Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 14  |  Issue : 4  |  Page : 815-819

Effect of low-frequency rotary magnetic fields on advanced gastric cancer: Survival and palliation of general symptoms


1 Cancer Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
2 Department of Head and Neck Radiotherapy, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
3 Shandong CRS Medical Technology Limited Company, Zibo, Shandong, China
4 Department of Bone and Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China

Date of Web Publication27-Jun-2018

Correspondence Address:
Hong Feng
Cancer Center, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, Shandong
China
Junqing Han
Cancer Center, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, Shandong
China
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_991_17

Rights and Permissions
 > Abstract 


Objective: The tumor inhibition by magnetic fields (MFs) has been reported in many in vivo and in vitro studies, while clinical trials have been rare. This report aimed to evaluate the improvement of survival and general symptoms in advanced cancer patients treated with MFs.
Subjects and Methods: In this study, we investigated 21 patients with advanced gastric cancer (AGC) treated with 420 r/min, 0.4-T low-frequency rotary MFs. The treatment area encompassed the primary tumor sites, metastatic sites, and metastatic lymph nodes. In addition, the patients were treated 2 h per day, 5 days per week for 6–12 weeks. The toxicity pilot human study was approved by the competent ethical committee. Toxicity and side effects were assessed according to the WHO criteria. The changes of general symptoms were analyzed during low-frequency rotary MFs treatment and 2 weeks after the end of therapy. Electrocardiogram, chest X-ray, physical examination, blood cell count and complete blood chemistry, biochemical, and kidney function tests were performed before and after the end of the treatment. All 21 patients were followed up by outpatient service or telephone interview.
Results: Our results demonstrated that low-frequency rotary MFs improved abdominal pain in 9/21 (42.9%), nausea/vomiting in 4/21 (19.0%), weight loss in 11/21 (52.4%), ongoing blood loss in 2/21 (9.5%), physical strength in 5/21 (23.8%), and sleep quality in 4/21 (19.0%) patients. No severe toxicity and side effect were observed in our trial. The median survival time was 8.0 months (95% confidence interval, 5.190–10.810). The 1-year survival rate was 25.8%.
Conclusion: Low-frequency rotary MFs may prolong survival and improve general symptom of AGC patients, as an effective, well-tolerated, and safe treatment choice.

Keywords: Advanced gastric cancer, general symptoms, low-frequency rotary magnetic fields, survival analysis, toxicity


How to cite this article:
Chen Z, Liu H, Wang H, Wu C, Feng H, Han J. Effect of low-frequency rotary magnetic fields on advanced gastric cancer: Survival and palliation of general symptoms. J Can Res Ther 2018;14:815-9

How to cite this URL:
Chen Z, Liu H, Wang H, Wu C, Feng H, Han J. Effect of low-frequency rotary magnetic fields on advanced gastric cancer: Survival and palliation of general symptoms. J Can Res Ther [serial online] 2018 [cited 2019 Nov 22];14:815-9. Available from: http://www.cancerjournal.net/text.asp?2018/14/4/815/235104




 > Introduction Top


Whether exposure to low-frequency rotary magnetic fields (MFs) was associated with an increased risk of childhood leukemia or cancer has engendered scientific debate.[1] Data from scientific literature were controversial. The possibility that MFs could contribute to cancer therapy has recently been investigated. Hisamitsu et al.[2] reported the induction of apoptosis in human leukemic cells by MFs. Dibirdik et al.[3] studied the effects of low-frequency rotary MFs on the tyrosine kinase-dependent phospholipase Cgamma2 activation in DT40 lymphoma B cells. Huang et al.[4] demonstrated the inhibition of cell growth and changes of cell ion concentration and osmolarity by 20-mT, 50-Hz sinusoidal MFs in two human cancer cell lines (HL-60 and SK-Hep-1). The same MF exposure was reported to induce significantly enhanced in vivo antitumor efficacy of cisplatin against Lewis lung carcinomas in C57BL/6 mice or B16 melanotic melanomas.[5] These findings supported a potential use of MF as an anticancer agent.

A mechanism of this activity is the possibility that free radical recombination process would be influenced by MFs, which activated P53 gene-dependent survival mechanisms.[6] DNA damage was also regarded as one of the possible mechanisms, because of the induced numerous DNA breaks and the overwhelming DNA repair processes.[7]

For the toxicity of MFs, many animal and human studies have been performed. Comparing to mice receiving chemotherapy, no clinical signs or toxicity was observed in any mice exposed to MFs, reported by Tofani et al.[5] Moreover, Lee et al.[8] confirmed that MFs did not increase toxicity in Sprague-Dawley rats after exposing them to 20 kHz triangular MFs. An ethical committee institute by law approved a hematological and nonhematological toxicity pilot human study. Accordingly, Ronchetto et al.[6] concluded that MFs may be safely administrated according to the appropriate exposure schedules.

The tumor inhibition by MFs has been reported in many in vivo and in vitro studies.[2],[3],[4],[5],[9] However, there was lack of clinical trials to evaluate the effects of low-frequency rotary MFs on advanced gastric cancer (AGC) patients. In this study, 21 AGC patients were enrolled in this study. This work aimed to evaluate the efficacy and safety of low-frequency rotary MFs in patients with AGC.


 > Subjects and Methods Top


Patient eligibility

Between December 2011 and November 2015, 21 patients with metastatic or recurrent gastric cancer (disease stage IV) were included in this study. Eligibility requirements for inclusion in the study were detailed in [Table 1]: histologically or cytologically confirmed AGC; disease stage IV according to the UICC TNM classification; Karnofsky performance status score ≥50; expected survival time ≥2 months; and patients had abandoned treatment after their disease recurred. There were also requirements concerning the functions of certain organs; patients with severe heart disease, liver cirrhosis or active hepatitis, and chronic renal failure were excluded from the study. Pregnant patients and children were also excluded. The exclusion criteria did not include patients who had received therapies previously, including surgery, chemotherapy, radiation therapy, or combination treatment. However, the treatment had to be at least 1 month before our study.
Table 1: Patient eligibility criteria

Click here to view


The study was designed and performed in compliance with all relevant regulations in force in our country. The research procedures were performed after obtaining the consent of the patients and ethics committee approval, which were also in accordance with the Helsinki Declaration of 1975, as revised in 1983.

Treatment schedule

Our study employed the instrument designed by Shandong Chaoruishi Medical Science and Technology Company (Zibo, China) and the instrument could generate static MFs. It consisted of two magnetic heads, in which a pair of fan-shaped NdFeB permanent magnets were embedded into a circular iron plate and arranged to establish MF. The bottom magnetic head was driven by an electromotor, while the top magnet would be synchronously rotated by the bottom magnetic head under the strong magnetic interaction. The treatment bed was made of plex glass located between the two magnetic heads. The intensity and frequency of the MFs were 0.38–0.42 T and 0–50 Hz. The rotation speed of the magnetic heads was regulated from 300 to 600 r/min.

When treatment was started, patients laid on the treatment bed of the low-frequency rotary MFs machine. The treatment schedule was as follows: patients were exposed to 420 r/min, 0.4-T MFs, 2 h per day, and 5 days per week for 6–12 weeks. The area of treatment encompassed the primary tumor sites, metastatic sites, and metastatic lymph nodes.

Toxicity and side effects were evaluated according to the WHO criteria. Before and after low-frequency rotary MFs treatment, all 21 patients received clinical tests, including electrocardiogram, chest X-ray, physical examination, blood cell count, complete blood biochemistry, and liver and kidney function tests to evaluate toxicity and side effects of low-frequency rotary MFs. During the treatment, patients were observed to determine whether there were severe side effects. If intolerable adverse events were reported, the treatment would be stopped.

Changes in general symptoms, including abdominal pain, nausea/vomiting, weight loss, ongoing blood loss, fatigue, and insomnia, were recorded during low-frequency rotary MFs treatment and 2 weeks after the completion of therapy.

Follow-up

The follow-up included outpatient service and telephone interview. Following low-frequency rotary MFs treatment, all the 21 patients were followed up every 3 months in the 1st year and every 6 months in the 2nd and 3rd year until the death of the patient, the last follow-up date or the loss of follow-up. The last date of the follow-up was January 20, 2017, and the median follow-up period was 7 months.

Statistical analysis

Overall, survival time was calculated from the date of completion of low-frequency rotary MFs treatment to the date of death or last follow-up date, which was expressed as months. Overall survival, the 1-year and 2-year survival rates and mortality or last follow-up results were evaluated with the Kaplan–Meier method. Statistical analyses were performed with SPSS 17.0 statistical software (Chicago, IL, USA). Statistical significance was defined as P < 0.05.


 > Results Top


Patient characteristics

The clinical characteristics of the patients were listed in [Table 2]. The total number of participants was 21, including 5 females and 16 males, with a median age of 63 years (ranged 48–82). Six were <60 years old and 15 were ≥60 years old. All patients suffered from metastatic diseases. Of these patients, 8 were single-site metastasis (4 with liver, 2 with bone, 1 with lung, and 1 with adrenal gland metastasis), 13 were multisite metastases. Before the study, 4 patients had not received antitumor treatment and the rest 17 patients had received treatments previously, including surgery, chemotherapy, and radiotherapy or combined treatments. All the participants experienced recurrence, and they abandoned treatment before receiving low-frequency rotary MFs.
Table 2: Characteristic of advanced gastric cancer patients (n=21)

Click here to view


Palliation of general symptoms

The clinical symptoms of all patients were monitored after the treatment of low-frequency rotary MFs. The improvement of the general symptoms of all participants was described in [Table 3]. Nine patients with abdominal pain were improved after receiving treatment. Four patients reported nausea/vomiting before the treatment, and the symptom disappeared during the treatment. Eleven patients gained weight at the end of the treatment. Two patients with ongoing blood loss, palliated gradually, and the symptom was disappeared at the end of the treatment. Other clinical symptoms, including improved physical strength and better sleep quality, were observed in 5 and 4 patients, respectively.
Table 3: Symptom improvement of advanced gastric cancer patients

Click here to view


Toxicity and side effects

During the treatment, the instrument generated noise which was tolerated. Fatigue was reported in 6 (28.6%) patients, respectively. Mild dull pain or pinching pain in the lesion sites were reported in 5 (23.8%) patients and disappeared after 3–8 days. Grade 1 and 2 arrest of bone marrow was observed in 3 (14.3%) and 1 (4.8%) patients, respectively. Increased heart rate of 5–10 bpm was detected in 2 (9.5%) patients. Increased temperature of 0.5–1.0°C was detected in 2 (9.5%) patients. All the patients were well tolerated with the exposure to low-frequency rotary MFs. No severe side effect or toxicity was observed in the 21 patients in our trial. These data were shown in [Table 4].
Table 4: Toxicity and side effects in advanced gastric cancer patients

Click here to view


Survival analysis

All the 21 patients were followed up for 14 months or until mortality or loss of follow-up. Therefore, there were 18 patients succumbed to the disease, 1 patient was lost to follow-up, and 2 patients were still alive. The median survival time was 8.0 months (95% confidence interval [CI], 5.190–10.810). The 1-year survival rate was 25.8% [Figure 1].
Figure 1: Cumulative survival curve of advanced gastric cancer patients (the median survival time was 8.0 months)

Click here to view



 > Discussion Top


Gastric cancer has been a leading cause of illness and death from cancer worldwide, with nearly a million new cases diagnosed each year. It was the fourth most common malignancy and the second leading cause of cancer-related death worldwide.[10],[11] The incidence of gastric cancer has been different globally. High incidence areas of gastric adenocarcinoma have been observed in East Asia, such as China and Japan. Low incidence rates were found in North and East Africa and North American.[12] As for early and locally AGC, surgery was still the first option of therapy. However, two-thirds of the patients were first diagnosed at an advanced stage of gastric cancer,[13],[14],[15] thus the treatment was limited, leading to poor survival. The optimum standard first-line chemotherapy regimen for AGC remains debatable, a double regimen comprising fluorouracil (or its oral prodrugs) plus platinum, or a triple regimen with the addition of epirubicin or docetaxel was most commonly applied.[16],[17] The systemic chemotherapy has been proved to palliate the general symptoms in patients with AGC, as well as prolonging the survival compared to the best supportive care; however, most responses to chemotherapy were partial and of short duration.[18] There has been no significant progress in the treatment of AGC within the last two decades.[19],[20]

Low-frequency rotary MFs have been reported to inhibit tumor cell proliferation by numerous studies in vitro and in vivo. In a clinical research, Ronchetto et al.[6] have assessed that MFs may be safely administrated under the exposure schedules. Sun et al.[21] have concluded that low-frequency rotary MFs may be an effective, well-tolerated, and safe treatment method for advanced nonsmall cell lung cancer, resulting in prolonged survival and moderately improved general symptoms. This study was aimed to evaluate the improvement of survival and general symptoms in 21 AGC patients treated with low-frequency rotary MFs.

Overall, survival and quality of life (QOL) have been the most important indicators for evaluating cancer treatments. Outcomes were extremely poor in patients with unresectable advanced or recurrent gastric cancer. The median survival time was ranged from 3 to 5 months with best supportive care.[19],[20],[22] While our results revealed that the median survival time was 8.0 month (95% CI, 5.190–10.810). Fluoropyrimidine combined with platinum has been referred as the standard chemotherapy for AGC, and the median overall survival time could be moderately improved to 1 year.[23] The median survival time of low-frequency rotary MFs, fluoropyrimidine combined with platinum chemotherapy, and best supportive care were listed in [Table 5].
Table 5: Median survival time of low-frequency rotary magnetic fields, best supportive care, docetaxel, cisplatin, and fluorouracil-, and cisplatin- and fluorouracil-treated patients

Click here to view


Comparing the median survival time of low-frequency rotary MFs with best supportive care, we concluded that AGC patients may benefit from low-frequency rotary MFs treatment. When comparing the low-frequency rotary MFs treatment and chemotherapy, there was no advantage on the median survival time of patients receiving low-frequency rotary MFs treatment, but low-frequency rotary MFs treatment showed more tolerability and less toxicity. Toxicity related to various treatments included neutropenia, stomatitis, thrombocytopenia, diarrhea, lethargy, nausea, vomiting, and fatigue,[17] which seriously affected QOL of AGC patients. In our trials, Grade 1 and 2 arrest of bone marrow was detected in 3 (14.3%) and 1 (4.8%) patients, respectively. Increased heart rate of 5–10 bpm was observed in 2 (9.5%) patients. Increased temperature of 0.5–1.0°C was detected in 2 (9.5%) patients [Table 4]. We concluded that no severe side effect or toxicity was observed in patients treated with low-frequency rotary MFs, which was in accordance with previous studies.[6]

The chance of achieving complete remission was limited for AGC patients, thus it was essential to improve QOL of these patients. For the effectiveness of low-frequency rotary MFs on general symptoms, the patients showed improvements in abdominal pain, nausea/vomiting, weight loss, ongoing blood loss, fatigue, and sleep quality. These findings demonstrated that low-frequency rotary MFs may moderately improve QOL of AGC patients.


 > Conclusion Top


The results of our study suggested that low-frequency rotary MFs may be an effective, well-tolerated, and safe treatment for AGC, providing prolonged survival and moderately improved general symptoms. Further, investigation should be warranted to confirm our observation.

Financial support and sponsorship

This work was supported by grants from the National Key Technology Support Program of China (No. 2012BAI15B03), National Natural Science Foundation of China (No. 81201865), Shandong Provincial Natural Science Foundation (No. ZR2017QH004), and Shandong Science and Technology Development Plan (No. 2011GSF11843 and No. 2015GSF118169).

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Schüz J, Ahlbom A. Exposure to electromagnetic fields and the risk of childhood leukaemia: A review. Radiat Prot Dosimetry 2008;132:202-11.  Back to cited text no. 1
    
2.
Hisamitsu T, Narita K, Kasahara T, Seto A, Yu Y, Asano K, et al. Induction of apoptosis in human leukemic cells by magnetic fields. Jpn J Physiol 1997;47:307-10.  Back to cited text no. 2
    
3.
Dibirdik I, Kristupaitis D, Kurosaki T, Tuel-Ahlgren L, Chu A, Pond D, et al. Stimulation of src family protein-tyrosine kinases as a proximal and mandatory step for SYK kinase-dependent phospholipase cgamma2 activation in lymphoma B cells exposed to low energy electromagnetic fields. J Biol Chem 1998;273:4035-9.  Back to cited text no. 3
[PUBMED]    
4.
Huang L, Dong L, Chen Y, Qi H, Xiao D. Effects of sinusoidal magnetic field observed on cell proliferation, ion concentration, and osmolarity in two human cancer cell lines. Electromagn Biol Med 2006;25:113-26.  Back to cited text no. 4
[PUBMED]    
5.
Tofani S, Barone D, Berardelli M, Berno E, Cintorino M, Foglia L, et al. Static and ELF magnetic fields enhance the in vivo anti-tumor efficacy of cis-platin against lewis lung carcinoma, but not of cyclophosphamide against B16 melanotic melanoma. Pharmacol Res 2003;48:83-90.  Back to cited text no. 5
[PUBMED]    
6.
Ronchetto F, Barone D, Cintorino M, Berardelli M, Lissolo S, Orlassino R, et al. Extremely low frequency-modulated static magnetic fields to treat cancer: A pilot study on patients with advanced neoplasm to assess safety and acute toxicity. Bioelectromagnetics 2004;25:563-71.  Back to cited text no. 6
[PUBMED]    
7.
Elson E. I. The little explored efficacy of magnetic fields in cancer treatment and postulation of the mechanism of action. Electromagn Biol Med 2009;28:275-82.  Back to cited text no. 7
[PUBMED]    
8.
Lee HJ, Gimm YM, Choi HD, Kim N, Kim SH, Lee YS, et al. Chronic exposure of sprague-dawley rats to 20 kHz triangular magnetic fields. Int J Radiat Biol 2010;86:384-9.  Back to cited text no. 8
    
9.
Gray JR, Frith CH, Parker JD.In vivo enhancement of chemotherapy with static electric or magnetic fields. Bioelectromagnetics 2000;21:575-83.  Back to cited text no. 9
[PUBMED]    
10.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D, et al. Global cancer statistics. CA Cancer J Clin 2011;61:69-90.  Back to cited text no. 10
    
11.
Wang X, Wu Y, Song X, Sun C, Wu C, Feng H, et al. Human epidermal growth factor receptor 2 amplification detection by droplet digital polymerase chain reaction in formalin-fixed paraffin-embedded breast and gastric cancer samples. J Cancer Res Ther 2017;13:730-4.  Back to cited text no. 11
    
12.
Salehi Z, Akrami H. Target genes prediction and functional analysis of microRNAs differentially expressed in gastric cancer stem cells MKN-45. J Cancer Res Ther 2017;13:477-83.  Back to cited text no. 12
[PUBMED]    
13.
Parkin DM, Pisani P, Ferlay J. Global cancer statistics. CA Cancer J Clin 1999;49:33-64, 1.  Back to cited text no. 13
[PUBMED]    
14.
Weidong C, Lijun X. S-1 combined with cisplatin chemotherapy for advanced gastric cancer. J Cancer Res Ther 2016;12:54-6.  Back to cited text no. 14
[PUBMED]    
15.
Turanli S, Atalay C, Berberoglu U, Gulben K. Adjuvant chemoradiation versus chemotherapy for stage III gastric cancer after surgery with curative intent. J Cancer Res Ther 2015;11:369-74.  Back to cited text no. 15
[PUBMED]    
16.
Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 2008;358:36-46.  Back to cited text no. 16
[PUBMED]    
17.
Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: A report of the V325 study group. J Clin Oncol 2006;24:4991-7.  Back to cited text no. 17
[PUBMED]    
18.
Wagner AD, Grothe W, Haerting J, Kleber G, Grothey A, Fleig WE, et al. Chemotherapy in advanced gastric cancer: A systematic review and meta-analysis based on aggregate data. J Clin Oncol 2006;24:2903-9.  Back to cited text no. 18
    
19.
Murad AM, Santiago FF, Petroianu A, Rocha PR, Rodrigues MA, Rausch M, et al. Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer. Cancer 1993;72:37-41.  Back to cited text no. 19
    
20.
Pyrhönen S, Kuitunen T, Nyandoto P, Kouri M. Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer. Br J Cancer 1995;71:587-91.  Back to cited text no. 20
    
21.
Sun C, Yu H, Wang X, Han J. A pilot study of extremely low-frequency magnetic fields in advanced non-small cell lung cancer: Effects on survival and palliation of general symptoms. Oncol Lett 2012;4:1130-4.  Back to cited text no. 21
[PUBMED]    
22.
Glimelius B, Hoffman K, Haglund U, Nyrén O, Sjödén PO. Initial or delayed chemotherapy with best supportive care in advanced gastric cancer. Ann Oncol 1994;5:189-90.  Back to cited text no. 22
    
23.
Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: A randomized, double-blind, placebo-controlled phase III study. J Clin Oncol 2011;29:3968-76.  Back to cited text no. 23
[PUBMED]    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  >Abstract>Introduction>Subjects and Methods>Results>Discussion>Conclusion>Article Figures>Article Tables
  In this article
>References

 Article Access Statistics
    Viewed946    
    Printed6    
    Emailed0    
    PDF Downloaded45    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]