Tumor treating fields (TTFields; 150 kHz) and FOLFOX combination treatment effects on gastric cancer in vitro.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 406-406
Author(s):  
Einav Zeevi ◽  
Karnit Gotlib ◽  
Rosa S Schneiderman ◽  
Mijal Munster ◽  
Yaara Porat ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Treatment ◽  
Combination Treatment ◽  
Apoptosis Induction ◽  
Optimal Frequency ◽  
Tumor Treating Fields ◽  
Cell Counts ◽  
Drug Concentrations ◽  
Clonogenic Potential ◽  
Gastric Cancer Treatment

406 Background: Gastric cancer is the third most common cause of cancer mortality worldwide, yet long-term survival in gastric cancer remains poor despite systemic therapeutic advances. FOLFOX (oxaliplatin, fluorouracil [5-FU], and leucovorin) is an approved chemotherapy regimen for gastric cancer treatment. Tumor Treating Fields (TTFields) are an antimitotic, loco-regional anticancer treatment delivered via non-invasive application of low intensity (1-3V/cm), intermediate frequency (100-500 kHz), alternating electrical fields. TTFields targets rapidly dividing cancer cells by disrupting microtubules leading to mitotic catastrophe, abnormal chromosome segregation, and apoptosis induction. We investigated the potential use of TTFields alone and in combination with FOLFOX for gastric carcinomas. Methods: Gastric cells (AGS and KATO III) were treated for 72 hours with TTFields (1.1 and 1.7 V/cm, respectively) at frequencies of 100-400 kHz using the inovitro system. Efficacy of TTFields and FOLFOX and its individual components was tested by applying TTFields at the optimal frequency in combination with various drug concentrations. Cell counts, apoptosis induction, clonogenic potential, and overall effect were determined. Results: The optimal TTFields frequency that led to the greatest cell count reduction (AGS, 55%; KATO III, 52%) was 150 kHz. The clonogenic potential was reduced by > 70% in both cell lines. TTFields combined with each FOLFOX component (oxaliplatin, 5-FU, or leucovorin) led to a significant reduction in AGS and KATO III cell survival (2-way ANOVA, P < 0.001 for each cell line) versus each treatment alone. In AGS, TTFields plus FOLFOX combination treatment led to a further reduction in the overall effect (cytotoxic and clonogenic; 79%) versus TTFields alone (65%) and FOLFOX alone (34%). Similar results were observed in KATO III cells. Conclusions: These results suggest that TTFields (150 kHz; optimal frequency) are an effective gastric cancer treatment; and combining TTFields with FOLFOX may further enhance efficacy. There is a strong rational to continue exploring the use of TTFields in combination with standard of care for gastric cancer treatment in the clinical settings.

The combined treatment of 150 kHz tumor treating fields (TTFields) and sorafenib inhibits hepatocellular carcinoma in vitro and in vivo.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15653-e15653 ◽  
Author(s):  
Uri Weinberg ◽  
Shiri Davidi ◽  
Catherine Tempel- Brami ◽  
Mijal Munster ◽  
Karnit Gotlib ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Combined Treatment ◽  
Control Group ◽  
Multikinase Inhibitor ◽  
Tumor Treating Fields ◽  
Cell Counts ◽  
Drug Concentrations ◽  
Clonogenic Potential ◽  
Hcc Cells

e15653 Background: Hepatocellular carcinoma (HCC) is the third cause of cancer related mortality and the primary cause of cancer death. Tumor Treating Fields (TTFields) therapy is an effective anti-neoplastic treatment modality delivered via noninvasive application of low intensity, intermediate frequency, alternating electric fields. Sorafenib, an oral multikinase inhibitor is approved for patients with advanced HCC, yet its survival benefit is still limited. In this work we explored the potential of the use of TTFields alone and in combination with Sorafenib as a treatment for HCC. Methods: HepG2 and Huh-7D12 cells were treated with various TTFields frequencies for 72 hours using the inovitro system. Efficacy of the combined treatment of TTFields and Sorafenib (36-3000 nM) was tested by applying TTFields at the optimal frequency together with various drug concentrations. Cell counts, induction of apoptosis, cell cycle and clonogenic potential were determined. TTFields (1.2 V/cm) and Sorafenib (10 mg/kg) were applied for 6 days to rats injected to the liver with N1S1 HCC cells. Tumor growth was followed using MRI. Results: The optimal TTFields frequency was 150 kHz for both cell lines. TTFields application (1.0 - 1.7 V/cm, 72 hours) at 150 kHz led to 36-40% reduction in cell counts and to additional reduction of over 70% in the clonogenic potential. The combined treatment of TTFields and Sorafenib led to a significant reduction in the number of cells (p < 0.001) as compared to each treatment alone. The averaged tumor volume fold increase of the combination treatment group was significantly lower than the one observed in the: control group, the TTFields group and the Sorafenib group. Conclusions: The results presented in this work demonstrate that TTFields can be an effective treatment against HCC cells and that the combination with Sorafenib may further enhance treatment efficacy.

In vitro and in vivo efficacy of the combined treatment of 150 khz tumor treating fields (TTFields) and sorafenib in hepatocellular carcinoma.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 333-333
Author(s):  
Uri Weinberg ◽  
Shiri Davidi ◽  
Karnit Gotlib ◽  
Einav Zeevi ◽  
Catherine Tempel- Brami ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Growth ◽  
Combined Treatment ◽  
Control Group ◽  
Multikinase Inhibitor ◽  
Tumor Treating Fields ◽  
Cell Counts ◽  
Drug Concentrations ◽  
Clonogenic Potential ◽  
Hcc Cells

333 Background: Hepatocellular carcinoma (HCC) is the third cause of cancer related mortality and the primary cause of cancer death. Sorafenib, an oral multikinase inhibitor is approved for patients with advanced HCC, yet its survival benefit is still limited. Tumor Treating Fields (TTFields) therapy is an effective anti-neoplastic treatment modality delivered via noninvasive application of low intensity, intermediate frequency, alternating electric fields. The aim of this work is to explore the potential of the use of TTFields alone and in combination with Sorafenib as a treatment for HCC. Methods: HepG2 and Huh-7D12 cells were treated with various TTFields frequencies for 72 hours using the inovitro system. Efficacy of the combined treatment of TTFields and Sorafenib (36-3000 nM) was tested by applying TTFields at the optimal frequency together with various drug concentrations. Cell counts, induction of apoptosis, cell cycle and clonogenic potential were determined. N1S1 HCC cells were injected to the left lobe of the liver of SD rats. After 1 week, TTFields (1.2 V/cm) and Sorafenib (10 mg/kg) were applied for 6 days and tumor growth was followed using MRI. Healthy rats were used to study safety of the use of TTFields (150 kHz) applied to the abdomen. Results: The optimal TTFields frequency was found to be 150 kHz for both cell lines. TTFields application (1.0 - 1.7 V/cm, 72 hours) at 150 kHz led to 53-64% reduction in cell counts and to additional reduction of over 70% in the clonogenic potential. The combined treatment of TTFields and Sorafenib led to a significant reduction in the number cells (2-way ANOVA, p < 0.001) as compared to each treatment alone. Tumor growth was significantly reduced by the combined group compared to the control group (student t test, p < 0.01). Safety studies did not reveal any adverse event associated with TTFields application to the rat abdomen. Conclusions: The results presented in this work demonstrate that TTFields can be a safe and effective treatment against HCC cells and that the combination with Sorafenib may further enhance treatment efficacy.

The combined treatment of 150 kHz tumor treating fields (TTFields) and cisplatin or pemetrexed inhibits mesothelioma cells in vitro and in vivo.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20069-e20069
Author(s):  
Uri Weinberg ◽  
Mijal Munster ◽  
Karnit Gotlib ◽  
Rosa S. Schneiderman ◽  
Yaara Porat ◽  
...  
Keyword(s):  
Overall Survival ◽  
Asbestos Exposure ◽  
Combined Treatment ◽  
Control Group ◽  
Optimal Frequency ◽  
Cell Counts ◽  
Drug Concentrations ◽  
Clonogenic Potential ◽  
Induction Of Apoptosis

e20069 Background: Malignant pleural mesothelioma (MPM) is an aggressive thoracic cancer mostly linked to asbestos exposure. The standard of care (SOC) therapy for unresectable MPM is cisplatin plus pemetrexed. Treating Fields (TTFields) therapy is an effective anti-neoplastic treatment modality delivered via noninvasive application of low intensity, intermediate frequency, alternating electric fields. We explored the potential use of TTFields alone and in combination with SOC as a treatment for MPM. Methods: NCI-H2052 and MSTO-211H cells were treated at various TTFields frequencies for 72 hours using the inovitro system. The combined treatment of TTFields and cisplatin or pemetrexed was tested by applying TTFields at the optimal frequency together with various drug concentrations. Cell counts, clonogenic potential and induction of apoptosis were determined. TTFields (1.2 V/cm) were applied for 8 days to rats injected to the intrapleural cavity with IL-45 cells, and overall survival was tested. Results: TTFields optimal frequency was 150 kHz for both human cell lines. TTFields application (1.1 V/cm, 72 hours) at 150 kHz led to 45%-51% reduction in cell counts and 46-64%% additional reduction in clonogenic potential. The combined treatment of TTFields and cisplatin or pemetrexed led to a significant reduction in cell count, induction of apoptosis and reduced clonogenic potential as compared to each modality alone (p < 0.0001(. TTFields significantly prolonged the survival of rats compared to control group. Safety studies did not reveal any adverse events associated with 150 kHz TTFields application to the rat torso. Conclusions: These results demonstrate that TTFields can be an effective treatment against mesothelioma and the combination with cisplatin or pemetrexed may further enhance treatment efficacy. These results are in consistency with the recent phase 2 study (EF-23 trial) that showed improved overall survival for combined treatment as compared to historical control with no increase in systemic toxicity.

Trastuzumab for gastric cancer treatment – Authors' reply

The Lancet ◽  
2010 ◽  
Vol 376 (9754) ◽  
pp. 1736-1737
Author(s):  
Alastair J Munro ◽  
Paddy G Niblock
Keyword(s):  
Gastric Cancer ◽  
Cancer Treatment ◽  
Gastric Cancer Treatment

scholarly journals II BRAZILIAN CONSENSUS ON GASTRIC CANCER BY THE BRAZILIAN GASTRIC CANCER ASSOCIATION

2020 ◽  
Vol 33 (2) ◽  
Author(s):  
Leandro Cardoso BARCHI ◽  
Marcus Fernando Kodama Pertille RAMOS ◽  
André Roncon DIAS ◽  
Nelson Adami ANDREOLLO ◽  
Antônio Carlos WESTON ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Literature Review ◽  
Cancer Treatment ◽  
New Concepts ◽  
New Knowledge ◽  
Gastric Cancer Treatment

ABSTRACT Background: Since the publication of the first Brazilian Consensus on Gastric Cancer (GC) in 2012 carried out by the Brazilian Gastric Cancer Association, new concepts on diagnosis, staging, treatment and follow-up have been incorporated. Aim: This new consensus is to promote an update to professionals working in the fight against GC and to provide guidelines for the management of patients with this condition. Methods: Fifty-nine experts answered 67 statements regarding the diagnosis, staging, treatment and prognosis of GC with five possible alternatives: 1) fully agree; 2) partially agree; 3) undecided; 4) disagree and 5) strongly disagree A consensus was adopted when at least 80% of the sum of the answers “fully agree” and “partially agree” was reached. This article presents only the responses of the participating experts. Comments on each statement, as well as a literature review, will be presented in future publications. Results: Of the 67 statements, there was consensus in 50 (74%). In 10 declarations, there was 100% agreement. Conclusion: The gastric cancer treatment has evolved considerably in recent years. This consensus gathers consolidated principles in the last decades, new knowledge acquired recently, as well as promising perspectives on the management of this disease.

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