust" in medical staff (86.6%) and in government research institutions (76.4%), and "very little trust" or "little trust" in pharmaceutical companies (35.4%) and health insurance companies (16.9%). CONCLUSION: Altruistic motives and trust in treating physicians were predominant motives for clinical trial participation. Older patients expected to receive the best available treatment during participation. Healthy volunteers who reported financial motives had participated in more clinical trials. Consistent with great trust in medical staff and government research institutions, little concern was expressed about the misuse of personal data during the trial.

Efficacy and safety of tumor-treating fields in recurrent glioblastoma: a systematic review and meta-analysis.

BACKGROUND: Tumor-treating fields (TTF) is a novel cancer treatment that uses alternating electric fields to interfere with tumor cell mitosis. It has been approved by the U.S. food and drug administration for the treatment of recurrent glioblastoma (rGBM). We designed this meta-analysis to evaluate the efficacy and safety of TTF in the treatment of rGBM. METHODS: The study was based on the PRISMA guideline. Systematic retrieval was performed in PubMed, Cochrane Library, and Embase databases. The outcomes were overall survival (OS) hazard ratio (HR), 1-year survival rate, and cutaneous toxicity. RESULTS: These studies included a total of 1048 rGBM patients who received TTF treatment. The overall survival time between the TTF group and the control group was HR 0.75 ([95%CI 0.63 to 0.89]; P = 0.001). Pooled 1-year overall survival rate and incidence of cutaneous toxicity were 0.47 and 0.48, respectively. Data were insufficient to evaluate the effect of MGMT methylation status and tumor recurrence times on heterogeneity. CONCLUSIONS: TTF therapy is effective for recurrent glioblastoma. However, most relevant trials should assess rGBM patient baseline characteristics such as age, KPS, MGMT methylation status, and number of tumor recurrence,. In addition, the risk of rashes caused by long-term wearing of devices should also be considered.

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.