Low energy amplitude modulated radiofrequency electromagnetic fields in combination with standard treatment or as monotherapy to show improvement in quality of life in patients with advanced hepatocellular carcinoma.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 290-290
Author(s):  
Micelange Carvalho Sousa ◽  
Frederico Costa ◽  
Pablo Diego Lima ◽  
Yone De Camargo Setogute ◽  
Brenda Pires Gumz ◽  
...  

290 Background: Hepatocellular carcinoma (HCC) is a fatal cancer without curative option for most patients. Hence the importance to improve health related quality of life (HRQoL). Amplitude-modulated radiofrequency electromagnetic fields (EMF), as a novel and non-toxic therapy, has potential for improving HRQoL in advanced HCC patients. Methods: An open-label, single center, prospective clinical protocol was performed in advanced HCC patients as an initial and salvage treatment modality. Systemic exposure to EMF was used in combination with a systemic conventional treatment or as a single treatment. A spoon-shaped antenna placed in the oral cavity delivered EMF over 90 minutes with monthly repetitions until death or consent withdrawal. The effect on HRQoL was the primary objective of this study. Patients answered the EORTC-C30 v3.0 questionnaires prior to every EMF exposure. Clinically meaningful change (CMC) and time to deterioration (TTD) for Global Health (QoL), Role Functioning (RF) and Physical Functioning (PF) were used in the analysis. Results: From March 2018 to April 2020, 55 advanced HCC patients were submitted to 373 EMF exposures. 41/55 (75%) patients had repetitive exposures (mean # 4, ranging from 2-16). 87% were male, median age was 67, 84% were BLCL-C, 16% were Child-Pugh B, 29% had extra-hepatic metastasis, 55% had failed previous treatment and 71% had documented radiological progression. 31(56%) patients received EMF in combination with systemic therapy (28 TKI and 3 anti-PDL1). 24 patients received EMF as a single treatment modality. The mean baseline score was 68.1 for QoL and 77.1 for RF and PF. 61%, 76% and 49% of patients experienced positive change in QoL, RF and PS scores immediately prior to the second exposure, respectively. +CMC was reported in 20%, 17% and 32% of patients, respectively for QoL, RF and PS. The median QoL TTD was not reached. The median RF TTD was 7.2 month and the median PF TTD was 11.9 month. The median RF TTD for patients in combination treatment was 11.4 months and in a single treatment was 13.5 month. The median PF TTD for patients in combination treatment was 12.8 months and in single treatment was 14.5 month. Conclusions: Advanced HCC patients showed positive changes in QoL, RF and PF HRQoL scores after single exposure to EMF. The benefit from EMF in HRQoL was durable both in combination with TKI or as a single modality in advanced HCC patients. These results support future development as a novel palliative treatment modality in advanced HCC patients. Clinical trial information: NCT 01686412.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 332-332
Author(s):  
Hugo Jimenez ◽  
Minghui Wang ◽  
Jacquelyn W. Zimmerman ◽  
Michael J. Pennison ◽  
Sambad Sharma ◽  
...  

332 Background: Amplitude-modulated 27.12 MHz radiofrequency electromagnetic fields (AM RF EMF) delivered via a spoon-shaped antenna placed on the patient’s tongue result in shrinkage of the primary and metastatic tumors in patients with advanced hepatocellular carcinoma (HCC). (Costa FP, et al. Br J Cancer. 2011;105:640-648.) The mechanism by which AM RF EMF have direct antiproliferative effect and disruption of the mitotic spindle on cancer cells is largely unknown. (Zimmerman JW, et al. Br J Cancer. 2012;106:307-313.) Methods: We assessed the Specific Absorption Rate (SAR) level and distribution inside the human body. In vitro experiments with HCC cells were performed as previously described (Zimmerman). Immunodeficient mice were subcutaneously implanted with Huh-7 HCC cells or patient-derived xenografts (PDX). Mice were exposed to HCC-specific AM RF EMF using systems replicating human exposure levels and treatment duration. Tumor samples were examined for EMT and cell cycle markers. Results: Intrabuccal delivery results in whole-body absorption of AM RF EMF. Proliferation of hepatitis B positive and negative cell lines as well as HCC cancer stem cells (CSCs) are blocked by AM RF EMF through Cav 3.2 T-type voltage gated calcium channels (VGCC). Proliferation of HCC is inhibited in vivo and tumor shrinkage occurs by dedifferentiation of HCC cells into quiescent myofibroblasts while the growth of intestinal and blood marrow cells is unaltered. Conclusions: Whole-body SAR ranges from 0.2 to 1 mW/kg and is significantly below the international safety limits for human exposure. Intrabucally-administered AM RF EMF is a novel targeted therapy for systemic treatment of advanced HCC with minimal off target effects. Inhibition of HCC CSCs may explain the extremely long term survival (>5 years) of several patients with advanced HCC.


2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 332-332
Author(s):  
Yone De Camargo Setogute ◽  
Frederico Costa ◽  
Micelange Carvalho Sousa ◽  
Pablo Diego Lima ◽  
Luciana Carvalho ◽  
...  

332 Background: Exposure to amplitude-modulated radiofrequency electromagnetic fields (EMF) in immortalized hepatocellular carcinoma (HCC) cell cultures and xenograft models demonstrated anti-tumor effect. Patients with advanced HCC exposed to systemic EMF showed objective response with potential survival benefit. Methods: An open-label, single center, prospective clinical protocol was performed in advanced HCC patients as an initial, second or third treatment modality. Systemic exposure to EMF modulated at patient-specific frequencies was applied as an add-on strategy (combination) to systemic conventional treatment or as a single therapeutic modality. A spoon-shaped antenna placed in the oral cavity delivered EMF over 90 minutes with monthly repetitions until death or consent of withdrawal. The primary objective was overall survival (OS) in comparison with historical control group of 45 advanced patients HCC from the same institution. Retrospective radiological review was conducted by two independent radiologists for objective response (OR) using RECIST1.1 criterion. Results: From March 2018 to April 2020, 55 advanced HCC patients were submitted to 373 EMF exposures. 87% were male, median age of 67, 84% were BLCL-C, 16% were Child-Pugh B, 29% had extra-hepatic metastasis, 55% had failed previous treatment and 71% had documented radiological progression. 31(56%) patients received EMF in combination with systemic therapy (25 sorafenib, 3 lenvatinib, 3 nivolumab). 24 patients received EMF as single treatment modality. The median OS for the entire patient cohort was 11.5 months. The median OS for combination treatment was 12.0 month and the median OS for single modality was 11.3 months. The median OS for the historical control was 5.3 month. The median OS from the entire cohort and the historical control were significant different (p = 0.0026) but the median OS from combination and single modality were not (p = 0.3434). Radiological images were available from 38(69%) patients. There were 6/38 (16%) documented objective responses (1 CR and 5 PR) and 30/38 (79%) patients experienced disease control. 4/21 (19%) OR were in patients using TKIs + EMF and 2/17 (12%) OR were in patients using EMF alone. Conclusions: EMF showed objective anti-tumor effect in combination with TKI or as single modality in advanced HCC patients. EMF showed improvement in overall survival in comparison with the historical control group supporting future development as a novel systemic treatment modality in advanced HCC patients. Clinical trial information: NCT 01686412.


Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 861 ◽  
Author(s):  
Kehua Zhou ◽  
Christos Fountzilas

Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers worldwide; most patients are diagnosed with advanced disease for which there is no known cure. Tremendous progress has been made over the past decade in the development of new agents for HCC, including small-molecule kinase inhibitors such as sorafenib, lenvatinib, cabozantinib, regorafenib, and monoclonal antibodies like ramucirumab, nivolumab, and pembrolizumab. Ideal use of these agents in clinics has improved the long-term outcome of patients with advanced HCC as well as introduced unique toxicities that can affect quality of life. These toxicities usually are thought to be partially related to cirrhosis, a major risk factor for the development of HCC and a pathophysiological barrier complicating the optimal delivery of antineoplastic therapy. Additionally, side effects of medications together with advanced HCC symptoms not only decrease quality of life, but also cause treatment interruptions and dose reductions that can potentially decrease efficacy. Physicians caring for patients with advanced HCC are called to optimally manage HCC along with cirrhosis in order to prolong life while at the same time preserve the quality of life. In this review, we aimed to summarize outcomes and quality of life with the use of modern systemic treatments in advanced HCC and provide a physician reference for treatment toxicity and cirrhosis management.


Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 841 ◽  
Author(s):  
Daneng Li ◽  
Sabrina Sedano ◽  
Rebecca Allen ◽  
Jun Gong ◽  
May Cho ◽  
...  

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer mortality worldwide. Heterogeneity of clinical conditions contributes to the complex management of care for patients with advanced HCC. Recently, the treatment landscape for advanced HCC has expanded rapidly, with the additional FDA approvals of several oral tyrosine kinase inhibitors (lenvatinib, regorafenib, and cabozantinib), as well as immunotherapies such as immune check point inhibitors (nivolumab and pembrolizumab) and the monoclonal IgG1 antibody, ramucirumab. This expansion has generated a need for novel treatment sequencing strategies in this patient population. In light of these developments, an evaluation of the impact of FDA-approved therapeutics on patient-centered outcomes such as health-related quality of life (HRQoL) is warranted. An increased understanding of HRQoL in patients included in advanced HCC clinical trials could potentially help physician decision-making for treatment sequencing in patients with advanced HCC.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15573-e15573
Author(s):  
F. P. Costa ◽  
A. C. de Oliveira ◽  
R. Meirelles ◽  
M. M. Machado ◽  
R. Surjan ◽  
...  

e15573 Background: Over the past few years we have identified tumor-specific frequencies for several common forms of cancer. The goal of this study was to assess the tolerability and effectiveness of electromagnetic fields amplitude-modulated at tumor-specific frequencies and administered by means of an intrabuccal spoon-shaped probe in patients with advanced hepatocellular carcinoma (HCC). Methods: From October 2005 to July 2007, patients with advanced HCC and Child-Pugh A or B were recruited in a phase II study. Three daily 60 min outpatient treatments were administered until disease progression or death. Imaging studies were performed every eight weeks. The primary efficacy end point was progression-free survival ≥ 6 months. Secondary efficacy end points were progression-free survival and overall survival. Results: A total of 41 patients were enrolled, 17 had Child-Pugh A, 20 Child-Pugh B disease. The median age was 64.0 years. Seventeen patients (34.1%) were progression-free for more than 6 months. Median progression-free and overall survivals were 4.8 months (95% CI 2.3–6.0) and 6.9 months (95 CI 4.8–11.1). As of December 2008, four patients are alive and two patients, who are still undergoing therapy, remain progression-free for 30.4 and 30.7 months, respectively. Four patients had partial response (9.8%) and sixteen had stable disease for at least 12 weeks (39.0%) according to the RECIST criteria resulting in 48.8% disease control. All responses were confirmed by independent review. There were no NCI grade 2, 3 or 4 toxicities. One patient developed grade 1 mucositis and one patient grade 1 fatigue. Conclusions: In patients with advanced HCC and impaired hepatic function, treatment with amplitude-modulated electromagnetic fields is safe, well tolerated, and shows evidence of anti-tumor effects, which are long-lasting in some patients. No significant financial relationships to disclose.


2017 ◽  
Vol 01 (02) ◽  
pp. 138-144
Author(s):  
William Rilling ◽  
Sarah White

AbstractHepatocellular carcinoma (HCC) is the third leading cause of cancer worldwide according to the National Cancer Institute. If treated with liver directed therapy, patients' median overall survival is significantly improved at 20.1 versus 4.3 months without treatment. The purpose of this article is to give an overview on when and how to treat, and when not to treat patients with advanced or terminal HCC. Treatment of patients with advanced HCC can be challenging, as patients are often already debilitated due to their chronic underlying liver disease. Performance status, hepatic function, tumor characteristics, and the patient's desire to maintain their quality of life should be at the forefront of deciding when and how to treat this patient population. If patients are found to be outside treatment criteria, referral to palliative care can be beneficial.


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