Radiological response patterns in the phase 2 STELLAR trial of TTFields with chemotherapy for first-line treatment of malignant pleural mesothelioma (MPM).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8551-8551
Author(s):  
Federica Grosso ◽  
Giovanni Luca Ceresoli
Keyword(s):  
Disease Progression ◽  
Electric Fields ◽  
Combined Therapy ◽  
Response Duration ◽  
Standard Of Care ◽  
First Line ◽  
Current Standard ◽  
Median Response ◽  
Tumor Treating Fields

8551 Background: Tumor Treating Fields (TTFields) are an anti-mitotic, regional treatment modality, utilizing low intensity alternating electric fields delivered non-invasively to the tumor using a portable, medical device. TTFields have significantly extended survival of patients with glioblastoma. In-vitro, human MPM cells were highly susceptible to TTFields. In the STELLAR study, patients with unresectable MPM treated with first line chemotherapy in combination with TTFields had a significantly higher median overall survival compared to historical controls (18.2 vs. 12.1 months). We report on analysis of radiological data from STELLAR patients whose tumors responded while receiving the combined therapy. Methods: The STELLAR trial accrued 80 patients with unresectable, previously untreated mesothelioma. Patients were treated with continuous 150 kHz TTFields (>18h/day) in combination with pemetrexed and cisplatin or carboplatin (at standard dosing). Inclusion criteria included ECOG PS of 0-1, pathologically proven mesothelioma and at least one measurable lesion according to modified RECIST criteria. Patients were followed q3w (CT scan q6w) until disease progression. Radiological assessments were done at each study site. Results: Partial responses (PRs) were seen in 40.3% of evaluable patients and clinical benefit (PR+SD) was seen in 97.2% of these patients. The median time between treatment start and PR was 1.8 months (range: 1.4-4.4 months). All patients presenting with PR during the STELLAR study had continuous reduction in the total sum of lesion diameters, suggesting no initial / pseudo-progression. 83% of the patients who responded to the combined therapy finally had disease progression within a median response duration of 5.7 months (range: 1.4-13 months), per Kaplan-Meier Estimator. One patient did not progress for more than 27 months. Conclusions: The STELLAR study met its primary endpoint of significant survival extension for previously untreated mesothelioma patients. Response rates were similar to the ones reported for the current standard of care treatment, but lasted longer with the addition of TTFields. Clinical trial information: NCT02397928.

scholarly journals Antitumor Activity of Curcumin in Glioblastoma

2020 ◽  
Vol 21 (24) ◽  
pp. 9435
Author(s):  
Blake C. Walker ◽  
Sandeep Mittal
Keyword(s):  
Curcuma Longa ◽  
Malignant Gliomas ◽  
Standard Of Care ◽  
Additional Treatment ◽  
Treatment Modalities ◽  
Molecular Signaling ◽  
Current Standard ◽  
Traditional Medicines ◽  
Tumor Treating Fields

Current standard-of-care treatment for glioblastoma, the most common malignant primary central nervous system (CNS) tumor, consists of surgical resection followed by adjuvant chemotherapy and radiation (Stupp protocol), providing an overall median survival of 15 months. With additional treatment using tumor-treating fields (Optune® therapy, Novocure Ltd., Haifa, Israel), survival can be extended up to 20 months. In spite of significant progress in our understanding of the molecular pathogenesis, the prognosis for patients with malignant gliomas remains poor and additional treatment modalities are critically needed. Curcumin is a bright yellow pigment found in the rhizome of the widely utilized spice, turmeric (Curcuma longa). It has long been used in South Asian traditional medicines and has been demonstrated to have in vitro antioxidant, anti-inflammatory, and antiproliferative effects. Curcumin has been demonstrated to induce multiple cytotoxic effects in tumor cells including cell cycle arrest, apoptosis, autophagy, changes in gene expression, and disruption of molecular signaling. Additionally, curcumin has been shown to potentiate the effect of radiation on cancer cells, while exhibiting a protective effect on normal tissue. Curcumin’s positive safety profile and widespread availability make it a promising compound for future clinical trials for high-grade gliomas.

scholarly journals Antitumor Activity of Nanoparticles Loaded with PHT-427, a Novel AKT/PDK1 Inhibitor, for the Treatment of Head and Neck Squamous Cell Carcinoma

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1242
Author(s):  
Joaquín Yanes-Díaz ◽  
Raquel Palao-Suay ◽  
María Rosa Aguilar ◽  
Juan Ignacio Riestra-Ayora ◽  
Antonio Ferruelo-Alonso ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Polymeric Nanoparticles ◽  
Growth Factor Receptor ◽  
Standard Of Care ◽  
Neck Squamous Cell Carcinoma ◽  
Current Standard

Currently, new treatments are required to supplement the current standard of care for head and neck squamous cell carcinoma (HNSCC). The phosphatidylinositol3-kinase (PI3K) signaling pathway is commonly altered and activated in HNSCC. PHT-427 is a dual PI3K-mammalian target of the AKT/PDK1 inhibitor; however, to the best of our knowledge, the effect of the PHT-427 inhibitor on HNSCC has not been investigated. This study aims to evaluate the antitumoral effect of PHT-427-loaded polymeric nanoparticles based on α-tocopheryl succinate (α-TOS). The in vitro activity of PHT-427 was tested in hypopharynx carcinoma squamous cells (FaDu) to measure the cell viability, PI3KCA/AKT/PDK1 gene expression, and PI3KCA/AKT/PDK1 levels. Apoptosis, epidermal growth factor receptor (EGFR), and reactive oxygen species (ROS) were also measured. The presence of PHT-427 significantly enhances its antiproliferative and proapoptotic activity by inactivating the PI3K/AKT/PDK1 pathway. Nanoparticles (NPs) effectively suppress AKT/PDK1 expression. Additionally, NPs loaded with PHT-427 produce high oxidative stress levels that induce apoptosis. In conclusion, these results are promising in the use of this nanoformulation as a PHT-427 delivery system for effective HNSCC treatment.

scholarly journals In Vitro Activity of Lefamulin against Sexually Transmitted Bacterial Pathogens

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Susanne Paukner ◽  
Astrid Gruss ◽  
Jørgen Skov Jensen
Keyword(s):  
Chlamydia Trachomatis ◽  
Bacterial Pathogens ◽  
Mycoplasma Genitalium ◽  
Standard Of Care ◽  
Multidrug Resistant ◽  
In Vitro Activity ◽  
First Line ◽  
Content Type ◽  
Sexually Transmitted

ABSTRACT The pleuromutilin antibiotic lefamulin demonstrated in vitro activity against the most relevant bacterial pathogens causing sexually transmitted infections (STI), including Chlamydia trachomatis (MIC 50/90 , 0.02/0.04 mg/liter; n = 15), susceptible and multidrug-resistant Mycoplasma genitalium (MIC range, 0.002 to 0.063 mg/liter; n = 6), and susceptible and resistant Neisseria gonorrhoeae (MIC 50/90 , 0.12/0.5 mg/liter; n = 25). The results suggest that lefamulin could be a promising first-line antibiotic for the treatment of STI, particularly in populations with high rates of resistance to standard-of-care antibiotics.

scholarly journals In VitroandIn VivoActivities of Zinc Linolenate, a Selective Antibacterial Agent againstHelicobacter pylori

2019 ◽  
Vol 63 (6) ◽  
Author(s):  
Yanqiang Huang ◽  
Xudong Hang ◽  
Xueqing Jiang ◽  
Liping Zeng ◽  
Jia Jia ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Therapeutic Potential ◽  
Combined Therapy ◽  
Peptic Ulcers ◽  
Current Standard ◽  
Gastric Diseases ◽  
Content Type ◽  
H Pylori

ABSTRACTHelicobacter pyloriis a major global pathogen, and its infection represents a key factor in the etiology of various gastric diseases, including gastritis, peptic ulcers, and gastric carcinoma. The efficacy of current standard treatment forH. pyloriinfection including two broad-spectrum antibiotics is compromised by toxicity toward the gut microbiota and the development of drug resistance, which will likely only be resolved through novel and selective antibacterial strategies. Here, we synthesized a small molecule, zinc linolenate (ZnLla), and investigated its therapeutic potential for the treatment ofH. pyloriinfection. ZnLla showed effective antibacterial activity against standard strains and drug-resistant clinical isolates ofH. pyloriin vitrowith no development of resistance during continuous serial passaging. The mechanisms of ZnLla action againstH. pyloriinvolved the disruption of bacterial cell membranes and generation of reactive oxygen species. In mouse models of multidrug-resistantH. pyloriinfection, ZnLla showedin vivokilling efficacy comparable and superior to the triple therapy approach when use as a monotherapy and a combined therapy with omeprazole, respectively. Moreover, ZnLla treatment induces negligible toxicity against normal tissues and causes minimal effects on both the diversity and composition of the murine gut microbiota. Thus, the high degree of selectivity of ZnLla forH. pyloriprovides an attractive candidate for novel targeted anti-H. pyloritreatment.

scholarly journals Left Atrial Appendage Closure Devices For Stroke Prevention

2014 ◽  
Vol 3 (1) ◽  
pp. 25-29 ◽  
Author(s):  
Sunil Kapur ◽  
Moussa Mansour
Keyword(s):  
Left Atrial ◽  
Left Atrial Appendage ◽  
Standard Of Care ◽  
Atrial Appendage ◽  
First Line ◽  
Current Standard ◽  
First Line Therapy ◽  
Line Therapy ◽  
Patients At Risk ◽  
Review Current

Cardioembolic stroke is a major cause of morbidity and mortality in patients with atrial fibrillation (AF). The left atrial appendage (LAA) is the prominent source of clot formation. While systemic anticoagulation is the current standard of care, anticoagulants carry many contraindications and possible complications. Techniques for elimination of the LAA are in various stages of development and early clinical use. In the coming years, accumulating data will help guide the management of AF patients at risk of bleeding as well as potentially become first-line therapy to reduce the risk of thromboembolic stroke. The purpose of this article is to review current endovascular and epicardial catheter-based LAA occlusion devices and the clinical data supporting their use.

scholarly journals EXTH-31. COMBINATION OF TUMOR TREATING FIELDS (TTFIELDS) AND PACLITAXEL PRODUCES ADDITIVE REDUCTIONS IN PROLIFERATION AND CLONOGENICITY IN PATIENT-DERIVED METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) CELLS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi88-vi88
Author(s):  
Sharon Michelhaugh ◽  
Sandeep Mittal
Keyword(s):  
Brain Metastases ◽  
Clonogenic Assay ◽  
Brain Lesion ◽  
Left Lung ◽  
Standard Of Care ◽  
Cell Number ◽  
Tumor Treating Fields ◽  
Institutional Review ◽  
Previously Treated

Abstract Clinical trials are underway to test the efficacy of TTFields in patients with progressive NSCLC or NSCLC brain metastases following standard-of-care or radiosurgery, respectively. Our study utilized patient-derived cells isolated from NSCLC brain metastases from a patient previously treated with standard-of-care chemo-radiation prior to progression to brain metastasis. These patient-derived cells underwent TTFields application in vitro with and without paclitaxel to determine if the response to the combination of TTFields with paclitaxel would be different from either treatment alone. Use of patient tissues was approved by the Institutional Review Board. Written informed consent was obtained from the patient, who was 60 years-old and female. She received concurrent carboplatin/paclitaxel and radiotherapy to the upper lobe of her left lung prior to discovery and resection of a solitary brain lesion. Cells isolated from the metastatic brain tumor were cultured for 3 passages prior to plating on coverslips (4×104 each) in DMEM/F12 media with 10% fetal bovine serum. TTFields were applied at ~1.6 V/cm at 150 kHz. Paclitaxel was added to the media to a final concentration of 5 nM. After 14 days, cell lysates were assayed for lactase dehydrogenase (LDH) to represent cell number (n=5) or were harvested and replated in triplicate for the clonogenic assay (n=3). Groups were compared with one-way ANOVA. Mean ± SD of LDH for the control, TTFields-alone, paclitaxel-alone, and the combination were 1.83 ± 0.09, 1.34 ± 0.15, 0.81 ± 0.04, and 0.46 ± 0.21, respectively (ANOVA p< 0.0001). Clonogenic assay counts for the same groups were 26641 ± 4625, 17399 ± 5998, 8697 ± 1617, and 1598 ± 598 (ANOVA p= 0.0003). The additive effects of TTFields and paclitaxel suggest that they target different cell populations within a heterogeneous tumor, and that patients previously treated with standard-of-care may benefit from TTFields therapy.

scholarly journals Response to Immunotherapy in Combination With Mitotane in Patients With Metastatic Adrenocortical Cancer

2019 ◽  
Vol 3 (12) ◽  
pp. 2295-2304 ◽  
Author(s):  
Lia Head ◽  
Katja Kiseljak-Vassiliades ◽  
Toshimasa J Clark ◽  
Hilary Somerset ◽  
Jonathan King ◽  
...  
Keyword(s):  
Evaluation Criteria ◽  
Standard Of Care ◽  
Response Evaluation ◽  
Adrenocortical Cancer ◽  
First Line ◽  
Current Standard ◽  
Dismal Prognosis ◽  
Grade 3 ◽  
Combined Immunotherapy ◽  
First Line Treatment

Abstract Adrenocortical carcinoma (ACC) is a rare orphan disease with a dismal prognosis. Surgery remains the first-line treatment, but most patients eventually develop metastatic disease. Mitotane is often used with chemotherapy with modest success. Little information is available concerning the efficacy of immunotherapy in combination with mitotane. We conducted a retrospective review of our initial six patients with metastatic ACC, for whom mitotane alone or with chemotherapy failed, and who were subsequently treated with a combination of pembrolizumab and mitotane, between July 2016 and March 2019. Imaging was analyzed per Response Evaluation Criteria in Solid Tumours 1.1 criteria. Two patients had a partial response and four patients had stable disease (8 to 19 months). One patient had grade 3 hepatitis and pembrolizumab was discontinued after 8 months. She died with disease progression 16 months after initiating pembrolizumab. One patient developed brain metastasis after 19 months of treatment and was transitioned to hospice. One patient had focal pneumonitis after 18 months of treatment, and pembrolizumab was discontinued. Three remaining patients continue pembrolizumab plus mitotane at the time of this writing. The current standard of care for ACC is a combination of etoposide, doxorubicin, cisplatin, and mitotane with an overall survival of 14.8 months. All six patients lived for at least 16 months after starting pembrolizumab added to mitotane therapy. The therapy appeared to be effective in both microsatellite instability-high and microsatellite stable tumors, suggesting some synergistic effect with mitotane. Combined immunotherapy and mitotane should be considered in future clinical trials in patients with ACC.

scholarly journals Radiotherapy of glioblastoma 15 years after the landmark Stupp’s trial: more controversies than standards?

2018 ◽  
Vol 52 (2) ◽  
pp. 121-128 ◽  
Author(s):  
Tomas Kazda ◽  
Adam Dziacky ◽  
Petr Burkon ◽  
Petr Pospisil ◽  
Marek Slavik ◽  
...  
Keyword(s):  
Concurrent Chemoradiotherapy ◽  
Standard Of Care ◽  
Primary Brain Tumor ◽  
Current Standard ◽  
Tumor Treating Fields ◽  
Integrated Boost ◽  
Hippocampal Sparing ◽  
New Treatment ◽  
Personalized Approach

Abstract Background The current standard of care of glioblastoma, the most common primary brain tumor in adults, has remained unchanged for over a decade. Nevertheless, some improvements in patient outcomes have occurred as a consequence of modern surgery, improved radiotherapy and up-to-date management of toxicity. Patients from control arms (receiving standard concurrent chemoradiotherapy and adjuvant chemotherapy with temozolomide) of recent clinical trials achieve better outcomes compared to the median survival of 14.6 months reported in Stupp’s landmark clinical trial in 2005. The approach to radiotherapy that emerged from Stupp’s trial, which continues to be a basis for the current standard of care, is no longer applicable and there is a need to develop updated guidelines for radiotherapy within the daily clinical practice that address or at least acknowledge existing controversies in the planning of radiotherapy. The goal of this review is to provoke critical thinking about potentially controversial aspects in the radiotherapy of glioblastoma, including among others the issue of target definitions, simultaneously integrated boost technique, and hippocampal sparing. Conclusions In conjunction with new treatment approaches such as tumor-treating fields (TTF) and immunotherapy, the role of adjuvant radiotherapy will be further defined. The personalized approach in daily radiotherapy practice is enabled with modern radiotherapy systems.

scholarly journals Tumor treating fields in the management of Glioblastoma: opportunities for advanced imaging

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Vikram S. Soni ◽  
Ted K. Yanagihara
Keyword(s):  
Clinical Trials ◽  
Cancer Therapy ◽  
Electric Fields ◽  
Randomized Clinical Trials ◽  
Phase Iii ◽  
Imaging Biomarkers ◽  
Tumor Treating Fields ◽  
Alternating Electric Fields ◽  
Promising Line

AbstractAlternating 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.

Novel Neonatal Umbilical Catheter Protection and Stabilization Device in In vitro Model of Catheterized Human Umbilical Cords: Effect of Material and Venting on Bacterial Colonization

2019 ◽  
Author(s):  
Lauren S. Y. Wood ◽  
Janene H. Fuerch ◽  
Carl L. Dambkowski ◽  
Eric F. Chehab ◽  
Shivani Torres ◽  
...  
Keyword(s):  
Bacterial Colonization ◽  
Bacterial Load ◽  
Standard Of Care ◽  
Adhesive Tape ◽  
Human Umbilical Cord ◽  
Current Standard ◽  
Central Lines ◽  
Umbilical Cords

Abstract Objective Umbilical central lines deliver life-saving medications and nutrition for neonates; however, complications associated with umbilical catheters (UCs) occur more frequently than in adults with central lines (i.e., line migration, systemic infection). We have developed a device for neonatal UC protection and stabilization to reduce catheter exposure to bacteria compared with the standard of care: “goal post” tape configuration. This study analyzes the effect of device venting and material on bacterial load of human umbilical cords in vitro. Study Design Catheters were inserted into human umbilical cord segments in vitro, secured with plastic or silicone vented prototype versus tape, and levels of bacterial colonization were compared between groups after 7 days of incubation. Results Nonvented plastic prototype showed increased bacterial load compared with goal post (p = 0.04). Colonization was comparable between the goal post and all vented plastic prototypes (p ≥ 0.30) and when compared with the vented silicone device (p = 1). Conclusion A novel silicone device does not increase external bacterial colonization compared with the current standard of care for line securement, and may provide a safe, convenient alternative to standard adhesive tape for UC stabilization. Future studies are anticipated to establish safety in vivo, alongside benefits such as migration and infection reduction.

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