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      Treatment outcome analysis of chemotherapy combined with modulated electro-hyperthermia compared with chemotherapy alone for recurrent cervical cancer, following irradiation

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          Abstract

          The survival of patients with recurrent cervical cancer following irradiation remains poor. Chemotherapy combined with hyperthermia has been demonstrated to improve the response rate. The present study was performed to evaluate the effect of modulated electro-hyperthermia combined with conventional chemotherapy compared with chemotherapy alone on recurrent cervical cancer previously treated with irradiation. A total of 20 patients were treated with chemotherapy alone, and 18 were treated with chemotherapy combined with modulated electro-hyperthermia. A single patient was treated with chemo-radiotherapy as primary treatment and then relapsed; the tumor was inoperable and radio-refractory upon recurrence. Local metastases, including metastasis of the para-aortic lymph nodes and adjacent pelvic lymph nodes were included, but distant metastases were excluded. Modulated electro-hyperthermia was performed three times per week beginning at chemotherapy initiation, and patients underwent a total of 36 sessions. The overall response (complete remission + partial remission + stable disease/progressive disease) to treatment was significantly greater in the group of patients who underwent chemotherapy combined with modulated electro-hyperthermia (P=0.0461), and at the evaluation conducted at the last follow-up visit, the response rate was significantly higher (P=0.0218). Additionally, severe complications were not reported. In the present study, of patients with recurrent cervical cancer previously treated with irradiation, the overall response rate for patients treated with chemotherapy combined with modulated electro-hyperthermia was significantly greater than that for those treated with chemotherapy alone.

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          Effect of local hyperthermia on blood flow and microenvironment: a review.

          C W Song (1984)
          The blood flow in tumors varies considerably among different tumor types. Even in the same tumor, the distribution of vasculature and blood flow is quite heterogeneous. The tumor blood flow generally decreases as the tumors grow larger, owing partially to progressive deterioration of vascular beds and to the rapid growth of tumor cell population relative to vascular beds. Contrary to the general notion that blood flow is less in tumors than in normal tissues, blood flow in many tumors, particularly in small tumors, is actually greater than that in surrounding normal tissues at normothermic conditions. Compared to the normal tissue blood flow, however, the capacity of tumor blood flow to increase upon heating appears to be rather limited. Consequently, the heat dissipation by blood flow in tumors is slower than that in normal tissues, and thus the temperature of tumor rises higher than that in normal tissue during heating. Preferential heating of tumors, however, may not be achieved all the time because the relative blood perfusion in some tumors remains greater than that in the surrounding normal tissues despite the profound increase in normal tissue blood flow during heating. The vasculature in tumor can be significantly damaged at temperatures which may alter but do not damage the vasculature of normal tissue. Upon heating, the intratumor environment becomes acidic, hypoxic, and nutritionally deprived due probably to vascular damage. Such a suboptimal environment in the heated tumors potentiates the response of tumor cells to hyperthermia, inhibits the repair of thermal damage, and also interferes with the development of thermal tolerance. The acidic environment also appears to potentiate the response of tumor cells to certain drugs at elevated temperatures. The changes in oxygenation of tumors and normal tissues caused by the changes in blood flow may have significant implications in the effectiveness of different sequences of hyperthermia and radiotherapy in the combined use of these two modalities. Changes in the distribution of drugs in tumors and normal tissues due to changes in blood flow will also determine the optimal use of hyperthermia in conjunction with chemotherapy.
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            Hyperthermia versus Oncothermia: Cellular Effects in Complementary Cancer Therapy

            Hyperthermia means overheating of the living object completely or partly. Hyperthermia, the procedure of raising the temperature of a part of or the whole body above normal for a defined period of time, is applied alone or as an adjunctive with various established cancer treatment modalities such as radiotherapy and chemotherapy. However, hyperthermia is not generally accepted as conventional therapy. The problem is its controversial performance. The controversy is originated from the complications of the deep heating and the focusing of the heat effect. The idea of oncothermia solves the selective deep action on nearly cellular resolution. We would like to demonstrate the force and perspectives of oncothermia, as a highly specialized hyperthermia in clinical oncology. Our aim is to prove the ability of oncothermia to be a candidate to become a widely accepted modality of the standard cancer care. We would like to show the proofs and the challenges of the hyperthermia and oncothermia applications to provide the presently available data and summarize the knowledge in the topic. Like many early stage therapies, oncothermia lacks adequate treatment experience and long-range, comprehensive statistics that can help us optimize its use for all indications.
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              DNA fragmentation and caspase-independent programmed cell death by modulated electrohyperthermia.

              The electric field and the concomitant heat (electrohyperthermia) can synergistically induce cell death in tumor tissue, due to elevated glycolysis, ion concentration, and permittivity in malignant compared with nonmalignant tissues. Here we studied the mechanism and time course of tumor destruction caused by electrohyperthermia.
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                Author and article information

                Journal
                Oncol Lett
                Oncol Lett
                OL
                Oncology Letters
                D.A. Spandidos
                1792-1074
                1792-1082
                July 2017
                04 May 2017
                04 May 2017
                : 14
                : 1
                : 73-78
                Affiliations
                [1 ]Department of Radiation Oncology, Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju, Jeollabukdo 561-712, Republic of Korea
                [2 ]Institute of Clinical Medicine, Chonbuk National University-Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Jeollabukdo 561-712, Republic of Korea
                [3 ]Division of Hematology/Oncology, Department of Internal Medicine, Jeonju, Jeollabukdo 561-712, Republic of Korea
                [4 ]Department of Obstetrics and Gynecology, Chonbuk National University Hospital-Chonbuk National University Medical School, Jeonju, Jeollabukdo 561-712, Republic of Korea
                Author notes
                Correspondence to: Professor Jung Soo Kim, Department of Radiation Oncology, Institute for Medical Sciences, Chonbuk National University Medical School, 20 Geonji-ro, Jeonju, Jeollabukdo 561-712, Republic of Korea, E-mail: jskim@ 123456jbnu.ac.kr
                [*]

                Contributed equally

                Article
                OL-0-0-6117
                10.3892/ol.2017.6117
                5494813
                28693137
                881fd73f-ad54-4251-893f-547d65cfda6f
                Copyright: © Lee et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 30 January 2016
                : 23 February 2017
                Categories
                Articles

                Oncology & Radiotherapy
                concurrent chemo-modulated electro-hyperthermia,chemotherapy alone,recurrent cervical cancer,treatment outcome

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