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Sample records for combining chemotherapy hyperthermia

  1. The effect of hyperthermia in the preoperative combined treatment of radiation, hyperthermia and chemotherapy for rectal carcinoma

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    Konishi, Fumio; Furuta, Kazuhiro; Saito, Yukio; Kataoka, Takashi; Kashiwagi, Hiroshi; Okada, Masaki; Kanazawa, Kyotaro; Sugahara, Tadashi; Shinohara, Naohiro (Jichi Medical School, Minamikawachi, Tochigi (Japan))

    1994-03-01

    To investigate the effectiveness of hyperthermia in the preoperative combined treatment of radiation, chemotherapy and hyperthermia for rectal carcinoma, two groups were compared. Group A consisted of 18 patients in whom hyperthermia, radiation and chemotherapy were performed. Group B consisted of 18 patients in whom only chemotherapy and radiation were performed. The total dose of radiation in both of the two groups was 40.5 Gy, and a radiation field covering the whole pelvis was used. Hyperthermia was performed using 8 MHz radiofrequency waves (Thermotron RF8, Yamamoto Vinyter, Japan), and tumors were heated at about 42 degrees C for 50 minutes. Hyperthermia was repeated five times during the preoperative treatment. Chemotherapy was performed by giving 5-fluorouracil suppositories to a total dose of 3400 mg. Mean tumor reduction rates on barium enema were 31.8% in group A and 18.2% in group B. The difference was statistically significant. The result of the histological assessment of tumor necrosis showed that there was a significantly higher degree of necrosis in group A than in group B. These results showed that the addition of hyperthermia enhanced tumor necrosis. It was concluded that the addition of hyperthermia would be an effective preoperative treatment of rectal carcinoma. (author).

  2. The effect of hyperthermia in the preoperative combined treatment of radiation, hyperthermia and chemotherapy for rectal carcinoma

    International Nuclear Information System (INIS)

    Konishi, Fumio; Furuta, Kazuhiro; Saito, Yukio; Kataoka, Takashi; Kashiwagi, Hiroshi; Okada, Masaki; Kanazawa, Kyotaro; Sugahara, Tadashi; Shinohara, Naohiro

    1994-01-01

    To investigate the effectiveness of hyperthermia in the preoperative combined treatment of radiation, chemotherapy and hyperthermia for rectal carcinoma, two groups were compared. Group A consisted of 18 patients in whom hyperthermia, radiation and chemotherapy were performed. Group B consisted of 18 patients in whom only chemotherapy and radiation were performed. The total dose of radiation in both of the two groups was 40.5 Gy, and a radiation field covering the whole pelvis was used. Hyperthermia was performed using 8 MHz radiofrequency waves (Thermotron RF8, Yamamoto Vinyter, Japan), and tumors were heated at about 42 degrees C for 50 minutes. Hyperthermia was repeated five times during the preoperative treatment. Chemotherapy was performed by giving 5-fluorouracil suppositories to a total dose of 3400 mg. Mean tumor reduction rates on barium enema were 31.8% in group A and 18.2% in group B. The difference was statistically significant. The result of the histological assessment of tumor necrosis showed that there was a significantly higher degree of necrosis in group A than in group B. These results showed that the addition of hyperthermia enhanced tumor necrosis. It was concluded that the addition of hyperthermia would be an effective preoperative treatment of rectal carcinoma. (author)

  3. Hyperthermia of locally advanced or recurrent gynecological cancer. The effect of combination with irradiation or chemotherapy

    International Nuclear Information System (INIS)

    Terashima, Hiromi; Imada, Hajime; Egashira, Kanji; Nakata, Hajime; Kunugita, Naoki; Matsuura, Yuusuke; Kashimura, Masamichi

    1995-01-01

    Between May 1986 and April 1994, 15 patients with advanced or recurrent gynecological cancer were treated with combined therapy of hyperthermia and irradiation or chemotherapy at UOEH Hospital. Initial cases were treated by hyperthermia combined with irradiation in 4 and with chemotherapy in 2. Recurrent 9 cases were treated by hyperthermia combined with chemotherapy or by hyperthermia alone. Radiotherapy was given in a conventional way 5 fractions per week and hyperthermia was performed using RF capacitive heating equipment, Thermotron RF-8, once or twice a week. Intratumoral temperature was measured by thermocouple inserted into the tumor and kept at 42-44degC for 30-40 minutes. Complete response (CR) and partial response (PR), defined as 50% or more regression, was obtained in 8/15 (53%). Response rates (CR+PR/all cases) were good in initially treated cases (5/6, 83%), irradiated cases (7/8, 88%) and cases hearted over 42degC (7/9, 78%). Combined therapy of hyperthermia and radiotherapy seemed to be useful for controlling advanced gynecological cancers. (author)

  4. Hyperthermia and chemotherapy agent

    International Nuclear Information System (INIS)

    Roizin-Towle, L.; Hall, E.J.

    1981-01-01

    The use of chemotherapeutic agents for the treatment of cancer dates back to the late 19th century, but the modern era of chemotherapy drugs was ushered in during the 1940's with the development of the polyfunctional alkylating agent. Since then, numerous classes of drugs have evolved and the combined use of antineoplastic agents with other treatment modalities such as radiation or heat, remains a large relatively unexplored area. This approach, combining local hyperthermia with chemotherapy agents affords a measure of targeting and selective toxicity not previously available for drugs. In this paper, the effects of adriamycin, bleomycin and cis-platinum are examined. The adjuvant use of heat may also reverse the resistance of hypoxic cells noted for some chemotherapy agents

  5. ‘Smart’ gold nanoshells for combined cancer chemotherapy and hyperthermia

    International Nuclear Information System (INIS)

    Liang, Zhongshi; Xie, Yegui; Liu, Shunying; Li, Xingui

    2014-01-01

    Nanomaterials that circulate in the body have great potential in the diagnosis and treatment of diseases. Here we report that ‘smart’ gold nanoshells can carry a drug payload, and that their intrinsic near-infrared (NIR) plasmon resonance enables the combination of chemotherapeutic and hyperthermia therapies. The ‘smart’ gold nanoshells (named DOX/A54@GNs) consist of (a) gold nanoshells (GNs) with NIR plasmon resonance, which not only act as nanoblocks but also produce local heat to allow hyperthermia; (b) an anticancer drug, doxorubicin (DOX), which was conjugated onto the nanoblocks by pH-dependent biodegradable copolymer thiol poly(ethylene glycol) derivatives via carbamate linkage; and (c) the targeting peptide A54 (AGKGTPSLETTP) to facilitate its orientation to liver cancer cells and enhance cellular uptake. The conjugated DOX was released from the DOX/A54@GNs much more rapidly in an acidic environment (pH 5.3) than in a neutral environment (pH 7.4), which is a desirable characteristic for intracellular tumor drug release. DOX-modified GNs showed pH-dependent release behavior, and the in vitro cell uptake experiment using ICP-AES and microscopy showed greater internalization of A54-modified GNs in the human liver cancer cell line BEL-7402 than of those without A54. Flow cytometry and fluoroscopy analysis were conducted to reveal the enhanced cell apoptosis caused by the A54-modified GNs under combined chemotherapeutic and hyperthermia therapies. These results imply that DOX/A54@GNs could be used as a multifunctional nanomaterial system with pH-triggered drug-releasing properties for tumor-targeted chemotherapy and hyperthermia. (paper)

  6. Multimodal treatment combining chemotherapy, hyperthermia and radiotherapy for ovarian cancer

    International Nuclear Information System (INIS)

    Nagashima, Kei

    1992-01-01

    There has been increasing interest in the use of heat in the treatment of cancer. Theoretically cells are the most sensitive to ionizing radiation at mitosis, whereas the cycle phase that is the most resistant to ionizing radiation namely late in the DNA. Synthetic phase (late S) is the most sensitive to hyperthermia. Hyperthermia has been reported to enhance the cytocidal effects of several active chemotherapeutic agents. When thermal potentiation of chemotherapeutic agents against malignant cells is contemplated, normal tissues have a relatively high ambient blood flow which increases in response to thermal stress, thereby dissipating heat, compared to tumors. Tumors, with relatively poor blood flow and a responsive neovasculature, are in capable of augmenting flow and acting as a heat reservoir. This is the phenomenon of a heat reservoir which is one factor to enhance the cytocidal effects of several active anticancer agents for enhancing the uptake in tumor. The importance is in the adjuvant chemotherapy treated for post operative, advanced and recurrent ovarian cancer. Heating enhances the effects of radiotherapy and chemotherapy. Thirty patients with ovarian cancer were subjected to the multidisciplinary treatment with combination of hyperthermochemotherapy and radiation. The 30 patients consisted of 18 with endometrioid adenocarcinoma and 7 with serious post operative or recurrent status. Two types of equipments with rediofrequencies of 70 MHz (BSD-1000) or 434 MHZ (TAG MED·HS 434) were used for hyperthermia. Chemotherapeutic agents such as adriamycin, cis DDP, cyclophosphamide and etoposide were injected intravenously. Arterial infusion with reservoir was very effective in advanced stage of ovarian cancer. No severe or fatal side effects were observed. Hyperthermochemotherapy is useful and effective for the postoperative management or the treatment of recurrent cancer of the ovary. (J.P.N.)

  7. Chemotherapy and Radiofrequency-Induced Mild Hyperthermia Combined Treatment of Orthotopic Pancreatic Ductal Adenocarcinoma Xenografts.

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    Krzykawska-Serda, Martyna; Agha, Mahdi S; Ho, Jason Chak-Shing; Ware, Matthew J; Law, Justin J; Newton, Jared M; Nguyen, Lam; Curley, Steven A; Corr, Stuart J

    2018-04-02

    Patients with pancreatic ductal adenocarcinomas (PDAC) have one of the poorest survival rates of all cancers. The main reason for this is related to the unique tumor stroma and poor vascularization of PDAC. As a consequence, chemotherapeutic drugs, such as nab-paclitaxel and gemcitabine, cannot efficiently penetrate into the tumor tissue. Non-invasive radiofrequency (RF) mild hyperthermia treatment was proposed as a synergistic therapy to enhance drug uptake into the tumor by increasing tumor vascular inflow and perfusion, thus, increasing the effect of chemotherapy. RF-induced hyperthermia is a safer and non-invasive technique of tumor heating compared to conventional contact heating procedures. In this study, we investigated the short- and long-term effects (~20 days and 65 days, respectively) of combination chemotherapy and RF hyperthermia in an orthotopic PDAC model in mice. The benefit of nab-paclitaxel and gemcitabine treatment was confirmed in mice; however, the effect of treatment was statistically insignificant in comparison to saline treated mice during long-term observation. The benefit of RF was minimal in the short-term and completely insignificant during long-term observation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Bevacizumab-Based Chemotherapy Combined with Regional Deep Capacitive Hyperthermia in Metastatic Cancer Patients: A Pilot Study.

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    Ranieri, Girolamo; Ferrari, Cristina; Di Palo, Alessandra; Marech, Ilaria; Porcelli, Mariangela; Falagario, Gianmarco; Ritrovato, Fabiana; Ramunni, Luigi; Fanelli, Margherita; Rubini, Giuseppe; Gadaleta, Cosmo Damiano

    2017-07-06

    As an angiogenesis inhibitor, bevacizumab has been investigated in combination with different chemotherapeutic agents, achieving an established role for metastatic cancer treatment. However, potential synergic anti-angiogenic effects of hyperthermia have not tested to date in literature. The aim of our study was to analyze efficacy, safety, and survival of anti-angiogenic-based chemotherapy associated to regional deep capacitive hyperthermia (HT) in metastatic cancer patients. Twenty-three patients with metastatic colorectal ( n = 16), ovarian ( n = 5), and breast ( n = 2) cancer were treated with HT in addition to a standard bevacizumab-based chemotherapy regimen. Treatment response assessment was performed, according to the modified Response Evaluation Criteria for Solid Tumors (mRECIST), at 80 days (timepoint-1) and at 160 days (timepoint-2) after therapy. Disease Response Rate (DRR), considered as the proportion of patients who had the best response rating (complete response (CR), partial response (PR), or stable disease (SD)), was assessed at timepoint-1 and timepoint-2. Chi-squared for linear trend test was performed to evaluated the association between response groups (R/NR) and the number of previous treatment (none, 1, 2, 3), number of chemotherapy cycles (12), number of hyperthermia sessions (24), and lines of chemotherapy (I, II). Survival curves were estimated by Kaplan-Meier method. DRR was 85.7% and 72.2% at timepoint-1 and timepoint-2, respectively. HT was well tolerated without additional adverse effects on chemotherapy-related toxicity. Chi-squared for linear trend test demonstrated that the percentage of responders grew in relation to the number of chemotherapy cycles ( p = 0.015) and to number of HT sessions ( p chemotherapy cycles ( p chemotherapy with HT has a favorable tumor response, is feasible and well tolerated, and offers a potentially promising option for metastatic cancer patients.

  9. Regional hyperthermia combined with chemotherapy in paediatric, adolescent and young adult patients: current and future perspectives

    International Nuclear Information System (INIS)

    Seifert, Georg; Budach, Volker; Keilholz, Ulrich; Wust, Peter; Eggert, Angelika; Ghadjar, Pirus

    2016-01-01

    Here we evaluate the current status of clinical research on regional hyperthermia (RHT) in combination with chemotherapy or radiation therapy in paediatric oncology. Data were identified in searches of MEDLINE, Current Contents, PubMed, and references from relevant articles using medical subject headings including hyperthermia, cancer, paediatric oncology, children, radiation therapy and chemotherapy. Currently, only two RHT centres exist in Europe which treat children. Clinical RHT research in paediatric oncology has as yet been limited to children with sarcomas and germ cell tumours that respond poorly to or recur after chemotherapy. RHT is a safe and effective treatment delivering local thermic effects, which may also stimulate immunological processes via heat-shock protein reactions. RHT is used chiefly in children and adolescents with sarcomas or germ cell tumours located in the abdomino-pelvic region, chest wall or extremities to improve operability or render the tumour operable. It could potentially be combined with radiation therapy in a post-operative R1 setting where more radical surgery is not possible or combined with chemotherapy instead of radiation therapy in cases where the necessary radiation dose is impossible to achieve or would have mutilating consequences. RHT might also be an option for chemotherapy intensification in the neoadjuvant first-line treatment setting for children and adolescents, as was recently reflected in the promising long-term outcome data in adults with high-risk soft tissue sarcomas (EORTC 62961/ESHO trial). The limited data available indicate that combining RHT with chemotherapy is a promising option to treat germ cell tumours and, potentially, sarcomas. RHT may also be beneficial in first-line therapy in children, adolescents and young adults. The research should focus on optimising necessary technical demands and then initiate several clinical trials incorporating RHT into interdisciplinary treatment of children

  10. Iron oxide nanoparticle hyperthermia and chemotherapy cancer treatment

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    Petryk, A. A.; Giustini, A. J.; Ryan, P.; Strawbridge, R. R.; Hoopes, P. J.

    2009-02-01

    The benefit of combining hyperthermia and chemotherapy to treat cancer is well established. However, combined therapy has not yet achieved standard of care status. The reasons are numerous and varied, however the lack of significantly greater tumor cell sensitivity to heat (as compared to normal cells) and the inability to deliver heat to the tumor in a precise manner have been major factors. Iron oxide nanoparticle (IONP) hyperthermia, alone and combined with other modalities, offers a new direction in hyperthermia cancer therapy via improved tumor targeting and an improved therapeutic ratio. Our preliminary studies have demonstrated tumor cell cytotoxicity (in vitro and in vivo) with IONP heat and cisplatinum (CDDP) doses lower than those necessary when using conventional heating techniques or cisplatinum alone. Ongoing studies suggest such treatment could be further improved through the use of targeted nanoparticles.

  11. A seven-year disease-free survivor of malignant pleural mesothelioma treated with hyperthermia and chemotherapy: a case report

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    Okonogi Noriyuki

    2012-12-01

    Full Text Available Abstract Introduction Malignant pleural mesothelioma was once a rare finding but its incidence is increasing worldwide, most likely because of widespread exposure to asbestos. Although complete surgical resection is considered the only curative treatment, the results of surgery have shown a median survival time of only one year. In inoperable cases, chemotherapy, radiotherapy, and a combination of both have been considered as palliative therapy. Therefore, outcomes for inoperable cases have been poor. Here, we report the case of a long-term survivor treated with hyperthermia and chemotherapy. Case presentation A 61-year-old Japanese man with a performance status of 1 due to chest pain was referred to our hospital. He had a history of asbestos exposure for approximately five years. A computed tomography scan showed diffuse extensive right pleural thickening with small nodular lesions, and video-assisted thoracoscopy revealed tumor invasion of the ipsilateral chest wall muscles. The histopathologic findings were consistent with a diagnosis of malignant pleural mesothelioma (sarcomatoid type. The tumor was diagnosed as being stage cT3N0M0. Our patient refused any invasive therapies including surgery and radiotherapy, and was therefore treated with hyperthermia and systemic chemotherapy with agents such as cisplatin and irinotecan. He underwent three hyperthermia sessions and a single course of chemotherapy without any severe complications. One month after treatment, a follow-up computed tomography scan showed no definitive abnormality in the thoracic space. Our patient has subsequently survived without any evident disease for more than seven years. Conclusions The combination of hyperthermia and chemotherapy may be a novel and safe therapeutic option for malignant pleural mesothelioma, and can be considered for patients ineligible for radical treatment. Further clinical studies of the combination of hyperthermia and chemotherapy are needed to

  12. Combining chemotherapy and/or hyperthermia with radiation in the treatment of malignant melanoma

    International Nuclear Information System (INIS)

    Douple, E.B.

    1984-01-01

    Radiation survival curves for some but not all human melanoma cells show broad shoulders and recovery of potentially lethal radiation damage (PLD), both in vitro and in situ as xenografts in mice. Studies have also demonstrated a significant hypoxic melanoma cell population. Chemotherapy and/or hyperthermia with radiation offers the potential for additive cell killing plus modification of the terminal slope and/or shoulder as a result of supra-additive killing via radiosensitization of hypoxic cells and/or post-irradiation inhibition of cellular recovery from PLD. Such interactions should provide a therapeutic gain factor, expecially if the long-term normal tissue damage is not based on PLD repair. Higher radiation doses per fraction warrant use of PLD recovery inhibitors and would accommodate a practical consideration for the use of fewer drug/heat doses. Peak heat or drug concentrations should probably be present just before and immediately following irradiation. This paper reviews the radiobiological experiments to support the rationale for the addition of chemotherapy and/or hyperthermia to melanoma. The author stresses the problems which remain including the paucity of appropriate preclinical experiments as well as clinical problems of tumor heterogeneity, pharmacokinetics and anatomy

  13. Preliminary results of M-VAC chemotherapy combined with mild hyperthermia, a new therapeutic strategy for advanced or metastatic transitional cell carcinoma of the urothelium.

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    Yamada, Yoshiaki; Itoh, Youko; Aoki, Shigeyuki; Nakamura, Kogenta; Taki, Tomohiro; Naruse, Katsuya; Tobiume, Motoi; Zennami, Kenji; Katsuda, Remi; Kato, Yoshiharu; Watanabe, Masahito; Nishikawa, Genya; Minami, Miwako; Nakahira, Mariko; Ukai, Sayaka; Sawada, Masaki; Kitamura, Akiko; Honda, Nobuaki

    2009-11-01

    We evaluated the efficacy and safety of M-VAC chemotherapy combined with mild hyperthermia, a new therapeutic strategy for advanced metastatic transitional cell carcinoma of the urothelium. The subjects were 12 patients diagnosed with advanced metastatic transitional cell carcinoma of the urothelium. For mild hyperthermia, the patients' oral temperature was elevated to about 38 degrees C by heating for 20 min and retaining the heat for 20 min with a far-infrared heater. The antitumor effect was evaluated according to the RECIST, while adverse drug reactions were assessed based on the NCI-CTC. The antitumor effect was rated as partial remission (PR) in 10 of the 12 patients and stable disease in 2 patients, with an efficacy rate of 83% (10/12). All 10 patients who had achieved PR received three courses of treatment. Of the 12 patients, 5 died during the observation period, with survival for 9-23 months (mean: 15.6 months). Adverse drug reactions included myelosuppression in all patients (Grade 3 in 4 patients, Grade 4 in 8), and gastrointestinal toxicity, such as nausea or vomiting, which was mild (Grade 0 in 2 patients, Grade 1 in 8, Grade 2 in 1, Grade 3 in 1). The results of the present study suggest that M-VAC chemotherapy combined with mild hyperthermia, which potentiates the anticancer effect and reduces adverse drug reactions such as gastrointestinal symptoms, is a useful and safe method for the treatment of advanced transitional cell carcinoma of the urothelium.

  14. Hyperthermia effects in the presence of gold nanoparticles together with chemotherapy on Saos-2 cell line

    International Nuclear Information System (INIS)

    Sazgarnia, A.; Bahreyni Toosi, M. H.; Haji Ghahremani, F.; Rajabi, O.; Aledavood, A.; Esmaily, H.

    2011-01-01

    Hyperthermia created by microwave, infrared, ultrasound and other methods, is often utilized as an adjuvant to sensitize cancer cells to the effects of chemotherapy and radiation therapy. We investigated the efficacy of hyperthermia using microwave in synergy with chemotherapy in the presence and absence and gold nanoparticles. Material and Methods: After culturing and proliferation of the Saos-2 cell line derived from human osteogenic sarcoma, the cells were incubated at two concentrations of gold nanoparticles in two diameters of 20 and 40 nm and in the absence and presence of doxorubicin in different groups. Forty eight hours after irradiating the cells with microwave up to a temperature of 42 d egree C , cell survival rate was determined using the MTT method, in order to study the effectiveness of the therapeutic parameters. Results: Cell survival in the presence of gold nanoparticles was greater than 95%. After chemotherapy by doxorubicin with and without 40 nm gold nanoparticles, cell survival rates were determined as 62.8% and 37.1 %, declining down to 17% and 4.1% respectively following the combined treatment with microwave and chemotherapy in the presence of 20 and 40 nm gold nanoparticles. Discussion and Conclusions: Gold nanoparticles did not induce any cytotoxicity by themselves; their presence along with microwave provided a reduction in survival rate that was comparable in severity with the lethal effects of doxorubicin. microwave hyperthermia with gold nanoparticles produced a higher treatment efficiency in comparison to similar groups in which gold nanoparticles were absent. The synergism observed between hyperthermia and chemotherapy was dependent in gold nanoparticles' size and concentration. This finding could be caused by increased uptake of doxorubicin by the cells in the presence of gold nanoparticles.

  15. A clinical study on combined modality therapy, radio-hyperthermo-chemotherapy, for pancreatic cancer

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    Yamamoto, Yoshikazu

    1989-01-01

    A new multimodality therapy, radio-hyperthermo-chemotherapy, has been performed in a total of 31 pancreatic cancer patients with the purpose of improving treatment outcome. Combination of hyperthermia and chemotherapy was given as a pre-irradiation therapy in 7 resectable cancer patients. Among 24 unresectable cancer patients, 17 had irradiation in combination with hyperthermia and chemotherpay. Although both degeneration and necrosis of cancer cells were observed in all resectable cases at biopsy, these were not predictive of a better outcome. Of evaluable 17 patients with unresectable cancer, tumor regression was observed in 5 (29.4%). Although 22 patients had pain before therapy, 8 and 5 patients had remarkable and moderate pain relief, respectively, with therapy. Performance status was improved in 7 patients (29.2%). Survival rate at 12 months was still low (8.3%). However, the radio-hyperthermo-chemotherapy appears to help in increasing the quality of life in view of pain relief. (N.K.)

  16. The application of hyperthermia in regional chemotherapy.

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    Di Filippo, F; Anzà, M; Rossi, C R; Cavaliere, F; Botti, C; Lise, M; Garinei, R; Giannarelli, D; Vasselli, S; Zupi, G; Cavaliere, R

    1998-01-01

    To evaluate the role of hyperthermia combined with chemotherapy in the loco-regional treatment of tumors, a retrospective analysis was done with 228 limb melanoma patients treated with hyperthermic antiblastic perfusion (HAP). A series of treatment- and tumor-related prognostic factors was analyzed to establish their influence on tumor response, loco-regional control, and survival. Concerning tumor response, the logistic model showed that the number of lesions and the minimal tumor temperature (min T) maintained their individual predictive values (P < 0.000001 and P = 0.04, respectively). For loco-regional control, only the number of lesions had a significant predictive value. No direct correlation was found between the treatment-related variables and loco-regional control. However, the 5-year survival rate was significantly higher for patients who achieved a complete response (CR) (51.5%, P = 0.0033) as compared to those who did not (33.3%), providing indirect evidence of the role of the treatment. Multivariate analysis showed that both disease-free and overall survival are strongly influenced by numerous clinical variables and the min T always maintained its significance. When analyzing the subgroup of 119 patients evaluable for tumor response, the Cox model selected the tumor response as the dominant factor for both disease-free and overall survival. These data seem to demonstrate that the optimization of treatment parameters is crucial in determining the CR rate, which, in turn, positively affects the disease outcome. HAP is the treatment of choice for recurrent limb melanoma, and hyperthermia plays an important role in exploiting the efficacy of this technique.

  17. THE FIRST EXPERIENCE OF USING LOCAL HYPERTHERMIA IN COMBINED MODALITY TREATMENT OF OPERABLE NON-SMALL CELL LUNG CANCER

    Directory of Open Access Journals (Sweden)

    A. Yu. Dobrodeev

    2015-01-01

    Full Text Available The paper presents the first experience in treating 5 patients with stage II–III non-small cell lung cancer using combined modality treatment including 40 Gy preoperative hyperfractionated radiotherapy with concurrent 2 cycles of paclitaxel/carboplatin chemotherapy and local hyperthermia (10 sessions followed by radical surgery. The overal response rate to preoperative treatment was 80 %. Chemotherapy was well tolerated and hyperthermia resulted no in adverse effects. All patients underwent surgery (4 lobectomies and 1 pneumonectomy. No complications were observed in the postoperative period. The follow-up period ranged from 6 to 20 months. No evidence of disease progression and radiation-induced damages were observed.

  18. pH- and NIR Light-Responsive Polymeric Prodrug Micelles for Hyperthermia-Assisted Site-Specific Chemotherapy to Reverse Drug Resistance in Cancer Treatment.

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    Li, Zuhong; Wang, Haibo; Chen, Yangjun; Wang, Yin; Li, Huan; Han, Haijie; Chen, Tingting; Jin, Qiao; Ji, Jian

    2016-05-01

    Despite the exciting advances in cancer chemotherapy over past decades, drug resistance in cancer treatment remains one of the primary reasons for therapeutic failure. IR-780 loaded pH-responsive polymeric prodrug micelles with near infrared (NIR) photothermal effect are developed to circumvent the drug resistance in cancer treatment. The polymeric prodrug micelles are stable in physiological environment, while exhibit fast doxorubicin (DOX) release in acidic condition and significant temperature elevation under NIR laser irradiation. Phosphorylcholine-based biomimetic micellar shell and acid-sensitive drug conjugation endow them with prolonged circulation time and reduced premature drug release during circulation to conduct tumor site-specific chemotherapy. The polymeric prodrug micelles combined with NIR laser irradiation could significantly enhance intracellular DOX accumulation and synergistically induce the cell apoptosis in DOX-resistant MCF-7/ADR cells. Meanwhile, the tumor site-specific chemotherapy combined with hyperthermia effect induces significant inhibition of MCF-7/ADR tumor growth in tumor-bearing mice. These results demonstrate that the well-designed IR-780 loaded polymeric prodrug micelles for hyperthermia-assisted site-specific chemotherapy present an effective approach to reverse drug resistance. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft-tissue sarcoma: a randomised phase 3 multicentre study

    DEFF Research Database (Denmark)

    Issels, Rolf D; Lindner, Lars H; Verweij, Jaap

    2010-01-01

    The optimum treatment for high-risk soft-tissue sarcoma (STS) in adults is unclear. Regional hyperthermia concentrates the action of chemotherapy within the heated tumour region. Phase 2 studies have shown that chemotherapy with regional hyperthermia improves local control compared with chemother...

  20. The combination of hyperthermia or chemotherapy with gimeracil for effective radiosensitization

    Energy Technology Data Exchange (ETDEWEB)

    Takagi, M.; Sakata, K.; Someya, M.; Hareyama, M. [Sapporo Medical Univ. (Japan). Dept. of Radiology; Matsumoto, Y. [Tokyo Institute of Technology, Tokyo (Japan). Research Laboratory for Nuclear Reactors; Tauchi, H. [Ibaraki Univ. (Japan). Dept. of Environmental Sciences; Fukushima, M. [Taiho Pharmaceutical Co., Ltd., Tokushima (Japan). Pharmacokinetics Research Lab.

    2012-03-15

    5-chloro-2,4-dihydroxypyridine (gimeracil) is a component of the oral fluoropyrimidine derivative S-1. Gimeracil was originally added to S-1 to yield prolonged 5-fluorouracil (5-FU) concentrations in serum and tumor tissues by inhibiting dihydropyrimidine dehydrogenase, which degrades 5-FU. We previously demonstrated that gimeracil enhances the efficacy of radiotherapy through the suppression of homologous recombination (HR) in DNA double strand repair. The goal of this paper was to examine the effects of gimeracil on the sensitivity of anticancer drugs and hyperthermia in order to obtain effective radiosensitization. Various cell lines, including DLD 1 (human colon carcinoma cells) and cells deficient in HR or nonhomologous end-joining (NHEJ), were used in clonogenic assays. The survival of these cells after various treatments (e.g., drug treatment, heat treatment, and radiation) was determined based on their colony-forming ability. Gimeracil enhanced cell-killing effects of camptothecin (CPT), 5-FU, and hydroxyurea. Gimeracil sensitized effects of CPT or 5-FU to cells deficient in HR or NHEJ to a similar extent as in other cells (DLD1 and a parent cell), indicating that its sensitizing mechanisms may be different from inhibition of HR or NHEJ. Combination of gimeracil and CPT or 5-FU sensitized radiation more effectively than each modality alone. Gimeracil also enhanced heat sensitivity at 42 C or more. The degree of heat sensitization with gimeracil increased as the temperature increased, and the combination of gimeracil and heat-sensitized radiation was more effective than each modality alone. Gimeracil enhanced sensitivity of CPT, 5-FU, and hyperthermia. Combination of these modalities sensitized radiation more efficiently than each modality alone.

  1. Ultrasound guided pO2 measurement of breast cancer reoxygenation after neoadjuvant chemotherapy and hyperthermia treatment.

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    Vujaskovic, Z; Rosen, E L; Blackwell, K L; Jones, E L; Brizel, D M; Prosnitz, L R; Samulski, T V; Dewhirst, M W

    2003-01-01

    The objective of this study was to determine whether neoadjuvant chemotherapy in combination with hyperthermia (HT) would improve oxygenation in locally advanced breast tumours. The study describes a new optimized ultrasound guided technique of pO2 measurement using Eppendorf polarographic oxygen probes in 18 stage IIB-III breast cancer patients. Prior to treatment, tumour hypoxia (median pO2pO2=3.2 mmHg). Seven patients had well oxygenated tumours (median pO2 of 48.3 mmHg). Eight patients with hypoxic tumours prior to treatment had a significant improvement (p=0.0008) in tumour pO2 after treatment (pO2 increased to 19.2 mmHg). In three patients, tumours remained hypoxic (average median pO2=4.5 mmHg). The advantages of the ultrasound guided pO2 probe are in the accuracy of the Eppendorf electrode placement in tumour tissue, the ability to monitor electrode movement through the tumour tissue during the measurement and the ability to avoid electrode placement near or in large blood vessels by using colour Doppler imaging. The results of this preliminary study suggest that the combination of neoadjuvant chemotherapy and hyperthermia improves oxygenation in locally advanced breast tumours that are initially hypoxic.

  2. Magnetic nanoparticle hyperthermia as an adjuvant cancer therapy with chemotherapy

    Science.gov (United States)

    Petryk, Alicia Ailie

    Magnetic nanoparticle hyperthermia (mNPH) is an emerging cancer therapy which has shown to be most effective when applied in the adjuvant setting with chemotherapy, radiation or surgery. Although mNPH employs heat as a primary therapeutic modality, conventional heat may not be the only cytotoxic effect. As such, my studies have focused on the mechanism and use of mNPH alone and in conjunction with cisplatinum chemotherapy in murine breast cancer cells and a related in vivo model. MNPH was compared to conventional microwave tumor heating, with results suggesting that mNPH (mNP directly injected into the tumor and immediately activated) and 915 MHz microwave hyperthermia, at the same thermal dose, result in similar tumor regrowth delay kinetics. However, mNPH shows significantly less peri-tumor normal tissue damage. MNPH combined with cisplatinum also demonstrated significant improvements in regrowth delay over either modality applied as a monotherapy. Additional studies demonstrated that a relatively short tumor incubation time prior to AMF exposure (less than 10 minutes) as compared to a 4-hour incubation time, resulted in faster heating rates, but similar regrowth delays when treated to the same thermal dose. The reduction of heating rate correlated well with the observed reduction in mNP concentration in the tumor observed with 4 hour incubation. The ability to effectively deliver cytotoxic mNPs to metastatic tumors is the hope and goal of systemic mNP therapy. However, delivering relevant levels of mNP is proving to be a formidable challenge. To address this issue, I assessed the ability of cisplatinum to simultaneously treat a tumor and improve the uptake of systemically delivered mNPs. Following a cisplatinum pretreatment, systemic mNPs uptake was increased by 3.1 X, in implanted murine breast tumors. Additional in vitro studies showed the necessity of a specific mNP/ Fe architecture and spatial relation for heat-based cytotoxicity in cultured cells.

  3. Cellular and tissue effects of hyperthermia and radiation

    International Nuclear Information System (INIS)

    Field, S.B.

    1989-01-01

    This paper presents the idea that hyperthermia is likely to be most effective in poorly perfused regions, which is where radiotherapy and chemotherapy are least effective. The author suggests that a therapeutic gain might, therefore, be obtained by combined treatments

  4. Current Status and Perspectives of Hyperthermia in Cancer Therapy

    Science.gov (United States)

    Hiraoka, Masahiro; Nagata, Yasushi; Mitsumori, Michihide; Sakamoto, Masashi; Masunaga, Shin-ichiro

    2004-08-01

    Clinical trials of hyperthermia in combination with radiation therapy or chemotherapy undertaken over the past decades in Japan have been reviewed. Originally developed heating devices were mostly used for these trials, which include RF (radiofrequency) capacitive heating devices, a microwave heating device with a lens applicator, an RF intracavitary heating device, an RF current interstitial heating device, and ferromagnetic implant heating device. Non-randomized trials for various cancers, demonstrated higher response rate in thermoradiotherapy than in radiotherapy alone. Randomized trials undertaken for esophageal cancers also demonstrated improved local response with the combined use of hyperthermia. Furthermore, the complications associated with treatment were not generally serious. These clinical results indicate the benefit of combined treatment of hyperthermia and radiotherapy for various malignancies. On the other hand, the presently available heating devices are not satisfactory from the clinical viewpoints. With the advancement of heating and thermometry technologies, hyperthermia will be more widely and safely used in the treatment of cancers.

  5. Comparative evaluation of combined irradiation and hyperthermia versus irradiation alone

    International Nuclear Information System (INIS)

    Sawas-Dimopoulou, C.; Iordanou, I.; Uzunoglu, N.; Dardoufas, K.; Kouloulias, V.; Maris, T.; Kotaridis, S.

    1994-01-01

    Controvesy remains as to the treatment schedule producing better results in combined hyperthermia and X-ray therapy. Our experience concerning combined therapy of the solid tumour Walker carcinoma is reported. Male Wistar rats were submitted to treatment on the ninth day after transplantation of the tumour. Two groups of rats received either a therapeutic X-ray dose of 800 cGy by a 6-MeV linear accelerator (Mevatron, Siemens) or treatment by 432 MHz of microwaves with continuous control of tumour tissue temperature to 44±1 C for 45 min. Another group of rats was submitted to a combined treatment, with X-ray therapy preceding hyperthermia by 24 h. The last group of animals constituted the control rats. Greater tumour regression and longer survival times were obtained with the combined treatment. The gain factor for survival time was equal to 1.85 after combined treatment compared with 1.30 after X-ray therapy and 1.05 after hyperthermia. In conclusion, the results suggest that in the above schedule of combined treatment, hyperthermia applied to a solid tumour 24 h after a single dose of X-rays enhances the beneficial effect of therapy. (orig.)

  6. Numerical modeling for an electric-field hyperthermia applicator

    Science.gov (United States)

    Wu, Te-Kao; Chou, C. K.; Chan, K. W.; Mcdougall, J.

    1993-01-01

    Hyperthermia, in conjunction with radiation and chemotherapy for treatment of cancers, is an area of current concern. Experiments have shown that hyperthermia can increase the potency of many chemotherapy drugs and the effectiveness of radiation for treating cancer. A combination of whole body or regional hyperthermia with chemotherapy or radiation should improve treatment results. Conventional methods for inducing whole body hyperthermia, such as exposing a patient in a radiant cabinet or under a hot water blanket, conduct heat very slowly from the skin to the body core. Thus a more efficient system, such as the three-plate electric-field hyperthermia applicator (EHA), is developed. This three-plate EHA has one top plate over and two lower plates beneath the patient. It is driven at 27.12 MHz with 500 Watts through a matching circuit. Using this applicator, a 50 kg pig was successfully heated to 42 C within 45 minutes. However, phantom and animal studies have indicated non-uniform heating near the side of the body. In addition, changes in the size and distance between the electrode plates can affect the heating (or electromagnetic field) pattern. Therefore, numerical models using the method of moments (MOM) or the finite difference time domain (FDTD) technique are developed to optimize the heating pattern of this EHA before it is used for human trials. The accuracy of the numerical modeling has been achieved by the good agreement between the MOM and FDTD results for the three-plate EHA without a biological body. The versatile FDTD technique is then applied to optimize the EHA design with a human body. Both the numerical and measured data in phantom blocks will be presented. The results of this study will be used to design an optimized system for whole body or regional hyperthermia.

  7. Radiotherapy and local hyperthermia plus androgen suppression in locally advanced prostate cancer

    International Nuclear Information System (INIS)

    Maluta, S.; Marciai, N.; Gabbani, M.; Palazzi, M.; Dall'Oglio, S.; Grandinetti, A.

    2005-01-01

    Full text: In advanced prostatic cancer, hyperthermia may be useful in order to enhance irradiation efficacy so to avoid delivering of too high dose of radiotherapy which increases acute and late sequelae. A multi-centric phase II study is warranted to give hyperthermia a level 3 evidence in prostate cancer treatment. A randomized phase III study to demonstrate efficacy of hyperthermia is not available because of the optimal results obtained by using radiotherapy combined with androgen suppression. To evaluate hyperthermia gain, LHT should be combined with radiotherapy alone in patients refusing androgen suppression or affected by hormone refractory prostate carcinoma (HRPC). Patients with HRPC have multiple possibilities of treatment improving performance status and median survival, as chemotherapy regimens, and new agents. All these treatments modalities need to be confirmed by phase III trials. Also hyperthermia may be considered among these promising approaches. (author)

  8. Combination hyperthermia and intraarterial 5-FU for metastatic colon carcinoma to liver

    International Nuclear Information System (INIS)

    Moseley, H.S.; Palmquist, M.

    1984-01-01

    Metastatic colorectal carcinoma to the liver remains a formidable challenge. Responses to chemotherapy are brief and the number of effective drugs is very limited. A phase II trial of hepatic hyperthermia and intraarterial chemotherapy was undertaken to attempt to improve response rates and duration. Patients were given a 10 day course of IA 5-FU at 15 mg/kg. During the infusion hyperthermia was given five times using the BSD Annular Phased Array (APA). Thermistors were placed percutaneously into normal liver and tumor using ultrasound or CT scan guidance. Six patients have been treated. Significant problems in positioning ill patients in the APA were encountered, and there was difficulty also in preventing heating throughout the abdominal cavity. Four patients, all with poor performance status, failed to benefit. One patient had improvement in liver function studies for two months and failed to respond on a repeat course. One patient had a complete response which is continuing over 18 months with a liver scan reverting to normal and CEA returning to normal. These preliminary results are promising and warrant further trials

  9. Boosted Hyperthermia Therapy by Combined AC Magnetic and Photothermal Exposures in Ag/Fe3O4 Nanoflowers.

    Science.gov (United States)

    Das, R; Rinaldi-Montes, N; Alonso, J; Amghouz, Z; Garaio, E; García, J A; Gorria, P; Blanco, J A; Phan, M H; Srikanth, H

    2016-09-28

    Over the past two decades, magnetic hyperthermia and photothermal therapy are becoming very promising supplementary techniques to well-established cancer treatments such as radiotherapy and chemotherapy. These techniques have dramatically improved their ability to perform controlled treatments, relying on the procedure of delivering nanoscale objects into targeted tumor tissues, which can release therapeutic killing doses of heat either upon AC magnetic field exposure or laser irradiation. Although an intense research effort has been made in recent years to study, separately, magnetic hyperthermia using iron oxide nanoparticles and photothermal therapy based on gold or silver plasmonic nanostructures, the full potential of combining both techniques has not yet been systematically explored. Here we present a proof-of-principle experiment showing that designing multifunctional silver/magnetite (Ag/Fe3O4) nanoflowers acting as dual hyperthermia agents is an efficient route for enhancing their heating ability or specific absorption rate (SAR). Interestingly, the SAR of the nanoflowers is increased by at least 1 order of magnitude under the application of both an external magnetic field of 200 Oe and simultaneous laser irradiation. Furthermore, our results show that the synergistic exploitation of the magnetic and photothermal properties of the nanoflowers reduces the magnetic field and laser intensities that would be required in the case that both external stimuli were applied separately. This constitutes a key step toward optimizing the hyperthermia therapy through a combined multifunctional magnetic and photothermal treatment and improving our understanding of the therapeutic process to specific applications that will entail coordinated efforts in physics, engineering, biology, and medicine.

  10. Re-irradiation and hyperthermia after surgery for recurrent breast cancer

    International Nuclear Information System (INIS)

    Linthorst, Marianne; Geel, Albert N. van; Baaijens, Margreet; Ameziane, Ali; Ghidey, Wendim; Rhoon, Gerard C. van; Zee, Jacoba van der

    2013-01-01

    Purpose: Evaluation of efficacy and side effects of combined re-irradiation and hyperthermia electively or for subclinical disease in the management of locoregional recurrent breast cancer. Methods and materials: Records of 198 patients with recurrent breast cancer treated with re-irradiation and hyperthermia from 1993 to 2010 were reviewed. Prior treatments included surgery (100%), radiotherapy (100%), chemotherapy (42%), and hormonal therapy (57%). Ninety-one patients were treated for microscopic residual disease following resection or systemic therapy and 107 patients were treated electively for areas at high risk for local recurrences. All patients were re-irradiated to 28–36 Gy (median 32) and treated with 3–8 hyperthermia treatments (mean 4.36). Forty percent of the patients received concurrent hormonal therapy. Patient and tumor characteristics predictive for actuarial local control (LC) and toxicity were studied in univariate and multivariate analysis. Results: The median follow-up was 42 months. Three and 5 year LC-rates were 83% and 78%. Mean of T90 (tenth percentile of temperature distribution), maximum and average temperatures were 39.8 °C, 43.6 °C, and 41.2 °C, respectively. Mean of the cumulative equivalent minutes (CEM43) at T90 was 4.58 min. Number of previous chemotherapy and surgical procedures were most predictive for LC. Cumulative incidence of grade 3 and 4 late toxicity at 5 years was 11.9%. The number of thermometry sensors and depth of treatment volume were associated with acute hyperthermia toxicity. Conclusions: The combination of re-irradiation and hyperthermia results in a high LC-rate with acceptable toxicity

  11. Combining radiation with hyperthermochemotherapy (Cis-DDP) for advanced, recurrent esophageal cancer

    International Nuclear Information System (INIS)

    Endou, Masaru; Suzuki, Hirotoshi; Nakashima, Yukihiro

    1991-01-01

    We treated 20 cases of squamous cell carcinoma of the esophagus, combining radiation, chemotherapy and hyperthermia. Hyperthermia combining chemotherapy consisting of cis-dichlorodiamine platinum (25∼75 mg/body, every week) in the form continuous intravenous infusion was given. The hyperthermochemotherapy only had limited effectiveness but good response was noted for post-operative and post-irradiative adjuvant hyperthermochemotherapy. Heating could alleviate some chemotherapeutic side effects, especially renal damage or audiometric disturbance. Furthermore, hyperthermia relieved some radiation side effects, such as radiation-induced scleroderma probably due to hypercirculation. We believe that combining hyperthermochemotherapy with radiation is promising for advanced, recurrent esophageal cancer. (author)

  12. Combining radiation with hyperthermochemotherapy (Cis-DDP) for advanced, recurrent esophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Endou, Masaru; Suzuki, Hirotoshi; Nakashima, Yukihiro (Saint Marianna Univ., Kawasaki, Kanagawa (Japan). School of Medicine) (and others)

    1991-10-01

    We treated 20 cases of squamous cell carcinoma of the esophagus, combining radiation, chemotherapy and hyperthermia. Hyperthermia combining chemotherapy consisting of cis-dichlorodiamine platinum (25{approx}75 mg/body, every week) in the form continuous intravenous infusion was given. The hyperthermochemotherapy only had limited effectiveness but good response was noted for post-operative and post-irradiative adjuvant hyperthermochemotherapy. Heating could alleviate some chemotherapeutic side effects, especially renal damage or audiometric disturbance. Furthermore, hyperthermia relieved some radiation side effects, such as radiation-induced scleroderma probably due to hypercirculation. We believe that combining hyperthermochemotherapy with radiation is promising for advanced, recurrent esophageal cancer. (author).

  13. The application of early post-operative combination therapy with interstitial hyperthermia in the treatment of malignant gliomas

    International Nuclear Information System (INIS)

    Stahl, H.; Wust, P.; Maier-Hauff, K.; Seebass, M.; Mischel, M.; Grammler, M.; Golde, G.; Loeffel, J.; Felix, R.

    1995-01-01

    A pilot study was performed to examine practicality, tolerability, effectiveness and scope for improvement in early postoperative hyperthermia treatment following catheter implantation as part of (partial) tumor resection. Each CT data set was transferred into a VAX 3100 workstation for retrospective analysis of the hyperthermia treatment. The implanted catheters were segmented and the distributions of power density and temperature were simulated. We sought to achieve the best possible temperature distributions by optimising the catheter arrangement in the planning calculations. The corresponding Ir-192-source brachytherapy treatments were simulated in a similar way using the implanted, as well as optimised catheter arrays. Intraoperative catheter implantation in 4 patients was problem-free. Postoperative complications were not observed, neither were infections. Interstitial microwave hyperthermia in combination with percutaneous irradiation or chemotherapy a few days after the operation was also tolerated well by all patients. Effective temperatures (of at least 42 C) were regularly achieved at measurement points, but the temperature distributions were unsatisfactory, with T 90 values (the temperature reached in at least 90% of the target volume) of under 38 C. Measured temperature/position curves showed qualitative correlation with the simulated calculations. The catheter positions determined by optimisation varied significantly from the positions clinically used. (orig./MG) [de

  14. Effect of hyperthermia in combination with radiation therapy in a rat glioma model

    International Nuclear Information System (INIS)

    Tamura, Masaru; Zama, Akira; Kunimine, Hideo; Tamaki, Yoshio; Niibe, Hideo

    1988-01-01

    Rat glioma model was used to evaluate the effect of hyperthermia with and without radiation therapy. The animal model was induced by left frontal burr hole opening and inoculation of a small piece of G-XII glioma tissue to 6- to 8-week-old rats. The therapeutical experiments were given 10 - 14 days after inoculation of the tumor. Interstitial heating at 44 and 45 deg C at the surface of the inserting probe using 2450 MHz microwave was delivered for 30 minutes. Deep X-ray whole head irradiation of 800 R using Stabilipan 2 (Siemens) was given just after the hyperthermia therapy. The survival of treated animals of hyperthermia, radiation, and combination of hyperthermia and radiation was significantly superior to that of non-treated control group. There was no significant difference of survival among the treated groups, though median survival was longest in the group of combination therapy of hyperthermia and radiation. Large tumors developed at the time of death in all the control and the treated animals. Histological examination showed some tendencies of macrophage infiltration in tumor tissue of hyperthermia therapy. (author)

  15. Assessment of immunomodulating action of combined therapy with UHF-hyperthermia in children with osteogenic sarcoma

    International Nuclear Information System (INIS)

    Neprina, G.S.; Panteleeva, E.S.; Vatin, O.E.; Bizer, V.A.; Bojko, I.N.

    1989-01-01

    The paper is concerned with immunological evaluation of different stages of combined therapy with local UHF-hyperthermia in children with osteogenic sarcoma. Combined therapy (polychemo- and raditherapy) was shown to cause a decrease in the number of immunocompetent cells, to enhance dysbalance of immunoregulatory T-lymphocytes, to weaken T-lymphocyte function on PHA; immunosuppressive action of combined therapy did not depend on a tumor site. The incorporation of UHF-hyperthermia in the therapeutic scheme weakened the manifestations of secondary immunodeficiency, got back to normal structure of T-lymphocyte population. A favorable immunomodulating effect of hyperthermia was more frequently observed in patients with crural bone tumors. The effect of hyperthermia was revealed after direct influence of thermotherapy but it was absent in continuation of combined treatment

  16. Biological effects of hyperthermia

    International Nuclear Information System (INIS)

    Okumura, Hiroshi

    1980-01-01

    Biological effects of hyperthermia and application of hyperthermia to cancer therapy were outlined. As to independent effects of hyperthermia, heat sensitivity of cancer cells, targets of hyperthermia, thermal tolerance of cancer cells, effects of pH on hyperthermic cell survival, effects of hyperthermia on normal tissues, and possibility of clinical application of hyperthermia were described. Combined effect of hyperthermia and x-irradiation to enhance radiosensitivity of cancer cells, its mechanism, effects of oxygen on cancer cells treated with hyperthermia and irradiation, and therapeutic ratio of combined hyperthermia and irradiation were also described. Finally, sensitizers were mentioned. (Tsunoda, M.)

  17. On the improvement of regional hyperthermia treatment

    NARCIS (Netherlands)

    Kroeze, Hugo

    2002-01-01

    Hyperthermia is an adjuvant treatment modality to radiotherapy and/or chemotherapy, with the aim of increasing the tumour killing effect of the treatment. It involves the elevation of the tumour temperature to ~ 42oC. Radiofrequent heating is a practical method for hyperthermia: a number of

  18. Hyperthermia and radiotherapy

    International Nuclear Information System (INIS)

    Fitspatrick, C.

    1990-01-01

    Hyperthermia and radiotherapy have for long been used to assist in the control of tumours, either as separate entities, or, in a combined treatment scheme. This paper outlines why hyperthermia works, thermal dose and the considerations required in the timing when hyperthermia is combined with radiotherapy. Previously reported results for hyperthermia and radiotherapy used together are also presented. 8 refs., 8 tabs

  19. Application and possible mechanisms of combining LLLT (low level laser therapy), infrared hyperthermia and ionizing radiation in the treatment of cancer

    Science.gov (United States)

    Abraham, Edward H.; Woo, Van H.; Harlin-Jones, Cheryl; Heselich, Anja; Frohns, Florian

    2014-02-01

    Benefit of concomitant infrared hyperthermia and low level laser therapy and ionizing radiation is evaluated in this study. The purpose/objectives: presentation with locally advanced bulky superficial tumors is clinically challenging. To enhance the efficacy of chemotherapy and IMRT (intensity-modulated radiation therapy) and/or electron beam therapy we have developed an inexpensive and clinically effective infrared hyperthermia approach that combines black-body infrared radiation with halogen spectrum radiation and discrete wave length infrared clinical lasers LLLT. The goal is to produce a composite spectrum extending from the far infrared to near infrared and portions of the visible spectrum with discrete penetrating wavelengths generated by the clinical infrared lasers with frequencies of 810 nm and/or 830 nm. The composite spectrum from these sources is applied before and after radiation therapy. We monitor the surface and in some cases deeper temperatures with thermal probes, but use an array of surface probes as the limiting safe thermal constraint in patient treatment while at the same time maximizing infrared entry to deeper tissue layers. Fever-grade infrared hyperthermia is produced in the first centimeters while non-thermal infrared effects act at deeper tissue layers. The combination of these effects with ionizing radiation leads to improved tumor control in many cancers.

  20. Radiation therapy combined with hyperthermia in advanced cancer

    International Nuclear Information System (INIS)

    Okuma, Akiko; Terashima, Hiromi; Torii, Yoshikuni; Nakata, Hajime; Inatomi, Hisato

    1986-01-01

    Radiation therapy combined with radiofrequency (RF) hyperthermia was performed on 5 advanced cancer patients. Included were one each with urinary bladder cancer, hepatoma with left axillary node metastasis, breast cancer, tongue cancer with left cervical metastasis, and mandibular cancer. All had large tumors, which were judged to be uncontrollable by radiotherapy alone. They were treated with irradiation (Linac: 10 MV X-ray 1.8 - 2.0 Gy/day, 5 days/week), followed within an hour by RF hyperthermia once or twice a week. Partial response was obtained in the urinary bladder cancer patient. Surface overheating around the margin of electrodes occurred in all but no severe complications were observed. (author)

  1. Findings in young pigs following combined treatment by hyperthermia and irradiation

    International Nuclear Information System (INIS)

    Schorcht, J.; Herrmann, T.; Barke, R.; Johannsen, U.

    1985-01-01

    In a pilot study, 8 store pigs were submitted to a combined treatment with hyperthermia (5 x 60 min; 42 0 C in the thoracic region) followed by telecobalt irradiation of the right lung (5 x 4 Gy). Radiologic checks of the thoracic organs and laboratory diagnostics provided useful data as to the temporal course of the radiogenic pulmonary affections and the tolerability of fractionated whole-body hyperthermia including superimposed local heating on store pigs. Histologic examinations of sections of heated and irradiated (right) as compared to exclusively heated (left) lung lobes of 4 animals suggested that hyperthermia exerted a radiosensitizing effect on the right lungs. Histologically confirmed irreversible lung fibrosis occurred there after exposure to even lower total doses following hyperthermia as compared to sole irradiation. (author)

  2. Hyperthermia for the Treatment of Locally Advanced Cervix Cancer

    NARCIS (Netherlands)

    M. Franckena (Martine)

    2010-01-01

    textabstract(English): There is a strong biological rationale for the use of hyperthermia as an oncological treatment modality. Fifteen randomized trials have shown significant improvement in clinical outcome when hyperthermia was added to radiotherapy, chemotherapy or both. At temperatures ≥ 40

  3. Radiation plus local hyperthermia versus radiation plus the combination of local and whole-body hyperthermia in canine sarcomas

    International Nuclear Information System (INIS)

    Thrall, Donald E.; Prescott, Deborah M.; Samulski, Thaddeus V.; Rosner, Gary L.; Denman, David L.; Legorreta, Roberto L.; Dodge, Richard K.; Page, Rodney L.; Cline, J. Mark; Lee Jihjong; Case, Beth C.; Evans, Sydney M.; Oleson, James R.; Dewhirst, Mark W.

    1996-01-01

    Purpose: The purpose of this study was to assess the effect of increasing intratumoral temperatures by the combination of local hyperthermia (LH) and whole body hyperthermia (WBH) on the radiation response of canine sarcomas. Methods and Materials: Dogs with spontaneous soft tissue sarcomas and no evidence of metastasis were randomized to be treated with radiation combined with either LH alone or LH + WBH. Dogs were accessioned for treatment at two institutions. The radiation dose was 56.25 Gy, given in 25 2.25 Gy daily fractions. Two hyperthermia treatments were given; one during the first and one during the last week of treatment. Dogs were evaluated after treatment for local recurrence, metastasis, and complications. Results: Sixty-four dogs were treated between 1989 and 1993. The use of LH+WBH resulted in statistically significant increases in the low and middle regions of the temperature distributions. The largest increase was in the low temperatures with median CEM 43 T90 values of 4 vs. 49 min for LH vs. LH + WBH, respectively (p < 0.001). There was no difference in duration of local tumor control between hyperthermia groups (p = 0.59). The time to metastasis was shorter for dogs receiving LH + WBH (p = 0.02); the hazard ratio for metastatic disease for dogs in the LH + WBH group was 2.5 (95% confidence interval, 1.2-5.4) with respect to dogs in the LH group. Complications were greater in larger tumors and in tumors treated with LH + WBH. Conclusion: The combination of LH + WBH with radiation therapy, as described herein, was not associated with an increase in local tumor control in comparison to use of LH with radiation therapy. The combination of LH + WBH also appeared to alter the biology of the metastatic process and was associated with more complications than LH. We identified no rationale for further study of LH + WBH in combination with radiation for treatment of solid tumors

  4. Combination (RaHPP) of radiotherapy, hyperthermia and chemotherapy (peplomycin and picibanil) for bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Washida, Hiroto; Tsugaya, Masayuki; Hirao, Noriaki; Hachisuka, Yusuke

    1984-09-01

    Four patients with urinary bladder carcinoma were treated by combination therapy which consisted of hyperthermia vesical irrigation of two anticancer drugs (peplomycin and picibanil), intravesical instillation of those drugs and radiation. Following the therapeutic method we planned, 40 mg of peplomycin and 10 KE of picibanil in 1,500 ml of sterile distilled water was irrigated at 42 to 43/sup 0/C into the bladder for 3 hours; 40 mg of peplomycin and 10 KE of picibanil in 40 ml of sterile distilled water was instilled into the bladder; and, the focus was irradiated with /sup 60/Co to a focal dose of 200 rad 30 minutes later. This pattern of treatment was repeated once a week, 3 to 5 times in total. On the days this pattern was not taken, 5 KE of picibanil in 20 ml of sterile distilled water was instilled into the bladder cavity. Complete response was observed in one patient and partial response in 3 patients. The side effect was temporary irritable bladder symptom. (author).

  5. Combination (RaHPP) of radiotherapy, hyperthermia and chemotherapy (peplomycin and picibanil) for bladder cancer

    International Nuclear Information System (INIS)

    Washida, Hiroto; Tsugaya, Masayuki; Hirao, Noriaki; Hachisuka, Yusuke

    1984-01-01

    Four patients with urinary bladder carcinoma were treated by combination therapy which consisted of hyperthermia vesical irrigation of two anticancer drugs (peplomycin and picibanil), intravesical instillation of those drugs and radiation. Following the therapeutic method we planned, 40 mg of peplomycin and 10 KE of picibanil in 1,500 ml of sterile distilled water was irrigated at 42 to 43 0 C into the bladder for 3 hours; 40 mg of peplomycin and 10 KE of picibanil in 40 ml of sterile distilled water was instilled into the bladder; and, the focus was irradiated with 60 Co to a focal dose of 200 rad 30 minutes later. This pattern of treatment was repeated once a week, 3 to 5 times in total. On the days this pattern was not taken, 5 KE of picibanil in 20 ml of sterile distilled water was instilled into the bladder cavity. Complete response was observed in one patient and partial response in 3 patients. The side effect was temporary irritable bladder symptom. (author)

  6. An experimental study on the alteration of thermal enhancement ratio by combination of split dose hyperthermia irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sun Ok; Kim, Hee Seup [Ewha Womens University College of Medicine, Seoul (Korea, Republic of)

    1983-06-15

    The study was undertaken to evaluate the alteration of thermal enhancement ratio as a function of time intervals between two split dose hyperthermias followed by irradiation. For the experiments, 330 mice were divided into 3 groups; the first, 72 mice were used to evaluate the heat reaction by single dose hyperthermia and heat resistance by split dose hyperthermia, the second, 36 mice were used to evaluate the radiation reaction by irradiation only, and the third, 222 mice were used for TER observation by combination of single dose hyperthermia and irradiation, and TER alteration by combination of split dose hyperthermia and irradiation. For each group the skin reaction score of mouse tail was used for observation and evaluation of the result of heat and irradiation. The results obtained are summarized as follows: 1. The heating time resulting 50% necrosis (ND{sub 5}0) Was 101 minutes in 43 .deg. C and 24 minutes in 45 .deg. C hyperthermia, which indicated that three is reciprocal proportion between temperature and heating time. 2. Development of heat resistance was observed by split dose hyperthermia. 3. The degree of skin reaction by irradiation only was increased proportionally as a function of radiation dose, and calculated radiation dose corresponding to skin score 1.5 (D{sub 1}.5) was 4,137 rads. 4. Obtained thermal enhancement ratio by combination of single dose hyperthermia and irradiation was increased proportionally as a function of heating time. 5. Thermal enhancement ratio was decreased by combination of split dose hyperthermia and irradiation, which was less intense and lasted longer than development of heat resistance. In summary, these studies indicate that the alteration of thermal enhancement ratio has influence on heat resistance by split dose hyperthermia and irradiation.

  7. Deep RF-hyperthermia: an effective treatment of advanced gliomas

    International Nuclear Information System (INIS)

    Sahinbas, H.; Groenemeyer, D.H.W.

    2005-01-01

    Full text: Contrary to the enormous efforts, results of conventional treatments of high-grade malignant gliomas are unsatisfactory. The prognosis of that tumor type is poor, its overall median survival time (MST) less than a year. Most of the cases are inoperable or only partially resectable, and their response to the various chemotherapies and/or radiotherapy is poor. The chemo-therapies which are successful for other locations often fail due to the effective brain-blood barrier (BBB). Probably the modification of the BBB by electromagnetic fields together with the direct electromagnetic-field heating are the main factors for the success of electro-hyperthermia. Primary aim of this study was to present the therapy tolerance for patients of electro-hyperthermia (EHY) for advanced malignant gliomas and as main intention to show the increase of the median survival time (MST). Our study was performed between 2000 - 2004; for patients with inoperable, partially resected or recurrent gliomas (WHO grade III and IV) with progression after radio- and/or chemotherapy and a Karnofsky Performance Score ≤30-40 %. 105 pts were involved in this study: 38 astrocytoma pts, 56 glioblastoma pts and 12 pts with other brain malignancies. All patients were heavily and unsatisfactory pretreated. EHY was applied over 4 weeks, 3 times a week over 1 hour in average by 100 Watt, as mono- or combined therapy (chemotherapy, irradiation therapy). The set of patients as well as the frequency of EHY was well documented for future evaluations. The historic reference of the MST from the first diagnosis for gliomas grade III and IV in our institute is 11.42 months (range 1-62), which is in good agreement with the relevant literature. The median survival time (MST) in our institute with EHY increases to 44.2 m, 23.2 m and 61.0 m for astrocytoma, glioblastoma and other brain malignancies, respectively. The therapy results were controlled by MRI images. EHY is a feasible treatment for advanced

  8. Cisplatin, hyperthermia, and radiation (trimodal therapy) in patients with locally advanced head and neck tumors: A phase I-II study

    International Nuclear Information System (INIS)

    Amichetti, M.; Graiff, C.; Fellin, G.; Pani, G.; Bolner, A.; Maluta, S.; Valdagni, R.

    1993-01-01

    Hyperthermia is now being widely used to treat clinical malignancies, especially combined with radiotherapy and more rarely with chemotherapy. The combination of heat, radiation, and chemotherapy (trimodality) can lead to potent interaction. The present Phase I-II study was conducted to evaluate the feasibility and acute toxicity of a combination of cisplantin, hyperthermia, and irradiation in the treatment of superficial cervical nodal metastases from head and neck cancer. Eighteen patients with measurable neck metastases from previously untreated squamous cell head and neck tumors were entered into the trial. Therapy consisted of a conventional irradiation (total dose 70 Gy, 2 Gy five times a week) combined with a weekly administration of 20 mg/m 2 iv of cisplatin and a total of two sessions of local external microwave hyperthermia (desired temperature of 42.5 degrees C for 30 min). Feasibility of the treatment was demonstrated. Acute local toxicity was mild; no thermal blisters or ulcerations were reported and only two patients experienced local pain during hyperthermia. Cutaneous toxicity appeared greater than in previous studies with irradiation plus hyperthermia and irradiation plus cisplatin. Systematic toxicity was moderate with major toxic effects observed in three patients (World Health Organization (WHO) grade 3 anaemia). Even though it was not an aim of the study to evaluate the nodal response, they observed a complete response rate of 72.2% (95% confidence interval 51-93.4%), 16.6% of partial response and 11.1% of no change. The study confirms the feasibility of the combination of cisplantin, heat, and radiation with an acceptable toxicity profile. The trimodal therapy deserves further evaluation as a way to enhance the efficacy of irradiation in the treatment of nodal metastases from head and neck tumors. 43 refs., 3 figs., 4 tabs

  9. Trial of radiation therapy combined with hyperthermia

    Energy Technology Data Exchange (ETDEWEB)

    Takegawa, Y; Fujiwara, K; Oe, J; Nagase, M; Akiyama, H [Tokushima Univ. (Japan). School of Medicine

    1978-08-01

    Nine patients were treated by the combination therapy of external irradiation and hyperthermia, 5 patients with metastatic lesions; two breast cancer, one lung cancer, one malignant melanoma, one vulva cancer, 1 patient with recurrent lesion of skin cancer and 3 patients with bladder cancer. All patients were treated by heating locally (42/sup 0/C, 30 min) followed by external irradiation with 4,000 - 5,000 rad over 4 to 5 weeks. No local recurrence was found in 4 of 9 patients.

  10. Local hyperthermia, radiation, and chemotherapy in recurrent breast cancer is feasible and effective except for inflammatory disease

    Energy Technology Data Exchange (ETDEWEB)

    Feyerabend, Thomas; Wiedemann, Guenter Joseph; Jaeger, Birgit; Vesely, Hugo; Mahlmann, Birgit; Richter, Eckart

    2001-04-01

    Purpose: To investigate the feasibility and effectiveness of radiochemothermotherapy (triple-modality therapy) in patients with inoperable recurrent breast cancer. Patients and Methods: Patients with inoperable recurrent lesions, World Health Organization (WHO) performance status of 2 or greater, life expectancy of more than 3 months, adequate bone marrow, hepatic and renal function were eligible for this Phase I/II study. Conventionally fractionated or hyperfractionated radiotherapy (RT) was performed. Once-weekly local hyperthermia (HT) combined with chemotherapy (CT; epirubicin 20 mg/m{sup 2}, ifosfamide 1.5 g/m{sup 2}) was applied within 30 min after RT. Results: Twenty-five patients, all heavily pretreated (18/25 preirradiated), received a mean total dose of 49 Gy. The median number of HT/CT sessions was 4. Skin toxicity was low, whereas bone marrow toxicity was significant (leucopenia Grade 3/4 in 14/1 patients). The overall response rate was 80% with a complete response (CR) rate of 44%. Response rates in patients with noninflammatory disease (n=14; CR 10 patients, partial response [PR] 3 patients) were far better than in patients with inflammatory disease (n=11; CR 1 patient, PR 6 patients). Conclusions: In patients with recurrent breast cancer, triple-modality therapy is feasible with acceptable toxicity. High remission rates can be achieved in noninflammatory disease, however, local control is limited to a few months. Whether the addition of chemotherapy has a clear-cut advantage to radiothermotherapy alone remains an open question.

  11. Local hyperthermia, radiation, and chemotherapy in recurrent breast cancer is feasible and effective except for inflammatory disease

    International Nuclear Information System (INIS)

    Feyerabend, Thomas; Wiedemann, Guenter Joseph; Jaeger, Birgit; Vesely, Hugo; Mahlmann, Birgit; Richter, Eckart

    2001-01-01

    Purpose: To investigate the feasibility and effectiveness of radiochemothermotherapy (triple-modality therapy) in patients with inoperable recurrent breast cancer. Patients and Methods: Patients with inoperable recurrent lesions, World Health Organization (WHO) performance status of 2 or greater, life expectancy of more than 3 months, adequate bone marrow, hepatic and renal function were eligible for this Phase I/II study. Conventionally fractionated or hyperfractionated radiotherapy (RT) was performed. Once-weekly local hyperthermia (HT) combined with chemotherapy (CT; epirubicin 20 mg/m 2 , ifosfamide 1.5 g/m 2 ) was applied within 30 min after RT. Results: Twenty-five patients, all heavily pretreated (18/25 preirradiated), received a mean total dose of 49 Gy. The median number of HT/CT sessions was 4. Skin toxicity was low, whereas bone marrow toxicity was significant (leucopenia Grade 3/4 in 14/1 patients). The overall response rate was 80% with a complete response (CR) rate of 44%. Response rates in patients with noninflammatory disease (n=14; CR 10 patients, partial response [PR] 3 patients) were far better than in patients with inflammatory disease (n=11; CR 1 patient, PR 6 patients). Conclusions: In patients with recurrent breast cancer, triple-modality therapy is feasible with acceptable toxicity. High remission rates can be achieved in noninflammatory disease, however, local control is limited to a few months. Whether the addition of chemotherapy has a clear-cut advantage to radiothermotherapy alone remains an open question

  12. Hormonal, Biochemical and Haematological Changes in Response to Acute Hyperthermia in Rabbits

    International Nuclear Information System (INIS)

    Zahran, N.A.R.M.

    2004-01-01

    Today, hyperthermia plays a significant role in the evidence-based on treatment of cancer patients. Such promising endeavor is due to the fact that neoplastic cells are more heat sensitive than normal cells. the prospect of using hyperthermia alone to treat cancer tumours is appealing because hyperthermia is a physical treatment and so would have fewer side effects than chemotherapy or radiotherapy and, it could be used in combination with these therapeutic approaches. much more consistent evidence has been obtained experimentally, and continuing clinical interest has been encouraged by confirmation that, at relatively low temperature (37-41.5 C), heat enhances cell growth and may well enhance also the growth and proliferation of tumours, while above 45 C heat begins to damage both normal and malignant cells in both animal and human. So, the goal is to achieve a selective temperature elevation between 42-45 C at the tumour site while maintaining healthy tissue temperatures in a physiological save range.This study was undertaken to investigate the effect of acute whole body hyperthermia , (WBH) (rectal temperature 43 c) on biochemical , hormonal and haematological changes in normal healthy local strain (baladi) rabbits.The thermal late effects (recovery) at 24 hr-post whole body hyperthermia was also undertaken , in the attempt to evaluate the degree of safety , when hyperthermia is applied in the clinic for treating cancer and other diseases

  13. Hyperthermia-induced degradation of BRCA2 : from bedside to bench and back again

    NARCIS (Netherlands)

    N. van den Tempel (Nathalie)

    2017-01-01

    markdownabstractLocal hyperthermia, a method during which the temperature of a tumor is elevated, clinically increases the efficacy of radiotherapy and chemotherapy, without increasing side-effects. One of the reasons that explains why hyperthermia increases effectivity of these therapies is that it

  14. Local hyperthermia and artificial hyperglycemia in combined treatment of patients with rectum cancer

    International Nuclear Information System (INIS)

    Bezmen, V.A.; Illarionov, A.A.; Novokhrost, V.I.; Shilov, N.I.; Ospishchev, A.A.; Kejs, G.D.

    1990-01-01

    To study prospects of application of local hyperthermia, artificial hyperglycemia and radiotherapy in a preoperative period, 31 patients with rectum cancer were studied. The treatment included 3-hour artificial hyperglycemia first, then local SHF hyperthermia and telegamma irradiation using large-fractioned doses (ROD is 5 Gy, COD is 20 Gy). No serious side-effects were observed during the preoperative treatment period. The immediate and early results of combined treatment promise to improve the effectiveness of treatment of patients with rectum cancer. 3 refs

  15. The individual and combined effects of γ rays and hyperthermia on the development of embryonic brains

    International Nuclear Information System (INIS)

    Yang Yepeng; Ruan Ming; Liu Jingyuan; Hong Min; Lu Chunlin

    2000-01-01

    Objective: To observe the individual and combined effects of exposure to γ rays and hyperthermia on the development of embryonic brains. Methods: the pregnant LACA mice were exposed to 1.0 Gy 60 Co-γ rays, 42 degree C hyperthermia for 10 minutes or the two treatments combined together on day 9 of pregnancy. The females were sacrificed on day 18 of pregnancy and the fetuses were gained by cesarean section. The appearance of fetuses was observed and, then, the weight of fetal brains, the cell number of whole brains, the contents of nucleic acid and protein in brain tissue and the activity of acetylcholine esterase (AChE) in brain tissue as a marker for cholinergic neurons were determined. Results: Nervous tube defects did not occur in all groups. Compared with the control group, all the indices determined significantly declined in the radiation group while the cell number of whole brains and the AChE activity in brain tissue significantly decreased in the hyperthermia group. In the group of hyperthermia in advance, 4 hours later, followed by exposure to radiation, the AChE activity in brain tissue was significantly higher than the single radiation group. In the group of prior radiation exposure, 4 hours later, followed by hyperthermia, all the indices did not present significant difference from the single radiation group. Conclusion: The effects of 42 degree C hyperthermia for 10 minutes on the development of mouse embryo's brains are much weaker than 1.0 Gy γ radiation. It seems that the hyperthermia in advance can induce mouse fetuses to produce the cross adaptability to the following exposure to radiation. Exposure to γ radiation followed by hyperthermia does not present and additive action or a synergistic action

  16. Combined radiotherapy-chemotherapy

    International Nuclear Information System (INIS)

    Steel, G.G.

    1989-01-01

    This paper presents the clinically confirmed benefits of combined chemotherapy-radiotherapy. They have been found in a small group of diseases that respond to chemotherapy alone. According to the author, only when a drug or drug combination has the ability to eradicate occult disease or substantially to reduce the size of objectively measurable disease is there likely to be an demonstrable benefit from its use in conjunction with radiotherapy. It is the author's belief that the immediate future lies in selecting drugs and patients in which a good chemotherapeutic response can be expected, avoiding drugs that seriously enhance radiation damage to normal tissues and keeping drug and radiation treatments far enough apart in time to minimize interactions

  17. Can magneto-plasmonic nanohybrids efficiently combine photothermia with magnetic hyperthermia?

    Science.gov (United States)

    Espinosa, Ana; Bugnet, Mathieu; Radtke, Guillaume; Neveu, Sophie; Botton, Gianluigi A.; Wilhelm, Claire; Abou-Hassan, Ali

    2015-11-01

    Multifunctional hybrid-design nanomaterials appear to be a promising route to meet the current therapeutics needs required for efficient cancer treatment. Herein, two efficient heat nano-generators were combined into a multifunctional single nanohybrid (a multi-core iron oxide nanoparticle optimized for magnetic hyperthermia, and a gold branched shell with tunable plasmonic properties in the NIR region, for photothermal therapy) which impressively enhanced heat generation, in suspension or in vivo in tumours, opening up exciting new therapeutic perspectives.Multifunctional hybrid-design nanomaterials appear to be a promising route to meet the current therapeutics needs required for efficient cancer treatment. Herein, two efficient heat nano-generators were combined into a multifunctional single nanohybrid (a multi-core iron oxide nanoparticle optimized for magnetic hyperthermia, and a gold branched shell with tunable plasmonic properties in the NIR region, for photothermal therapy) which impressively enhanced heat generation, in suspension or in vivo in tumours, opening up exciting new therapeutic perspectives. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06168g

  18. Combined therapy of radiation and hyperthermia on a metastatic tumor of angiosarcoma

    International Nuclear Information System (INIS)

    Yasuda, Hiroshi; Kitayama, Yoshiaki

    1987-01-01

    A combined therapy of radiation and hyperthermia is said to be fairly effective when applied to certain malignant tumors. However, the utility of this therapy for the treatment of angiosarcoma has not been well discussed. Recently, we have had a chance to treat a patient with metastatic angiosarcoma of the neck by using this combined therapy. In this paper, the clinical course of this patient and the availability of this combined therapy for angiosarcoma is reported. The patient was a 77-year-old man, having a primary lesion on the head and a metastatic tumor over the left cheek and neck. This combined therapy was used for the treatment of the metastatic tumor which caused severe pain and uncontrollable bleeding. The results were considered good ; the tumor decreased in size, pain disappeared and no further bleeding or severe side effects were observed. Though the patient died of another metastatic lesion which could not be treated with this combined therapy because the area of its localization could not allow placement in our hyperthermal apparatus, it is concluded that the combined therapy of radiation and hyperthermia is useful selectively for the treatment for angiosarcoma. (author)

  19. Chemotherapy in combined and multimodality treatment

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

    It is shown that chemotherapy of tumors of various localizations developes intensively in the last few years. It is connected with discovery and adoption of new active antitumoral preparations, such as alkylating preparations, antimetabolites, antitumoral antibiotics, hormonal preparations. To create the rational effective conditions of chemotherapy a study was made on kinetics of tumor gowth, molecular mechanisms of interaction of cytostatics and cells of malignant tumor. Main factors of chemotherapy combination with radiotherapy when treating numerous malignant tumors were considered. Effectiveness of using chemotherapy in combination with other methods of treatment was shown

  20. Combined transperineal radiofrequency (RF) interstitial hyperthermia and brachytherapy for localized prostate cancer (PC)

    International Nuclear Information System (INIS)

    Urakami, Shinji; Gonda, Nobuko; Kikuno, Nobuyuki

    2001-01-01

    Hyperthermia has been used effectively as a radiation sensitizer. Interstitial hyperthermoradiotherapy has been therefore utilized as a minimal invasive therapy in attempts to improve local tumor control for various cancers, but not for urological cancer. The purpose of this study was to investigate the safety and feasibility of transperineal hyperthermoradiotherapy for localized PC. Based on our basic study of hyperthermoradiotherapy, we devised the procedure of combined transperineal RF interstitial hyperthermia and brachytherapy for localized prostate cancer. Two patients with localized PC underwent transperineal RF interstitial hyperthermia combined with brachytherapy operation the 192-Ir remote after-loading system (RALS). Under transrectal ultrasound guidance, a total number of 12-18 stainless steel needles for 192-Ir RALS were implanted into the prostatic gland and seminal vesicles (SV) in an optimized pattern. Eight of the needles were used as electrodes for hyperthermia, and were electrically insultated using the vinyl catheter along the length of the subdermal fatty tissue to protect from overheating. Three other needles were utilized for continuous temperature mapping in the prostate. Rectal temperature was also monitored. Total radiation doses of 70 Gy to the prostate and SV were planned as a combination of brachytherapy (24 Gy/4 fraction) and external irradiation using a four-field box technique (46 Gy/23 fraction). Hyperthermic treatment (goal of 42 to 43 deg C for 60 minutes) was performed twice following the 1st and 4th brachytherapy at an interval of more than 48 hours for the recovery of cancer cells from thermotolerance. Both patients reached the treatment goal of all intraprostatic temperatures >43.0 deg C, which was considered favorable for hyperthermia, and the rectal temperatures of both patients remained <38 deg C during hyperthermia. In serial PSA measurements of both patients, serum PSA was less than 1.0 ng/ml within 3 months and has since

  1. SR-1000 radiofrequency chemo-hyperthermia for recurrent and metastatic peritoneo-pelvic malignant tumors

    International Nuclear Information System (INIS)

    Luo Jingwei; Xiong Jinghong; Xu Guozhen; Yu Zihao; Li Yexiong; Yin Weibo

    2002-01-01

    Objective: To evaluate the efficacy and tolerance of intraperitoneal chemo-hyperthermia (IPCH) with SR-1000 radiofrequency (RF) for recurrent or metastatic peritoneo-pelvic malignant tumors. Methods: Twenty-one patients with recurrent or metastatic peritoneo-pelvic malignant tumors received chemo-hyperthermia, with 9 having local pain and 14 having ascites. The Karnofsky scores were 40-80. After abdominal cavity aspiration and infusion of hot NS and chemotherapeutic agents, the temperature of abdominal cavity was increased and maintained at 40.5-42.5 degree C for 60-90 minutes with SR-1000 RF. Hyperthermia was given twice per week and chemotherapy once per week, with the whole treatment lasting for 2-4 weeks. The commonly used drugs were DDP, MMC, 5-FU and so on. Results: Local pain was relieved in 8 of 9 patients, complete disappearance of ascites in 10 of 14. The common side-effects were fat necrosis (14.3%) and abdominal pain (24.8%). Conclusions: Intraperitoneal chemo-hyperthermia with SR-1000 RF appears to be a promising new approach for patients with recurrent or metastatic peritoneo-pelvic malignant tumors, especially for those who did not response to systemic chemotherapy or whose tumor recurred after chemotherapy. As to bulky lesions, local supplementary radiotherapy should be given in order to obtain better local control

  2. Interstitial hyperthermia and iridium-192 treatment alone vs. interstitial iridium-192 treatment/hyperthermia and low dose cisplatinum infusion in the treatment of locally advanced head and neck malignancies

    International Nuclear Information System (INIS)

    Schreiber, David P.; Overett, Thomas K.

    1995-01-01

    Purpose: To determine whether the addition of low dose platinum infusional chemotherapy adds to the effectiveness of interstitial hyperthermia/iridium-192 management of locally advanced head and neck malignancies. Methods and Materials: From 1987 to 1993, 36 patients with locally advanced head and neck malignancies were treated locally with interstitial hyperthermia and iridium-192 as part or all of their management. Twenty-two of the above-mentioned patients also received low dose infusional cisplatinum chemotherapy at 20 mg/M 2 per day during the time of the implant. No patient received greater than 100 mg/M 2 total dose. Implant times ranged from 38.5 to 134 h and total doses delivered with the radiation implants ranged from 15 to 39.9 Gy. Average implant volume was 50 cc. Twenty-three patients received external beam irradiation supplementation in a dose range from 25.2 to 64 Gy. Results: Median follow-up for the entire group was 8, months with 7 months for the chemotherapy group vs. 12 months for the no-chemotherapy group. Freedom from relapse rates for the chemotherapy group vs. the no-chemotherapy group were 70% at 41 months vs. 63% at 60 months, p not significant (p = NS). Overall survival by Life Table Analysis was 28% for the chemotherapy group at 41 months vs. 31% for the no-chemotherapy group at 60 months (p = NS). Complete response (CR) rates were 93% for the chemotherapy group vs. 86% for the no-chemotherapy group. Seven patients in the chemotherapy group had recurrent disease and four patients in the no-chemotherapy group were being treated for recurrent disease. Complication rates were similar in both groups, with two patients in the chemotherapy arm requiring hyperbaric oxygen treatments and one patient in the no-chemotherapy arm requiring hyperbaric oxygen treatments (for soft tissue necrosis). Conclusion: It appears that low dose platinum infusional chemotherapy can be added safely to patients receiving interstitial iridium-192 implants along with

  3. Combination Chemotherapy for Influenza

    Directory of Open Access Journals (Sweden)

    Robert G. Webster

    2010-07-01

    Full Text Available The emergence of pandemic H1N1 influenza viruses in April 2009 and the continuous evolution of highly pathogenic H5N1 influenza viruses underscore the urgency of novel approaches to chemotherapy for human influenza infection. Anti-influenza drugs are currently limited to the neuraminidase inhibitors (oseltamivir and zanamivir and to M2 ion channel blockers (amantadine and rimantadine, although resistance to the latter class develops rapidly. Potential targets for the development of new anti-influenza agents include the viral polymerase (and endonuclease, the hemagglutinin, and the non-structural protein NS1. The limitations of monotherapy and the emergence of drug-resistant variants make combination chemotherapy the logical therapeutic option. Here we review the experimental data on combination chemotherapy with currently available agents and the development of new agents and therapy targets.

  4. Modeling the heat transfer problem for the novel combined cryosurgery and hyperthermia system.

    Science.gov (United States)

    Zhao, Gang; Bai, Xue-Fei; Luo, Da-Wei; Gao, Da-Yong

    2006-01-01

    A multidimensional, finite element analysis (FEA) for the freezing, holding, rewarming and heating processes of biological tissues during the cryosurgery process of the new Combined Cryosurgery/Hyperthermia System is presented to theoretically test its validity. The tissues are treated as nonideal materials freezing over a temperature range, and the thermophysical properties of which are temperature dependent. The enthalpy method is applied to solve the highly nonlinear problem. It was found that when the same boundary condition and the same target tissue presented, the novel Cryosurgery/Hyperthermia System could supply the target tissue an approximative cooling rate, a much lower minimal temperature, a much greater warming rate, and a much greater thermal gradients compared with that of the simplified Endocare system. The numerical simulation indicates that the novel combined cryosurgery and hyperthermia system can provide an excellent curative effect in the corresponding cryotherapy. And the most attractive feature of this FEA framework is that it can be easily mastered by the surgeon without in-depth theory of heat transfer to analyze the cryosurgery process beforehand due to the friendly GUI (graphical user interface) of Ansys software.

  5. Combined chemotherapy including platinum derivatives for medulloblastoma. The usefulness as maintenance chemotherapy

    International Nuclear Information System (INIS)

    Sasaki, Hikaru; Otani, Mitsuhiro; Yoshida, Kazunari; Kagami, Hiroshi; Shimazaki, Kenji; Toya, Shigeo; Kawase, Takeshi

    1997-01-01

    The authors reviewed 24 cerebellar medulloblastoma patients treated at Keio University to determine usefulness of combined chemotherapy including platinum derivatives (cisplatin, carboplatin) as the induction and maintenance treatment. All patients underwent radical surgery and craniospinal irradiation. Ten received adjuvant chemotherapy other than platinum derivatives (mainly with nitrosourea compounds), five were treated by induction and maintenance chemotherapy including platinum derivatives, and nine patients did not undergo chemotherapy. The progression-free survival rate of patients treated with platinum derivatives was better than that of patients treated with other modes of chemotherapy and also that of patients who did not receive chemotherapy. The results were especially good in the case of four patients treated with maintenance chemotherapy consisting of carboplatin and etoposide, two of whom had been free from relapse beyond the risk period of Collins. The occurrences of toxicity in maintenance chemotherapy with carboplatin and etoposide were limited to transient leucopenia. The present study indicates combined chemotherapy including platinum derivatives benefits patients with medulloblastoma, and could be useful, especially as maintenance treatment. (author)

  6. Effect of combined radiotherapy, hyperthermia, radioprotective agent and hypoxic cell sensitizer on mice testes

    Energy Technology Data Exchange (ETDEWEB)

    Nakano, Yasuhiko

    1985-08-01

    Application of hyperthermia was executed by immersing pelvis, testes and legs of mice in a thermostatically controlled water bath. Irradiation was carried out using Toshiba KXC-18 type X-ray therapy machine. Mice were killed 30 days after treatment. The testis weights obtained after hypertheramia alone were compared with that of the control and the relative testis weight ratios were calculated. The testis weights of mice treated for 5, 10, 20 and 40 min. in 40 deg C water and for 5 and 10 min. in 43 deg C water were not significantly different from the control. Their weights were reduced when treated for 20 min. in 43 deg C water and for 5 min. in 46 deg C water and their testis weight ratios were 0.81 and 0.46, respectively. The testis weights of irradiated mice decreased to about 45 % of the control at 250 rad. Beyond this dose, reduction of their weights was slowed down and testis weight at 1,000 rad was 28 %. There was not significantly difference between the relative testis weight ratios of the irradiation alone and that of the radiotherapy combined with YM-08310 (S-2-)3-aminopropylamino) ethyl phosphorothioic acid monohydrate). But when hyperthermia was added to their treatment, the effectiveness of the YM-08310 was slightly increased. The relative testis weight ratio on 400 rad X-ray combined with YM-08310 was 0.32 of the control, while its ratio on the radiotherapy and YM-08310 combined with the hyperthermia (43 deg C, 10 min.) was 0.43. (p < 0.01). The misonidazole treatments at 50, 100 and 200 rads were found to be effectuve. Radiation alone gave the relative testis weight ratios of 0.78, 0.71 and 0.49, respectively. In contrast, its ratios on the irradiation combined with the misonidazole were 0.57 (p < 0.01), 0.46 (p < 0.01) and 0.41 (p < 0.001). But, the additional hyperthermia combined with their treatment was found to be ineffective. (J.P.N.).

  7. Quantifying the Combined Effect of Radiation Therapy and Hyperthermia in Terms of Equivalent Dose Distributions

    International Nuclear Information System (INIS)

    Kok, H. Petra; Crezee, Johannes; Franken, Nicolaas A.P.; Stalpers, Lukas J.A.; Barendsen, Gerrit W.; Bel, Arjan

    2014-01-01

    Purpose: To develop a method to quantify the therapeutic effect of radiosensitization by hyperthermia; to this end, a numerical method was proposed to convert radiation therapy dose distributions with hyperthermia to equivalent dose distributions without hyperthermia. Methods and Materials: Clinical intensity modulated radiation therapy plans were created for 15 prostate cancer cases. To simulate a clinically relevant heterogeneous temperature distribution, hyperthermia treatment planning was performed for heating with the AMC-8 system. The temperature-dependent parameters α (Gy −1 ) and β (Gy −2 ) of the linear–quadratic model for prostate cancer were estimated from the literature. No thermal enhancement was assumed for normal tissue. The intensity modulated radiation therapy plans and temperature distributions were exported to our in-house-developed radiation therapy treatment planning system, APlan, and equivalent dose distributions without hyperthermia were calculated voxel by voxel using the linear–quadratic model. Results: The planned average tumor temperatures T90, T50, and T10 in the planning target volume were 40.5°C, 41.6°C, and 42.4°C, respectively. The planned minimum, mean, and maximum radiation therapy doses were 62.9 Gy, 76.0 Gy, and 81.0 Gy, respectively. Adding hyperthermia yielded an equivalent dose distribution with an extended 95% isodose level. The equivalent minimum, mean, and maximum doses reflecting the radiosensitization by hyperthermia were 70.3 Gy, 86.3 Gy, and 93.6 Gy, respectively, for a linear increase of α with temperature. This can be considered similar to a dose escalation with a substantial increase in tumor control probability for high-risk prostate carcinoma. Conclusion: A model to quantify the effect of combined radiation therapy and hyperthermia in terms of equivalent dose distributions was presented. This model is particularly instructive to estimate the potential effects of interaction from different treatment

  8. Cisplatin combined with hyperthermia kills HepG2 cells in intraoperative blood salvage but preserves the function of erythrocytes.

    Science.gov (United States)

    Yang, Jin-ting; Tang, Li-hui; Liu, Yun-qing; Wang, Yin; Wang, Lie-ju; Zhang, Feng-jiang; Yan, Min

    2015-05-01

    The safe use of intraoperative blood salvage (IBS) in cancer surgery remains controversial. Here, we investigated the killing effect of cisplatin combined with hyperthermia on human hepatocarcinoma (HepG2) cells and erythrocytes from IBS in vitro. HepG2 cells were mixed with concentrated erythrocytes and pretreated with cisplatin (50, 100, and 200 μg/ml) alone at 37 °C for 60 min and cisplatin (25, 50, 100, and 200 μg/ml) combined with hyperthermia at 42 °C for 60 min. After pretreatment, the cell viability, colony formation and DNA metabolism in HepG2 and the Na(+)-K(+)-ATPase activity, 2,3-diphosphoglycerate (2,3-DPG) concentration, free hemoglobin (Hb) level, osmotic fragility, membrane phosphatidylserine externalization, and blood gas variables in erythrocytes were determined. Pretreatment with cisplatin (50, 100, and 200 μg/ml) combined with hyperthermia (42 °C) for 60 min significantly decreased HepG2 cell viability, and completely inhibited colony formation and DNA metabolism when the HepG2 cell concentration was 5×10(4) ml(-1) in the erythrocyte (P2,3-DPG level, phosphatidylserine externalization, and extra-erythrocytic free Hb were significantly altered by hyperthermia plus high concentrations of cisplatin (100 and 200 μg/ml) (P0.05). In conclusion, pretreatment with cisplatin (50 μg/ml) combined with hyperthermia (42 °C) for 60 min effectively eliminated HepG2 cells from IBS but did not significantly affect erythrocytes in vitro.

  9. Combination radiotherapy and chemotherapy for primary lung cancer

    International Nuclear Information System (INIS)

    Nishikawa, Kiyoshi; Koga, Kenji; Kusuhara, Toshiyuki; Kodama, Takao; Takeuchi, Midori; Watanabe, Katsushi

    1984-01-01

    Fifty-six patients with carcinoma of the lung treated with radiotherapy alone or combination of chemotherapy were reviewed. Radiation was given with a 10MV photon beam by a linear accelerator. A fraction dose of 2Gy (200 rad) was given routinely 5 times a week. Combined durgs consist of 5FU or FT-207 in monochemotherapy and METT, MFC, or METVFC in combination chemotherapy. 5 year survival rate of all patients was 3.8%. As for the stage classification, 5 year survival rate is 30% in Stage I and II cancer, but there was no 3 year survivor in Stage III cancer and 2 year survivor in Stage IV cancer. As for the cell types, cases of adenocarcinoma had worse prognosis than them of squamous cell carcinoma and small cell carcinoma. The prognosis of patients treated with combination of radiotherapy and chemotherapy was similar to that of patients treated with radiotherapy alone. These results suggest that combined chemotherapy did not influence tumor control. Some discussion on the treatment modality of chemotherapy are made, emphasizing untoward effect of chemotherapy on immunopotency. (author)

  10. Experimental study on combination of chemotherapy and radiotherapy

    International Nuclear Information System (INIS)

    Tanaka, Juichi

    1986-01-01

    Recently, by applying multidrug therapy using cisplatin and bleomycin to the treatment of head and neck cancer, the response rate of chemotherapy has been markedly increased and thus, chemotherapy has taken an important part in the treatment of head and neck cancer. In this paper a clinical application of chemotherapy in combination with radiotherapy was evaluated from the point of the cure rate and also preservation of the structures and the functions of the head and neck region. In order to test the advantage or usefulness of initial chemotherapy followed by radiotherapy (= pre-radiation chemotherapy), the experimental study on combination of chemotherapy and radiotherapy was designed by using ICR mice and Ehrlich solid carcinoma. Cisplatin and peplomycin, a newly developed derivative of bleomycin, were used as chemotherapeutic agents. Tumor growth delay rate was chosen as a parameter to indicate the effectiveness. Results obtained are as follows. 1. Combination chemotherapy of cisplatin and peplomycin was more effective than each single agent on Ehrlich solid carcinoma. Synergistic effect was obtained by higher dose. So, the combination of cisplatin and peplomycin was proved to be eligible for pre-radiation chemotherapy. 2. Synergistic effect of chemotherapy and radiotherapy was observed when chemotherapy was used prior to radiotherapy on Ehrlich solid carcinoma. 3. Even their additional effect was not recognized when radiotherapy preceded to chemotherapy on Ehrlich solid carcinoma. 4. No severe toxic effect was seen in the mice. The experimental results made it clear that pre-radiation chemotherapy is beneficial to the treatment of head and neck cancer. (author)

  11. Enhancement of immunological activity after mild hyperthermia

    International Nuclear Information System (INIS)

    Noguchi, Kenichi; Hasegawa, Takeo; Takahashi, Tohru

    2002-01-01

    At present, hyperthermia is clinically very important as interdisciplinary therapeutic method, and studies are being performed on combined effects with surgical treatment, radiotherapy, chemotherapy and gene therapy for the treatment of malignant tumors. We evaluated the effects of hyperthermia under temperature of 42.5C and demonstrated that the activation of immunological response is increased and anti-tumor effect cabn be obtained in this studies. We used animals were C3H mice (male,7W) bearing SCC-VII tumor on femur skin. Then, the mice were divided to 10 mice in each group, and only femur region was immersed in warm water for thermal treatment. Also we measured the tumor growth, changes of blood cell fraction and NK cell activity. The results of the present study confirmed: (1) Anti-tumor effect can be given by thermal treatment at relatively mild temperature (mild temperature at 39C-42C); (2) The increase of neutrophils is dependent on the quantity of heat added; (3) Immunological response of monocytes and lymphocytes is associated with it; (4) Activity of the immunological potency as a whole such as activation of NK cells was also confirmed

  12. Regional hyperthermia of the liver

    International Nuclear Information System (INIS)

    Petrovich, Z.; Langholz, B.; Astrahan, M.; Emami, B.; Oleson, J.R.

    1989-01-01

    From 1981 through 1986, 49 patients with metastatic liver tumors received deep regional hyperthermia in phase I protocols in six major medical centers in the United States. Adenocarcinoma was seen in 80% of patients with colon as the primary site in 26%. The remaining patients had the following histological diagnoses: Soft tissue sarcoma in seven, malignant melanoma in two and transitional cell carcinoma in one. Deep regional hyperthermia treatments with a BSD-1000 annular phased array were given once or twice a week with a total of 167 treatment sessions, mean 3.4 (range 1 to 8). In addition to deep regional hyperthermia, 17 patients received radiotherapy, and 14 received chemotherapy. The median survival for all patients was 25 weeks. Complete response was obtained in two patients and partial response in four patients. An additional ten patients had nominal response. There was no complete or partial response among the 14 hyperthermia alone treated patients. Of the 26 patients who presented with severe pain, five had complete pain relief, five had partial relief and the majority had a lesser degree of pain relief or no pain relief. Acute treatment toxicity consisted of pain in ten, systemic temperature increase to 39 0 C in four tachycardia in two, claustrophobia in one. The majority of patients did not experience acute toxicity. No late toxicity was recorded in this group of 49 patients. (orig./MG)

  13. Combined effects of hyperthermia and radiation in cultured mammalian cells

    International Nuclear Information System (INIS)

    Ben-Hur, E.; Elkind, M.M.; Riklis, E.

    1977-01-01

    Hyperthermia (temperatures of 39 0 C or higher) enhances the killing of mammalian cells by ionizing radiation (fission-spectrum neutrons and x-rays). The nature and the magnitude of the enhanced radiation killing varies with temperature and for a fixed temperature during irradiation, the enhanced lethality varies inversely with dose rate. For temperatures up to 41 0 C, dose fractionation measurements indicate that hyperthermia inhibits the repair of sublethal damage. At higher temperatures, the expression of potentially lethal damage is enhanced. Since the effect of heat is greatest in cells irradiated during DNA synthesis, the radiation age-response pattern is flattened by hyperthermia. In addition to the enhanced cell killing described above, three other features of the effect of hyperthermia are important in connection with the radiation treatment of cancer. The first is that heat selectively sensitizes S-phase cells to radiation. The second is that it takes radiation survivors 10 to 20 hrs after a modest heat treatment to recover their ability to repair sublethal damage. And the third is that hyperthermia reduces the magnitude of the oxygen enhancement ratio. Thus, heat if applied selectively, could significantly increase the margin of damage between tumors and normal tissues

  14. Effects of X-ray irradiation combined with hyperthermia on human bone marrow cells

    International Nuclear Information System (INIS)

    Xie Huaijiang; Niu Rongjiu; Liu Xiaodong; Liu Huanqin

    1996-01-01

    The authors report on the effects of X-ray irradiation combined with hyperthermia on human bone marrow cells (BMC) in vitro. Observation was made on the morphology of treated cells under optic microscope and ultrastructural changes under electron microscope. The change was not obvious at first after treatment i,e, only the vacuolar degeneration was observed in a few cells under the EM. The survival of BMC alone after irradiation decreased with increase of the irradiation dose. The morphological changes included vacuolar degeneration of cells, swelling of mitochondria, and disintegration of nuclear membranes. The survival rate of BMC after irradiation combined with hyperthermia was significantly lower than that after treatment by either of them alone (P<0.01). The morphological changes were as follows: the cell structure was destroyed, the cell support system and cell organelles were destroyed, the cell membrane and nuclear membranes were destroyed, and the cell plasma and nuclear sap overflowed

  15. Study on the usefulness of high-frequency analysis of the combined treatment of cancer with hyperthermia

    International Nuclear Information System (INIS)

    Ji, Youn Sang; Dong, Kyung Rae; Yeo, Hwa Yeon

    2016-01-01

    In order to understand the usefulness to the high-frequency thermal therapy of cancer staging according to the TNM classification treatment, was to evaluate the effect of high frequency hyperthermia treatment approach through other means and whether other organs, according to the combined presence of transition. Targeted to receive more than a total of 1 cycle high frequency heat treatment at C hospital that performed the high-frequency hyperthermia cancer patients 92 people out stage, depending on the presence or absence of metastasis, combined hyperthermia patients for statistics before and after treatment the therapeutic effect of the therapeutic classification. Out of a total of 92 patients decrease 11 patients, stable 71 patients, with increase 10 patients, the rate of increase is the result of about 11% patients showed a decrease of about 89% is occupied by patients and a stable rate. There is strong evidence for the usefulness as a secondary therapy to maintain the quality of life, while slowing the progression of cancer by a high-frequency heat treatment

  16. Study on the usefulness of high-frequency analysis of the combined treatment of cancer with hyperthermia

    Energy Technology Data Exchange (ETDEWEB)

    Ji, Youn Sang; Dong, Kyung Rae [Dept. of Radiological Technology, Gwangju Health University, Gwangju (Korea, Republic of); Yeo, Hwa Yeon [Dept. of of Radiology, Nambu University, Gwangju (Korea, Republic of)

    2016-11-15

    In order to understand the usefulness to the high-frequency thermal therapy of cancer staging according to the TNM classification treatment, was to evaluate the effect of high frequency hyperthermia treatment approach through other means and whether other organs, according to the combined presence of transition. Targeted to receive more than a total of 1 cycle high frequency heat treatment at C hospital that performed the high-frequency hyperthermia cancer patients 92 people out stage, depending on the presence or absence of metastasis, combined hyperthermia patients for statistics before and after treatment the therapeutic effect of the therapeutic classification. Out of a total of 92 patients decrease 11 patients, stable 71 patients, with increase 10 patients, the rate of increase is the result of about 11% patients showed a decrease of about 89% is occupied by patients and a stable rate. There is strong evidence for the usefulness as a secondary therapy to maintain the quality of life, while slowing the progression of cancer by a high-frequency heat treatment.

  17. Radiotherapy of esophageal cancer in combination with chemotherapy

    International Nuclear Information System (INIS)

    Jinnouchi, Shoshi; Koga, Kenji; Nishikawa, Kiyoshi; Kihara, Yasushi; Kusuhara, Toshiyuki; Watanabe, Katuji

    1983-01-01

    The significance of combination of chemotherapy in radiotherapy for esophageal cancer was evaluated in 32 patients. They were irradiated routinely in 5 times a weeks with a fraction dose of 200 rad by 10MV-X-ray linear accelerator. Combined drugs consist of Bleomycin or Pepleomycin in two-third and 5FU or FT-207 in one-third. There was statistically no significance between the results of radiation alone and combined chemotherapy, and the improvement of survival rate could not be obtained by combining chemotherapy. Some discussion on the causes of this unimprovement were made. (author)

  18. Combined radiotherapy and chemotherapy for head and neck cancer

    International Nuclear Information System (INIS)

    Inuyama, Yukio; Fujii, Masato; Tanaka, Juichi; Takaoka, Tetsuro; Hosoda, Hyonosuke; Kawaura, Mitsuhiro; Toji, Masao

    1988-01-01

    There are 4 modalities of combined radiotherapy and chemotherapy which include (1) concurrent radiotherapy and chemotherapy, (2) sequential use of radiotherapy and chemotherapy (pre-radiation chemotherapy), (3) pre-radiation chemotherapy followed by concurrent radiation and chemotherapy, and (4) alternating use of radiotherapy and chemotherapy based upon Looney's hypothesis. We studied concurrent use of radiotherapy and UFT by means of animal experimentation and clinical trials. The results obtained revealed that UFT was a most suitable agent together with 5-fluorouracil for concurrent application of radiotherapy and chemotherapy. Neo-adjuvant chemotherapy including pre-radiation chemotherapy was also studied in cases of maxillary sinus carcinoma and nasopharyngeal carcinoma. From the results, it seemed desirable to use cisplatin and bleomycin analogs sequentially in combined chemotherapy and radiotherapy. Neo-adjuvant chemotherapy should be studied successively to improve local tumor control rates and prevent distant metastases. For future perspectives, new trials of alternating radiotherapy and chemotherapy based upon Looney's hypothesis seem necessary. (author)

  19. Salvage prostate HDR brachytherapy combined with interstitial hyperthermia for local recurrence after radiation therapy failure

    Energy Technology Data Exchange (ETDEWEB)

    Kukielka, A.M.; Hetnal, M.; Dabrowski, T.; Walasek, T.; Brandys, P.; Reinfuss, M. [Centre of Oncology, M. Sklodowska - Curie Institute, Krakow Branch, Department of Radiotherapy, Krakow (Poland); Nahajowski, D.; Kudzia, R.; Dybek, D. [Centre of Oncology, M. Sklodowska - Curie Institute, Krakow Branch, Department of Medical Physics, Department of Radiotherapy, Krakow (Poland)

    2014-02-15

    The aim of the present retrospective study is to evaluate toxicity and early clinical outcomes of interstitial hyperthermia (IHT) combined with high-dose rate (HDR) brachytherapy as a salvage treatment in patients with biopsy-confirmed local recurrence of prostate cancer after previous external beam radiotherapy. Between September 2008 and March 2013, 25 patients with local recurrence of previously irradiated prostate cancer were treated. The main eligibility criteria for salvage prostate HDR brachytherapy combined with interstitial hyperthermia were biopsy confirmed local recurrence and absence of nodal and distant metastases. All patients were treated with a dose of 30 Gy in 3 fractions at 21-day intervals. We performed 62 hyperthermia procedures out of 75 planned (83 %). The aim of the hyperthermia treatment was to heat the prostate to 41-43 C for 60 min. Toxicity for the organs of the genitourinary system and rectum was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, v. 4.03). Determination of subsequent biochemical failure was based on the Phoenix definition (nadir + 2 ng/ml). The median age was 71 years (range 62-83 years), the median initial PSA level was 16.3 ng/ml (range 6.37-64 ng/ml), and the median salvage PSA level was 2.8 ng/ml (1.044-25.346 ng/ml). The median follow-up was 13 months (range 4-48 months). The combination of HDR brachytherapy and IHT was well tolerated. The most frequent complications were nocturia, weak urine stream, urinary frequency, hematuria, and urgency. Grade 2 rectal hemorrhage was observed in 1 patient. No grade 3 or higher complications were observed. The 2-year Kaplan-Meier estimate of biochemical control after salvage treatment was 74 %. The PSA in 20 patients decreased below the presalvage level, while 11 patients achieved a PSA nadir < 0.5 ng/ml. All patients are still alive. Of the 7 patients who experienced biochemical failure, bone metastases were found in 2 patients. IHT in combination

  20. Thermometric analysis of intra-cavitary hyperthermia for esophageal cancer.

    Science.gov (United States)

    Qi, C; Li, D J

    1999-01-01

    Thermometric analysis was carried out in 51 patients with esophageal cancer treated with intra-cavitary hyperthermia combined with radio chemotherapy, to test whether temperature index (T20, T50) and T90) could be used as an indicator for tumour control. Hyperthermia was administered by intra-cavitary microwave applicator. The T20, T50 and T90 were deducted from the temperature sensors T0 and T3 situated at the center of the tumour surface and 3cm from it. Eighteen patients with local control > or =36 months were named long term control patients (LC), 24 patients with local recurrence within 24 months (LR) (there were no events occurring between 24 and 36 months) and nine patients died of metastasis without local recurrence (DM). The overall survival rates were 80.4 +/- 5.6% at 1 year, 38.3 +/- 6.9% at 3 years and 31 +/- 6.7% at 5 years, respectively. Chi-square test showed no influence of the number of hyperthermia sessions on the local control (p > 0.25). The 5-year local control rate was 18.8% for the patients with T90 or = 43 degrees C (p < 0.01). The average T90 was 43.76 +/- 0.74 degrees C for the LC patients and 43.17 +/- 0.57 degrees C for those LR (p = 0.024). The mean T90 was higher than 43 degrees C in 94.4% of LC, whereas in 58.8% of LR. The study suggested that T90 was a good parameter for thermal dose in the intracavitary hyperthermia for the treatment of esophageal cancer.

  1. Targeting chemotherapy-resistant leukemia by combining DNT cellular therapy with conventional chemotherapy.

    Science.gov (United States)

    Chen, Branson; Lee, Jong Bok; Kang, Hyeonjeong; Minden, Mark D; Zhang, Li

    2018-04-24

    While conventional chemotherapy is effective at eliminating the bulk of leukemic cells, chemotherapy resistance in acute myeloid leukemia (AML) is a prevalent problem that hinders conventional therapies and contributes to disease relapse, and ultimately patient death. We have recently shown that allogeneic double negative T cells (DNTs) are able to target the majority of primary AML blasts in vitro and in patient-derived xenograft models. However, some primary AML blast samples are resistant to DNT cell therapy. Given the differences in the modes of action of DNTs and chemotherapy, we hypothesize that DNT therapy can be used in combination with conventional chemotherapy to further improve their anti-leukemic effects and to target chemotherapy-resistant disease. Drug titration assays and flow-based cytotoxicity assays using ex vivo expanded allogeneic DNTs were performed on multiple AML cell lines to identify therapy-resistance. Primary AML samples were also tested to validate our in vitro findings. Further, a xenograft model was employed to demonstrate the feasibility of combining conventional chemotherapy and adoptive DNT therapy to target therapy-resistant AML. Lastly, blocking assays with neutralizing antibodies were employed to determine the mechanism by which chemotherapy increases the susceptibility of AML to DNT-mediated cytotoxicity. Here, we demonstrate that KG1a, a stem-like AML cell line that is resistant to DNTs and chemotherapy, and chemotherapy-resistant primary AML samples both became more susceptible to DNT-mediated cytotoxicity in vitro following pre-treatment with daunorubicin. Moreover, chemotherapy treatment followed by adoptive DNT cell therapy significantly decreased bone marrow engraftment of KG1a in a xenograft model. Mechanistically, daunorubicin increased the expression of NKG2D and DNAM-1 ligands on KG1a; blocking of these pathways attenuated DNT-mediated cytotoxicity. Our results demonstrate the feasibility and benefit of using DNTs as

  2. Hyperthermia system working in combination with an MR imaging unit

    International Nuclear Information System (INIS)

    LeBihan, D.J.; Delannoy, J.; Levin, R.L.; Hoult, D.I.

    1988-01-01

    The authors propose a hyperthermia device to be used for temperature monitoring. It consists of a modified miniannular phased array (MAPA) radio-frequency applicator designed for limb tumor treatment that works in combination with a whole-body MR imaging unit operating at 21 MHz. Highly accurate (0.5 0 c/0.8 cm 2 ) temperature images are obtained noninvasively throughout the heated volume from MR images of molecular diffusion, the relation of which with temperature is well known. The MAPA, electrically modified to be compatible with MR imagers, can be centered inside the MR head coil. The combined system was tested on a phantom in which the temperature distribution was confirmed by miniature thermocouples

  3. Computational evaluation of amplitude modulation for enhanced magnetic nanoparticle hyperthermia.

    Science.gov (United States)

    Soetaert, Frederik; Dupré, Luc; Ivkov, Robert; Crevecoeur, Guillaume

    2015-10-01

    Magnetic nanoparticles (MNPs) can interact with alternating magnetic fields (AMFs) to deposit localized energy for hyperthermia treatment of cancer. Hyperthermia is useful in the context of multimodality treatments with radiation or chemotherapy to enhance disease control without increased toxicity. The unique attributes of heat deposition and transfer with MNPs have generated considerable attention and have been the focus of extensive investigations to elucidate mechanisms and optimize performance. Three-dimensional (3D) simulations are often conducted with the finite element method (FEM) using the Pennes' bioheat equation. In the current study, the Pennes' equation was modified to include a thermal damage-dependent perfusion profile to improve model predictions with respect to known physiological responses to tissue heating. A normal distribution of MNPs in a model liver tumor was combined with empirical nanoparticle heating data to calculate tumor temperature distributions and resulting survival fraction of cancer cells. In addition, calculated spatiotemporal temperature changes were compared among magnetic field amplitude modulations of a base 150-kHz sinusoidal waveform, specifically, no modulation, sinusoidal, rectangular, and triangular modulation. Complex relationships were observed between nanoparticle heating and cancer tissue damage when amplitude modulation and damage-related perfusion profiles were varied. These results are tantalizing and motivate further exploration of amplitude modulation as a means to enhance efficiency of and overcome technical challenges associated with magnetic nanoparticle hyperthermia (MNH).

  4. Improving efficacy of hyperthermia in oncology by exploiting biological mechanisms

    DEFF Research Database (Denmark)

    van den Tempel, Nathalie; Horsman, Michael R; Kanaar, Roland

    2016-01-01

    It has long been established that hyperthermia increases the therapeutic benefit of radiation and chemotherapy in cancer treatment. During the last few years there have been substantial technical improvements in the sources used to apply and measure heat, which greatly increases enthusiasm for th...

  5. Similarities and differences in ablative and non-ablative iron oxide nanoparticle hyperthermia cancer treatment

    Science.gov (United States)

    Petryk, Alicia A.; Misra, Adwiteeya; Kastner, Elliot J.; Mazur, Courtney M.; Petryk, James D.; Hoopes, P. Jack

    2015-03-01

    The use of hyperthermia to treat cancer is well studied and has utilized numerous delivery techniques, including microwaves, radio frequency, focused ultrasound, induction heating, infrared radiation, warmed perfusion liquids (combined with chemotherapy), and recently, metallic nanoparticles (NP) activated by near infrared radiation (NIR) and alternating magnetic field (AMF) based platforms. It has been demonstrated by many research groups that ablative temperatures and cytotoxicity can be produced with locally NP-based hyperthermia. Such ablative NP techniques have demonstrated the potential for success. Much attention has also been given to the fact that NP may be administered systemically, resulting in a broader cancer therapy approach, a lower level of tumor NP content and a different type of NP cancer therapy (most likely in the adjuvant setting). To use NP based hyperthermia successfully as a cancer treatment, the technique and its goal must be understood and utilized in the appropriate clinical context. The parameters include, but are not limited to, NP access to the tumor (large vs. small quantity), cancer cell-specific targeting, drug carrying capacity, potential as an ionizing radiation sensitizer, and the material properties (magnetic characteristics, size and charge). In addition to their potential for cytotoxicity, the material properties of the NP must also be optimized for imaging, detection and direction. In this paper we will discuss the differences between, and potential applications for, ablative and non-ablative magnetic nanoparticle hyperthermia.

  6. Radiochemotherapy in combination with regional hyperthermia in preirradiated patients with recurrent rectal cancer

    International Nuclear Information System (INIS)

    Milani, V.; Issels, R.D.; Buecklein, V.; Institute of Molecular Immunology, Muenchen; Pazos, M.; Schaffer, P.; Wilkowski, R.; Duehmke, E.; Rahman, S.; Tschoep, K.; Schaffer, M.

    2008-01-01

    Background and Purpose: Encouraging results of phase II studies combining chemotherapy with radiotherapy have been published. In this study, the results of a multimodal salvage therapy including radiochemotherapy (RCT) and regional hyperthermia (RHT) in preirradiated patients with recurrent rectal cancer are reported. Patients and Methods: All patients enrolled had received previous pelvic irradiation (median dose 50.4 Gy). The median time interval between prior radiotherapy and the onset of local recurrence was 34 months. The combined treatment consisted of reirradiation with a median dose of 39.6 Gy (30.0-45.0 Gy), delivered in fractions of 1.8 Gy/day. 5-fluorouracil was given as continuous infusion 350 mg/m2/day five times weekly, and RHT (BSD-2000 system) was applied twice a week within 1 h after radiotherapy. The primary endpoint was local progression-free survival (LPFS); secondary endpoints were overall survival, symptom control, and toxicity. Results: 24 patients (median age 59 years) with a previously irradiated locally recurrent adenocarcinoma of the rectum were enrolled. The median LPFS was 15 months (95% confidence interval 12-18 months) with a median follow-up of 27 months (16-37 months). The overall 1-year and 3-year survival rates were 87% and 30%, respectively. Pain was the main symptom in 17 patients. Release of pain was achieved in 12/17 patients (70%). No grade 3 or 4 hematologic or skin toxicity occurred. Grade 3 gastrointestinal acute toxicity was observed in 12.5% of the patients. Paratumoral thermometry revealed a homogeneous distribution of temperatures. Conclusion: RCT combined with RHT is an efficient salvage therapy showing high efficacy with acceptable toxicity and can be recommended as treatment option for this unfavorable group of preirradiated patients with local recurrence of rectal cancer. (orig.)

  7. Radiochemotherapy in combination with regional hyperthermia in preirradiated patients with recurrent rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Milani, V.; Issels, R.D.; Buecklein, V. [Ludwig-Maximilians-Univ., Muenchen (Germany). Univ. Hospital Grosshadern, Dept. of Internal Medicine III; Institute of Molecular Immunology, Muenchen (Germany). KKG Hyperthermie GSF-Haematologikum; Pazos, M.; Schaffer, P.; Wilkowski, R.; Duehmke, E. [Ludwig-Maximilians-Univ., Muenchen (Germany). Univ. Hospital Grosshadern, Dept. of Radiation Oncology; Rahman, S.; Tschoep, K.; Schaffer, M. [Ludwig-Maximilians-Univ., Muenchen (Germany). Univ. Hospital Grosshadern, Dept. of Internal Medicine III

    2008-03-15

    Background and Purpose: Encouraging results of phase II studies combining chemotherapy with radiotherapy have been published. In this study, the results of a multimodal salvage therapy including radiochemotherapy (RCT) and regional hyperthermia (RHT) in preirradiated patients with recurrent rectal cancer are reported. Patients and Methods: All patients enrolled had received previous pelvic irradiation (median dose 50.4 Gy). The median time interval between prior radiotherapy and the onset of local recurrence was 34 months. The combined treatment consisted of reirradiation with a median dose of 39.6 Gy (30.0-45.0 Gy), delivered in fractions of 1.8 Gy/day. 5-fluorouracil was given as continuous infusion 350 mg/m2/day five times weekly, and RHT (BSD-2000 system) was applied twice a week within 1 h after radiotherapy. The primary endpoint was local progression-free survival (LPFS); secondary endpoints were overall survival, symptom control, and toxicity. Results: 24 patients (median age 59 years) with a previously irradiated locally recurrent adenocarcinoma of the rectum were enrolled. The median LPFS was 15 months (95% confidence interval 12-18 months) with a median follow-up of 27 months (16-37 months). The overall 1-year and 3-year survival rates were 87% and 30%, respectively. Pain was the main symptom in 17 patients. Release of pain was achieved in 12/17 patients (70%). No grade 3 or 4 hematologic or skin toxicity occurred. Grade 3 gastrointestinal acute toxicity was observed in 12.5% of the patients. Paratumoral thermometry revealed a homogeneous distribution of temperatures. Conclusion: RCT combined with RHT is an efficient salvage therapy showing high efficacy with acceptable toxicity and can be recommended as treatment option for this unfavorable group of preirradiated patients with local recurrence of rectal cancer. (orig.)

  8. Local superficial hyperthermia in combination with low-dose radiation therapy for palliation of superficially localized metastases

    International Nuclear Information System (INIS)

    Owczarek, G.; Miszczyk, L.

    2005-01-01

    Full text: The aim of this study is to evaluate the response of superficially located metastases and local toxicity to microwave hyperthermia combined with radiation therapy. From May 2003 through December 2004 58 patients (33 male, 25 female; mean age 60 years) with lymph nodes or skin metastases were treated with microwave superficial hyperthermia combined with low-dose radiation therapy. Hyperthermia was administered twice weekly with high frequency applicator (∼900 Mhz) with water bolus. The temperature was set to 43 o C for 45 minutes. Radiotherapy was performed daily with dose 2 Gy or 4 Gy per fraction, to a total dose 20 Gy. There were 47 patients with carcinoma, 4 with sarcoma, 7 with melanoma. Treated regions were: head and neck (37 patients), chest wall 8, abdomen wall and groins 4, upper and lower limb 2 and 8 patients respectively. Primary tumor sites were: head and neck region (9 patients), lung 15, alimentary tract 8, breast 5, soft tissue 8, urogenital 4 and 9 patients with primary tumor site unknown. The toxicity was evaluated using 6 step scale: 0-no skin reaction, 1-faint red mark, 2-distinct red mark, 3-blisters, 4-brown mark, 5-necrosis. Presence of pain and its intensity were also analyzed. Diameter of tumor after the treatment was observed. Complete response was achieved in 5 patients (8.5 %), and partial response in 29 patients (50 %), no response was observed in 12 patients (20 %) and progression of tumor in 7 patients (12 %). No skin reaction was observed in 3 patients, faint red mark in 14 patients, distinct red mark in 28 patients, blisters in 8 patients, brown mark in 4 patients and necrosis in 1 patient. The pain occurred in 9 patients but it was no the cause of stopping treatment. Local superficial hyperthermia combined with low-dose radiation therapy is an effective method of treatment in a proportion of patients with superficial metastases. This combination of treatment modalities is well tolerated and is useful for palliation

  9. Tolerance of radiotherapy combined with adjuvant chemotherapy in breast cancer

    International Nuclear Information System (INIS)

    Hrafnkelsson, J.; Nilsson, K.; Soederberg, M.

    1987-01-01

    Forty-three postmenopausal breast cancer patients with axillary lymph node metastasis were randomized to receive postoperative radiotherapy (45 Gy) or the combination of radiotherapy and 6 months of chemotherapy. Forty-three premenopausal patients had postoperative radiotherapy and were randomized to receive one of two different chemotherapy combinations. Pulmonary fibrosis was roentgenologically registered in approximately 70% of the total patient population six months after initiation of therapy. Addition of chemotherapy with doxorubicin and cyclophosphamide significantly increased the proportion of patients with pulmonary fibrosis compared with patients treated with radiotherapy only or radiotherapy combined with cyclophosphamide, methotrexate and 5-fluorouracil. Premenopausal patients tolerated the combination of radiotherapy and chemotherapy better than postmenopausal patients of whom approximately 30% did not tolerate 65% or more of prescribed total dose of chemotherapy. (orig.)

  10. Pathological changes in the rabbit lungs after irradiation and after combined irradiation and hyperthermia

    International Nuclear Information System (INIS)

    Zinner, M.

    1984-01-01

    The effects of combined irradiation and hyperthermia and of irradiation alone on normal lung tissue was investigated in rabbits. The animals of both therapy groups were irradiated with 2 Gy five times a week for a 6-week period. The animals of group 1 were additionally exposed to hyperthermia 3 times a week after irradiation. The method applied was the condenser field method (25 to 35 Watt/min). Only the right lung was treated in all animals. The animals were sacrificed 3 months after termination of the therapy, and large-surface lung sections were prepared. The following results were obtained: There is a quantifiable difference in the severeness of fibrosis between groups 1 and 2. Fibrosis was more pronounced in group 1 but the difference was not statistically significant. In both groups, fibrosis was unevenly distributed in the different lung areas. Fibrosis was highest in the ventral and apical regions. These were the regions where the highest local temperature rise was recorded during hyperthermia and where the highest local radiation dose was applied. Histologically, signs of acute inflammatory processes were observed in both groups in parallel to regeneration and repair processes involving neogenesis. (orig./MG) [de

  11. Long-Term Improvement in Treatment Outcome After Radiotherapy and Hyperthermia in Locoregionally Advanced Cervix Cancer: An Update of the Dutch Deep Hyperthermia Trial

    International Nuclear Information System (INIS)

    Franckena, Martine; Stalpers, Lukas J.A.; Koper, Peter C.M.; Wiggenraad, Ruud G.J.; Hoogenraad, Wim J.; Dijk, Jan D.P. van; Warlam-Rodenhuis, Carla C.; Jobsen, Jan J.; Rhoon, Gerard C. van; Zee, Jacoba van der

    2008-01-01

    Purpose: The local failure rate in patients with locoregionally advanced cervical cancer is 41-72% after radiotherapy (RT) alone, whereas local control is a prerequisite for cure. The Dutch Deep Hyperthermia Trial showed that combining RT with hyperthermia (HT) improved 3-year local control rates of 41-61%, as we reported earlier. In this study, we evaluate long-term results of the Dutch Deep Hyperthermia Trial after 12 years of follow-up. Methods and Materials: From 1990 to 1996, a total of 114 women with locoregionally advanced cervical carcinoma were randomly assigned to RT or RT + HT. The RT was applied to a median total dose of 68 Gy. The HT was given once weekly. The primary end point was local control. Secondary end points were overall survival and late toxicity. Results: At the 12-year follow-up, local control remained better in the RT + HT group (37% vs. 56%; p = 0.01). Survival was persistently better after 12 years: 20% (RT) and 37% (RT + HT; p = 0.03). World Health Organization (WHO) performance status was a significant prognostic factor for local control. The WHO performance status, International Federation of Gynaecology and Obstetrics (FIGO) stage, and tumor diameter were significant for survival. The benefit of HT remained significant after correction for these factors. European Organization for Research and Treatment of Cancer Grade 3 or higher radiation-induced late toxicities were similar in both groups. Conclusions: For locoregionally advanced cervical cancer, the addition of HT to RT resulted in long-term major improvement in local control and survival without increasing late toxicity. This combined treatment should be considered for patients who are unfit to receive chemotherapy. For other patients, the optimal treatment strategy is the subject of ongoing research

  12. Long duration mild temperature hyperthermia and brachytherapy.

    Science.gov (United States)

    Armour, E P; Raaphorst, G P

    2004-03-01

    Combining long duration mild temperature hyperthermia (LDMH) and low dose-rate (LDR) brachytherapy to enhance therapeutic killing of cancer cells was proposed many years ago. The cellular and tumour research that supports this hypothesis is presented in this review. Research describing LDMH interaction with pulsed brachytherapy and high dose-rate brachytherapy using clinically relevant parameters are compared with LDMH/LDR brachytherapy. The mechanism by which LDMH sensitizes LDR has been established as the inhibition of sublethal damage repair. The molecular mechanisms have been shown to involve DNA repair enzymes, but the exact nature of these processes is still under investigation. The relative differences between LDMH interactions with human and rodent cells are presented to help in the understanding of possible roles of LDMH in clinical application. The role of LDMH in modifying tumour blood flow and its possible role in LDR sensitization of tumours is also presented. The positive aspects of LDMH-brachytherapy for clinical application are sixfold; (1) the thermal goals (temperature, time and volume) are achievable with currently available technology, (2) the hyperthermia by itself has no detectable toxic effects, (3) thermotolerance appears to play a minor if any role in radiation sensitization, (4) TER of around 2 can be expected, (5) hypoxic fraction may be decreased due to blood flow modification and (6) simultaneous chemotherapy may also be sensitized. Combined LDMH and brachytherapy is a cancer therapy that has established biological rationale and sufficient technical and clinical advancements to be appropriately applied. This modality is ripe for clinical testing.

  13. Radiofrequency hyperthermia for advanced malignant liver tumors

    International Nuclear Information System (INIS)

    Nagata, Y.; Okuno, Y.; Mitsumori, M.; Akuta, K.; Nishimura, Y.; Masunaga, S.; Kanamori, S.; Fujishiro, M.; Hiraoka, M.; Takahashi, M.; Abe, M.

    1996-01-01

    Purpose: To evaluate thermometry and the clinical results of radiofrequency (RF) thermotherapy for advanced malignant liver tumors. Materials and Methods One-hundred and seventy-three patients with malignant liver tumors treated between 1983 and 1995 underwent hyperthermia. Surgery were contraindicated in all patients. The 173 tumors consisted of 114 hepatocellular carcinomas(HCCs), and 59 non-HCCs(45 metastatic liver tumors and 12 cholangiocarcinomas). Eight MHz RF capacitive heating equipment was used for hyperthermia. Two opposing 25-cm or 30-cm electrodes were generally used for heating liver tumors. Our standard protocol was to administer hyperthermia 40-50 minutes twice a week to a total of 8 sessions. Temperature of the liver tumor was measured by microthermocouples. In each patient, a single catheter was inserted into the liver tumor through the normal liver. Transcatheter arterial embolization, radiotherapy, immunotherapy, and chemotherapy were combined with hyperthermia depending on the patient's liver function and tumor location. The therapeutic efficacy was evaluated by the change in tumor size assessed by computed tomography (CT) three or four months after the completion of treatment. Results One-hundred and forty (81%) of 173 patients underwent hyperthermia more than 4 times. Thermometry could be performed in 77(55%) of these 140 patients. Neither systolic nor diastolic blood pressure changed significantly after hyperthermia. However, pulse rate significantly increased from 82.8 ± 1.1 to 96.5 ± 1.3 beats/min. Only 21 patients (11%) showed a decrease in pulse rate after hyperthermia. Body temperature increased from 36.3 ±0.1 to 37.4±0.2 after hyperthermia. Sequelae of hyperthermia included focal fat burning in 20 (12%), gastric ulceration in 4 (2%), and liver necrosis in 1(1%). Sequelae of thermometry were severe peritoneal pain in 7 (11%), intraperitoneal hematoma in 1(1%), and pneumothorax in one (1%) patient. The maximal tumor temperature

  14. Changes in tumor oxygenation during a combined treatment with fractionated irradiation and hyperthermia: an experimental study.

    Science.gov (United States)

    Zywietz, F; Reeker, W; Kochs, E

    1997-01-01

    To determine the influence of adjuvant hyperthermia on the oxygenation status of fractionated irradiated tumors. Oxygen partial pressure (pO2) in rat rhabdomyosarcomas (R1H) was measured sequentially at weekly intervals during a fractionated irradiation with 60Co-gamma-rays (60 Gy/20f/4 weeks) in combination with local hyperthermia (8 f(HT) at 43 degrees C, 1 h/4 weeks). Tumors were heated twice weekly with a 2450 MHz microwave device at 43 degrees C, 1 h starting 10 min after irradiation. The pO2 measurements (pO2-histograph, Eppendorf, Germany) were performed in anesthetized animals during mechanical ventilation and in hemodynamic steady state. All tumor pO2 measurements were correlated to measurements of the arterial oxygen partial pressure (paO2) determined by a blood gas analyzer. The oxygenation status of R1H tumors decreased continuously from the start of the combined treatment, with increasing radiation dose and number of heat fractions. In untreated controls a median tumor pO2 of 23 +/- 2 mmHg (mean +/- SEM) was measured. Tumor pO2 decreased to 11 +/- 2 mmHg after 30 Gy + 4 HT (2 weeks), and to 6 +/- 2 mmHg after 60 Gy + 8HT (4 weeks). The increase in the frequency of pO2-values below 5 mmHg and the decrease in the range of the pO2 histograms [delta p(10/90)] further indicated that tumor hypoxia increased relatively rapidly from the start of combined treatment. After 60 Gy + 8HT 48 +/- 5% (mean +/- SEM) of the pO2-values recorded were below 5 mmHg. These findings suggest that adjuvant hyperthermia to radiotherapy induces greater changes in tumor oxygenation than radiation alone [cf. (39)]. This might be of importance for the temporary application of hyperthermia in the course of a conventional radiation treatment.

  15. Early experience in the combination of regional hyperthermia and radiotherapy

    International Nuclear Information System (INIS)

    Howard, G.C.W.; Bleehen, N.M.

    1987-01-01

    An annular array of radiative radiofrequency applicators (APA) has been developed by the BSD Corporation, Salt Lake City (USA) which has been shown to be capable of deep heating. The BSD 1000 clinical hyperthermia system has been installed at Cambridge for 18 months and a pilot study has been performed to assess the feasibility of pelvic regional hyperthermia in the treatment of extensive pelvic malignancy. The study confirms published data that the APA is capable of heating at depth within the pelvis. Therapeutic temperatures may be reached in the majority of treatments but are difficult to maintain due to acute toxicity. Steering of the area of maximal energy deposition may improve treatments considerably. A randomised trial is now being designed to assess whether the synergism between radiation and hyperthermia seen in superficial lesions can be demonstrated in tumours occurring in the pelvis. (orig./MG)

  16. Combined anti-tumor therapeutic effect of targeted gene, hyperthermia, radionuclide brachytherapy in breast carcinoma

    International Nuclear Information System (INIS)

    Chen Daozhen; Tang Qiusha; Xiang Jingying; Xu Fei; Zhang Li; Wang Junfeng

    2011-01-01

    Objective: To investigate the antitumor therapeutic effect of combined therapy of magnetic induction heating by nano-magnetic particles, herpes simplex virus thymidine kinase gene (HSV-tk suicide gene) and internal radiation in mice bearing MCF-7 breast carcinoma. Methods: The transfection reagents, plasmids heat shock protein-HSV-tk (pHSP-HSV-tk), ferroso-ferric oxide nano-magnetic fluid flow and 188 Re-ganciclovir-bovine serum albumin-nanopaticles (GCV-BSA-NP) were prepared. The heating experiments in vivo were carried out using ferroso-ferric oxide nano-magnetic fluid flow. Sixty mice tumor models bearing MCF-7 breast carcinoma were established and randomly divided into six groups. Group A was the control group, B was gene transfection therapy group, C was hyperthermia group, D was gene transfection therapy combined with radionuclide brachytherapy group, E was gene therapy combined with hyperthermia group, and F was gene therapy, hyperthermia combined with radionuclide brachytherapy group. The tumor growth, tumor mass and histopathological changes were evaluated. The expression of HSV-tk in the groups of B, D, E and F was detected by RT-PCR. Poisson distribution and one-way analysis of variance (ANOVA) were used for statistical analysis by SPSS 10.0 software. Results: In the animal heating experiments, the temperature of tumor increased up to 39.6 degree C, 43.2 degree C, and 48.1 degree C quickly with different injected doses (2, 4 and 6 mg respectively) of nano-magnetic particles and maintained for 40 min. The temperature of tumor tissue reduced to 36.8 degree C, 37.5 degree C and 37.8 degree C in 10 min when alternating magnetic field (AMF) stopped. The tumor mass in Groups C ((452.50±30.29) mg), D ((240.98±35.32)mg), E((231.87±27.41) mg) and F ((141.55±23.78) mg) were much lower than that in Group A ((719.12±22.65) mg) (F=800.07, P<0.01), with the most significant treatment effect in Group F.The tumor mass in Group B((684.05±24.02) mg) was higher than

  17. An overview of interstitial brachytherapy and hyperthermia

    International Nuclear Information System (INIS)

    Brandt, B.B.; Harney, J.

    1989-01-01

    Interstitial thermoradiotherapy, an experimental cancer treatment that combines interstitial radiation implants (brachytherapy) and interstitial hyperthermia, is in the early stages of investigation. In accordance with the procedure used in a current national trial protocol, a 60-minute hyperthermia treatment is administered after catheters are placed into the tumor area while the patient is under general anesthesia. This is immediately followed by loading of radioactive Iridium-192 seeds into the catheters for a defined period of time. Once the prescribed radiation dose is delivered, the radioactive sources are removed and a second, 60-minute hyperthermia treatment is administered. Clinical trials with hyperthermia in combination with radiation have increased in recent years. Nurses caring for these patients need to become more knowledgeable about this investigational therapy. This paper provides an overview of the biologic rationale for this therapy, as well as a description of the delivery method and clinical application. Specific related nursing interventions are defined in a nursing protocol.23 references

  18. Covalent DNA-protein crosslinking occurs after hyperthermia and radiation

    International Nuclear Information System (INIS)

    Cress, A.E.; Bowden, G.T.

    1983-01-01

    Covalent DNA-protein crosslinks occur in exponentially growing mouse leukemia cells (L1210) after exposure to ionizing radiation. The amount of DNA-protein crosslinks as measured by a filter binding assay is dose dependent upon X irradiation. Although hyperthermia and radiation in combination are synergistic with respect to cell lethality, the combination does not result in an increase of DNA-protein crosslinks when assayed immediately following treatments. Hyperthermia (43 degrees C/15 min) given prior to radiation does not alter the radiation dose dependency of the amount of initial crosslinking. In addition, the amount of DNA-protein crosslinking produced by heat plus radiation is independent of the length of heating the cells at 43 degrees C. The DNA-protein crosslinks produced by 50-Gy X ray alone are removed after 2 hr at 37 degrees C. However, if hyperthermia (43 degrees C/15 min) is given prior to 100-Gy X ray, the removal of DNA-protein crosslinks is delayed until 4.0 hr after radiation. Phospho-serine and phospho-threonine bonds are not produced with either radiation or the combination of hyperthermia plus radiation as judged by the resistance of the bonds to guanidine hydrochloride. However, hyperthermia plus radiation causes an increase in phosphate to nitrogen type bonding. These results show that radiation alone causes covalent DNA-protein crosslinks. Hyperthermia in combination with radiation does not increase the total amount of the crosslinks but delays the removal of the crosslinks and alters the distribution of the types of chemical bonding. These data suggest that the synergistic action on hyperthermia with radiation is more related to the rate of removal and the type of chemical bonding involved in the covalent DNA-protein crosslinks rather than the amount of DNA-protein crosslinks

  19. Covalent DNA-protein crosslinking occurs after hyperthermia and radiation

    International Nuclear Information System (INIS)

    Cress, A.E.; Bowden, G.T.

    1983-01-01

    Covalent DNA-protein crosslinks occur in exponentially growing mouse leukemia cells (L1210) after exposure to ionizing radiation. The amount of DNA-protein crosslinks as measured by a filter binding assay is dose dependent upon x irradiation. Although hyperthermia and radiation in combination are synergistic with respect to cell lethality, the combination does not result in an increase of DNA-protein crosslinks when assayed immediately following treatments. Hyperthermia (43 0 C/15 min) given prior to radiation dose not alter the radiation dose dependency of the amount of initial crosslinking. In addition, the amount of DNA-protein crosslinking produced by heat plus radiation is independent of the length of heating the cells at 43 0 C. The DNA-protein crosslinks produced y 50-Gy x ray alone are removed after 2 hr at 37 0 C. However, if hyperthermia (43 0 C/15 min) is given prior to 100-Gy x ray, the removal of DNA-protein crosslinks is delayed until 4.0 hr after radiation. Phospho-serine and phospho-threonine bonds are not produced with either radiation or the combination of hyperthermia plus radiation as judged by the resistance of the bonds to guanidine hydrochloride. However, hyperthermia plus radiation causes an increase in phosphate to nitrogen type bonding. These results show that radiation alone causes covalent DNA-protein crosslinks. Hyperthermia in combination with radiation does not increase the total amount of the crosslinks but delays the removal of the crosslinks and alters the distribution of the types of chemical bonding

  20. A novel hyperthermia treatment for bone metastases using magnetic materials

    International Nuclear Information System (INIS)

    Matsumine, Akihiko; Asanuma, Kunihiro; Matsubara, Takao; Nakamura, Tomoki; Uchida, Atsumasa; Sudo, Akihiro; Takegami, Kenji

    2011-01-01

    Patients with bone metastases in the extremities sometimes require surgical intervention to prevent deterioration of quality of life due to a pathological fracture. The use of localized radiotherapy combined with surgical reinforcement has been a gold standard for the treatment of bone metastases. However, radiotherapy sometimes induces soft tissue damage, including muscle induration and joint contracture. Moreover, cancer cells are not always radiosensitive. Hyperthermia has been studied since the 1940s using an experimental animal model to treat various types of advanced cancer, and studies have now reached the stage of clinical application, especially in conjunction with radiotherapy or chemotherapy. Nevertheless, bone metastases have several special properties which discourage oncologists from developing hyperthermic therapeutic strategies. First, the bone is located deep in the body, and has low thermal conductivity due to the thickness of cortical bone and the highly vascularized medulla. To address these issues, we developed new hyperthermic strategies which generate heat using magnetic materials under an alternating electromagnetic field, and started clinical application of this treatment modality. The purpose of this review is to summarize the latest studies on hyperthermic treatment in the field of musculoskeletal tumors, and to introduce the treatment strategy employing our novel hyperthermia approach. (author)

  1. Effect of radiation combined with hyperthermia on human prostatic carcinoma cell lines in culture

    International Nuclear Information System (INIS)

    Kaver, I.; Ware, J.L.; Wilson, J.D.; Koontz, W.W. Jr.

    1991-01-01

    The effect of radiation combined with heat on three human prostatic carcinoma cell lines growing in vitro was investigated. Cells were exposed to different radiation doses followed by heat treatment at 43 degrees C for one hour. Heat treatment, given ten minutes after radiation, significantly enhanced the radiation response of all the cell lines studied. The combined effect of radiation and heat produced greater cytotoxicity than predicted from the additive effects of the two individual treatment modalities alone. These results indicate that a combined treatment regimen of radiation plus hyperthermia (43 degrees, 1 hr) might be an important tool in maintaining a better local control of prostatic cancer

  2. A JASTRO study group report. A randomized phase III trial of hyperthermia in combination with radiotherapy for superficial tumors

    International Nuclear Information System (INIS)

    Hiraoka, Masahiro; Nishimura, Yasumasa; Mitsumori, Michihide

    1998-01-01

    Result of study about local effect of hyperthermia in combination with radiotherapy for superficial tumors was reported. The irradiation was more than 90% isodose for lesion, and total dose was 60 Gy in cases with anamnesis and 40-50 Gy and without anamnesis at a rate of five times a week and 2 Gy at one time. Hyperthermia was carried out four times; once a week, at 42.5 degrees on tumor side edge, and for 40 minutes. Total 53 cases (neck lymph node metastasis 30 cases, relapse breast cancer 11, advanced breast cancer 1, other superficial tumor 11) were divided into 2 groups. Radiotherapy without hyperthermia (group R) was 27 cases, radiotherapy with hyperthermia (group H) was 26 cases. CR and CR+PR within 2 months after treatment were as follows: Group R: 50%, 85%, Group H: 64%, 100%. The CR+PR was superior in group H (p=0.0497). The CR at maximum effect after treatment was 65% of group R and 86% of group H (p=0.17). The local control rate after CR was not different in both groups. (K.H.)

  3. Effect of hyperthermia, radiation and adriamycin combinations on tumor vascular function

    International Nuclear Information System (INIS)

    Eddy, H.A.; Chmielewski, G.

    1982-01-01

    Pathophysiologic studies of tumor vascular responses to hyperthermia, radiation or adriamycin given alone or in specific combinations have been made in the cervical carcinoma grown in the transparent cheek pouch chamber of the Syrian hamster. A specially designed chamber containing a compartment for flowing water enabled controlled heating of the tumor and pouch to within 0.2 0 C; the desired temperatures were achieved within one minute. Heating at 42 0 C for 30 minutes was followed, at 1, 5 or 24 hours, by a second heating for 30 minutes at 42 0 C. In addition, the same period of heating was preceded or followed, at 1, 5 or 24 hour intervals, by a single exposure to 2000R or a single intravenous injectionof adriamycin given at a rate of 0.45 mg/100 gm body weight. Of the three modalities, heat appeared to have the greatest acute effect on the tumor vascular system. A single dose of heat produced a rapid but transient constriction followed by a prominent dilation of vessels. Two heating periods given at a 1 hour interval caused persistent stasis in the tumor which progressed to coagulation necrosis. Although heating prior to irradiation or adriamycin, in general, increased the vascular responses to these agents, this sequence gave no tumor control. Radiation or adriamycin given prior to heating had relatively little effect on the vascular response to heating and produced no tumor control except when heat was applied shortly after irradiation. These studies indicate that changes in the microvasculature and perfusion in tumors, in response to hyperthermia alone or combined in specific sequences with radiation, can alter the internal environment of the tumor to produce a greater degree of tumor control than can be attributed to direct cell killing by these agents

  4. Novel Combination Chemotherapy for Localized Ewing Sarcoma

    Science.gov (United States)

    In this clinical trial, researchers will test whether the addition of the drug combination vincristine, topotecan, and cyclophosphamide to a standard chemotherapy regimen improves overall survival in patients with extracranial Ewing

  5. Combined radio- and chemotherapy from the point of view of the internist-oncologist

    International Nuclear Information System (INIS)

    Engelhardt, R.

    1979-01-01

    The indications for a combined radio- and chemotherapy can be summarized from three points of view: 1) Intensifying local radiotherapy by chemotherapy. 2) Extending local radiotherapy by systematical chemotherapy. 3) Supporting chemotherapy by radiotherapy. The side effects of the combination are discussed, classified as immediate type and long-term type. It is indicated that in all combinations the drug-specific and/or organ-specific side effects of the cytostatics must be taken into consideration. The substantial therapeutical aspect lies in prophylaxis. Exact data concerning the reduction of the dosage of the radiotherapy and/or the chemotherapy must be found after exact observation of the complications. Knowing the side effects of the immediate-type and taking into consideration the long-term damage which can be expected, there are today clear indications for a combined radio- and chemotherapy. (orig./MG) 891 MG/orig.- 892 RDG [de

  6. Inhibitory effect of sequential combined chemotherapy and radiotherapy on growth of implanted tumor in mice

    International Nuclear Information System (INIS)

    Okada, Kouji

    1983-01-01

    Sequential chemotherapy using FT-207, adriamycin and mitomycin C followed by radiotherapy was attempted to achieve effective inhibition against implanted tumor in C57BL/6 black mice bearing YM-12 tumors. Sequential combined chemotherapy was more effective than single drug chemotherapy or combined chemotherapy of other drugs. Addition of radiotherapy to the sequential combined chemotherapy was successful for enhancing therapeutic effect. (author)

  7. Intestinal cell proliferation following hyperthermia-radiation combinations

    International Nuclear Information System (INIS)

    Burholt, D.R.; Wilkinson, D.A.; Shrivastava, P.N.

    1987-01-01

    The present work is an investigation of the extent to which hyperthermia enhances x-ray induced inhibition of intestinal epithelial cell proliferation in mice. Hyperthermia was achieved by whole body immersion of anesthetized ice in a temperature controlled water bath (+-0.1 0 C). Post-treatment proliferative activity was monitored by determining the incorporation of /sup 3/H-TdR into intestinal crypt cells and by the counting of epithelial cell mitotic figures. Initial levels of cell kill were assessed by the microcolony crypt survival technique. All heat treatments were 41.5 0 C for 0.5h. Heat alone reduced the /sup 3/H-TdR incorporation to 50% of the control value by 2h post-treatment. This was followed by a return to control value by 10h and a slight hyperplasia at 24h. Heat either immediately before or after 2Gy abdominal field x-irradiation produced a prolonged period of depressed cell proliferation: /sup 3/H-TdR incorporation remained below control value for the first 24h. As the heat and radiation were separated in time from each other (up to 4h) the interaction between the two decreased. The development of thermotolerance was observed following the second and third treatment during either a heat-only or a heat-radiation multifraction treatments schedule with the treatment spaced 24h apart

  8. Combination of hyperthermia and photodynamic therapy on mesenchymal stem cell line treated with chloroaluminum phthalocyanine magnetic-nanoemulsion

    Energy Technology Data Exchange (ETDEWEB)

    Paula, Leonardo B. de [Departamento de Química, Centro de Nanotecnologia e Engenharia Tecidual, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP 14040-901 (Brazil); Departamento de Genética, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP 14049-900 (Brazil); Primo, Fernando L. [Departamento de Química, Centro de Nanotecnologia e Engenharia Tecidual, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP 14040-901 (Brazil); Nanophoton Company, SUPERA Innovation and Technology Park, Av. Doutora Nadir de Aguiar, 1805, Universidade de São Paulo, Ribeirão Preto, P 14056-680 (Brazil); Pinto, Marcelo R. [Departamento de Química, Laboratório de Enzimologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP 14040-901 (Brazil); Morais, Paulo C. [Instituto de Física, Universidade de Brasília, Brasília, DF 70910-900 (Brazil); School of Automation, Huazhong University of Science and Technology, Wuhan 430074 (China); and others

    2015-04-15

    The present study reports on the preparation and the cell viability assay of two nanoemulsions loaded with magnetic nanoparticle and chloroaluminum phthalocyanine. The preparations contain equal amount of chloroaluminum phthalocyanine (0.05 mg/mL) but different contents of magnetic nanoparticle (0.15×10{sup 13} or 1.50×10{sup 13} particle/mL). The human bone marrow mesenchymal stem cell line was used as the model to assess the cell viability and this type of cell can be used as a model to mimic cancer stem cells. The cell viability assays were performed in isolated as well as under combined magnetic hyperthermia and photodynamic therapy treatments. We found from the cell viability assay that under the hyperthermia treatment (1 MHz and 40 Oe magnetic field amplitude) the cell viability reduction was about 10%, regardless the magnetic nanoparticle content within the magnetic nanoparticle/chloroaluminum phthalocyanine formulation. However, cell viability reduction of about 50% and 60% were found while applying the photodynamic therapy treatment using the magnetic nanoparticle/chloroaluminum phthalocyanine formulation containing 0.15×10{sup 13} or 1.50×10{sup 13} magnetic particle/mL, respectively. Finally, an average reduction in cell viability of about 66% was found while combining the hyperthermia and photodynamic therapy treatments. - Highlights: • Current protocols in nanotechnology allow for biocompatible magnetic nanoparticles being associated with photosensitizer photoactive drugs, which could lead to perfectly controlled drug release. • The combination of the HPT and PDT therapies can be useful to develop further protocols for both advanced in vitro and in vivo assays. • Magnetic nanodevices associated with therapies have led to the decreased of proliferation of cell population that provides a favorable environment for tumor progression.

  9. Combination of hyperthermia and photodynamic therapy on mesenchymal stem cell line treated with chloroaluminum phthalocyanine magnetic-nanoemulsion

    International Nuclear Information System (INIS)

    Paula, Leonardo B. de; Primo, Fernando L.; Pinto, Marcelo R.; Morais, Paulo C.

    2015-01-01

    The present study reports on the preparation and the cell viability assay of two nanoemulsions loaded with magnetic nanoparticle and chloroaluminum phthalocyanine. The preparations contain equal amount of chloroaluminum phthalocyanine (0.05 mg/mL) but different contents of magnetic nanoparticle (0.15×10 13 or 1.50×10 13 particle/mL). The human bone marrow mesenchymal stem cell line was used as the model to assess the cell viability and this type of cell can be used as a model to mimic cancer stem cells. The cell viability assays were performed in isolated as well as under combined magnetic hyperthermia and photodynamic therapy treatments. We found from the cell viability assay that under the hyperthermia treatment (1 MHz and 40 Oe magnetic field amplitude) the cell viability reduction was about 10%, regardless the magnetic nanoparticle content within the magnetic nanoparticle/chloroaluminum phthalocyanine formulation. However, cell viability reduction of about 50% and 60% were found while applying the photodynamic therapy treatment using the magnetic nanoparticle/chloroaluminum phthalocyanine formulation containing 0.15×10 13 or 1.50×10 13 magnetic particle/mL, respectively. Finally, an average reduction in cell viability of about 66% was found while combining the hyperthermia and photodynamic therapy treatments. - Highlights: • Current protocols in nanotechnology allow for biocompatible magnetic nanoparticles being associated with photosensitizer photoactive drugs, which could lead to perfectly controlled drug release. • The combination of the HPT and PDT therapies can be useful to develop further protocols for both advanced in vitro and in vivo assays. • Magnetic nanodevices associated with therapies have led to the decreased of proliferation of cell population that provides a favorable environment for tumor progression

  10. A review of topotecan in combination chemotherapy for advanced cervical cancer

    Directory of Open Access Journals (Sweden)

    Minoo Robati

    2008-03-01

    Full Text Available Minoo Robati, David Holtz, Charles J DuntonDepartment of Obstetrics and Gynecology, Main Line Gynecologic Oncology, Lankenau Hospital, Wynnewood, PA, USAAbstract: Treatment of advanced, recurrent or persistent cervical cancer includes radiotherapy and chemotherapy. Radiation has been the primary treatment modality for locoregionally advanced cervical cancer. Concomitant systemic cisplatin chemotherapy and radiation have shown high response rates with improvements in durable remissions and overall survival. Cisplatin has been the standard medication for the treatment of advanced cervical cancer. Combinations with other chemotherapeutic agents have been the subject of clinical trials with varying results. The toxicity of combination chemotherapy and tolerability of patients are other factors that should be considered in the management of patients with advanced disease. Recently topotecan, in combination with cisplatin, achieved increased response and overall survival rates without further compromising the patients’ quality of life. This review focuses on the mechanism of action and toxicities of topotecan, as well as its role as a radio-sensitizer and chemotherapeutic agent in the management of advanced, recurrent, or persistent cervical cancer. Other combination modalities and dosages are also discussed.Keywords: topotecan, combination chemotherapy, advanced cervical cancer

  11. Esho 2005. 22nd annual meeting of the European society for hyperthermic oncology. Book of abstracts

    International Nuclear Information System (INIS)

    Rehak, P.H.; Tscheliessnigg, K.H.

    2005-01-01

    Full text: In this book of abstracts were treated the role of hyperthermia in oncology, the combination of hyperthermia with radiotherapy and chemotherapy, the risk factors and the toxicity of regional hyperthermia combined with radiochemotherapy and the hyperthermia treatment planning in neoplasms using invasive thermometry and the prognostic significance for clinical outcome. (botek)

  12. Esho 2005. 22{sup nd} annual meeting of the European society for hyperthermic oncology. Book of abstracts

    Energy Technology Data Exchange (ETDEWEB)

    Rehak, P H; Tscheliessnigg, K H [Medical University of Graz, Department of Surgery, Graz (Austria)

    2005-07-01

    Full text: In this book of abstracts were treated the role of hyperthermia in oncology, the combination of hyperthermia with radiotherapy and chemotherapy, the risk factors and the toxicity of regional hyperthermia combined with radiochemotherapy and the hyperthermia treatment planning in neoplasms using invasive thermometry and the prognostic significance for clinical outcome. (botek)

  13. Efficacy and limitations of hyperthermia using a 13.56 MHz radiofrequency capacitive heating system

    International Nuclear Information System (INIS)

    Kawamori, Jiro; Ito, Hideo; Kato, Ken-ichi; Hayasaka, Kazumasa; Saito, Tsutomu; Urahashi, Shingo; Tanaka, Yoshiaki

    1996-01-01

    Between August 1989 and June 1995, 123 patients were treated with hyperthermia using a 13.56 MHz RF capacitive heating system (HEH 500C/OMRON). Hyperthermia was combined with radiation therapy in 103 patients, with radiochemotherapy in 15 patients, with chemotherapy in 3 patients, and was used in 2 patients. Among the 123 patients, 92 completed hyperthermia and the remaining 31 discontinued it. Of these 31 patients, hyperthermia was discontinued because of local pain during heating in 22 cases and because of the poor general condition the remaining 9 patients. The initial response rate of the 92 patients completing therapy was 54.3%. CR, PR, NC and PD were achieved in 15, 35, 37, and 5 case, respectively. Initial response rates for head/neck, breast, and bone/soft tissue tumors were better than for other primary sites. The initial response rate for superficial tumors was better than that for deep seated tumors. Prognostic factors that significantly influenced the initial response rate were the radiation dose, number of heating sessions, tumor histology, and primary site. Concerning pain during heating, severe pain or discontinuation due to pain occurred were observed in 49 cases (39.8%). The factors having a significant correlation with pain during heating were applicator arrangement, applicator size, heating site, and tumor depth. In 24 patients, erosions or ulcers occurred (27.2%). The factors having a significant correlation with acute skin reactions, were applicator arrangement, applicator size, radiation therapy, tumor depth, and proximity to bone. In 12 cases, fat necrosis was observed (13%). Multiple regression analysis showed that the thickness of the subcutaneous fat, and the applicator arrangement had a significant correlation with the occurrence of fat necrosis. (K.H.)

  14. Preliminary clinical results of locoregional hyperthermia for primary and secondary bone tumors

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, J.L.; Nagata, Yasushi; Kanamori, Shuichi; Mitsumori, Michihide; Okuno, Yoshishige; Horii, Naotoshi; Nishimura, Yasumasa; Masunaga, Shinitiro; Hiraoka, Masahiro [Kyoto Univ. (Japan). Graduate School of Medicine

    2000-03-01

    Nineteen primary and secondary bone tumors in 16 patients were treated with hyperthermia plus radiotherapy and/or chemotherapy between 1982 and 1997 at Kyoto University Hospital. The thermometric and clinical results were analyzed retrospectively. In 55 of 86 hyperthermia sessions, the intratumor temperature was measured using a thermometer. Of the 19 tumors, 16 (84%) received heat treatment 4-7 times, and 3 (16%) received 1 or 2 treatments of hyperthermia. The mean maximum, mean minimum and average intratumor temperatures were 42.9, 40.4 and 41.6 deg C, respectively, and 12 (67%) reached a tumor maximum temperature above 42.5 deg C. The durations that intratumor points exceeded 42, 41 and 40 deg C were 27, 34 and 38 min, respectively. The local tumor response to treatment was assessed using X-ray computed tomography. The local response rate was 16% and the local pain relief rate was 63%. The 1-year cumulative survival rate was 60%. Our preliminary results indicated that thermoradiotherapy and thermochemotherapy are clinicaly feasible and potentially beneficial in the management of locally advanced bone tumors. (author)

  15. Combined radiotherapy-chemotherapy in clinical practice

    International Nuclear Information System (INIS)

    Horwich, A.

    1989-01-01

    This paper investigates the combination of radiotherapy and chemotherapy performed over the last 15 years. The improvement of the therapeutic ratio of anti- cancer effect to normal tissue toxicity and its requirement of a thorough understanding of the biological effects of each modality and of how these effects may interact is presented. Early studies and conclusions are examined

  16. Hyperthermia treatment planning

    International Nuclear Information System (INIS)

    Lagendijk, J.J.W.

    2000-01-01

    The development of hyperthermia, the treatment of tumours with elevated temperatures in the range of 40-44 deg. C with treatment times over 30 min, greatly benefits from the development of hyperthermia treatment planning. This review briefly describes the state of the art in hyperthermia technology, followed by an overview of the developments in hyperthermia treatment planning. It particularly highlights the significant problems encountered with heating realistic tissue volumes and shows how treatment planning can help in designing better heating technology. Hyperthermia treatment planning will ultimately provide information about the actual temperature distributions obtained and thus the tumour control probabilities to be expected. This will improve our understanding of the present clinical results of thermoradiotherapy and thermochemotherapy, and will greatly help both in optimizing clinical heating technology and in designing optimal clinical trials. (author)

  17. Magnetic Hyperthermia and Radiation Therapy: Radiobiological Principles and Current Practice †

    Directory of Open Access Journals (Sweden)

    Spiridon V. Spirou

    2018-06-01

    Full Text Available Hyperthermia, though by itself generally non-curative for cancer, can significantly increase the efficacy of radiation therapy, as demonstrated by in vitro, in vivo, and clinical results. Its limited use in the clinic is mainly due to various practical implementation difficulties, the most important being how to adequately heat the tumor, especially deep-seated ones. In this work, we first review the effects of hyperthermia on tissue, the limitations of radiation therapy and the radiobiological rationale for combining the two treatment modalities. Subsequently, we review the theory and evidence for magnetic hyperthermia that is based on magnetic nanoparticles, its advantages compared with other methods of hyperthermia, and how it can be used to overcome the problems associated with traditional techniques of hyperthermia.

  18. ADPRT inhibitors and hyperthermia as radiosensitizers

    International Nuclear Information System (INIS)

    Jonsson, G.G.

    1985-01-01

    Hyperthermia given in combination with gamma radiation has given considerable improvement in the therapeutic results for treatment of malignant tumors. The mechanism behind the hyperthermia effect is probably operative at the tissue level as well as at the molecular level. The metabolism of NAD + in relation to the activity of the chromosomal enzyme ADP-ribosyl transferase (ADPRT) has been studied as a possible molecular mechanism for this effect. The ADPRT activity was measured after radiosensitization with both hyperthermia and nicotinamide, which is a potent inhibitor of ADPRT. The results indicate that hyperthermia can improve the effect of radiotherapy by reducing the supply of NAD + , which is a co-substrate for ADPRT, while nicotinamide functions as a radiosensitizing agent by direct inhibition of the enzyme. The hypothesis is discussed in the thesis where inhibition of ADPRT might increase the radiosensitivity because the radiation-induced DNA damage can not be repaired with normal efficiency. The function of nicotinamide as a radiosensitizer was verified by studies on C3H mice with transplanted spontaneous mammary tumors. Because nicotinamide is not toxic, it seems quite attractive to test this vitamin as a radiosensitizing agent against human tumors. (251 refs.) (author)

  19. Modification of radiosensitivity of mammalian cells by means of hyperthermia and chemical agent. Coordinated programme on improvement of cancer therapy by the combination of treatment by conventional radiation and physical or chemical means

    International Nuclear Information System (INIS)

    Djordjevic, O.

    1984-11-01

    The effect of the treatment of the cultured mammalian cells with a relatively new anti-cancer drug teniposide (VM26), radiation (4 Gy), hyperthermia (42 deg. C and 45 deg. C) and caffeine, in various combinations, has been studied. The following conclusions can be drawn from the data obtained: The cultured mammalian cells respond to the anti-cancer drug VM26 treatment in a dose and time dependent manner. Significant potentiation of cell killing was demonstrated when they are exposed simultaneously to VM26 and hyperthermia. Post-treatment incubation of the cells in non-toxic concentration of caffeine (2 mM) has produced a marked potentiation of the lethal effect, indicating that caffeine interferes with the repair processes in these cells. Combination of VM26, hyperthermia and caffeine produced a maximum killing effect compared to VM26 treatment only. When the cells are exposed to initial (90 min. at 42 deg. C or 40 min. at 45 deg. C) and subsequent hyperthermia (60 min. at 42 deg. C or 60 min. at 45 deg. C) the thermotolerance will develop depending on the degree of initial and subsequent temperature. The combination of hyperthermia with irradiation results in a potentiation of the effect of treatment compared to the treatment with only irradiation or hyperthermia. Maximum killing of the cells will be obtained when irradiation is applied immediately after hyperthermia. The results obtained should be regarded as useful in case of clinical application of the tested agents

  20. Malignant cliomas treated after surgery by combination chemotherapy and delayed irradiation. Pt. 1

    International Nuclear Information System (INIS)

    Poisson, M.; Mashaly, R.; Pertuiset, B.F.; Metzger, J.

    1979-01-01

    Forty-six patients with gliomas were introduced after surgery into a therapeutic programme of six cycles of combination chemotherapy with VM 26 and CCNU, followed by delayed irradiation six months after surgery with an average dose of 5,800 rads. After irradiation the same preradiation chemotherapy was readministered for an average of four cycles. The results were compared to those from another group of 28 patients treated only by the same chemotherapy (CRC and C groups successively). Twelve patients (26%) died before irradiation in the CRC groups, six patients (13%) had recurrences at the time of irradiation, and 28 patients (61%) had no clinical or radiological signs of recurrence at the time of irradiation. For the total of treated patients the median survival after surgery was 17 months, and 46% of the patients were surviving at 18 months. The percentage of survivors at 18 months was significantly more elevated in the group treated by combination chemotherapy and delayed irradiation than in a control group treated by the same combination chemotherapy alone. This result suggests that in approximately 50% of cases combination chemotherapy after surgery, and delayed irradiation six months after surgery, cumulated their effects on survival time. (author)

  1. Role of combination chemotherapy in non-Hodgkin's lymphoma in children

    International Nuclear Information System (INIS)

    Dutta, H.S.; Chandra, A.B.; Mitter, M.; Mukherjee, D.; Batabyal, S.; Samaddar, A.S.; Mukherjee, S.

    1980-01-01

    Eighteen children suffering from Non-Hodgkin's lymphoma were studied. Of these eighteen children, eight (44.4 percent) had well differentiated diffuse lymphocytic lymphoma and six (33.3 percent) had poorly differentiated diffuse lymphocytic lymphoma and four (22.3 percent) had histiocytic lymphoma. Histological study was based on the concept of Rappaport (1966). Children belonging to Stage IIB were treated with radiotherapy followed by combination chemotherapy and those with Stage IIIB and Stage IVB were treated with combination chemotherapy utilising cyclophosphamide, oncovin and prednisolone. The result of combination chemotherapy (COP) was dramatic and appears to have resulted in long term disease free survival. In well differentiated diffuse lymphocytic lymphoma in Stage IIB the life expectancy of two children was extended to 12 years with well maintained remission for 9.5 years. Recurrence rate was 44.4 percent. Death rate was 61.1 percent and median survival time was 26.7 months. In histiocytic lymphomas the results were unsatisfactory. Median survival time was 9.5 months. (author)

  2. Super-selective interventional chemotherapy combined with systemic chemotherapy for the treatment of postoperative gliomas:a clinical study

    International Nuclear Information System (INIS)

    Chen Jian; Hu Qinglei; Sun Yanchun; Feng Lei; Liu Yunzhen; Liu Ju; Kong Ruifen

    2010-01-01

    Objective: To evaluate super-selective interventional chemotherapy combined with systemic chemotherapy in treating postoperative gliomas. Methods: During the period of 2005-2009, a total of 46 patients with glioma were encountered in our hospital. According to the principle of patient's free will the involved patients were divided into two groups. Study group (n = 25): after operation the patients received routine radiotherapy, which was followed by super-selective interventional chemotherapy combined simultaneously with systemic chemotherapy. Control group (n = 21): after operation the patients received routine radiotherapy, which was followed by systemic chemotherapy only. The patients were regularly followed up. Cranial CT checkups were made to determine the tumor size, and the results were evaluated with Karnofsky scores. The clinical data were analyzed and compared between two groups. Results: In the study group, the side-effects and complications included epileptic seizures (n = 3), eye pain (n = 5), headache (n = 9), nausea and vomiting (n = 8) and thrombopenia (n = 1). In the control group,the side-effects and complications were as follows: epileptic seizures (n = 1), headache (n = 7), nausea and vomiting (n = 6) and thrombopenia(n = 3). No death occurred in either of the two groups. The patients were followed up for an average period of 2.3 years. Before chemotherapy no statistically significant difference in tumor size existed between two groups (P > 0.05). One year after the chemotherapy, the tumor volume in study group was reduced by 67.11%, while it was 45.79% in control group. By using independent sample t test analysis, the difference between two groups was of statistical significance (P < 0.05). Wilcoxon rank sum test and Karnofsky prognostic score analysis indicated that the prognosis of study group was much better than that of control group (P < 0.05). Conclusion: In comparison with routine radiotherapy plus simple systemic chemotherapy, routine

  3. [Effects of pamidronate disodium (Bonin) combined with chemotherapy on bone pain in multiple myeloma].

    Science.gov (United States)

    Leng, Yun; Chen, Shi-lun; Shi, Hong-zhi

    2002-10-01

    Objective. To evaluate the therapeutic effects of Disodium Pamidronate (Bonin) on bone pain in multiple myeloma. Method. 18 patients received only chemotherapy and 16 patients with addition of Bonin were compared. Result. The bone pain was significantly relieved both in chemotherapy alone group and in the combination group of Bonin with chemotherapy after treatment (P<0.01, as compared with before therapy). However, the effects of combination group were more dramatical than that of the other group (P<0.05). No obvious side-effects were observed except mild fever in one patient in the combination group. Conclusion. Bonin, as a safe and effective Bisphosphonates preparation, could relieve bone pain in multiple myeloma more effectively when combined with chemotherapy.

  4. Effects of hyperthermia and X-irradiation on mouse stromal tissue

    International Nuclear Information System (INIS)

    Wondergem, J.; Haveman, J.

    1986-01-01

    The sensitivity of normal stroma to heat, irradiation and heat combined with irradiation, was studied using the tumour bed effect (TBE) assay. Irradiation before implantation led to a TBE, dose dependent below 15 Gy, but remaining relatively constant above. The interval (0-90 days) between irradiation and tumour implantation did not influence the magnitude of the TBE. Hyperthermia with large heat doses (45-60 min at 44 0 C) before implantation may lead to a TBE. The interval between hyperthermia and tumour implantation was very important. Results showed that the recovery from heat-induced stromal damage is very rapid. When the interval between hyperthermia and tumour implantation was 10 days or longer, no TBE could be observed. Irradiation combined with large heat doses (30-60 min at 44 0 C) decreased the radiation-induced TBE. The combination of irradiation with mild heat treatments (15 min at 44 0 C) could lead to a larger TBE then after irradiation alone. When hyperthermia was given prior to irradiation, the interval between heat and irradiation proved to be very important. With large intervals (21 days or longer), TBE values were about the same as with irradiation alone. When heat was given after irradiation, irradiation-induced TBE was always reduced. (UK)

  5. 31P-MRS study for the assessment of tumor response after radiotherapy and/or hyperthermia

    International Nuclear Information System (INIS)

    Kimura, Hirohiko; Itho, Satoshi; Nakatsugawa, Sigekazu; Maeda, Masayuki; Iwasaki, Toshiko; Yamamoto, Kazutaka; Ishii, Yasushi

    1992-01-01

    The metabolic changes of human lung cancer implanted in nude mice were studied by the use of in vivo 31 P nuclear magnetic resonance spectroscopy ( 31 P-MRS) after radiotherapy, hyperthermia or the combined therapy of radiation and hyperthermia. 31 P-MRS of the tumors showed increased Pi/β-NTP ratio and acidic pH value on 1 day after hyperthermia, that indicated metabolic decline caused by hyperthermia. On the other hand, lower Pi/β-NTP ratios during 3 to 10 days after irradiation suggested metabolic activation of the tumors. In the tumors treated with the combined therapy, 31 P-MRS revealed increase of Pi/β-NTP ratio within 1 day and its decrease subsequent 6 to 10 days after treatment, that indicated additive bi-phasic changes induced by radiation and hyperthermia, respectively. Since Pi/β-NTP ratio had significant correlation to the tumor blood perfusion measured by hydrogen gas clearance studies, these bi-phasic changes were considered to correspond to two different physiological states, namely, ischemic and reperfused states. 31 P-MRS obtained from tumors could be useful to asses the physiological consequence following radiation, hyperthermia or the combined therapy. (author)

  6. Two cases of fatal necrosis of the lesser pelvis in patients treated with combined radiotherapy and hyperthermia for cervical carcinoma

    NARCIS (Netherlands)

    Wiggenraad, R.; Koning, C.; Westermann, C.; Jansen, C.; van der Zee, J.

    2005-01-01

    This study reports two cases of fatal necrosis of the lesser pelvis in patients with advanced cervical carcinoma, who had received combined radiotherapy and hyperthermia. The necrosis reached far from the high dose area, in one of the cases even outside the radiation portals. Both patients initially

  7. Cellular radiation effects and hyperthermia cell cycle kinetics of radiation sensitive mutants of saccharomyces cerevisiae after x-irradiation and hyperthermia

    International Nuclear Information System (INIS)

    Fingerhut, R.; Kiefer, J.; Otto, F.

    1983-01-01

    Radiosensitive mutants rad2, rad9, and rad51 of Saccharomyces cerevisiae were X-irradiated with 120 Gy or 60 Gy, heated at 50 0 C for 30 min or treated with a combination of both and incubated in nutrient medium at 30 0 C. Cell number, percentage of budding cells, and cell cycle progression were determined in 45-min intervals. Cell cycle kinetics were investigated by flow cytofluorometry. Hyperthermia leads mainly to a lengthening of G1, whereas X-rays arrest cells of the rad2 and rad9 mutant in G2 and the rad51 - mutant additionaly in a state with DNA contents above G2. Cell division dealy is influenced by oxygen in all strains but to a lesser extent in the rad2 mutant. The effect of the combined treatment appears to be merely additive in the rad2 and rad9 mutant while the rad51 mutant is sensitized to X-irradiation by hyperthermia. No selective action of hyperthermia on hypoxic cells was found. (orig.)

  8. Destruction of radiation-resistant cell populations by hyperthermia

    International Nuclear Information System (INIS)

    Roettinger, E.M.; Gerweck, L.E.

    1979-01-01

    Animal experiments with local hyperthermia have shown that the radiauion dose necessary for the local control of 50% of the tumours examined was essentially reduced by heating to 42,5 0 C. In-vitro experients indicated selective destruction of relatively radiation-resistent cell populations by the combination of hyperthermie and reduced hydrogen ion concentration. Experiments with glioblastoma cells confirmed these results qualitatively, but showed quantitatively considerably lower sensitivity towards hyperthermia. (orig.) 891 MG/orig. 892 RDG [de

  9. Recommendations for In Vitro and In Vivo Testing of Magnetic Nanoparticle Hyperthermia Combined with Radiation Therapy

    Directory of Open Access Journals (Sweden)

    Spiridon V. Spirou

    2018-05-01

    Full Text Available Magnetic nanoparticle (MNP-mediated hyperthermia (MH coupled with radiation therapy (RT is a novel approach that has the potential to overcome various practical difficulties encountered in cancer treatment. In this work, we present recommendations for the in vitro and in vivo testing and application of the two treatment techniques. These recommendations were developed by the members of Working Group 3 of COST Action TD 1402: Multifunctional Nanoparticles for Magnetic Hyperthermia and Indirect Radiation Therapy (“Radiomag”. The purpose of the recommendations is not to provide definitive answers and directions but, rather, to outline those tests and considerations that a researcher must address in order to perform in vitro and in vivo studies. The recommendations are divided into 5 parts: (a in vitro evaluation of MNPs; (b in vitro evaluation of MNP-cell interactions; (c in vivo evaluation of the MNPs; (d MH combined with RT; and (e pharmacokinetic studies of MNPs. Synthesis and characterization of the MNPs, as well as RT protocols, are beyond the scope of this work.

  10. Efficiency of lipofection combined with hyperthermia in Lewis lung carcinoma cells and a rodent pleural dissemination model of lung carcinoma.

    Science.gov (United States)

    Okita, Atsushi; Mushiake, Hiroyuki; Tsukuda, Kazunori; Aoe, Motoi; Murakami, Masakazu; Andou, Akio; Shimizu, Nobuyoshi

    2004-06-01

    We have previously reported that hyperthermia at 41 degrees C enhanced lipofection-mediated gene transduction into cultured cells. In this study, we adapted hyperthermia technique to novel cationic liposome (Lipofectamine 2000) mediated gene transfection into Lewis lung carcinoma cells in vitro and in vivo. In vitro, transfection efficiencies were 38.9+/-3.3% by lipofection alone and 52.1+/-2.6% by lipofection with hyperthermia for 30 min, and 62.5+/-5.5% and 81.4+/-3.2% for 1 h, respectively. Hyperthermia significantly enhanced gene transfection efficiency 1.2-1.4 times more than that with lipofection only. We also evaluated the effect of hyperthermia with a pleural dissemination model of lung carcinoma of mice. We developed a model which was well-tolerated with hyperthermia with lipofection by the mice. In spite of repeated treatments, transfection efficiencies were very low and we could not show the augmentation of gene transfection by hyperthermia. Though Lipofectamine 2000 showed strong gene transduction effect and hyperthermia augmented its effect in vitro, further evaluation is needed to adapt both techniques in vivo.

  11. The combination of chemotherapy and radiotherapy towards more efficient drug delivery.

    Science.gov (United States)

    Cao, Wei; Gu, Yuwei; Meineck, Myriam; Xu, Huaping

    2014-01-01

    Research on anticancer therapies has advanced significantly in recent years. New therapeutic platforms that can further improve the health of patients are still highly demanded. We propose the idea of combining regular chemotherapy with radiation therapy to minimize side effects as well as increase drug-delivery efficiency. In this Focus Review, we seek to provide an overview of recent advances that can combine chemotherapy and radiotherapy. We begin by reviewing the current state of systems that can combine chemotherapy and gamma radiation. Among them, diselenide-containing polymers are highlighted as sensitive drug-delivery vehicles that can disassemble under gamma radiation. Then X-ray responsive materials as promising alternative systems are summarized, including X-ray responsive drug-delivery vehicles, prodrugs that can be activated by X-rays, and radiation-site-targeting systems. Finally, we describe strategies that involve phototherapies. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Clinical research on cancer treatment with combined radiotherapy and chemotherapy

    International Nuclear Information System (INIS)

    Fuwa, Nobukazu; Ito, Yoshiyuki; Kato, Eriko; Koyama, Kazuyuki; Morita, Kozo

    1993-01-01

    There are two purposes of using combined chemotherapy and radiotherapy in the treatment of cancers. One is to suppress distant metastasis, especially micrometastasis; the other is to improve localized control. As a trial of the utility of the former, systemic chemotherapy with CDDP and 5 FU was given successively with radiotherapy to treat nasopharyngeal cancer. The survival rate was significantly improved compared with historical control cases. The main reason for this effectiveness was the improvement of localized control. The suppression of distant metastasis is the subject of future research. As a trial of the utility of the latter, a super-selective intraarterial chemotherapy with CBDCA combined with radiotherapy was used to head and neck localized progressive cancers. The control of localized cancer was remarkably effective. This treatment is considered to be especially suitable for locally advanced tongue cancer and cancer of the root of the tongue. (author)

  13. Study on combined chemotherapy and radiotherapy of the microcellular bronchial carcinoma (CCR study): chemo-/radiotherapy opposed to radio-/chemotherapy

    International Nuclear Information System (INIS)

    Heilmann, H.P.; Buenemann, H.; Arnal, M.L.; Calavrezos, A.; Engel, J.; Hain, E.; Koschel, G.; Seysen, U.; Allgemeines Krankenhaus Harburg, Hamburg; Franke, H.D.; Juengst, G.; Kohl, F.V.; Wichert, P. v.

    1983-01-01

    The authors studied the effect of a chemo-/radiotherapy or radio-/chemotherapy on 52 cases of microcellular bronchial carcinoma, classification ''limited disease''. The survival curves were slightly better for the patients submitted to primary chemotherapy, but the difference was not statistically significant, and the curves coincided again after 18 months. 60 to 80% of the patients had no complaints or only unimportant complaints during more than half of their survival time. In 23 patients with ''extensive disease'' who received only a symptomatic therapy or a combined palliative chemotherapy, chemotherapy had a slightly better effect, but this was not statistically significant. (orig.) [de

  14. Present clinical status of hyperthermia associated with radiotherapy

    International Nuclear Information System (INIS)

    Jaulerry, C.; Bataini, J.P.; Brunin, F.; Gaboriaud, G.

    1981-01-01

    Improved techniques for inducing heat: ultrasound, microwaves, diathermy with different application modalities, capable of producing localized superficial or deep, regional or total body hyperthermia have been responsible for the multiplication of clinical trials. These studies have confirmed the tumoricidal effect of hyperthermia alone, or more especially when combined with radiotherapy, and the good tolerance of normal tissues to localized temperatures of 42 to 43.5 0 C even in previously irradiated cases. Localized heating does not seem to increase the incidence of metastasis. Enhancement ratios and therapeutic gain with respect to normal tissues are not yet well documented. Many problems, including the heterogenicity of tissues to be heated, difficulties with temperature monitoring, and selection of appropriate sequential scheduling of radiation and hyperthermia remain unsolved and further investigationss are required [fr

  15. Oral combination chemotherapy in the treatment of AIDS ...

    African Journals Online (AJOL)

    Objectives: To determine the effectiveness of an oral combination chemotherapy regimen administered to patients with AIDS-associated Hodgkin's disease. Design: Prospective, pilot phase II clinical trial. Setting: Consecutive patient recruitment occurred at two medical centers in the United States: Albany Medical Center, ...

  16. Chemotherapy response as a prognosticator for survival in patients with limited squamous cell lung cancer treated with combined chemotherapy and radiotherapy

    International Nuclear Information System (INIS)

    Eagan, R.T.; Fleming, T.R.; Lee, R.E.; Ingle, J.N.; Frytak, S.; Creagan, E.T.

    1980-01-01

    Twenty-two patients with limited unresectable squamous cell lung cancer were treated with 6 courses of combination chemotherapy consisting of cyclophosphamide, adriamycin, cisplatin, and bleomycin (CAP-Bleo) and short-course thoracic irradiation started after the first 4 weeks of chemotherapy. Of 20 patients with visible tumor who were treated with 4 weeks of chemotherapy alone, 10 (50%) had a tumor regression in that 4 week period and 10 did not. Those patients with tumor regression had significantly better progression free and overall survivals than did patients with no chemotherapy regressions (medians of 258 days vs. 136 days and 356 days vs. 150 days respectively). The original bleomycin dose had to be reduced by 50% primarily because of excessive radiation esophagitis that has not been reported with use of either the CAP regimen or bleomycin along in conjunction with thoracic irradiation. An initial chemotherapy regression seems to be a good prognosticator for progression-free and overall survival in patients with limited squamous cell lung cancer treated with combined chemotherapy and radiotherapy

  17. Tumour eradication using synchronous thermal ablation and Hsp90 chemotherapy with protein engineered triblock biopolymer-geldanamycin conjugates.

    Science.gov (United States)

    Chen, Yizhe; Youn, Pilju; Pysher, Theodore J; Scaife, Courtney L; Furgeson, Darin Y

    2014-12-01

    Hepatocellular carcinoma (HCC) suffers high tumour recurrence rate after thermal ablation. Heat shock protein 90 (Hsp90) induced post-ablation is critical for tumour survival and progression. A combination therapy of thermal ablation and polymer conjugated Hsp90 chemotherapy was designed and evaluated for complete tumour eradication of HCC. A thermo-responsive, elastin-like polypeptide (ELP)-based tri-block biopolymer was developed and conjugated with a potent Hsp90 inhibitor, geldanamycin (GA). The anti-cancer efficacy of conjugates was evaluated in HCC cell cultures with and without hyperthermia (43 °C). The conjugates were also administered twice weekly in a murine HCC model as a single treatment or in combination with single electrocautery as the ablation method. ELP-GA conjugates displayed enhanced cytotoxicity in vitro and effective heat shock inhibition under hyperthermia. The conjugates alone significantly slowed the tumour growth without systemic toxicity. Four doses of thermo-responsive ELP-GA conjugates with concomitant simple electrocautery accomplished significant Hsp90 inhibition and sustained tumour suppression. Hsp90 inhibition plays a key role in preventing the recurrence of HCC, and the combination of ablation with targeted therapy holds great potential to improve prognosis and survival of HCC patients.

  18. Combined radiation therapy and intraarterial chemotherapy for advanced oral or oropharngeal carcinoma

    International Nuclear Information System (INIS)

    Okawa, Tomohiko; Kita, Midori; Tanaka, Makiko; Ishii, Tetsuo

    1989-01-01

    During the period 1982-1988, 34 patients with advanced oral or oropharyngeal carcinoma were treated with radical radiation therapy combined with intraarterial chemotherapy. Five patients were clinically staged as Stage II,15 as Stage III, and 14 as Stage IV. For intraarterial chemotherapy, ACNU (25mg/body) or CDDP (20 mg/m 2 ) plus MMC (6 mg/m 2 ) was used. Overall, the complete response rate was 56%: it was independent of the site of carcinoma, clinical stage, and the kind of drugs. The two-year cumulative survival rate was 80% for Stage II, 56% for Stage III, and 61% for Stage IV. Side effects were not so severe as to continue with the withdrawal of chemotherapy. In view of the efficacy and safety, combined radiation therapy and intraarterial chemotherapy should be performed in the treatment of oral or oropharyngeal carcinoma. (N.K.)

  19. Interaction of the effects of hyperthermia and ionizing radiation on cell survival

    International Nuclear Information System (INIS)

    Loshek, D.D.

    1976-09-01

    The literature concerning the effects of hyperthermia and radiation on cellular reproductive integrity is reviewed. The cell line and the physical and biological aspects of the experiments are described. Preliminary experiments revealed that the experimental stability was adequate for inter-experiment comparisons, provided that sufficient control data were obtained. Further experiments provided a cursory examination of several aspects of the interaction between radiation and hyperthermia. A simple sensitization model that would account for the observed results for any single value of the perturbing radiation or hyperthermia dose was developed. Using the concept of the survival surface, this simple model was expanded to describe simultaneously survivals for any combination of the radiation and hyperthermia dose. The interaction component of this model is first order in both hyperthermia exposure and radiation dose. The mechanism by which radiation contributes to the interaction was investigated by altering the radiation quality. The results suggest that high LET events contribute to the interaction. The mechanism by which hyperthermia contributes to the interaction was investigated by altering the hyperthermia temperature. A thermodynamic analysis of the data reveals parallels with the effects of hyperthermia and radiation on protein, suggesting a possible involvement of protein denaturation in cell inactivation. (author)

  20. Hyperthermia and PARP1-inhibition for sensitization of radiation and cisplatin treatment of cervical carcinoma cells

    International Nuclear Information System (INIS)

    Franken, Nicolaas; Oei, Arlene; Leeuwen, Caspar van; Stalpers, Lukas; Rodermond, Hans; Bel, Arjan; Kok, Petra; Crezee, Hans

    2014-01-01

    Ionizing radiation causes single and double strand breaks (SSBs and DSBs). DSBs are among the most critical DNA lesions and can be repaired via either non-homologous end joining (NHEJ) in which PARP1, Ku70 and DNA-PKcs are important, or homologous recombination (HR), where BRCA2 and Rad51 are essential. Hyperthermia disturbs HR by temporary inactivation of BRCA2. Cisplatin disrupts NHEJ and PARP1-inhibitor blocks Poly-(ADP-ribose)polymerase- 1, which is important in SSB repair, NHEJ and backup-NHEJ. Our goal was to investigate the additional effectiveness of hyperthermia and PARP1-inhibition on radiation and/or cisplatin treatment. Cervical carcinoma cells (SiHa) were treated at different temperature levels levels (41.0-43.0℃, PARP1-inhibitor (100 μM; NU1025), gamma-irradiation doses (0-8 Gy) or cisplatin (1'R for 1 h). Clonogenic assays were carried out to measure survival and γH2AX staining was used to visualize DSBs. To elucidate mechanisms of action expression levels of DNA repair proteins BRCA2 and DNA-PKcs were investigated after 42.0℃ (1 h) using western blot. Combined hyperthermia and radiation resulted in an increased number of γH2AX foci as compared to radiation alone. Hyperthermia treatment in combination with cisplatin and PARP1 inhibitor and with radiation and PARP1 inhibitor significantly decreased cell survival. Western blot demonstrated a decreased expression of BRCA2 protein at 30 min after hyperthermia treatment. Adding PARP1-inhibitor significantly improves the effectiveness of combined hyperthermia radiotherapy and combined hyperthermia-cisplatin treatment on cervical carcinoma cells. Hyperthermia affects DNA-DSB repair as is indicated by increased γH2AX foci numbers and decreased BRCA2 expression. (author)

  1. Polymodification. Short-term hyperglycemia and local hyperthermia in hypoxiradiotherapy of transplantable solid tumors

    International Nuclear Information System (INIS)

    Kozin, S.V.; Krimker, V.M.; Yarmonenko, S.P.

    1984-01-01

    Application possibilities of hyperglycemia and local hyperthermia in combination with hypoxiradiotherapy of solid tumors, have been evaluated. The experiments conducted have shown the great possibilities of combined use of radiation, hyperglycemia, hyperthermia, for selective affection of tumours, and application of gaseous hypoxia during irradiation - for simultaneous principal protection of normal tissues. Interaction of all the agents will undoubtedly require a versatile study to develop the optimum regimes of action

  2. Interaction of hyperthermia and radiation: radiation quality

    International Nuclear Information System (INIS)

    Loshek, D.D.; Orr, J.S.; Solomonidis, E.

    1981-01-01

    Cell-survival data were collected to determine the survival response of asynchronous CHO cells subject to radiation and hyperthermia. The irradiation was at room temperature 100 minutes before exposure to hyperthermia at 42 0 C. The survival response to the combination of these two agents is expressed by means of a survival surface, a three-dimensional concept relating cell survival to heat dose and radiation dose. The survival surface could be approximately described by a survival model comprising three components of cell killing: the unperturbed radiation component, the unperturbed hyperthermia component and the interaction component. The dependence of the radiation component and the interaction component on radiation quality were investigated by irradiating with either 60 Co γ rays, 250 kV X rays or 14.7 MeV neutrons. An analysis suggests that the interaction component and the radiation component exhibit similar dependencies on radiation quality both for the deposition of damage and the repair or accumulation of that damage. (U.K.)

  3. Peculiarities of tumor blood supply and their role in radiotherapy, hyperthermia and hyperglycemia

    International Nuclear Information System (INIS)

    Kozin, S.V.; Furmanchuk, A.V.

    1986-01-01

    Development regularities and functional peculiarities of tumor microcirculatory channel (MCC) are considered. The role of microcirculation changes under radiotherapy and it's combinations with hyperthermia and hyperglycemia is estimated. The conclusion is drawn, that MCC reactions play a substantial role in realization of hyperthermia and hyperglycemia radiomodifying action

  4. The case for SAR as the major component of a hyperthermia treatment unit

    International Nuclear Information System (INIS)

    Scott, R.S.

    1985-01-01

    A major problem facing clinical hyperthermia is the lack of a useful unit of treatment. Most attempts at a treatment unit have utilized some function of temperature and time. Having accepted the validity of such a hypothetical units, one is faced with the formidable problem of obtaining a three dimensional temperature profile so that thermal dose can be determined. A corollary is the desirability of obtaining uniform temperature in the treatment volume. Various studies suggest that a uniform SAR is a more desirable goal when radiotherapy is to be used in combination with hyperthermia. The synergy between radiation and hyperthermia is maximized in low pH regions of tumor which are presumably also hypoxic. These regions are poorly perfused, likely to heat readily, and are resistant to the cytotoxic effects of radiation alone. On the other hand, well perfused regions of tumor are likely sensitive to radiation, and benefit less from the combination treatment. Other studies have definitely shown that tissue temperatures in the range normally associated with desirable hyperthermia treatment result in severe vascular damage. This damage could be expected to unnecessarily compromise the effectiveness of radiotherapy. Models in the literature can be combined to verify these observations

  5. Histopathologic findings of radiotherapy combined with chemotherapy on head and neck cancer

    International Nuclear Information System (INIS)

    Sakaino, Koji; Matsumoto, Mitsuomi; Satake, Bunsuke; Takahashi, Keiichi; Makino, Sotaro

    1979-01-01

    We studied in this series about histopathologic changes in radiotherapy of squamous cell carcinoma of head and neck. Then we recognized that radiotherapy combined with chemotherapy is useful for radioresistant squamous cell carcinoma. In this series, we studied about cancer of the tongue as one of the keratinizing squamous cell carcinoma and used Bleomycin as a chemotherapeutic drug. We commented as follows: 1. Radiotherapy combined with chemotherapy had benefit decreasing of a period for radium therapy. 2. Severs complication was not occurred in this series, then this combined therapy was useful for aged or handicapped patient. (author)

  6. Combined treatment of 8 MHz radiofrequency hyperthermia and irradiation for advanced urological malignancies

    International Nuclear Information System (INIS)

    Nakajima, Kazuyoshi; Hisazumi, Haruo; Yamamoto, Hajime; Naito, Katsusuke; Misaki, Toshimitsu; Kobashi, Kazunori; Yokoyama, Osamu; Saito, Yasuo

    1986-01-01

    A combined therapy of irradiation and 8 MHz radiofrequency hyperthermia using Thermotron-RF Model 8 was carried out in a total of 26 patients with urological malignancies; 9 renal cancers, 1 renal capsular tumor, multiple liver metastatic lesions of renal cancer, a postoperative mediastinal metastasis of renal cancer, 2 ureteral cancers associated with bladder cancers, 4 bladder cancers, 4 prostatic cancers, a postoperative local recurrent tumor of an adult type Wilms' tumor, and multiple skin metastatic lesions of a penile cancer. Previous therapies were unsuccessful, or surgical interventions were not indicated because of poor general conditions. They were irradiated with daily 1.8 to 2.0 Gy, 5 times a week, or daily 2.0 to 4.0 Gy twice a week. Hyperthermia was induced twice a week within one hour after each irradiation, in total 10 times for 5 weeks. Intratumoral temperature was kept between 42.0 to 44.0 deg C. Clinical efficacy was evaluated by CT, ultrasound and biochemical data. Partial tumor regression, defined as the regression of 50 % or more, was obtained in one of the 9 renal cancers, in the mediastinal metastasis of renal cancer, 2 of the 4 prostatic cancers, one of the 4 bladder cancers and the 2 ureteral cancers, CR was obtained in the 2 associated bladder cancers. As side effects, a mild skin burns and anorexia were observed in approximately 50 % of the cases. Subcutaneous fat tissue indurations occurred in 6 of the 30 patients, who had 15 mm or more thickness of subdermal fat tissues, after treatment. (author)

  7. Clinical application of radiotherapy combined with chemotherapy

    International Nuclear Information System (INIS)

    Morita, Kozo

    1978-01-01

    In clinical application of radiation therapy combined with chemotherapy, it is important to gain the maximal therapeutic benefit. At present we have no agents that improve the therapeutic ratio by enhancing the effect of radiation on the tumor cell selectively. Therefore, it is necessary to use combining some or all of following procedures: (1) the intraarterial infusion of the agents, (2) the selective localization by reason of the biological affinity of the agents, (3) the surgical removal of the non-sensitized tumor residue and (4) the selective sensitization of the tumor due to its shorter cell cycle. (author)

  8. Combined modality treatment with radiotherapy and chemotherapy

    International Nuclear Information System (INIS)

    Tannock, I.F.; Toronto Univ., ON

    1989-01-01

    The present paper discusses some of the methodological issues which can confound the interpretation of clinical trials of combined modality treatment. It reviews some of the larger randomized trials which have evaluated combined modality treatment in cancers of the head and neck, lung, gastrointestinal tract and bladder. It concludes that adequate trials have yet to be performed in many of thses sites, but that at present, evidence for long-term benefit from adjunctivechemotherapy is meagre. Finally, it suggests some possible mechanisms which might heve limited the benefit of chemotherapy when added to radiation treatment. (Author). 87 refs.; 4 figs.; 4 tabs

  9. Intravenous chemotherapy combined with intravesical chemotherapy to treat T1G3 bladder urothelial carcinoma after transurethral resection of bladder tumor: results of a retrospective study

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2016-01-01

    Full Text Available Yu Zhang,1,* Linguo Xie,1,* Tao Chen,1,* Wanqin Xie,2 Zhouliang Wu,1 Hao Xu,1 Chen Xing,1 Nan Sha,1 Zhonghua Shen,1 Yunkai Qie,1 Xiaoteng Liu,1 Hailong Hu,1 Changli Wu1 1Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin, 2Key Laboratory of Genetics and Birth Health of Hunan Province, The Family Planning Research Institute of Hunan Province, Changsha, People’s Republic of China *These authors contributed equally to this work Objective: The management of stage 1 and grade 3 (T1G3 bladder cancer continues to be controversial. Although the transurethral resection of bladder tumor (TURBT followed by intravesical chemotherapy is a conservative strategy for treatment of T1G3 bladder cancer, a relatively high risk of tumor recurrence and progression remains regarding the therapy. This study aimed to compare the efficacy of intravenous chemotherapy combined with intravesical chemotherapy versus intravesical chemotherapy alone for T1G3 bladder cancer after TURBT surgery. Methods: We retrospectively reviewed the cases of 457 patients who were newly diagnosed with T1G3 bladder urothelial carcinoma between January 2009 and March 2014. After TURBT, 281 patients received intravesical chemotherapy alone, whereas 176 patients underwent intravesical chemotherapy in combination with intravenous chemotherapy. Tumor recurrence and progression were monitored periodically by urine cytology and cystoscopy in follow-up. Recurrence-free survival and progression-free survival of the two chemotherapy strategies following TURBT were analyzed. Univariable and multivariable Cox hazards analyses were performed to predict the prognostic factors for tumor recurrence and progression. Results: The tumor recurrence rate was 36.7% for patients who received intravesical chemotherapy alone after TURBT, compared with 19.9% for patients who received intravenous chemotherapy combined with intravesical chemotherapy after

  10. Comparison of microwave and magnetic nanoparticle hyperthermia radiosensitization in murine breast tumors

    Science.gov (United States)

    Giustini, Andrew J.; Petryk, Alicia A.; Hoopes, Paul J.

    2011-03-01

    Hyperthermia has been shown to be an effective radiosensitizer. Its utility as a clinical modality has been limited by a minimally selective tumor sensitivity and the inability to be delivered in a tumor-specific manner. Recent in vivo studies (rodent and human) have shown that cancer cell-specific cytotoxicity can be effectively and safely delivered via iron oxide magnetic nanoparticles (mNP) and an appropriately matched noninvasive alternating magnetic field (AMF). To explore the tumor radiosensitization potential of mNP hyperthermia we used a syngeneic mouse breast cancer model, dextran-coated 110 nm hydrodynamic diameter mNP and a 169 kHz / 450 Oe (35.8 kA/m) AMF. Intradermally implanted (flank) tumors (150 +/- 40 mm3) were treated by injection of 0.04 ml mNP (7.5 mg Fe) / cm3 into the tumor and an AMF (35.8 kA/m and 169 kHz) exposure necessary to achieve a CEM (cumulative equivalent minute) thermal dose of 60 (CEM 60). Tumors were treated with mNP hyperthermia (CEM 60), radiation alone (15 Gy, single dose) and in combination. Compared to the radiation and heat alone treatments, the combined treatment resulted in a greater than two-fold increase in tumor regrowth tripling time (tumor treatment efficacy). None of the treatments resulted in significant normal tissue toxicity or morbidity. Studies were also conducted to compare the radiosensitization effect of mNP hyperthermia with that of microwave-induced hyperthermia. The effects of incubation of nanoparticles within tumors (to allow nanoparticles to be endocytosed) before application of AMF and radiation were determined. This preliminary information suggests cancer cell specific hyperthermia (i.e. antibody-directed or anatomically-directed mNP) is capable of providing significantly greater radiosensitization / therapeutic ratio enhancement than other forms of hyperthermia delivery.

  11. Hyperthermia quality assurance

    International Nuclear Information System (INIS)

    Shrivastava, P.N.; Paliwal, B.R.

    1984-01-01

    Hyperthermia Physics Center (HPC) operating under contract with the National Cancer Institute is developing a Quality Assurance program for local and regional hyperthermia. The major clinical problem in hyperthermia treatments is that they are extremely difficult to plan, execute, monitor and reproduce. A scientific basis for treatment planning can be established only after ensuring that the performance of heat generating and temperature monitoring systems are reliable. The HPC is presently concentrating on providing uniform NBS traceable calibration of thermometers and evaluation of reproducibility for power generator operation, applicator performance, phanta compositions, system calibrations and personnel shielding. The organizational plan together with recommended evaluation measurements, procedures and criteria are presented

  12. Preferential radiosensitization of human prostatic carcinoma cells by mild hyperthermia

    International Nuclear Information System (INIS)

    Ryu, Samuel; Brown, Stephen L.; Kim, Sang-Hie; Khil, Mark S.; Kim, Jae Ho

    1996-01-01

    Purpose: Recent cell culture studies by us and others suggest that some human carcinoma cells are more sensitive to heat than are rodent cells following mild hyperthermia. In studying the cellular mechanism of enhanced thermosensitivity of human tumor cells to hyperthermia, prostatic carcinoma cells of human origin were found to be more sensitive to mild hyperthermia than other human cancer cells. The present study was designed to determine the magnitude of radiosensitization of human prostatic carcinoma cells by mild hyperthermia and to examine whether the thermal radiosensitization is related to the intrinsic thermosensitivity of cancer cells. Methods and Materials: Two human prostatic carcinoma cell lines (DU-145 and PC-3) and other carcinoma cells of human origin, in particular, colon (HT-29), breast (MCF-7), lung (A-549), and brain (U-251) were exposed to temperatures of 40-41 deg. C. Single acute dose rate radiation and fractionated radiation were combined with mild hyperthermia to determine thermal radiosensitization. The end point of the study was the colony-forming ability of single-plated cells. Results: DU-145 and PC-3 cells were found to be exceedingly thermosensitive to 41 deg. C for 24 h, relative to other cancer cell lines. Ninety percent of the prostatic cancer cells were killed by a 24 h heat exposure. Prostatic carcinoma cells exposed to a short duration of heating at 41 deg. C for 2 h resulted in a substantial enhancement of radiation-induced cytotoxicity. The thermal enhancement ratios (TERs) of single acute dose radiation following heat treatment 41 deg. C for 2 h were 2.0 in DU-145 cells and 1.4 in PC-3 cells. The TERs of fractionated irradiation combined with continuous heating at 40 deg. C were similarly in the range of 2.1 to 1.4 in prostate carcinoma cells. No significant radiosensitization was observed in MCF-7 and HT-29 cells under the same conditions. Conclusion: The present data suggest that a significant radiosensitization of

  13. Treatment of lymphatic nodes metastasis in advanced cancer with interventional chemotherapy combined radiotherapy

    International Nuclear Information System (INIS)

    Xia Shian; Guo Weijian; Wu Guohua; Lin Qing; Jiang Mawei; Yao Yuan

    2000-01-01

    Objective: To evaluate the clinical effects of treatment with interventional chemotherapy combined radiotherapy for lymphatic nodes metastasis in advanced cancer. Methods: Treated with interventional chemotherapy for 27 cases of lymphatic rode metastasis once a month with average 2-3 times totally. Simultaneously treated with linear accelerator radiotherapy with average dose of 40-50 Gy/20-25 times/4-5 weeks. Results: To evaluate the clinical effects after finished the whole treatment program two months later. CR + PR reached 77.8% (24/27). All patients showed tolerance to accept the treatment. Conclusion: Treatment for lymphatic node metastasis in advanced cancer with interventional chemotherapy combined radiation therapy seems to be a valuable way

  14. Early experience of proton beam therapy combined with chemotherapy for locally advanced oropharyngeal cancer

    International Nuclear Information System (INIS)

    Ishikawa, Youjirou; Nakamura, Tatsuya; Takada, Akinori; Takayama, Kanako; Makita, Chiyoko; Suzuki, Motohisa; Azami, Yusuke; Kikuchi, Yasuhiro; Fuwa, Nobukazu

    2013-01-01

    Between 2009 and 2012, 10 patients with advanced oropharyngeal cancer underwent proton therapy combined with chemotherapy. The initial results of this therapy were 8 complete response (CR) and 2 partial response (PR), local recurrence was detected 1 patient. Proton beam therapy combined with chemotherapy is thought to be an effective treatment for locally advanced oropharyngeal cancer. (author)

  15. Significance of fractionation regimens in radiation and combined hyperthermia using a murine fibrosarcoma

    International Nuclear Information System (INIS)

    Hahn, E.W.; Alfieri, A.A.; Kim, J.H.

    1978-01-01

    The significance of time--dose ralationships in the use of local tumor hyperthermia (LTH) when combined with radiation (RAD) was studied in a murine fibrosarcoma. RAD, either alone or combined with LTH, was delivered in four equal fractions (total doses, 1.8 to 4.2 krad) separated by 1 to 4 days. LTH (43.1 C +- .05 C for 15 minutes, water bath) was applied immediately after RAD. In this tumor system, RAD was most effective when delivered every 2nd or 3rd day, by a factor of 1.25 over the response achieved when the four fractions were delivered every 1 or 4 days. At all levels studied, RAD + LTH produced a superior tumor response compared to RAD alone. The ratio of the RAD + LTH/RAD doses to achieve an isobiological response ranged from 1.7 to 2.5. Most significant was the finding that the RAD + LTH treatment response was independent of the fractionation scheme used and more dependent on the total RAD dose delivered

  16. Postradiation DNA repair in mammalian cells under the combined effect of hyperthermia and 8-bromocaffeine and actinomycin D

    International Nuclear Information System (INIS)

    Rezvaya, S.P.; Khanson, K.P.

    1981-01-01

    A study was made of the influence of postirradiation hyperthermia combined with chemical inhibitirors of DNA repa on rejoining the singlestranded DNA breaks induced by X-irradiation (50 Gy) of LL, cells. Separation of single- and double-stranded DNA fragments on a column with hydroxyapatite has revealed that elevation of the postradiation incubation temperature up to 41 deg C does not influence the degree of repair of single-stranded breaks. No repair is detected at 43 deg C. 8-Bromocaffeine and actinomycin combined with the elevated temperature (41 deg C) remove the inhibitory effect of the preparations on the postradiation repair of DNA [ru

  17. Combined chemotherapy and radiation therapy in limited disease small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Moon Kyung; Ahn, Yong Chan; Park, Keun Chil; Lim Do Hoon; Huh, Seung Jae; Kim, Dae Yong; Shin, Kyung Hwan; Lee, Kyu Chan; Kwon, O Jung [College of Medicine, Sungkyunkwan Univ., Seoul (Korea, Republic of)

    1999-03-01

    This is a retrospective study to evaluate the response rate, acute toxicity, and survival rate of a combined chemotherapy and radiation therapy in limited disease small cell lung cancer. Forty six patients with limited disease small-cell lung cancer who underwent combined chemotherapy and radiation therapy between October 1994 and April 1998 were evaluated. Six cycles of chemotherapy were planned either using a VIP regimen (etoposide, ifosfamide, and cis-platin) or a EP regimen (etoposide and cis-platin). Thoracic radiation therapy was planned to deliver 44 Gy using 10MV X-ray, starting concurrently with chemotherapy. Response was evaluated 4 weeks after the completion of the planned chemotherapy and radiation therapy, and the prophylactic cranial irradiation was planned only for the patients with complete responses. Acute toxicity was evaluated using the SWOG toxicity criteria, and the overall survival and disease-free survival were calculated using the Kaplan-Meier Method. The median follow-up period was 16 months (range:2 to 41 months). Complete response was achieved in 30 (65%) patients, of which 22 patients received prophylactic cranial irradiations. Acute toxicities over grade III were granulocytopenia in 23 (50%), anemia in 17 (37%), thrombo-cytopenia in nine (20%), alopecia in nine (20%), nausea/vomiting in five (11%), and peripheral neuropathy in one (2%). Chemotherapy was delayed in one patient, and the chemotherapy doses were reduced in 58 (24%) out of the total 246 cycles. No radiation esophagitis over grade III was observed, while interruption during radiation therapy for a mean of 8.3 days occurred in 21 patients. The local recurrences were observed in 8 patients and local progressions were in 6 patients, and the distant metastases in 17 patients. Among these, four patients had both the local relapse and the distant metastasis. Brain was the most common metastatic site (10 patients), followed by the liver as the next common site (4 patients). The

  18. Combined chemotherapy and radiation therapy in limited disease small-cell lung cancer

    International Nuclear Information System (INIS)

    Kim, Moon Kyung; Ahn, Yong Chan; Park, Keun Chil; Lim Do Hoon; Huh, Seung Jae; Kim, Dae Yong; Shin, Kyung Hwan; Lee, Kyu Chan; Kwon, O Jung

    1999-01-01

    This is a retrospective study to evaluate the response rate, acute toxicity, and survival rate of a combined chemotherapy and radiation therapy in limited disease small cell lung cancer. Forty six patients with limited disease small-cell lung cancer who underwent combined chemotherapy and radiation therapy between October 1994 and April 1998 were evaluated. Six cycles of chemotherapy were planned either using a VIP regimen (etoposide, ifosfamide, and cis-platin) or a EP regimen (etoposide and cis-platin). Thoracic radiation therapy was planned to deliver 44 Gy using 10MV X-ray, starting concurrently with chemotherapy. Response was evaluated 4 weeks after the completion of the planned chemotherapy and radiation therapy, and the prophylactic cranial irradiation was planned only for the patients with complete responses. Acute toxicity was evaluated using the SWOG toxicity criteria, and the overall survival and disease-free survival were calculated using the Kaplan-Meier Method. The median follow-up period was 16 months (range:2 to 41 months). Complete response was achieved in 30 (65%) patients, of which 22 patients received prophylactic cranial irradiations. Acute toxicities over grade III were granulocytopenia in 23 (50%), anemia in 17 (37%), thrombo-cytopenia in nine (20%), alopecia in nine (20%), nausea/vomiting in five (11%), and peripheral neuropathy in one (2%). Chemotherapy was delayed in one patient, and the chemotherapy doses were reduced in 58 (24%) out of the total 246 cycles. No radiation esophagitis over grade III was observed, while interruption during radiation therapy for a mean of 8.3 days occurred in 21 patients. The local recurrences were observed in 8 patients and local progressions were in 6 patients, and the distant metastases in 17 patients. Among these, four patients had both the local relapse and the distant metastasis. Brain was the most common metastatic site (10 patients), followed by the liver as the next common site (4 patients). The

  19. Regional hyperthermia combined with radiotherapy for locally advanced non-small cell lung cancers. A multi-institutional prospective randomized trial of the International Atomic Energy Agency

    International Nuclear Information System (INIS)

    Mitsumori, Michihide; Hiraoka, Masahiro; Zeng Zhifan; Oliynychenko, P.; Park, Jeong-Ho; Choi, Ihl-Bohng; Tatsuzaki, Hideo; Tanaka, Yoshiaki

    2007-01-01

    An International Atomic Energy Agency (IAEA)-sponsored, multi-institutional prospective randomized trial was conducted to clarify whether the combination of hyperthermia and radiotherapy improves the local response rate of locally advanced non-small cell lung cancer (NSCLC) compared with that obtained by radiotherapy alone. Between October 1998 and April 2002, 80 patients with locally advanced NSCLC were randomized to receive either standard radiation therapy alone (RT) or radiation therapy combined with hyperthermia (RT+HT). The primary endpoint was the local response rate. The secondary endpoints were local progression-free survival and overall survival. The median follow-up period was 204 days for all patients and 450 days for surviving patients. There were no significant differences between the two arms with regard to local response rate (P=0.49) or overall survival rate (P=0.868). However, local progression-free survival was significantly better in the RT+HT arm (P=0.036). Toxicity was generally mild and no grade 3 late toxicity was observed in either arm. Although improvement of local progression-free survival was observed in the RT+HT arm, this prospective randomized study failed to show any substantial benefit from the addition of hyperthermia to radiotherapy in the treatment of locally advanced NSCLC. (author)

  20. Combining biological agents and chemotherapy in the treatment of cholangiocarcinoma

    DEFF Research Database (Denmark)

    Jensen, Lars Henrik; Jakobsen, Anders

    2011-01-01

    is not always possible. Chemotherapy is effective and the combination of cisplatin and gemcitabine is considered a standard treatment of inoperable cholangiocarcinoma. Biological targeted treatment to date has minor effect when given as monotherapy, but some of the drugs hold promise as an adjunct...... to chemotherapy. It should, however, be noted that most of the trials are based on few patients, and thus far the literature does not allow for a conclusion as to the role of biological treatment on cholangiocarcinoma. This situation calls for well-designed randomized trials, and international cooperation as well...

  1. SEROTONIN METABOLISM FOLLOWING PLATINUM-BASED CHEMOTHERAPY COMBINED WITH THE SEROTONIN TYPE-3 ANTAGONIST TROPISETRON

    NARCIS (Netherlands)

    SCHRODER, CP; VANDERGRAAF, WTA; KEMA, IP; GROENEWEGEN, A; SLEIJFER, DT; DEVRIES, EGE

    1995-01-01

    The administration of platinum-based chemotherapy induces serotonin release from the enterochromaffin cells, causing nausea and vomiting. This study was conducted to evaluate parameters of serotonin metabolism following platinum-based chemotherapy given in combination with the serotonin type-3

  2. Effects of intraoperative irradiation (IORT) and intraoperative hyperthermia (IOHT) on canine sciatic nerve: histopathological and morphometric studies

    International Nuclear Information System (INIS)

    Vujaskovic, Zeljko; Powers, Barbara E.; Paardekoper, Gabriel; Gillette, Sharon M.; Gillette, Edward L.; Colacchio, Thomas A.

    1999-01-01

    Purpose/Objective: Peripheral neuropathies have emerged as the major dose-limiting complication reported after intraoperative radiation therapy (IORT). The combination of IORT with hyperthermia may further increase the risk of peripheral nerve injury. The objective of this study was to evaluate histopathological and histomorphometric changes in the sciatic nerve of dogs, after IORT with or without hyperthermia treatment. Methods and Materials: Young adult beagle dogs were randomized into five groups of 3-5 dogs each to receive IORT doses of 16, 20, 24, 28, or 32 Gy. Six groups of 4-5 dogs each received IORT doses of 12, 16, 20, 24, or 28 Gy simultaneously with 44 deg. C of intraoperative hyperthermia (IOHT) for 60 min. One group of dogs acted as hyperthermia-alone controls. Two years after the treatment, dogs were euthanized, and histopathological and morphometric analyses were performed. Results: Qualitative histological analysis showed prominant changes such as focal necrosis, mineralization, fibrosis, and severe fiber loss in dogs which received combined treatment. Histomorphometric results showed a significantly higher decrease in axon and myelin and small blood vessels, with a corresponding increase in connective tissue in dogs receiving IORT plus hyperthermia treatment. The effective dose for 50% of nerve fiber loss (ED 50 ) in dogs exposed to IORT only was 25.3 Gy. The ED 50 for nerve fiber loss in dogs exposed to IORT combined with IOHT was 14.8 Gy. The thermal enhancement ratio (TER) was 1.7. Conclusion: The probability of developing peripheral neuropathies in a large animal model is higher when IORT is combined with IOHT, when compared to IORT application alone. To minimize the risk of peripheral neuropathy, clinical treatment protocols for the combination of IORT and hyperthermia should not assume a thermal enhancement ratio (TER) to be lower than 1.5

  3. Temperature mapping and thermal dose calculation in combined radiation therapy and 13.56 MHz radiofrequency hyperthermia for tumor treatment

    Science.gov (United States)

    Kim, Jung Kyung; Prasad, Bibin; Kim, Suzy

    2017-02-01

    To evaluate the synergistic effect of radiotherapy and radiofrequency hyperthermia therapy in the treatment of lung and liver cancers, we studied the mechanism of heat absorption and transfer in the tumor using electro-thermal simulation and high-resolution temperature mapping techniques. A realistic tumor-induced mouse anatomy, which was reconstructed and segmented from computed tomography images, was used to determine the thermal distribution in tumors during radiofrequency (RF) heating at 13.56 MHz. An RF electrode was used as a heat source, and computations were performed with the aid of the multiphysics simulation platform Sim4Life. Experiments were carried out on a tumor-mimicking agar phantom and a mouse tumor model to obtain a spatiotemporal temperature map and thermal dose distribution. A high temperature increase was achieved in the tumor from both the computation and measurement, which elucidated that there was selective high-energy absorption in tumor tissue compared to the normal surrounding tissues. The study allows for effective treatment planning for combined radiation and hyperthermia therapy based on the high-resolution temperature mapping and high-precision thermal dose calculation.

  4. Interstitial hyperthermia using 8 MHz radiofrequency and stereotaxic brachytherapy for brain tumors

    International Nuclear Information System (INIS)

    Nishimura, Satoshi

    1990-01-01

    As a preliminary study of the interstitial hyperthermia combined with interstitial irradiation (brachytherapy) for the treatment of malignant brain tumors, we performed an experiment of interstitial hyperthermia of brain tissue of dogs. Nine afterloading tubes, four for needle electrodes and five for thermisters, were inserted in the brain tissue of dogs. Rise and stability of temperature were ascertained, and clinical safety was confirmed. Thereafter this combined therapy was applied on seven cases, in which three were malignant gliomas and four were metastatic tumors. Through the guide tubes, 192 Ir thin wires were implanted stereotaxically, and interstitial irradiation was carried out. After removal of 192 Ir wires, needle electrodes were inserted through the same tubes, and also a thermister was guided at the center of electrodes. And interstitial hyperthermia using 8 MHz radiofrequency was carried out. The results of the treatment were evaluated with CT scan based on criteria of the Japan Neurological Society. In cases of malignant gliomas, 2 PRs (partial remission), and 1 NC (no change) were obtained. In cases of metastatic tumors, 1 CR (complete remission), 2 PRs, 1 NC were obtaind. In cases of NCs, progression of tumors have been suppressed for 10 and 17 months, and still alive. As complication, transient worsening of neurological symptoms were observed in four cases (increased paresis: two cases, nausea and vomiting: two cases). The author have had an impression that interstitial hyperthermia combined with interstitial irradiation might become an effective means of treatment of brain tumors. (author)

  5. Photothermal enhancement of chemotherapy mediated by gold-silica nanoshell-loaded macrophages: in vitro squamous cell carcinoma study

    Science.gov (United States)

    Madsen, Steen J.; Shih, En-Chung; Peng, Qian; Christie, Catherine; Krasieva, Tatiana; Hirschberg, Henry

    2016-01-01

    Moderate hyperthermia (MHT) has been shown to enhance the effects of chemotherapeutic agents in a wide variety of cancers. The purpose of this study was to investigate the combined effects of commonly used chemotherapeutic agents with MHT induced by near-infrared (NIR) activation of gold nanoshell (AuNS)-loaded macrophages (Ma). AuNS-loaded murine Ma combined with human FaDu squamous cells, in hybrid monolayers, were subjected to three cytotoxic drugs (doxorubicin, bleomycin, cisplatin) with or without NIR laser irradiation. For all three drugs, efficacy was increased by NIR activation of AuNS-loaded Ma. The results of this in vitro study provide proof-of-concept for the use of AuNS-loaded Ma for photothermal enhancement of the effects of chemotherapy on squamous cell carcinoma.

  6. Effect of Hyperthermic Intraperitoneal Perfusion Chemotherapy in Combination with Intravenous Chemotherapy as Postoperative Adjuvant Therapy for Advanced Gastric Cancer.

    Science.gov (United States)

    Wu, Zhibing; Ma, Shenglin; Jing, Saisai; Deng, Qinghua; Zheng, Zhishuang; Wu, Kan; Li, Juan; Chen, Sumei; Tang, Rongjun; Li, Xiadong

    2014-06-01

    The aim is to evaluate the preliminary efficacy and side effects of paclitaxel, 5-fluorouracil, and leucovorin intravenous chemotherapy in combination with cisplatin hyperthermic intraperitoneal perfusion chemotherapy (HIPEC) as postoperative adjuvant therapy for patients of locally advanced gastric cancer (GC) at high risk for recurrence after curative resection. Four GC patients who underwent radical gastrectomy with D2 lymphadenectomy were enrolled. All patients received paclitaxel 135 mg/m2 on day 1, 5-FU 500 mg/m2 on days 1-5, LV 200 mg/m2 on days 1-5 intravenous chemotherapy, cisplatin 75 mg/m2 on day 5, and HIPEC one month after surgery. It was repeated at 3 weeks intervals and at least two cycles administered. A total of 181 cycles of chemotherapy were administered (median, 4 cycles). The median disease free survival time of patients was 40.8 months. The median overall survival time was 48.0 months. The one-, two-, and three-year recurrence rates were 14.6%, 26.8%, and 46.3%, respectively. The main relapse patterns were remnant GC and metastases of retroperitoneal lymph nodes. The morbidity of grade 3 and 4 toxicities of myelosuppression, nausea/ vomiting were less than 10%. The side effects of grade 1 and 2 of hematologic toxicity, nausea and vomiting, abnormal function of liver, kidney or cardiac, fatigue and neurotoxicity were well tolerated. Cisplatin HIPEC combined with paclitaxel, 5-fluorouracil, and leucovorin intravenous chemotherapy regimen could improve the survival rate and decrease the postoperative recurrence of locally advanced GC.

  7. Chemotherapy and molecular target therapy combined with radiation therapy

    International Nuclear Information System (INIS)

    Akimoto, Tetsuo

    2012-01-01

    Combined chemotherapy and radiation therapy has been established as standard treatment approach for locally advanced head and neck cancer, esophageal cancer and so on through randomized clinical trials. However, radiation-related morbidity such as acute toxicity also increased as treatment intensity has increased. In underlining mechanism for enhancement of normal tissue reaction in chemo-radiation therapy, chemotherapy enhanced radiosensitivity of normal tissues in addition to cancer cells. Molecular target-based drugs combined with radiation therapy have been expected as promising approach that makes it possible to achieve cancer-specific enhancement of radiosensitivity, and clinical trials using combined modalities have been performed to evaluate the feasibility and efficacy of this approach. In order to obtain maximum radiotherapeutic gain, a detailed understanding of the mechanism underlying the interaction between radiation and Molecular target-based drugs is indispensable. Among molecular target-based drugs, inhibitors targeting epidermal growth factor receptor (EGFR) and its signal transduction pathways have been vigorously investigated, and mechanisms regarding the radiosensitizing effect have been getting clear. In addition, the results of randomized clinical trials demonstrated that radiation therapy combined with cetuximab resulted in improvement of overall and disease-specific survival rate compared with radiation therapy in locally advanced head and neck cancer. In this review, clinical usefulness of chemo-radiation therapy and potential molecular targets for potentiation of radiation-induced cell killing are summarized. (author)

  8. Effects of multidose combination chemotherapy on the humoral immune system

    NARCIS (Netherlands)

    Zandvoort, A; Lodewijk, ME; Klok, PA; Timens, W

    Patients receiving multidose combination chemotherapy are at risk for severe, life-threatening infections, caused by among others encapsulated bacteria like Streptococcus pneumoniae. The splenic marginal zone is essential in the initiation of immune responses to S. pneumoniae. We analyzed effects of

  9. Comparing Intra-Arterial Chemotherapy Combined With Intravesical Chemotherapy Versus Intravesical Chemotherapy Alone: A Randomised Prospective Pilot Study for T1G3 Bladder Transitional Cell Carcinoma After Bladder-Preserving Surgery

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Junxing, E-mail: Junxingchen@hotmail.com; Yao, Zhijun, E-mail: yaozhijun1985@qq.com; Qiu, Shaopeng, E-mail: qiushp@mail.sysu.edu.cn; Chen, Lingwu, E-mail: chenlingwu@hotmail.com [First Affiliated Hospital of Sun Yat-Sen University, Department of Urology (China); Wang, Yu, E-mail: zsyyjr@163.com; Yang, Jianyong, E-mail: yangjianyong_2011@163.com; Li, Jiaping, E-mail: jpli3s@126.com [First Affiliated Hospital of Sun Yat-Sen University, Department of Interventional Oncology (China)

    2013-12-15

    Purpose: To compare the efficacy of intra-arterial chemotherapy combined with intravesical chemotherapy versus intravesical chemotherapy alone for T1G3 bladder transitional cell carcinoma (BTCC) followed by bladder-preserving surgery. Materials and Methods: Sixty patients with T1G3 BTCC were randomly divided into two groups. After bladder-preserving surgery, 29 patients (age 30-80 years, 24 male and 5 female) received intra-arterial chemotherapy in combination with intravesical chemotherapy (group A), whereas 31 patients (age 29-83 years, 26 male and 5 female) were treated with intravesical chemotherapy alone (group B). Twenty-nine patients were treated with intra-arterial epirubicin (50 mg/m{sup 2}) + cisplatin (60 mg/m{sup 2}) chemotherapy 2-3 weeks after bladder-preserving surgery once every 4-6 weeks. All of the patients received the same intravesical chemotherapy: An immediate prophylactic was administered in the first 6 h. After that, therapy was administered one time per week for 8 weeks and then one time per month for 8 months. The instillation drug was epirubicin (50 mg/m{sup 2}) and lasted for 30-40 min each time. The end points were tumour recurrence (stage Ta, T1), tumour progression (to T2 or greater), and disease-specific survival. During median follow-up of 22 months, the overall survival rate, tumour-specific death rate, recurrence rate, progression rate, time to first recurrence, and adverse reactions were compared between groups. Results: The recurrence rates were 10.3 % (3 of 29) in group A and 45.2 % (14 of 31) in group B, and the progression rates were 0 % (0 of 29) in group A and 22.6 % (7 of 31) in group B. There was a significant difference between the two groups regarding recurrence (p = 0.004) and progression rates (p = 0.011). Median times to first recurrence in the two groups were 15 and 6.5 months, respectively. The overall survival rates were 96.6 and 87.1 %, and the tumour-specific death rates were 0 % (0 of 29) and 13.5 % (4 of 31

  10. Changes in regional blood flow of normal and tumor tissues following hyperthermia and combined X-ray irradiation

    International Nuclear Information System (INIS)

    Suga, Kazuyoshi

    1986-01-01

    Hyperthermia and X-ray irradiation were given to Ehrlich tumors, which were induced in the ventrum of the right hind foot of ICR mice, and to the normal tissues. Their effects on regional blood flow were examined using Xe-133 local clearance method. Blood flow of the normal tissues remained unchanged by heating at 41 deg C for 30 minutes, and increased by heating at 43 deg C and 45 deg C for 30 minutes. On the contrary, blood flow of the tumors decreased with an increase in temperature. When hypertermia (43 deg C for 30 minutes) was combined with irradiation of 30 Gy, decrease in blood flow of the tumors was greater than the normal tissues at 24 hours. Blood flow of the tumors depended on tumor size. The decreased amount of blood flow by hyperthermia was more for tumors > 250 mm 3 than tumors 3 . Blood flow ratios of tumor to normal tissues were also smaller in tumors > 250 mm 3 than tumors 3 . In the case of tumors 3 , blood flow tended to return to normal at 3 hr after heating at 43 deg C for 30 min. However, this was not seen in tumors > 250 mm 3 . (Namekawa, K.)

  11. Induction chemotherapy for locoregional lung cancer using paclitaxel combination. A preliminary report

    International Nuclear Information System (INIS)

    Takita, H.; Pitoniak, R.F.

    2000-01-01

    Induction chemotherapy has been reported to be effective in treatment of locally advanced, borderline resectable, (Stage III), non small cell lung carcinoma (NSCLC). A logical extension of the indication for the induction chemotherapy may be to treat earlier stage resectable lung cancers (stages I and II) because the cure rate of the resectable lung cancers still remains poor and is below 60% except for stage I A. Thirty eight patients with a diagnosis of loco-regional NSCLC were treated with paclitaxel combination chemotherapy. Following two courses of induction chemotherapy, patients underwent surgical therapy whenever possible. There ten patients with stage I disease, four patients with stage II, 13 with stage IIIA, nine had stage IIIB, and two with stage IV. An overall response rate of 74% was observed. The response rate for 14 resectable patients (stage I and II) was 86%. The chemotherapy regimen was well tolerated and apart from one instance of anaphylaxis, no serious side effects were observed

  12. Combination of hyperthermia and radiation in the treatment of experimental tumours in mice

    International Nuclear Information System (INIS)

    Jansen, W.

    1980-01-01

    The effects of hyperthermia as a single agent and in interaction with ionizing radiation are investigated on tumours in mice. The degree of enhancement of the radiation reaction by heat proved to be similar to that found for mouse skin. (Auth.)

  13. Modification of radiation damage in CHO cells by hyperthermia at 40 and 450C

    International Nuclear Information System (INIS)

    Henle, K.J.; Leeper, D.B.

    1977-01-01

    Low hyperthermia at 40 0 C either before or after X irradiation did not alter the slope of the radiation dose-cell survival curve but reduced the D/sub q/ from 145 to 41 or to 0 rad for a pre- or postirradiation incubation period of 2 hr at 40 0 C, respectively. In contrast, hyperthermia at 45 0 C increased the slope of the radiation survival curve by a factor of 1.7 for a radiation pretreatment of 10 min at 45 0 C, but only by 1.3 for the same treatment immediately after irradiation. The corresponding D/sub q/'s were 262 and 138 rad, respectively. A combination of 45 and 40 0 C hyperthermia (10 min at 45 0 C + 2 hr at 40 0 C + X) resulted in a superposition of the individual effects of 45 or 40 0 C hyperthermia on the radiation survival curve. In addition, the radiation survival curve was shifted downward by a factor of three due to the potentiation of 45 0 C hyperthermia damage by postincubation at 40 0 C. Repair of sublethal radiation damage was completely suppressed during incubation at 40 following hyperthermia at 45 0 C. However, when cells were returned to 37 0 C, even after 6 hr at 40 following 45 0 C hyperthermia, the capacity to accumulate and repair sublethal radiation damage was immediately restored. These findings imply that the hyperthermia damage from low or high temperatures interacts differentially with radiation damage. Low hyperthermia at 40 0 C may affect principally the radiation repair system, whereas 45 0 C hyperthermia probably alters the radiation target more severely than the repair system

  14. Experimental animal studies on effects of hyperthermia on the central nervous system: an overview

    Energy Technology Data Exchange (ETDEWEB)

    Haveman, J; Hulshof, M C.C.M. [Department of Radiotherapy, Academisch Medisch Centrum, Amsterdam (Netherlands); Sminia, P [Department of Radiation Oncology, Section Radiobiology, VU Medical Center, Amsterdam (Netherlands); Wondergem, J [Department of Occupational Health and Risk Assessment, Leids Universitair Medisch Centrum, Leiden (Netherlands); Zee van der, J [Department of Radiation Oncology, Hyperthermia Unit, Erasmus MC - Daniel den Hoed Cancer Center, Rotterdam (Netherlands)

    2005-07-01

    grey matter as data on the rat lumbosacral cord and cauda equina show that this part of the spinal cord is slightly less sensitive to heat than the cervical and thoracolumbar spinal cord. This difference can be explained by the smaller volume of grey matter in the lumbosacral region. Experimental data demonstrate that heat injury to a small volume of the white matter of the cord does not inevitably result in functional impairment and can be repaired in about one month. Still of course the choice whether or not to exceed the critical heat dose, obtained from laboratory studies, in clinical practice is very much dependent on the clinical situation such as anatomical site or volume of the tissue involved and of course prior therapy. Data on the combined effects of X-ray irradiation and hyperthermia on rodent spinal cord clearly show that the radiation response can be enhanced with a factor of 1.1 to 1.3. In all studies on thermal enhancement, a heat dose was administered in a well tolerated range. The latent period for expression of late irradiation effects was slightly shortened in most of the studies. Histopathological changes after irradiation in combination with hyperthermia were not different from those after irradiation only. As long as there are no clinical data on effects of combined heat and X-rays on spinal cord or on brain, it seems justified to state that the results obtained in experimental animals on thermal enhancement indicate that when hyperthermia is applied in the clinic with a short interval before or after radiotherapy vigilance is required. This is evidently the case in clinical practice where treatment of sites is involved near the spinal cord; this may lead to unexpected sensitization of the cord. To our knowledge there are no clear experimental data indicating an increase in adverse effects specific to the CNS after localized or whole body hyperthermia as a result of combined treatment with chemotherapy. Thermotolerance in CNS is evidently

  15. Experimental animal studies on effects of hyperthermia on the central nervous system: an overview

    International Nuclear Information System (INIS)

    Haveman, J.; Hulshof, M.C.C.M.; Sminia, P.; Wondergem, J.; Zee van der, J.

    2005-01-01

    on the rat lumbosacral cord and cauda equina show that this part of the spinal cord is slightly less sensitive to heat than the cervical and thoracolumbar spinal cord. This difference can be explained by the smaller volume of grey matter in the lumbosacral region. Experimental data demonstrate that heat injury to a small volume of the white matter of the cord does not inevitably result in functional impairment and can be repaired in about one month. Still of course the choice whether or not to exceed the critical heat dose, obtained from laboratory studies, in clinical practice is very much dependent on the clinical situation such as anatomical site or volume of the tissue involved and of course prior therapy. Data on the combined effects of X-ray irradiation and hyperthermia on rodent spinal cord clearly show that the radiation response can be enhanced with a factor of 1.1 to 1.3. In all studies on thermal enhancement, a heat dose was administered in a well tolerated range. The latent period for expression of late irradiation effects was slightly shortened in most of the studies. Histopathological changes after irradiation in combination with hyperthermia were not different from those after irradiation only. As long as there are no clinical data on effects of combined heat and X-rays on spinal cord or on brain, it seems justified to state that the results obtained in experimental animals on thermal enhancement indicate that when hyperthermia is applied in the clinic with a short interval before or after radiotherapy vigilance is required. This is evidently the case in clinical practice where treatment of sites is involved near the spinal cord; this may lead to unexpected sensitization of the cord. To our knowledge there are no clear experimental data indicating an increase in adverse effects specific to the CNS after localized or whole body hyperthermia as a result of combined treatment with chemotherapy. Thermotolerance in CNS is evidently associated with

  16. Combination cancer chemotherapy with one compound: pluripotent bradykinin antagonists.

    Science.gov (United States)

    Stewart, John M; Gera, Lajos; Chan, Daniel C; York, Eunice J; Simkeviciene, Vitalija; Bunn, Paul A; Taraseviciene-Stewart, Laimute

    2005-08-01

    Lung and prostate cancers are major health problems worldwide. Treatments with standard chemotherapy agents are relatively ineffective. Combination chemotherapy gives better treatment than a single agent because the drugs can inhibit the cancer in different pathways, but new therapeutic agents are needed for the treatment of both tumor types. Bradykinin (BK) antagonists offer advantages of combination therapy in one compound. These promising multitargeted anti-cancer compounds selectively stimulate apoptosis in cancers and also inhibit both angiogenesis and matrix metalloprotease (MMP) action in treated lung and prostate tumors in nude mice. The highly potent, metabolism-resistant bradykinin antagonist peptide dimer, B-9870 [SUIM-(DArg-Arg-Pro-Hyp-Gly-Igl-Ser-DIgl-Oic-Arg)2] (SUIM=suberimidyl; Hyp=4-hydroxyproline; Igl=alpha-(2-indanyl)glycine; Oic=octahydroindole-2-carboxylic acid) and its non-peptide mimetic, BKM-570 [2,3,4,5,6-pentafluorocinnamoyl-(o-2,6-dichlorobenzyl)-L-tyrosine-N-(4-amino-2,2,6,6-tetramethylpiperidyl)amide] are superior to the widely used but toxic chemotherapeutic drugs cisplatin and taxotere. In certain combinations, they act synergistically with standard anti-cancer drugs. Due to its structure and biological activity, BKM-570 is an attractive lead compound for derivatization and evaluation for lung and prostate cancer drugs.

  17. [Efficacy of MVP chemotherapy combined with concurrent radiotherapy for advanced non-small cell lung cancer].

    Science.gov (United States)

    Qiao, Tiankui; Zhou, Daoan; Chen, Wei; Wang, Xianglian

    2004-12-20

    To observe the effects of MVP chemotherapy combined with concurrent radiotherapy for stage IIIB-IV non-small cell lung cancer. Sixty-two patients with stage IIIB-IV non-small cell lung cancer were randomized into two groups, concurrent radiochemotherapy group and MVP che-motherapy group. All patients in two groups were treated with MVP regimen (mitomycin C 6 mg/m² on day 1, vindesine 2 mg/m² on days 1, 8, and cisplatin 80-100 mg/m²). Patients in concurrent radiochemotherapy group received concurrent radiotherapy (46-56 Gy in 5-6 weeks). All patients received 2-4 cycles of MVP chemotherapy. The response rate was 48.4% and 19.4% in concurrent radiochemotherapy group and MVP group respectively (P MVP group.. The results show that efficacy of MVP chemotherapy combined with concurrent radiotherapy is significantly higher than that of MVP chemotherapy alone for advanced non-small cell lung cancer.

  18. Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance.

    Science.gov (United States)

    Khdair, Ayman; Chen, Di; Patil, Yogesh; Ma, Linan; Dou, Q Ping; Shekhar, Malathy P V; Panyam, Jayanth

    2010-01-25

    Tumor drug resistance significantly limits the success of chemotherapy in the clinic. Tumor cells utilize multiple mechanisms to prevent the accumulation of anticancer drugs at their intracellular site of action. In this study, we investigated the anticancer efficacy of doxorubicin in combination with photodynamic therapy using methylene blue in a drug-resistant mouse tumor model. Surfactant-polymer hybrid nanoparticles formulated using an anionic surfactant, Aerosol-OT (AOT), and a naturally occurring polysaccharide polymer, sodium alginate, were used for synchronized delivery of the two drugs. Balb/c mice bearing syngeneic JC tumors (mammary adenocarcinoma) were used as a drug-resistant tumor model. Nanoparticle-mediated combination therapy significantly inhibited tumor growth and improved animal survival. Nanoparticle-mediated combination treatment resulted in enhanced tumor accumulation of both doxorubicin and methylene blue, significant inhibition of tumor cell proliferation, and increased induction of apoptosis. These data suggest that nanoparticle-mediated combination chemotherapy and photodynamic therapy using doxorubicin and methylene blue has significant therapeutic potential against drug-resistant tumors. Copyright 2009 Elsevier B.V. All rights reserved.

  19. Toxicity and first treatment results after of neoadjuvant thermal radiochemotherapy in operable oesophageal cancer

    International Nuclear Information System (INIS)

    Hulshof, M.C.C.M; Crezee, J.; Zum Vorde sive Vording, P.; Geijssen, D; Lanschot van, J.J.B.; Richel, D.J.

    2005-01-01

    Full text: To demonstrate the toxicity and preliminary treatment results of neo-adjuvant regional hyperthermia combined with concurrent radiochemotherapy in oesophageal cancer. Background: In 2002 a phase I study was completed with neo-adjuvant regional hyperthermia combined with chemotherapy (cisplatin and etoposide) in patients with operable oesophageal cancer. It was concluded that hyperthermia was feasible. However, the toxicity of the concurrent chemotherapy was very high, resulting in only 31 % of patients receiving the planned three hyperthermia sessions and 27 % receiving not more than one hyperthermia session. Based on these results we planned to continue hyperthermia in a phase II study aiming at a decrease of (chemotherapy induced) toxicity and an improvement of response rate compared to previous radiochemotherapy studies. In August 2003 a phase II study was started combining five times regional hyperthermia with concurrent radiochemotherapy over a 4,5 weeks period consisting of weekly carboplatin (AUC = 2) and paclitaxel (50 mg/m 2 ) plus 41,4 Gy radiotherapy in 1.8 Gy daily fractions. Chemotherapy was infused during hyperthermia. An oesophagus resection was planned at 4-6 weeks after the end of radiotherapy. 28 patients have entered the study so far, 94 % with a T3 tumor and 59 % with N1 disease on echo-endosonography. Median follow-up is 9 months and 23 patients are evaluable for histological response. Toxicity was much less compared to the previous cisplatin/etoposide study; all five hyperthermia sessions were given in 88 % of patients (and 96 % had at least four sessions). No haematological toxicity was seen and nausea ≤ grade 2 in only 24 %. Dysphagia and weight loss during treatment were absent in 68 % and 81 % of patients respectively. A histological confirmed complete remission rate (CR) was found in 17 % and only residual microscopic tumor foci (Pmic) in an extra 33 %. Partial remission (PR) was accomplished in 33 %. Mean T90 in patients with

  20. Toxicity and first treatment results after of neoadjuvant thermal radiochemotherapy in operable oesophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hulshof, M C.C.M; Crezee, J; Zum Vorde sive Vording, P.; Geijssen, D; Lanschot van, J J.B.; Richel, D J [Academical Medical Center of Amsterdam (Netherlands)

    2005-07-01

    Full text: To demonstrate the toxicity and preliminary treatment results of neo-adjuvant regional hyperthermia combined with concurrent radiochemotherapy in oesophageal cancer. Background: In 2002 a phase I study was completed with neo-adjuvant regional hyperthermia combined with chemotherapy (cisplatin and etoposide) in patients with operable oesophageal cancer. It was concluded that hyperthermia was feasible. However, the toxicity of the concurrent chemotherapy was very high, resulting in only 31 % of patients receiving the planned three hyperthermia sessions and 27 % receiving not more than one hyperthermia session. Based on these results we planned to continue hyperthermia in a phase II study aiming at a decrease of (chemotherapy induced) toxicity and an improvement of response rate compared to previous radiochemotherapy studies. In August 2003 a phase II study was started combining five times regional hyperthermia with concurrent radiochemotherapy over a 4,5 weeks period consisting of weekly carboplatin (AUC = 2) and paclitaxel (50 mg/m{sup 2}) plus 41,4 Gy radiotherapy in 1.8 Gy daily fractions. Chemotherapy was infused during hyperthermia. An oesophagus resection was planned at 4-6 weeks after the end of radiotherapy. 28 patients have entered the study so far, 94 % with a T3 tumor and 59 % with N1 disease on echo-endosonography. Median follow-up is 9 months and 23 patients are evaluable for histological response. Toxicity was much less compared to the previous cisplatin/etoposide study; all five hyperthermia sessions were given in 88 % of patients (and 96 % had at least four sessions). No haematological toxicity was seen and nausea {<=} grade 2 in only 24 %. Dysphagia and weight loss during treatment were absent in 68 % and 81 % of patients respectively. A histological confirmed complete remission rate (CR) was found in 17 % and only residual microscopic tumor foci (Pmic) in an extra 33 %. Partial remission (PR) was accomplished in 33 %. Mean T90 in patients

  1. Local hyperthermia of cervical N2/N3 lymph node metastases - a phase-I/II-study

    International Nuclear Information System (INIS)

    Stahl, H.; Wust, P.; Graf, R.; Loeffel, J.; Bier, J.; Riess, H.; Jahnke, V.; Felix, R.

    1997-01-01

    50 patients with primary advanced, recurrent or persistent N2/N3 lymph node metastases were treated with microwave hyperthermia in addition to their standard therapy (radiotherapy or radiochemotherapy). For the thermometry, closed-end catheters were implanted in the cervical lesions under CT monitoring. Temperature/time and temperature/position curves were analysed with regard to power density, effective perfusion, tissue depth, index temperatures T 90 , T 50 , T 20 , cum min T 60 ≥40.5 C, and equ min T 90 at 43 C. Radiation dose, total irradiation time and chemotherapy were also recorded as therapy parameters. Repeated CT scans for assessing response were taken for a subgroup of 32 patients following primary potentially curative radiotherapy (with and without chemotherapy) and local hyperthermia. All therapy parameters were subjected to a variance analysis with regard to response. At a tissue depth of 3 cm, relative and absolute power densities were on average of 50% less than at the surface. Therapeutic temperature increases of more than 4 C (i.e. more than 41 C) were not reached at tissue depths greater than 5 cm. The effective perfusion under local hyperthermia is significantly higher than under basal conditions. The mean T 90 was 39.9 C, and the mean T 20 value was 42.3 C. T 90 , cum min T 90 ≥40.5 C, equ min T 90 43 C, radiation dose and total irradiation time have a significant influence on response. The tumor volume correlates negatively with response, and this results in the thermal gradients correlating negatively with response and survival. The quality of the temperature distribution, represented by the value of cum min T 90 ≥40.5 C, showed a tendency to correlate positively with the survival in the subgroup of patients who underwent primary therapy. (orig./AJ) [de

  2. Hyperthermia and hyperglycemia in oncology

    International Nuclear Information System (INIS)

    Zhavrid, Eh.A.; Osinskij, S.P.; Fradkin, S.Z.

    1987-01-01

    Consideration is being given to publication data and results of author's investigations into the effect of hyperthermia and hyperglycemia on physico-chemical characteristics and growth of various experimental tumors. Factors, modifying thermosensitivity, mechanisms of hyperthermia effect, various aspects of thermochimio- and thermoradiotherapy have been analyzed. Effect of artificial hyperglycemia on metabolism and kinetics of tumor and some normal cells is considered in detail. Many data, testifying to sufficient growth of efficiency of oncologic patient treatment under conditions of multimodality therapy including hyperthermia and hyperglycemia are presented

  3. Mechanisms of hyperthermia induced radiatiosensitization for treatment of human papillomavirus positive tumors

    International Nuclear Information System (INIS)

    Oei, Arlene; Leeuwen, Caspar van; Stalpers, Lukas; Rodermond, Hans; Kok, Petra; Crezee, Hans; Franken, Nicolaas

    2016-01-01

    HPV is associated with cervical cancer, the third most common cancer in women. In over 70% of cervical cancers, the high-risk HPV-types 16 and 18 are found. In these tumors, functionality of p53 is suppressed by the presence of protein E6. Hyperthermia is a clinical application of heat in which tumour temperatures are raised to 40-43°C and combined hyperthermia with radiation is very effective in the treatment of cervical cancer

  4. Utility and translatability of mathematical modeling, cell culture and small and large animal models in magnetic nanoparticle hyperthermia cancer treatment research

    Science.gov (United States)

    Hoopes, P. J.; Petryk, Alicia A.; Misra, Adwiteeya; Kastner, Elliot J.; Pearce, John A.; Ryan, Thomas P.

    2015-03-01

    For more than 50 years, hyperthermia-based cancer researchers have utilized mathematical models, cell culture studies and animal models to better understand, develop and validate potential new treatments. It has been, and remains, unclear how and to what degree these research techniques depend on, complement and, ultimately, translate accurately to a successful clinical treatment. In the past, when mathematical models have not proven accurate in a clinical treatment situation, the initiating quantitative scientists (engineers, mathematicians and physicists) have tended to believe the biomedical parameters provided to them were inaccurately determined or reported. In a similar manner, experienced biomedical scientists often tend to question the value of mathematical models and cell culture results since those data typically lack the level of biologic and medical variability and complexity that are essential to accurately study and predict complex diseases and subsequent treatments. Such quantitative and biomedical interdependence, variability, diversity and promise have never been greater than they are within magnetic nanoparticle hyperthermia cancer treatment. The use of hyperthermia to treat cancer is well studied and has utilized numerous delivery techniques, including microwaves, radio frequency, focused ultrasound, induction heating, infrared radiation, warmed perfusion liquids (combined with chemotherapy), and, recently, metallic nanoparticles (NP) activated by near infrared radiation (NIR) and alternating magnetic field (AMF) based platforms. The goal of this paper is to use proven concepts and current research to address the potential pathobiology, modeling and quantification of the effects of treatment as pertaining to the similarities and differences in energy delivered by known external delivery techniques and iron oxide nanoparticles.

  5. [Combination Chemotherapy Including Intraperitoneal(IP)Administration of Paclitaxel(PTX)followed by PTX, CDDP and S-1Triplet Chemotherapy for CY1P0 Gastric Cancer].

    Science.gov (United States)

    Shinkai, Masayuki; Imano, Motohiro; Hiraki, Yoko; Kato, Hiroaki; Iwama, Mitsuru; Shiraishi, Osamu; Yasuda, Atsushi; Kimura, Yutaka; Imamoto, Haruhiko; Furukawa, Hiroshi; Yasuda, Takushi

    2017-11-01

    We evaluate the feasibility and efficacy of combination chemotherapy including single intraperitoneal( IP)administration of paclitaxel(PTX), followed by triplet chemotherapy(PTX, cisplatin[CDDP]and S-1: PCS)for CY1P0 gastric cancer. First of all, we performed staging laparoscopy and confirmed CY1P0, and secondary, administrated PTX intraperitoneally. Thirdly, patients received PCS chemotherapy for 2 courses. After antitumor effect had been confirmed, we performed second look laparoscopy. In the case of CY0P0, we performed gastrectomy with D2 lymph nodes dissection. Total 4 patients were enrolled. Grade 3 leukopenia and neutropenia were observed in one patient while intraperitoneal and systemic-chemotherapy. One patients showed PR and 3 patients showed SD. All patients underwent second look laparoscopy. CY0P0 was observed in all patients and gastrectomy with D2 dissection was performed for all patients. Postoperative complications were observed in 2 patients. Two patients were still alive without recurrence, while the remaining 2 had died of liver metastasis and #16 LN metastasis. Combination chemotherapy including single IP PTX followed by PCS systemic-chemotherapy for CY1P0 gastric cancer is feasible and efficient.

  6. Magnetic Resonance–Guided High-Intensity Focused Ultrasound Hyperthermia for Recurrent Rectal Cancer: MR Thermometry Evaluation and Preclinical Validation

    International Nuclear Information System (INIS)

    Chu, William; Staruch, Robert M.; Pichardo, Samuel; Tillander, Matti; Köhler, Max O.; Huang, Yuexi; Ylihautala, Mika; McGuffin, Merrylee; Czarnota, Gregory; Hynynen, Kullervo

    2016-01-01

    Purpose: To evaluate the feasibility of magnetic resonance–guided high-intensity focused ultrasound (MR-HIFU) mild hyperthermia in deep tissue targets for enhancing radiation therapy and chemotherapy in the context of recurrent rectal cancer. A preclinical study was performed to evaluate the safety and performance of MR-HIFU mild hyperthermia. A prospective imaging study was performed in volunteers with rectal cancer to evaluate MR thermometry quality near the rectum and accessibility of rectal tumors using MR-HIFU. Methods and Materials: Mild hyperthermia was performed in pig thigh (9 sonications, 6 pigs) using a clinical MR-HIFU system. Targets near the rectal wall and deep thigh were evaluated. Thermal maps obtained in 6 planes every 3.2 seconds were used to control sonications in 18-mm diameter treatment regions at temperatures of 42°C to 42.5°C for 10 to 60 minutes. Volunteer imaging-only studies to assess the quality of MR thermometry (without heating) were approved by the institutional research ethics board. Anatomic and MR thermometry images were acquired in consenting volunteers with rectal cancer. In 3 of 6 study participants, rectal filling with saline was used to reduce motion-related MR thermometry artifacts near the tumor. Results: In pigs, mean target temperature matched the desired hyperthermia temperature within 0.2°C; temporal standard deviation ≤0.5°C. With optimized control thresholds, no undesired tissue damage was observed. In human volunteers, MR temperature measurements had adequate precision and stability, especially when rectal filling was used to reduce bowel motion. Conclusions: In pigs, MR-HIFU can safely deliver mild hyperthermia (41°C-43°C) to a targeted volume for 30 minutes. In humans, careful patient selection and preparation will enable adequate targeting for recurrent rectal cancers and sufficient MR temperature mapping stability to control mild hyperthermia. These results enable human trials of MR-HIFU hyperthermia.

  7. Magnetic Resonance–Guided High-Intensity Focused Ultrasound Hyperthermia for Recurrent Rectal Cancer: MR Thermometry Evaluation and Preclinical Validation

    Energy Technology Data Exchange (ETDEWEB)

    Chu, William, E-mail: William.Chu@sunnybrook.ca [Department of Radiation Oncology, Sunnybrook Health Sciences Centre and the University of Toronto, Toronto, Ontario (Canada); Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario (Canada); Staruch, Robert M. [Clinical Sites Research Program, Philips Research, Cambridge, Massachusetts (United States); Pichardo, Samuel [Thunder Bay Regional Research Institute, Thunder Bay, Ontario (Canada); Physics and Electrical Engineering, Lakehead University, Thunder Bay, Ontario (Canada); Tillander, Matti; Köhler, Max O. [MR Therapy, Philips Healthcare, Vantaa (Finland); Huang, Yuexi [Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario (Canada); Ylihautala, Mika [MR Therapy, Philips Healthcare, Vantaa (Finland); McGuffin, Merrylee [Department of Radiation Oncology, Sunnybrook Health Sciences Centre and the University of Toronto, Toronto, Ontario (Canada); Czarnota, Gregory [Department of Radiation Oncology, Sunnybrook Health Sciences Centre and the University of Toronto, Toronto, Ontario (Canada); Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario (Canada); Hynynen, Kullervo [Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario (Canada)

    2016-07-15

    Purpose: To evaluate the feasibility of magnetic resonance–guided high-intensity focused ultrasound (MR-HIFU) mild hyperthermia in deep tissue targets for enhancing radiation therapy and chemotherapy in the context of recurrent rectal cancer. A preclinical study was performed to evaluate the safety and performance of MR-HIFU mild hyperthermia. A prospective imaging study was performed in volunteers with rectal cancer to evaluate MR thermometry quality near the rectum and accessibility of rectal tumors using MR-HIFU. Methods and Materials: Mild hyperthermia was performed in pig thigh (9 sonications, 6 pigs) using a clinical MR-HIFU system. Targets near the rectal wall and deep thigh were evaluated. Thermal maps obtained in 6 planes every 3.2 seconds were used to control sonications in 18-mm diameter treatment regions at temperatures of 42°C to 42.5°C for 10 to 60 minutes. Volunteer imaging-only studies to assess the quality of MR thermometry (without heating) were approved by the institutional research ethics board. Anatomic and MR thermometry images were acquired in consenting volunteers with rectal cancer. In 3 of 6 study participants, rectal filling with saline was used to reduce motion-related MR thermometry artifacts near the tumor. Results: In pigs, mean target temperature matched the desired hyperthermia temperature within 0.2°C; temporal standard deviation ≤0.5°C. With optimized control thresholds, no undesired tissue damage was observed. In human volunteers, MR temperature measurements had adequate precision and stability, especially when rectal filling was used to reduce bowel motion. Conclusions: In pigs, MR-HIFU can safely deliver mild hyperthermia (41°C-43°C) to a targeted volume for 30 minutes. In humans, careful patient selection and preparation will enable adequate targeting for recurrent rectal cancers and sufficient MR temperature mapping stability to control mild hyperthermia. These results enable human trials of MR-HIFU hyperthermia.

  8. Re-irradiation of the chest wall for local breast cancer recurrence. Results of salvage brachytherapy with hyperthermia

    Energy Technology Data Exchange (ETDEWEB)

    Auoragh, A. [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany); Hospital Fuerth, Department of Radiation Oncology, Fuerth (Germany); Strnad, V.; Ott, O.J.; Fietkau, R. [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany); Beckmann, M.W. [University Hospital Erlangen, Department of Gynecology and Obstetrics, Erlangen (Germany)

    2016-09-15

    Following mastectomy and adjuvant external beam radiation therapy in patients with breast cancer, the incidence of local or locoregional recurrence is approximately 9 % (2-20 %). Alongside the often limited possibilities of surgical treatment, radiation therapy combined with superficial hyperthermia is the most effective local therapy. In the present work, a retrospective analysis of salvage brachytherapy combined with superficial hyperthermia for chest wall recurrences is presented. Between 2004 and 2011, 18 patients with a total of 23 target volumes resulting from chest wall recurrences after previously mastectomy and external beam radiation therapy (median 56 Gy, range 50-68 Gy) were treated with superficial brachytherapy as salvage treatment: 8 patients (44 %) had macroscopic tumor, 3 (17 %) had microscopic tumor (R1), and 7 (39 %) had undergone R0 resection and were treated due to risk factors. A dose of 50 Gy was given (high-dose rate [HDR] and pulsed-dose rate [PDR] procedures). In all, 5 of 23 patients (22 %) received additional concurrent chemotherapy, and in 20 of 23 (87 %) target volumes additional superficial hyperthermia was carried out twice weekly. The 5-year local recurrence-free survival was 56 %, the disease-free survival was 28 %, and a 5-year overall survival was 22 %. Late side effects Common Toxicity Criteria (CTC) grade 3 were reported in 17 % of the patients: 2 of 18 (11 %) had CTC grade 3 fibrosis, and 1 of 18 (6 %) had a chronic wound healing disorder. Re-irradiation as salvage brachytherapy with superficial hyperthermia for chest wall recurrences is a feasible and safe treatment with good local control results and acceptable late side effects. (orig.) [German] Nach einer Mastektomie und adjuvanter Strahlentherapie bei Patientinnen mit Mammakarzinom kommt es bei 9 % (2-20 %) zum lokalen bzw. lokoregionaeren Rezidiv. Neben den oft limitierten operativen Behandlungsmoeglichkeiten ist die Strahlentherapie mit Oberflaechenhyperthermie die

  9. Cell biological effects of hyperthermia alone or combined with radiation or drugs : A short introduction to newcomers in the field

    NARCIS (Netherlands)

    Kampinga, HH

    Hyperthermia results in protein unfolding that, if not properly chaperoned by Heat Shock Proteins (HSP), can lead to irreversible and toxic protein aggregates. Elevating HSP prior to heating makes cells thermotolerant. Hyperthermia also can enhance the sensitivity of cells to radiation and drugs.

  10. Neuropsychological evaluation of patients with inoperable non-small cell lung cancer treated with combination chemotherapy or radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Kaasa, S; Olsnes, B T; Mastekaasa, A

    1988-01-01

    Neuropsychological tests were used to evaluate possible central nervous system dysfunction in patients treated with chemotherapy. Ninety-five patients with non-small cell lung cancer limited disease were randomized to either radiotherapy (2.8 Gyx15) or combination chemotherapy with cisplatin and etoposide. In order to evaluate cognitive functions three neuropsychological tests were applied: Trail Making, Benton Visual Retention Test and Verbal Learning. Changes in the patients' test scores before and after treatment were compared. The chemotherapy patients showed reduced performance on some of the neuropsychological tests compared to the radiotherapy group. This indicates a treatment related effect on the central nervous system, possibly caused by the combination chemotherapy.

  11. Neuropsychological evaluation of patients with inoperable non-small cell lung cancer treated with combination chemotherapy or radiotherapy

    International Nuclear Information System (INIS)

    Kaasa, S.; Olsnes, B.T.; Mastekaasa, A.

    1988-01-01

    Neuropsychological tests were used to evaluate possible central nervous system dysfunction in patients treated with chemotherapy. Ninety-five patients with non-small cell lung cancer limited disease were randomized to either radiotherapy (2.8 Gyx15) or combination chemotherapy with cisplatin and etoposide. In order to evaluate cognitive functions three neuropsychological tests were applied: Trail Making, Benton Visual Retention Test and Verbal Learning. Changes in the patients' test scores before and after treatment were compared. The chemotherapy patients showed reduced performance on some of the neuropsychological tests compared to the radiotherapy group. This indicates a treatment related effect on the central nervous system, possibly caused by the combination chemotherapy. (orig.)

  12. Combination chemotherapy with Regorafenib in metastatic colorectal cancer treatment: A single center, retrospective study.

    Directory of Open Access Journals (Sweden)

    Chun-Yu Lin

    Full Text Available Regorafenib has been demonstrated as effective in refractory metastatic colorectal cancer. Combination use with chemotherapy has not been reported. We examined the efficacy and safety of adding chemotherapy to Regorafenib for the treatment of metastatic colorectal cancer(mCRC patients.We recruited mCRC patients at our institute who received either regorafenib monotherapy or regorafenib in combination with other chemotherapies. All patients had received chemo and target therapies and presented with disease progression before regorafenib treatment. The primary end point was overall survival.Between September1, 2015 and May 31, 2017, 100 mCRC patients at our institute received regorafenib treatment. 39 patients were excluded due to poor performance, lack of timely treatment, or inadequate clinical data. A total of 34 patients received regorafenib combined with other chemotherapies, and 27 patients received regorafenib alone. Median follow up time was 10.4 and 6.1 months, respectively. The primary end point of median OS was higher in the combination group than in the single use group (20.9m vs 10.3m, p = 0.015. The most frequent adverse events were hand-foot skin reactions(16[47.1%]vs 12[44.4%], fatigue(6[17.6%] vs 7[25.9%], gastrointestinal discomfort (7[20.6%] vs 6[22.2%], neutropenia (4[11.8%] vs 1[3.7%], diarrhea(4[11.8%] vs 1[3.7%], and mucositis(5[14.7%] vs 1[3.7%].The present study showed the efficacy and side effects of regorafenib combination treatment. Superiority in median OS and median PFS was noted in the combination group. The sampling difference between the study and observation groups effects justifies the comparison. Further clinical evidence of combination therapy efficacy is pending future studies.

  13. Combination chemotherapy with Regorafenib in metastatic colorectal cancer treatment: A single center, retrospective study.

    Science.gov (United States)

    Lin, Chun-Yu; Lin, Tseng-Hsi; Chen, Chou-Chen; Chen, Ming-Cheng; Chen, Chou-Pin

    2018-01-01

    Regorafenib has been demonstrated as effective in refractory metastatic colorectal cancer. Combination use with chemotherapy has not been reported. We examined the efficacy and safety of adding chemotherapy to Regorafenib for the treatment of metastatic colorectal cancer(mCRC) patients. We recruited mCRC patients at our institute who received either regorafenib monotherapy or regorafenib in combination with other chemotherapies. All patients had received chemo and target therapies and presented with disease progression before regorafenib treatment. The primary end point was overall survival. Between September1, 2015 and May 31, 2017, 100 mCRC patients at our institute received regorafenib treatment. 39 patients were excluded due to poor performance, lack of timely treatment, or inadequate clinical data. A total of 34 patients received regorafenib combined with other chemotherapies, and 27 patients received regorafenib alone. Median follow up time was 10.4 and 6.1 months, respectively. The primary end point of median OS was higher in the combination group than in the single use group (20.9m vs 10.3m, p = 0.015). The most frequent adverse events were hand-foot skin reactions(16[47.1%]vs 12[44.4%]), fatigue(6[17.6%] vs 7[25.9%]), gastrointestinal discomfort (7[20.6%] vs 6[22.2%]), neutropenia (4[11.8%] vs 1[3.7%]), diarrhea(4[11.8%] vs 1[3.7%]), and mucositis(5[14.7%] vs 1[3.7%]). The present study showed the efficacy and side effects of regorafenib combination treatment. Superiority in median OS and median PFS was noted in the combination group. The sampling difference between the study and observation groups effects justifies the comparison. Further clinical evidence of combination therapy efficacy is pending future studies.

  14. Combination chemotherapy with Regorafenib in metastatic colorectal cancer treatment: A single center, retrospective study

    Science.gov (United States)

    Lin, Chun-Yu; Lin, Tseng-Hsi; Chen, Chou-Chen; Chen, Ming-Cheng

    2018-01-01

    Background Regorafenib has been demonstrated as effective in refractory metastatic colorectal cancer. Combination use with chemotherapy has not been reported. We examined the efficacy and safety of adding chemotherapy to Regorafenib for the treatment of metastatic colorectal cancer(mCRC) patients. Methods We recruited mCRC patients at our institute who received either regorafenib monotherapy or regorafenib in combination with other chemotherapies. All patients had received chemo and target therapies and presented with disease progression before regorafenib treatment. The primary end point was overall survival. Findings Between September1, 2015 and May 31, 2017, 100 mCRC patients at our institute received regorafenib treatment. 39 patients were excluded due to poor performance, lack of timely treatment, or inadequate clinical data. A total of 34 patients received regorafenib combined with other chemotherapies, and 27 patients received regorafenib alone. Median follow up time was 10.4 and 6.1 months, respectively. The primary end point of median OS was higher in the combination group than in the single use group (20.9m vs 10.3m, p = 0.015). The most frequent adverse events were hand-foot skin reactions(16[47.1%]vs 12[44.4%]), fatigue(6[17.6%] vs 7[25.9%]), gastrointestinal discomfort (7[20.6%] vs 6[22.2%]), neutropenia (4[11.8%] vs 1[3.7%]), diarrhea(4[11.8%] vs 1[3.7%]), and mucositis(5[14.7%] vs 1[3.7%]). Conclusion The present study showed the efficacy and side effects of regorafenib combination treatment. Superiority in median OS and median PFS was noted in the combination group. The sampling difference between the study and observation groups effects justifies the comparison. Further clinical evidence of combination therapy efficacy is pending future studies. PMID:29304109

  15. A combined radiation and platinum chemotherapy for esophageal carcinoma

    International Nuclear Information System (INIS)

    Takamura, Akio; Saito, Hiroya; Sakurai, Yasuo; Horio, Keiji; Mizoe, Junetsu.

    1993-01-01

    The prognosis of the patients with advanced esophageal carcinoma treated by definitive radiotherapy is still dismal with a reported 5-year survival rate of 5-10% in most series. Since 1986, combined radiotherapy with chemotherapy using platinum analogue was initiated at Asahikawa and Obihiro Kosei Hospitals in order to improve local-regional control and the survival of the patients. From 1980 to 1992, 81 patients with unresectable esophageal carcinoma were treated with radiotherapy. Since April 1986, 37 out of the 81 patients received both radiotherapy and chemotherapy with platinum. Platinum was used during the course of radiotherapy. The method of administration of platinum was as follows; Cisplatin intravenously (50 mg, weekly, total 200 mg) in 9 patients, Carboplatin intravenously (100-150 mg, weekly, total 400-900 mg) in 11 patients and Cisplatin intraarterially (100 mg, at a 3-4 week interval, total 100-300 mg) in 17 patients. These 37 patients (Group A) were compared to 44 patients treated by radiotherapy alone (Group B) with respect to initial response and survival rate. Response was defined according to the guidelines recommended by Japanese Society for Esophageal Diseases. Response rates were 59.1% (19 CR and 7 PR) in Group B and 70.3% (7 CR and 19 PR) in Group A. Primary relapse-free rates were 36.4% in Group B and 37.8% in Group A. The cumulative survival at 3 years were 11.7% in Group B and 10.6% in Group A. Enhancement of side effects by chemotherapy was minimal and acceptable. Improvement of local-regional control and survival was not obvious by adding a concomitant platinum-chemotherapy. A definite conclusion, however, could not be drawn because of the retrospective, non-controlled nature of this study. Introduction of more intensive, multiple agents chemotherapy seems necessary if one aims at improving the results. (author)

  16. Effectivity of intravescical thermo-chemotherapy prophylaxis for patients with high recurrence and progression risk for non-muscle invasive bladder cancer.

    Science.gov (United States)

    Gözen, Ali Serdar; Umari, Paolo; Scheitlin, Walter; Su, Fuat Ernis; Akin, Yigit; Rassweiler, Jens

    2017-06-30

    Background&Aim: High grade non-muscle invasive bladder cancer (NMIBC) is common in urological practice. Most of these cancers are or become refractory to intravesical immunotherapy and chemotherapy. Here we evaluated the efficacy of combined local bladder hyperthermia and intravesical mitomycin-C (MMC) instillation in patients with high-risk recurrent NMIBC. Between February 2014 and December 2015, 18 patients with high risk NMIBC were enrolled. Patients were treated in an outpatient basis with 6 weekly induction sessions followed by monthly maintenance sessions with intravesical MMC in local hyperthermia with bladder wall thermo-chemotherapy (BWT) system (PelvixTT system, Elmedical Ltd., Hod Hasharon, Israel). The follow-up regimen included cystoscopy after the induction cycle and thereafter with regular intervals. Time to disease recurrence was defined as time from the first intravesical treatment to endoscopic or histological documentation of a new bladder tumour. Adverse events were recorded according to CTC 4.0 (Common Toxicity Criteria) score system. Mean age was 72 (32-87) years. 10 patients had multifocal disease, 9 had CIS, 6 had recurrent disease and 2 had highly recurrent disease (> 3 recurrences in a 24 months period). 6 patients underwent previous intravesical chemotherapy with MMC. The average number of maintenance sessions per patient was 7.6. After a mean follow-up of 433 days, 15 patients (83.3%) were recurrence-free. 3 patients had tumour recurrence after a mean period of 248 days without progression. Side effects were limited to grade 1 in 2 patients and grade 2 in 1 patient. BWT seems to be feasible and safe in high grade NMIBC. More studies are needed to identify the subgroup of patients who may benefit more from this treatment.

  17. Thermo-sensitively and magnetically ordered mesoporous carbon nanospheres for targeted controlled drug release and hyperthermia application.

    Science.gov (United States)

    Chen, Lin; Zhang, Huan; Zheng, Jing; Yu, Shiping; Du, Jinglei; Yang, Yongzhen; Liu, Xuguang

    2018-03-01

    A multifunctional nanoplatform based on thermo-sensitively and magnetically ordered mesoporous carbon nanospheres (TMOMCNs) is developed for effective targeted controlled release of doxorubicin hydrochloride (DOX) and hyperthermia in this work. The morphology, specific surface area, porosity, thermo-stability, thermo-sensitivity, as well as magnetism properties of TMOMCNs were verified by high resolution transmission electron microscopy, field emission scanning electron microscopy, thermo-gravimetric analysis, X-ray diffraction, Brunauer-Emmeltt-Teller surface area analysis, dynamic light scattering and vibrating sample magnetometry measurement. The results indicate that TMOMCNs have an average diameter of ~146nm with a lower critical solution temperature at around 39.5°C. They are superparamagnetic with a magnetization of 10.15emu/g at 20kOe. They generate heat when inductive magnetic field is applied to them and have a normalized specific absorption rate of 30.23W/g at 230kHz and 290Oe, showing good potential for hyperthermia. The DOX loading and release results illustrate that the loading capacity is 135.10mg/g and release performance could be regulated by changing pH and temperature. The good targeting, DOX loading and release and hyperthermia properties of TMOMCNs offer new probabilities for high effectiveness and low toxicity of cancer chemotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Intra-arterial and intra-venous chemotherapy combined with radiation in the treatment of brain tumours

    International Nuclear Information System (INIS)

    Watne, K.

    1992-01-01

    The present investigations were undertaken to study the effect of combining different modalities of chemotherapy with radiation in post-operative treatment of brain tumours. The conclusions and clinical implication of the investigations are as follows: The combination of combined intra-arterial chemotherapy followed by radiation leads to an increased median survival with more long term survivors in patients with anaplastic astrocytomas and in patients older than 40 years with astrocytomas. In patients with glioblastoma multiforme, this modality of treatment do not improve median survival, but an increased number of long-term survivors may be seen. Patients younger than 40 years with astrocytomas do not benefit from this modality of treatment. A parallelism exists between sensitivity to chemotherapy and response to radiotherapy. Patients who will benefit from the treatment may be selected early, normally two months after treatment start. Combining intra-arterial chemotherapy and radiation does not lead to an increased incidence of adverse CNS reactions. Specific transient abnormalities in the brain may occur during the first year after treatment and may be misinterpreted as tumour recurrence. EEG may be valuable in predicting adverse CNS reactions following treatment. Nuclear brain scan may be of valuable in selecting the patients who are in danger of developing adverse CNS reactions. Intra-arterial chemotherapy does have an effect in patients with brain tumours who have recurrent tumour after radiation. The most important prognostic factors are age, corticosteroid dependency at treatment start, performance status, histology and frontal lobe location. 103 refs., 2 tabs

  19. Effect of cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy on esophageal cancer cell proliferation and invasion

    Directory of Open Access Journals (Sweden)

    Yu-Lin Zhao

    2017-07-01

    Full Text Available Objective: To study the effect of cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy on esophageal cancer cell proliferation and invasion. Methods: A total of 62 patients with esophageal cancer who were treated in the hospital between January 2015 and December 2016 were collected and divided into control group and observation group according to random number table, with 31 cases in each group. Control group of patients received paclitaxel + cisplatin neoadjuvant chemotherapy + surgery, and observation group of patients accepted cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy + surgery. The differences in proliferation and invasion gene expression in the tumor tissue were compared between two groups of patients before and after chemotherapy. Results: Before chemotherapy, differences in proliferation and invasion gene expression in tumor tissue were not statistically significant between two groups of patients. After chemotherapy, proproliferation genes FOXA1, ABCE1, USP39 and Nestin mRNA expression in tumor tissue of observation group were significantly lower than those of control group; anti-proliferation genes PETN, KLF4, TSLC1 and AnnexinA2 mRNA expression were significantly higher than those of control group; pro-invasion genes γ-synuclein, CXCR4 and Snail mRNA expression were significantly lower than those of control group; anti-invasion genes CIAPIN1, Fez and Lrig1 mRNA expression were significantly higher than that of control group. Conclusions: Cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy can effectively inhibit the malignant degree of esophageal cancer cells and inhibit its proliferation and invasion.

  20. Effect of prior hyperthermia on subsequent thermal enhancement of radiation damage in mouse intestine

    International Nuclear Information System (INIS)

    Marigold, J.C.L.; Hume, S.P.

    1982-01-01

    Hyperthermia given in conjunction with X-rays results in a greater level of radiation injury than following X-rays alone, giving a thermal enhancement ratio (TER). The effect of prior hyperthermia ('priming') on TER was studied in the small intestine of mouse by giving 42.0 deg C for 1 hour at various times before the combined heat and X-ray treatments. Radiation damage was assessed by measuring crypt survival 4 days after radiation. TER was reduced when 'priming' hyperthermia was given 24-48 hours before the combined treatments. The reduction in effectiveness of the second heat treatment corresponded to a reduction in hyperthermal temperature of approximately 0.5 deg C, a value similar to that previously reported for induced resistance to heat given alone ('thermotolerance') (Hume and Marigold 1980). However, the time courses for development and decay of the TER response were much longer than those for 'thermotolerance', suggesting that different mechanisms are involved in thermal damage following heat alone and thermal enhancement of radiation damage

  1. Study of the therapeutic effect of 188Re labeled folate targeting albumin nanoparticle coupled with cis-diamminedichloroplatinum cisplatin on human ovarian cancer.

    Science.gov (United States)

    Tang, Qiusha; Chen, Daozhen

    2014-01-01

    This paper aimed to investigate the treatment efficiency of 188Re labeled folate targeting albumin nanoparticles with cis-Diamminedichloroplatinum Cisplatin (188Re-folate-CDDP/HAS MNP) on human ovarian cancer. SKOV3 cells or tumor-bearing mice were divided into different groups and treated as follow: (A) negative control; (B) chemotherapy; (C) radiotherapy; (D) hyperthermia; (E) chemotherapy and radiotherapy; (F) chemotherapy and hyperthermia; (G) radiotherapy and hyperthermia; (H) chemotherapy, radiotherapy and hyperthermia. Treatment of B to H inhibited proliferation of SKOV3 cells, with the greatest inhibition being observed in group H (P<0.05). Obvious apoptotic hypodiploid peak appeared beside G1 phase in groups of B to H. The apoptotic rates of SKOV3 cells in groups of A to H were 0.08%, 7.56%, 8.64%, 17.14%, 21.64%, 23.77%, 33.94% and 57.16%, respectively. Our findings in vivo study showed that the mass of tumor in each group of B to H was significantly lower than that in the negative control (p <0.05). In addition, compared with each group of B to G, group H showed highest inhibition of tumor growth (p<0.05). In conclusion, the combination of magnetic induced hyperthermia, chemotherapy and targeted radionuclide of radiation exposure can effectively inhibit the growth of ovarian cancer, which indicates a potential applications in ovarian cancer treatment.

  2. Long term survival with the combination of interferon and chemotherapy in metastatic melanoma

    International Nuclear Information System (INIS)

    Karagoz, B.; Bilgi, O.; Ozgun, A.; Emirzeoglu, L.; Celika, S.; Ozet, A.

    2015-01-01

    The prognosis of metastatic melanoma is poor. Pre-targeted treatment era, the combination of interferon-α (IF-α) plus chemotherapy had been used and have generally short response duration. Herein, we present a metastatic melanoma case that achieved long-term durable complete response (CR) IF-α plus chemotherapy and IF-α maintenance therapy and had lower Regulatory T (Treg) cells. A fifty-year old woman was admitted to the hospital with metastatic melanoma. Lactate dehydrogenase (LDH) level was 660 U/L. The percentage of CD4+CD25+ Treg cells was 2.4% in CD4+ lymphocytes. The IF-α plus chemotherapy and IF-α maintenance were administered. After six courses of chemotherapy, CR was achieved. Vitiligo and hypothyroidism occurred. The patient has remained in CR for approximately 7 years until second pleural metastases were detected and death. The patient has positive prognostic factors such as induction of auto immunity, small tumor volume, mild elevated LDH level, and lower Treg cell percentage. She survived long term with CR after IF-α treatment with concurrent chemotherapy and maintenance. IF-α plus chemotherapy may be a treatment option for metastatic melanoma in selected cases who cannot reach new targeted drugs

  3. Evaluation of magnetic fluid hyperthermia (MFH) combined with external radiation in an orthotopic rat model of prostate cancer

    International Nuclear Information System (INIS)

    Johannsen, M.; Thiesen, B.; Taymoorian, K.; Gneveckow, U.; Waldoefner, N.; Koch, M.; Scholz, R.; Lein, M.; Jung, K.; Loening, S.A.; Jordan, A.

    2005-01-01

    Full text: Magnetic fluid hyperthermia (MFH) is a new concept of cancer treatment based on AC magnetic field-induced excitation of biocompatible superparamagnetic nanoparticles. Preliminary studies of MFH using nanoscaled aminosilan-coated magnetites have demonstrated the feasibility of minimally invasive MFH in the Dunning tumor model. Here we evaluated the effect of two sequential MFH treatments, combined with external radiation, in an orthotopic Dunning R3327-MatLyLu prostate cancer model. MFH led to a significant growth inhibition in this orthotopic model of the aggressive MatLyLu tumor variant. Furthermore, combined MFH and radiation with 20 Gy equally effective in inhibiting tumor growth as radiation with 60 Gy, suggesting a significant synergistic effect. Intratumoral deposition of magnetic fluids was found to be stable, allowing for serial MFH treatments without repeated injection. The optimal treatment schedules of this combination regarding temperatures, sequencing and fractionation need to be defined in further experimental studies. (author)

  4. Cellular radiation effects and hyperthermia: Cytokinetic investigations with stationary phase yeast cells

    International Nuclear Information System (INIS)

    Fingerhut, R.; Otto, F.; Oldiges, H.; Kiefer, J.

    1980-01-01

    Wild type diploid yeast, Saccharomyces cerevisiae strain 211, was subjected to 250 kV X-rays or 50 0 C heat treatment for 30 min or to a combination of both. X-ray exposure took place either in air or in nitrogen. Cell number, percentage of budding cells and cell cycle progression was followed for up to 12 h post irradiation. The distribution of cell cycle stages was determined by flow cytofluorometry. All treatments cause a retardation of cell division rate. Hyperthermia leads mainly to a lengthening of G 1 , whereas X-rays arrest the cells reversibly in G 2 . The effect of the combined treatment appears to be merely additive. No selective action of hyperthermia on hypoxic cells was found. (orig.) [de

  5. Outcome of combination chemotherapy in extensive stage small-cell lung cancer

    DEFF Research Database (Denmark)

    Lassen, U N; Hirsch, F R; Osterlind, K

    1998-01-01

    During the past two decades many different treatment regimens of combination chemotherapy have been applied in extensive stage small-cell lung cancer (SCLC). This study was carried out to identify whether these modifications have resulted in an improved overall survival for extensive stage during...

  6. Successful treatment of ovarian cancer with apatinib combined with chemotherapy: A case report.

    Science.gov (United States)

    Zhang, Mingzi; Tian, Zhongkai; Sun, Yehong

    2017-11-01

    The standard treatment for ovarian cancer is chemotherapy with 2 drugs (taxanes and platinum drugs). However, the traditional combination of the 2 drugs has many adverse effects (AEs) and the cancer cells will quickly become resistant to the drugs. Apatinib is a small-molecule antiangiogenic agent which has shown promising therapeutic effects against diverse tumor types, but it still remains unknown whether apatinib has an antitumor effect in patients with ovarian cancer. Herein, we present a successfully treated case of ovarian cancer using chemotherapy and apatinib, in order to demonstrate the effectiveness of this new combined regimen in ovarian cancer. A 51-year-old Chinese woman presented with ovarian cancer >4.5 years. The disease and the cancer antigen 125 (CA-125) had been controlled well by surgical treatment and following chemotherapy. However, the drugs could not control the disease anymore as the CA-125 level was significantly increasing. Ovarian cancer. The patient was treated with apatinib combined with epirubicin. Apatinib was administered orally, at an initial daily dose of 500 mg, and was then reduced to 250 mg qd after the appearance of intolerable hand-foot syndrome (HFS) and oral ulcer. Then, the oral ulcer disappeared and the HFS was controlled by dose adjustment, oral vitamin B6, and hand cream application. The CA-125 reverted to the normal value after treatment with the new regimen. Magnetic resonance imaging showed that the original tumor lesions had disappeared. Apatinib monotherapy as maintenance therapy was then used to successfully control the cancer with a complete response. Our study is the first, to our knowledge, to report the therapeutic effects of apatinib and epirubicin on ovarian cancer. Apatinib combined with chemotherapy and apatinib monotherapy as maintenance therapy could be a new therapeutic strategy for ovarian cancer, especially adenocarcinomas.

  7. Is there any advantage to combined trastuzumab and chemotherapy in perioperative setting her 2neu positive localized gastric adenocarcinoma?

    Directory of Open Access Journals (Sweden)

    Albouzidi Abderrahmane

    2011-09-01

    Full Text Available Abstract We report here a 44-year-old Moroccan man with resectable gastric adenocarcinoma with overexpression of human epidermal growth factor receptor 2 (HER2 by immunohistochemistry who was treated with trastuzumab in combination with chemotherapy in perioperative setting. He received 3 cycles of neoadjuvant chemotherapy consisting of trastuzumab, oxaliplatin, and capecitabine. Afterwards, he received total gastrectomy with extended D2 lymphadenectomy without spleno-pancreatectomy. A pathologic complete response was obtained with a combination of trastuzumab and oxaliplatin and capecitabine. He received 3 more cycles of trastuzumab containing regimen postoperatively. We conclude that resectable gastric carcinoma with overexpression of the c-erbB-2 protein should ideally be managed with perioperative combination of trastuzumab with chemotherapy. Further research to evaluate trastuzumab in combination with chemotherapy regimens in the perioperative and adjuvant setting is urgently needed.

  8. Hyperthermia-enhanced TRAIL- and mapatumumab-induced apoptotic death is mediated through mitochondria in human colon cancer cells.

    Science.gov (United States)

    Song, Xinxin; Kim, Han-Cheon; Kim, Seog-Young; Basse, Per; Park, Bae-Hang; Lee, Byeong-Chel; Lee, Yong J

    2012-05-01

    Colorectal cancer is the third leading cause of cancer-related mortality in the world; death usually results from uncontrolled metastatic disease. Previously, we developed a novel strategy of TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) in combination with hyperthermia to treat hepatic colorectal metastases. However, previous studies suggest a potential hepatocyte cytotoxicity with TRAIL. Unlike TRAIL, anti-human TRAIL receptor antibody induces apoptosis without hepatocyte toxicity. In this study, we evaluated the anti-tumor efficacy of humanized anti-death receptor 4 (DR4) antibody mapatumumab (Mapa) by comparing it with TRAIL in combination with hyperthermia. TRAIL, which binds to both DR4 and death receptor 5 (DR5), was approximately tenfold more effective than Mapa in inducing apoptosis. However, hyperthermia enhances apoptosis induced by either agent. We observed that the synergistic effect was mediated through elevation of reactive oxygen species, c-Jun N-terminal kinase activation, Bax oligomerization, and translocalization to the mitochondria, loss of mitochondrial membrane potential, release of cytochrome c to cytosol, activation of caspases, and increase in poly(ADP-ribose) polymerase cleavage. We believe that the successful outcome of this study will support the application of Mapa in combination with hyperthermia to colorectal hepatic metastases. Copyright © 2011 Wiley Periodicals, Inc.

  9. Clinical comparative investigation using intensity-modulated radiotherapy combined with concurrent chemotherapy for the local advanced nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Zhao Yingchao; Dai Xiaofang; Wu Gang; Zhao Yanxia; Luo Ming

    2009-01-01

    Objective: To research the early effects and side-effects of the local advanced nasopharyngeal carcinoma patients using intensity-modulated radiotherapy (IMRT) combined with concurrent chemotherapy. Methods: From January 2005 to January 2007, 60 patients with nasopharyngeal carcinoma of stage m-IV b were received IMRT combined with concurrent chemotherapy in our center. Sixty patients were divided into paclitaxel concurrent group (32 patients) and cisplatin concurrent group (28 patients). The prescribing doses of the primary tumor were 68-72 Gy for each group. The patients of paclitaxel concurrent group received 5-7 times pacitaxel liposome chemotherapy of 30 mg · m -2 ·. The patients of cisplatin concurrent group received 5-7 times cisplatin chemotherapy of 30 mg · m -2 · week -1 . Results: As to the side-effects, the patients of the cisplatin concurrent group got earlier radiodermatitis and radiation-induced mucositis but also got significantly higher rate of radiodermatitis, radiation-induced mucositis, radiation-induced leucopenia and gastrointestinal toxicity, as well as the loss of weight. No significant difference was found on liver and renal functions between two groups.Four patients (12.5%) of the paclitaxel concurrent group were broken-off, which was much better than the cisplatin concurrent group. There was no significant difference on the specific length of break-off time, the 2-year overall survival rate and the 2-year diseaee-free survival rate between two groups. Conclusions: IMRT combined with concurrent chemotherapy of paclitaxel liposome for local advanced nasopharyngeal carcinoma results in less side-effects and better tolerance than IMRT combined with concurrent cisplatin chemotherapy. (authors)

  10. Hyperthermia

    International Nuclear Information System (INIS)

    Perez, C.A.; Emami, B.; Nussbaum, G.; Sapareto, S.

    1987-01-01

    The effect on heat on malignant tumors was first reported by Hippocrates. In 1856 another described the disappearance of a soft tissue sarcoma following high fever in a patient with erysipelas. Later, another induced fever by injecting bacterial toxins, and others used localized hyperthermia to produce tumor regression in patients. There were 32 patients with advanced cancer of various types treated with a combination of heat, induced with pyrogenic substances, and x-ray therapy. Twenty-nine of these patients improved for 1 to 6 months. In the past 10 years interest has been rekindled to the clinical application of this modality because numerous papers have indicated that there may be a significant advantage to the use of heat alone or combined with irradiation and cytotoxic drugs to enhance the killing of tumor cells. The clinical use of heat has been hampered by a lack of adequate equipment to deliver effective heat in deep-seated lesions and of thermometry techniques that provide reliable information on heat distribution in target tissues. However, significant progress has been made. About 30% to 50% of patients with solid tumors have recurrences at the primary site. Many of these patients have regional lymph node recurrences. Both failure patterns could be improved if effective radiation sensitizers are developed

  11. Mild hyperthermia can induce adaptation to cytogenetic damage caused by subsequent X irradiation

    International Nuclear Information System (INIS)

    Cai, Lu.; Jiang, Jie.

    1995-01-01

    Many low-level environmental agents are able to induce an increased resistance to subsequent mutagenic effects induced by ionizing radiation. In this paper, an induced cytogenetic adaptation to radiation in human lymphocytes was studied with mild hyperthermia as the adaptive treatment and compared with that induced by low-dose radiation. We found that this adaptation could be induced not only in PHA-stimulated human lymphocytes (at 14, 38 and 42 h after addition of PHA), but also in unstimulated G 0 -phase cells (before addition of PHA) by mild hyperthermia (41 degrees C for 1 h) as well as 50 mGy X rays. When the two adaptive treatments were combined, no additive effects on the magnitude of the adaptation induced were observed, suggesting that low-dose radiation and hyperthermia may share one mechanism of induction of adaptation to cytogenetic damage. Some mechanisms which may be involved in the induction of adaptation to cytogenetic damage by low-dose radiation are discussed and compared with the effects of mild hyperthermia in inducing thermotolerance and radioresistance. 56 refs., 4 figs., 3 tabs

  12. Malignant gliomas treated after surgery by combination chemotherapy and delayed radiation therapy. Pt. 2

    International Nuclear Information System (INIS)

    Poisson, M.; Mashaly, R.; Pertuiset, B.F.; Metzger, J.

    1979-01-01

    34 patients operated on for malignant gliomas were successively treated by combination chemotherapy with VM 26 and CCNU and conventional radiation therapy with an average dosage of 5,800 rads, six months after surgery. The general and haematological tolerance of delayed irradiation after chemotherapy was satisfactory. Twelve patients developed neurological complications during or after irradiation. The complications were early in 10 cases, and delayed in 2. They were probably due to tumour growth in five cases, and secondary to irradiation in seven. In four of the seven cases the preradiation chemotherapy seemed to potentiate the radiation effect on the central nervous system. (author)

  13. Effects of hyperthermia on repair of radiation-induced DNA strand breaks

    International Nuclear Information System (INIS)

    Mills, M.D.; Meyn, R.E.

    1981-01-01

    Previous reports have suggested a relationship between the heat-induced changes in nucleoprotein and the hyperthermic enhancement of radiation sensitivity. In an effort to further understand these relationships, we measured the level of initial DNA strand break damage and the DNA strand break rejoining kinetics in Chinese hamster ovary cells following combined hyperthermia and ionizing radiation treatments. The amount of protein associated with DNA measured as the ratio of [ 3 H)leucine to [ 14 C]thymidine was also compared in chromatin isolated from both heated and unheated cells. The results of these experiments show that the initial level of radiation-induced DNA strand breaks is significantly enhanced by a prior hyperthermia treatment of 43 0 C for 30 min. Treatments at higher temperatures and longer treatments at the same temperature magnified this effect. Hyperthermia was also shown to cause a substantial inhibition of the DNA strand break rejoining after irradiation. Both the initial level of DNA damage and the rejoining kinetics recovered to normal levels with incubation at 37 0 C between the hyperthermia and radiation treatments. Recovery of these parameters coincided with the return of the amount of protein associated with DNA to normal values, further suggesting a relationship between the changes in nucleoprotein and the hyperthermic enhancement of radiation sensivivity

  14. Combined regional chemotherapy and radiation therapy in the treatment of epidermoid carcinoma in the oro-facial region

    Energy Technology Data Exchange (ETDEWEB)

    Danko, J; Satko, I [Komenskeho Univ., Bratislava (Czechoslovakia). Lekarska Fakulta; Durkovsky, J [Institute of Clinical Oncology, Bratislava (Czechoslovakia)

    1979-01-01

    Treatment was studied of oro-facial epidermoid carcinoma by combined chemo- and radiotherapy and eventual surgery. Cytostatic drugs were applied intraarterially. After a monocytostatic treatment trial with Methotrexate (MTX), a combined cytostatic program was developed alternating two cytostatic drugs, viz., MTX and Bleomycin (BLM). The usefulness of chemotherapy and its inclusion in the treatment of epidermoid carcinoma in the oro-facial region was found justified for combined therapy. The selected intraarterial administration, however, is not suitable for routine application. For this reason, the combination irradiation or surgical therapy with chemotherapy was adopted.

  15. Effectivity of intravescical thermo-chemotherapy prophylaxis for patients with high recurrence and progression risk for non-muscle invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    Ali Serdar Gözen

    2017-06-01

    Full Text Available Background&Aim: High grade non-muscle invasive bladder cancer (NMIBC is common in urological practice. Most of these cancers are or become refractory to intravesical immunotherapy and chemotherapy. Here we evaluated the efficacy of combined local bladder hyperthermia and intravesical mitomycin-C (MMC instillation in patients with high-risk recurrent NMIBC. Materials and methods: Between February 2014 and December 2015, 18 patients with high risk NMIBC were enrolled. Patients were treated in an outpatient basis with 6 weekly induction sessions followed by monthly maintenance sessions with intravesical MMC in local hyperthermia with bladder wall thermo-chemotherapy (BWT system (PelvixTT system, Elmedical Ltd., Hod Hasharon, Israel. The follow-up regimen included cystoscopy after the induction cycle and thereafter with regular intervals. Time to disease recurrence was defined as time from the first intravesical treatment to endoscopic or histological documentation of a new bladder tumour. Adverse events were recorded according to CTC 4.0 (Common Toxicity Criteria score system. Results: Mean age was 72 (32-87 years. 10 patients had multifocal disease, 9 had CIS, 6 had recurrent disease and 2 had highly recurrent disease (> 3 recurrences in a 24 months period. 6 patients underwent previous intravesical chemotherapy with MMC. The average number of maintenance sessions per patient was 7.6. After a mean follow-up of 433 days, 15 patients (83.3% were recurrence-free. 3 patients had tumour recurrence after a mean period of 248 days without progression. Side effects were limited to grade 1 in 2 patients and grade 2 in 1 patient. Conclusions: BWT seems to be feasible and safe in high grade NMIBC. More studies are needed to identify the subgroup of patients who may benefit more from this treatment.

  16. Combination therapy of gastric carcinoma with radiation and chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Asakawa, Hiroshi; Otawa, Hirokazu; Yamada, Shogo; Matsumoto, Ko [Miyagi Prefectural Adult Disease Center, Natori (Japan)

    1982-08-01

    The concurrent combination therapy of radiation and chemotherapy was performed in a total of 134 cases of stomach cancer. Radiation response of tumor was remarkable in 35 (37%) of 95 cases, irradiated more than 5,000 rad. Yearly survival rates in 81 cases, in which the scheduled curative treatment was completed, were 63% in one, 31% in two, 21% in three, 17% in four and 13% in five years. These rates were intimately correlated to tumor size and cancer type. However, this combination therapy accompanied some fatal complications in a few percent. From the results, it was concluded that this combination therapy should be valuable to prolong the life of patients with gastric cancer, and that the curable indications for this treatment should be T1-T3: M0 cases with radio-responsive tumor.

  17. When Combined with Chemotherapy, Bevacizumab Is Associated with Increased Risk of Death

    Science.gov (United States)

    Cancer patients who receive the targeted therapy bevacizumab (Avastin) in combination with chemotherapy are at increased risk of serious side effects that may lead to death, according to a meta-analysis of 16 clinical trials that was published February 2,

  18. Feasibility study of local ultrasound hyperthermia in cancer therapy

    International Nuclear Information System (INIS)

    Jones, K.G.; Straube, W.; Emami, B.; Perez, C.A.

    1987-01-01

    This paper describes a retrospective analysis of patients treated at Washington University for recurrent or persistent cancer with Ultrasound Hyperthermia between October 1984 and June 1986. Fifteen of 102 lesions were treated during this time period with Ultrasound Hyperthermia instead of microwave hyperthermia due to the size of the lesion needing heat at depths greater than 4 cm. Also, the patients' lesion could not be implanted for interstitial microwave hyperthermia. Fourteen of the treated patients received concomitant radiotherapy, while one received concomitant Bleomycin. There were 79 total hyperthermia treatments delivered, of which 67 achieved a therapeutic temperature of 43 0 C for 60 minutes. During 15/79 treatments, patients experienced pain; of which 11/15 lead to poor heating. Only one treatment of the twelve poor treatments was secondary to technical difficulties. Complete local control was accomplished in seven patients, a partial response in four patients. The results of therapeutic heating and its relationship to the site of treatment and local control are presented, along with phantom studies of Ultrasound microwave hyperthermia reemphasizing the feasibility of using Ultrasound Hyperthermia

  19. Effect of hypothermia on cell kinetics and response to hyperthermia and x rays

    International Nuclear Information System (INIS)

    van Rijn, J.; van den Berg, J.; Kipp, J.B.A.; Schamhart, D.H.J.; van Wijk, R.

    1985-01-01

    Hyperthermia is a potent radio enhancer. Studies using hypothermia in combination with irradiation have given confusing results due to lack of uniformity in experimental design. This report shows that hypothermia might have potential significance in the treatment of malignant cells with both thermo- and radiotherapy. Reuber H35 hepatoma cells, clone KRC-7 were used to study the effect of hypothermia on cell kinetics and subsequent response to hyperthermia and/or X rays. Cells were incubated at 8.5 0 C or between 25 and 37 0 C for 24 hr prior to hyperthermia or irradiation. Hypothermia caused sensitization to both hyperthermia and X rays. In contrast to the effect of hypothermia on either hyperthermia or X rays alone, thermal radiosensitization was decreased in hypothermically pretreated cells (24 hr at 25 0 C) compared to control cells (37 0 C). The expression of thermotolerance and the rate of development at 37 0 C after an initial heating at 42.5 0 C were not influenced after preincubation at 25 0 C for 24 hr. The expression of thermotolerance for heat or heat plus X rays during incubation at 41 0 C occurred in a significantly smaller number of cells after 24 hr preincubation at 25 0 C. The enhanced thermo- and radiosensitivity in hypothermically treated cells disappeared in approximately 6 hr after return to 37 0 C

  20. Contributions of different modes of TRPV1 activation to TRPV1 antagonist-induced hyperthermia.

    Science.gov (United States)

    Garami, Andras; Shimansky, Yury P; Pakai, Eszter; Oliveira, Daniela L; Gavva, Narender R; Romanovsky, Andrej A

    2010-01-27

    Transient receptor potential vanilloid-1 (TRPV1) antagonists are widely viewed as next-generation pain therapeutics. However, these compounds cause hyperthermia, a serious side effect. TRPV1 antagonists differentially block three modes of TRPV1 activation: by heat, protons, and chemical ligands (e.g., capsaicin). We asked what combination of potencies in these three modes of TRPV1 activation corresponds to the lowest potency of a TRPV1 antagonist to cause hyperthermia. We studied hyperthermic responses of rats, mice, and guinea pigs to eight TRPV1 antagonists with different pharmacological profiles and used mathematical modeling to find a relative contribution of the blockade of each activation mode to the development of hyperthermia. We found that the hyperthermic effect has the highest sensitivity to the extent of TRPV1 blockade in the proton mode (0.43 to 0.65) with no to moderate sensitivity in the capsaicin mode (-0.01 to 0.34) and no sensitivity in the heat mode (0.00 to 0.01). We conclude that hyperthermia-free TRPV1 antagonists do not block TRPV1 activation by protons, even if they are potent blockers of the heat mode, and that decreasing the potency to block the capsaicin mode may further decrease the potency to cause hyperthermia.

  1. Clinical experience with RF thermotherapy for nonresectable primary and secondary liver tumors

    International Nuclear Information System (INIS)

    Yonemura, Yutaka; Fujimura, Takashi; Takegawa, Shigeru; Miyata, Ryuwa; Kamata, Toru; Miyazaki, Itsuo; Nakajima, Kazuyoshi; Hisazumi, Haruo; Saito, Yasuo

    1987-01-01

    Twenty two patients with primary or secondary liver tumors were treated by radiofrequency hyperthermia (8 MHz) combined with radiation or chemotherapy. Hyperthermia was administered twice a week for 40 - 60 minutes per session up to a total of 5 - 48 sessions. Five fractions per week of irradiation (10 MV X ray) at 180 - 200 cGy or intraarterial chemotherapy using mitomycin C, cis-diamminedichroloplatinum or adriamycine were carried out. Intratumor temperature over 42.5 deg C were obtained in 9 of 17 patients. Of the 22 patients treated, 2 (9 %) showed complete response, 8 (36 %) partial response, 3 (14 %) minor response, 7 (32 %) no change and 2 (9 %) progressive disease. 7 out of 14 tumors, heated over 42.5 deg C showed complete or partial response but only 1 out of 5 tumors, heated under 42.5 deg C was responder. Complication observed were thrombocytopenia and leukopenia in 30 % of cases. These results showed that combined treatment of hyperthermia radiation and chemotherapy appear to be useful from of therapy for the patients with liver tumor. (author)

  2. The search for therapeutic gain in the combination of radiotherapy and chemotherapy

    International Nuclear Information System (INIS)

    Steel, G.G.

    1988-01-01

    The literature on combined treatment with radiation and cytotoxic drugs in experimental tumours and normal tissues of laboratory animals is reviewed in the context of the four previously proposed mechanisms whereby a therapeutic advantage might be gained. There is evidence for strong time-dependent processes occurring in some normal tissues. In tumours, the evidence is much weaker and there is considerable disparity among experimental tumours in optimum timing. This review leads to the conclusion that the clinical use of drug-radiation combinations should not be based on an anticipated beneficial interaction; gain will most probably come from the best radiotherapy and the best chemotherapy given as far as possible independently. Deleterious interactions can be reduced by allowing a gap of some weeks between chemotherapy and radiotherapy and by avoiding drugs that are known to enhance radiation damage to the normal tissues that are irradiated. 131 refs.; 4 figs.; 5 tabs

  3. Chemotherapy disruption of efficient radiotherapy

    International Nuclear Information System (INIS)

    Nervi, C.; Friedman, M.

    1974-01-01

    Studies on the use of chemotherapy in combination with radiotherapy are reviewed. Some topics discussed are: indications for the use of combined chemotherapy and radiotherapy; improvement of the therapeutic ratio following the use of methotrexate; advantages of preirradiation and postirradiation chemotherapy; side effects following simultaneous chemotherapy and radiotherapy; and effects of chemotherapy on cure rate of radiosensitive and radioresistant tumors. (U.S.)

  4. Combination therapy with hormonal, radiation and chemotherapy for stage C prostate cancer

    International Nuclear Information System (INIS)

    Iwasawa, Toshihisa; Matsumoto, Hidetsugu

    1996-01-01

    To improve the effectiveness of treatment for patients with stage C prostate cancer, therapy in combination with hormonal, radiation and chemotherapy was given for the initial period, and there after, hormonal therapy was continuously administered to 18 patients with chemotherapy and three patients without it. At the Social Health Insurance Medical Center, between May 1988 and August 1991, 21 patients were diagnosed to have stage C histologically confirmed adenocarcinoma of the prostate. The average age of the patients was 69.0 years. The tumor was well, moderate and poorly differentiated in 5, 6 and 10 patients, respectively. As hormonal therapy, orchiectomy was performed on 19 of the 21 patients. Furthermore, 11 patients were administered estramustine phosphate, 9 chlormadinone acetate, and one diethylstilbesterol diphosphate. As, radiation therapy, all patients were treated with AP-PA parallel opposing technique to small pelvis with a 12 cm x 12 cm treatment field (44-45 Gy) combined with conformation radiotherapy to prostate (20-26 Gy). Chemotherapy was performed using either one or a combination of the following; cis-diamminedichloroplatinum, adriamycin, cyclophosphamide, 5-fluorouracil, methotrexate and etoposide. The observation period was 54.5 months on the average. Recurrence was observed in 3 patients, for all of which the sites were at bone. The 5-year non-recurrence rate was 90.4% by Kaplan-Meier's method. There were 4 deaths, three were due to prostate cancer and one to gastric cancer. The 5-year cumulative survival rate by Kaplan-Meier's method was 90.5%. In conclusion, this treatment was effective for stage C cases of prostate cancer. (author)

  5. Combination of chemotherapy and heavy-ion particle therapy for pancreas cancer

    International Nuclear Information System (INIS)

    Yamada, Shigeru; Ando, Koichi

    2003-01-01

    The purpose of this study is to investigate the combination of chemotherapy and heavy-ion particle therapy for pancreas cancer. We measured surviving fractions in four culture pancreas cancer cells. The cell killing of heavy-ion irradiation is more effective compared to that of X ray irradiation. Gemcitabine induced radiosensitization for pancreas cancer cells. (author)

  6. Combination of chemotherapy and heavy-ion particle therapy for pancreas cancer

    International Nuclear Information System (INIS)

    Yamada, Shigeru; Ando, Koichi

    2004-01-01

    The purpose of this study is to investigate the combination of chemotherapy and heavy-ion particle therapy for pancreas cancer. We measured surviving fractions in four culture pancreas cancer cells. The cell killing of heavy-ion irradiation is more effective compared to that of X ray irradiation. Gemcitabine induced radiosensitization for pancreas cancer cells. (author)

  7. Chemo-radiotherapy plus hyperthermia in locally advanced cervical cancer: preliminary results of an institutional phase II study

    International Nuclear Information System (INIS)

    Gabbani, M.; Marciai, N.; Maluta, S.; Griso, C.; Merlin, F.; Cassandrini, P.; Giudici, S.; Franchi, M.; Zanini, L.

    2005-01-01

    Full text: Radiotherapy given concurrently with a cisplatin-based regimen has shown a benefit in patients with locally advanced cervical cancer so becoming the new standard treatment according to EBM criteria. Addition of hyperthermia to radiotherapy has also been proved to yield an advantage in survival and local control in pts affected by recurrent and local advanced cervical cancer in the Dutch Phase III trial so that the Consensus Forum of Kadota (Osaha June 2004) included cervical cancer among tumors treatable with hyperthermia. In our institutional multidisciplinary team a pilot study has been designed in order to evaluate feasibility, outcome and toxicity of tri-modality treatment in pts with locally advanced cervical cancer in our daily practice. Since January 2003 to now eight patients affected by cervical cancer with stage IB2 through IVA N0-N+ pelvic or paraaortic were entered the study. Six patients were treated at initial diagnosis and two patients after chemotherapy which had achieved stable disease. Treatment regimen consisted in 5 courses of weekly chemotherapy (cisplatin 40 mg/mq) with concurrent external radiotherapy to a total dose of 64-66 Gy on CTV1 and 45 Gy on para-aortic nodes plus boost in pts with enlarged nodes identified by imaging. Five weekly sessions of hyperthermia were performed by using BSD 2000 system and sigma 60 applicator. No significant toxicity occurred and all of the patients completed tri-modality treatment in accordance with the study protocol. Seven pts experienced a complete clinical remission and one patient a partial remission as defined by clinical and imaging examinations. After four months from the end of the treatment a patient with Stage IIB bulky tumor plus one pelvic positive node who was in complete remission (Clinical examination, MRI and TAC-PET three months from the end of the treatment were negative for evidence of disease) developed a bleeding recto-vaginal fistula plus central pelvic necrosis for which an

  8. Nanotechnology in hyperthermia cancer therapy: From fundamental principles to advanced applications.

    Science.gov (United States)

    Beik, Jaber; Abed, Ziaeddin; Ghoreishi, Fatemeh S; Hosseini-Nami, Samira; Mehrzadi, Saeed; Shakeri-Zadeh, Ali; Kamrava, S Kamran

    2016-08-10

    In this work, we present an in-depth review of recent breakthroughs in nanotechnology for hyperthermia cancer therapy. Conventional hyperthermia methods do not thermally discriminate between the target and the surrounding normal tissues, and this non-selective tissue heating can lead to serious side effects. Nanotechnology is expected to have great potential to revolutionize current hyperthermia methods. To find an appropriate place in cancer treatment, all nanotechnology-based hyperthermia methods and their risks/benefits must be thoroughly understood. In this review paper, we extensively examine and compare four modern nanotechnology-based hyperthermia methods. For each method, the possible physical mechanisms of heat generation and enhancement due to the presence of nanoparticles are explained, and recent in vitro and in vivo studies are reviewed and discussed. Nano-Photo-Thermal Therapy (NPTT) and Nano-Magnetic Hyperthermia (NMH) are reviewed as the two first exciting approaches for targeted hyperthermia. The third novel hyperthermia method, Nano-Radio-Frequency Ablation (NaRFA) is discussed together with the thermal effects of novel nanoparticles in the presence of radiofrequency waves. Finally, Nano-Ultrasound Hyperthermia (NUH) is described as the fourth modern method for cancer hyperthermia. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Chemotherapy by superselective intraarterial infusion of nedaplatin combined with radiotherapy for oral cancer

    International Nuclear Information System (INIS)

    Yamashita, Yoshio; Goto, Masaaki; Katsuki, Takeshi

    2002-01-01

    Nedaplatin (CDGP), which is a CDDP derivative, has been reported to be an effective anticancer agent for head and neck cancer. This study was performed to assess the feasibility of chemotherapy by superselective intraarterial infusion of nedaplatin (CDGP) in patients with oral cancers. Ten patients were treated with chemotherapy by superselective intraarterial infusion of CDGP combined with radiotherapy. The complete and partial response rates were 7/10 (70%) and 3/10 (30%), respectively. Nine patients showed grade 1-2 hematological toxicity including leukocytopenia and anemia. Thrombocytopenia of grade 4 was seen in only one patient. However, all the patients were free from renal dysfunction. From these results, it is suggested that this combination therapy might be quite effective and safe. Further study will be needed to determine its efficacy against oral cancer. (author)

  10. Chemotherapy by superselective intraarterial infusion of nedaplatin combined with radiotherapy for oral cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yamashita, Yoshio; Goto, Masaaki; Katsuki, Takeshi [Saga Medical School (Japan)

    2002-06-01

    Nedaplatin (CDGP), which is a CDDP derivative, has been reported to be an effective anticancer agent for head and neck cancer. This study was performed to assess the feasibility of chemotherapy by superselective intraarterial infusion of nedaplatin (CDGP) in patients with oral cancers. Ten patients were treated with chemotherapy by superselective intraarterial infusion of CDGP combined with radiotherapy. The complete and partial response rates were 7/10 (70%) and 3/10 (30%), respectively. Nine patients showed grade 1-2 hematological toxicity including leukocytopenia and anemia. Thrombocytopenia of grade 4 was seen in only one patient. However, all the patients were free from renal dysfunction. From these results, it is suggested that this combination therapy might be quite effective and safe. Further study will be needed to determine its efficacy against oral cancer. (author)

  11. Hyperthermia enhances mapatumumab-induced apoptotic death through ubiquitin-mediated degradation of cellular FLIP(long) in human colon cancer cells.

    Science.gov (United States)

    Song, X; Kim, S-Y; Zhou, Z; Lagasse, E; Kwon, Y T; Lee, Y J

    2013-04-04

    Colorectal cancer is the third leading cause of cancer-related mortality in the world; the main cause of death of colorectal cancer is hepatic metastases, which can be treated with hyperthermia using isolated hepatic perfusion (IHP). In this study, we report that mild hyperthermia potently reduced cellular FLIP(long), (c-FLIP(L)), a major regulator of the death receptor (DR) pathway of apoptosis, thereby enhancing humanized anti-DR4 antibody mapatumumab (Mapa)-mediated mitochondria-independent apoptosis. We observed that overexpression of c-FLIP(L) in CX-1 cells abrogated the synergistic effect of Mapa and hyperthermia, whereas silencing of c-FLIP in CX-1 cells enhanced Mapa-induced apoptosis. Hyperthermia altered c-FLIP(L) protein stability without concomitant reductions in FLIP mRNA. Ubiquitination of c-FLIP(L) was increased by hyperthermia, and proteasome inhibitor MG132 prevented heat-induced downregulation of c-FLIP(L). These results suggest the involvement of the ubiquitin-proteasome system in this process. We also found lysine residue 195 (K195) to be essential for c-FLIP(L) ubiquitination and proteolysis, as mutant c-FLIP(L) lysine 195 arginine (arginine replacing lysine) was left virtually un-ubiquitinated and was refractory to hyperthermia-triggered degradation, and thus partially blocked the synergistic effect of Mapa and hyperthermia. Our observations reveal that hyperthermia transiently reduced c-FLIP(L) by proteolysis linked to K195 ubiquitination, which contributed to the synergistic effect between Mapa and hyperthermia. This study supports the application of hyperthermia combined with other regimens to treat colorectal hepatic metastases.

  12. Combination of radiotherapy and selective chemotherapy in the treatment of advanced ovarian carcinomas

    International Nuclear Information System (INIS)

    Dietz, R.; Brachetti, A.; Universitaet des Saarlandes, Homburg/Saar

    1982-01-01

    A report is given on 160 patients suffering from ovarian carcinomas the stages which were exactly determined by TNM classification. 32 patients had tumors of the stages T1-T3, 128 patients had tumors of the stage T4. All T3 subgroups showed favorable results after radical surgery and a postoperative combination of radiotherapy and selective cytostatic chemotherapy. The therapy plans including radiotherapy had more advantages than those without radiotherapy. Furthermore, the cytostatic treatment was more successful after a chemotherapy resistance test than after blind administration of cytostatic drugs. (orig.) [de

  13. CT-based patient modeling for head and neck hyperthermia treatment planning: manual versus automatic normal-tissue-segmentation.

    Science.gov (United States)

    Verhaart, René F; Fortunati, Valerio; Verduijn, Gerda M; van Walsum, Theo; Veenland, Jifke F; Paulides, Margarethus M

    2014-04-01

    Clinical trials have shown that hyperthermia, as adjuvant to radiotherapy and/or chemotherapy, improves treatment of patients with locally advanced or recurrent head and neck (H&N) carcinoma. Hyperthermia treatment planning (HTP) guided H&N hyperthermia is being investigated, which requires patient specific 3D patient models derived from Computed Tomography (CT)-images. To decide whether a recently developed automatic-segmentation algorithm can be introduced in the clinic, we compared the impact of manual- and automatic normal-tissue-segmentation variations on HTP quality. CT images of seven patients were segmented automatically and manually by four observers, to study inter-observer and intra-observer geometrical variation. To determine the impact of this variation on HTP quality, HTP was performed using the automatic and manual segmentation of each observer, for each patient. This impact was compared to other sources of patient model uncertainties, i.e. varying gridsizes and dielectric tissue properties. Despite geometrical variations, manual and automatic generated 3D patient models resulted in an equal, i.e. 1%, variation in HTP quality. This variation was minor with respect to the total of other sources of patient model uncertainties, i.e. 11.7%. Automatically generated 3D patient models can be introduced in the clinic for H&N HTP. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. CT-based patient modeling for head and neck hyperthermia treatment planning: Manual versus automatic normal-tissue-segmentation

    International Nuclear Information System (INIS)

    Verhaart, René F.; Fortunati, Valerio; Verduijn, Gerda M.; Walsum, Theo van; Veenland, Jifke F.; Paulides, Margarethus M.

    2014-01-01

    Background and purpose: Clinical trials have shown that hyperthermia, as adjuvant to radiotherapy and/or chemotherapy, improves treatment of patients with locally advanced or recurrent head and neck (H and N) carcinoma. Hyperthermia treatment planning (HTP) guided H and N hyperthermia is being investigated, which requires patient specific 3D patient models derived from Computed Tomography (CT)-images. To decide whether a recently developed automatic-segmentation algorithm can be introduced in the clinic, we compared the impact of manual- and automatic normal-tissue-segmentation variations on HTP quality. Material and methods: CT images of seven patients were segmented automatically and manually by four observers, to study inter-observer and intra-observer geometrical variation. To determine the impact of this variation on HTP quality, HTP was performed using the automatic and manual segmentation of each observer, for each patient. This impact was compared to other sources of patient model uncertainties, i.e. varying gridsizes and dielectric tissue properties. Results: Despite geometrical variations, manual and automatic generated 3D patient models resulted in an equal, i.e. 1%, variation in HTP quality. This variation was minor with respect to the total of other sources of patient model uncertainties, i.e. 11.7%. Conclusions: Automatically generated 3D patient models can be introduced in the clinic for H and N HTP

  15. Hyperthermia: clinical results

    International Nuclear Information System (INIS)

    Bicher, H.I.

    1982-01-01

    A large number of patients have now been entered into a phase I/II protocol to examine the effects of fractionated hyperthermia and radiation on tumor response. Included in the study were 11 different histologies with anatomical locations varying between peripheral and superficial metastases to deep-seated, solid tumors. Patients were treated with four fractions of microwave-induced hyperthermia (45.0 +- 0.5 0 C), each separated by intervals of 72 hours. Microwaves at frequencies of 915 MHz or 300 MHz were employed, Patients were given a one week rest following the first four treatments, following which a second series of four fractions were administered, again at 72 hour intervals. Each of these fractions consisted of a 400 rad dose of radiation followed within 20 min by hyperthermia (42.5 +- 5 0 C) for 1.5 hours. To date 121 fields have been treated by 82 patients. Total regression is seen in 65% of all cases, partial regression in 35% and no response is seen in only 5% of treatments. Adverse effects were rare. Site specific trials are currently in progress to study the feasibility of deep-seated heating with intracavitary antennae as well as to assess tumor response. In addition, a randomized trial to examine the clinical relevance of thermotolerance has been started

  16. Hyperthermia and radiotherapy

    International Nuclear Information System (INIS)

    Dietzel, F.

    1979-01-01

    Of decisive importance for superadditive enhancement is the close temporal correlation of hyperthermia and radiotherapy. It is recommended to first irradiate and then use heat treatment in order to ensure that dividable tumour cells are irradiated before hyperthermia. To achieve an optimal enhancing effect, temperatures of appr. 42 0 are sufficient. In order to be able to neglect temperature regulation and convection effects, hyperthermia for clinical use must be carried out in doses high enough to ensure that it can be finished within 3-4 minutes. It is necessary to make efforts to find out which forms of application can be realised in order to reach deeper tissue regions, thus making possible at least a half-depth-therapy. Up to day, only the 2 cm near to the surface can be heated in a sufficiently homogeneous way. In the FRG, there are more than 200 high-volt-therapy systems, including electron accelerators and telegamma systems. This is a dense network of radiation-therapeutical supply. An improved therapy effect of loose ionising rays which, with the help of the hypertherming, would almost be equal to irradiation with high ionisation density, is not only of scientific interest, but also of high interest for public health. (orig./MG) 891 MG/orig.- 892 RDG [de

  17. The Efficacy of Synchronous Combination of Chemotherapy and EGFR TKIs for the First-Line Treatment of NSCLC: A Systematic Analysis.

    Directory of Open Access Journals (Sweden)

    Han Yan

    Full Text Available The combination of chemotherapy and epidermal growth factor receptor (EGFR tyrosine kinase inhibitors (TKIs currently has become the hotspot issue in the treatment of non-small lung cancer (NSCLC. This systematic review was conducted to compare the efficacy and safety of the synchronous combination of these two treatments with EGFR TKIs or chemotherapy alone in advanced NSCLC.EMBASE, PubMed, the Central Registry of Controlled Trials in the Cochrane Library (CENTRAL, Chinese biomedical literature database (CNKI and meeting summaries were searched. The Phase II/III randomized controlled trials were selected by which patients with advanced NSCLC were randomized to receive a combination of EGFR TKIs and chemotherapy by synchronous mode vs. EGFR TKIs or chemotherapy alone.A total of six randomized controlled trials (RCTs including 4675 patients were enrolled in the systematic review. The meta-analysis demonstrated that the synchronous combination group of chemotherapy and EGFR TKIs did not reach satisfactory results; there was no significant difference in overall survival (OS, time to progression (TTP and objective response rate (ORR, compared with monotherapy (OS: HR = 1.05, 95%CI = 0.98-1.12; TTP: HR = 0.94, 95%CI = 0.89-1.00; ORR: RR = 1.07, 95%CI = 0.98-1.17, and no significant difference in OS and progression-free survival (PFS, compared with EGFR TKIs alone (OS: HR = 1.10, 95% CI = 0.83-1.46; PFS: HR = 0.86, 95% CI = 0.67-1.10. The patients who received synchronous combined therapy presented with increased incidences of grade 3/4 anemia (RR = 1.40, 95% CI = 1.10-1.79 and rash (RR = 7.43, 95% CI = 4.56-12.09, compared with chemotherapy, grade 3/4 anemia (RR = 6.71, 95% CI = 1.25-35.93 and fatigue (RR = 9.60, 95% CI = 2.28-40.86 compared with EGFR TKI monotherapy.The synchronous combination of chemotherapy and TKIs is not superior to chemotherapy or EGFR TKIs alone for the first-line treatment of NSCLC.

  18. Formula to estimate the thermal enhancement ratio of a single simultaneous hyperthermia and radiation treatment

    International Nuclear Information System (INIS)

    Overgaard, J.

    1984-01-01

    An experimental model composed of a C 3 H mammary carcinoma and its surrounding skin has been exposed to simultaneous radiation and hyperthermia given with different combinations of the heating time and temperature. Based on the thermal enhancement ratio (TER) values obtained in the temperature range 41.5 to 43.5 0 C, a linear relationship between TER and the heating time was achieved at each temperature. The slopes of the curves drawn at each temperature were found to have a log-linear relationship with the treatment temperature. With these relationships it was possible to make a formula expressing the TER as a function of treatment temperature and time. This formula gives a crude but probably acceptable estimate of the TER following a single simultaneous radiation and heat treatment. Although subject to several limitations, the formula represents an attempt to describe a heat dose concept for the radiosensitizing effect of hyperthermia. This may be useful to establish the tolerance level of a given radiation treatment when combined with hyperthermia. (Auth.)

  19. Hyperthermia: Clinical promise and current challenges

    International Nuclear Information System (INIS)

    Kapp, D.S.

    1987-01-01

    Local-regional hyperthermia (HT) when used in conjunction with radiation therapy (XRT), has been shown in numerous clinical trials to result in considerable improvement in response rates and local tumor control rates when compared with treatment by XRT alone. Although considerable progress has been made in understanding the biological basis for hyperthermia induced cytotoxicity and radiosensitization, additional research remains in establishing the optimal treatment schedules for the clinical utilization of HT-XRT. The number of HT treatments; the sequencing of HT and XRT; the frequency of administration of HT; and the ideal temperature-time parameters all remain to be better defined for the clinical setting. The role of tumor blood flow on the thermal distributions also warrants further investigation. In addition, considerable effort is needed to improve hyperthermia equipment in order to provide more uniform therapeutic temperature distributions (temperatures ≥42.5%C). Better heating equipment is particularly needed for the treatment of deep seeted tumors. Pertinent clinical literature will be presented summarizing the clinical promise of hyperthermia and the above mentioned clinical challenges

  20. Combination of chemotherapy, radiotherapy and surgery in the treatment of oral cancer

    International Nuclear Information System (INIS)

    Ayyagiri, S.; Gupta, B.D.; Dutta, T.K.

    1980-01-01

    In locally advanced oral cancer, the main modalities of treatment, e.g. surgery and radiotherapy, most often fail to control the disease when used singly. A combination policy of surgery and radiotherapy achieves adequate control of the disease. In order to improve the results in advanced oral cancer, chemotherapy given prior to and during radiation treatment and judicious combination of surgery offer the best possible approach in the management. The experience in the combination policy in the treatment of oral cancer in Northern India is dealt with. (auth.)

  1. Malignant Esophagogastric Junction Obstruction: Efficacy of Balloon Dilation Combined with Chemotherapy and/or Radiation Therapy

    International Nuclear Information System (INIS)

    Ko, Gi-Young; Song, Ho-Young; Hong, Heuk-Jin; Sung, Kyu-Bo; Seo, Tae-Seok; Yoon, Hyun-Ki

    2003-01-01

    Purpose: To assess the efficacy of balloon dilation combined with chemotherapy and/or radiation therapy for palliation of dysphagia due to malignant esophagogastric junction strictures. Methods: Fluoroscopically guided balloon dilation was attempted in 20 patients. The causes of strictures were gastric adenocarcinoma (n = 10) and esophageal squamous cell carcinoma (n = 10). Scheduled chemotherapy and/or radiation therapy followed balloon dilation in all patients. Results: There were no technical failures or major complications. After balloon dilation, 15 (75%) patients showed improvement of dysphagia. No patient complained of reflux esophagitis during the follow-up period. Among the 15 patients, seven needed no further treatment for palliation of dysphagia until their deaths. The remaining eight patients underwent repeat balloon dilation(n = 4) or stent placement (n = 4)3-43 weeks (mean 15 weeks) after the initial balloon dilation because of recurrent dysphagia. Conclusion: Balloon dilation combined with chemotherapy and/or radiation therapy seems to be an easy and reasonably effective palliative treatment for malignant esophagogastric strictures

  2. Developing a theoretical predictive model for cellular response to combined actions of low radiation and hyperthermia

    International Nuclear Information System (INIS)

    Jin Kyu Kim; Petin, V.G.; Mishra, K.P.

    2007-01-01

    Complete text of publication follows. Background: Organisms in their living environment are not exposed to merely a single stress agent. Several factors such as radiation and heat may simultaneously exert their stressful effect to the organisms. The combined exposure to two stressors can result in an enhanced effect that would be expected from the addition of the separate exposures to individual agents. Objective: This study has been undertaken to develop a theoretical model for assessment of combined effects of low dose radiation and mild heat for predictive cellular response assay. Rationale: Present study was motivated from the belief that synergism may occur in terms of lethal lesions arising from the interaction of non-lethal sub-lesions induced by individual agents. The sub-lesions induced by each agent may be negligible or undetectable. But, there exists a possibility of some cross talk between sublesions produced by radiation and heat. These processes may reflect the real mechanisms for inflicting the lethal damage by otherwise ignorable or undetectable insults to exposed organisms. Results: A theoretically developed mathematical model of the synergy was formulated which was tested for validation on the experimental data. The model predictions fairly closely corresponded with several experimental results. .The significance of synergistic effects for radiation biology has been demonstrated. A number of common peculiarities of synergistic interactions were found to play their roles. A unified biophysical concept for synergistic interaction has been suggested. Conclusions: For a constant dose rate, synergistic interaction between radiation and hyperthermia especially at low intensity is realized only within a certain range of temperature, independently of the target object analyzed. For temperatures below the range, the synergistic effect was not observed and cell killing was mainly determined by the damage induced by ionizing radiation. On the contrary, the

  3. Low dose combined chemotherapy/radiotherapy in the management of locally advanced urethral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Johnson, D.W.; Kessler, J.F.; Ferrigni, R.G.; Anderson, J.D.

    1989-01-01

    The successful treatment of a patient with bulky squamous cell carcinoma of the urethra using low dose preoperative radiation therapy and concurrent chemotherapy is described. Dramatic rapid tumor response facilitated surgical resection of the remaining microscopic disease. This clinical behavior is remarkably similar to that seen with squamous cell carcinoma of the anal canal and esophagus when a similar regimen is used. At the latter tumor sites the successful use of combination radiotherapy and chemotherapy has reduced the morbidity of subsequent surgery, and in selected cases has obviated the need for a radical operation. Further investigation of such combination treatment is warranted for urethral carcinoma

  4. Neuronal Rat Brain Damage Caused by Endogenous and Exogenous Hyperthermia

    Directory of Open Access Journals (Sweden)

    Mustafa Aydın

    2012-03-01

    Full Text Available OBJECTIVE: Hyperthermia may induce pathologic alterations within body systems and organs including brain. In this study, neuronal effects of endogenous and exogenous hyperthermia (41°C were studied in rats. METHODS: The endogenous hyperthermia (41°C was induced by lipopolysaccharide and the exogenous by an (electric heater. Possible neuronal damage was evaluated by examining healthy, apoptotic and necrotic cells, and heat shock proteins (HSP 27, HSP 70 in the cerebral cortex, cerebellum and hypothalamus RESULTS: At cellular level, when all neuronal tissues are taken into account; (i a significant increase in the necrotic cells was observed in the both groups (p0.05. CONCLUSION: The neural tissue of brain can show different degree of response to hyperthermia. But we can conclude that endogenous hyperthermia is more harmful to central nervous system than exogenous hyperthermia

  5. Peritoneal metastases of colorectal origin - cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). The financial aspect.

    Science.gov (United States)

    Jastrzębski, Tomasz; Bębenek, Marek

    2017-12-30

    The incidence of peritoneal carcinomatosis of colorectal cancer amounts to 5%-15% for synchronous metastases and as much as 40% in cases of local recurrence. Best results are obtained for cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC). This treatment offers much better outcomes, leading to 5-year survival rates of as much as 30%-50%. The procedures require significant experience in abdominal surgery, are time-consuming (mean duration of the procedure ranging from 6 to 8 hours) and are burdened by complications that are due not only to the procedure itself but also to the intraperitoneal administration of the cytostatic drug at elevated temperature (41.5 °C). After the procedure, patients are required to be admitted to intensive care units due to potential complications associated with the extent and duration of the procedure as well as chemotherapy administered in hyperthermia. Postoperative management of these patients requires appropriate experience of the entire medical and nursing team. Cytoreductive surgeries combined with HIPEC as highly specialized medical procedures should be assessed for their potential long-term benefits and their costs should be appropriately calculated with consideration to realistic reimbursement rates. Realistic valuation and reimbursement covering the overall average cost of the procedure is recommended by the National Consultant in Surgical Oncology as well as the ESMO consensus guidelines.

  6. Acute whole-body cooling for exercise-induced hyperthermia: a systematic review.

    Science.gov (United States)

    McDermott, Brendon P; Casa, Douglas J; Ganio, Matthew S; Lopez, Rebecca M; Yeargin, Susan W; Armstrong, Lawrence E; Maresh, Carl M

    2009-01-01

    To assess existing original research addressing the efficiency of whole-body cooling modalities in the treatment of exertional hyperthermia. During April 2007, we searched MEDLINE, EMBASE, Scopus, SportDiscus, CINAHL, and Cochrane Reviews databases as well as ProQuest for theses and dissertations to identify research studies evaluating whole-body cooling treatments without limits. Key words were cooling, cryotherapy, water immersion, cold-water immersion, ice-water immersion, icing, fanning, bath, baths, cooling modality, heat illness, heat illnesses, exertional heatstroke, exertional heat stroke, heat exhaustion, hyperthermia, hyperthermic, hyperpyrexia, exercise, exertion, running, football, military, runners, marathoner, physical activity, marathoning, soccer, and tennis. Two independent reviewers graded each study on the Physiotherapy Evidence Database (PEDro) scale. Seven of 89 research articles met all inclusion criteria and a minimum score of 4 out of 10 on the PEDro scale. After an extensive and critical review of the available research on whole-body cooling for the treatment of exertional hyperthermia, we concluded that ice-water immersion provides the most efficient cooling. Further research comparing whole-body cooling modalities is needed to identify other acceptable means. When ice-water immersion is not possible, continual dousing with water combined with fanning the patient is an alternative method until more advanced cooling means can be used. Until future investigators identify other acceptable whole-body cooling modalities for exercise-induced hyperthermia, ice-water immersion and cold-water immersion are the methods proven to have the fastest cooling rates.

  7. Rib fractures after reirradiation plus hyperthermia for recurrent breast cancer: Predictive factors

    NARCIS (Netherlands)

    Oldenborg, Sabine; Valk, Christel; van Os, Rob; Oei, Bing; Venselaar, Jack; Vörding, Paul Zum Vörde Sive; van Randen, Adriënne; Crezee, Hans; van Tienhoven, Geertjan; Rasch, Coen

    2016-01-01

    Combining reirradiation (reRT) and hyperthermia (HT) has shown high therapeutic value for patients with locoregional recurrent breast cancer (LR). However, additional toxicity of reirradiation (e.g., rib fractures) may occur. The aim of this study is to determine the impact of potential risk factors

  8. Combination of chemotherapy and heavy-ion particle therapy for gastrointestinal cancer

    International Nuclear Information System (INIS)

    Yamada, Shigeru; Kitabayashi, Hiroyuki; Furusawa, Yoshiya; Ando, Koichi

    2005-01-01

    The purpose of this study is to investigate the combination of chemotherapy and heavy-ion particle therapy for pancreas and esophageal cancer. We measured surviving fractions in four culture pancreas and esophageal cancer cells. The cell killing of heavy-ion irradiation is more effective compared to that of X ray irradiation. Gemcitabine induced radiosensitization for pancreas cancer cells and also taxotel for esophageal cancer. (author)

  9. Transarterial infusion chemotherapy combined with high intensity focused ultrasound for the treatment of pancreatic carcinomas: a clinical study

    International Nuclear Information System (INIS)

    Zhang Yiping; Zhao Jingzhi; Qiao Xinrong; Huang Hankui

    2011-01-01

    Objective: To assess the clinical value of transarterial infusion chemotherapy combined with high intensity focused ultrasound (HIFU) for the treatment of pancreatic carcinomas. Methods: A total of 64 patients with inoperable pancreatic carcinomas were randomly divided into study group (n=32) and control group (n=32). Transarterial infusion chemotherapy combined with HIFU was employed in patients of study group, while simple transarterial infusion chemotherapy was conducted in patients of control group. The effective rate, the clinical benefit rate (CBR), the occurrence of side effect and the survival time of the two groups were recorded. The results were compared between the two groups. Results: The effective rate (PR + MR), the median survival time and the one-year survival rate of the study group were 55.56%, 13.0 months and 68.75% respectively, while the effective rate (PR + MR), the median survival time and the one-year survival rate of the control group were 28.57%, 9.0 months and 43.75% respectively. Both the effective rate and the one-year survival rate of the study group were significantly higher than those of the control group (P<0.05). Conclusion: Compared with pure transarterial infusion chemotherapy, transarterial infusion chemotherapy combined with HIFU can significantly improve the short-term efficacy and increase the one-year survival rate for patients with advanced pancreatic carcinomas. (authors)

  10. Meta-analysis of gemcitabine and cisplatin combination chemotherapy versus gemcitabine alone for pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Diyu Huang

    2016-01-01

    Conclusions: Overall response rate, stable disease, and progressive disease, as well as 1-year survival rate in patients who received GEM + CIS, were superior to those treated with GEM alone. Combination chemotherapy with GEM and CIS may offer greater benefits in the treatment of pancreatic cancer than that of GEM alone although the combination group had higher hematological toxicities.

  11. Morphologic alterations in normal and neoplastic tissues following hyperthermia treatment

    International Nuclear Information System (INIS)

    Badylak, S.F.; Babbs, C.F.

    1984-01-01

    The sequential morphologic alterations in normal skeletal muscle in rats, Walker 256 tumors in rats, and transmissible venereal tumors (TVT) in dogs following microwave-induced hyperthermia (43 0 C and 45 0 for 20 minutes) were studied by light and electron microscopy. Normal muscle and Walker 256 tumors showed vascular damage at 5 minutes post-heating (PH), followed by suppuration and thrombosis at 6 and 48 hours PH, and by regeneration and repair at 7 days PH. Endothelial damage and parenchymal degeneration were present 5 minutes PH. Progressive ischemic injury occurred for at least 48 hours PH. Two hyperthermia treatments, separated by a 30 or 60 minute cooling interval, were applied to rats implanted with Walker 256 tumors. Increased selective heating of tumor tissue versus surrounding normal tissue, and increased intratumoral temperatures were found during the second hyperthermia treatment. Canine TVTs were resistant to hyperthermia damage. These results characterized the sequential morphologic alterations following hyperthermia treatment and showed that: 1) vascular damage contributed to the immediate and latent cytotoxic effects of hyperthermia, 2) selective heating occurred in the neoplastic tissue disrupted by prior heat treatment, and 3) not all neoplasms are responsive to hyperthermia treatment

  12. Desoxyribonucleic acid (DNA) synthesis in vitro by thymus and spleen cells of the rat after hyperthermia

    Energy Technology Data Exchange (ETDEWEB)

    Tempel, K.; Spath, A.

    1988-03-01

    The inhibition of the semiconservative and restorative DNA synthesis caused by hyperthermia (30 to 60 min, 43/sup 0/C) was significantly higher in spleen cells than in thymus cells. The DNA repair synthesis of thymus cells measured at 37/sup 0/C was increased by about two times the initial value after a pre-incubation of 30 to 90 min and 30 to 60 min, respectively, with 37 and 43/sup 0/C, respectively. Under the same conditions, the /sup 3/H-thymidine incorporation into the DNA of spleen cells diminished proportionally to the pre-incubation time after a pre-incubation of 30 and 45 min, respectively, with 43 and 37/sup 0/C, respectively. When hyperthermia and inhibitors of DNA synthesis or DNA repair (hydroxyurea, 1-..beta..-D-arabinofuranosylcytosine, 3', 5'-didesoxythymidine, and 3-aminobenzamide) were combined, overadditive effects - without cellspecific particularities - were seen only in the case of 3-aminobenzamide. Only in thymus cells, the inhibitor of DNA topoisomerase II novobiocin caused an overadditive reinforcement of the inhibition induced by hyperthermia of the semiconservative DNA synthesis. The stimulation of DNA repair synthesis in thymus cells caused by novobiocin with the aid of DNA polymerase ..beta.. could be compensated by hyperthermia. The sedimentation of thymus and spleen cell nucleoids was increased after hyperthermia. The results suggest a special importance of DNA topology and of the DNA polymerase ..beta.. activity for the cellular effect of hyperthermia.

  13. Jianpi Bushen, a Traditional Chinese Medicine Therapy, Combined with Chemotherapy for Gastric Cancer Treatment: A Meta-Analysis of Randomized Controlled Trials

    Science.gov (United States)

    Chen, Yunbo; Zhang, Guijuan; Chen, Xiaoping; Jiang, Xuefeng; Yuan, Naijun; Wang, Yurong; Hao, Xiaoqian

    2018-01-01

    Objective. To investigate the effects of Jianpi Bushen (JPBS), a traditional Chinese medicine that is used to invigorate the spleen and tonify the kidney, combined with chemotherapy for the treatment of gastric cancer. Methods. Literature retrieval was performed in PubMed, EMBASE, Cochrane Library, MEDLINE, CNKI, Wanfang Data Information Site, and VIP from inception to October 2017. Randomized controlled trials to evaluate the effects of JPBS combined with chemotherapy were identified. The primary reported outcomes were KPS (Karnofsky Performance Status), clinical curative efficiency, immune function, blood system, and nonhematologic system. Review Manager 5.3 (RevMan 5.3) was used for data analysis, and the quality of the studies was also appraised. Results. A total of 26 studies were included with 3098 individuals. The results of the meta-analysis indicated that treatment of gastric cancer with the combination of JPBS and chemotherapy resulted in better outcomes compared to chemotherapy alone. Conclusion. Evidence from the meta-analysis suggested that JPBS combined with chemotherapy has a positive effect on gastric cancer treatment. However, additional rigorously designed and large sample randomized controlled trials are required to confirm the efficacy and safety of this treatment. PMID:29675052

  14. Gold nanorod-mediated hyperthermia enhances the efficacy of HPMA copolymer-90Y conjugates in treatment of prostate tumors

    International Nuclear Information System (INIS)

    Buckway, Brandon; Frazier, Nick; Gormley, Adam J.; Ray, Abhijit; Ghandehari, Hamidreza

    2014-01-01

    Introduction: The treatment of prostate cancer using a radiotherapeutic 90 Y labeled N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer can be enhanced with localized tumor hyperthermia. An 111 In labeled HPMA copolymer system for single photon emission computerized tomography (SPECT) was developed to observe the biodistribution changes associated with hyperthermia. Efficacy studies were conducted in prostate tumor bearing mice using the 90 Y HPMA copolymer with hyperthermia. Methods: HPMA copolymers containing 1, 4, 7, 10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) were synthesized by reversible addition-fragmentation transfer (RAFT) copolymerization and subsequently labeled with either 111 In for imaging or 90 Y for efficacy studies. Radiolabel stability was characterized in vitro with mouse serum. Imaging and efficacy studies were conducted in DU145 prostate tumor bearing mice. Imaging was performed using single photon emission computerized tomography (SPECT). Localized mild tumor hyperthermia was achieved by plasmonic photothermal therapy using gold nanorods. Results: HPMA copolymer-DOTA conjugates demonstrated efficient labeling and stability for both radionuclides. Imaging analysis showed a marked increase of radiolabeled copolymer within the hyperthermia treated prostate tumors, with no significant accumulation in non-targeted tissues. The greatest reduction in tumor growth was observed in the hyperthermia treated tumors with 90 Y HPMA copolymer conjugates. Histological analysis confirmed treatment efficacy and safety. Conclusion: HPMA copolymer-DOTA conjugates radiolabeled with both the imaging and treatment radioisotopes, when combined with hyperthermia can serve as an image guided approach for efficacious treatment of prostate tumors

  15. Comparative analyses of the effect of radiotherapy and chemotherapy or chemotherapy alone on patients' electrocardiogram

    International Nuclear Information System (INIS)

    Liang Li; Zhang Shulan; Zhang Zhaohui; Wang Junjie; Jia Tingzhen

    2005-01-01

    Objective: To investigate the change of breast cancer patients' electrocardiogram during combined radiotherapy and chemotherapy or chemotherapy alone for the sake of predicting the cardiotoxicity of combined radiotherapy and chemotherapy. Methods: From January, 1998 to June, 2004, 47 postoperative breast cancer patients were enrolled. Among them 29 patients received chemotherapy combined with radiotherapy (combinative group), and 18 patients received chemotherapy alone (non combinative group). The changes of electrocardiogram were observed and correlation factors were analyzed. Results: Abnormal electrocardiograms were noted in 11 (37.9%) and 2 patients (11.1%) of the combinative group and the non-combinative group respectively(z=-1.977, P=0.048). In the combinative group, heart events were significantly increased in patients above 60 years old (z=- 2.094 P=0.036). The changes of electrocardiogram were not significantly correlative with hypertension history, tumor site, dose of radiotherapy or chemotherapeutic drugs. But the incidence of abnormal electrocardiogram was higher in patients with a hypertension history than in those without it (54.5% vs 27.8%). Conclusion: The abnormalities of electrocardiogram were are more frequent in patients treated with both radiotherapy combined with chemotherapy. Our results suggest that breast cancer patients should be regularly reexamined with electrocardiography during therapy, especially whose age was those have a hypertension history and above 60 years old. (authors)

  16. Induction chemotherapy combined with three-dimensional conformal radiation therapy for locally advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Zheng Aiqing; Yu Jinming; Zhao Xianguang; Wang Xuetao; Wei Guangsheng

    2005-01-01

    Objective: To evaluate the effect and complication of induction chemotherapy combined with three-dimensional conformal radiation therapy (3DCRT) for locally advanced non small cell lung cancer (NSCLC). Methods: Ninety-two such patients were randomized into radiation therapy alone group(RT-, 50 patients) and induction chemotherapy combined radiotherapy group (CMT-, 42 patients). The induction chemotherapy consisted of 2-4 cycles of platinum-based regimen. Results: The overall median survival time was 15 months with 12 months in the RT group and 18 months in the CMT group (P=0.014) respectively. The 1-year overall survival rates were 48.6% and 71.2% in RT and CMT group, respectively (P=0.004). The 2-year survival rates were 20.8% and 37.6% in RT and CMT group, respectively (P=0.041). Treatment was well tolerated and the toxicities were similar in either group. Conclusion: The addition of induction chemotherapy to 3DCRT takes a survival advantage over 3DCRT alone for Stage III NSCLC without increasing toxicities. (authors)

  17. Doxorubicin loaded magnetic polymersomes: theranostic nanocarriers for MR imaging and magneto-chemotherapy.

    Science.gov (United States)

    Sanson, Charles; Diou, Odile; Thévenot, Julie; Ibarboure, Emmanuel; Soum, Alain; Brûlet, Annie; Miraux, Sylvain; Thiaudière, Eric; Tan, Sisareuth; Brisson, Alain; Dupuis, Vincent; Sandre, Olivier; Lecommandoux, Sébastien

    2011-02-22

    Hydrophobically modified maghemite (γ-Fe(2)O(3)) nanoparticles were encapsulated within the membrane of poly(trimethylene carbonate)-b-poly(l-glutamic acid) (PTMC-b-PGA) block copolymer vesicles using a nanoprecipitation process. This formation method gives simple access to highly magnetic nanoparticles (MNPs) (loaded up to 70 wt %) together with good control over the vesicles size (100-400 nm). The simultaneous loading of maghemite nanoparticles and doxorubicin was also achieved by nanoprecipitation. The deformation of the vesicle membrane under an applied magnetic field has been evidenced by small angle neutron scattering. These superparamagnetic hybrid self-assemblies display enhanced contrast properties that open potential applications for magnetic resonance imaging. They can also be guided in a magnetic field gradient. The feasibility of controlled drug release by radio frequency magnetic hyperthermia was demonstrated in the case of encapsulated doxorubicin molecules, showing the viability of the concept of magneto-chemotherapy. These magnetic polymersomes can be used as efficient multifunctional nanocarriers for combined therapy and imaging.

  18. Photoacoustic-Based-Close-Loop Temperature Control for Nanoparticle Hyperthermia.

    Science.gov (United States)

    Xiaohua, Feng; Fei, Gao; Yuanjin, Zheng

    2015-07-01

    Hyperthermia therapy requires tight temperature control to achieve selective killing of cancerous tissue with minimal damage on surrounding healthy tissues. To this end, accurate temperature monitoring and subsequent heating control are critical. However, an economic, portable, and real-time temperature control solution is currently lacking. To bridge this gap, we present a novel portable close-loop system for hyperthermia temperature control, in which photoacoustic technique is proposed for noninvasive real-time temperature measurement. Exploiting the high sensitivity of photoacoustics, the temperature is monitored with an accuracy of around 0.18 °C and then fed back to a controller implemented on field programmable gate array (FPGA) for temperature control. Dubbed as portable hyperthermia feedback controller (pHFC), it stabilizes the temperature at preset values by regulating the hyperthermia power with a proportional-integral-derivative (PID) algorithm; and to facilitate digital implementation, the pHFC further converts the PID output into switching values (0 and 1) with the pulse width modulation (PWM) algorithm. Proof-of-concept hyperthermia experiments demonstrate that the pHFC system is able to bring the temperature from baseline to predetermined value with an accuracy of 0.3° and a negligible temperature overshoot. The pHFC can potentially be translated to clinical applications with customized hyperthermia system design. This paper can facilitate future efforts in seamless integration of close-loop temperature control solution and various clinical hyperthermia systems.

  19. The Role of Bcl-xL in Synergistic Induction of Apoptosis by Mapatumumab and Oxaliplatin in Combination with Hyperthermia on Human Colon Cancer

    Science.gov (United States)

    Song, Xinxin; Kim, Seog-Young; Lee, Yong J.

    2012-01-01

    Colorectal cancer is the third leading cause of cancer-related mortality in the world. The main cause of death of colorectal cancer is hepatic metastases which can be treated using isolated hepatic perfusion (IHP), allowing treatment of colorectal metastasis with various methods. In this study we present a novel potent multimodality strategy comprising humanized death receptor 4 (DR4) antibody mapatumumab (Mapa) in combination with oxaliplatin and hyperthermia to treat human colon cancer cells. Oxaliplatin and hyperthermia sensitized colon cancer cells to Mapa in the mitochondrial dependent apoptotic pathway and increased reactive oxygen species production, leading to Bcl-xL phosphorylation at Serine 62 in a c-Jun N-terminal kinase (JNK)-dependent manner. Overexpression of Bcl-xL reduced the efficacy of the multimodality treatment, while phosphorylation of Bcl-xL decreased its anti-apoptotic activity. The multimodality treatment dissociated Bcl-xL from Bax, allowing Bax oligomerization to induce cytochrome c release from mitochondria. In addition, the multimodality treatment significantly inhibited colorectal cancer xenografts’ tumor growth. The successful outcome of this study will support the application of multimodality strategy to colorectal hepatic metastases. PMID:23051936

  20. Combined chemotherapy and radiotherapy in recurrent tumors of the head and neck region

    International Nuclear Information System (INIS)

    Tsuji, Hiroshi; Tsujii, Hirohiko; Kamada, Tadashi; Takamura, Akio; Shirato, Hiroki; Matsuoka, Yoshisuke; Irie, Goro

    1987-01-01

    Over the past four years, 27 patients with recurrent tumors of the head and neck region have been treated with chemotherapy. The regimens used were BCMF (bleomycin 15 mg i.v. for 3 days, cyclophosphamide 500 mg i.v., methotrexate 50 mg i.v. and 5-fluorouracil 500 mg i.v.) and CMU (cyclophosphamide 350 mg/m 2 i.v., methotrexate 30 mg/m 2 i.v. and UFT 600 mg p.o. for 14 days). Of the 27 patients, eight were treated with combined radiation and chemotherapy, and either CR or PR was obtained. Nineteen patients were treated with chemotherapy alone, for which the response (CR + PR) rates were 8 % (1/12) for BCMF and 43 % (3/7) for CMU, respectively. No serious toxicities were observed as a result of these regimens. It was thus demonstrated that the CMU regimen was of great value in terms of improved response and minor toxicity in the treatment of head and neck tumors. (author)

  1. Combination chemotherapy versus single-agent therapy as first- and second-line treatment in metastatic breast cancer

    DEFF Research Database (Denmark)

    Joensuu, H; Holli, K; Heikkinen, M

    1998-01-01

    PURPOSE: We report results of a randomized prospective study that compared single agents of low toxicity given both as the first-line and second-line chemotherapy with combination chemotherapy in advanced breast cancer with distant metastases. PATIENTS AND METHODS: Patients in the single-agent arm...... (n = 153) received weekly epirubicin (E) 20 mg/m2 until progression or until the cumulative dose of 1,000 mg/m2, followed by mitomycin (M) 8 mg/m2 every 4 weeks, and those in the combination chemotherapy arm (n = 150) were first given cyclophosphamide 500 mg/m2, E 60 mg/m2, and fluorouracil 500 mg/m2...... younger than 50. RESULTS: An objective response (complete [CR] or partial [PR]) was obtained in 55%, 48%, 16%, and 7% of patients treated with CEF, E, M, and MV, respectively. A response to CEF tended to last longer than a response to E (median, 12 v 10.5 months; P = .07). Treatment-related toxicity...

  2. Effects of hyperthermia and x irradiation on sister chromatid exchange (SCE) frequency in Chinese hamster ovary (CHO) cells

    International Nuclear Information System (INIS)

    Livingston, G.K.; Dethlefsen, L.A.

    1979-01-01

    The BrdUrd labeling method was used to evaluate the effects of hyperthermia, x irradiation, and the combined treatment on the incidence of sister chromatid exchange (SCE) in Chinese hamster ovary (CHO) cells. Cells cultured in McCoy's 5A media containing 10 μM 5-bromodeoxyuridine were synchronized after one cell cycle by mitotic shake-off. Early-G 1 cells were heated by submerging culture flasks in a 44 +- 0.05 0 C water bath for periods of 20, 40, and 60 min. By the same method, other cultures were x irradiated at doses of 100, 200, 400, and 600 rad. A third protocol involved combined treatment of 20 min at 44 0 C followed immediately by one of the above radiation doses. A fourth protocol reversed the sequence of the combined treatment applying x irradiation (200 or 400 rad) followed immediately by hyperthermia. The data showed that hyperthermia and x irradiation both elevated the frequency of SCEs significantly whether applied separately or together. The combined treatment (heat: 20 min at 44 0 C plus varying x-radiation doses) produced results suggestive of a synergistic interaction. The sequence of the heat and x irradiation did not appear to have a significant effect on the production of SCE

  3. Investigation properties of superparamagnetic nanoparticles and magnetic field-dependent hyperthermia therapy

    Science.gov (United States)

    Hedayatnasab, Z.; Abnisa, F.; Daud, W. M. A. Wan

    2018-03-01

    The application of superparamagnetic nanoparticles as heating agents in hyperthermia therapy has made a therapeutic breakthrough in cancer treatment. The high efficiency of this magnetic hyperthermia therapy has derived from a great capability of superparamagnetic nanoparticles to generate focused heat in inaccessible tumors being effectively inactivated. The main challenges of this therapy are the improvement of the induction heating power of superparamagnetic nanoparticles and the control of the hyperthermia temperature in a secure range of 42 °C to 47 °C, at targeted area. The variation of these hyperthermia properties is principally dependent on the magnetic nanoparticles as well as the magnetic field leading to enhance the efficiency of magnetic hyperthermia therapy at targeted area and also avoid undue heating to healthy cells. The present study evaluates the magnetic hyperthermia therapy through the determination of superparamagnetic nanoparticles properties and magnetic field’ parameters.

  4. Effects of hyperthermia, x-ray irradiation and their combination on ascites tumor cells of mice

    International Nuclear Information System (INIS)

    Kaneko, Itsuo

    1982-01-01

    Fibrosarcoma ascites tumor cells (PB8) from NMRI mice were used to investigate cell loss by hyperthermia and/or x-ray irradiation. The tumor cells were labelled by an injection of 125 I-deoxyuridine to the abdominal cavity of the donors 2 days before the physical treatments. The labelled cells, transfered in test tubes, were heated at 44 0 C for 10-20 min and/or irradiated by x-ray at 250-1612 rad, and were transplanted in the recipient abdominal cavity as soon as possible after the treatments. The radioactivity of the tumor cells, as an indicator of cell loss, was measured with a gamma spectrometer. In the irradiated group, the ratio of cell loss increased in a dose-dependent manner, starting from the 4th day after the transplantation to the 9th day. In the heated group, the ratio of cell loss increased in proportion to the heating time, starting without delay after transplantation. In the combination group, the effect of the treatments was more marked than that by each single treatment. In the early stage of this group, cell loss was by heating and then, from the 4th day, the irradiation effect mostly dominated. It is concluded from the above results that cell loss by heating or irradiation is independent and that the effect of the combination is additive. (author)

  5. Metronomic Cyclophosphamide and Methotrexate Chemotherapy Combined with 1E10 Anti-Idiotype Vaccine in Metastatic Breast Cancer

    International Nuclear Information System (INIS)

    Soriano, J.L.; Batista, N.; Lima, M.; Gonzalez, J.; Garcia, R.; Zarza, Y.; Lopez, M.V.; Rodriguez, M.; Loys, J.L.; Montejo, N.; Santiesteban, E.; Aguirre, F.; Macias, A.; Vazquez, A.M.

    2011-01-01

    The use of low doses of cytotoxic agents continuously for prolonged periods is an alternative for the treatment of patients with metastatic breast cancer who have developed resistance to conventional chemotherapy. The combination of metronomic chemotherapy with therapeutic vaccines might increase the efficacy of the treatment. Twenty one patients with metastatic breast cancer in progression and a Karnosky index =60%, were treated with metronomic chemotherapy (50?mg of cyclophosphamide orally daily and 2.5 mg of methotrexate orally bi-daily), in combination with five bi-weekly subcutaneous injections of 1 mg of aluminum hydroxide-precipitated 1E10 anti-idiotype MAb (1E10-Alum), followed by re immunizations every 28 days. Five patients achieved objective response, eight showed stable disease and eight had disease progression. Median time to progression was 9,8 months, while median overall survival time was 12,93 months. The median duration of the response (CR+PR+SD) was 18,43 months (12,20-24,10 months), being higher than 12 months in 76,9% of the patients. Overall toxicity was generally mild. Metronomic chemotherapy combined with 1E10-Alum vaccine immunotherapy might be a useful therapeutic option for the treatment of metastatic breast cancer due to its potential impact on survival and patient quality of live, low toxicity and advantages of the administration.

  6. Combination chemotherapy concurrent with small dose radiation therapy for small cell carcinoma of the lung

    International Nuclear Information System (INIS)

    Tada, Toshihiko; Fujita, Hiroji; Shintomi, Takenori

    1987-01-01

    Forty consecutive patients with small cell carcinoma of the lung were treated with chemotherapy, radiotherapy or both. Of 34 patients treated with chemotherapy, 24 were treated with combination chemotherapy, containing cyclophosphamide vincristine methotrexate and procarbazine, concurrent with small dose radiation therapy (500 cGy/5 fraction) as a chemosensitizer (COMPrt). The response rate to this regimen was 81 % (29 % complete) and the 2 year survival rate was 28.6 %. These results have been superior to other regimens and the toxicity was not see to be any higher. After completion of COMPrt regimen, 10 patients were treated with intrathoracic radiation therapy (average dose 3000 cGy) and 3 recieved surgical treatment. Radiation therapy improved the 2-year survival rate (42.2 %) when compared with those patients who received no radiation therapy (18.2 %). Three patients received surgical treatment were considered to be disease-free for 23, 17, and 9 months respectively, after induction of chemotherapy. (author)

  7. Transarterial infusion chemotherapy with a combination of gemcitabine and 5-fluorouracil in advanced pancreatic carcinoma

    International Nuclear Information System (INIS)

    Shi Haifeng; Jin Zhengyu; Yang Ning; Liu Wei; Pan Jie; Cai Lixing; Zhao Yupei; Zhou Zhiqiang

    2002-01-01

    Objective: To retrospectively analyze the effectiveness of transarterial infusion chemotherapy of gemcitabine and 5-fluorouracil in advanced pancreatic carcinoma. Methods: Twenty-two patients with advanced pancreatic carcinoma were treated with transarterial infusion chemotherapy. Gemcitabine and 5-fluorouracil was administered to the patients via an interarterial catheter. Then the tumor response rate and clinical benefit were observed. Results: A clinical benefit was obtained in 8 patients (36.4%). The tumor response rate was 13.6%. Median survival for all the patients was 6.1 months. Median time to tumor progression was 2.9 months. Conclusion: Transarterial infusion chemotherapy with a combination of gemcitabine and 5-fluorouracil appears to have good clinical benefit and may prolong the survival time of patients with advanced pancreatic carcinoma

  8. Low-magnetization magnetic microcapsules: A synergistic theranostic platform for remote cancer cells therapy and imaging

    KAUST Repository

    Zhang, Wei; Deng, Lin; Wang, Guangchao; Guo, Xianrong; Li, Qiujin; Zhang, Jianfei; Khashab, Niveen M.

    2014-01-01

    Multifunctional magnetic microcapsules (MMCs) for the combined cancer cells hyperthermia and chemotherapy in addition to MR imaging are successfully developed. A classical layer-by-layer technique of oppositely charged polyelectrolytes (poly

  9. Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance in vitro.

    Science.gov (United States)

    Khdair, Ayman; Handa, Hitesh; Mao, Guangzhao; Panyam, Jayanth

    2009-02-01

    Drug resistance limits the success of many anticancer drugs. Reduced accumulation of the drug at its intracellular site of action because of overexpression of efflux transporters such as P-glycoprotein (P-gp) is a major mechanism of drug resistance. In this study, we investigated whether photodynamic therapy (PDT) using methylene blue, also a P-gp inhibitor, can be used to enhance doxorubicin-induced cytotoxicity in drug-resistant tumor cells. Aerosol OT (AOT)-alginate nanoparticles were used as a carrier for the simultaneous cellular delivery of doxorubicin and methylene blue. Methylene blue was photoactivated using light of 665 nm wavelength. Induction of apoptosis and necrosis following treatment with combination chemotherapy and PDT was investigated in drug-resistant NCI/ADR-RES cells using flow cytometry and fluorescence microscopy. Effect of encapsulation in nanoparticles on the intracellular accumulation of doxorubicin and methylene blue was investigated qualitatively using fluorescence microscopy and was quantitated using HPLC. Encapsulation in AOT-alginate nanoparticles significantly enhanced the cytotoxicity of combination therapy in resistant tumor cells. Nanoparticle-mediated combination therapy resulted in a significant induction of both apoptosis and necrosis. Improvement in cytotoxicity could be correlated with enhanced intracellular and nuclear delivery of the two drugs. Further, nanoparticle-mediated combination therapy resulted in significantly elevated reactive oxygen species (ROS) production compared to single drug treatment. In conclusion, nanoparticle-mediated combination chemotherapy and PDT using doxorubicin and methylene blue was able to overcome resistance mechanisms and resulted in improved cytotoxicity in drug-resistant tumor cells.

  10. Combination of chemotherapy, surgery and radiation in carcinoma ovary

    International Nuclear Information System (INIS)

    Dutta, T.K.; Mapa, M.K.; Gupta, B.D.; Dhall, G.I.

    1979-01-01

    The management of ovarian carcinoma is difficult mainly due to the fact that ovary, unlike other organs in the body remains the seat of wide variety of histological type of tumor with even wider biological behaviour and response to each modality of treatment. The objective of present paper is to evaluate the changing policy towards this tumor with emphasis on the combination plan in general and chemotherapy supplement in particular. Prognosis of advanced cancer which forms the bulk of the cases almost in every centre remains dismal. In this group of patients in a retrospective analysis, a guideline of treatment has been formulated. (auth.)

  11. Preclinical safety, toxicology, and biodistribution study of adenoviral gene therapy with sVEGFR-2 and sVEGFR-3 combined with chemotherapy for ovarian cancer.

    Science.gov (United States)

    Tuppurainen, Laura; Sallinen, Hanna; Kokki, Emmi; Koponen, Jonna; Anttila, Maarit; Pulkkinen, Kati; Heikura, Tommi; Toivanen, Pyry; Hämäläinen, Kirsi; Kosma, Veli-Matti; Heinonen, Seppo; Alitalo, Kari; Ylä-Herttuala, Seppo

    2013-03-01

    Abstract Antiangiogenic and antilymphangiogenic gene therapy with soluble vascular endothelial growth factor receptor-2 (VEGFR-2) and soluble VEGFR-3 in combination with chemotherapy is a potential new treatment for ovarian carcinoma. We evaluated the safety, toxicology, and biodistribution of intravenous AdsVEGFR-2 and AdsVEGFR-3 combined with chemotherapy in healthy rats (n=90) before entering a clinical setting. The study groups were: AdLacZ and AdLacZ with chemotherapy as control groups, low dose AdsVEGFR-2 and AdsVEGFR-3, high dose AdsVEGFR-2 and AdsVEGFR-3, combination of low dose AdsVEGFR-2 and AdsVEGFR-3 with chemotherapy, combination of high dose AdsVEGFR-2 and AdVEGFR-3 with chemotherapy, and chemotherapy only. The follow-up time was 4 weeks. Safety and toxicology were assessed by monitoring the clinical status of the animals and by histological, hematological, and clinical chemistry parameters. For the biodistribution studies, quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used. Low dose (2×10(10) vp) AdsVEGFR-2 and AdsVEGFR-3 gene therapy was well tolerated, even when gene therapy was combined with chemotherapy. Notably, only transient elevation of liver enzymes and mild regenerative changes were seen in liver after the gene transfer in the groups that received high doses (2×10(11) vp) of AdsVEGFR-2 and AdsVEGFR-3 with or without chemotherapy. No life-threatening adverse effects were noticed in any of the treatment groups. The highest protein concentration of soluble VEGFR-2 (sVEGFR-2) in circulation was seen 1 week after the gene transfer. The combination of chemotherapy to gene therapy seemed to prolong the time of detectable transgene protein at least 1 week in the circulation. The expression of AdsVEGFR-2 and AdsVEGFR-3 transgenes was mainly seen in the liver and spleen as detected by qRT-PCR. According to these results, AdsVEGFR-2 and AdsVEGFR-3 gene therapy combined with

  12. Pre- and Postoperative Chemotherapy in Localized Extremity Soft Tissue Sarcoma: A European Organization for Research and Treatment of Cancer Expert Survey.

    Science.gov (United States)

    Rothermundt, Christian; Fischer, Galina F; Bauer, Sebastian; Blay, Jean-Yves; Grünwald, Viktor; Italiano, Antoine; Kasper, Bernd; Kollár, Attila; Lindner, Lars H; Miah, Aisha; Sleijfer, Stefan; Stacchiotti, Silvia; Putora, Paul Martin

    2018-04-01

    The management of localized extremity soft tissue sarcomas (STS) is challenging and the role of pre- and postoperative chemotherapy is unclear and debated among experts. Medical oncology experts of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group were asked to participate in this survey on the use of pre- and postoperative chemotherapy in STS. Experts from 12 centers in Belgium, France, Germany, Great Britain, Italy, Switzerland, and The Netherlands agreed to participate and provided their treatment algorithm. Answers were converted into decision trees based on the objective consensus methodology. The decision trees were used as a basis to identify consensus and discrepancies. Several criteria used for decision-making in extremity STS were identified: chemosensitivity, fitness, grading, location, and size. In addition, resectability and resection status were relevant in the pre- and postoperative setting, respectively. Preoperative chemotherapy is considered in most centers for marginally resectable tumors only. Yet, in some centers, neoadjuvant chemotherapy is used routinely and partially combined with hyperthermia. Although most centers do not recommend postoperative chemotherapy, some offer this treatment on a regular basis. Radiotherapy is an undisputed treatment modality in extremity STS. Due to lacking evidence on the utility of pre- and postoperative chemotherapy in localized extremity STS, treatment strategies vary considerably among European experts. The majority recommended neoadjuvant chemotherapy for marginally resectable grade 2-3 tumors; the majority did not recommend postoperative chemotherapy in any setting. The management of localized extremity soft tissue sarcomas (STS) is challenging and the role of pre- and postoperative chemotherapy is unclear and debated among experts. This study analyzed the decision-making process among 12 European experts on systemic therapy for STS. A wide range of

  13. The comparative effect of wrapping solid gold nanoparticles and hollow gold nanoparticles with doxorubicin-loaded thermosensitive liposomes for cancer thermo-chemotherapy.

    Science.gov (United States)

    Li, Yanan; He, Dongsheng; Tu, Jiasheng; Wang, Ru; Zu, Chang; Chen, You; Yang, Wenqian; Shi, Di; Webster, Thomas J; Shen, Yan

    2018-04-26

    Since conventional chemotherapy is a systemic treatment that affects the body globally and will not concentrate inside the tumor, it causes adverse side effects to patients. In this study, doxorubicin (DOX) together with solid gold nanoparticles (GNPs) or hollow gold nanoparticles (HGNPs), respectively, is loaded inside thermosensitive liposomes (GNPs&DOX-TLs and HGNPs&DOX-TLs), where the GNPs and HGNPs act as a "nanoswitch" for killing tumor cells directly by hyperthermia and triggering DOX release from TLs in the tumor quickly by near infrared laser (NIR) illumination. In addition, this study investigated the photothermal transformation ability, NIR triggered drug release behavior, and the intracellular uptake and cytotoxicity of breast tumor cells and the thermo-chemotherapy mediated by the co-delivery of GNPs&DOX-TLs and HGNPs&DOX-TLs. GNPs and HGNPs had very different light-to-heat transduction efficiencies, while the hollow HGNPs had the advantage of NIR surface plasmon tunability, resulting in the photothermal ablation of tumors with 800 nm light penetration in tissue. The prepared HGNPs&DOX-TLs exhibited a spherical shape with a diameter of 190 nm and a ξ potential of -29 mV, which were steadily dispersed for at least one month. The co-encapsulated DOX was released under hyperthermia caused by NIR-responsive HGNPs and the local drug concentration increased along with the disintegration of the liposomal membrane. This co-delivery of HGNPs&DOX-TLs produced a synergistic cytotoxicity response, thereby enhancing anticancer efficacy 8-fold and increasing the survival time compared to GNPs&DOX-TLs. This work suggested that the co-delivery of HGNPs&DOX-TLs followed by burst-release of DOX using NIR-responsive HGNPs sensitized cancer cells to the chemotherapeutic compound, which provided a novel concept for the combination strategy of chemotherapy and photothermal therapy. These results suggest that the markedly improved therapeutic efficacy and decreased systemic

  14. Assessment of serum tumor markers, tumor cell apoptosis and immune response in patients with advanced colon cancer after DC-CIK combined with intravenous chemotherapy

    Directory of Open Access Journals (Sweden)

    Lei-Fan Li

    2016-12-01

    Full Text Available Objective: To study the effect of DC-CIK combined with intravenous chemotherapy on serum tumor markers, tumor cell apoptosis and immune response in patients with advanced colon cancer. Methods: A total of 79 patients with advanced colon cancer conservatively treated in our hospital between May 2012 and October 2015 were retrospectively studied and divided into DC-CIK group and intravenous chemotherapy group according to different therapeutic regimens, DC-CIK group received DC-CIK combined with intravenous chemotherapy and intravenous chemotherapy group received conventional intravenous chemotherapy. After three cycles of chemotherapy, the content of tumor markers in serum, expression levels of apoptotic molecules in tumor lesions as well as immune function indexes were determined. Results: After 3 cycles of chemotherapy, CEA, CA199, CA242, HIF-1α, IL-4, IL-5 and IL-10 content in serum of DC-CIK group were significantly lower than those of intravenous chemotherapy group; p53, FAM96B, PTEN, PHLPP, ASPP2 and RASSF10 mRNA content in tumor lesions of DC-CIK group were significantly higher than those of intravenous chemotherapy group; the fluorescence intensity of CD3, CD4 and CD56 on peripheral blood mononuclear cell surface of DC-CIK group were significantly higher than those of intravenous chemotherapy group while the fluorescence intensity of CD8 and CD25 were significantly lower than those of intravenous chemotherapy group; IL-2 and IFN-γ content in serum of DC-CIK group were significantly higher than those of intravenous chemotherapy group while IL-4, IL-5 and IL-10 content were significantly lower than those of intravenous chemotherapy group. Conclusions: DC-CIK combined with intravenous chemotherapy has better effect on killing colon cancer cells and inducing colon cancer cell apoptosis than conventional intravenous chemotherapy, and can also improve the body's anti-tumor immune response.

  15. Outcome of 289 locally advanced non-small cell lung cancer treated with radiotherapy alone and radiotherapy combined with chemotherapy

    International Nuclear Information System (INIS)

    Ou Guangfei; Wang Lvhua; Zhang Hongxing; Chen Dongfu; Xiao Zefen; Feng Qinfu; Zhou Zongmei; Lv Jima; Liang Jun; Wang Mei; Yin Weibo

    2007-01-01

    Objective: To retrospectively analyze the outcome of locally advanced non-small cell lung cancer patients treated with radiotherapy and chemoradiotherapy. Methods: 289 patients who were treated either by radiotherapy alone (168 patients) or radiotherapy plus chemotherapy (121 patients) from Dec. 1999 to Dec. 2002 were entered into the database for analysis. Pathological types: squamous cancer (152), adenocarcinoma(74), squamoadenocarcinoma(2) and other types (2). 24 showed cancer unclassificable and 35 were diagnosed without pathological proof. Stages: 74 had III A and 215 III B stage disease. Among the 121 patients treated with combined modality, 24 were treated with concurrent chemoradiotherapy, 78 radiotherapy after chemotherapy(C + R), and 19 radiotherapy followed by chemotherapy(R + C). In patients treated by concurrent chemoradiotherapy or C + R, 38 received consolidation chemotherapy after induction treatment. Results: The 1-, 3-, 5-year overall survival, and the median survival were: 45% , 16% , 8%, and 16.2 months for all patients; 57%, 27%, 11%, and 21.7 months for stage IIIA; 41%, 12%, 7%, and 15.3 months for IIIB. By logrank test, clinical stage, KPS performance, tumor volume, hemoglobin level before treatment, consolidation chemotherapy, radiation dose, and response to treatment showed statistically dramatic impact on overall survival. The overall survival rate and median survival time were slightly higher in the combined group than in the radiotherapy alone group, but the difference is statistically insignificant. In Cox multivariable regression, stage and consolidation chemotherapy were independent prognostic factors; KPS performance, radiation dose, and response to treatment were at the margin of statistical significance. Esophagitis and pneumonitis of Grade II or higher were 24% and 8%, respectively. Failure sites included in the thorax(41%), outside of thorax(48%), and both in and outside the thorax(11%). There was no difference between the

  16. Nanosized As2O3/Fe2O3 complexes combined with magnetic fluid hyperthermia selectively target liver cancer cells.

    Science.gov (United States)

    Wang, Zi-Yu; Song, Jian; Zhang, Dong-Sheng

    2009-06-28

    To study the methods of preparing the magnetic nano-microspheres of Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) complexes and their therapeutic effects with magnetic fluid hyperthermia (MFH). Nanospheres were prepared by chemical co-precipitation and their shape and diameter were observed. Hemolysis, micronucleus, cell viability, and LD(50) along with other in vivo tests were performed to evaluate the Fe(2)O(3) microsphere biocompatibility. The inhibition ratio of tumors after Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) injections combined with induced hyperthermia in xenograft human hepatocarcinoma was calculated. Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) particles were round with an average diameter of 20 nm and 100 nm as observed under transmission electron microscope. Upon exposure to an alternating magnetic field (AMF), the temperature of the suspension of magnetic particles increased to 41-51 degrees C, depending on different particle concentrations, and remained stable thereafter. Nanosized Fe(2)O(3) microspheres are a new kind of biomaterial without cytotoxic effects. The LD(50) of both Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) in mice was higher than 5 g/kg. One to four weeks after Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) complex injections into healthy pig livers, no significant differences were found in serum AST, ALT, BUN and Cr levels among the pigs of all groups (P > 0.05), and no obvious pathological alterations were observed. After exposure to alternating magnetic fields, the inhibition ratio of the tumors was significantly different from controls in the Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) groups (68.74% and 82.79%, respectively; P < 0.01). Tumors of mice in treatment groups showed obvious necrosis, while normal tissues adjoining the tumor and internal organs did not. Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) complexes exerted radiofrequency-induced hyperthermia and drug toxicity on tumors without any liver or kidney damage. Therefore, nanospheres are ideal carriers for tumor-targeted therapy.

  17. Laser-assisted delivery of synergistic combination chemotherapy in in vivo skin.

    Science.gov (United States)

    Wenande, Emily; Tam, Joshua; Bhayana, Brijesh; Schlosser, Steven Kyle; Ishak, Emily; Farinelli, William A; Chlopik, Agata; Hoang, Mai P; Pinkhasov, Omar R; Caravan, Peter; Rox Anderson, R; Haedersdal, Merete

    2018-04-10

    The effectiveness of topical drugs for treatment of non-melanoma skin cancer is greatly reduced by insufficient penetration to deep skin layers. Ablative fractional lasers (AFLs) are known to enhance topical drug uptake by generating narrow microchannels through the skin, but information on AFL-drug delivery in in vivo conditions is limited. In this study, we examined pharmacokinetics, biodistribution and toxicity of two synergistic chemotherapy agents, cisplatin and 5-fluorouracil (5-FU), following AFL-assisted delivery alone or in combination in in vivo porcine skin. Detected at 0-120 h using mass spectrometry techniques, we demonstrated that fractional CO 2 laser pretreatment (196 microchannels/cm 2 , 852 μm ablation depth) leads to rapid drug uptake in 1500 μm deep skin layers, with a sixfold enhancement in peak cisplatin concentrations versus non-laser-treated controls (5 h, P = 0.005). Similarly, maximum 5-FU deposition was measured within an hour of AFL-delivery, and exceeded peak deposition in non-laser-exposed skin that had undergone topical drug exposure for 5 days. Overall, this accelerated and deeper cutaneous drug uptake resulted in significantly increased inflammatory and histopathological effects. Based on clinical scores and transepidermal water loss measurement, AFL intensified local toxic responses to drugs delivered alone and in combination, while systemic drug exposure remained undetectable. Quantitative histopathologic analyses correspondingly revealed significantly reduced epidermal proliferation and greater cellular apoptosis after AFL-drug delivery; particularly after combined cisplatin + 5-FU exposure. In sum, by overcoming the primary limitation of topical drug penetration and providing accelerated, enhanced and deeper delivery, AFL-assisted combination chemotherapy may represent a promising treatment strategy for non-melanoma skin cancer. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Whole body hyperthermia, but not skin hyperthermia, accelerates brain and locomotor limb circulatory strain and impairs exercise capacity in humans

    DEFF Research Database (Denmark)

    Trangmar, Steven J; Chiesa, Scott T; Kalsi, Kameljit K

    2017-01-01

    Cardiovascular strain and hyperthermia are thought to be important factors limiting exercise capacity in heat-stressed humans, however, the contribution of elevations in skin (Tsk) versus whole body temperatures on exercise capacity has not been characterized. To ascertain their relationships...... was associated with a plateau in MCA and two-legged vascular conductance (VC). Mechanistically, the falling MCA VC was coupled to reductions in PaCO2, whereas the plateau in leg vascular conductance was related to markedly elevated plasma [NA] and a plateau in plasma ATP These findings reveal that whole-body...... hyperthermia, but not skin hyperthermia, compromises exercise capacity in heat-stressed humans through the early attenuation of brain and active muscle blood flow....

  19. Bladder cancer: the combination of chemotherapy and irradiation in the treatment of patients with muscle-invading tumors

    International Nuclear Information System (INIS)

    Shipley, William U.; Zietman, Anthony L.

    1995-01-01

    In the USA the recommended treatment for patients with muscle-invading transitional cell cancer of the bladder is usually radical cystectomy. Conservative surgery (transurethral resection and partial cystectomy), irradiation, and cis-platinum based systemic chemotherapy are, however, each effective for some patients. Although they provide the opportunity for bladder preservation, each modality, when used alone, is inferior to radical cystectomy in terms of local control and, perhaps, survival. Initial response and local control rates are improved when a multimodality approach is used. Up to 85% of patients selected for bladder sparing therapy on the basis of their initial response to chemo-radiation may keep their bladders. This figure could increase further when other powerful prognostic factors, such as the presence of hydronephrosis or carcinoma in situ, are taken into account in initial patient selection. Deferring the patient from immediate cystectomy does not appear to compromise survival. The most appropriate sequencing of radiation and chemotherapy is yet to be established. Concomitant cis-platinum and irradiation improves local control and bladder preservation when compared with irradiation alone but does not decrease the metastatic rate. It is hoped that the well recognized activity of cis-platinum based combination chemotherapy in advanced disease will translate into effective eradication of micrometastatic disease (known to be present in up to 40% of patients at diagnosis). This has yet to be clearly demonstrated in a randomized trial. The addition of combination chemotherapy to radiation does not increase bladder morbidity but carries a considerable systemic risk. Thus, despite promising phase II studies, until a survival benefit is proven in a randomized trial, neoadjuvant or adjuvant combination chemotherapy in conjunction with irradiation should continue to be regarded as experimental

  20. A randomized clinical trial of hyperthermia and radiation versus radiation alone for superficially located cancers

    International Nuclear Information System (INIS)

    Egawa, Sunao; Tsukiyama, Iwao; Watanabe, Shaw

    1989-01-01

    A randomized clinical trial was performed in order to evaluate the effect of combined hyperthermia and radiation for superficially located tumors. Ten institutions participated in this study and 92 evaluable patients were entered from September 1985 to March 1987 (44 patients for radiation plus hyperthermia and 48 for radiation only). Superficially located tumors, more than 3x3 cm in diameter, regardless of whether they were primary or metastatic, and of their histology, were included in the study. Radiotherapy was performed by the conventional fractionation method (2 Gyx5/week). Hyperthermia was conducted once a week. There was no statistical difference between the two groups regarding age, sex, the distribution of tumors and treatment parameters. The complete response (CR) and partial response (PR) rate for the hyperthermia plus radiation group was 81.8%, while the rate for the radiation alone group was 62.6% (p<0.05). Six factors were selected for analysis of the above effect by a multiple logistic model. Sex contributed the most (p=0.001), then the site of the tumor (p=0.016) and the method of treatment (p=0.023). Sex and the site influenced the results. Age, irradiation dose and frequency and duration of heating were not significant factors for response to treatment. (author)

  1. Role of regional radiofrequency hyperthermia after hepatic artery block in the normal pit liver

    International Nuclear Information System (INIS)

    Luo Jingwei; Xu Guozhen; Xiong Jinghong; Liu Xiaoyun; Wang Weihu; Li Yexiong

    2003-01-01

    Objective: To study the temperature difference, tolerated high temperature, pathological changes between normal and blocked hepatic artery in radiofrequency hyperthermia for pig liver. Methods: Mature pig was used with iodine blocked right hepatic artery. Heat of the whole liver was given for 1 hour by SR-1000 radiofrequency hyperthermia with four thermocouple probes to measure the temperature of the right hepatic artery, right and left normal liver and rectum. Results: Temperature of blocked right liver increased by 10.2 degree C from 39.1 degree C to 49.3 degree C as compared with the left liver of which the temperature rose by 6.8 degree C from 39.7 degree C to 46.5 degree C but the temperature of right hepatic artery and rectum rose only by 3.3 degree C, 3.2 degree C respectively. After sacrificing the pig one week later, on lobe exploration, severe necrosis was observed in the right lobe but the left lobe was normal with a clear demarcation between the two lobes. Conclusions: Hepatic arterial iodine embolization potentiates radiofrequency hyperthermia in the liver. Liver with blocked artery showed conspicuous necrosis but liver with normal un-blocked artery was able to tolerate 46.5 degree C. This provides some evidence for the combination of regional hyperthermia and hepatic artery block in the treatment of advanced liver cancer

  2. The effect of hyperthermia and radiation on lysosomal enzyme activity of mouse mammary tumours

    International Nuclear Information System (INIS)

    Barratt, G.M.; Wills, E.D.

    1979-01-01

    The effects of hyperthermia and radiation have been studied on the acid phosphatase and β-glucuronidase activities in lysosomes of C3H mice mammary tumours and of the spleen. Quantitative histochemical methods have been used. Hyperthermic treatment of both spontaneous and transplanted tumours caused an increase in the activity of both acid phosphatase and β-glucuronase when measured immediately after treatment, but the activities returned to normal after 24 hours. In contrast a radiation dose of 3500 rad did not cause an increase in activity of either enzyme immediately, but a large activation was observed after 24 hr. Combination of hyperthermic and radiation treatment caused increases in enzyme activities which were dependent on the time after treatment. Hyperthermic treatment of the lower body of mice bearing tumours also caused activation of lysosomal enzymes in the spleen. This may be hormone mediated. It is considered that the increased lysosomal enzyme activity observed after hyperthermia may be a consequence of increased permeability of the lysosomal membrane caused by hyperthermia. (author)

  3. Smart IR780 Theranostic Nanocarrier for Tumor-Specific Therapy: Hyperthermia-Mediated Bubble-Generating and Folate-Targeted Liposomes.

    Science.gov (United States)

    Guo, Fang; Yu, Meng; Wang, Jinping; Tan, Fengping; Li, Nan

    2015-09-23

    The therapeutic effectiveness of chemotherapy was hampered by dose-limiting toxicity and was optimal only when tumor cells were subjected to a maximum drug exposure. The purpose of this work was to design a dual-functional thermosensitive bubble-generating liposome (BTSL) combined with conjugated targeted ligand (folate, FA) and photothermal agent (IR780), to realize enhanced therapeutic and diagnostic functions. This drug carrier was proposed to target tumor cells owing to FA-specific binding, followed by triggering drug release due to the decomposition of encapsulated ammonium bicarbonate (NH4HCO3) (generated CO2 bubbles) by being subjected to near-infrared (near-IR) laser irradiation, creating permeable defects in the lipid bilayer that rapidly release drug. In vitro temperature-triggered release study indicated the BTSL system was sensitive to heat triggering, resulting in rapid drug release under hyperthermia. For in vitro cellular uptake experiments, different results were observed on human epidermoid carcinoma cells (KB cells) and human lung cancer cells (A549 cells) due to their different (positive or negative) response to FA receptor. Furthermore, in vivo biodistribution analysis and antitumor study indicated IR780-BTSL-FA could specifically target KB tumor cells, exhibiting longer circulation time than free drug. In the pharmacodynamics experiments, IR780-BTSL-FA efficiently inhibited tumor growth in nude mice with no evident side effect to normal tissues and organs. Results of this study demonstrated that the constructed smart theranostic nanocarrier IR780-BTSL-FA might contribute to establishment of tumor-selective and effective chemotherapy.

  4. TH-C-17A-11: Hyperthermia-Driven Immunotherapy Using Non-Invasive Radiowaves

    Energy Technology Data Exchange (ETDEWEB)

    Serda, R; Savage, D; Corr, S; Curley, S [Baylor College of Medicine, Houston, TX (United States)

    2014-06-15

    Purpose: The sad truth is that cancer is blamed for the death of nearly one in four people in the US. Immunotherapy offers hope for stimulating cancer immunity leading to targeted killing of cancer cells and a preventative measure for cancer recurrence. Unfortunately, the clinical efficacy of immunotherapy has not yet been established, however novel approaches are being developed, including combining immunotherapy with traditional chemotherapy, radiotherapy or thermal therapy. Therapeutics such as radiofrequency (RF) ablation and select chemotherapeutics induce mild anticancer immune responses. This project seeks to enhance the immune responses stimulated by these agents by co-delivery of nanoparticle-based chemotherapeutics and immune modulators in the presence of RF induced hyperthermia. Methods: A 4T1 mouse model of breast cancer is used to test the ability of RF waves to enhance accumulation of nanoparticles in tumor tissue by increasing blood flow and extravation of nanoparticles from hyperpermeable vessels. Images of particle and cell trafficking in the tumor are captured using an integrated RF and confocal imaging system, and tumor growth is monitored by tumor bioluminescence and caliper measurements. Results: Here we demonstrate enhanced intratumoral blood flow induced by non-invasive RF waves and an increase in nanoparticle accumulation in the tumor. IL-12 is shown to have powerful anti-tumor effects leading to tumor regression and the release of Th1-biased cytokines. Doxorubicin nanoparticles combined with adjuvant nanoparticles exhibited superior antitumor effects to single agent therapy. Conclusion: RF therapy combined with nanotherapeutics is a promising approach to enhance the delivery of therapeutics to the tumor and to stimulate a tumor microenvironment that supports the development of cancer-specific immune responses. This research was supported by the National Institute of Health grant numbers U54 CA143837 and U54 CA151668, and the Kanzius

  5. TH-C-17A-11: Hyperthermia-Driven Immunotherapy Using Non-Invasive Radiowaves

    International Nuclear Information System (INIS)

    Serda, R; Savage, D; Corr, S; Curley, S

    2014-01-01

    Purpose: The sad truth is that cancer is blamed for the death of nearly one in four people in the US. Immunotherapy offers hope for stimulating cancer immunity leading to targeted killing of cancer cells and a preventative measure for cancer recurrence. Unfortunately, the clinical efficacy of immunotherapy has not yet been established, however novel approaches are being developed, including combining immunotherapy with traditional chemotherapy, radiotherapy or thermal therapy. Therapeutics such as radiofrequency (RF) ablation and select chemotherapeutics induce mild anticancer immune responses. This project seeks to enhance the immune responses stimulated by these agents by co-delivery of nanoparticle-based chemotherapeutics and immune modulators in the presence of RF induced hyperthermia. Methods: A 4T1 mouse model of breast cancer is used to test the ability of RF waves to enhance accumulation of nanoparticles in tumor tissue by increasing blood flow and extravation of nanoparticles from hyperpermeable vessels. Images of particle and cell trafficking in the tumor are captured using an integrated RF and confocal imaging system, and tumor growth is monitored by tumor bioluminescence and caliper measurements. Results: Here we demonstrate enhanced intratumoral blood flow induced by non-invasive RF waves and an increase in nanoparticle accumulation in the tumor. IL-12 is shown to have powerful anti-tumor effects leading to tumor regression and the release of Th1-biased cytokines. Doxorubicin nanoparticles combined with adjuvant nanoparticles exhibited superior antitumor effects to single agent therapy. Conclusion: RF therapy combined with nanotherapeutics is a promising approach to enhance the delivery of therapeutics to the tumor and to stimulate a tumor microenvironment that supports the development of cancer-specific immune responses. This research was supported by the National Institute of Health grant numbers U54 CA143837 and U54 CA151668, and the Kanzius

  6. The combination of radiotherapy and chemotherapy in the treatment of malignant tumours: indications and dangers

    International Nuclear Information System (INIS)

    Bartelink, H.; Somers, R.

    1980-01-01

    The combination of radiotherapy and chemotherapy has improved the results of treatment of certain malignant tumours. However, during both experimental investigations and clinical treatment, a number of severe side effects have been observed, during as well as some time after the administration, especially with use of actinomycin and adriamycin. Also the possibility exists that more secondary tumours are induced as the consequence of combination therapy. (Auth.)

  7. The effect of hyperglycemia with or without hyperthermia on the radiation response of a spontaneous mouse fibrosarcoma

    International Nuclear Information System (INIS)

    Urano, M.; Todoroki, T.; Kahn, J.

    1985-01-01

    Hyperglycemia facilitates glycolysis with a resultant decrease in the tissue, particularly tumor pH. Another effect of hyperglycemia is to increase osmotic pressure in the extracellular fluid. The affect of hyperglycemia on the radiation response of our spontaneous tumor, FSa-II was examined. Further experiment includes the effect of hyperglycemia given 1 hour before local hyperthermia which was given in a 43.5 0 C water bath. Animals were C/sub 3/Hf/Sed mice from our defined flora colony. Tumor cell suspension was transplanted into the animal foot and the treatment was given when tumors reached an average diameter of 7 mm. Tumors were irradiated under clamped hypoxia, in air or under HPO (30 psi). Hyperglycemia, 5 mg/g given 1 hour before radiation, increased hypoxic cell fraction of the tumor without altering the slope fo the dose response curve. Hyperthermia enhanced the tumor response and increased hypoxic cell fraction. Further increase in the hypoxic cell fraction was noted following combined hyperglycemia and hyperthermia. Hyperthermia given 24 hours before radiation with or without glucose also increased hypoxic cell fraction, but decrease chronically hypoxic cell fraction (fraction not oxygenated under HPO)

  8. The long term effect and outcome of preoperative chemotherapy combined with radiation therapy for bladder cancer

    International Nuclear Information System (INIS)

    Nasu, Takahito; Nakane, Hiroshi; Kamata, Seiji; Mitsui, Hiroshi; Hayashida, Shigeaki; Shinohara, Youichi.

    1996-01-01

    The object of this study is to evaluate the efficacy of preoperative chemotherapy combined with radiation therapy for bladder cancer. A total of 44 patients with bladder cancer were treated by preoperative chemotherapy combined with radiation therapy between October, 1981 and December, 1986. Clinical stages included 4 patients in Ta, 25 in T1, 11 in T2, and 4 in T3. Each patient was treated twice with 15 gray of radiation to the small pelvic cavity and a chemotherapy combination of adriamycin, cis-platinum, tegaful, and peplomycin. The average observation time after the therapy was 83 month, with the maximum being 146 months. Complete remission was included in 5 patients, partial remission in 27, and no change in 12. Thus, the overall effective rate was 72.8%. Operations, selected by the results of the preoperative therapy, included transurethral resection on 28 patients, transurethral fulguration on 2, partial cystectomy on 4, resection of tumor on 4, and total cystectomy on 3. Operations were not performed on 2 patients and not allowed on 1 patient. The outcome during the long-term follow-up included cancer related deaths in 4 patients, and death resulting from other disorders in 9. The 5-year survival rates for superficial and invasive bladder cancer were 92.4%, and 83.9%, respectively. The 10-year survival rates for superficial and invasive bladder cancer were also 92.4% and 83.9%, respectively. The 3-year and 5-year non-recurrence rates for superficial bladder cancer were 75.8%, and 66.9% respectively, according to the Kaplan-Meier method. On the other hand, the 3-year and 5-year non-recurrence rates for invasive bladder cancer were both 73.8%. During the follow-up between 9 and 11 years, 3 upper tract tumor were diagnosed (2 ureteral cancer, and 1 renal pelvic cancer). We concluded that preoperative chemotherapy combined with radiation therapy may be effective for the treatment of bladder cancer. (author)

  9. Endometrial carcinoma in vitro chemosensitivity testing of single and combination chemotherapy regimens using the novel microculture kinetic apoptosis assay: implications for endometrial cancer treatment.

    Science.gov (United States)

    Ballard, Karen S; Homesley, Howard D; Hodson, Charles; Presant, Cary A; Rutledge, James; Hallquist, Allan; Perree, Mathieu

    2010-03-01

    The in vitro microculture kinetic (MiCK) apoptosis assay has been used to predict single or combination chemotherapy response in leukemia patients. This feasibility study addressed MiCK in endometrial cancer specimens. Endometrial cancer specimens from total abdominal hysterectomies were processed at a central laboratory. Single cell suspensions of viable endometrial cancer cells were plated in individual wells. Single and combination regimens were tested: combinations of doxorubicin, cisplatin, and paclitaxel and carboplatin and paclitaxel (Gynecologic Oncology Group [GOG] 209 endometrial cancer phase III trial arms) as well as single agent testing with paclitaxel, carboplatin, doxorubicin, cisplatin, ifosfamide, and vincristine (active agents in GOG trials). Apoptosis was measured continuously over 48 hours. Fifteen of nineteen patients had successful assays. The highest mean chemo sensitivity was noted in the combination of cisplatin, doxorubicin, and paclitaxel with lower mean chemosensitivity for carboplatin and paclitaxel. Combination chemotherapy had higher chemosensitivity than single drug chemotherapy. However, in 25% of patients a single drug had higher chemosensitivity than combination chemotherapy. As single agents, ifosfamide, cisplatin, and paclitaxel had the highest kinetic unit values. Using a panel of agents simulating clinical dose regimens, the MiCK assay was feasible in evaluating in vitro chemosensitivity of endometrial cancer. MiCK assay results correlated with GOG clinical trial results. However, 25% of patients might be best treated with single agent chemotherapy selected by MiCK. Ifosfamide, cisplatin, and paclitaxel appear to have high activity as single agents. MiCK may be useful in future new drug testing and individualizing endometrial cancer patient's chemotherapy management.

  10. Simultaneous hyperthermia and doxorubicin delivery from polymer-coated magnetite nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Iglesias, G.R., E-mail: iglesias@ugr.es [Department of Applied Physics, University of Granada, Granada 18071 (Spain); Delgado, A.V.; González-Caballero, F. [Department of Applied Physics, University of Granada, Granada 18071 (Spain); Ramos-Tejada, M.M. [Department of Physics, University of Jaén, Linares 23700 (Spain)

    2017-06-01

    In this work, the hyperthermia response, (i.e., heating induced by an externally applied alternating magnetic field) and the simultaneous release of an anti-cancer drug (doxorubicin) by polymer-coated magnetite nanoparticles have been investigated. After describing the setup for hyperthermia measurements in suspensions of magnetic nanoparticles, the hyperthermia (represented by the rate of suspension heating and, ultimately, by the specific absorption rate or SAR) of magnetite nanoparticles (both bare and polymer-coated as drug nanocarriers) is discussed. The effect of the applied ac magnetic field on doxorubicin release is also studied, and it is concluded that the field does not interfere with the release process, demonstrating the double functionality of the investigated particles. - Highlights: • Magnetite NPs coated with polymers are used for drug delivery and hyperthermia. • The SAR of polyelectrolyte-coated NPs is larger because of their improved stability. • The antitumor drug doxorubicin is adsorbed on the coated particles. • The release rate of the drug is not affected by the ac magnetic field used in hyperthermia.

  11. The Results of Combined External Radiotherapy and Chemotherapy in the Management of Esophageal Cancer

    International Nuclear Information System (INIS)

    Lee, Hyun Joo; Suh, Hyun Suk; Kim, Jun Hee; Kim, Chul Soo; Kim, Sung Rok; Kim, Re Hwe

    1996-01-01

    Purpose : To evaluate the role of combination therapy of external radiotherapy and chemotherapy in the management of advanced esophageal cancer as a primary treatment compared with radiation therapy alone. Methods and Materials : A retrospective review of evaluable 55 esophageal cancer patients referred to the Department of Therapeutic Radiology, Paik Hospital for the external radiotherapy between Jul. 1983 and Dec.1994 was undertaken. Combined therapy patients (A group) were 30 and radiation alone patients (B group) were 25. Median age was 60 years old in A group(ranges : 42-81) and 65 years old in B group (ranges : 50-81). The male patients were 53. The fifty patients had squamous cell carcinomas. Radiation doses of 2520-6480c Gy were delivered over a period of 4-7 weeks. using 4MV LIVAC. Chemotherapy was administered in bolus injection before, after, or during the course of external radiotherapy. The local control rate and patterns of failure according to both treatment modalities and 1,2 year survival rates according to prognostic factors (stage, tumor length, radiation dose etc.) were analysed. Results : Median follow up period was 7 months (range : 2-73 months). Median survival was 7.5 months (20 days-29 months) in A group and 5 months(20 days-73 months) in B group. The 1,2 YSRs were 26.7%, 8.9% in A group. 12.7%, 4.3% in B group (p>0.05), respectively. The 1,2 YSRs according to stage(II/III), tumor length (5cm more or less). radiation dose(5000c Gy more or less) of A and B group were analyzed and the differences of survival rates of both treatments were not statistically significant. But among group B, patients who received 5000c Gy or more showed significant survival benefits (p<0.05). The treatment response rates of A and B group were 43.8%, 25.0%, respectively. Complete response rate of 25.0% in A and 8.3% in B were achieved. The local failure and distant metastasis were 52.4%, 23.8% in A group. 64.3%, 14.3% in B group, respectively. The combination

  12. Defining the dose of gemtuzumab ozogamicin in combination with induction chemotherapy in acute myeloid leukemia

    DEFF Research Database (Denmark)

    Burnett, Alan; Cavenagh, Jamie; Russell, Nigel

    2016-01-01

    Arecent source data meta-analysis of randomized trials in adults assessing the immunoconjugate gemtuzumab ozogamicin combined with standard chemotherapy in acute myeloid leukemia showed a significant survival benefit in patients without an adverse karyotype. It is not clear whether the optimal dose...

  13. Results of radiotherapy and a combined radio- and chemotherapy for hypopharyngeal carcinomas

    International Nuclear Information System (INIS)

    Mariya, Yasushi; Tarusawa, Nobuko; Takekawa, Shoichi; Yodono, Hiraku; Mori, Isao; Shinkawa, Hidekazu; Watanabe, Sadao; Miyano, Kazuo; Kattou, Keiichi.

    1992-01-01

    We analyzed the results of radiotherapy in 36 patients with hypopharyngeal carcinoma. The overall 2-year and 5-year survival rates were 45.3% and 31.1%, respectively. For 23 patients given radical irradiation, the corresponding figures were 37.8% and 28.3%. However, in 16 patients receiving a combined therapy of radical irradiation and chemotherapy, mainly an intraarterial injection of cisplatin, the survivals were better; the 2-year survival rate was 50.0% and four patients have survived for more than three years without recurrence. In managing patients with hypopharyngeal carcinoma, this combined therapy would improve therapeutic outcome and also assist in larynx preservation. (J.P.N.)

  14. Chemotherapy or radio-chemotherapy for advanced adenocarcinoma of the oesophagus and cardiac orifice

    International Nuclear Information System (INIS)

    Seitz, J.F.; Duffaud, F.; Dahan, L.; Ries, P.; Ville, E.; Laugier, R.

    2001-01-01

    Adenocarcinomas of esophagus and cardia represent in France approximately 20 to 40% of the esophagus cancers. They have a high risk to develop lymph nodes metastases and liver metastases. Currently, only 50 to 70% of patients may benefit from surgical curative resection at diagnosis, but more than 50% of them will recur. The standard of treatment of these metastatic adenocarcinomas is chemotherapy. Three large randomized comparative studies, between chemotherapy and supportive care, showed that chemotherapy significantly extends the median of survival (from 3-4 months to 10-12 months) and improves the quality of life. Currently, the combination of epirubicin-cisplatin-continuous 5FU (ECF) is the most effective regimen but it is difficult to administer and tolerate because of the long continuous 5FU infusion. In France, the most commonly used combination regimen still associates 5FU and cisplatin. New drugs (such as docetaxel, CPT11, oxaliplatin) used alone or in combination, especially with 5U, are very promising. Radio-chemotherapy is the preferred treatment for locoregional recurrences, because it improves dysphagia and enables to obtain complete tumor responses. Current results from concomitant radio-chemotherapy studies for esophagus cancer, based on 5FU alone, 5FU-cisplatin or 5FU-mitomycin, given as preoperative treatment or as exclusive treatment, support to use radio-chemotherapy for the treatment of loco-regional recurrences after surgical resection. Nevertheless, the optimal radio-chemotherapy schedule still remain to be defined (dose, duration, splitting of radiotherapy, choice of anticancer drugs). (authors)

  15. Effects of Radiofrequency Induced local Hyperthermia on Normal Canine Liver

    International Nuclear Information System (INIS)

    Suh, Chang Ok; Loh, John J. K.; Seong, Jin Sil

    1991-01-01

    In order to assess the effects of radiofrequency-induced local hyperthermia on the normal liver, histopathologic findings and biochemical changes after localized hyperthermia in canine liver were studied. Hyperthermia was externally administered using the Thermotron RF-8 (Yamamoto Vinyter Co., Japan; Capacitive type heating machine) with parallel opposed electrodes. Thirteen dogs were used and allocated into one control group (N=3) and two treatment groups according to the treatment temperature. Group I (N=5) was heated with 42.5±0.5.deg.C for 30 minutes, and Group(N=5) was heated with 45±0.5.deg.C for 15-30 minutes. Samples of liver tissue were obtained through a needle biopsy immediately after hyperthermia and 7, 14 and 28 days after treatment and examined for SGOT, SGPT and alkaline phosphatase. Although SGOT and SGPT were elevated after hyperthermia in both groups (three of five in each group), there was no liver cell necrosis or hyperthermia related mortality in Group I. A hydropic swelling of hepatocytes was prominent histologic finding. Hyperthermia with 45.deg.C for 30 minutes was fatal and showed extensive liver cell necrosis. In conclusion, liver damage day heat of 42.5±0.5.deg.C for 30 minutes is reversible, and liver damage by heat of 45±0.5.deg.C for 30 minutes can be fatal or irreversible. However, these results cannot be applied directly to human trial. Therefore, in order to apply hyperthermic treatment on human liver tumor safely, close observation of temperature with proper thermometry is mandatory. Hyperthermic treatment should be confined to the tumor area while sparing a normal liver as much as possible

  16. Hyperthermia stimulates HIV-1 replication.

    Directory of Open Access Journals (Sweden)

    Ferdinand Roesch

    Full Text Available HIV-infected individuals may experience fever episodes. Fever is an elevation of the body temperature accompanied by inflammation. It is usually beneficial for the host through enhancement of immunological defenses. In cultures, transient non-physiological heat shock (42-45°C and Heat Shock Proteins (HSPs modulate HIV-1 replication, through poorly defined mechanisms. The effect of physiological hyperthermia (38-40°C on HIV-1 infection has not been extensively investigated. Here, we show that culturing primary CD4+ T lymphocytes and cell lines at a fever-like temperature (39.5°C increased the efficiency of HIV-1 replication by 2 to 7 fold. Hyperthermia did not facilitate viral entry nor reverse transcription, but increased Tat transactivation of the LTR viral promoter. Hyperthermia also boosted HIV-1 reactivation in a model of latently-infected cells. By imaging HIV-1 transcription, we further show that Hsp90 co-localized with actively transcribing provirus, and this phenomenon was enhanced at 39.5°C. The Hsp90 inhibitor 17-AAG abrogated the increase of HIV-1 replication in hyperthermic cells. Altogether, our results indicate that fever may directly stimulate HIV-1 replication, in a process involving Hsp90 and facilitation of Tat-mediated LTR activity.

  17. Description and characterization of the novel hyperthermia- and thermoablation-system MFHregistered300F for clinical magnetic fluid hyperthermia

    International Nuclear Information System (INIS)

    Gneveckow, Uwe; Jordan, Andreas; Scholz, Regina; Bruess, Volker; Waldoefner, Norbert; Ricke, Jens; Feussner, Annelie; Hildebrandt, Bert; Rau, Beate; Wust, Peter

    2004-01-01

    Magnetic fluid hyperthermia (MFH) is a new approach to deposit heat power in deep tissues by overcoming limitations of conventional heat treatments. After infiltration of the target tissue with nanosized magnetic particles, the power of an alternating magnetic field is transformed into heat. The combination of the 100 kHz magnetic field applicator MFH registered 300F and the magnetofluid (MF), which both are designed for medical use, is investigated with respect to its dosage recommendations and clinical applicability. We found a magnetic field strength of up to 18 kA/m in a cylindrical treatment area of 20 cm diameter and aperture height up to 300 mm. The specific absorption rate (SAR) can be controlled directly by the magnetic field strength during the treatment. The relationship between magnetic field strength and the iron normalized SAR (SAR Fe ) is only slightly depending on the concentration of the MF and can be used for planning the target SAR. The achievable energy absorption rates of the MF distributed in the tissue is sufficient for either hyperthermia or thermoablation. The fluid has a visible contrast in therapeutic concentrations on a CT scanner and can be detected down to 0.01 g/l Fe in the MRI. The system has proved its capability and practicability for heat treatment in deep regions of the human body

  18. Malignant strictures involving the esophagogastric junction : palliative treatment with balloon dilation combined with chemotherapy and/or radiotherapy

    International Nuclear Information System (INIS)

    Hong, Hyoek Jin; Ko, Gi Young; Song, Ho Young; Cho, Yong Soo; Sung, Kyu Bo

    2001-01-01

    To overcome the limitations of expandable metallic stent placement by using balloon dilation combined with chemotherapy or radiation therapy in the treatment of malignant esophageal strictures involving the esophagogastric junction (EGJ). Fluoroscopically guided balloon dilation was performed in 14 patients with strictures due to squamous cell carcinoma (n=5) or adenocarcinoma (n=9). After balloon dilation all patients underwent chemotherapy or radiation therapy. There were no failures or major complications After dilation, dysphagia improved in 13 (92%) of 14 patients, and the long-term success rate was 50%. Six of the seven patients in whom the condition recurred underwent further balloon dilation (n=4) or placement of an expandable metallic stent (n=2). Ten of the 13 who were followed up died after diffuse metastasis. Prior to their eventual death (mean survial, 20 weeks), the dysphagia experienced by seven (70%) of these ten improved, and thus they required no further treatment. Balloon dilation combined with chemotherapy or radiation therapy seems to be a safe and effective secondary therapy for patients with dysphagia due to malignant stricture involving the EGJ

  19. Combined photothermo-chemotherapy using gold nanoshells on drug-loaded micelles for colorectal cancer treatment

    Science.gov (United States)

    Lee, Shin-Yu; Shieh, Ming-Jium

    2018-02-01

    Combined photothermo-chemotherapy is a new strategy for cancer treatment which improves the therapeutic outcome by synergistic effects of both therapies. Here, we presented a multifunctional gold nanoshell that exhibited excellent photothermal conversion and delivered the hydrophobic chemotherapy drug, SN-38. The positively charged SN-38-loaded PDMA-PCL micelles were decorated with a gold layer by in situ reduction of chloroauric acid on the surface of micelles. Scanning and transmission electron microscopy images proved micelles were successfully decorated and the resulting gold nanoshells had a spherical morphology with a narrow size distribution. The synthesized gold nanoshells displayed a broad surface plasmon resonance peak in the near-infrared wavelength region and a great photothermal conversion ability. After pegylation, gold nanoshells were stable in biological media and appeared highly biocompatible in the absence of laser irradiation. Upon near-infrared laser irradiation, incident energy was converted into heat by gold nanoshells on SN-38-loaded micelles (SN-38@pGNS), which causes local temperature increase and triggers the release of encapsulated drug. Compared to SN-38, SN-38-loaded micelles, or laser with drug-free gold nanoshells alone, combined photothermo-chemotherapy using SN-38@pGNS with laser irradiation killed colorectal cancer cells with higher efficacy in vitro and demonstrated significant tumor suppression in vivo, suggesting that gold nanoshells on drug-loaded micelles delivered SN-38 and photothermal therapy in synergistic actions and might be a potential candidate for future colorectal cancer therapy.

  20. Magnetic hyperthermia with hard-magnetic nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Kashevsky, Bronislav E., E-mail: bekas@itmo.by [A.V Luikov Heat and Mass Transfer Institute, Belarus Academy of Sciences, P. Brovka str. 15, Minsk 220072 (Belarus); Kashevsky, Sergey B.; Korenkov, Victor S. [A.V Luikov Heat and Mass Transfer Institute, Belarus Academy of Sciences, P. Brovka str. 15, Minsk 220072 (Belarus); Istomin, Yuri P. [N. N. Alexandrov National Cancer Center of Belarus, Lesnoy-2, Minsk 223040 (Belarus); Terpinskaya, Tatyana I.; Ulashchik, Vladimir S. [Institute of Physiology, Belarus Academy of Sciences, Akademicheskaya str. 28, Minsk 220072 (Belarus)

    2015-04-15

    Recent clinical trials of magnetic hyperthermia have proved, and even hardened, the Ankinson-Brezovich restriction as upon magnetic field conditions applicable to any site of human body. Subject to this restriction, which is harshly violated in numerous laboratory and small animal studies, magnetic hyperthermia can relay on rather moderate heat source, so that optimization of the whole hyperthermia system remains, after all, the basic problem predetermining its clinical perspectives. We present short account of our complex (theoretical, laboratory and small animal) studies to demonstrate that such perspectives should be related with the hyperthermia system based on hard-magnetic (Stoner–Wohlfarth type) nanoparticles and strong low-frequency fields rather than with superparamagnetic (Brownian or Neél) nanoparticles and weak high-frequency fields. This conclusion is backed by an analytical evaluation of the maximum absorption rates possible under the field restriction in the ideal hard-magnetic (Stoner–Wohlarth) and the ideal superparamagnetic (single relaxation time) systems, by theoretical and experimental studies of the dynamic magnetic hysteresis in suspensions of movable hard-magnetic particles, by producing nanoparticles with adjusted coercivity and suspensions of such particles capable of effective energy absorption and intratumoral penetration, and finally, by successful treatment of a mice model tumor under field conditions acceptable for whole human body. - Highlights: • Hard-magnetic nanoparticles are shown superior for hyperthetmia to superparamagnetic. • Optimal system parameters are found from magnetic reversal model in movable particle. • Penetrating suspension of HM particles with aggregation-independent SAR is developed. • For the first time, mice with tumors are healed in AC field acceptable for human body.

  1. Depression of DNA synthesis rate following hyperthermia, gamma irradiation, cyclotron neutrons and mixed modalities

    International Nuclear Information System (INIS)

    Weber, H.J.; Muehlensiepen, H.; Porschen, W.; Feinendegen, L.E.; Dietzel, F.

    1978-01-01

    The incorporation of the thymidine analogue I-UdR is proportional to the activity of DNA synthesis. The maximum depression of 125-I-UdR incorporation occurs approximately 4 hours after all kinds of treatment. The increase which follow reflects cell processes like reoxygeneration, recovery, recycling and recruitment (although a direct relation is not yet demonstrable). The degree of depression 4 hours after treatment and the time required needs to reach control level is dependent on dose and radiation quaility but no such dependence could be clearly seen for the times of hyperthermia treatment we used. Neutron irradiation and the combination gamma irradiation + hyperthermia show a higher depression and a slower return to normal than gamma irradiation at the same dose. (orig.) [de

  2. Combined treatment of radiotherapy and local hyperthermia using 8 MHz RF-wave for advanced carcinoma of the breast

    Energy Technology Data Exchange (ETDEWEB)

    Fuwa, Nobukazu

    1988-01-01

    During the period from January 1983 through September 1986, 13 patients with carcinoma of the breast were treated with local hyperthermia combined with radiotherapy. Six patients were inoperable advanced cases and the other 7 were recurrent cases. Local heat was applied with an 8-MHz RF-capacitive heating equipment, once or twice a week after radiotherapy, for 40 approx. 60 minutes per session. Of the 6 cases with inoperable advanced lesions, 4 achieved CR and the other 2 achieved PRa (80 approx. 100 % regression), and of the 7 cases with local recurrent tumors, 3 achieved CR and the other 4 achieved PRa. As complications of the thermoradiotherapy, grade I-II skin burns were observed in 9 cases, pain around the ribs in 8 cases, mild lassitude in 2 cases, persistent tachycardia in 1 case and acute erosive gastritis in 1 case. It is worth noting that CR was achieved in these huge tumors, which can not be controlled by radiotherapy alone.

  3. Combined treatment of radiotherapy and local hyperthermia using 8 MHz RF-wave for advanced carcinoma of the breast

    International Nuclear Information System (INIS)

    Fuwa, Nobukazu

    1988-01-01

    During the period from January 1983 through September 1986, 13 patients with carcinoma of the breast were treated with local hyperthermia combined with radiotherapy. Six patients were inoperable advanced cases and the other 7 were recurrent cases. Local heat was applied with an 8-MHz RF-capacitive heating equipment, once or twice a week after radiotherapy, for 40 ∼ 60 minutes per session. Of the 6 cases with inoperable advanced lesions, 4 achieved CR and the other 2 achieved PRa (80 ∼ 100 % regression), and of the 7 cases with local recurrent tumors, 3 achieved CR and the other 4 achieved PRa. As complications of the thermoradiotherapy, grade I-II skin burns were observed in 9 cases, pain around the ribs in 8 cases, mild lassitude in 2 cases, persistent tachycardia in 1 case and acute erosive gastritis in 1 case. It is worth noting that CR was achieved in these huge tumors, which can not be controlled by radiotherapy alone. (author)

  4. The effect of hypofractionated radiation and magnetic nanoparticle hyperthermia on tumor immunogenicity and overall treatment response

    Science.gov (United States)

    Hoopes, P. Jack; Wagner, Robert J.; Song, Ailin; Osterberg, Bjorn; Gladstone, David J.; Bursey, Alicea A.; Fiering, Steven N.; Giustini, Andrew J.

    2017-02-01

    It is now known that many tumors develop molecular signals (immune checkpoint modulators) that inhibit an effective tumor immune response. New information also suggest that even well-known cancer treatment modalities such as radiation and hyperthermia generate potentially beneficial immune responses that have been blocked or mitigated by such immune checkpoints, or similar molecules. The cancer therapy challenge is to; a) identify these treatment-based immune signals (proteins, antigens, etc.); b) the treatment doses or regimens that produce them; and c) the mechanisms that block or have the potential to promote them. The goal of this preliminary study, using the B6 mouse - B16 tumor model, clinically relevant radiation doses and fractionation schemes (including those used clinically in hypofractionated radiation therapy), magnetic nanoparticle hyperthermia (mNPH) and sophisticated protein, immune and tumor growth analysis techniques and modulators, is to determine the effect of specific radiation or hyperthermia alone and combined on overall treatment efficacy and immunologic response mechanisms. Preliminary analysis suggests that radiation dose (10 Gy vs. 2 Gy) significantly alters the mechanism of cell death (apoptosis vs. mitosis vs. necrosis) and the resulting immunogenicity. Our hypothesis and data suggest this difference is protein/antigen and immune recognition-based. Similarly, our evidence suggest that radiation doses larger than the conventional 2 Gy dose and specific hyperthermia doses and techniques (including mNP hyperthermia treatment) can be immunologically different, and potentially superior to, the radiation and heat therapy regimens that are typically used in research and clinical practice.

  5. Effects of hyperthermia on the hamster immune system

    International Nuclear Information System (INIS)

    Gangavalli, R.; Cain, C.A.; Tompkins, W.A.F.

    1984-01-01

    In previous studies, the authors have shown that hyperthermia can enhance antibody-complement chytotoxicity of hamster and human tumor cells. Moreover, whole body microwave exposure of hamsters resulted in activation of peritoneal macrophages to a viricidal state and transient suppression of natural killer (NK) cell activity. In this study, the authors compare the effects of whole body heating by microwaves or by an environmental chamber (hot air) on the hamster immune system. Microwave exposure (25mW/cm/sup 2/; 1 hr) caused viricidal activation of peritoneal macrophages which resulted in restriction of vaccinia and vesicular stomatitis virs (VSV) growth. However, heating in an environmental chamber (41 0 C; 1 hr) did not activate macrophages to a viricidal state. Both microwave and hot air hyperthermia caused significant augmentation of antibody producing spleen cell response to sheep red blood cells (SRBC), using the Jerne hymolytic plaque assay, four days post exposure and immunization with SRBC. Natural killer spleen cell cytotoxicity was suppressed by microwave and hot air hyperthermia showing that NK lymphocytes are extremely sensitive to changes in temperature. These alterations in cellular immune response due to hyperthermia could be of significance in treatment of tumors and viral infections

  6. Effect of preoperative oral S-1 combined with regional intra-arterial chemotherapy on malignant molecule expression in locally advanced unresectable gastric cancer tissue

    Directory of Open Access Journals (Sweden)

    Lei Liu

    2016-11-01

    Full Text Available Objective: To study the effect of preoperative oral S-1 combined with regional intra-arterial chemotherapy on malignant molecule expression in locally advanced unresectable gastric cancer tissue. Methods: A total of 144 patients with locally advanced gastric cancer receiving surgical resection after neoadjuvant chemotherapy in our hospital between May 2012 and August 2015 were selected and randomly divided into experimental group who received preoperative oral S-1 combined with regional intra-arterial chemotherapy and control group who received preoperative intravenous systemic chemotherapy. The levels of serum tumor markers were determined after chemotherapy, and the expression levels of tumor suppressor genes and cell cycle-related molecules in tumor tissue were determined after surgical resection. Results: After neoadjuvant chemotherapy, the serum G-17, TK-1, CEA, CA19-9, CA12-5, CA72-4 and CK, CK-MB, ALT, AST levels of experimental group were significantly lower than those of control group; after surgical resection, the p16, p27, PTEN and TXNIP mRNA levels in tumor tissue of experimental group were significantly higher than those of control group while CyclinB2, CyclinD1, CyclinE, CDK1 and CDK2 mRNA levels were significantly lower than those of control group. Conclusions: Preoperative oral S-1 combined with regional intra-arterial chemotherapy can more effectively kill gastric cancer cells, reduce tumor load, inhibit cell cycle and promote cell apoptosis.

  7. Ovarian carcinoma: Role of radiation therapy versus chemotherapy

    International Nuclear Information System (INIS)

    Shehata, W.M.; Meyer, R.L.; Cormier, W.J.; Jazy, F.K.

    1986-01-01

    The authors evaluated 83 patients with ovarian cancer who were irradiated or treated by a combination of cytoxan, adriamycin, and cisplatin. According to FIGO stage, eight patients had stage I disease, 12 had stage II disease, 61 had stage II disease and two has stage IV disease. Fifty patients had bulky disease and 33 had minimal disease of 2 cm or less. Sixty patients were irradiated to an open abdominopelvic field (30 Gy delivered over 4 weeks), with or without a pelvic boost. Fifty-five patients received combination chemotherapy and 30 received a single agent as initial therapy. The patients were divided into three groups. The 26 patients in group I received primary radiation therapy with or with out adjuvant single-agent chemotherapy, then combination chemotherapy to salvage. The 34 patients in group II were irradiated after chemotherapy, mainly combination chemotherapy, failed. The 23 patients in group III received, mainly combination chemotherapy with second-line drugs for salvage

  8. Efficacy and Safety of rh-Endostatin Combined with Chemotherapy 
versus Chemotherapy Alone for Advanced NSCLC: A Meta-analysis Review

    Directory of Open Access Journals (Sweden)

    Jinzhong ZHANG

    2011-05-01

    Full Text Available Background and objective In recent years, there has been a large number of studies and reports about the efficacy and safety of recombinant human endostatin (rh-endostatin, an anti-angiogenic drug, in treatment of advanced lung cancer. Authentic assessment of rh-endostatin treatment in lung cancer is important. The aim of this study is to assess the clinical efficacy and safety of rh-endostatin combined with chemotherapy in the treatment of patients with non-small cell lung cancer (NSCLC. Methods Cochrane systematic review methods were used in the data selection, and data were selected from the Cochrane Library, EMBASE, Medline, SCI, CBM, CNKI, and etc electronic database to get all clinical controlled trials. The retrieval time was March 2010. The objects of these randomized controlled trials were advanced NSCLC patients and in the experimental group was rh-endostatin combination chemotherapy, in the control group was chemotherapy alone to compare the efficacy of two groups. The quality of included trials were evaluated by two reviewers independently. The software RevMan 5.0 was used for meta-analyses. Results Fifteen trials with 1,326 patients were included according to the including criterion. All trials were randomized controlled trials, and two trials were adequate in reporting randomization. Thirteen trials didn’t mention the blinding methods. Meta analysis indicated that the NPE arm (Vinorelbine+cisplatin+rh-endostatin had a different response rate compared with NP (Vinorelbine+cisplatin arm (OR=2.16, 95%CI: 1.57-2.99. The incidences of severe leukopenia (OR=0.94, 95%CI: 0.66-1.32 and severe thrombocytopenia (OR=1.00, 95%CI: 0.64-1.57 and nausea and vomiting (OR=0.85, 95%CI: 0.61-1.20 were similar in the NPE arm compared with those in the NP arm. The NPE plus radiotherapy (RT arm had a similar response rate compared with NP plus RT arm (OR=2.39, 95%CI: 0.99-5.79. The incidences of leukopenia (OR=0.83, 95%CI: 0.35-1.94 and

  9. FDTD analysis of a noninvasive hyperthermia system for brain tumors.

    Science.gov (United States)

    Yacoob, Sulafa M; Hassan, Noha S

    2012-08-14

    Hyperthermia is considered one of the new therapeutic modalities for cancer treatment and is based on the difference in thermal sensitivity between healthy tissues and tumors. During hyperthermia treatment, the temperature of the tumor is raised to 40-45°C for a definite period resulting in the destruction of cancer cells. This paper investigates design, modeling and simulation of a new non-invasive hyperthermia applicator system capable of effectively heating deep seated as well as superficial brain tumors using inexpensive, simple, and easy to fabricate components without harming surrounding healthy brain tissues. The proposed hyperthermia applicator system is composed of an air filled partial half ellipsoidal chamber, a patch antenna, and a head model with an embedded tumor at an arbitrary location. The irradiating antenna is placed at one of the foci of the hyperthermia chamber while the center of the brain tumor is placed at the other focus. The finite difference time domain (FDTD) method is used to compute both the SAR patterns and the temperature distribution in three different head models due to two different patch antennas at a frequency of 915 MHz. The obtained results suggest that by using the proposed noninvasive hyperthermia system it is feasible to achieve sufficient and focused energy deposition and temperature rise to therapeutic values in deep seated as well as superficial brain tumors without harming surrounding healthy tissue. The proposed noninvasive hyperthermia system proved suitable for raising the temperature in tumors embedded in the brain to therapeutic values by carefully selecting the systems components. The operator of the system only needs to place the center of the brain tumor at a pre-specified location and excite the antenna at a single frequency of 915 MHz. Our study may provide a basis for a clinical applicator prototype capable of heating brain tumors.

  10. Micronucleus formation compared to the survival rate of human melanoma cells after X-ray and neutron irradiation and hyperthermia

    Energy Technology Data Exchange (ETDEWEB)

    van Beuningen, D.; Streffer, C.; Bertholdt, G.

    1981-09-01

    After neutron and X-ray irradiation and combined X-ray irradiation and hyperthermia (3 hours, 42/sup 0/C), the survival rate of human melanoma cells was measured by means of the colony formation test and compared to the formation of micronuclei. Neutrons had a stronger effect on the formation of micronuclei than the combination of X-rays and hyperthermia. X-rays had the lowest effect. The dose effect curve showed a break at that dose level at which a reduction of cells was observed in the cultures. A good relation between survival rate and formation of micronuclei was found for the X-ray irradiation, but not for the neutron irradiation and the combined treatment. These observations are discussed. At least for X-rays, the micronucleus test has turned out to be a good screening method for the radiosensitivity of a biologic system.

  11. Association of rectal toxicity with thermal dose parameters in treatment of locally advanced prostate cancer with radiation and hyperthermia

    International Nuclear Information System (INIS)

    Hurwitz, Mark D.; Kaplan, Irving D.; Hansen, Jorgen L.; Prokopios-Davos, Savina; Topulos, George P.; Wishnow, Kenneth; Manola, Judith; Bornstein, Bruce A.; Hynynen, Kullervo

    2002-01-01

    Purpose: Although hyperthermia has been used for more than two decades in the treatment of pelvic tumors, little is known about the potential impact of heat on rectal toxicity when combined with other treatment modalities. Because rectal toxicity is a concern with radiation and may be exacerbated by hyperthermia, definition of the association of thermal dose parameters with rectal toxicity is important. In this report, we correlate rectal toxicity with thermal dose parameters for patients treated with hyperthermia and radiation for prostate cancer. Methods and Materials: Thirty patients with T2b-T3b disease (1992 American Joint Committee On Cancer criteria) enrolled in a Phase II study of external beam radiation ± androgen-suppressive therapy with two transrectal ultrasound hyperthermia treatments were assessed for rectal toxicity. Prostatic and anterior rectal wall temperatures were monitored for all treatments. Rectal wall temperatures were limited to 40 deg. C in 19 patients, 41 deg. C in 3 patients, and 42 deg. C in 8 patients. Logistic regression was used to estimate the log hazard of developing National Cancer Institute Common Toxicity Criteria Grade 2 toxicity based on temperature parameters. The following were calculated: hazard ratios, 95% confidence intervals, p values for statistical significance of each parameter, and proportion of variability explained for each parameter. Results: Gastrointestinal toxicity was limited to Grade 2. The rate of acute Grade 2 proctitis was greater for patients with an allowable rectal wall temperature of >40 deg. C. In this group, 7 of 11 patients experienced acute Grade 2 proctitis, as opposed to 3 of 19 patients in the group with rectal wall temperatures limited to 40 deg. C (p=0.004). Preliminary assessment of long-term toxicity revealed no differences in toxicity. Hazard ratios for acute Grade 2 proctitis for allowable rectal wall temperature, average rectal wall Tmax, and average prostate Tmax were 9.33 (p=0.01), 3

  12. Gemcitabine-Based Combination Chemotherapy Followed by Radiation With Capecitabine as Adjuvant Therapy for Resected Pancreas Cancer

    International Nuclear Information System (INIS)

    Desai, Sameer; Ben-Josef, Edgar; Griffith, Kent A.; Simeone, Diane; Greenson, Joel K.; Francis, Isaac R.; Hampton, Janet; Colletti, Lisa; Chang, Alfred E.; Lawrence, Theodore S.; Zalupski, Mark M.

    2009-01-01

    Purpose: To report outcomes for patients with resected pancreas cancer treated with an adjuvant regimen consisting of gemcitabine-based combination chemotherapy followed by capecitabine and radiation. Patients and Methods: We performed a retrospective review of a series of patients treated at a single institution with a common postoperative adjuvant program. Between January 2002 and August 2006, 43 resected pancreas cancer patients were offered treatment consisting of 4, 21-day cycles of gemcitabine 1 g/m 2 intravenously over 30 min on Days 1 and 8, with either cisplatin 35 mg/m 2 intravenously on Days 1 and 8 or capecitabine 1500 mg/m 2 orally in divided doses on Days 1-14. After completion of combination chemotherapy, patients received a course of radiotherapy (54 Gy) with concurrent capecitabine (1330 mg/m 2 orally in divided doses) day 1 to treatment completion. Results: Forty-one patients were treated. Median progression-free survival for the entire group was 21.7 months (95% confidence interval 13.9-34.5 months), and median overall survival was 45.9 months. In multivariate analysis a postoperative CA 19-9 level of ≥180 U/mL predicted relapse and death. Toxicity was mild, with only two hospitalizations during adjuvant therapy. Conclusions: A postoperative adjuvant program using combination chemotherapy with gemcitabine and either cisplatin or capecitabine followed by radiotherapy with capecitabine is tolerable and efficacious and should be considered for Phase III testing in this group of patients.

  13. Hemangiosarcoma in a Dog: Unusual Presentation and Increased Survival Using a Complementary/Holistic Approach Combined with Metronomic Chemotherapy

    Directory of Open Access Journals (Sweden)

    Philip Chaikin

    2018-01-01

    Full Text Available This case report documents the clinical and pathologic findings in a 12-year-old terrier mix with intraocular and splenic hemangiosarcoma. Pathologic findings in both the spleen and globe were consistent with hemangiosarcoma with a low mitotic count. Initial treatment consisted of enucleation and then splenectomy followed by one cycle of conventional doxorubicin chemotherapy. Due to poor tolerance, a subsequent treatment regimen consisted of metronomic chemotherapy with chlorambucil combined with an alternative/complementary regimen of I’m-Yunity (polysaccharopeptide and Yunnan Baiyao. Follow-up thoracic radiographs and abdominal ultrasounds over a period of 24 months showed no evidence of pulmonary, hepatic, or right atrial metastases, during which time the patient had an excellent quality of life. However, shortly after achieving two-year survival, the patient developed new onset seizures unresponsive to anticonvulsant therapy. Therefore, a decision was made to euthanize the dog given that the most likely etiology of the seizures was a brain tumor. Overall, this is an exceptional treatment response given the poor survival statistics of hemangiosarcoma even with conventional chemotherapy. However, additional clinical pharmacology and clinical trial data are needed to further support the use of a complementary/holistic approach in combination with metronomic chemotherapy.

  14. Potent antitumor activities of recombinant human PDCD5 protein in combination with chemotherapy drugs in K562 cells

    International Nuclear Information System (INIS)

    Shi, Lin; Song, Quansheng; Zhang, Yingmei; Lou, Yaxin; Wang, Yanfang; Tian, Linjie; Zheng, Yi; Ma, Dalong; Ke, Xiaoyan; Wang, Ying

    2010-01-01

    Conventional chemotherapy is still frequently used. Programmed cell death 5 (PDCD5) enhances apoptosis of various tumor cells triggered by certain stimuli and is lowly expressed in leukemic cells from chronic myelogenous leukemia patients. Here, we describe for the first time that recombinant human PDCD5 protein (rhPDCD5) in combination with chemotherapy drugs has potent antitumor effects on chronic myelogenous leukemia K562 cells in vitro and in vivo. The antitumor efficacy of rhPDCD5 protein with chemotherapy drugs, idarubicin (IDR) or cytarabine (Ara-C), was examined in K562 cells in vitro and K562 xenograft tumor models in vivo. rhPDCD5 protein markedly increased the apoptosis rates and decreased the colony-forming capability of K562 cells after the combined treatment with IDR or Ara-C. rhPDCD5 protein by intraperitoneal administration dramatically improved the antitumor effects of IDR treatment in the K562 xenograft model. The tumor sizes and cell proliferation were significantly decreased; and TUNEL positive cells were significantly increased in the combined group with rhPDCD5 protein and IDR treatment compared with single IDR treatment groups. rhPDCD5 protein, in combination with IDR, has potent antitumor effects on chronic myelogenous leukemia K562 cells and may be a novel and promising agent for the treatment of chronic myelogenous leukemia.

  15. Advanced epithelial ovarian cancer: toxicity of whole abdominal irradiation after operation, combination chemotherapy, and reoperation

    International Nuclear Information System (INIS)

    Schray, M.F.; Martinez, A.; Howes, A.E.; Ballon, S.C.; Podratz, K.C.; Sikic, B.I.; Malkasian, G.D.

    1986-01-01

    Thirty-five patients with advanced ovarian cancer have received, as salvage therapy, irradiation consisting of 30 Gy to the entire abdominal contents with partial liver/kidney shielding and boosts to 42 and 51 Gy for the paraaortic/diaphragmatic and pelvic regions, respectively. These patients had received 6 to 25 cycles (median, 11 cycles) of prior combination chemotherapy (included cisplatin in 30), with second-look laparotomy performed in 33; 24 (68%) had three or more laparotomies. Acute gastrointestinal toxicity was generally mild. Significant hematologic toxicity (leukocytes less than 2000/mm3; or platelets less than 100,000/mm3) was seen in 19 (54%); platelet suppression occurred in 18 of these 19. Nine patients failed to complete the prescribed course of therapy; in seven, this was secondary to hematologic toxicity. Amount of prior chemotherapy and advanced age correlated with degree of hematologic toxicity. Five patients without evidence of disease (laparotomy confirmed) have developed treatment-related bowel obstruction. No other chronic toxicity of clinical significance has been observed. Seven patients have developed bowel obstruction associated with progressive neoplasm. Irradiation was well tolerated symptomatically, but hematologic toxicity associated with prior chemotherapy prevented its completion in 20% of patients. Clinical manifestations of radiation bowel toxicity have been moderate to date and should be interpreted in the context of the aggressive combined modality program

  16. Small-cell carcinoma of the esophagus with regression after combination chemotherapy and radiation therapy

    International Nuclear Information System (INIS)

    Hirsch, J.A.; Levine, M.S.; Silberg, D.G.; Phillipe, L.

    1995-01-01

    The authors present an unusual case of small-cell carcinoma of the esophagus, which manifested on double-contrast esophagography as an ulcerated submucosal mass. The lesion underwent dramatic regression after combination chemotherapy and radiation therapy, which has occasionally been used as an alternative to surgery in patients with this rare but aggressive esophageal neoplasm. (author). 8 refs., 4 figs

  17. One-dimensional phased array with mechanical motion for conformal ultrasound hyperthermia

    International Nuclear Information System (INIS)

    Ju, Kuen-Cheng; Chen, Yung-Yaw; Lin, Win-Li; Kuo, Te-Son

    2003-01-01

    This paper investigates the feasibility of conformal heating for external ultrasound hyperthermia by using a phased array transducer with mechanical motion. In this system, a one-dimensional phased array is arranged on a shaft and moves along the shaft, while dynamically focusing on the planning target volume (PTV) with numerous focal spots. To prevent overheating in the intervening tissue between the skin and the PTV, the shaft and the phased array are rotated together to enlarge the acoustical window. With the purpose of conformal heating, the power deposition of the PTV is constructed by combinations of the focal spots and an iterative gradient descent method is then used to determine an optimal set of power weightings for the focal spots. Different tumour shapes are evaluated and the simulation results demonstrate that the volume percentage of the PTV with temperatures higher than 43 deg. C is over 95%. The overheating volume outside the PTV is less than 25% of the PTV. This method provides good conformal heating for external ultrasound hyperthermia. The concept of combining electrical focusing and mechanical motion has the advantages of both enlarging the acoustic window and providing dynamic focusing ability, which is essential for successful conformal heating

  18. Strategies to reduce hyperthermia in ambulatory multiple sclerosis patients.

    Science.gov (United States)

    Edlich, Richard F; Buschbacher, Ralph M; Cox, Mary Jude; Long, William B; Winters, Kathryne L; Becker, Daniel G

    2004-01-01

    Approximately 400,000 Americans have multiple sclerosis. Worldwide, multiple sclerosis affects 2.5 million individuals. Multiple sclerosis affects two to three times as many women as men. The adverse effects of hyperthermia in patients with multiple sclerosis have been known since 1890. While most patients with multiple sclerosis experience reversible worsening of their neurologic deficits, some patients experience irreversible neurologic deficits. In fact, heat-induced fatalities have been encountered in multiple sclerosis patients subjected to hyperthermia. Hyperthermia can be caused through sun exposure, exercise, and infection. During the last 50 years, numerous strategies have evolved to reduce hyperthermia in individuals with multiple sclerosis, such as photoprotective clothing, sunglasses, sunscreens, hydrotherapy, and prevention of urinary tract infections. Hydrotherapy has become an essential component of rehabilitation for multiple sclerosis patients in hospitals throughout the world. On the basis of this positive hospital experience, hydrotherapy has been expanded through the use of compact aquatic exercise pools at home along with personal cooling devices that promote local and systemic hypothermia in multiple sclerosis patients. The Multiple Sclerosis Association of America and NASA have played leadership roles in developing and recommending technology that will prevent hyperthermia in multiple sclerosis patients and should be consulted for new technological advances that will benefit the multiple sclerosis patient. In addition, products recommended for photoprotection by The Skin Cancer Foundation may also be helpful to the multiple sclerosis patient's defense against hyperthermia. Infections in the urinary tract, especially detrusor-external sphincter dyssynergia, are initially managed conservatively with intermittent self-catheterization and pharmacologic therapy. In those cases, refractory to conservative therapy, transurethral external

  19. Histopathological studies of radiation-combined intra-arterial chemotherapy on squamous cell carcinoma of the mandible

    International Nuclear Information System (INIS)

    Yonemochi, Takemi

    1996-01-01

    The 2nd Department of Oral and Maxillofacial Surgery, Faculty of Dentistry Hospital, Iwate Medical University has performed radiation-combined intra-arterial chemotherapy as a preoperative treatment and subsequent mandibulectomy. During a 20 year-period from 1975 to 1994, clinical and histopathological examination of the above therapy was made for its effect and usefulness by using 15 primary cases of mandibular gingival squamous cell carcinoma, which were all identifiable. Roentgenological examination by bone resorptive pattern (invasive type, erosive type) and by bone resorptive depth (degree 0-III) revealed that early infiltration case and advanced case were predominant in the erosive type and the invasive type respectively. Histopathologically, the therapeutical effect of the radiation-combined intra-arterial chemotherapy on the tumor cells was examined using osteoclast, fibrous connective tissue, osteoblast, new bone, site of neoosteogenesis, and post-treatment site of residual tumor ceils as findings in the healing process. The histological therapeutic effect was good on well-differentiated type cases, and the histological effect on osteo-infiltrated region was as good as, or better than on soft tissue region. The cases with good histological therapeutic effect scarcely showed osteoclast, but showed remarkable hyperplasia of fibrous connective tissue, appearance of osteoblast and repair mechanism via neoosteogenesis. Invasive type tumor was persistent in the depth of the mandible, while erosive type tumor showed a tendency to be persistent in superficial layer. The results suggested that the application of the present radiation-combined intra-arterial chemotherapy to mandibular gingival squamous cell carcinoma is very useful leading to the improvement in radical curability of the tumor in its primary focus and the preservation of mandibular continuity in surgery. (author)

  20. Effect of hyperthermia and misonidazole on the radiosensitivity of a transplant murine tumor: influence of factors modifying the fraction of hypoxic cells

    International Nuclear Information System (INIS)

    Wondergem, J.; Haveman, J.; van der Schueren, E.; van den Hoeven, H.; Breur, K.

    1982-01-01

    Hypoxia has been demonstrated to play an important role in the effect of hyperthermia on tumors. The influence of different factors modifying the oxygenation status of a transplantable murine mammary adenocarcinoma has been studied. The effect of hyperthermia alone on the tumor is not significantly influenced by the change in oxygenation status during the growth of the tumor. Also, the large increase of the acutely hypoxic cell fraction, as a result of anesthesia, does not change the effect of hyperthermia alone. In the combined irradiation-heat treatment there is a clear influence of the chronically hypoxic cell fraction on the response to hyperthermia: an increase in tumor size, resulting in a larger hypoxic cell fraction, leads to an increase in thermal enhancement ratio. However, the increased acutely hypoxic cell fraction, resulting from anesthesia, did not lead to an increase in thermal enhancement ratio; in fact the enhancement ratio apparently decreased. In spite of the fact that hyperthermia was applied immediately after irradiation no potentiation of radiation effects was found. The thermal enhancement of the radiation response was never larger than the enhancement as a result of misonidazole

  1. Thermosensitive Nanostructured Media for imaging and Hyperthermia Cancer Treatment

    Science.gov (United States)

    Martirosyan, Karen

    2011-03-01

    Hyperthermia has been used for many years to treat a wide variety of tumors in patients. The most commonly applied method of hyperthermia is capacitive heating by using microwave. Magnetic fluids based on iron oxide (Fe3O4), stabilized by biocompatible surfactants are typically used as heating agent. However, significant limitations of using commercial available magnetic particles are non-selectivity and overheating of surrounding normal tissues. To improve the efficacy of hyperthermia treatment we intend to develop Curie temperature (Tc)-tuned nanostructured media having T2 relaxation response on MRI for selective and self-controlled hyperthermia cancer treatment. As an active part of this media we fabricated superparamagnetic, biocompatible and dextran coated ferrite nanoparticles Mg1+xTixFe2(1-x)O4 at 0.3 x connected to a hydrocarbon chain, such as glycine, hydrazine, or urea. Our experiments revealed that ferrite with formula Mg1.35Ti0.35Fe1.3O4 appears with Curie temperature within 46-50rC. NSF, grant # 0933140.

  2. Effects of hyperthermia, radiotherapy and thermoradiotherapy on tumor microvasculature

    International Nuclear Information System (INIS)

    Fujiwara, Kouji

    1987-01-01

    The therapeutic effects of hyperthermia (immersion of tumor-bearing leg in a water bath at 46 deg C for 60 min), radiotherapy (500 rad or 1000 rad) and thermoradiotherapy on VX-2 tumors of the rabbits were studied morphologically. Especially, vascular morphological changes and vascular permeability to ferritin after treatment were investigated by electron microscopy. As assessed by decrease in tumor volume, local hyperthermia potentiated the destructive effect of radiotherapy. The light microscopic pictures invariably suggested prolonged necrotic tendency of tumor cells following thermoradiotherapy. Electron microscopically, 1 day and 3 days after thermoradiotherapy, small blood vessels in the tumors showed swelling and protrusion of endothelial cells in the lumen. Similar morphological changes were obtained only at 3 days after radiotherapy. When vascular permeability to ferritin was examined by electron microscopy, an increase in tumor vascular permeability was occured at 1 day after hyperthermia or thermoradiotherapy, while at 3 days after radiotherapy. These results suggest that the early reaction of tumor microvasculature may be a contributing factor to delayed cell death in tumors after hyperthermia or thermoradiotherapy. (author)

  3. Intra-arterial chemotherapy combined with irradiation for invasive bladder cancer

    International Nuclear Information System (INIS)

    Fujimoto, Naohiro; Sato, Hideki; Harada, Shuji; Matsumoto, Tetsuro; Ikuyama, Toshihiro

    2004-01-01

    Total cystectomy and urinary diversion are the standard treatments for invasive bladder cancer. However, total cystectomy is not possible in some patients due to advanced age, a poor general condition, or refusal to undergo cystectomy. In such cases, intra-arterial chemotherapy (IAC) and/or radiotherapy are the alternative treatments. We performed IAC with cisplatin and adriamycin in 9 patients with invasive bladder cancer and obtained complete response (CR) in 5 out of the 9 patients (55.6%). However, 3 of these 5 CR patients developed local recurrence within 1 year. In an effort to improve the efficacy, we performed combination therapy comprising IAC plus radiotherapy in 12 patients with invasive bladder cancer. CR was obtained in 58.3% and the bladder was preserved in 91.7% with this combination therapy. However, distant metastases developed in 33.3% after the combined treatment of IAC plus radiation therapy. These findings suggest that the combination of radiotherapy and IAC is useful for local control of invasive bladder cancer. Data from more cases and results from a longer follow-up are needed to fully confirm the efficacy of this type of treatment. In addition, therapeutic modalities to prevent distant metastasis need to be considered. (author)

  4. Combined chemotherapy and radiotherapy in the treatment of lung cancer

    International Nuclear Information System (INIS)

    Wolf, M.

    1992-01-01

    In the past decade the prognosis of patients with locally advanced lung cancer has not been altered significantly. In both small and non-small cell lung cancer cure rates are poor and 5-year survival rate still has not exceeded the 5% borderline. Despite of initially high response rates, a vast majority of patients suffered from tumor progression within 2 years after the start of treatment. Sites of tumor progression are either the primary tumor or the occurrence of distant metastases. Therefore, improvements of both local and systemic tumor control are necessary to increase long-term survival rate in lung cancer. Combined chemo- and radiotherapy may be an appropriate treatment approach to reach these aims. In patients with locally advanced lung cancer combined chemo-radiotherapy aims at overcoming radio- and chemo-therapy resistance as a cause of local treatment failure and at early eradication of distant micrometastases as a cause of systemic treatment failure. (author). 29 refs., 2 figs., 6 tabs

  5. Magnetic fluid hyperthermia probed by both calorimetric and dynamic hysteresis measurements

    Energy Technology Data Exchange (ETDEWEB)

    Guibert, Clément; Fresnais, Jérôme; Peyre, Véronique; Dupuis, Vincent, E-mail: vincent.dupuis@upmc.fr

    2017-01-01

    In this paper, we report an investigation of magnetic fluid hyperthermia (MFH) using combined calorimetric and newly implemented dynamic hysteresis measurements for two sets of well characterized size-sorted maghemite nanoparticles (with diameters of about 10 nm and 20 nm) dispersed in water and in glycerol. Our primary goal was to assess the influence of viscosity on the heating efficiency of magnetic nanoparticles described in terms of specific loss power (SLP or specific absorption rate, SAR) and dynamic hysteresis. In particular, we aimed to investigate how this SLP depends on the transition from Néelian to Brownian behavior of nanoparticles expected to occur between 10 nm and 20 nm (for maghemite) and dependent on the viscosity. While we observed a good agreement between calorimetric and dynamic hysteresis measurements, we found that the SLP measured for the different systems do not depend noticeably on the viscosity of solvent. Calculations performed according to Rosensweig's linear model [1] allow us to quantitatively reproduce our results at low field intensities, provided we use a value for the magnetic anisotropy constant much smaller than the one commonly used in the literature. This raises the question of the temperature dependance of the magnetic anisotropy constant and its relevance for a quantitative description of MFH. - Highlights: • Dynamic hysteresis measurements are a promising tool to study magnetic hyperthermia. • Dynamic hysteresis cycles can be reproduced using a simple model. • The effect of viscosity on hyperthermia of maghemite is weaker than expected.

  6. Phase II study of gemcitabine plus cisplatin chemotherapy combined with intensity modulated radiotherapy in locoregionally advanced nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Ou Dan; He Xiayun; Hu Chaosu; Ying Hongmei; Zhu Guopei

    2012-01-01

    Objective: To evaluate the efficacy and toxicity of gemcitabine plus cisplatin (GP) chemotherapy combined with intensity-modulated radiation therapy (IMRT) in locoregionally advanced nasopharyngeal carcinoma (NPC). Methods: 71 patients (Stage III: 41, Stage IV A : 30) with locoregionally advanced NPC were entered this study. Neoadjuvant chemotherapy was consisted of cisplatin 25 mg/m 2 intravenously on d1-3 and gemcitabine 1000 mg/m 2 in 30 minutes intravenous infusion on days 1 and 8, every 3 weeks for 2 cycles. Adjuvant chemotherapy consisted of 2 cycles of the same GP regimen was given at 28 days after the end of radiotherapy. The prescription doses was 66.0-70.4 Gy to the gross tumor volume, 66 Gy to positive neck nodes, 60 Gy to the high-risk clinical target volume, 54 Gy to the low-risk clinical target volume. Results: The overall response rate to neoadjuvant chemotherapy was 91.2%, acute toxicity was mainly grade 1-2 myleosuppression. All patients completed IMRT. The median follow-up duration was 38 months. The 3-year nasopharyngeal local control, regional control, distant metastasis-free survival rate and overall survival rate were 93%, 99%, 91%, 90%, respectively. Severe late toxicities included grade 3 trismus in 1 patient, grade 3 hearing impairment in 2 patients and cranial nerve palsy in 2 patients, respectively. No grade 4 late toxicities were observed. Conclusions: The combination of GP chemotherapy and IMRT for locoregionally advanced nasopharyngeal carcinoma is well-tolerated, convenient, effective, and warrants further studies of more proper cycles of GP regimen. (authors)

  7. Metronomic chemotherapy.

    Science.gov (United States)

    Mutsaers, Anthony J

    2009-08-01

    Chemotherapy drugs are usually administered at doses that are high enough to result in an obligatory break period to allow for the observation of potential side effects and institution of supportive care, if required. In recent years, efforts to administer chemotherapy on a more continuous basis, with a much shorter break period, or none at all, have received increased interest, and the practice has come to be known as metronomic chemotherapy. The basis for success with this currently investigational approach may be rooted in continuous drug exposure to susceptible cancer cells, inhibition of tumor blood vessel growth-a process known as tumor angiogenesis, and/or alterations in tumor immunology. Increased benefit also appears to occur when metronomic chemotherapy is used in combination with newer, targeted antiangiogenic agents, and therefore represents a promising approach to combination therapy, particularly as targeted oncology drugs make their way into veterinary oncology applications. There is still much to be learned in this field, especially with regard to optimization of the proper drugs, dose, schedule, and tumor applications. However, the low cost, ease of administration, and acceptable toxicity profiles potentially associated with this therapeutic strategy make metronomic chemotherapy protocols attractive and suitable to veterinary applications. Preliminary clinical trial results have now been reported in both human and veterinary medicine, including adjuvant treatment of canine splenic hemangiosarcoma and incompletely resected soft tissue sarcoma, and, further, more powerful studies are currently ongoing.

  8. Effects of intraoperative irradiation (IORT) and intraoperative hyperthermia (IOHT) on canine sciatic nerve : Histopathological and morphometric studies

    NARCIS (Netherlands)

    Vujaskovic, Z; Powers, BE; Paardekoper, G; Gillette, SM; Gillette, EL; Colacchio, TA

    1999-01-01

    Purpose/Objective: Peripheral neuropathies have emerged as the major dose-limiting complication reported after intraoperative radiation therapy (IORT). The combination of IORT with hyperthermia may further increase the risk of peripheral nerve injury. The objective of this study was to evaluate

  9. The influence of hyperthermia and irradiation on some bioelectric parameters of the cells

    International Nuclear Information System (INIS)

    Solic, F.; Milotic, B.; Stipcic-Solic, N.

    1986-01-01

    The simultaneously influence of hyperthermia and low intensity gamma irradiation on the biopotential and the resistance of Nitella cells were investigated. The effect induced by irradiation and hyperthermia is manifested as membrane repolarization while hyperthermia alone induced depolarization. The resistance of cells is in positive correlation with membrane potential. (author)

  10. Preparation and characterization of composite microspheres for brachytherapy and hyperthermia treatment of cancer

    International Nuclear Information System (INIS)

    Zhao Di; Huang Wenhai; Rahaman, Mohamed N.; Day, Delbert E.; Wang Deping; Gu Yifei

    2012-01-01

    Composite microspheres were prepared by coating yttrium–aluminum–silicate (YAS) glass microspheres (20–30 μm) with a layer of Fe 3 O 4 nanoparticles and evaluated for potential use in brachytherapy and hyperthermia treatment of cancer. After neutron activation to form the β-emitting 90 Y radionuclide, the composite microspheres can be injected into a patient to destroy cancerous tumors; at the same time, the composite microspheres can generate heat upon application of a magnetic field to also destroy the tumors. The results showed that the composite microspheres were chemically durable when immersed in a simulated body fluid (SBF), with ∼ 0.25% weight loss and ∼ 3.2% yttrium dissolved into the SBF after 30 days at 37 °C. The composite microspheres also showed ferromagnetic properties as a result of the Fe 3 O 4 coating; when immersed in water at 20 °C (20 mg in 1 mL of water), the application of an alternating magnetic field produced a temperature increase from 20 °C to 38−46 °C depending on the thickness of the Fe 3 O 4 coating. The results indicate that these composite microspheres have promising potential in combined brachytherapy and hyperthermia treatment of cancerous tumors. - Highlights: ► Composite microspheres for brachytherapy and hyperthermia treatment of cancer. ► Fe 3 O 4 nanoparticles coated on the yttrium–aluminum–silicate glass microspheres. ► Microspheres are chemically stable in SBF. ► Microspheres can generate heat for hyperthermia under an alternating magnetic field. ► Microspheres can emit β-rays for brachytherapy after neutron activation.

  11. Effect of hyperthermia on radiation damage and its repair in Tribolium confusum

    International Nuclear Information System (INIS)

    Lai, P.K.

    1977-01-01

    A series of temperature tolerance curves from 43.5 0 C to 46.0 0 C in 0.5 0 C increment were determined. Two non-lethal hyperthermia schemes, i.e., 45.0 0 C for 2 hr and 43.0 0 C for 2 hr were chosen to examine the sensitizing effect of heat on lethality produced by radiation in flour beetles. When hyperthermia was applied either immediately before or after irradiation, the sensitizing effect of hyperthermia was indicated by the shifting of the regression line of survival in probits on dose to the left of that of the control. The sensitizing effect as measured by decreased LD 50 did not reveal any definite trend related to the order of application of the two modalities in immediate sequence. The effect of hyperthermia was more dramatic in dose-fractionation experiments. Flour beetles exhibited typical Elkind kinetics of split-dose repair and recovery, and the amount of the sparing effect of dose-fractionation (sdf) was influenced by interfraction temperature. Both interfraction hypothermia (i.e., less than or equal to 10 0 C) and interfraction hyperthermia (i.e., > 42.0 0 C) completely suppress sdf. However, the mechanism involved in the suppression of sdf by hypothermia was different than that by hyperthermia. In the former, the suppression of sdf was reversible immediately upon return to the normal incubation temperature of 30 0 C; in the latter, the suppression of sdf was protracted and the reversibility of sdf depended on the severity of the hyperthermia treatment. Hyperthermia of 43.0 0 C for 2 hr, applied either immediately before or after the first radiation dose, suppressed sdf for 6-10 hr, and then sdf reappeared slowly, so that the final level of survival was slightly less than that of the comparable groups maintained at 30 0 C. With the more severe hyperthermia treatment of 45.0 0 C for 2 hr, sdf was suppressed for almost 36 hr after return to 30 0 C although there were some slight surges in survival

  12. Preoperative radiochemotherapy in locally advanced or recurrent rectal cancer: regional radiofrequency hyperthermia correlates with clinical parameters

    International Nuclear Information System (INIS)

    Rau, B.; Wust, P.; Tilly, W.; Gellermann, J.; Harder, C.; Riess, H.; Budach, V.; Felix, R.; Schlag, P.M.

    2000-01-01

    Purpose: Preoperative radiochemotherapy (RCT) is a widely used means of treatment for patients suffering from primary, locally advanced, or recurrent rectal cancer. We evaluated the efficacy of treatment due to additional application of regional hyperthermia (HRCT) to this conventional therapy regime in a Phase II study, employing the annular phased-array system BSD-2000 (SIGMA-60 applicator). The clinical results of the trial were encouraging. We investigated the relationship between a variety of thermal and clinical parameters in order to assess the adequacy of thermometry, the effectiveness of hyperthermia therapy, and its potential contribution to clinical endpoints. Methods and Materials: A preoperative combination of radiotherapy (1.8 Gy for 5 days a week, total dose 45 Gy applied over 5 weeks) and chemotherapy (low-dose 5-fluorouracil [5-FU] plus leucovorin in the first and fourth week) was administered to 37 patients with primary rectal cancer (PRC) and 18 patients with recurrent rectal cancer (RRC). Regional hyperthermia (RHT) was applied once a week prior to the daily irradiation fraction of 1.8 Gy. Temperatures were registered along rectal catheters using Bowman thermistors. Measurement points related to the tumor were specified after estimating the section of the catheter in near contact with the tumor. Three patients with local recurrence after abdominoperineal resection, had their catheters positioned transgluteally under CT guidance, where the section of the catheter related to the tumor was estimated from the CT scans. Index temperatures (especially T max , T 90 ) averaged over time, cumulative minutes (cum min) (here for T 90 > reference temperature 40.5 deg. C), and equivalent minutes (equ min) (with respect to 43 deg. C) were derived from repetitive temperature-position scans (5- to 10-min intervals) utilizing software specially developed for this purpose on a PC platform. Using the statistical software package SPSS a careful analysis was

  13. Implantation of the maxillary antrum for delivery of iridium brachytherapy and microwave induced hyperthermia

    International Nuclear Information System (INIS)

    Coughlin, C.T.; Wong, T.Z.; Geurkink, N.

    1985-01-01

    A 63 year-old male was referred tp Dartmouth in March 1984 for a locally advanced recurrent squamous cell carcinoma of the left maxillary antrum. This had been initially diagnosed in January 1983 by a Caldwell-Luc procedure and had failed partial resection, external radiation therapy, and multiagent chemotherapy. Our initial evaluation revealed disease replacing the left maxillary antrum, extending into the pterygomaxillary fossa, the lateral aspect of the superior alveloar ridge, and into the soft palate. He was taken to the operating room and under general anesthesia was implanted the 7 catheters through this tumor volume. Two days later a therapeutic (>42 0 C for 1 hour) hyperthermia treatment was administered followed by iridium placement. A second heating was performed upon removal of the iridium and was accomplished without major side effects. Thermometry data and follow-up are presented

  14. Effects of hyperthermia on the normal liver using scintigraphic methods. Functional changes of the rabbit whole-liver by local hyperthermia

    International Nuclear Information System (INIS)

    Ryu, Kiyotaka; Shinotsuka, Akira; Takenaka, Hiroki; Hirono, Yoshisada

    1995-01-01

    An experimental study was conducted to investigate effect of hyperthermia to the liver in rabbits. The whole liver was heated at 43degC for 30 min by a RF capacitive heating device, and subsequent changes were observed by scintigraphy using 99m Tc-EHIDA and 99m Tc-Sn-colloid. The excretory ratio (Ke value) of 99m Tc-EHIDA and the uptake ratio (K value) of 99m Tc-Sn-colloid were measured to estimate hyperthermia induced hepatic injury for a month. Blood chemistry analysis was also conducted during this period. Also, the uptake of 3 H-methyl-thymidine into the DNA of hepatocyted was assayed 2 and 5 days after heating. Concurrently, histopathological changes were observed. The Ke value showed a transient increase and returned to the level prior to heating after approximately one week. A distinct increase in GPT was observed. The uptake of 3 H-methyl-thymidine showed a marked rise 2 days after hyperthermia, which demonstrated regeneration of the previously damaged hepatocytes. Pathologically, overall liver congestion and hepatocytes necrosis were noted. Also, both enlargement of the nuclei and binuclear hepatocytes were present, pathologically proving hepatocytes regeneration. The K value showed a transient decrease, showing that the reticuloendothelial function and blood flow of the liver were temporarily reduced. These results indicate the whole liver function damaged by hyperthermia is reversible. (author)

  15. Acute emesis: moderately emetogenic chemotherapy

    DEFF Research Database (Denmark)

    Herrstedt, Jørn; Rapoport, Bernardo; Warr, David

    2011-01-01

    This paper is a review of the recommendations for the prophylaxis of acute emesis induced by moderately emetogenic chemotherapy as concluded at the third Perugia Consensus Conference, which took place in June 2009. The review will focus on new studies appearing since the Second consensus conference...... receiving multiple cycles of moderately emetogenic chemotherapy will be reviewed. Consensus statements are given, including optimal dose and schedule of serotonin(3) receptor antagonists, dexamethasone, and neurokinin(1) receptor antagonists. The most significant recommendations (and changes since the 2004...... version of the guidelines) are as follows: the best prophylaxis in patients receiving moderately emetogenic chemotherapy (not including a combination of an anthracycline plus cyclophosphamide) is the combination of palonosetron and dexamethasone on the day of chemotherapy, followed by dexamethasone...

  16. Effect of Kanglaite combined with chemotherapy on myelosuppression, immune function and tumor markers levels in patients with breast cancer

    Directory of Open Access Journals (Sweden)

    Qi Pan

    2017-09-01

    Full Text Available Objective: To investigate the effect of Kanglaite combined with chemotherapy on myelosuppression, immune function and tumor markers levels in patients with breast cancer. Methods: A total of 90 breast cancer patients in our hospital were randomly divided into control group (45 cases and observation group (45 cases. The two groups received CAF chemotherapy, and the observation group was additionally given Kanglaite injection (200 mL/d for 2 weeks continuously. Both groups had chemotherapy for 6 courses. The effect on myelosuppression, immune function and tumor markers levels was detected and compared before and after treatment in two groups. Results: After treatment, myelosuppression was found in both groups, and the levels of leukocyte, hemoglobin and platelet decreased significantly compared with before treatment (P0.05, and the levels of immune function indexes (CD3+, CD4+, CD4+/ CD8+ of the observation group were significantly higher than those in the control group (P<0.05) . After treatment, the levels of two tumor markers (CEA, CA15-3 decreased significantly than before treatment in both groups (P<0.05, and the decrease amplitude in the observation group was higher than that in the control group (P<0.05. Conclusions: Kanglaite combined with chemotherapy has evident therapeutic effect on breast cancer. It can alleviate the myelosuppression caused by chemotherapy, improve immune function, and reduce the concentration of tumor markers in patients with breast cancer.

  17. Porcine malignant hyperthermia susceptibility: hypersensitive calcium-release mechanism of skeletal muscle sarcoplasmic reticulum.

    Science.gov (United States)

    O'Brien, P J

    1986-01-01

    This study tested the hypothesis that calcium-release from sarcoplasmic reticulum isolated from malignant hyperthermia swine had abnormal concentration-dependency on release modulators. Halothane stimulated half-maximal calcium-release at similar concentrations for malignant hyperthermia and control sarcoplasmic reticulum (0.10 +/- 0.04 mM). However, concentrations causing half-maximal calcium-release were lower for malignant hyperthermia sarcoplasmic reticulum (P less than 0.001) by an order of magnitude for Ca2+ (28.1 +/- 8.3 versus 1.23 +/- 0.45 nM), adenosine triphosphate (0.33 +/- 0.09 versus 0.023 +/- 0.014 mM) and caffeine (7.79 +/- 1.56 versus 0.80 +/- 0.44 mM). Half-maximal inhibition by Mg2+ occurred at threefold higher concentrations for malignant hyperthermia sarcoplasmic reticulum (0.23 +/- 0.02 versus 0.78 +/- 0.17 mM). The Ca2+-sensitivity curves for calcium-release by sarcoplasmic reticulum isolated from heterozygotes for the malignant hyperthermia-defect were indistinguishable from the averages of the curves for controls and malignant hyperthermia-homozygotes. Results of this study suggest that malignant hyperthermia is initiated due to a hypersensitive calcium-release mechanism which is inherited in an autosomal, codominant pattern and may be diagnosed using calcium-release sensitivity-tests on isolated sarcoplasmic reticulum. Images Fig. 1. PMID:3742367

  18. Genetics Home Reference: malignant hyperthermia

    Science.gov (United States)

    ... 1722-30. Review. Citation on PubMed Litman RS, Rosenberg H. Malignant hyperthermia: update on susceptibility testing. JAMA. ... 27(10):977-89. Review. Citation on PubMed Rosenberg H, Davis M, James D, Pollock N, Stowell ...

  19. Radiotherapy with or without hyperthermia in the treatment of superficial localized breast cancer: results from five randomized controlled trials

    International Nuclear Information System (INIS)

    Vernon, Clare C.; Hand, Jeffrey W.; Field, Stanley B.; Machin, David; Whaley, Jill B.; Zee, Jacoba van der; Putten, Wim L.J. van; Rhoon, Gerard C. van; Dijk, Jan D.P. van; Gonzalez, Dionisio Gonzalez; Liu, F.-F.; Goodman, Phyllis; Sherar, Michael

    1996-01-01

    Purpose: Claims for the value of hyperthermia as an adjunct to radiotherapy in the treatment of cancer have mostly been based on small Phase I or II trials. To test the benefit of this form of treatment, randomized Phase III trials were needed. Methods and Materials: Five randomized trials addressing this question were started between 1988 and 1991. In these trials, patients were eligible if they had advanced primary or recurrent breast cancer, and local radiotherapy was indicated in preference to surgery. In addition, heating of the lesions and treatment with a prescribed (re)irradiation schedule had to be feasible and informed consent was obtained. The primary endpoint of all trials was local complete response. Slow recruitment led to a decision to collaborate and combine the trial results in one analysis, and report them simultaneously in one publication. Interim analyses were carried out and the trials were closed to recruitment when a previously agreed statistically significant difference in complete response rate was observed in the two larger trials. Results: We report on pretreatment characteristics, the treatments received, the local response observed, duration of response, time to local failure, distant progression and survival, and treatment toxicity of the 306 patients randomized. The overall CR rate for RT alone was 41% and for the combined treatment arm was 59%, giving, after stratification by trial, an odds ratio of 2.3. Not all trials demonstrated an advantage for the combined treatment, although the 95% confidence intervals of the different trials all contain the pooled odds ratio. The greatest effect was observed in patients with recurrent lesions in previously irradiated areas, where further irradiation was limited to low doses. Conclusion: The combined result of the five trials has demonstrated the efficacy of hyperthermia as an adjunct to radiotherapy for treatment of recurrent breast cancer. The implication of these encouraging results is that

  20. FDTD analysis of a noninvasive hyperthermia system for brain tumors

    Directory of Open Access Journals (Sweden)

    Yacoob Sulafa M

    2012-08-01

    Full Text Available Abstract Background Hyperthermia is considered one of the new therapeutic modalities for cancer treatment and is based on the difference in thermal sensitivity between healthy tissues and tumors. During hyperthermia treatment, the temperature of the tumor is raised to 40–45°C for a definite period resulting in the destruction of cancer cells. This paper investigates design, modeling and simulation of a new non-invasive hyperthermia applicator system capable of effectively heating deep seated as well as superficial brain tumors using inexpensive, simple, and easy to fabricate components without harming surrounding healthy brain tissues. Methods The proposed hyperthermia applicator system is composed of an air filled partial half ellipsoidal chamber, a patch antenna, and a head model with an embedded tumor at an arbitrary location. The irradiating antenna is placed at one of the foci of the hyperthermia chamber while the center of the brain tumor is placed at the other focus. The finite difference time domain (FDTD method is used to compute both the SAR patterns and the temperature distribution in three different head models due to two different patch antennas at a frequency of 915 MHz. Results The obtained results suggest that by using the proposed noninvasive hyperthermia system it is feasible to achieve sufficient and focused energy deposition and temperature rise to therapeutic values in deep seated as well as superficial brain tumors without harming surrounding healthy tissue. Conclusions The proposed noninvasive hyperthermia system proved suitable for raising the temperature in tumors embedded in the brain to therapeutic values by carefully selecting the systems components. The operator of the system only needs to place the center of the brain tumor at a pre-specified location and excite the antenna at a single frequency of 915 MHz. Our study may provide a basis for a clinical applicator prototype capable of heating brain tumors.

  1. Microwave Ablation in Combination with Chemotherapy for the Treatment of Advanced Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Zhigang, E-mail: weizhigang321321@163.com; Ye, Xin, E-mail: yexintaian@aliyun.com; Yang, Xia, E-mail: yangxjinan@163.com; Zheng, Aimin, E-mail: am-zheng@163.com; Huang, Guanghui, E-mail: hgh3612@163.com; Li, Wenhong, E-mail: wenghong-li@163.com; Ni, Xiang, E-mail: asuka2521@hotmail.com; Wang, Jiao; Han, Xiaoying, E-mail: mylittlecarol@sina.com [Shandong Provincial Hospital Affiliated to Shandong University, Department of Oncology (China)

    2015-02-15

    PurposeTo verify whether microwave ablation (MWA) used as a local control treatment had an improved outcome regarding advanced non-small cell lung cancer (NSCLC) when combined with chemotherapy.MethodsThirty-nine patients with histologically verified advanced NSCLC and at least one measurable site other than the ablative sites were enrolled. Primary tumors underwent MWA followed by platinum-based doublet chemotherapy. Modified response evaluation criteria in solid tumors (mRECIST) and RECIST were used to evaluate therapeutic response. Complications were assessed using the National Cancer Institute Common Toxicity Criteria (version 3.0).ResultsMWA was administered to 39 tumors in 39 patients. The mean and median diameters of the primary tumor were 3.84 cm and 3.30 cm, respectively, with a range of 1.00–9.00 cm. Thirty-three (84.6 %) patients achieved a partial response. No correlation was found between MWA efficacy and clinicopathologic characteristics. For chemotherapy, 11 patients (28.2 %) achieved a partial response, 18 (46.2 %) showed stable disease, and 10 (25.6 %) had progressive disease. The overall objective response rate and disease control rate were 28.2 and 74.4 %, respectively. The median progression-free survival time was 8.7 months (95 % CI 5.5–11.9). The median overall survival time was 21.3 months (95 % CI 17.0–25.4). Complications were observed in 22 (56.4 %) patients, and grade 3 adverse events were observed in 3 (7.9 %) patients.ConclusionsPatients with advanced NSCLC could benefit from MWA in combination with chemotherapy. Complications associated with MWA were common but tolerable.

  2. Social factors modulate restraint stress induced hyperthermia in mice.

    Science.gov (United States)

    Watanabe, Shigeru

    2015-10-22

    Stress-induced hyperthermia (SIH) was examined in three different social conditions in mice by thermographic measurement of the body surface temperature. Placing animals in cylindrical holders induced restraint stress. I examined the effect of the social factors in SIH using the thermograph (body surface temperature). Mice restrained in the holders alone showed SIH. Mice restrained in the holders at the same time as other similarly restrained cage mates (social equality condition) showed less hyperthermia. Interestingly, restrained mice with free moving cage mates (social inequality condition) showed the highest hyperthermia. These results are consistent with a previous experiment measuring the memory-enhancing effects of stress and the stress-induced elevation of corticosterone, and suggest that social inequality enhances stress. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. The effect of icotinib combined with chemotherapy in untreated non-small-cell lung cancer that harbored EGFR-sensitive mutations in a real-life setting: a retrospective analysis.

    Science.gov (United States)

    Wang, Lulu; Li, Yan; Li, Luchun; Wu, Zhijuan; Yang, Dan; Ma, Huiwen; Wang, Donglin

    2018-01-01

    This study was conducted to compare the efficacy of a combination of icotinib and chemotherapy with icotinib or chemotherapy alone in untreated non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR)-sensitive mutations and to analyze the curative effect of different treatments on different genetic mutations (EGFR 19 exon deletion and L858R mutation) in a real-life setting. One hundred ninety-one patients were studied in this retrospective analysis from January 2013 to December 2015. The baseline characteristics, curative effects and adverse events of patients were analyzed. The primary endpoint was progression free survival (PFS). Longer PFS and overall survival (OS), and better objective response rate (ORR) were observed in the combination group compared to icotinib or chemotherapy along. For patients with an EGFR 19 exon deletion, the PFS, OS, and ORR in the combination group were superior to those in the icotinib or chemotherapy group. For the patients with the EGFR L858R mutation, better PFS and ORR were observed in the combination group, but OS was not obviously prolonged. Grade 3 or 4 adverse events were most commonly reported with combination therapy or chemotherapy alone. No possible drug-related interstitial lung disease or of drug related deaths occurred. The combination of icotinib and chemotherapy in patients with untreated NSCLC harboring sensitive EGFR mutations resulted in improved PFS and OS, especially in those who harbored the EGFR exon 19 deletion.

  4. Clinical effect of systemic chemotherapy combined with transcatheter arterial chemoembolization in treatment of breast cancer with liver metastases

    Directory of Open Access Journals (Sweden)

    LI Liye

    2016-01-01

    Full Text Available ObjectiveTo investigate the clinical effect of systemic chemotherapy combined with transcatheter arterial chemoembolization (TACE in the treatment of breast cancer with liver metastases. MethodsA total of 86 female breast cancer patients with liver metastases who were treated in the Affiliated Hospital of Shandong Academy of Medical Sciences from December 2012 to December 2014 were selected and equally divided into experimental group and control group. The patients in the control group received systemic chemotherapy, and those in the experimental group received systemic chemotherapy combined with TACE. The clinical effect, changes in lesions, and patients′ quality of life (QOL scores after treatment were compared between two groups. The t-test was applied for comparison of continuous data between the two groups, and the chi-square test was applied for comparison of categorical data between the two groups. ResultsThe experimental group had a significantly higher overall response rate than the control group (90.70% vs 58.14%, χ2=13.07, P=0.001. Compared with the control group, the experimental group had significantly smaller diameters of tumors and lymph nodes after treatment (t=4.26 and 4.63, both P<0.001, as well as significantly higher QOL scores at 3 and 6 months after treatment (t=6.30 and 3.89, both P<0001. ConclusionSystemic chemotherapy combined with TACE has a significant therapeutic effect in breast cancer patients with liver metastases, and can improve patients′ symptoms, reduce adverse drug reactions, and improve QOL. As a safe and reliable therapeutic method, it is worthy of clinical application.

  5. Chemotherapy for head and neck cancer

    International Nuclear Information System (INIS)

    Pfister, David G.

    1997-01-01

    Purpose/Objective: The role of chemotherapy in the management of squamous cell carcinoma of the upper aerodigestive tract is undergoing rapid evolution. Historically, the use of chemotherapy was limited to patients with incurable disease who had exhausted all surgical and radiation therapy options. The results of recent randomized trials, however, suggest an increasing role for chemotherapy as part of primary management in patients with unresectable disease; advanced larynx or hypopharynx cancer with the intent of larynx preservation, or advanced nasopharynx cancer. This refresher course will provide a comprehensive overview of the current indications for chemotherapy in the management of these malignancies, and will highlight areas of controversy and future directions of investigation. More specifically, the following areas will be emphasized. 1. The identification of drugs commonly used in the management of head and neck cancer, their customary dosing and side effects. 2. The impact of induction and/or adjuvant chemotherapy combined with surgery and radiation therapy as defined by randomized trials, including a discussion of the Head and Neck Contracts program and the Intergroup adjuvant trial. 3. The development of larynx/function preservation treatment programs, including a review of the Veterans Administration and EORTC larynx preservation studies. 4. The evolving role of chemotherapy as part of innovative combined modality programs, especially in patients with unresectable disease. The rationale and utility of sequential versus concomitant/alternating chemotherapy-radiation strategies, and relevant randomized clinical trials comparing the different strategies will be discussed. 5. The appropriate application of chemotherapy in the palliative setting, including a discussion of the relative merits of single-agent versus combination chemotherapy

  6. Chemotherapy for head and neck cancer

    International Nuclear Information System (INIS)

    Pfister, David G.

    1995-01-01

    Purpose/Objective: The role of chemotherapy in the management of squamous cell carcinoma of the upper aerodigestive tract is undergoing rapid evolution. Historically, the use of chemotherapy was limited to patients with incurable disease who had exhausted all surgical and radiation therapy options. The results of recent randomized trials, however, suggest an increasing role for chemotherapy as part of primary management in patients seeking to avoid potentially morbid surgical procedures or with unresectable disease. This refresher course will provide a comprehensive overview of the current indications for chemotherapy in the management of these malignancies, and will highlight areas of controversy and future directions of investigation. More specifically, the following areas will be emphasized. 1. The identification of drugs commonly used in the management of head and neck cancer, their customary dosing and side effects. 2. The impact of induction and/or adjuvant chemotherapy combined with surgery and radiation therapy as defined by randomized trials, including a discussion of the Head and Neck Contracts program and the Intergroup adjuvant trial. 3. The development of larynx/function preservation treatment programs, including a review of the Memorial Hospital experience with larynx preservation and the Veterans Administration larynx preservation study. 4. The evolving role of chemotherapy as part of innovative combined modality programs, especially in patients with unresectable disease. The rationale and utility of sequential versus concomitant/alternating chemotherapy-radiation strategies, and relevant randomized clinical trials comparing the different strategies will be discussed. 5. The appropriate application of chemotherapy in the palliative setting, including a discussion of the relative merits of single-agent versus combination chemotherapy

  7. Hyperthermia, a modality in the wings

    Directory of Open Access Journals (Sweden)

    Szasz A

    2007-01-01

    Full Text Available Hyperthermia is a heat-treatment. It is widely used in various medical fields and has a well-recognized effect in oncology. Its effect is achieved by overheating of the targeted tissues. It is an ancient treatment and a promising physical approach with lack of acceptance by the serious medical use. To accept the method we need strong proofs and stable, reproducible treatment quality, but we are limited by biological, physical/technical and physiological problems. However, the main point - I believe - is the incorrect characterization and unrealistic expectations from this capable method. The temperature concept of the quality assurance guidelines has to be replaced by the heat-dose sensitive characterization, pointing the essence of the hyperthermia method.

  8. Ways of improvement of treatment of esophageal cancer

    International Nuclear Information System (INIS)

    Kochegarov, A.A.

    1984-01-01

    An analysis of the results of treatment of 344 patients with cancer of the thoracic part of the esophagus was performed. Out of those, 104 received surgical and combined treatment and 240 (inoperable cancer) were given radiotherapy alone or in cOmbination with local hyperthermia, general chemotherapy or intratumoral iontophoresis of chemotherapeutic agents. The operation after Dobromyslov-Torek proved to be insufficient in most of surgical cases because there were metastatic lesions below the diaphragm. Local hyperthermia potentiated the effect of radiation treatment. The early results of treatment improved after intratumoral sarcolysin ionophoresis was used in conjunction with radiation therapy

  9. Influence of interventional chemotherapy combined with traditional Chinese medicine on the immune function of elderly patients with advanced lung cancer

    International Nuclear Information System (INIS)

    Jiang Tinghui; Wu Shiyan; Chen Yue; Zhang Qingquan; Zhang Weiwei; Shen Xubo; Wang Qianyao

    2010-01-01

    Objective: To investigate the influence of interventional chemotherapy combined with traditional Chinese medicine on the immune function in elderly patients with advanced lung cancer and to establish a comprehensive therapeutic pattern which is effective and economical with lower side-effects. Methods: A total of 60 aged patients with lung cancer were randomly and equally divided into two groups with 30 patients in each group. Patients in group A were purely treated with traditional Chinese medicine and patients in group B were treated with a combination of interventional chemotherapy and traditional Chinese medicine. And two therapeutic courses (6-8 weeks) were conducted in both groups. The serum T-lymphocyte subsets levels of CD3, CD4, CD8, CD4/CD8, NK cells and CD4 + CD25 + Treg cell levels were estimated with flow cytometry. The results were statistically analyzed. Results: No significant difference in serum levels of T cell subsets and CD4 + CD25 + Treg cell levels existed between the two groups, both before and after the treatment (P > 0.05). However, after the treatment the CD4 + CD25 + Treg cell level in group B was significantly lower than that in group A (P < 0.05). The short-term effective rate and the total clinical benefit rate in group B were 40% and 73.3% respectively, which were much better than those in group A (20% and 63.3% respectively). Conclusion: Interventional chemotherapy combined with traditional Chinese medicine will not damage the immune function of elderly patients with advanced lung cancer, on the contrary, the combination therapy, through effectively reducing the suppressor T cell level,shows excellent short-term effect. It indicates that interventional chemotherapy combined with Chinese medicine is an effective comprehensive therapeutic mode for elderly patients with advanced lung cancer. (authors)

  10. Prospective phase II trial of regional hyperthermia and whole liver irradiation for numerous chemorefratory liver metastases from colerectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Jeong Il; Park, Hee Chul; Choi, Doo Ho [Dept. of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); and others

    2016-03-15

    A prospective phase II trial was conducted to evaluate the effectiveness and toxicity of regional hyperthermia and whole liver irradiation (WLI) for numerous chemorefractory liver metastases from colorectal cancer. Enrolled patients had numerous chemorefractory hepatic metastases from colorectal cancer. Five sessions of hyperthermia and seven fractions of 3-gray WLI were planned. Health-related quality of life (HRQoL) was determined using the Korean version of the European Organization for Research and Treatment of Cancer quality of life questionnaire C-30 and the Functional Assessment of Cancer Therapy-Hepatobiliary version 4.0. Objective and pain response was evaluated. A total of 12 patients consented to the study and the 10 who received WLI and hyperthermia were analyzed. WLI was completed as planned in nine patients and hyperthermia in eight. Pain response was partial in four patients and stable in four. Partial objective response was achieved in three patients (30.0%) and stable disease was seen in four patients at the 1-month follow-up. One patient died 1 month after treatment because of respiratory failure related to pleural metastasis progression. Other grade III or higher toxicities were detected in three patients; however, all severe toxicities were related to disease progression rather than treatment. No significant difference in HRQoL was noted at the time of assessment for patients who were available for questionnaires. Combined WLI and hyperthermia were well tolerated without severe treatment-related toxicity with a promising response from numerous chemorefractory hepatic metastases from colorectal cancer.

  11. Nanotechnology for Cancer Therapy Based on Chemotherapy

    Directory of Open Access Journals (Sweden)

    Chen-Yang Zhao

    2018-04-01

    Full Text Available Chemotherapy has been widely applied in clinics. However, the therapeutic potential of chemotherapy against cancer is seriously dissatisfactory due to the nonspecific drug distribution, multidrug resistance (MDR and the heterogeneity of cancer. Therefore, combinational therapy based on chemotherapy mediated by nanotechnology, has been the trend in clinical research at present, which can result in a remarkably increased therapeutic efficiency with few side effects to normal tissues. Moreover, to achieve the accurate pre-diagnosis and real-time monitoring for tumor, the research of nano-theranostics, which integrates diagnosis with treatment process, is a promising field in cancer treatment. In this review, the recent studies on combinational therapy based on chemotherapy will be systematically discussed. Furthermore, as a current trend in cancer treatment, advance in theranostic nanoparticles based on chemotherapy will be exemplified briefly. Finally, the present challenges and improvement tips will be presented in combination therapy and nano-theranostics.

  12. Doxorubicin and ifosfamide combination chemotherapy in previously treated acute leukemia in adults: a Southwest Oncology Group pilot study.

    Science.gov (United States)

    Ryan, D H; Bickers, J N; Vial, R H; Hussein, K; Bottomley, R; Hewlett, J S; Wilson, H E; Stuckey, W J

    1980-01-01

    The Southwest Oncology Group did a limited institutional pilot study of the combination of doxorubicin and ifosfamide in the treatment of previously treated adult patients with acute leukemia. Thirty-four patients received one or two courses of the combination. All patients had received prior chemotherapy and 32 had received prior anthracycline chemotherapy. Three patients died before their responses could be fully evaluated. Fourteen patients achieved complete remission (41%) and one patient achieved partial remission. The complete remission rate was 27% for patients with acute myeloblastic leukemia (myelomonoblastic leukemia, monoblastic leukemia, and erythroleukemia) and 89% for patients with acute lymphocytic and undifferentiated leukemia (ALL). Toxic effects included severe hematologic reactions in 33 of 34 patients, hematuria in six patients, altered sensorium in one patient, and congestive heart failure in one patient. The safety of the combination was established and toxic side effects of this therapy were tolerable. The 89% complete remission rate for previously treated patients with ALL suggests that the combination of doxorubicin and ifosfamide may be particularly effective in ALL.

  13. The effect of icotinib combined with chemotherapy in untreated non-small-cell lung cancer that harbored EGFR-sensitive mutations in a real-life setting: a retrospective analysis

    Directory of Open Access Journals (Sweden)

    Wang LL

    2018-04-01

    Full Text Available Lulu Wang, Yan Li, Luchun Li, Zhijuan Wu, Dan Yang, Huiwen Ma, Donglin Wang Oncology Department, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Shapingba District, Chongqing, China Purpose: This study was conducted to compare the efficacy of a combination of icotinib and chemotherapy with icotinib or chemotherapy alone in untreated non-small cell lung cancer (NSCLC patients harboring epidermal growth factor receptor (EGFR-sensitive mutations and to analyze the curative effect of different treatments on different genetic mutations (EGFR 19 exon deletion and L858R mutation in a real-life setting. Patients and methods: One hundred ninety-one patients were studied in this retrospective analysis from January 2013 to December 2015. The baseline characteristics, curative effects and adverse events of patients were analyzed. The primary endpoint was progression free survival (PFS. Results: Longer PFS and overall survival (OS, and better objective response rate (ORR were observed in the combination group compared to icotinib or chemotherapy along. For patients with an EGFR 19 exon deletion, the PFS, OS, and ORR in the combination group were superior to those in the icotinib or chemotherapy group. For the patients with the EGFR L858R mutation, better PFS and ORR were observed in the combination group, but OS was not obviously prolonged. Grade 3 or 4 adverse events were most commonly reported with combination therapy or chemotherapy alone. No possible drug-related interstitial lung disease or of drug related deaths occurred. Conclusion: The combination of icotinib and chemotherapy in patients with untreated NSCLC harboring sensitive EGFR mutations resulted in improved PFS and OS,especially in those who harbored the EGFR exon 19 deletion. Keywords: non-small-cell lung cancer, EGFR-TKI, icotinib, chemotherapy, first-line treatment

  14. Overview of different available chemotherapy regimens combined with radiotherapy for the neoadjuvant and definitive treatment of esophageal cancer.

    Science.gov (United States)

    Tomasello, Gianluca; Ghidini, Michele; Barni, Sandro; Passalacqua, Rodolfo; Petrelli, Fausto

    2017-06-01

    Neoadjuvant chemoradiotherapy (CTRT) is the current standard of care for treatment of locally advanced cancer of the esophagus or gastroesophageal junction. Many efforts have been made over the last years to identify the best chemotherapy and radiotherapy combination regimen, but specific randomized trials addressing this issue are still lacking. Areas covered: A systematic review of the literature was performed searching in PubMed all published studies of combinations CTRT regimens for operable or unresectable esophageal cancer to describe activity and toxicity. Studies considered were prospective series or clinical phase II-III trials including at least 40 patients and published in English language. Expert commentary: Long-term results of CROSS trial have established RT combined with carboplatin plus paclitaxel chemotherapy as the preferred neoadjuvant treatment option for both squamous and adenocarcinoma of the esophagus. More effective multimodal treatment strategies integrating novel biological agents including immunotherapy and based on an extensive molecular tumor characterization are eagerly awaited.

  15. Magnetic Properties of Magnetic Nanoparticles for Efficient Hyperthermia

    Directory of Open Access Journals (Sweden)

    Ihab M. Obaidat

    2015-01-01

    Full Text Available Localized magnetic hyperthermia using magnetic nanoparticles (MNPs under the application of small magnetic fields is a promising tool for treating small or deep-seated tumors. For this method to be applicable, the amount of MNPs used should be minimized. Hence, it is essential to enhance the power dissipation or heating efficiency of MNPs. Several factors influence the heating efficiency of MNPs, such as the amplitude and frequency of the applied magnetic field and the structural and magnetic properties of MNPs. We discuss some of the physics principles for effective heating of MNPs focusing on the role of surface anisotropy, interface exchange anisotropy and dipolar interactions. Basic magnetic properties of MNPs such as their superparamagnetic behavior, are briefly reviewed. The influence of temperature on anisotropy and magnetization of MNPs is discussed. Recent development in self-regulated hyperthermia is briefly discussed. Some physical and practical limitations of using MNPs in magnetic hyperthermia are also briefly discussed.

  16. Magnetomotive Optical Coherence Elastography for Magnetic Hyperthermia Dosimetry Based on Dynamic Tissue Biomechanics

    Science.gov (United States)

    Huang, Pin-Chieh; Pande, Paritosh; Ahmad, Adeel; Marjanovic, Marina; Spillman, Darold R.; Odintsov, Boris; Boppart, Stephen A.

    2016-01-01

    Magnetic nanoparticles (MNPs) have been used in many diagnostic and therapeutic biomedical applications over the past few decades to enhance imaging contrast, steer drugs to targets, and treat tumors via hyperthermia. Optical coherence tomography (OCT) is an optical biomedical imaging modality that relies on the detection of backscattered light to generate high-resolution cross-sectional images of biological tissue. MNPs have been utilized as imaging contrast and perturbative mechanical agents in OCT in techniques called magnetomotive OCT (MM-OCT) and magnetomotive elastography (MM-OCE), respectively. MNPs have also been independently used for magnetic hyperthermia treatments, enabling therapeutic functions such as killing tumor cells. It is well known that the localized tissue heating during hyperthermia treatments result in a change in the biomechanical properties of the tissue. Therefore, we propose a novel dosimetric technique for hyperthermia treatment based on the viscoelasticity change detected by MM-OCE, further enabling the theranostic function of MNPs. In this paper, we first review the basic principles and applications of MM-OCT, MM-OCE, and magnetic hyperthermia, and present new preliminary results supporting the concept of MM-OCE-based hyperthermia dosimetry. PMID:28163565

  17. Microwave hyperthermia as an adjuvant to radiation therapy. Summary experience of 256 multifraction treatment cases

    International Nuclear Information System (INIS)

    Bicher, H.I.

    1985-01-01

    Analysis is presented of a series of 256 human tumors treated under multifraction protocol regimes with standard controlled hyperthermia parameters and increasing doses of radiation therapy. Air cooled microwave applicators intracavitary and interstitial antennae operating at 915 or 300 MHz were used in various sites. Temperatures were measured by micro-thermocouples. Minimum tumor temperatures of 42 0 C were maintained at 1 hour, twice weekly. Treatment included a radiation dose of 1600-1700 rads. Tumor response was 94% with 60% or more total response. Frequency and duration of total responses depended mainly on the radiation dose. Skin tumors, melanomas, chest wall recurrences responded better than head and neck or intrapelvic recurrences. Side effects observed were minor burns; proctitis or oesophagitis with intracavitary devices; ulcerations or fistulae due to rapid tumor regression; 4 cases of pleuritis treating chest wall. Overall toxicity was less than 5%. In conclusion: 1) Combination heat-low dose radiation offers good palliation. 2) Response depends on radiation dose. 3) Combination of full dose radiation therapy plus hyperthermia proves to be well tolerated

  18. Effects of hyperthermia and radiation on mouse testis stem cells

    International Nuclear Information System (INIS)

    Reid, B.O.; Mason, K.A.; Withers, H.R.; West, J.

    1981-01-01

    The response of mouse testis stem cells to hyperthermia and combined hyperthermia-radiation treatments was assayed by spermatogenic colony regrowth, sperm head counts, testis weight loss, and fertility. With the use of spermatogenic colony assay, thermal enhancement ratios at an isosurvival level of 0.1 were 1.27 at 41 degrees, 1.80 at 42 degrees, and 3.97 at 43 degrees for testes exposed to heat for 30 min prior to irradiation. Sperm head counts were reduced by heat alone from a surviving fraction of 0.58 at 41 degrees to 0.003 at 42.5-43.5 degrees. Curves for sperm head survival measured 56 days after the testes had been heated for 30 min prior to irradiation were biphasic and showed a progressive downward displacement to lower survival with increasing temperature. The 41, 42, and 43 degrees curves were displaced downward by factors of 2, 58, and 175, respectively. The proportion of animals remaining sterile after 30 min of heat (41-43 degrees) and the median sterility period in days increased with increasing temperature. The minimum sperm count necessary to regain fertility was 13% of the normal mouse level

  19. [Efficacy of granisetron for preventing chemotherapy-induced nausea and vomiting in patients with acute myelogenous leukemia treated with a combination of anthracycline and cytarabine].

    Science.gov (United States)

    Goto, Takashi; Tanimoto, Kazuki; Ishibashi, Makoto; Okamura, Seiichi

    2012-08-01

    In Japan, the combination of anthracycline and cytarabine(Ara-C)is a standard therapy for acute myelogenous leukemia(AML). Chemotherapy-induced nausea and vomiting(CINV)are frequently reported as side effects related to the administration of these regimens. In our hospital, patients received prophylactic granisetron at a dose of 3 mg daily during chemotherapy. However, granisetron is known to induce constipation as a side effect. The present study evaluated the efficacy of a single dose of granisetron administered throughout the entire period of chemotherapy in AML patients receiving anthracycline and Ara-C combination therapy, and also examined the incidence of constipation during chemotherapy. From July 2008 to December 2010, all patients with AML treated using anthracycline and Ara-C combination therapy were registered in the study. This retrospective study investigated the patients' background and the incidence of CINV and constipation from the patients' records. The efficacy of granisetron was measured on each day using the complete regression(no vomiting and no rescue medication; CR)rate. A total of 45 patients were included in the study(27 male; 18 female), and received a total 68 courses(56 of induction therapy; 12 of consolidation therapy)of the regimens. The CR rate and the incidence of constipation on the final day of chemotherapy were 61. 8% and 63. 2%, respectively. As the duration of chemotherapy increased, the CR rate tended to decrease, whereas the incidence of constipation tended to increase. The CR rate in this study was 61. 8%, thus indicating that there is still room for improvement. The combination of dexamethasone and a neurokinin-1 receptor antagonist, or the changeover from granisetron to palonosetron could therefore increase the CR rate.

  20. Adjuvant chemotherapy and cancer cure

    International Nuclear Information System (INIS)

    Bertino, J.R.

    1983-01-01

    The use of chemotherapy as an adjuvant to surgery and/or radiotherapy is well founded in experimental tumor systems and appears to be effective in patients in some circumstances. It is clear from both clinical and experimental studies that (1) the dose is important, (2) the earlier chemotherapy is started after primary therapy the better, and (3) combination chemotherapy may be more effective than single-agent treatment. The better the estimation of risk of recurrence, the better the assessment of the risk-benefit ratio with adjuvant therapy. Salvage therapy as well as relative risk of recurrence are considerations in the choice of patients to be treated. Finally, some evidence is presented to indicate that alkylating agents may not be necessary in combination regimens for adjuvant therapy if effective antimetabolite combinations are available

  1. Chemotherapy alone versus chemotherapy plus radiotherapy for adults with early stage Hodgkin lymphoma (Review)

    DEFF Research Database (Denmark)

    Blank, Oliver; von Tresckow, Bastian; Monsef, Ina

    2017-01-01

    BACKGROUND: Combined modality treatment consisting of chemotherapy followed by localised radiotherapy is the standard treatment for patients with early stage Hodgkin lymphoma (HL). However, due to long- term adverse effects such as secondary malignancies the role of radiotherapy has been questioned...... recently and some clinical study groups advocate chemotherapy only for this indication. OBJECTIVES: To assess the effects of chemotherapy alone compared to chemotherapy plus radiotherapy in adults with early stage HL . SEARCH METHODS: For the or i ginal version of this review, we searched MEDLINE, Embase......-related mortality (RR 0.99; 95% CI 0.14 to 6.90; P = 0.99; low-quality evidence), there is no evidence for a difference between the use of chemotherapy alone and chemotherapy plus radiotherapy. CRR rate was not reported. AUTHORS' CONCLUSIONS: This systematic review compared the effects of chemotherapy alone...

  2. Combined radiotherapy and chemotherapy for pediatric medulloblastoma: a clinical study of 33 cases

    Directory of Open Access Journals (Sweden)

    Wei ZHENG

    2011-06-01

    Full Text Available Objective To retrospectively review the clinical characteristics of medulloblastoma,discuss the optimized treatment regimen,and analyze the prognostic influential factors.Methods Thirty-three children with pathologically certified medulloblastoma(aged 3-14 years with average of 6.5 years,admitted from Aug.2004 to Dec.2007,received radiotherapy within 3 weeks post surgery.Ratiotherapy consisted of 28~36Gy whole craniospinal radiation and a supplementary radiation aimed at tumors by three-dimensional conformal radiotherapy(3D-CRT for a total dose of 50~54Gy(conventional fraction dose of 1.8-2.0Gy.A part of patients received hyperfractionation radiotherapy(1.0Gy/f,2f/d for alleviating the tardive adverse events.Meanwhile,a synchronized chemotherapy,consisting of lomustine + vincristine + cisplatin,or isophosphamide + carboplatin + etoposide,was administered after the completion of whole craniospinal radiation,and 3-5 courses of sequential chemotherapy were given after the overall radiotherapy was finished.According to the metastasis,and the residual tumor and its size,the 33 patients were divided into 2 groups as follows: low-risk group(n=24: no metastases,total or sub-total excision of tumors(residual tumors ≤1.5cm3;high-risk group(n=9: either metastases or residual tumor > 1.5cm3.The 3-year survival rates of two groups were then compared.Results The combined radiotherapy and chemotherapy was effective to 10 of the 11 patients(90.9% with residual tumors.Out of the 33 patients,31 obtained complete remission(93.9%,and 2 patients showed partial remission or stable status(3.0%,respectively.The median survival time of 33 patients was 51 months,3-year disease free survival(DFS was 75.8%,and 3-year overall survival(OS was 78.8%,including 33.3% in high-risk group and 95.8% in low-risk group(P < 0.01.The major side effects occurred in haematological system and digestive system,such as an incidence of 21.2%(7/33 with grade Ⅲ-Ⅳ bone marrow suppression

  3. Clinical Observation of Recombinant Human Vascular Endostatin Durative Transfusion Combined with Window Period Arterial Infusion Chemotherapy in the Treatment of 
Advanced Lung Squamous Carcinoma

    Directory of Open Access Journals (Sweden)

    Yuan LV

    2015-08-01

    Full Text Available Background and objective Lung cancer is one of the most common malignant tumors in China. The aim of this study is to observe the efficacy and safety of recombinant human vascular endostatin (endostar durative transfusion combined with window period arterial infusion chemotherapy in the treatment of advanced lung squamous carcinoma. Methods From February 2014 to January 2015, 10 cases of the cytological or histological pathology diagnosed stage IIIb - stage IV lung squamous carcinoma were treated with recombinant human vascular endostatin (30 mg/d durative transfusion combined with window period arterial infusion chemotherapy. Over the same period of 10 cases stage IIIb - stage IV lung squamous carcinoma patients for pure arterial perfusion chemotherapy were compared. Recombinant human vascular endostatin was durative transfused every 24 hours for 7 days in combination group, and in the 4th day of window period, the 10 patients were received artery infusion chemotherapy, using docetaxel combined with cisplatin. Pure treatment group received the same arterial perfusion chemotherapy regimen. 4 weeks was a cycle. 4 weeks after 2 cycles, to evaluate the short-term effects and the adverse drug reactions. Results 2 groups of patients were received 2 cycles treatments. The response rate (RR was 70.0%, and the disease control rate (DCR was 90.0% in the combination group; In the pure treatment group were 50.0%, 70.0% respectively, there were no statistically significant difference (P=0.650, 0.582. The adverse reactions of the treatment were mild, including level 1-2 of gastrointestinal reaction and blood toxicity, there were no statistically significant difference (P=0.999, P=0.628. In the combination group, 1 patient occurred level 1 of cardiac toxicity. Conclusion Recombinant human vascular endostatin durative transfusion combined with window period arterial infusion chemotherapy in the treatment of advanced lung squamous carcinoma could take a

  4. Hyperthermia on skin immune system and its application in the treatment of HPV-infected skin diseases

    Institute of Scientific and Technical Information of China (English)

    Gao Xinghua; Chen Hongduo

    2014-01-01

    In this paper, the effects of hyperthermia on cells and immune system are introduced briefly. The mechanism of action of hyperthermia on human papilloma virus (HPV)-infected skin diseases was elaborated as an example in this paper. Many studies have proved that hyperthermia affects a number of cellular and molecu- lar constitutes in the skin immune system, involving both innate and adaptive immune responses; the efficacy of hyperthermia in treating some infectious and cancerous conditions has been validated and applied in clinics, while molecular mechanisms of hyperthermia affecting the immunereaction is still unclear.

  5. Effects of combined irradiation and hyperthermia on creatine kinase activity in rat tissues

    Energy Technology Data Exchange (ETDEWEB)

    Matyushichev, V B; Taratukhin, V P; Shamratova, V G; Yuzhakova, G A [Leningradskij Gosudarstvennyj Univ. (USSR)

    1977-09-01

    The effects of different doses of beta- and X-irradiations on creatine kinase activity (CKA) in cerebrum and liver of rats were investigated under hyperthermia conditions. Beta irradiation was carried out at 2.50, 3.05, 4.45 or 7.40 Krad doses under heat load. After withdrawal of the animals from the chamber they were exposed to 25,50,100,250 or 400 R X-ray doses (for beta irradiation 2.50,2.50,3.05,4.45 or 7.40 Krad, respectively). In 5,12,19 and 26 days after exposure the animals were decapitated and CKA of aqueous extracts of cerebral hemispheres and livers were determined. It has been established, that the thermal stress decreases the radiosensitivity of cerebral CKA, but intensifies the irradiation consequences in respect to liver activity.

  6. Comparison of efficacy and tolerance between combination therapy and monotherapy as first-line chemotherapy in elderly patients with advanced gastric cancer: Study protocol for a randomized controlled trial.

    Science.gov (United States)

    Lee, Keun-Wook; Zang, Dae Young; Ryu, Min-Hee; Kim, Ki Hyang; Kim, Mi-Jung; Han, Hye Sook; Koh, Sung Ae; Park, Jin Hyun; Kim, Jin Won; Nam, Byung-Ho; Choi, In Sil

    2017-12-01

    The combination of a fluoropyrimidine [5-fluorouracil (5-FU), capecitabine, or S-1] with a platinum analog (cisplatin or oxaliplatin) is the most widely accepted first-line chemotherapy regimen for metastatic or recurrent advanced gastric cancer (AGC), based on the results of clinical trials. However, there is little evidence to guide chemotherapy for elderly patients with AGC because of under-representation of this age group in clinical trials. Thus, the aim of this study is to determine the optimal chemotherapy regimen for elderly patients with AGC by comparing the efficacies and safeties of combination therapy versus monotherapy as first-line chemotherapy. This study is a randomized, controlled, multicenter, phase III trial. A total of 246 elderly patients (≥70 years old) with metastatic or recurrent AGC who have not received previous palliative chemotherapy will be randomly allocated to a combination therapy group or a monotherapy group. Patients randomized to the combination therapy group will receive fluoropyrimidine plus platinum combination chemotherapy (capecitabine/cisplatin, S-1/cisplatin, capecitabine/oxaliplatin, or 5-FU/oxaliplatin), and those randomized to the monotherapy group will receive fluoropyrimidine monotherapy (capecitabine, S-1, or 5-FU). The primary outcome is the overall survival of patients in each treatment group. The secondary outcomes include progression-free survival, response rate, quality of life, and safety. We are conducting this pragmatic trial to determine whether elderly patients with AGC will obtain the same benefit from chemotherapy as younger patients. We expect that this study will help guide decision-making for the optimal treatment of elderly patients with AGC.

  7. Clinical and histopathological studies on the squamous cell carcinoma of the tongue treated with radiation-combined intra-arterial chemotherapy

    International Nuclear Information System (INIS)

    Hoshi, Hideki

    2000-01-01

    Because oral cancer treatment has advanced, resulting in a higher survival rate, it is necessary to treat the preserved oral functions such as speech, mastication, and deglutition, as well as the aesthetics. Oral cancer treatment has been performed mainly by surgical therapy and radiation therapy, however, integrated treatment including chemotherapy has recently been performed. In this study, we evaluated the effectiveness and usefulness of radiation-combined intra-arterial chemotherapy for carcinomas of the tongue, which shows a high incident rate among oral cancers and has become more common recently, to establish treatment methods for preserving the function and morphology. The subjects were 63 patients who consulted our department and underwent radiation-combined intra-arterial chemotherapy. With this therapy, the case of complete response (CR) was clinically obtained in 43 patients, and the case of partial response (PR) was obtained in 17 patients with a 68.3% CR rate and a 95.2% therapeutic effectiveness rate. Maintenance therapy was performed in 44 patients without performing surgical therapy of the primary lesion in the primary treatment. Twenty-nine among 44 patients showed a good clinical course without recurrence of primary lesion. Regarding T4, a good clinical course without recurrence was observed in 3 patients in which PR was obtained, and surgical therapy was added to the primary treatment, showing a 57.1% local control rate in T4. Considering these results, there is a high possibility that radiation-combined intra-arterial chemotherapy for carcinomas of the tongue can be implemented for avoiding surgical therapy of the primary lesion in the primary treatment, and it is useful for preserving the function and morphology with a high local control rate. (author)

  8. Clinical and histopathological studies on the squamous cell carcinoma of the tongue treated with radiation-combined intra-arterial chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Hoshi, Hideki [Iwate Medical Coll., Morioka (Japan). School of Dentistry

    2000-12-01

    Because oral cancer treatment has advanced, resulting in a higher survival rate, it is necessary to treat the preserved oral functions such as speech, mastication, and deglutition, as well as the aesthetics. Oral cancer treatment has been performed mainly by surgical therapy and radiation therapy, however, integrated treatment including chemotherapy has recently been performed. In this study, we evaluated the effectiveness and usefulness of radiation-combined intra-arterial chemotherapy for carcinomas of the tongue, which shows a high incident rate among oral cancers and has become more common recently, to establish treatment methods for preserving the function and morphology. The subjects were 63 patients who consulted our department and underwent radiation-combined intra-arterial chemotherapy. With this therapy, the case of complete response (CR) was clinically obtained in 43 patients, and the case of partial response (PR) was obtained in 17 patients with a 68.3% CR rate and a 95.2% therapeutic effectiveness rate. Maintenance therapy was performed in 44 patients without performing surgical therapy of the primary lesion in the primary treatment. Twenty-nine among 44 patients showed a good clinical course without recurrence of primary lesion. Regarding T4, a good clinical course without recurrence was observed in 3 patients in which PR was obtained, and surgical therapy was added to the primary treatment, showing a 57.1% local control rate in T4. Considering these results, there is a high possibility that radiation-combined intra-arterial chemotherapy for carcinomas of the tongue can be implemented for avoiding surgical therapy of the primary lesion in the primary treatment, and it is useful for preserving the function and morphology with a high local control rate. (author)

  9. Chemotherapy for advanced gastric cancer.

    Science.gov (United States)

    Wagner, Anna Dorothea; Syn, Nicholas Lx; Moehler, Markus; Grothe, Wilfried; Yong, Wei Peng; Tai, Bee-Choo; Ho, Jingshan; Unverzagt, Susanne

    2017-08-29

    Gastric cancer is the fifth most common cancer worldwide. In "Western" countries, most people are either diagnosed at an advanced stage, or develop a relapse after surgery with curative intent. In people with advanced disease, significant benefits from targeted therapies are currently limited to HER-2 positive disease treated with trastuzumab, in combination with chemotherapy, in first-line. In second-line, ramucirumab, alone or in combination with paclitaxel, demonstrated significant survival benefits. Thus, systemic chemotherapy remains the mainstay of treatment for advanced gastric cancer. Uncertainty remains regarding the choice of the regimen. To assess the efficacy of chemotherapy versus best supportive care (BSC), combination versus single-agent chemotherapy and different chemotherapy combinations in advanced gastric cancer. We searched the Cochrane Central Register of Controlled Trials, MEDLINE and Embase up to June 2016, reference lists of studies, and contacted pharmaceutical companies and experts to identify randomised controlled trials (RCTs). We considered only RCTs on systemic, intravenous or oral chemotherapy versus BSC, combination versus single-agent chemotherapy and different chemotherapy regimens in advanced gastric cancer. Two review authors independently identified studies and extracted data. A third investigator was consulted in case of disagreements. We contacted study authors to obtain missing information. We included 64 RCTs, of which 60 RCTs (11,698 participants) provided data for the meta-analysis of overall survival. We found chemotherapy extends overall survival (OS) by approximately 6.7 months more than BSC (hazard ratio (HR) 0.3, 95% confidence intervals (CI) 0.24 to 0.55, 184 participants, three studies, moderate-quality evidence). Combination chemotherapy extends OS slightly (by an additional month) versus single-agent chemotherapy (HR 0.84, 95% CI 0.79 to 0.89, 4447 participants, 23 studies, moderate-quality evidence), which is

  10. Targeting HSP70 and GRP78 in canine osteosarcoma cells in combination with doxorubicin chemotherapy.

    Science.gov (United States)

    Asling, Jonathan; Morrison, Jodi; Mutsaers, Anthony J

    2016-11-01

    Heat shock proteins (HSPs) are molecular chaperones subdivided into several families based on their molecular weight. Due to their cytoprotective roles, these proteins may help protect cancer cells against chemotherapy-induced cell death. Investigation into the biologic activity of HSPs in a variety of cancers including primary bone tumors, such as osteosarcoma (OSA), is of great interest. Both human and canine OSA tumor samples have aberrant production of HSP70. This study assessed the response of canine OSA cells to inhibition of HSP70 and GRP78 by the ATP-mimetic VER-155008 and whether this treatment strategy could sensitize cells to doxorubicin chemotherapy. Single-agent VER-155008 treatment decreased cellular viability and clonogenic survival and increased apoptosis in canine OSA cell lines. However, combination schedules with doxorubicin after pretreatment with VER-155008 did not improve inhibition of cellular viability, apoptosis, or clonogenic survival. Treatment with VER-155008 prior to chemotherapy resulted in an upregulation of target proteins HSP70 and GRP78 in addition to the co-chaperone proteins Herp, C/EBP homologous transcription protein (CHOP), and BAG-1. The increased GRP78 was more cytoplasmic in location compared to untreated cells. Single-agent treatment also revealed a dose-dependent reduction in activated and total Akt. Based on these results, targeting GRP78 and HSP70 may have biologic activity in canine osteosarcoma. Further studies are required to determine if and how this strategy may impact the response of osteosarcoma cells to chemotherapy.

  11. The response of previously irradiated mouse skin to heat alone or combined with irradiation: influence of thermotolerance

    NARCIS (Netherlands)

    Wondergem, J.; Haveman, J.

    1983-01-01

    The skin of the mouse foot was used to study the effects of previous irradiation on the response to hyperthermia (44 degrees C), to irradiation, or to irradiation combined with hyperthermia (43 degrees C or 44 degrees C). Hyperthermia was applied by immersing the mouse foot into a hot waterbath and

  12. Targeting therapy-resistant cancer stem cells by hyperthermia

    DEFF Research Database (Denmark)

    Oei, A L; Vriend, L E M; Krawczyk, P M

    2017-01-01

    Eradication of all malignant cells is the ultimate but challenging goal of anti-cancer treatment; most traditional clinically-available approaches fail because there are cells in a tumour that either escape therapy or become therapy-resistant. A subpopulation of cancer cells, the cancer stem cells...... are limited. Here, we argue that hyperthermia - a therapeutic approach based on local heating of a tumour - is potentially beneficial for targeting CSCs in solid tumours. First, hyperthermia has been described to target cells in hypoxic and nutrient-deprived tumour areas where CSCs reside and ionising...

  13. Eight-MHz RF-hyperthermia for advanced urological malignancies

    International Nuclear Information System (INIS)

    Hisazumi, Haruo; Nakajima, Kazuyoshi

    1986-01-01

    Eight-MHz radiofrequency hyperthermia (H) using a Thermotron-RF Model 8, and its combination with irradiation (RH), anticancer drugs (CH) or anticancer drugs plus irradiation (CRH), were carried out for a total of 48 urological malignancies: 10 cases of renal cancer, 1 of renal pelvic cancer, 2 of uretetral cancer, 19 of bladder cancer, 5 of prostatic cancer, 9 of metastatic lesion of urological cancers and 2 of other urological cancers. All had failed in previous treatments, or had not undergone surgery because of their poor general condition. Four cases, including 2 of bladder cancer, 1 of prostatic cancer and 1 of metastatic lesion of bladder cancer, were treated with H. Twenty-five cases, including 3 renal cancer cases, were treated with RH. Seven of the 10 cases of renal cancer were treated with mitomycin C-microcapsule embolization prior to RH (CRH). Twelve of the 23 cases with urothelial cancer or its metastasis, including 1 of renal pelvic cancer, 10 of bladder cancer and 1 of metastatic lesion of bladder cancer, received combined treatment of THP-adriamycin, one of the derivatives of adriamycin, by i.v. and RF-heating (CH). Hyperthermia was given twice a week, totalling 10 sessions in 5 weeks. Intratumoral temperature was kept above 42.5 deg C for 30 to 40 minutes during one-hour heating. Complete tumor disappearance was obtained in the 5 bladder cancer cases. Partial tumor regression, defined as a regression of 50 % or more, was obtained in 11 cases. As side effects, mild skin burns and anorexia were observed in approximately 30 to 40 % of cases. Seven obese cases, who had subcutaneous tissue 15 mm thick or more, developed fat tissue induration after treatment. (author)

  14. A randomized trial of combined multidrug chemotherapy and radiotherapy in advanced squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    1986-01-01

    This report concerns the design and results of a randomized prospective trial (SECOG I) in the treatment of advanced Stage III and IV head and neck cancer with radical radiotherapy combined with polychemotherapy. Synchronous administration of chemotherapy and radiotherapy was compared with sequential chemotherapy and radiotherapy and VBM (vincristine, bleomycin and methotrexate) compared with VBM plus 5-fluorouracil in a 2 x 2 standard factorial design. Two-hundred-and-seventy patients were entered and 267 were included in the analysis. Treatment did not present serious problems of toxicity. The addition of 5-fluorouracil to VBM produced a significant improvement in disease-free survival (P=0.04) though not in overall survival. Synchronous chemotherapy was similarly better than sequential chemotherapy, though not significantly so (P=0.1). A new study (SECOG II), based on this was started in February 1984, and one-third of the patients are now being allocated to treatment by radiotherapy as the sole method of treatment. (author)

  15. The role of hyperthermia in the water economy of desert birds

    NARCIS (Netherlands)

    Tieleman, B.I.; Williams, J.B.

    1999-01-01

    A number of authors have suggested that hyperthermia, the elevation of body temperature (T-b) 2 degrees-4 degrees C above normal, contributes to a reduction in total evaporative water loss (TEWL) in birds. Information about the role of hyperthermia in the water economy of birds is scattered

  16. Chemotherapy alone versus chemotherapy plus radiotherapy for early stage Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Herbst, Christine; Rehan, Fareed Ahmed; Skoetz, Nicole

    2011-01-01

    BACKGROUND: Combined modality treatment (CMT) consisting of chemotherapy followed by localised radiotherapy is standard treatment for patients with early stage Hodgkin lymphoma (HL). However, due to long term adverse effects such as secondary malignancies, the role of radiotherapy has been...... chemotherapy regimen plus radiotherapy. SELECTION CRITERIA: Randomised controlled trials comparing chemotherapy alone with CMT in patients with early stage HL. Trials in which the chemotherapy differed between treatment arms were excluded. Trials with more than 20% of patients in advanced stage were also...... excluded. DATA COLLECTION AND ANALYSIS: Effect measures used were hazard ratios (HR) for tumour control and OS as well as relative risks for response rates. Two review authors independently extracted data and assessed quality of trials. We contacted study authors to obtain missing information. Since none...

  17. Combination of Intensive Chemotherapy and Anticancer Vaccines in the Treatment of Human Malignancies: The Hematological Experience

    Directory of Open Access Journals (Sweden)

    Knut Liseth

    2010-01-01

    Full Text Available In vitro studies have demonstrated that cancer-specific T cell cytotoxicity can be induced both ex vivo and in vivo, but this therapeutic strategy should probably be used as an integrated part of a cancer treatment regimen. Initial chemotherapy should be administered to reduce the cancer cell burden and disease-induced immune defects. This could be followed by autologous stem cell transplantation that is a safe procedure including both high-dose disease-directed chemotherapy and the possibility for ex vivo enrichment of the immunocompetent graft cells. The most intensive conventional chemotherapy and stem cell transplantation are used especially in the treatment of aggressive hematologic malignancies; both strategies induce T cell defects that may last for several months but cancer-specific T cell reactivity is maintained after both procedures. Enhancement of anticancer T cell cytotoxicity is possible but posttransplant vaccination therapy should probably be combined with optimalisation of immunoregulatory networks. Such combinatory regimens should be suitable for patients with aggressive hematological malignancies and probably also for other cancer patients.

  18. Clinically Relevant Pharmacological Strategies That Reverse MDMA-Induced Brain Hyperthermia Potentiated by Social Interaction.

    Science.gov (United States)

    Kiyatkin, Eugene A; Ren, Suelynn; Wakabayashi, Ken T; Baumann, Michael H; Shaham, Yavin

    2016-01-01

    MDMA-induced hyperthermia is highly variable, unpredictable, and greatly potentiated by the social and environmental conditions of recreational drug use. Current strategies to treat pathological MDMA-induced hyperthermia in humans are palliative and marginally effective, and there are no specific pharmacological treatments to counteract this potentially life-threatening condition. Here, we tested the efficacy of mixed adrenoceptor blockers carvedilol and labetalol, and the atypical antipsychotic clozapine, in reversing MDMA-induced brain and body hyperthermia. We injected rats with a moderate non-toxic dose of MDMA (9 mg/kg) during social interaction, and we administered potential treatment drugs after the development of robust hyperthermia (>2.5 °C), thus mimicking the clinical situation of acute MDMA intoxication. Brain temperature was our primary focus, but we also simultaneously recorded temperatures from the deep temporal muscle and skin, allowing us to determine the basic physiological mechanisms of the treatment drug action. Carvedilol was modestly effective in attenuating MDMA-induced hyperthermia by moderately inhibiting skin vasoconstriction, and labetalol was ineffective. In contrast, clozapine induced a marked and immediate reversal of MDMA-induced hyperthermia via inhibition of brain metabolic activation and blockade of skin vasoconstriction. Our findings suggest that clozapine, and related centrally acting drugs, might be highly effective for reversing MDMA-induced brain and body hyperthermia in emergency clinical situations, with possible life-saving results.

  19. Chemotherapy in thyroid carcinoma

    International Nuclear Information System (INIS)

    Samuel, A.M.; Shah, D.H.

    1999-01-01

    Chemotherapy alone, either as a single drug or a combination of drugs with or without external radiation (ER) is useful for treatment of locally advanced disease and non iodine concentrating metastasis in differentiated thyroid cancers (DTC). The reported response is not encouraging, but the absence of better alternatives leave no choice for the treatment of such cases. However, for treatment of anaplastic thyroid cancers (ANC), chemotherapy (CT) in combination with ER results in local control. In medullary thyroid cancers (MTC), the results obtained with multimodal treatment are encouraging

  20. Outcomes of Preoperative Chemoradiotherapy and Combined Chemotherapy with Radiotherapy Without Surgery for Locally Advanced Rectal Cancer.

    Science.gov (United States)

    Supaadirek, Chunsri; Pesee, Montien; Thamronganantasakul, Komsan; Thalangsri, Pimsiree; Krusun, Srichai; Supakalin, Narudom

    2016-01-01

    To evaluate the treatment outcomes of patients with locally advanced rectal cancer treated with preoperative concurrent chemoradiotherapy (CCRT) or combined chemotherapy together with radiotherapy (CMTRT) without surgery. A total of 84 patients with locally advanced rectal adenocarcinoma (stage II or III) between January 1st, 2003 and December 31st, 2013 were enrolled, 48 treated with preoperative CCRT (Gr.I) and 36 with combined chemotherapy and radiotherapy (CMTRT) without surgery (Gr.II). The chemotherapeutic agents used concurrent with radiotherapy were either 5fluorouracil short infusion plus leucovorin and/or capecitabine or 5fluorouracil infusion alone. All patients received pelvic irradiation. There were 5 patients (10.4%) with a complete pathological response. The 3 yearoverall survival rates were 83.2% in Gr.I and 24.8 % in Gr.II (prectal cancer demonstrated that in preoperative CCRT a sphincter sparing procedure can be performed. The results of treatment with preoperative CCRT for locally advanced rectal cancer showed comparable rates of overall survival and sphincter sparing procedures as compared to previous studies.

  1. ROLE OF ADJUVANT INTRAVESICAL CHEMOTHERAPY IN THE COMBINED ORGAN-SPARING TREATMENT OF NON-MUSCLE-INVASIVE BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    A. Yu. Zubko

    2014-01-01

    Full Text Available Objective: to enhance the efficiency of combined treatment for non-muscle-invasive bladder cancer ((NMIBC and to assess the results of its treatment using transurethral resection (TUR as monotherapy and in combination with intravesical adjuvant chemotherapy (CT.Subjects and methods. The results of treatment were analyzed in 59 patients with NMIBC. Twenty-two patients underwent TUR in Group 1; TUR and single intravesical injection of drugs were performed in 19 patients in Group 2; 18 patients had TUR and long-term intravesical CT.Results and discussion. The recurrence rates were 59.1, 57.9, and 38.89 % in Groups 1, 2, and 3, respectively. Intravesical CT was found to appreciably affect the prevention of recurrence in the area of resection. The rate of this recurrence was 31.81, 26.32, and 5.56 % in Groups 1, 2, and 3, respectively. Conclusion. Adjuvant intravesical chemotherapy CT is an effective method to prevent recurrent bladder cancer.

  2. Randomised study of sequential versus combination chemotherapy with capecitabine, irinotecan and oxaliplatin in advanced colorectal cancer, an interim safety analysis. A Dutch Colorectal Cancer Group (DCCG) phase III study.

    NARCIS (Netherlands)

    Koopman, M.; Antonini, N.; Douma, J.; Wals, J.; Honkoop, A.H.; Erdkamp, F.L.; Jong, R.S. de; Rodenburg, C.J.; Vreugdenhil, G.R.; Akkermans-Vogelaar, J.M.; Punt, C.J.A.

    2006-01-01

    BACKGROUND: Results on overall survival in randomised studies of mono- versus combination chemotherapy in advanced colorectal cancer patients may have been biased by an imbalance in salvage treatments. This is the first randomised study that evaluates sequential versus combination chemotherapy with

  3. Randomised study of sequential versus combination chemotherapy with capecitabine, irinotecan and oxaliplatin in advanced colorectal cancer, an interim safety analysis. A Dutch Colorectal Cancer Group (DCCG) phase III study

    NARCIS (Netherlands)

    Koopman, M.; Antonini, N. F.; Douma, J.; Wals, J.; Honkoop, A. H.; Erdkamp, F. L. G.; de Jong, R. S.; Rodenburg, C. J.; Vreugdenhil, G.; Akkermans-Vogelaar, J. M.; Punt, C. J. A.

    2006-01-01

    Results on overall survival in randomised studies of mono- versus combination chemotherapy in advanced colorectal cancer patients may have been biased by an imbalance in salvage treatments. This is the first randomised study that evaluates sequential versus combination chemotherapy with a

  4. Acute volume expansion attenuates hyperthermia-induced reductions in cerebral perfusion during simulated hemorrhage

    DEFF Research Database (Denmark)

    Schlader, Zachary J; Seifert, Thomas; Wilson, Thad E

    2013-01-01

    Hyperthermia reduces the capacity to withstand a simulated hemorrhagic challenge, but volume loading preserves this capacity. This study tested the hypotheses that acute volume expansion during hyperthermia increases cerebral perfusion and attenuates reductions in cerebral perfusion during...... infusion while hyperthermic. Primary dependent variables were mean middle cerebral artery blood velocity (MCAvmean), serving as an index of cerebral perfusion; mean arterial pressure (MAP); and cardiac output (thermodilution). During baseline, hyperthermia reduced MCAvmean (P = 0.001) by 12 ± 9% relative...

  5. The effect of resveratrol in combination with irradiation and chemotherapy. Study using Merkel cell carcinoma cell lines

    International Nuclear Information System (INIS)

    Heiduschka, G.; Lill, C.; Brunner, M.; Thurnher, D.; Seemann, R.; Schmid, R.; Houben, R.; Bigenzahn, J.

    2014-01-01

    Merkel cell carcinoma (MCC) is a rare, but highly malignant tumor of the skin. In case of systemic disease, possible therapeutic options include irradiation or chemotherapy. The aim of this study was to evaluate whether the flavonoid resveratrol enhances the effect of radiotherapy or chemotherapy in MCC cell lines. The two MCC cell lines MCC13 and MCC26 were treated with increasing doses of resveratrol. Combination experiments were conducted with cisplatin and etoposide. Colony forming assays were performed after sequential irradiation with 1, 2, 3, 4, 6, and 8 Gy and apoptosis was assessed with flow cytometry. Expression of cancer drug targets was analyzed by real-time PCR array. Resveratrol is cytotoxic in MCC cell lines. Cell growth is inhibited by induction of apoptosis. The combination with cisplatin and etoposide resulted in a partially synergistic inhibition of cell proliferation. Resveratrol and irradiation led to a synergistic reduction in colony formation compared to irradiation alone. Evaluation of gene expression did not show significant difference between the cell lines. Due to its radiosensitizing effect, resveratrol seems to be a promising agent in combination with radiation therapy. The amount of chemosensitizing depends on the cell lines tested. (orig.) [de

  6. High dose lansoprazole combined with metronomic chemotherapy: a phase I/II study in companion animals with spontaneously occurring tumors.

    Science.gov (United States)

    Spugnini, Enrico P; Buglioni, Sabrina; Carocci, Francesca; Francesco, Menicagli; Vincenzi, Bruno; Fanciulli, Maurizio; Fais, Stefano

    2014-08-21

    The treatment of human cancer has been seriously hampered for decades by resistance to chemotherapeutic drugs. A very efficient mechanism of tumor resistance to drugs is the proton pumps-mediated acidification of tumor microenvironment. Metronomic chemotherapy has shown efficacy in adjuvant fashion as well as in the treatment of pets with advanced disease. Moreover, we have shown in veterinary clinical settings that pre-treatment with proton-pumps inhibitors (PPI) increases tumor responsiveness to chemotherapeutics. In this study pet with spontaneously occurring cancer have been recruited to be treated by a combination of metronomic chemotherapy and high dose PPIs and their responses have been matched to those of a historical control of ten patients treated with metronomic chemotherapy alone. Single arm, non randomized phase II open study, with historical control group, evaluating safety and efficacy of the combination of metronomic chemotherapy and alkalization. Twenty-four companion animals (22 dogs and 2 cats) were treated adding to their metronomic chemotherapy protocol the pump inhibitor lansoprazole at high dose, and a water alkalizer. Their responses have been evaluated by clinical and instrumental evaluation and matched to those of the control group. The protocol was overall well tolerated, with only two dogs experiencing side effects due to gastric hypochlorhydria consisting with vomiting and or diarrhea. In terms of overall response, in the alkalized cohort, 18 out of 24 had partial or complete responses (75%), two patients had a stable disease and the remaining patients experienced no response or progressive disease. On the other hand, only one patient in the control group experienced a complete response (10%) and three other experienced short lived responses. Median time to terminal event was 34 weeks for the experimental group versus 2 weeks in the controls (p= 0.042). Patient alkalization has shown to be well tolerated and to increase tumor response

  7. Intra-arterial chemotherapy for locally advanced bladder cancer

    International Nuclear Information System (INIS)

    Aota, Yasuhiro; Yoshida, Kazuhiko

    1999-01-01

    A total of 83 patients with locally advanced bladder cancer (T1, n=5; T2, n=28; T3a, n=21; T3b, n=21; T4, n=8) were treated with intra-arterial (i.a.) cisplatin and adriamycin (or epirubicin) chemotherapy. In 51 of the 83 cases, we combined this treatment with radiotherapy. The pathological complete response (CR) rate was 68% for all patients, 84% for i.a. chemotherapy combined with radiotherapy and only 41% for i.a. chemotherapy. The 5-year survival rate was 57% for all patients, 71% for i.a. chemotherapy combined with radiotherapy and only 44% for i.a. chemotherapy. The 5-year survival as a function of the clinical stage was 82% for T1+T2, 66% for T3a, 28% for T3b, 25% for T4 (T1+T2 vs. T3b: p<0.001, T1+T2 vs. T4: p<0.0001, T3a vs. T3b: p<0.0263, T3a vs. T4: p<0.0214, T3b vs. T4: p<0.029). In 46% of all patients, we succeeded in preserving the bladder; especially noteworthy, is that in 65% of the patients undergoing i.a. chemotherapy combined with radiotherapy, we succeeded in preserving the bladder. These results demonstrate that i.a. chemotherapy combined with radiotherapy is a useful method for locally advanced bladder cancer which may make preservation of the bladder function feasible. (author)

  8. Effect of Xiao Chaihu Tang combined with intravenous chemotherapy on tumor markers and immune function in patients with advanced breast cancer

    Directory of Open Access Journals (Sweden)

    Jian-Ping Zhong

    2017-05-01

    Full Text Available Objective: To study the effect of Xiao Chaihu Tang combined with intravenous chemotherapy on tumor markers and immune function in patients with advanced breast cancer. Methods: 76 patients with advanced breast cancer treated in our hospital between May 2012 and November 2015 were collected and divided into the combined treatment group (n=34 who accepted Xiao Chaihu Tang combined with intravenous chemotherapy and the control group (n=42 who accepted intravenous chemotherapy alone according to different treatment, and the treatment cycle was 3 months for both groups. Before treatment and 3 months after treatment, ELISA method was used to detect serum levels of broad-spectrum tumor markers and breast cancerspecific tumor markers; flow cytometer was used to detect cellular immune function index levels, and turbidimetric immunoassay was used to detect humoral immune function index levels in peripheral blood. Results: Before treatment, differences in serum tumor marker levels as well as cellular immunity and humoral immunity index levels in peripheral blood were not statistically significant between two groups of patients (P>0.05; after 3 months of treatment, broad-spectrum tumor markers carcinoembryonic antigen (CEA, carbohydrate antigen 153 (CA153 and carbohydrate antigen 125 (CA125 levels in serum of combined treatment group were lower than those of control group, and breast cancer-specific tumor markers insulin-like growth factor-1 (IGF-1, midkine (MK, soluble E-cadherin (sEC and thymidine kinase 1 (TK1 levels were lower than those of control group (P<0.05; CD3+ and CD4+ T lymphocyte levels as well as CD4+/CD8+ ratio in peripheral blood of combined treatment group were higher than those of control group while CD8+ T lymphocyte level was lower than that of control group, and immunoglobulin G (IgG, immunoglobulin A (IgA and immunoglobulin M (IgM levels in peripheral blood were higher than those of control group (P<0.05. Conclusions: Xiao Chaihu Tang

  9. nNOS inhibitors attenuate methamphetamine-induced dopaminergic neurotoxicity but not hyperthermia in mice.

    Science.gov (United States)

    Itzhak, Y; Martin, J L; Ail, S F

    2000-09-11

    Methamphetamine (METH)-induced dopaminergic neurotoxicity is associated with hyperthermia. We investigated the effect of several neuronal nitric oxide synthase (nNOS) inhibitors on METH-induced hyperthermia and striatal dopaminergic neurotoxicity. Administration of METH (5 mg/kg; q. 3 h x 3) to Swiss Webster mice produced marked hyperthermia and 50-60% depletion of striatal dopaminergic markers 72 h after METH administration. Pretreatment with the nNOS inhibitors S-methylthiocitrulline (SMTC; 10 mg/kg) or 3-bromo-7-nitroindazole (3-Br-7-NI; 20 mg/kg) before each METH injection did not affect the persistent hyperthermia produced by METH, but afforded protection against the depletion of dopaminergic markers. A low dose (25 mg/kg) of the nNOS inhibitor 7-nitroindazole (7-NI) did not affect METH-induced hyperthermia, but a high dose (50 mg/kg) produced significant hypothermia. These findings indicate that low dose of selective nNOS inhibitors protect against METH-induced neurotoxicity with no effect on body temperature and support the hypothesis that nitric oxide (NO) and peroxynitrite have a major role in METH-induced dopaminergic neurotoxicity.

  10. Treatment of recurrent head and neck cancers: results of two radio chemotherapy combinations

    Energy Technology Data Exchange (ETDEWEB)

    Khanfir, K.; Wibault, P.; Koscielny, S.; Crevoisier, R. de; Biron, B.; Domenge, C.; Lusinchi, A.; Luboinski, B.; Eschewege, F.; Bourhis, J. [Institut Gustave Roussy, 94 - Villejuif (France)

    2002-11-01

    Despite much more intense treatment in the 3 - D group, the acute toxicity was not significantly different between the two groups. A complete tumor regression was observed in 41 % of the patients in the 2- D group and 58 % in the 3- D group. however, given the short follow-up and the relatively limited number of patients in the 3 - D group, conclusions regarding tumor response need further investigations. The use of 3 - D conformal radiotherapy allowed to increase the dose intensity of re irradiation combined with chemotherapy, without increasing deleterious effect. (N.C.)

  11. Pharmacogenetics and pathophysiology of CACNA1S mutations in malignant hyperthermia.

    Science.gov (United States)

    Beam, Teresa A; Loudermilk, Emily F; Kisor, David F

    2017-02-01

    A review of the pharmacogenetics (PGt) and pathophysiology of calcium voltage-gated channel subunit alpha1 S (CACNA1S) mutations in malignant hyperthermia susceptibility type 5 (MHS5; MIM #60188) is presented. Malignant hyperthermia (MH) is a life-threatening hypermetabolic state of skeletal muscle usually induced by volatile, halogenated anesthetics and/or the depolarizing neuromuscular blocker succinylcholine. In addition to ryanodine receptor 1 (RYR1) mutations, several CACNA1S mutations are known to be risk factors for increased susceptibility to MH (MHS). However, the presence of these pathogenic CACNA1S gene variations cannot be used to positively predict MH since the condition is genetically heterogeneous with variable expression and incomplete penetrance. At present, one or at most six CACNA1S mutations display significant linkage or association either to clinically diagnosed MH or to MHS as determined by contracture testing. Additional pathogenic variants in CACNA1S, either alone or in combination with genes affecting Ca 2+ homeostasis, are likely to be discovered in association to MH as whole exome sequencing becomes more commonplace. Copyright © 2017 the American Physiological Society.

  12. Treatment results and complications in clinical combinations of radiation and chemotherapy in the treatment of localized cancer in the head and neck

    International Nuclear Information System (INIS)

    Masaki, Norie; Shigematsu, Yasushi

    1981-01-01

    By using chemotherapy combined with radiotherapy, significant improvements were achieved in treatment results of localized non-Hodgkin's lymphoma, intraoral cancer, and carcinoma of the maxillary sinus. Administering chemotherapy with radiation was given sumultaneously in the patients with intraoral cancer (BLM iv) and with carcinoma of the maxillary sinus (5-FU ia). In the patients with non-Hodgkin's lymphoma, chemotherapy (1 or 2 cycles of COPP) was administered and followed by radiotherapy. If radiation dose were reduced by about 50% in the intraoral cancer, 20% in carcinoma of the maxillary sinus, and 10% in non-Hodgkin's lymphoma, acute and/or chronic complications were within tolerable limits in this series of observations, although toxicity was dose-related for both chemotherapy and radiotherapy. (author)

  13. Prognostic value of hemoglobin concentrations in patients with advanced head and neck cancer treated with combined radio-chemotherapy and surgery

    International Nuclear Information System (INIS)

    Wagner, W.; Hermann, R.; Koch, O.; Hartlapp, J.; Krech, R.

    2000-01-01

    Purpose: Hemoglobin levels are currently the focus of interest as prognostic factors in patients with head and neck cancer. Most published clinical trials have confirmed hemoglobin to process a significant influence on survival in patients treated with radiotherapy. In our study we have investigated the prognostic value of hemoglobin in a combined modality schedule. Patients and Methods: Forty-three patients with advanced head and neck tumors were treated with combined radiochemotherapy. The therapy comprised 2 courses of induction chemotherapy with ifosfamide (1,500 mg/m 2 , day 1 to 5) and cisplatin (60 mg/m 2 , day 5) followed by hyperfractionated accelerated radiotherapy with a total dose of only 30 Gy. Surgery involved tumor resection and neck dissection. Results: The 1-year overall survival rate and the 2-year survival rate were 79% and 56%, respectively. The 1- and 2-year recurrence-free survival rates were 68% and 49%, respectively. Prognostic factors with an impact on survival were seen in tumor size (T3 vs T4, p=0.0088), response to radio-chemotherapy at the primary site (no vital tumor rest vs vital tumor rest, p=0.045), response to lymph node radio-chemotherapy (no vital tumor cells vs vital tumor cells, p=0.013) and level of hemoglobin after radio-chemotherapy (Hb≥11.5 g/dl vs [de

  14. Frequency Of Hyperthermia In Acute Ischemic Stroke Patients Visiting A Tertiary Care Hospital

    International Nuclear Information System (INIS)

    Maheshwari, A. K.; Kumar, P.; Alam, M. T.; Aurangzeb, M.; Imran, K.; Masroor, M.; Parkash, J.

    2016-01-01

    Objective: To determine the frequency of hyperthermia in acute ischemic stroke patients visiting a tertiary care hospital in a developing country. Study Design: Cross-sectional, observational study. Place and Duration of Study: Medical Wards of Civil Hospital, Karachi, from January to June 2013. Methodology: Patients aged = 18 years of either gender with acute ischemic stroke presenting within 24 hours of onset of symptoms were included. Written informed consent was obtained from all participants as well as approval of ethical review committee of the institute. Axillary temperature by mercury thermometer was monitored at the time of admission and after every 6 hours for 3 days. The data was analyzed using SPSS version 17.0 (SPSS Inc., IL, Chicago, USA). Result: A total of 106 patients of ischemic stroke were included. The mean age of enrolled participants was 60.1 ±9.5 years. Among these, 61 (57.5 percentage) were males and 45 (42.5 percentage) females. Among all patients, 51.9 percentage presented with loss of consciousness, 30.2 percentage with slurred speech, 77.4 percentage with limb weakness, and 9.4 percentage with decrease vision. A total of 17 (16 percentage) patients with ischemic stroke developed hyperthermia. When the prevalence of hyperthermia was stratified according to age, among patients of < 60 years of age, 26 percentage developed hyperthermia compared to 7.1 percentage in patients of = 60 years of age (p=0.008). On gender stratification, among male patients, 14.8 percentage developed hyperthermia compared to 17.8 percentage in female patients (p=0.43). Conclusion: It is concluded from this study that the frequency of hyperthermia in ischemic stroke was 16 percentage and it should be looked for as it has significant impact on the outcome. The hyperthermia was significantly more common in younger adults as compared to older adults. However, gender had no influence on the prevalence rate of hyperthermia. (author)

  15. Effects of hyperthermia on radiation-induced chromosome breakage and loss in excision repair deficient Drosophila melanogaster

    International Nuclear Information System (INIS)

    Mittler, S.

    1986-01-01

    Hyperthermia increased radiosensitivity with respect to γ-ray induced chromosome loss and breakage in all stages of spermatogenesis in the wild type Oregon R strain of Drosophila melanogaster, whereas hyperthermia increased radiosensitivity to a lesser extent in cn mus(2) 201sup(D1), an excision repair mutant with 0 per cent excision capacity and in mus(3) 308sup(D1), a strain with 24 per cent excision capacity. The differences in hyperthermia-induced radiation sensitivity between the excision repair mutants and the wild strain may be due to the hyperthermia affecting the excision repair mechanism, suggesting that one of the possible mechanisms involved in hyperthermia-increased radiosensitivity is an effect on excision repair. (author)

  16. Clinico-pathological studies on the effects of preoperative hyperthermo-chemo-radiotherapy for advanced esophageal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Tsutomu; Ide, Hiroko; Eguchi, Reiki (Tokyo Women' s Medical Coll. (Japan)) (and others)

    1991-12-01

    We report clinico-pathological studies on the effect of preoperative hyperthermia and chemotherapy combined with radiotherapy (HCR) for progress of the local curability of advanced esophageal carcinoma. The subjects of these studies were 17 patients who underwent subtotal esophagectomy after preoperative irradiation of 40 Gy from 1980 to 1989, of which 8 patients had HCR, 6 patients irradiation only (R), 3 patients both irradiation and chemotherapy (CR). The clinical response rate of the patients with R or CR was 33% (PR 3, MR 3, NC 3), and the histological effective (Ef{sub 3} or Ef{sub 2}) rate was 56% (Ef{sub 3} 1, Ef{sub 2} 4, Ef{sub 1} 4). The clinical response rate of the patients with HCR was 88% (PR 7, MR 1), and the histological effective rate was 100% (Ef{sub 3} 1, Ef{sub 2} 7). HCR was more effective than R or CR for the local lesion of esophageal carcinoma histopathologically (p<0.05). However, the survival rate of patients with HCR was similar to R and CR, respectively. These results suggest that further improvement of the heating methods and the methods of combining hyperthermia with irradiation and chemotherapy is needed. (author).

  17. Clinico-pathological studies on the effects of preoperative hyperthermo-chemo-radiotherapy for advanced esophageal carcinoma

    International Nuclear Information System (INIS)

    Nakamura, Tsutomu; Ide, Hiroko; Eguchi, Reiki

    1991-01-01

    We report clinico-pathological studies on the effect of preoperative hyperthermia and chemotherapy combined with radiotherapy (HCR) for progress of the local curability of advanced esophageal carcinoma. The subjects of these studies were 17 patients who underwent subtotal esophagectomy after preoperative irradiation of 40 Gy from 1980 to 1989, of which 8 patients had HCR, 6 patients irradiation only (R), 3 patients both irradiation and chemotherapy (CR). The clinical response rate of the patients with R or CR was 33% (PR 3, MR 3, NC 3), and the histological effective (Ef 3 or Ef 2 ) rate was 56% (Ef 3 1, Ef 2 4, Ef 1 4). The clinical response rate of the patients with HCR was 88% (PR 7, MR 1), and the histological effective rate was 100% (Ef 3 1, Ef 2 7). HCR was more effective than R or CR for the local lesion of esophageal carcinoma histopathologically (p<0.05). However, the survival rate of patients with HCR was similar to R and CR, respectively. These results suggest that further improvement of the heating methods and the methods of combining hyperthermia with irradiation and chemotherapy is needed. (author)

  18. Combined CT-guided radiofrequency ablation with systemic chemotherapy improves the survival for nasopharyngeal carcinoma with oligometastasis in liver: Propensity score matching analysis.

    Science.gov (United States)

    Li, Wang; Bai, Yutong; Wu, Ming; Shen, Lujun; Shi, Feng; Sun, Xuqi; Lin, Caijin; Chang, Boyang; Pan, Changchuan; Li, Zhiwen; Wu, Peihong

    2017-08-08

    The aim of this study was to retrospectively compare the treatment efficacy of systemic chemotherapy combined with sequential CT-guided radiofrequency ablation (Chemo-RFA) to chemotherapy alone (Chemo-only) in the management of nasopharyngeal carcinoma (NPC) with liver metastasis. Between 2003 and 2011, 328 NPC patients diagnosed with liver metastasis at Sun Yat-sen University Cancer Center were enrolled. One-to-one matched pairs between Chemo-RFA group with the Chemo-only group were generated using propensity score matching. The associations of treatment modality with overall survival (OS) and progression-free survival (PFS) were determined by Cox regression. Of the patients enrolled, 37 patients (11.8 %) received combined treatment, 291 (82.2) received chemotherapy alone. The patients in Chemo-RFA group were more frequently classified as lower number (≤3) of liver metastatic lesions (Poligometastasis in liver, and should be considered if the ablation is technically feasible.

  19. The protein kinase C (PKC) inhibitors combined with chemotherapy in the treatment of advanced non-small cell lung cancer: meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Zhang, L L; Cao, F F; Wang, Y; Meng, F L; Zhang, Y; Zhong, D S; Zhou, Q H

    2015-05-01

    The application of newer signaling pathway-targeted agents has become an important addition to chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC). In this study, we evaluated the efficacy and toxicities of PKC inhibitors combined with chemotherapy versus chemotherapy alone for patients with advanced NSCLC systematically. Literature retrieval, trials selection and assessment, data collection, and statistic analysis were performed according to the Cochrane Handbook 5.1.0. The outcome measures were tumor response rate, disease control rate, progression-free survival (PFS), overall survival (OS), and adverse effects. Five randomized controlled trials, comprising totally 1,005 patients, were included in this study. Meta-analysis showed significantly decreased response rate (RR 0.79; 95 % CI 0.64-0.99) and disease control rate (RR 0.90; 95 % CI 0.82-0.99) in PKC inhibitors-chemotherapy groups versus chemotherapy groups. There was no significant difference between the two treatment groups regarding progression-free survival (PFS, HR 1.05; 95 % CI 0.91-1.22) and overall survival (OS, HR 1.00; 95 % CI 0.86-1.16). The risk of grade 3/4 neutropenia, leucopenia, and thrombosis/embolism increased significantly in PKC inhibitors combination groups as compared with chemotherapy alone groups. The use of PKC inhibitors in addition to chemotherapy was not a valid alternative for patients with advanced NSCLC.

  20. Clinical results after different protocols of combined local heat and radiation

    International Nuclear Information System (INIS)

    Arcangeli, G.; Cividalli, A.; Nervi, C.; Lovisolo, G.

    1983-01-01

    Since 1977, 69 patients with 138 multiple lesions have been treated with combined radiotherapy and hyperthermia, according to 3 protocols. Firstly, radiotherapy was given following a thrice-a-day fractionation scheme of 1.5 to 2 Gy/fraction, up to 60 Gy. Hyperthermia (42.5 0 C/45 min) was applied each other day, immediately after the 2nd radiation fraction. Immediate response resulted significantly higher in the combined group (76% clearances in comparison with 46% after radiotherapy alone). Secondly, tumors received 40 Gy/8 fractions, twice a week, and hyperthermia (42.5 0 C/45 min) was applied with each radiotherapy fraction, either immediately after irradiation (simultaneously) of 4 h later (sequentially). A remarkable improvement of radiation response was obtained, especially with the simultaneous treatment. Thirdly, tumors received 30 Gy/6 fractions, twice a week. Hyperthermia (45 0 C/30 min) was applied simultaneously with each radiotherapy fraction and the surrounding skin was cooled. Complete tumor clearance was achieved in 88% lesions in comparison with 31% after radiotherapy alone. As expected, the incidence of thermal damage on uncooled skin was also increased. In conclusion, the best therapeutic ratio was obtained with low fractional radiotherapy doses and low temperature hyperthermia. (orig.) [de

  1. Radiosensitization of hypoxic bacterial cells and animal tumours by membrane active drugs and hyperthermia

    International Nuclear Information System (INIS)

    Singh, B.B.; Srinivasan, V.T.; Shenoy, M.A.; George, K.C.; Maniar, H.S.; Rawat, K.P.

    1987-01-01

    The present report deals with the results on phenothiazine derivatives such as promethazine (PMZ), trimeprazine (TMZ), trifluoperazine (TFP) and prochlorperazine (PCP) and their comparison with that of chlorpromazine (CPZ). Their efficiency in combination with hyperthermia, radiation and other anti-cancer drugs in treating murine tumors has also been presented herein. In addition, results on bacterial cells dealing with their mechanistic aspects are also included. (author). 57 refs., 27 figures, 13 tables

  2. Combination of EGFR-TKIs and chemotherapy as first-line therapy for advanced NSCLC: a meta-analysis.

    Science.gov (United States)

    OuYang, Pu-Yun; Su, Zhen; Mao, Yan-Ping; Deng, Wuguo; Xie, Fang-Yun

    2013-01-01

    The impact of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy as first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) remains controversial. Therefore, randomized trials that compared this combined regimen with chemotherapy or EGFR-TKIs monotherapy were included for this meta-analysis. We used published hazard ratios (HRs), if available, or derived treatment estimates from other survival data. Pooled estimates of treatment efficacy of the combined regimen in the entire unselected population and selected patients by EGFR-mutation status and smoking history were calculated. Eight trials eventually entered into this meta-analysis, including 4585 patients. Overall, the combined regimen significantly delayed disease progression (HR = 0.81, 95% CI 0.69-0.95, P = 0.01); subgroup analysis showed significantly higher progression free survival advantages in Asian patients (Pchemotherapy (P = 0.02). In selected patients by EGFR-mutation, both mutation positive (HR = 0.48, 95% CI 0.28-0.83, P = 0.009) and negative (HR = 0.84, 95% CI 0.72-0.98, P = 0.02) patients gained progression free survival benefit from the combined regimen, albeit the magnitude of benefit was marginally larger in mutation positive patients (P = 0.05). In selected patients by smoking history, never/light smokers achieved a great progression free survival benefit from the combined regimen (HR = 0.51, 95% CI 0.35-0.74, P = 0.0004). Unfortunately, the combined regimen had no significant impact on overall survival, irrespective of ethnicity, dose schedules or EGFR-mutation status. Severe anorexia (RR = 2.01, 95% CI 1.11-3.63; P = 0.02) and diarrhea (RR = 2.70, 95% CI 1.94-3.76; Pchemotherapy deserved to be considered in the future, although it is not approved for advanced NSCLC at the moment.

  3. Combined radiotherapy and chemotherapy for high-grade brain tumours

    Science.gov (United States)

    Barazzuol, Lara

    Glioblastoma (GBM) is the most common primary brain tumour in adults and among the most aggressive of all tumours. For several decades, the standard care of GBM was surgical resection followed by radiotherapy alone. In 2005, a landmark phase III clinical trial coordinated by the European Organization for Research and Treatment of Cancer (EORTC) and the National Cancer Institute of Canada (NCIC) demonstrated the benefit of radiotherapy with concomitant and adjuvant temozolomide (TMZ) chemotherapy. With TMZ, the median life expectancy in optimally managed patients is still only 12-14 months, with only 25% surviving 24 months. There is an urgent need for new therapies in particular in those patients whose tumour has an unmethylated methylguanine methyltransferase gene (MGMT) promoter, which is a predictive factor of benefit from TMZ. In this dissertation, the nature of the interaction between TMZ and radiation is investigated using both a mathematical model, based on in vivo population statistics of survival, and in vitro experimentation on a panel of human GBM cell lines. The results show that TMZ has an additive effect in vitro and that the population-based model may be insufficient in predicting TMZ response. The combination of TMZ with particle therapy is also investigated. Very little preclinical data exists on the effects of charged particles on GBM cell lines as well as on the concomitant application of chemotherapy. In this study, human GBM cells are exposed to 3 MeV protons and 6 MeV alpha particles in concomitance with TMZ. The results suggest that the radiation quality does not affect the nature of the interaction between TMZ and radiation, showing reproducible additive cytotoxicity. Since TMZ and radiation cause DNA damage in cancer cells, there has been increased attention to the use of poly(ADP-ribose) polymerase (PARP) inhibitors. PARP is a family of enzymes that play a key role in the repair of DNA breaks. In this study, a novel PARP inhibitor, ABT-888

  4. Pilot studies of superfractionated radiotherapy and combination chemotherapy in limited oat cell carcinoma of the bronchus

    International Nuclear Information System (INIS)

    Hodson, D.I.; Malaker, K.; Meikle, A.L.; Levitt, M.

    1984-01-01

    There are sound radiobiologic and suggestive clinical rationale for superfractionating the radiotherapeutic regimens employed for the therapy of rapidly growing malignancies. Oat cell carcinoma of the bronchus is such a tumor. The authors report their experience combining aggressive systemic combination chemotherapy with supperfractionated radiotherapy for the treatment of limited oat cell carcinoma of the bronchus. Overall, patient tolerance was satisfactory and a complete remission rate of 74% was achieved. It remains to be proven, in a prospective randomized fashion, whether this approach is superior to current conventional management

  5. A phase II study of VP-16-ifosfamide-cisplatin combination chemotherapy plus early concurrent thoracic irradiation for previously untreated limited small cell lung cancer

    International Nuclear Information System (INIS)

    Woo, In Sook; Park, Young Suk; Kwon, Sung Hee

    2000-01-01

    At present the addition of thoracic irradiation to combination chemotherapy is a standard treatment for limited staged small cell ling cancer. However, there is still controversy about the optimum timing of chest irradiation. We conducted a phase II study of etoposide (VP-16)-ifosfamide-cisplatin (VIP) combination chemotherapy plus early concurrent thoracic irradiation for the patients with previously untreated limited small cell lung cancer in order to assess if the treatment modality could improve the response rate and the toxicity. Forty-four patients with limited small cell lung cancer were treated with etoposide-ifosfamide-cisplatin and concurrent thoracic irradiation. Combination chemotherapy consisted of etoposide 100 mg/m 2 (on day 1-3), ifosfamide 1000 mg/m 2 (on days 1 and 2) and cisplatin 100 mg/m 2 (on day 1). Concurrent thoracic irradiation consisted of a total of 4000 cGy over 4 weeks starting on the first day of the first chemotherapy. All patients who showed a complete response were given prophylactic cranial irradiation for 2.5 weeks. Forty-four of the 49 patients who entered the study from May 1994 to August 1998 were evaluable. The median age was 59 years and 40 patients had a performance status of 0 or 1. The median survival time was 22.5 months. Twenty-eight patients (62%) showed a complete response and 16 (38%) a partial response. Twenty-four patients (54%) developed grade 3 or 4 neutropenia; there was a 9% RTOG score 3 or 4 esophagitis. VIP combination chemotherapy and early concurrent thoracic irradiation for patients with limited stage small cell lung cancer revealed excellent antitumor response with tolerable toxicity. (author)

  6. Studies of murine tumor control using x-ray fractionation schedules alone or in combination with hyperthermia

    International Nuclear Information System (INIS)

    Imbra, R.J.

    1981-01-01

    The effectiveness of an experimental radiation fractionation schedule of decreasing-sized dose fractions administered at optimal time intervals was compared with a conventional fractionation schedule of constant-sized dose fractions administered five times per week. Also, the effect of the addition of hyperthermia (42.5 0 C) to radiation therapy was investigated. For some experiments, Ehrlich mammary tumors were growth in the right thighs of Swiss mice. The tumor response was determined by measuring the tumor-bearing leg diameter and converting this value to volume. The time for the treated tumor to regrow to its pre-tratment volume was used as an endpoint in Swiss mice. The maximum total treatment dose is limited by the amount of normal tissue damage. A total treatment dose of six thousand rads was most suitable for the further investigations. Definitive investigations were performed using the RIF-1 tumor grown in the right thigh of C3H mice. The length of mitotic delay of RIF-1 cells, in vivo, was determined after various single doses of x radiation. A direct (exponential) relationship betwen x-ray dose and mitotic delay time was observed. Times of release of the RIF-1 cells from radiation-induced mitotic delay were used to determine the optimum time intervals to deliver the decreasing-sized dose fractions. Six thousand rads administered as decreasing-sized dose fractions resulted in significantly greater RIF-1 tumor control, as compared to conventional radiation therapy. The best treatment schedule, overall, was decreasing-sized dose fractions plus hyperthermia

  7. Comparison of radiosensitization by 41 deg. C hyperthermia during low dose rate irradiation and during pulsed simulated low dose rate irradiation in human glioma cells

    International Nuclear Information System (INIS)

    Raaphorst, G. Peter; Ng, Cheng E.; Shahine, Bilal

    1999-01-01

    Purpose: Long duration mild hyperthermia has been shown to be an effective radiosensitizer when given concurrently with low dose rate irradiation. Pulsed simulated low dose rate (PSLDR) is now being used clinically, and we have set out to determine whether concurrent mild hyperthermia can be an effective radiosensitizer for the PSLDR protocol. Materials and Methods: Human glioma cells (U-87MG) were grown to plateau phase and treated in plateau phase in order to minimize cell cycle redistribution during protracted treatments. Low dose rate (LDR) irradiation and 41 deg. C hyperthermia were delivered by having a radium irradiator inside a temperature-controlled incubator. PSLDR was given using a 150 kVp X-ray unit and maintaining the cells at 41 deg. C between irradiations. The duration of irradiation and concurrent heating depended on total dose and extended up to 48 h. Results: When 41 deg. C hyperthermia was given currently with LDR or PSLDR, the thermal enhancement ratios (TER) were about the same if the average dose rate for PSLDR was the same as for LDR. At higher average dose rates for PSLDR the TERs became less. Conclusions: Our data show that concurrent mild hyperthermia can be an effective sensitizer for PSLDR. This sensitization can be as effective as for LDR if the same average dose rate is used and the TER increases with decreasing dose rate. Thus mild hyperthermia combined with PSLDR may be an effective clinical protocol

  8. The Dartmouth Center for Cancer Nanotechnology Excellence: magnetic hyperthermia.

    Science.gov (United States)

    Baker, Ian; Fiering, Steve N; Griswold, Karl E; Hoopes, P Jack; Kekalo, Katerina; Ndong, Christian; Paulsen, Keith; Petryk, Alicea A; Pogue, Brian; Shubitidze, Fridon; Weaver, John

    2015-01-01

    The Dartmouth Center for Cancer Nanotechnology Excellence - one of nine funded by the National Cancer Institute as part of the Alliance for Nanotechnology in Cancer - focuses on the use of magnetic nanoparticles for cancer diagnostics and hyperthermia therapy. It brings together a diverse team of engineers and biomedical researchers with expertise in nanomaterials, molecular targeting, advanced biomedical imaging and translational in vivo studies. The goal of successfully treating cancer is being approached by developing nanoparticles, conjugating them with Fabs, hyperthermia treatment, immunotherapy and sensing treatment response.

  9. Predicting thermal history a-priori for magnetic nanoparticle hyperthermia of internal carcinoma

    Science.gov (United States)

    Dhar, Purbarun; Sirisha Maganti, Lakshmi

    2017-08-01

    This article proposes a simplistic and realistic method where a direct analytical expression can be derived for the temperature field within a tumour during magnetic nanoparticle hyperthermia. The approximated analytical expression for thermal history within the tumour is derived based on the lumped capacitance approach and considers all therapy protocols and parameters. The present method is simplistic and provides an easy framework for estimating hyperthermia protocol parameters promptly. The model has been validated with respect to several experimental reports on animal models such as mice/rabbit/hamster and human clinical trials. It has been observed that the model is able to accurately estimate the thermal history within the carcinoma during the hyperthermia therapy. The present approach may find implications in a-priori estimation of the thermal history in internal tumours for optimizing magnetic hyperthermia treatment protocols with respect to the ablation time, tumour size, magnetic drug concentration, field strength, field frequency, nanoparticle material and size, tumour location, and so on.

  10. Treatment of small cell carcinoma of lung with combined high dose mediastinal irradiation, whole brain prophylaxis and chemotherapy

    International Nuclear Information System (INIS)

    Shank, B.; Natale, R.B.; Hilaris, B.S.; Wittes, R.E.

    1981-01-01

    Survival of patients with small cell carcinoma of lung, treated on a new combined radiotherapy-chemotherapy protocol, compares favorably with other regimens in the literature and our own previous combined approaches. Radiation, given after induction chemotherapy, consisted of whole brain prophylaxis in all 44 evaluable patients. Patients with limited disease were also treated to the primary and mediastinum to a high dose (5000 rad equivalent) using multiple fields. The new chemotherapy regimen consisted of induction with cyclophosphamide, doxorubicin, and vincristine alternated with cis-platinum and VP-16 (an epipodophyllotoxin) for two cycles, followed by consolidation with low dose cyclophosphamide and vincristine concurrent with irradiation. Patients with limited disease who achieved less than complete response, and all patients with extensive disease were not continued on maintenance chemotherapy. Out of 24 evaluable patients with limited disease, there was 73% survival at 1 year by life-table analysis, measured from treatment initiation. After induction, 16/24 of these limited disease patients were CR (complete responders): 20/24 were CR at completion of their irradiation. Out of 20 evaluable patients with extensive disease, there was 59% survival at 1 year by life-table analysis. Only 4/44 (9%) brain parenchymal relapses occurred, one at 3 months and one at 6 months after local failure and two in patients who did not become CRs, implicating a possible re-seeding mechanism. Five patients had central nervous system relapses outside of brain parenchyma (spinal epidural and leptomeningeal); in three patients this was the initial site of failure. Significant complications included leukopenia (50%) and thrombocytopenia (24%) primarily during induction, and chronic pulmonary fibrosis (25%), possibly contributing to two deaths

  11. [Supportive care during chemotherapy for lung cancer in daily practice].

    Science.gov (United States)

    Müller, Veronika; Tamási, Lilla; Gálffy, Gabriella; Losonczy, György

    2012-09-01

    Active oncotherapy, combination chemotherapy of lung cancer is accompanied with many side effects which may impair patients' quality of life and compromise the effectiveness of chemotherapy. Most side effects of chemotherapy are preventable or treatable with optimal supportive care which enhances success in patient care and treatment. The aim of this review is to summarize the most important conditions that may be associated with combined chemotherapy of lung cancer from the practical point of view.

  12. Nanoscaled red blood cells facilitate breast cancer treatment by combining photothermal/photodynamic therapy and chemotherapy.

    Science.gov (United States)

    Wan, Guoyun; Chen, Bowei; Li, Ling; Wang, Dan; Shi, Shurui; Zhang, Tao; Wang, Yue; Zhang, Lianyun; Wang, Yinsong

    2018-02-01

    Red blood cells (RBCs)-based vesicles have been widely used for drug delivery due to their unique advantages. Intact RBCs contain a large amount of oxyhemoglobin (oxyHb), which can assist with photodynamic therapy (PDT). Indocyanine green (ICG), a photosensitizer both for photothermal therapy (PTT) and PDT, shows potent anticancer efficacy when combined with chemotherapeutic drug doxorubicin (DOX). In this study, we prepared nanoscaled RBCs (RAs) containing oxyHb and gas-generating agent ammonium bicarbonate (ABC) for co-loading and controlled release of ICG and DOX, thus hoping to achieve synergistic effects of PTT/PDT and chemotherapy against breast cancer. Compared to free ICG, ICG and DOX co-loaded RAs (DIRAs) exhibited nearly identical PTT efficiency both in vitro and in vivo, but meanwhile their PDT efficiency was enhanced significantly. In mouse breast cancer cells, DIRAs significantly inhibited cell growth and induced cell apoptosis after laser irradiation. In breast tumor-bearing mice, intratumoral injection of DIRAs and followed by local laser irradiation almost completely ablated breast tumor and further suppressed tumor recurrence and metastasis. In conclusion, this biomimetic multifunctional nanosystem can facilitate breast cancer treatment by combining PTT/PDT and chemotherapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Bladder cancer: The combination of chemotherapy and irradiation in the treatment of patients with muscle-invading tumors

    International Nuclear Information System (INIS)

    Shipley, William U.; Zietman, Anthony L.

    1996-01-01

    In the USA the recommended treatment for patients with muscle-invading transitional cell cancer of the bladder is usually radical cystectomy. Conservative surgery irradiation, and cisplatin-based systemic chemotherapy are, however, each effective for some patients. Although they provide the opportunity for bladder preservation, each modality, when used alone, is inferior to radical cystectomy in terms of local control and, perhaps, survival. Many recent publications have now documented the efficacy of combined modality treatment protocols employing all three of these modalities together. All employ a selective approach in which the patients only receive full-dose radiation if they have had a complete response to induction CMT. Overall survival data for T2-T3a patients are certainly as good as any reported cystectomy series of similarly clinically staged and similar aged patients. Radiation adds very significantly to the transurethral resection and systemic chemotherapy to maintain the bladder free of tumor. Substantially higher rates of pathologic confirmation of complete response are found following transurethral surgery and chemoradiation when compared with transurethral surgery and chemotherapy omitting the radiation. Overall survival is as good as cystectomy based approaches at 48-54% and over 80% of these long-term survivors keep their bladders. Following such therapies, 20-30% will subsequently develop superficial tumors. These patients may still be well treated by standard methods using transurethral resection and intravesical drugs. The concern of urologists that the conserved irradiated bladder functions poorly has also been answered by recent reports using modern radiation techniques. The instance of cystectomy for bladder shrinkage is repeatedly below 2%. Furthermore, sexual function is commonly preserved. The systemic morbidity of the chemotherapy is relatively high, but new approached using anti-emetics and GCSF now allow this to be reduced. In many

  14. An ultrasound system for simultaneous ultrasound hyperthermia and photon beam irradiation

    International Nuclear Information System (INIS)

    Straube, William L.; Moros, Eduardo G.; Low, Daniel A.; Klein, Eric E.; Willcut, Virgil M.; Myerson, Robert J.

    1996-01-01

    Purpose: An existing ultrasound system has been adapted for simultaneous use with external photon beam irradiation. The system is being used to investigate the potential for increased biological benefit of simultaneously combined hyperthermia and external beam irradiation with currently achievable temperature distributions. Methods and Materials: An existing clinical ultrasound system has been modified for simultaneous operation with a 60 Co teletherapy machine. The generator, thermometry system, computer, and applicators are located inside the treatment room, while the monitor and system control are located at the control console. Two approaches have been used clinically to combine the two modalities. In the first approach, an en-face setup is used in which the ultrasound beam and the photon beam travel through the same window of entry to the tumor. This is achieved by a reflecting system designed to deflect the ultrasound to the tumor while positioning the ultrasound transducer outside the radiation beam. The reflecting system consists of water and water-equivalent materials except for a 1 mm sheet of polished brass that is used as the reflector. The relative pressure fields were measured in water at the same distance from the ultrasound source using a scanning hydrophone with and without the reflector at the two operating frequencies of the device (1.0 and 3.4 MHz) for two applicators. Radiation dosimetry measurements were performed to determine the relationship between 60 Co irradiation through the reflector and absorbed dose. In the second approach the ultrasound and the radiation beam travel into the tumor from different windows of entry such that the radiation beam passes through no portion of the water bolus prior to entering the patient. We have termed this approach the orthogonal approach. For both approaches, the radiation fraction is given in the middle of an uninterrupted 60-min hyperthermia treatment. Results: The system modifications did not impair

  15. Postirradiation soft tissue sarcoma occurring in breast cancer patients: report of seven cases and results of combination chemotherapy

    International Nuclear Information System (INIS)

    Kuten, A.; Sapir, D.; Cohen, Y.; Haim, N.; Borovik, R.; Robinson, E.

    1985-01-01

    Seven cases of soft tissue sarcoma developing after primary or postoperative radiotherapy for breast carcinoma are reported. The sarcomas occurred within the irradiated volume, after a latent period of 4-26 years. These cases conform well to established criteria for the diagnosis of radiation-induced sarcoma. Chemotherapy, consisting of the four-drug combination CYVADIC (cyclophosphamide, vincristine, adriamycin, DTIC) was employed in six of the seven patients. Only two of them achieved partial remission, lasting only 2 and 3 months, respectively. The effectiveness of adriamycin-containing chemotherapy regimens in soft tissue sarcomas as well as the remote hazard of radiation-related sarcoma in primary or postoperative breast irradiation are discussed

  16. A systematic review and meta-analysis of traditional insect Chinese medicines combined chemotherapy for non-surgical hepatocellular carcinoma therapy.

    Science.gov (United States)

    Shi, Zhaofeng; Song, Tiebing; Wan, Yi; Xie, Juan; Yan, Yiquan; Shi, Kekai; Du, Yongping; Shang, Lei

    2017-06-28

    On the background of high morbidity and mortality of hepatocellular carcinoma (HCC) and rapid development of traditional Chinese medicine (TCM), we conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to assess the clinical effectiveness and safety of traditional insect Chinese medicine and related preparation for non-surgical HCC. RCTs were searched based on standardized searching rules in mainstream medical databases from the inception up to May 2016. Ultimately, a total of 57 articles with 4,651 patients enrolled in this meta-analysis. We found that traditional insect Chinese medicine and related preparation combined chemotherapy show significantly effectiveness and safety in objective response rate (P traditional insect Chinese medicine and related preparations could be recommended as auxiliary therapy combined chemotherapy for HCC therapy.

  17. Phase I and pharmacologic study of the combination paclitaxel and carboplatin as first-line chemotherapy in stage III and IV ovarian cancer

    NARCIS (Netherlands)

    Huizing, M. T.; van Warmerdam, L. J.; Rosing, H.; Schaefers, M. C.; Lai, A.; Helmerhorst, T. J.; Veenhof, C. H.; Birkhofer, M. J.; Rodenhuis, S.; Beijnen, J. H.; ten Bokkel Huinink, W. W.

    1997-01-01

    To determine the maximum-tolerated dose for the combination paclitaxel and carboplatin administered every 4 weeks and to gain more insight into the pharmacokinetics and pharmacodynamics of this combination in previously untreated ovarian cancer patients. Thirty-five chemotherapy-naive patients with

  18. Sorafenib and locoregional deep electro-hyperthermia in advanced hepatocellular carcinoma: A phase II study

    Science.gov (United States)

    GADALETA-CALDAROLA, GENNARO; INFUSINO, STEFANIA; GALISE, IDA; RANIERI, GIROLAMO; VINCIARELLI, GIANLUCA; FAZIO, VITO; DIVELLA, ROSA; DANIELE, ANTONELLA; FILIPPELLI, GIANFRANCO; GADALETA, COSMO DAMIANO

    2014-01-01

    The standard treatment for advanced hepatocellular carcinoma (HCC) is sorafenib, a multikinase inhibitor of tumor cell proliferation and angiogenesis. Hyperthermia inhibits angiogenesis and promotes apoptosis. Potential synergic antiangiogenic and proapoptotic effects represent the rationale for combining sorafenib with electro-hyperthermia (EHY) in HCC. A total of 21 patients (median age, 64 years; range, 55–73 years) with advanced HCC were enrolled in the current study between February 2009 and September 2010. EHY was achieved by arranging capacitive electrodes with a deep hypothermia radiofrequency field of 13.56 Mhz at 80 W for 60 min, three times per week for six weeks, followed by two weeks without treatment, in combination with sorafenib at a dose of 800 mg every other day. According to the modified Response Evaluation Criteria in Solid Tumors criteria, 50% achieved stable disease, 5% achieved partial response and 45% achieved progressive disease. No complete response was observed. The progression-free survival (PFS) rate at six months was 38%, while the median PFS and overall survival times were 5.2 [95% confidence interval (CI), 4.2–6.2) and 10.4 (95% CI, 10–11) months, respectively. The overall incidence of treatment-related adverse events was 80%, predominantly of grade 1 or 2. Grade 3 toxicity included fatigue, diarrhea, hand-foot skin reaction and hypertension. In the present study, the sorafenib plus EHY combination was feasible and well tolerated, and no major complications were observed. The initial findings indicated that this combination offers a promising option for advanced HCC. PMID:25202410

  19. Rib fractures after reirradiation plus hyperthermia for recurrent breast cancer. Predictive factors

    International Nuclear Information System (INIS)

    Oldenborg, Sabine; Valk, Christel; Os, Rob van; Voerde Sive Voerding, Paul zum; Crezee, Hans; Tienhoven, Geertjan van; Rasch, Coen; Oei, Bing; Venselaar, Jack; Randen, Adrienne van

    2016-01-01

    Combining reirradiation (reRT) and hyperthermia (HT) has shown high therapeutic value for patients with locoregional recurrent breast cancer (LR). However, additional toxicity of reirradiation (e.g., rib fractures) may occur. The aim of this study is to determine the impact of potential risk factors on the occurrence of rib fractures. From 1982-2005, 234 patients were treated with adjuvant reRT + HT after surgery for LR. ReRT consisted typically of 8 fractions of 4 Gy twice a week, or 12 fractions of 3 Gy four times a week. A total of 118 patients were irradiated with abutted photon and electron fields. In all, 60 patients were irradiated using either one or alternating combinations of abutted AP electron fields. Hyperthermia was given once or twice a week. The 5-year infield local control (LC) rate was 70 %. Rib fractures were detected in 16 of 234 patients (actuarial risk: 7 % at 5 years). All rib fractures occurred in patients treated with a combination of photon and abutted electron fields (p = 0.000); in 15 of 16 patients fractures were located in the abutment regions. The other significant predictive factors for rib fractures were a higher fraction dose (p = 0.040), large RT fields, and treatment before the year 2000. ReRT + HT results in long-term LC. The majority of rib fractures were located in the photon/electron abutment area, emphasizing the disadvantage of field overlap. Large abutted photon/electron fields combined with 4 Gy fractions increase the number of rib fractures in this study group. However, as these factors were highly correlated no relative importance of the individual factors could be estimated. Increasing the number of HT sessions a week does not increase the risk of rib fractures. (orig.) [de

  20. Pifithrin-μ, an inhibitor of heat-shock protein 70, can increase the antitumor effects of hyperthermia against human prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Kazumasa Sekihara

    Full Text Available Hyperthermia (HT improves the efficacy of anti-cancer radiotherapy and chemotherapy. However, HT also inevitably evokes stress responses and increases the expression of heat-shock proteins (HSPs in cancer cells. Among the HSPs, HSP70 is known as a pro-survival protein. In this study, we investigated the sensitizing effect of pifithrin (PFT-μ, a small molecule inhibitor of HSP70, when three human prostate cancer cell lines (LNCaP, PC-3, and DU-145 were treated with HT (43°C for 2 h. All cell lines constitutively expressed HSP70, and HT further increased its expression in LNCaP and DU-145. Knockdown of HSP70 with RNA interference decreased the viability and colony-forming ability of cancer cells. PFT-μ decreased the viabilities of all cell lines at one-tenth the dose of Quercetin, a well-known HSP inhibitor. The combination therapy with suboptimal doses of PFT-μ and HT decreased the viability of cancer cells most effectively when PFT-μ was added immediately before HT, and this combination effect was abolished by pre-knockdown of HSP70, suggesting that the effect was mediated via HSP70 inhibition. The combination therapy induced cell death, partially caspase-dependent, and decreased proliferating cancer cells, with decreased expression of c-Myc and cyclin D1 and increased expression of p21(WAF1/Cip, indicating arrest of cell growth. Additionally, the combination therapy significantly decreased the colony-forming ability of cancer cells compared to therapy with either alone. Furthermore, in a xenograft mouse model, the combination therapy significantly inhibited PC-3 tumor growth. These findings suggest that PFT-μ can effectively enhance HT-induced antitumor effects via HSP70 inhibition by inducing cell death and arrest of cell growth, and that PFT-μ is a promising agent for use in combination with HT to treat prostate cancer.

  1. Responses to hyperthermia (420, 440) and/or radiation in four mammalian cell lines in vitro

    International Nuclear Information System (INIS)

    Miyakoshi, Junji

    1981-01-01

    Survival in response to hyperthermia at 42 and 44 0 C, both alone and in combination with X-irradiation was examined in vitro in Chinese hamster V-79, HeLa-S3, murine Ehrlich ascites tumor cells (EH) and murine L-fibroblasts. L-cells were markedly thermo- and radiosensitive, while the other three cell lines, although not so sensitive did show similar responses. When each cell line was exposed to split dose Hyperthermia in the 42 → 44 0 C sequence, survival after the second treatment was increased for V-79 and HeLa-S3 cells, but was not significantly changed for EH and L-cells. In the case of split dose exposure in the 44 → 42 0 C sequence, survival after the second treatment was markedly decreased for V-79, EH and HeLa-S3 cells, but only slightly for L-cells. When hyperthermia at 42 or 44 0 C was followed by X-irradiation immediately, V-79, EH and HeLa-S3 cells showed decrements in both D sub(q) and D sub(o) values, while L-cells showed a decrement only in D sub(q) but no significant change in D sub(o). From these results, it seems that the hyperthermic damage by exposure to 44 0 C may be different from that by exposure to 42 0 C. (author)

  2. Pregnancies and menstrual function before and after combined radiation (RT) and chemotherapy (TVPP) for Hodgkin's disease

    International Nuclear Information System (INIS)

    Lacher, M.J.; Toner, K.

    1986-01-01

    The menstrual cycle, pregnancies, and offspring were evaluated before and after initial combined radiation (RT) and chemotherapy with thiotepa, vinblastine, vincristine, procarbazine, and prednisone (TVPP), in 34 women between the ages of 18 and 44 (median 26.5 years) treated for Stage II and Stage III Hodgkin's disease. The median range of follow-up is 83.1 months (range 40.5-140). After therapy 94.1% (32/34) continued to menstruate. Two of the four patients over the age of 35 ceased to menstruate. All patients under the age of 35 continued to menstruate (30/30). Age at the time of diagnosis was the only factor affecting change in menses with a significant probability (p = .001) that women greater than 30 years of age will experience some change in menstrual pattern. Seventeen pregnancies occurred in 12 women after therapy; 2 had 4 elective abortions; 10 delivered 12 children with normal physical development; 1 will deliver six months from now. Twelve of thirteen patients who wanted to become pregnant have conceived. The ability to become pregnant and deliver normal children after intensive treatment with combined radiation and chemotherapy (RT/TVPP) was comparable to the patients' pretreatment record

  3. Assessment of the Radiation-Equivalent of Chemotherapy Contributions in 1-Phase Radio-chemotherapy Treatment of Muscle-Invasive Bladder Cancer

    International Nuclear Information System (INIS)

    Plataniotis, George A.; Dale, Roger G.

    2014-01-01

    Purpose: To estimate the radiation equivalent of the chemotherapy contribution to observed complete response rates in published results of 1-phase radio-chemotherapy of muscle-invasive bladder cancer. Methods and Materials: A standard logistic dose–response curve was fitted to data from radiation therapy-alone trials and then used as the platform from which to quantify the chemotherapy contribution in 1-phase radio-chemotherapy trials. Two possible mechanisms of chemotherapy effect were assumed (1) a fixed radiation-independent contribution to local control; or (2) a fixed degree of chemotherapy-induced radiosensitization. A combination of both mechanisms was also considered. Results: The respective best-fit values of the independent chemotherapy-induced complete response (CCR) and radiosensitization (s) coefficients were 0.40 (95% confidence interval −0.07 to 0.87) and 1.30 (95% confidence interval 0.86-1.70). Independent chemotherapy effect was slightly favored by the analysis, and the derived CCR value was consistent with reports of pathologic complete response rates seen in neoadjuvant chemotherapy-alone treatments of muscle-invasive bladder cancer. The radiation equivalent of the CCR was 36.3 Gy. Conclusion: Although the data points in the analyzed radio-chemotherapy studies are widely dispersed (largely on account of the diverse range of chemotherapy schedules used), it is nonetheless possible to fit plausible-looking response curves. The methodology used here is based on a standard technique for analyzing dose-response in radiation therapy-alone studies and is capable of application to other mixed-modality treatment combinations involving radiation therapy

  4. The combined effect of interferon synthesis inductors, radiosensitizing and antitumoral agents on solid tumors

    International Nuclear Information System (INIS)

    Leonidze, D.L.

    1987-01-01

    In experiments with mice bearing solid sarcoma 37 a study was conducted on the combined effect of radiation and inductors of endogenous inerferon synthesis (IEIS), together with hyperthermia or together with an alkylating and carbomoilating agent, dimethinur. The effect was estimated by the tumor growth coefficient and by the number of animals with the regressed tumors. Poly I; polyC was not shiown to influence the efficiency of hyperthermia combined with radiation with radiation; dextransulphate and tiloron increased the radiosensitizing effect of hyperthermia. Dimethinur aggravated the effect of radiation, but with IEIS used together with dimethynur and radiation, the response of the tumor increased insignificantly as compared to the effect of IEIS together with radiation

  5. Efficacy and safety of short course adjuvant trastuzumab combination chemotherapy in breast cancer

    Directory of Open Access Journals (Sweden)

    Sachin S Hingmire

    2017-01-01

    Full Text Available Background: The adjuvant short course 9-week trastuzumab combination therapy for human epidermal receptor 2 positive breast cancer patients may often be considered as a cost-effective and safe option and has important implications for the Indian subcontinent as well as other developing countries. However, such regimens of shorter duration trastuzumab therapy like FinHer, offered in view of economic constraints, may not be able to achieve globally comparable cure rates in early breast cancer especially with high-risk women with more than 3 lymph node positive. Methods and Material: Outcome of 21 patients with HER2 positive breast cancer was treated with short course trastuzumab combination chemotherapy in the adjuvant setting was studied. Results: Out of 21 patients 15 are alive and disease free with a follow up of up to 73 months (median follow up 42 months.

  6. Results of preoperative combined therapy with radiation and multi-drug chemotherapy for oral squamous cell carcinomas

    International Nuclear Information System (INIS)

    Iwai, Masayuki; Sawada, Toshiharu; Furuta, Isao; Sado, Tadashi; Terashima, Ryuichi; Ito, Shigeto

    1996-01-01

    We retrospectively analyzed the effectiveness of preoperative treatment with combined chemotherapy, including cisplatin (CDDP) and carboplatin (CBDCA), and radiotherapy. Among 19 patients with oral squamous cell carcinoma, the primary site was the tongue in 13, the oral floor in 3, and the maxilla, lip, and gingiva in 1 case each. The clinical stage was 7 cases Stage II, 5 cases Stage III, and 7 cases Stage IV. Chemotherapy was administered intravenously using CDDP 50-80 mg (1 time) or CBDCA 150 mg once a week in a total dose of 300-750 mg, PEP 5 mg twice a week in a total dose of 40-60 mg, and 5-FU or Tegaful 300-600 mg in a total dose of 9.0-18.0 g. Radiotherapy was carried out with Lineac (5 times a week) in a total dose of 20-40 Gy/10-20 f/10-20 days. The clinical response to treatment was evaluated as CR 3 cases, PR 9 cases, and NC 6 cases. The response rate was 12/18 (66.7%) cases. Histologic effectiveness, evaluated according to the classification of Oohoshi and Shimosato, was Grade IV 11 cases, Grade III 3 cases, and Grade II 5 cases. The following adverse reactions were reported: stomatitis 19 cases, fever 13 cases, leukopenia 12 cases, loss of appetite 12 cases, and neutropenia 10 cases. Fourteen of the 19 patients (73.7%) have a good prognosis, without any signs of recurrence or metastasis. The results indicate that multidrug chemotherapy combined with radiotherapy is effective even for highly malignant carcinoma in the oral cavity. (author)

  7. Radio-chemotherapy in advanced tumors of the oral cavity, oro- and hypopharynx

    International Nuclear Information System (INIS)

    Schmitt, G.; Schnabel, T.

    1992-01-01

    Among combined radio-chemotherapy regimens of advanced head and neck tumors four modalities can be discriminated: 1. Induction chemotherapy, 2. simultaneous radio-chemotherapy, 3. adjuvant chemotherapy, 4. accelerated-hyperfractionated radiotherapy and chemotherapy. The results of the presently available randomized trials are as follows: 1. Induction chemotherapy has no influence on long-term recurrence-free survival. 2. With respect to simultaneous radio-chemotherapy, recurrence-free survival has been unproved with 5-FU and Mitomycin C. 3. There is evidence that adjuvant cis-platin therapy improves recurrence-free survival. 4. No results are available to date using hyperfractionated accelerated radiotherapy regimens in combination with chemotherapy. (orig.) [de

  8. Comparison of the effects of photon versus carbon ion irradiation when combined with chemotherapy in vitro

    International Nuclear Information System (INIS)

    Schlaich, Fabian; Brons, Stephan; Haberer, Thomas; Debus, Jürgen; Combs, Stephanie E; Weber, Klaus-Josef

    2013-01-01

    Characterization of combination effects of chemotherapy drugs with carbon ions in comparison to photons in vitro. The human colon adenocarcinoma cell line WiDr was tested for combinations with camptothecin, cisplatin, gemcitabine and paclitaxel. In addition three other human tumour cell lines (A549: lung, LN-229: glioblastoma, PANC-1: pancreas) were tested for the combination with camptothecin. Cells were irradiated with photon doses of 2, 4, 6 and 8 Gy or carbon ion doses of 0.5, 1, 2 and 3 Gy. Cell survival was assessed using the clonogenic growth assay. Treatment dependent changes in cell cycle distribution (up to 12 hours post-treatment) were measured by FACS analysis after propidium-iodide staining. Apoptosis was monitored for up to 36 hours post-treatment by Nicoletti-assay (with qualitative verification using DAPI staining). All cell lines exhibited the well-known increase of killing efficacy per unit dose of carbon ion exposure, with relative biological efficiencies at 10% survival (RBE 10 ) ranging from 2.3 to 3.7 for the different cell lines. In combination with chemotherapy additive toxicity was the prevailing effect. Only in combination with gemcitabine or cisplatin (WiDr) or camptothecin (all cell lines) the photon sensitivity was slightly enhanced, whereas purely independent toxicities were found with the carbon ion irradiation, in all cases. Radiation-induced cell cycle changes displayed the generally observed dose-dependent G2-arrest with little effect on S-phase fraction for all cell lines for photons and for carbon ions. Only paclitaxel showed a significant induction of apoptosis in WiDr cell line but independent of the used radiation quality. Combined effects of different chemotherapeutics with photons or with carbon ions do neither display qualitative nor substantial quantitative differences. Small radiosensitizing effects, when observed with photons are decreased with carbon ions. The data support the idea that a radiochemotherapy with common

  9. [Anti-EGFR Antibody Combination Chemotherapy Was Effective against Locally Advanced Ascending Colon Cancer as Well as a Recurrent Lesion - A Case Report].

    Science.gov (United States)

    Yamada, Yasufumi; Yokomizo, Hajime; Yano, Yuki; Okayama, Sachiyo; Satake, Masaya; Ida, Arika; Usui, Takebumi; Yamaguchi, Kentaro; Shiozawa, Shunichi; Yoshimatsu, Kazuhiko; Shimakawa, Takeshi; Katsube, Takao; Naritaka, Yoshihiko; Kato, Hiroyuki

    2017-10-01

    Here we report a case in which a locally advanced ascending colon cancer was successfully treated with anti-EGFR immunotherapy combined with chemotherapy and curative resection, and recurrent cancer was treated with the same chemotherapy. A 71-year-old man was diagnosed with ascending colon cancer in our department. No distant metastasis was observed, but curative resection was considered impossible because of extensive local cancer invasion. Because a genetic analysis revealed the presence of the wild-type KRAS gene, 6 courses of mFOLFOX6 plus cetuximab were administered. A cPR was obtained and curative resection was performed. The final diagnosis was ypT3N1M0, ypStage III a colon cancer, and chemotherapy improved the cancer stage to Grade 1b. Six courses of FOLFOX6 were then administered, followed by observation. After 2 years 6 months, a tumor of approximately 5 cm in size was noted in the right buttock using surveillance CT and was diagnosed as recurrent colon cancer. We considered further curative resection difficult and therefore 6 courses of mFOLFOX6 plus panitumumab were administered, a cPR was obtained, and right hip tumor extirpation surgery was performed. These results suggest that chemotherapy combined with anti-EGFR antibody immunotherapy is effective in treating recurrent colon cancer.

  10. Thermal dosimetry for bladder hyperthermia treatment. An overview.

    Science.gov (United States)

    Schooneveldt, Gerben; Bakker, Akke; Balidemaj, Edmond; Chopra, Rajiv; Crezee, Johannes; Geijsen, Elisabeth D; Hartmann, Josefin; Hulshof, Maarten C C M; Kok, H Petra; Paulides, Margarethus M; Sousa-Escandon, Alejandro; Stauffer, Paul R; Maccarini, Paolo F

    2016-06-01

    The urinary bladder is a fluid-filled organ. This makes, on the one hand, the internal surface of the bladder wall relatively easy to heat and ensures in most cases a relatively homogeneous temperature distribution; on the other hand the variable volume, organ motion, and moving fluid cause artefacts for most non-invasive thermometry methods, and require additional efforts in planning accurate thermal treatment of bladder cancer. We give an overview of the thermometry methods currently used and investigated for hyperthermia treatments of bladder cancer, and discuss their advantages and disadvantages within the context of the specific disease (muscle-invasive or non-muscle-invasive bladder cancer) and the heating technique used. The role of treatment simulation to determine the thermal dose delivered is also discussed. Generally speaking, invasive measurement methods are more accurate than non-invasive methods, but provide more limited spatial information; therefore, a combination of both is desirable, preferably supplemented by simulations. Current efforts at research and clinical centres continue to improve non-invasive thermometry methods and the reliability of treatment planning and control software. Due to the challenges in measuring temperature across the non-stationary bladder wall and surrounding tissues, more research is needed to increase our knowledge about the penetration depth and typical heating pattern of the various hyperthermia devices, in order to further improve treatments. The ability to better determine the delivered thermal dose will enable clinicians to investigate the optimal treatment parameters, and consequentially, to give better controlled, thus even more reliable and effective, thermal treatments.

  11. SU-F-J-05: The Effect of Air Pockets in the Urinary Bladder During Bladder Hyperthermia Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Schooneveldt, G.; Kok, H.P.; Bakker, A.; Geijsen, E.D.; Reijke, T.M. de; Crezee, J. [Academisch Medisch Centrum / Universiteit van Amsterdam, Amsterdam (Netherlands)

    2016-06-15

    Purpose: Hyperthermia combined with Mitomycin C is used for the treatment of non-muscle invasive bladder cancer (NMIBC), using a phased array system of microwave antennas for bladder heating. Often some air is present in the bladder, which effectively blocks the microwave radiation, potentially preventing proper treatment of that part of the bladder. Air can be a relevant fraction of the bladder content and large air pockets are expected to have a noticeable influence on achieved temperatures. Methods: We analysed 14 NMIBC patients treated at our institute with our AMC-4 hyperthermia device with four 70MHz antennas around the pelvis. A CT scan was made after treatment and a physician delineated the bladder on the CT scan. On the same scan, the amount of air present in the bladder was delineated. Using our in-house developed hyperthermia treatment planning system, we simulated the treatment using the clinically applied device settings. We did this once with the air pocket delineated on the CT scan, and once with the same volume filled with bladder tissue. Results: The patients had on average 4.2ml (range 0.8–10.1ml) air in the bladder. The bladder volume was delineated by the physician, that is including air pocket and bladder wall, was on average 253ml (range 93–452ml). The average volume in which changes exceeded 0.25°C was 22ml (range 0–108 ml), with the bladder being up to 2°C cooler when an air pocket was present. Except for extreme cases, there was no evident relation between the quantity of air and the difference in temperature. Conclusion: The effect of an air pocket in the bladder during bladder hyperthermia treatment varies strongly between patients. Generally, this leads to lower temperatures in the bladder, potentially affecting treatment quality, and suggesting that care need be taken to minimise the size of air pockets during hyperthermia treatments. The KWF Dutch Cancer Society financially supported this work, grant UVA 2012-5539.

  12. Use of extremity insulation during whole body hyperthermia to reduce temperature nonuniformity

    International Nuclear Information System (INIS)

    Thrall, D.E.; Page, R.L.

    1987-01-01

    The author previously documented during whole body hyperthermia in dogs using a radiant heating device that temperature at superficial sites, including tibial bone marrow, falls below systemic arterial temperature during the plateau phase of heating. This may be due to direct heat loss to the environment. Sites where temperature is lower than systemic arterial temperature during the plateau phase may become sanctuary sites where tumor deposits are spared because they do not receive the prescribed thermal dose. In an attempt to decrease temperature nonuniformity and increase thermal dose delivered to such superficial sites, extremity insulation has been employed during whole body hyperthermia in dogs. The author measured temperature at cutaneous and subcutaneous sites and within tibial bone marrow in insulated and noninsulated extremities of dogs undergoing whole body hyperthermia in the radiant heating device. The author found that extremity insulation is effective in reducing extremity temperature nonuniformity. Specific results are presented. Extremity insulation may be necessary during whole body hyperthermia to assure that extremity tumor deposits receive a thermal dose similar to that prescribed for the entire body

  13. Further investigations on the synergistic interaction of hyperthermia with sparsely ionizing radiations

    International Nuclear Information System (INIS)

    Schrader-Reichhardt, U.; Markus, B.

    1978-01-01

    Experiments were performed with tetraploid asynchronous and synchronous Chinese hamster ovary fibroblasts. Irradiations were done with 15 MeV electrons at two different irradiation depths and with X-rays of 200 and 29 kV. For several diploid Chinese hamster cell lines it has been shown in literature that S-cells are much more sensitive to combined treatment of hyperthermia and radiation than G1-cells. With our tetraploid CHO fibroblasts we could find no additional enhancement of S-phase killing, converting radioresistant S-cells to the most radiation sensitive phase. (orig./AJ) [de

  14. On the temperature control in self-controlling hyperthermia therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ebrahimi, Mahyar, E-mail: ebrahimi_m@mehr.sharif.ir

    2016-10-15

    In self-controlling hyperthermia therapy, once the desired temperature is reached, the heat generation ceases and overheating is prevented. In order to design a system that generates sufficient heat without thermal ablation of surrounding healthy tissue, a good understanding of temperature distribution and its change with time is imperative. This study is conducted to extend our understanding about the heat generation and transfer, temperature distribution and temperature rise pattern in the tumor and surrounding tissue during self-controlling magnetic hyperthermia. A model consisting of two concentric spheres that represents the tumor and its surrounding tissue is considered and temperature change pattern and temperature distribution in tumor and surrounding tissue are studied. After describing the model and its governing equations and constants precisely, a typical numerical solution of the model is presented. Then it is showed that how different parameters like Curie temperature of nanoparticles, magnetic field amplitude and nanoparticles concentration can affect the temperature change pattern during self-controlling magnetic hyperthermia. The model system herein discussed can be useful to gain insight on the self-controlling magnetic hyperthermia while applied to cancer treatment in real scenario and can be useful for treatment strategy determination. - Highlights: • Temperature change pattern in tumor and surrounding tissue are studied. • The model system herein can be useful for treatment strategy determination. • In the work described herein, emphasis is on the effect of low Curie temperature. • If the equilibrium temperature can be tuned appropriately, the stay time will be infinite.

  15. On the temperature control in self-controlling hyperthermia therapy

    International Nuclear Information System (INIS)

    Ebrahimi, Mahyar

    2016-01-01

    In self-controlling hyperthermia therapy, once the desired temperature is reached, the heat generation ceases and overheating is prevented. In order to design a system that generates sufficient heat without thermal ablation of surrounding healthy tissue, a good understanding of temperature distribution and its change with time is imperative. This study is conducted to extend our understanding about the heat generation and transfer, temperature distribution and temperature rise pattern in the tumor and surrounding tissue during self-controlling magnetic hyperthermia. A model consisting of two concentric spheres that represents the tumor and its surrounding tissue is considered and temperature change pattern and temperature distribution in tumor and surrounding tissue are studied. After describing the model and its governing equations and constants precisely, a typical numerical solution of the model is presented. Then it is showed that how different parameters like Curie temperature of nanoparticles, magnetic field amplitude and nanoparticles concentration can affect the temperature change pattern during self-controlling magnetic hyperthermia. The model system herein discussed can be useful to gain insight on the self-controlling magnetic hyperthermia while applied to cancer treatment in real scenario and can be useful for treatment strategy determination. - Highlights: • Temperature change pattern in tumor and surrounding tissue are studied. • The model system herein can be useful for treatment strategy determination. • In the work described herein, emphasis is on the effect of low Curie temperature. • If the equilibrium temperature can be tuned appropriately, the stay time will be infinite.

  16. Gold nanocage decorated pH-sensitive micelle for highly effective photothermo-chemotherapy and photoacoustic imaging.

    Science.gov (United States)

    Zhou, Guoyong; Xiao, Hong; Li, Xiaoxia; Huang, Yi; Song, Wei; Song, Liang; Chen, Meiwan; Cheng, Du; Shuai, Xintao

    2017-12-01

    A pH-sensitive copolymer PAsp(DIP)-b-PAsp(MEA) (PDPM) was synthesized and self-assembled to micelle loading chemotherapeutic drug doxorubicin (DOX) and introducing a gold nanocage structure for photothermo-chemotherapy and photoacoustic imaging. After further surface modification with polyethylene glycol (PEG), the DOX-loaded pH-sensitive gold nanocage (D-PGNC) around 100 nm possessed a uniform spherical structure with a pH-sensitive core of PAsp(DIP) incorporating DOX, an interlayer crosslinked via disulfide bonds and decorated with discontinuous gold shell, and a PEG corona. The release of DOX from D-PGNC was turned off in bloodstream due to the cross-linking and gold decoration of interlayer but turned on inside tumor tissue by multiple stimulations including the low pH value of tumor tissue (≈6.8), the low lysosomal pH value of cancer cells (≈5.0) and near-infrared (NIR) irradiation. The gold nanocage receiving NIR irradiation could generate hyperthermia to ablate tumor cells. Moreover, the photoacoustic (PA) imaging and analysis of DOX fluorescence inside tumor tissue demonstrated that photothermal therapy based on the gold nanocage effectively drove DOX penetration inside tumor. Owing to the rapid intratumor release and deep tissue penetration of drug favorable for killing cancer cells survived the photothermal therapy, the combined therapy based on D-PGNC via NIR irradiation exhibited a synergistic treatment effect superior to either chemotherapy or NIR-induced photothermal therapy alone. The novelty of the manuscript is its multifunctional system which incorporates anticancer drug DOX in its pH-sensitive core and acts as a template to introduce a gold nanocage. This nanomedicine presents potentials of sequestrating drug molecules in blood circulation but releasing them inside tumor upon responding to the acidic microenvironment therein. Exposure to NIR laser further expedited the pH-sensitive DOX release and promoted DOX penetration into cancer

  17. Analysis of Perioperative Chemotherapy in Resected Pancreatic Cancer: Identifying the Number and Sequence of Chemotherapy Cycles Needed to Optimize Survival.

    Science.gov (United States)

    Epelboym, Irene; Zenati, Mazen S; Hamad, Ahmad; Steve, Jennifer; Lee, Kenneth K; Bahary, Nathan; Hogg, Melissa E; Zeh, Herbert J; Zureikat, Amer H

    2017-09-01

    Receipt of 6 cycles of adjuvant chemotherapy (AC) is standard of care in pancreatic cancer (PC). Neoadjuvant chemotherapy (NAC) is increasingly utilized; however, optimal number of cycles needed alone or in combination with AC remains unknown. We sought to determine the optimal number and sequence of perioperative chemotherapy cycles in PC. Single institutional review of all resected PCs from 2008 to 2015. The impact of cumulative number of chemotherapy cycles received (0, 1-5, and ≥6 cycles) and their sequence (NAC, AC, or NAC + AC) on overall survival was evaluated Cox-proportional hazard modeling, using 6 cycles of AC as reference. A total of 522 patients were analyzed. Based on sample size distribution, four combinations were evaluated: 0 cycles = 12.1%, 1-5 cycles of combined NAC + AC = 29%, 6 cycles of AC = 25%, and ≥6 cycles of combined NAC + AC = 34%, with corresponding survival. 13.1, 18.5, 37, and 36.8 months. On MVA (P cycles AC, receipt of 0 cycles [HR 3.57, confidence interval (CI) 2.47-5.18] or 1-5 cycles in any combination (HR 2.37, CI 1.73-3.23) was associated with increased hazard of death, whereas receipt of ≥6 cycles in any sequence was associated with optimal and comparable survival (HR 1.07, CI 0.78-1.47). Receipt of 6 or more perioperative cycles of chemotherapy either as combined neoadjuvant and adjuvant or adjuvant alone may be associated with optimal and comparable survival in resected PC.

  18. Granulocyte colony stimulating factor priming chemotherapy is more effective than standard chemotherapy as salvage therapy in relapsed acute myeloid leukemia.

    Science.gov (United States)

    Shen, Ying; He, Aili; Wang, Fangxia; Bai, Ju; Wang, Jianli; Zhao, Wanhong; Zhang, Wanggang; Cao, Xingmei; Chen, Yinxia; Liu, Jie; Ma, Xiaorong; Chen, Hongli; Feng, Yuandong; Yang, Yun

    2017-12-29

    To improve the complete remission (CR) rate of newly diagnosed acute myeloid leukemia (AML) patients and alleviate the severe side effects of double induction chemotherapy, we combined a standard regimen with granulocyte colony-stimulating factor (G-CSF) priming chemotherapy to compose a new double induction regimen for AML patients who failed to achieve CR after the first course. Ninety-seven patients with AML who did not achieve CR after the first course of standard chemotherapy were enrolled. Among them, 45 patients received G-CSF priming combined with low-dose chemotherapy during days 20-22 of the first course of chemotherapy, serving as priming group, 52 patients were administered standard chemotherapy again, serving as control group. Between the two groups there were no differences in the French-American-British (FAB) classification, risk status, the first course of chemotherapy, blood cell count or blasts percentage of bone marrow before the second course. But the CR rate was significantly higher and the adverse effect was much lower in the priming group than the control group. Cox multivariate regression analysis showed that WBC level before the second course and the selection of the second chemotherapy regimen were two independent factors for long survival of patients. These results elucidate that standard chemotherapy followed by G-CSF priming new double induction chemotherapy is an effective method for AML patients to improve CR rate and reduce adverse effects. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  19. Effectiveness of combinations of Ayurvedic drugs in alleviating drug toxicity and improving quality of life of cancer patients treated with chemotherapy.

    Science.gov (United States)

    Deshmukh, Vineeta; Kulkarni, Arvind; Bhargava, Sudhir; Patil, Tushar; Ramdasi, Vijay; Gangal, Sudha; Godse, Vasanti; Datar, Shrinivas; Gujar, Shweta; Sardeshmukh, Sadanand

    2014-11-01

    This study was conducted to assess the effectiveness of combinations of Ayurvedic drugs in alleviating the toxicity of chemotherapy and improving the quality of life of cancer patients. The following was the research question: Can Ayurvedic drugs be used to alleviate the side effects of chemotherapy and improve the quality of life of cancer patients? Random patients with malignancies of different tissues, grades, and stages were divided into two groups according to their treatment modality. Group 1 consisted of 15 patients treated with six cycles of chemotherapy alone and who did not receive any Ayurvedic drugs (control group). Group 2 consisted of patients (divided into three arms) who received Ayurvedic drugs during chemotherapy and after chemotherapy. Nineteen patients in arm 1 received the Ayurvedic drugs Mauktikyukta Kamdudha (MKD) and Mauktikyukta Praval Panchamruta (MPP) along with a full course of chemotherapy. Fifteen patients in arm 2 received the same Ayurvedic treatment, but the treatment was started after completing the sixth cycle of chemotherapy. Eighteen patients in arm 3 received the Suvarnabhasmadi formulation (SBD) in addition to MKD and MPP after completing the sixth cycle of chemotherapy. Treatment was given for 16 weeks in all three arms. Patients from both groups were observed for a period of 6 months. The assessment criteria depended on Common Toxicity Criteria (CTC designed by NIH and NCI): haemogram; weight; physical examination including Quality of Life Questionnaire (QLQ designed by the European Organization of Research and Treatment of Cancer (EORTC)) for functional, symptom and global scores; and Karnofsky score for assessment of general well-being and activities of daily life. ECOG (Eastern Cooperation Oncology Group) score was also additionally included for assessment of symptoms. From amongst the symptomatic criteria, there was significant improvement in all the three arms compared with the control group in nausea, loss of appetite

  20. A case report of suspected malignant hyperthermia where patient survived the episode

    OpenAIRE

    Iqbal, Asif; Badoo, Shoaib; Naqeeb, Ruqsana

    2017-01-01

    Malignant hyperthermia is rare inherited disorder in our part of the world; there are only few cases reported in literature in India who were suspected of having this condition. The overall incidence of malignant hyperthermia during general anesthesia is estimated to range from 1: 5000 to 1: 50,000–100,000 and mortality rate is estimated to be

  1. Optimization of combination chemotherapy based on the calculation of network entropy for protein-protein interactions in breast cancer cell lines

    Directory of Open Access Journals (Sweden)

    Carels Nicolas

    2015-12-01

    We propose several novel drug combinations using only the approved drugs for the inactivation of the target identified in this study with the purpose of increasing patient survival and lowering the deleterious side effects of cancer chemotherapy.

  2. Hyperthermia and radiotherapy

    International Nuclear Information System (INIS)

    Lindholm, C.E.

    1992-01-01

    Combined hyperthermia (HT 45 min once or twice per week) and low dose radiotherapy (LDRT 30-34.5 Gy in 2-3 weeks) have been given to 182 locally recurrent or metastatic superficial tumours in 133 patients. Tumour response was analysed in 137 tumours in 100 patients. The overall complete response (CR) was 50% with a median duration (DCR) of 13±3 months. When mammary carcinoma, representing 62% of the treated tumours, were analysed, CR was 62% with a DCR of 14±4 months. In a comparative, non-randomized study, on 34 matched tumour pairs in 24 patients, treatment was given with LDRT+HT to the larger and the same LDRT to the smaller tumour, the patients acting as their own control. A significant difference in CR was obtained in favour of the combined treatment (p=0.0013 all diagnosis and p=0.0027 mammary carcinoma). There was no significant difference in DCR between the two modalities. No significant difference in CR was seen when tumours were randomely treated with HT once (CR 56%) or twice (CR 69%) per week combined with the same LDRT. Predictive factors for CR, multivariately analysed (15 parameters), in mammary carcinoma recurring in earlier irradiated regions, were; the present LDRT absorbed dose (p=0.02) and the average minimum temperature in the best HT session (p=0.03). Significant skin toxicity was seen in 28% of all the 182 heated regions. Prognostic factors for skin damage, multivariately analysed, were; the extension of the heated region (p=0.007) and the highest average maximum temperature in any of the HT sessions (p=0.04). Pain was in some way correlated to severe toxicity but was not considered to be an optimal monitor for HT as many patients with severe and moderate pain were without any serious skin reactions, while slight or no pain sometimes were associated with severe reactions. 401 refs

  3. [Treatment of Chemotherapy Related Leukocytopenia by Oral Administration of Multiple Leucogenic Drugs Combined with G-CSF: an Experimental Study].

    Science.gov (United States)

    Zhang, Xi-ping; Zhang, Xiang; Yang, Hong-jian; Zou, De-hong; He, Xiang-ming; Yu, Xing-fei; Li, Yong-feng

    2015-07-01

    To evaluate efficacies of three commonly used oral drugs including Berbamine Hydrochloride Tablet (B), Qijiao Shengbai Capsule (Q), and Leucogen Tablet (L) (by single drug, two drugs or three drugs) combined with granulocyte colony-stimulating factor (G-CSF) for treat ment of chemotherapy related leukocytopenia in mice. Totally 156 Kunming male mice were divided into the normal control group (A, n=24), the model group (B, n=24), the G-CSF group (C, n =24), the G-CSF+Q group (D, n=12), G-CSF+ B (E, n=12), the G-CSF+L group (F, n=12), the G-CSF + Q + B group (G, n=12), the G-CSF + Q + L group (H, n=12), the G-CSF + L + B group (I, n=12), and the G-CSF + L + Q + B (J, n=12). Mouse models of chemotherapy related leukocytopenia were established by intraperitoneal injection of cyclophosphamide (CTX). A G-CSF group was set up as a positive control. Mice were treated by a single oral drug, a single oral drug combined with G-CSF, and two or three drugs combined with G-CSF respectively, and the death rate calculated. Hemocytes [such as white blood cells (WBC) and its classification, red blood cells (RBC), platelet (PLT), hemoglobin (Hb)] were calculated by hematology analyzer. Mice were anatomized and important organs weighed. Organ indices were calculated. There was no statistical difference in the mortality rate among all groups (P > 0.05). Compared with Group B, WBC was elevated in all other groups (P drug B and L (P chemotherapy related leukopenia or decreased three blood series was to administrate three commonly oral drugs combined with G-CSF. Authors speculated that G-CSF and Q might have a certain effect on CTX induced immune inhibition.

  4. Outcomes after environmental hyperthermia.

    Science.gov (United States)

    LoVecchio, Frank; Pizon, Anthony F; Berrett, Christopher; Balls, Adam

    2007-05-01

    This study was conducted to describe the characteristics and outcomes of patients who presented to the emergency department (ED) with presumed environmental hyperthermia. A retrospective chart review was performed in 2 institutions with patients who were seen in the ED and had a discharge diagnosis of hyperthermia, heat stroke, heat exhaustion, or heat cramps. Exclusion criteria were an alternative diagnosis potentially explaining the hyperthermia (pneumonia, etc). Research assistants, who were blinded to the purpose of the study, performed a systematic chart review after a structured training session. If necessary, a third reviewer acted as a tiebreaker. Data regarding patient demographics, comorbidities, vital signs, laboratory results, and short-term outcome were collected. Data were analyzed with Excel and STATA software. We enrolled 52 patients with a mean age of 42.6 years (range, 0.4-81 years) from August 1, 2003 to August 31, 2005. The mean high daily temperature was 103.6 degrees F (range, 88-118 degrees F). At presentation, the mean body temperature was 105.1 degrees F (range, 100.2-111.2 degrees F) and the Glasgow Coma Scale score was less than 14 in 36 (69.2%) patients. Laboratory results demonstrated that 21 (40.4%) patients had a creatinine level of more than 1.5 mg/dL, 35 (67.3%) patients had a creatine kinase (CK) of more than 200 U/L, 30 patients (57.7%) had a prothrombin time of more than 13 seconds, 29 (55.8%) patients had an aspartate aminotransferase (AST) of more than 45 U/L, and only 3 patients (5.7%) had a glucose of less than 60 mg/dL. Ethanol or illicit drugs were involved in 18 (34.6%) cases. The mean hospital stay was 4.7 days (range, 1-30 days), and there were 15 deaths (28.8%). A kappa score for interreviewer reliability was 0.69. Major limitations were the retrospective nature and lack of homogeneity in patient evaluation and test ordering. Hyperthermic patients with higher initial temperatures, hypotension, or low Glasgow Coma Scale

  5. High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.

    Directory of Open Access Journals (Sweden)

    L John Hoffer

    Full Text Available Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail.We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement.Despite IVC's biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC's value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type

  6. High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.

    Science.gov (United States)

    Hoffer, L John; Robitaille, Line; Zakarian, Robert; Melnychuk, David; Kavan, Petr; Agulnik, Jason; Cohen, Victor; Small, David; Miller, Wilson H

    2015-01-01

    Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC) could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail. We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement. Despite IVC's biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC's value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type, chemotherapy

  7. Reirradiation + hyperthermia for recurrent breast cancer en cuirasse

    Energy Technology Data Exchange (ETDEWEB)

    Oldenborg, Sabine; Rasch, Coen R.N.; Os, Rob van; Kusumanto, Yoka H.; Voerde Sive Voerding, Paul J. zum; Crezee, Hans; Tienhoven, Geertjan van [University of Amsterdam (AMC), Department of Radiation Oncology, Z1-215, Academic Medical Center, Amsterdam (Netherlands); Oei, Bing S.; Venselaar, Jack L. [Institute Verbeeten (BVI), Department of Radiation Oncology, Tilburg (Netherlands); Heymans, Martijn W. [VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam (Netherlands)

    2018-03-15

    Patients with irresectable locoregional recurrent breast cancer en cuirasse (BCEC) do not have effective curative treatment options. Hyperthermia, the elevation of tumor temperature to 40-45 C, is a well-established radio- and chemotherapy sensitizer. A total of 196 patients were treated with reirradiation and hyperthermia (reRT+HT) at two Dutch institutes from 1982-2005. The palliative effect was evaluated in terms of clinical outcome and toxicity. All patients received previous irradiation to a median dose of 50 Gy. In all, 75% of patients received 1-6 treatment modalities for previous tumor recurrences. ReRT consisted of 8 x 4 Gy given twice a week or 12 x 3 Gy given four times a week. Superficial hyperthermia was added once or twice a week. Tumor area comprised ≥1/2 of the ipsilateral chest wall. Overall clinical response rate was 72% (complete response [CR] 30%, partial response [PR] 42%, stable disease [SD] 22%, progressive disease [PD] 6%). The local progression-free rate at 1 year was 24%. Median survival was 6.9 months. Forty-three percent of our patients with CR, PR, SD after treatment remained infield progression-free until death or last follow-up. Acute ≥grade 3 toxicity occurred in 33% of patients, while late ≥grade 3 toxicity was recorded in 14% of patients. Tumor ulceration prior to treatment had a negative impact on both clinical outcome and toxicity. ReRT+HT provides sustainable palliative tumor control, despite refractory, extensive tumor growth. Compared to currently available systemic treatment options, reRT+HT is more effective with less toxicity. (orig.) [German] Fuer Patienten mit inoperablen lokoregionalen Rueckfaellen von Brustkrebs in Form eines Cancer en cuirasse (BCEC) gibt es keine effektiven kurativen Behandlungsoptionen. Die Hyperthermie, bei der die Tumortemperatur auf 40-45 C erhoeht wird, ist eine etablierte Methode zur Radio- und Chemotherapiesensibilisierung. Insgesamt 161 Patientinnen wurden in zwei niederlaendischen

  8. The study of combination therapy for arterial infusion chemotherapy and radiation therapy in unresectable gallbladder cancer

    International Nuclear Information System (INIS)

    Goto, Takuma; Saito, Hiroya; Yanagawa, Nobuyuki; Fujinaga, Akihiro; Saito, Yoshinori

    2013-01-01

    In this study, we investigated an effective strategy of treatment for unresectable gallbladder cancer (GBC) by the retrospective analysis of prognostic factors and anti-tumor therapies, especially combination therapy of arterial infusion chemotherapy and radiation therapy (AI+PT). Forty-three patients with unresectable GBC were enrolled, and prognostic factors were investigated by multivariate analysis using a proportional hazard model. In addition, we examined the indication and after-therapy by analyzing the each factor cumulative survival rates and anti-tumor effect about the AI + RT group (n=24). AI + RT and the responders to the first-line therapy were significant prognostic factors. In AI + RT group, median survival time, progression-free survival and the 1-year survival rate, the response and disease control rates was 15.5 months, 7.1 months, 62.5%. 54.2% and 95.8%, respectively; which suggested prolonged survival and high anti-tumor effect. Cumulative survival rate was significantly shorter in cases with distant metastasis except liver metastases, and has been tendency to extend in the group who underwent systemic chemotherapy as after-therapy. The treatment strategy, using the Al + RT as first-line with the systemic chemotherapy as after-therapy, suggested contribute to the prolonged survival in locally advanced and liver metastases cases of GBC. (author)

  9. Estimated radiation pneumonitis risk after photon versus proton therapy alone or combined with chemotherapy for lung cancer

    DEFF Research Database (Denmark)

    Vogelius, Ivan R.; Westerly, David C; Aznar, Marianne Camille

    2011-01-01

    Background. Traditionally, radiation therapy plans are optimized without consideration of chemotherapy. Here, we model the risk of radiation pneumonitis (RP) in the presence of a possible interaction between chemotherapy and radiation dose distribution. Material and methods. Three alternative......-radiation combinations could be an interesting indication for selecting patients for proton therapy. It is likely that the IMRT plans would perform better if the CERD was accounted for during optimization, but more clinical data is required to facilitate evidence-based plan optimization in the multi-modality setting....... treatment plans are compared in 18 non-small cell lung cancer patients previously treated with helical tomotherapy; the tomotherapy plan, an intensity modulated proton therapy plan (IMPT) and a three dimensional conformal radiotherapy (3D-CRT) plan. All plans are optimized without consideration...

  10. Nanotechnology for Cancer Therapy Based on Chemotherapy

    OpenAIRE

    Chen-Yang Zhao; Rui Cheng; Zhe Yang; Zhong-Min Tian

    2018-01-01

    Chemotherapy has been widely applied in clinics. However, the therapeutic potential of chemotherapy against cancer is seriously dissatisfactory due to the nonspecific drug distribution, multidrug resistance (MDR) and the heterogeneity of cancer. Therefore, combinational therapy based on chemotherapy mediated by nanotechnology, has been the trend in clinical research at present, which can result in a remarkably increased therapeutic efficiency with few side effects to normal tissues. Moreover,...

  11. Deep local and regional hyperthermia with annular phased array

    International Nuclear Information System (INIS)

    Uehara, S.; Omagari, J.; Hata, K.

    1989-01-01

    33 refractory tumors mainly located in the pelvic cavity after definitive treatment were treated by loco-regional hyperthermia alone (n = 11) or by heat in combination with radiotherapy (n = 22) by annular phased array (APA) manufactured by BSD Corp. Tumors were heated up to more than 42 0 C in 78% of 347 total heat sessions with induction time 22 ± 1 (S.D.) minutes during which those of intra-pelvic organs were elevated up to between 41 and 42 0 C. Tumor response was CR 18%, PR 50% by heat (11.2 ± 1.5 S.D. fractions) combined with radiotherapy (43.8 ± 12.5 S.D. Gy) and by heat alone (8.6 ± 1.3 S.D. fractions) CR 18%, PR 9%. In all heat sessions superficial pain 36%, skin burn (grade 1-2) 12% inside annular array and slight to moderate systemic heat stress 100% were the main adverse reactions we experienced. (orig.)

  12. Online Adaptive Hyperthermia Treatment Planning During Locoregional Heating to Suppress Treatment-Limiting Hot Spots

    NARCIS (Netherlands)

    Kok, H. Petra; Korshuize-van Straten, Linda; Bakker, Akke; de Kroon-Oldenhof, Rianne; Geijsen, Elisabeth D.; Stalpers, Lukas J. A.; Crezee, Johannes

    2017-01-01

    Adequate tumor temperatures during hyperthermia are essential for good clinical response, but excessive heating of normal tissue should be avoided. This makes locoregional heating using phased array systems technically challenging. Online application of hyperthermia treatment planning could help to

  13. The effect of resveratrol in combination with irradiation and chemotherapy. Study using Merkel cell carcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Heiduschka, G. [Medical University of Vienna, Department of Otorhinolaryngology, Head and Neck Surgery, Vienna (Austria); Medical University of Vienna, Clinical Pharmacology, Vienna (Austria); Lill, C.; Brunner, M.; Thurnher, D. [Medical University of Vienna, Department of Otorhinolaryngology, Head and Neck Surgery, Vienna (Austria); Seemann, R. [Medical University of Vienna, Maxillo-Facial Surgery, Vienna (Austria); Schmid, R. [Medical University of Vienna, Radiotherapy and -biology, Vienna (Austria); Houben, R. [University Hospital Wuerzburg, Department of Dermatology, Wuerzburg (Germany); Bigenzahn, J. [CeMM-Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna (Austria)

    2014-01-15

    Merkel cell carcinoma (MCC) is a rare, but highly malignant tumor of the skin. In case of systemic disease, possible therapeutic options include irradiation or chemotherapy. The aim of this study was to evaluate whether the flavonoid resveratrol enhances the effect of radiotherapy or chemotherapy in MCC cell lines. The two MCC cell lines MCC13 and MCC26 were treated with increasing doses of resveratrol. Combination experiments were conducted with cisplatin and etoposide. Colony forming assays were performed after sequential irradiation with 1, 2, 3, 4, 6, and 8 Gy and apoptosis was assessed with flow cytometry. Expression of cancer drug targets was analyzed by real-time PCR array. Resveratrol is cytotoxic in MCC cell lines. Cell growth is inhibited by induction of apoptosis. The combination with cisplatin and etoposide resulted in a partially synergistic inhibition of cell proliferation. Resveratrol and irradiation led to a synergistic reduction in colony formation compared to irradiation alone. Evaluation of gene expression did not show significant difference between the cell lines. Due to its radiosensitizing effect, resveratrol seems to be a promising agent in combination with radiation therapy. The amount of chemosensitizing depends on the cell lines tested. (orig.) [German] Das Merkelzellkarzinom (MCC) ist ein seltener, jedoch hochmaligner Tumor der Haut. Sowohl Strahlentherapie oder Chemotherapie sind moegliche therapeutische Optionen. In dieser Studie wurde untersucht, ob das Flavonoid Resveratrol die Wirkung der Strahlen- oder Chemotherapie in MCC-Zelllinien verbessert. Die beiden MCC-Zelllinien MCC13 und MCC26 wurden mit ansteigenden Dosen von Resveratrol behandelt. Kombinationsexperimente wurden mit Cisplatin und Etoposid durchgefuehrt und die Koloniebildung in ''Colony-Forming''-Assays nach erfolgter sequentieller Bestrahlung mit 1, 2, 3, 4, 6 und 8 Gy gemessen. Desweiteren wurde die Apoptose mittels Durchflusszytometrie bestimmt. Die

  14. [Long-term Efficacy of Radiofrequency Ablation Combined with Chemotherapy 
in the Treatment of Patients with Advanced Non-small Cell Lung Cancer
--A Retrospective Study].

    Science.gov (United States)

    Du, Shuhui; Qin, Da; Pang, Ruiqi; Zhang, Yeqing; Zhao, Siqi; Hu, Mu; Zhi, Xiuyi

    2017-10-20

    Radiofrequency ablation (RFA) combined with chemotherapy has a certain short-term therapeutic effect for the treatment of advanced non-small cell lung cancer (NSCLC), but whether it can improve the long-term survival rate of patients is still controversy. This study retrospectively analyzed the difference of long-term efficacy between RFA combined with chemotherapy and chemotherapy alone in the treatment of patients with advanced NSCLC. A total of 77 patients with stage IIIb and stage IV NSCLC who underwent radiofrequency ablation and chemotherapy in the Department of Thoracic Surgery, Xuanwu Hospital, Capital University of Medical Sciences from September 2009 to December 2015 were enrolled as the treatment group. Chemotherapy with no radiofrequency ablation was performed in 56 patients with stage IIIb and stage IV NSCLC as the control group. Two groups of patients were followed up by telephone about their living conditions. "Survival" package of R software version 3.4.1 was used for statistical analysis. Two sets of data baseline levels were tested by chi-square test. The bias was processed by Cox regression model and the survival curve was plotted using covariate mean substitution method. The first-year survival rate of the treatment group was 70.74%, the two-year survival rate was 39.31% and the median survival time was 22.1 months. The one-year survival rate was 54.54% in the control group, the two-year survival rate was 19.49%, the median survival for 18.1 months. The long-term survival rate of the treatment group was better than that of the control group (PRadiofrequency ablation of lung cancer combined with chemotherapy can significantly improve the 2-year survival rate of patients with stage IIIb and stage IV NSCLC.

  15. Recognizing and managing a malignant hyperthermia crisis: guidelines from the European Malignant Hyperthermia Group

    DEFF Research Database (Denmark)

    Glahn, K P E; Ellis, F R; Halsall, P J

    2010-01-01

    Survival from a malignant hyperthermia (MH) crisis is highly dependent on early recognition and prompt action. MH crises are very rare and an increasing use of total i.v. anaesthesia is likely to make it even rarer, leading to the potential risk of reduced awareness of MH. In addition, dantrolene....... The guidelines consist of two textboxes: Box 1 on recognizing MH and Box 2 on the treatment of an MH crisis....

  16. A case of malignant hyperthermia captured by an anesthesia information management system.

    Science.gov (United States)

    Maile, Michael D; Patel, Rajesh A; Blum, James M; Tremper, Kevin K

    2011-04-01

    Many cases of malignant hyperthermia triggered by volatile anesthetic agents have been described. However, to our knowledge, there has not been a report describing the precise changes in physiologic data of a human suffering from this process. Here we describe a case of malignant hyperthermia in which monitoring information was frequently and accurately captured by an anesthesia information management system.

  17. Gemcitabine and S-1 Combination Chemotherapy in Patients with Advanced Biliary Tract Cancer:A Retrospective Study

    Directory of Open Access Journals (Sweden)

    Kazuhito Mita

    2010-12-01

    Full Text Available Background:The aim of this study was to investigate the efficacy and safety of gemcitabine and S-1 combination chemotherapy in patients with advanced biliary tract cancer. Patients and Methods: A retrospective study was performed on 15 consecutive patients. Gemcitabine was administered intravenously at 1,000 mg/m2 on days 8 and 15. Oral S-1 (60 mg/m2 in 2 divided doses was given daily for the first 2 weeks, followed by 1 week of rest. This 3-week course of treatment was repeated. The primary endpoint was response rate, and the secondary endpoints were overall survival, progression-free survival, and safety. Results: The overall response rate was 26.7%, and the disease control rate was 73.4%. The overall survival was 12.0 months (95% CI, 9.5–14.5 months, and the progression-free survival was 8.0 months (95% CI, 4.3–11.7 months. Adverse events of grade 3 or 4 occurred in 33.3%, and the major grade 3/4 toxicities were anemia (20.0%, leukopenia (13.3%, and anorexia (13.3%. Conclusion:Gemcitabine and S-1 combination chemotherapy is effective and safe in patients with advanced biliary tract cancer.

  18. Randomized study: small cell anaplastic lung cancer treated by combination chemotherapy and adjuvant radiotherapy

    International Nuclear Information System (INIS)

    Fox, R.M.; Woods, R.L.; Brodie, G.N.; Tattersall, M.H.N.

    1980-01-01

    Chemotherapy and primary site radiation therapy were compared to chemotherapy alone in a randomized study of 125 patients with small cell cancer of the lung. The sites of initial relapse, as well as disease free and overall survival were analyzed. Radiotherapy to the primary site reduced the rate of local relapse, but median survival was not prolonged in patients with either limited or extensive disease, when the radiation therapy-chemotherapy group was compared to the group that received chemotherapy alone

  19. Concurrent thermochemoradiotherapy for brain high-grade glioma

    Energy Technology Data Exchange (ETDEWEB)

    Ryabova, A. I., E-mail: ranigor@mail.ru; Novikov, V. A.; Startseva, Zh. A.; Bober, E. E.; Frolova, I. G. [Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation); Choinzonov, E. L. [Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation); Siberian State Medical University, Tomsk, 634050 (Russian Federation); Gribova, O. V. [Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation); National Research Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation); Baranova, A. V. [National Research Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation)

    2016-08-02

    Despite the achievements in the current strategies for treatment, the prognosis in malignant glioma patients remains unsatisfactory. Hyperthermia is currently considered to be the most effective and universal modifier of radiotherapy and chemotherapy. Preliminary treatment outcomes for 28 patients with newly diagnosed (23) and recurrent (5) high-grade gliomas were presented. All the patients received multimodality treatment including surgery, thermoche-moradiotherapy followed by 4 cycles of adjuvant chemotherapy. All the patients endured thermochemoradiotherapy well. A complication, limited skin burn (II stage), was diagnosed in two cases and treated conservatively without treatment interruption. A month after thermochemoradiotherapy the results were as follows: complete regression was achieved in 4 cases, partial regression in 4 cases, stable disease in 14 cases and disease progression in 6 cases (one of them is pseudo-progression). After completing the adjuvant chemotherapy 2 more patients demonstrated complete response and 1 patient had disease progression. Introduction of local hyperthermia in multimodal therapy of malignant glioma does not impair the combined modality treatment tolerability of patients with malignant gliomas. A small number of studied patients and short follow-up time do not allow making reliable conclusions about the impact of local hyperthermia on the treatment outcomes; however, there is a tendency towards the increase in disease-free survival in the patients with newly diagnosed malignant gliomas.

  20. Differential responses to radiation and hyperthermia of cloned cell lines derived from a single human melanoma xenograft

    International Nuclear Information System (INIS)

    Rofstad, E.K.; Brustad, T.

    1984-01-01

    One uncloned and five cloned cell lines were derived from a single human melanoma xenograft. Cells from passages 7-12 were exposed to either radiation or hyperthermia (42.5 0 C, pH = 7.4) under aerobic conditions and the colony forming ability of the cells was assayed in soft agar. The five cloned lines showed individual and characteristic responses to radiation as well as to hyperthermia. The variation in the response to radiation was mainly reflected in the size of the shoulders of the survival curves rather than in the D 0 -values. The variation in the response to hyperthermia was mainly reflected in the terminal slopes of the survival curves. The survival curve of cells from the uncloned line, both when exposed to radiation and hyperthermia, was positioned in the midst of those of the cloned lines. The response of the cloned lines to radiation did not correlate with the response to hyperthermia, indicating that tumor cell subpopulations which are resistant to radiation may respond well to hyperthermia

  1. Influence of patient mispositioning on SAR distribution and simulated temperature in regional deep hyperthermia

    Science.gov (United States)

    Aklan, Bassim; Gierse, Pia; Hartmann, Josefin; Ott, Oliver J.; Fietkau, Rainer; Bert, Christoph

    2017-06-01

    Patient positioning plays an important role in regional deep hyperthermia to obtain a successful hyperthermia treatment. In this study, the influence of possible patient mispositioning was systematically assessed on specific absorption rate (SAR) and temperature distribution. With a finite difference time domain approach, the SAR and temperature distributions were predicted for six patients at 312 positions. Patient displacements and rotations as well as the combination of both were considered inside the Sigma-Eye applicator. Position sensitivity is assessed for hyperthermia treatment planning -guided steering, which relies on model-based optimization of the SAR and temperature distribution. The evaluation of the patient mispositioning was done with and without optimization. The evaluation without optimization was made by creating a treatment plan for the patient reference position in the center of the applicator and applied for all other positions, while the evaluation with optimization was based on creating an individual plan for each position. The parameter T90 was used for the temperature evaluation, which was defined as the temperature that covers 90% of the gross tumor volume (GTV). Furthermore, the hotspot tumor quotient (HTQ) was used as a goal function to assess the quality of the SAR and temperature distribution. The T90 was shown considerably dependent on the position within the applicator. Without optimization, the T90 was clearly decreased below 40 °C by patient shifts and the combination of shifts and rotations. However, the application of optimization for each positon led to an increase of T90 in the GTV. Position inaccuracies of less than 1 cm in the X-and Y-directions and 2 cm in the Z-direction, resulted in an increase of HTQ of less than 5%, which does not significantly affect the SAR and temperature distribution. Current positioning precision is sufficient in the X (right-left)-direction, but position accuracy is required in the Y-and Z-directions.

  2. [Early detection of the cardiotoxicity induced by chemotherapy drug through two-dimensional speckle tracking echocardiography combined with high-sensitive cardiac troponin T].

    Science.gov (United States)

    Wang, W; Kang, Y; Shu, X H; Shen, X D; He, B

    2017-11-23

    Objective: To investigate the clinical value of two-dimensional speckle tracking echocardiography(2D-STE) combined with high-sensitive cardiac troponin T (hs-cTnT) in early detection of the cardiotoxicity induced by chemotherapy drug. Methods: Seventy-five non-Hodgkin's lymphoma patients who received the CHOP regimen were recruited in this study. Conventional echocardiography and 2D-STE were performed on these patients before chemotherapy, the second day after the third course of chemotherapy (during chemotherapy) and the second day after the last course of chemotherapy (after chemotherapy). The parameters included left ventricular ejection fraction (LVEF), global longitudinal strain (LS), global circumferential strain (CS) and global radial strain (RS). The serum hs-cTNT levels were tested simultaneously. Results: Three cycles of CHOP were completed in 30 patients and 6-8 cycles of CHOP were completed in 45 patients. The LVEF of 75 patients before, during and after chemotherapy was (63.8±2.6)%, (63.8±2.8)% and (64.0±3.3)%, respectively, without significant difference ( P =0.91). However, the LS of 75 patients before, during and after chemotherapy was (-18.5±1.7)%, (-16.5±1.9)% and (-16.0±1.6)%, respectively. The CS was (-20.9±2.9)%, (-19.3±3.5)% and (-19.2±3.2)%, respectively. The RS was (39.2±6.4)%, (35.3±5.2)% and (35.0±6.2)%, respectively. The hs-cTnT was (0.001 0±0.002 0)ng/ml, (0.006 3±0.008 9)ng/ml and (0.007 3±0.003 8)ng/ml, respectively. The LS, CS and RS were significantly decreased while hs-cTnT was significantly increased during chemotherapy when compared to those before chemotherapy (all of P chemotherapy were marginally different from those during chemotherapy (all of P >0.05). Moreover, T(LS-SD), T(CS-SD) and T(RS-SD) showed no significant difference before, during and after chemotherapy (all of P >0.05). The reduction of LS was positively associated with the enhancement of hs-cTnT after chemotherapy ( r =0.60, P effectively and

  3. Gelatine-assisted synthesis of magnetite nanoparticles for magnetic hyperthermia

    Energy Technology Data Exchange (ETDEWEB)

    Alves, André F.; Mendo, Sofia G. [Universidade de Lisboa, Centro de Química e Bioquímica, Faculdade de Ciências (Portugal); Ferreira, Liliana P. [Universidade de Lisboa, Biosystems and Integrative Sciences Institute, Faculdade de Ciências (Portugal); Mendonça, Maria Helena [Universidade de Lisboa, Centro de Química e Bioquímica, Faculdade de Ciências (Portugal); Ferreira, Paula [University of Aveiro, Department of Materials and Ceramic Engineering, CICECO - Aveiro Institute of Materials (Portugal); Godinho, Margarida; Cruz, Maria Margarida [Universidade de Lisboa, Biosystems and Integrative Sciences Institute, Faculdade de Ciências (Portugal); Carvalho, Maria Deus, E-mail: mdcarvalho@ciencias.ulisboa.pt [Universidade de Lisboa, Centro de Química e Bioquímica, Faculdade de Ciências (Portugal)

    2016-01-15

    Magnetite nanoparticles were synthesized by the co-precipitation method exploring the use of gelatine and agar as additives. For comparison, magnetite nanoparticles were also prepared by standard co-precipitation, by co-precipitation with the addition of a surfactant (sodium dodecyl sulphate) and by the thermal decomposition method. The structure and morphology of the synthesized nanoparticles were investigated by powder X-ray diffraction and transmission electron microscopy. Their magnetic properties were studied by SQUID magnetometry and {sup 57}Fe Mössbauer spectroscopy. The nanoparticles potential for applications in magnetic hyperthermia was evaluated through heating efficiency under alternating magnetic field. The results show that all synthesis methods produce Fe{sub 3−x}O{sub 4} nanoparticles with similar sizes. The nanoparticles synthesized in the gelatine medium display the narrowest particle size distribution, the lowest oxidation degree, one of the highest saturation magnetization values and the best hyperthermia efficiency, proving that this gelatine-assisted synthesis is an efficient, environmental friendly, and low-cost method to produce magnetite nanoparticles. Graphical Abstract: A new gelatine-assisted method is an efficient and low-cost way to synthesize magnetite nanoparticles with enhanced magnetic hyperthermia.

  4. Neoadjuvant chemotherapy in locally advanced nasopharyngeal carcinoma: Defining high-risk patients who may benefit before concurrent chemotherapy combined with intensity-modulated radiotherapy.

    Science.gov (United States)

    Du, Xiao-Jing; Tang, Ling-Long; Chen, Lei; Mao, Yan-Ping; Guo, Rui; Liu, Xu; Sun, Ying; Zeng, Mu-Sheng; Kang, Tie-Bang; Shao, Jian-Yong; Lin, Ai-Hua; Ma, Jun

    2015-11-13

    The purpose of this study was to create a prognostic model for distant metastasis in patients with locally advanced NPC who accept concurrent chemotherapy combined with intensity-modulated radiotherapy (CCRT) to identify high-risk patients who may benefit from neoadjuvant chemotherapy (NACT). A total of 881 patients with newly-diagnosed, non-disseminated, biopsy-proven locoregionally advanced NPC were retrospectively reviewed; 411 (46.7%) accepted CCRT and 470 (53.3%) accepted NACT followed by CCRT. Multivariate analysis demonstrated N2-3 disease, plasma Epstein-Barr virus (EBV) DNA > 4000 copies/mL, serum albumin ≤ 46 g/L and platelet count >300 k/cc were independent prognostic factors for distant metastasis in the CCRT group. Using these four factors, a prognostic model was developed, as follows: 1) low-risk group: 0-1 risk factors; and 2) high-risk group: 2-4 risk factors. In the high-risk group, patients who accepted NACT + CCRT had significantly higher distant metastasis-free survival and progression-free survival rates than the CCRT group (P = 0.001; P = 0.011). This simple prognostic model for distant metastasis in locoregionally advanced NPC may facilitate with the selection of high-risk patients who may benefit from NACT prior to CCRT.

  5. Combined photothermal-chemotherapy of breast cancer by near infrared light responsive hyaluronic acid-decorated nanostructured lipid carriers

    Science.gov (United States)

    Zheng, Shaohui; Du Nguyen, Van; Song, Seung Yoon; Han, Jiwon; Park, Jong-Oh

    2017-10-01

    In this study, a novel type of hyaluronic acid (HA)-decorated nanostructured lipid carrier (NLC) was prepared and investigated as a light-triggered drug release and combined photothermal-chemotherapy for cancer treatment. Polyhedral gold nanoparticles (Au NPs) with an average size of 10 nm were synthesized and co-encapsulated with doxorubicin (DOX) in the matrix of NLCs with a high drug loading efficiency (above 80%). HA decoration was achieved by the electrostatic interaction between HA and CTAB on the NLC surface. A remarkable temperature increase was observed by exposing the Au NP-loaded NLCs to an NIR laser, which heated the samples sufficiently (above 40 °C) to kill tumor cells. The entrapped DOX exhibited a sustained, stepwise NIR laser-triggered drug release pattern. The biocompatibility of the NLCs was investigated by MTT assay and the cell viability was maintained above 85%, even at high concentrations. The intracellular uptake of free DOX and entrapped DOX, observed by confocal microscopy, revealed two distinct uptake mechanisms, i.e. passive diffusion and endocytosis, respectively. In particular, internalization of the HA-Au-DOX-NLCs was more extensively enhanced than the Au-DOX-NLCs, which was attributed to HA-CD44 receptor-mediated endocytosis. Meanwhile, the internalized NLCs successfully escaped from the lysosomes, increasing the intracellular DOX. The HA-Au-DOX-NLCs IC50 value decreased from 2.3 to 0.6 μg ml-1 with NIR irradiation at 72 h, indicating the excellent synergistic antitumor effect of photothermal-chemotherapy. The photothermal ablation was further confirmed by a live/dead cell staining assay. Thus, a combined photothermal-chemotherapy approach has been proposed as a promising strategy for cancer treatment.

  6. Efficacy of S-1 plus nedaplatin compared to standard second-line chemotherapy in EGFR-negative lung adenocarcinoma after failure of first-line chemotherapy.

    Science.gov (United States)

    Tang, Yu; Wang, Wei; Teng, Xiu-Zhi; Shi, Lin

    2014-09-01

    For patients with advanced non-small cell lung adenocarcinoma that fail to respond to first-line chemotherapy and that do not involve epidermal growth factor receptor (EGFR) mutations, previous empirical analysis showed that a single second-line chemotherapy agent may be inadequate for the control of further tumor development. This study examines the combination of S-1 drugs and nedaplatin that has no cross-resistance to first-line treatments; 179 cases of IIIb-IV stage non-small-cell lung adenocarcinoma that failed to respond to first-line chemotherapy were included, and these subjects did not have mutated EGFRs. In the present study, S-1 plus nedaplatin chemotherapy was better than standard second-line chemotherapy options in the treatment of advanced lung adenocarcinoma that did not involve EGFR mutations and that failed to respond to first-line chemotherapy. Additionally, the combination of S-1 and nedaplatin seemed to be well tolerated, making this chemotherapy technique a potentially strong candidate for the treatment of advanced non-small-cell lung adenocarcinoma.

  7. Safety and feasibility of fasting in combination with platinum-based chemotherapy.

    Science.gov (United States)

    Dorff, Tanya B; Groshen, Susan; Garcia, Agustin; Shah, Manali; Tsao-Wei, Denice; Pham, Huyen; Cheng, Chia-Wei; Brandhorst, Sebastian; Cohen, Pinchas; Wei, Min; Longo, Valter; Quinn, David I

    2016-06-10

    Short-term starvation prior to chemotherapy administration protects mice against toxicity. We undertook dose-escalation of fasting prior to platinum-based chemotherapy to determine safety and feasibility in cancer patients. 3 cohorts fasted before chemotherapy for 24, 48 and 72 h (divided as 48 pre-chemo and 24 post-chemo) and recorded all calories consumed. Feasibility was defined as ≥ 3/6 subjects in each cohort consuming ≤ 200 kcal per 24 h during the fast period without excess toxicity. Oxidative stress was evaluated in leukocytes using the COMET assay. Insulin, glucose, ketones, insulin-like growth factor-1 (IGF-1) and IGF binding proteins (IGFBPs) were measured as biomarkers of the fasting state. The median age of our 20 subjects was 61, and 85 % were women. Feasibility criteria were met. Fasting-related toxicities were limited to ≤ grade 2, most commonly fatigue, headache, and dizziness. The COMET assay indicated reduced DNA damage in leukocytes from subjects who fasted for ≥48 h (p = 0.08). There was a non-significant trend toward less grade 3 or 4 neutropenia in the 48 and 72 h cohorts compared to 24 h cohort (p = 0.17). IGF-1 levels decreased by 30, 33 and 8 % in the 24, 48 and 72 h fasting cohorts respectively after the first fasting period. Fasting for 72 h around chemotherapy administration is safe and feasible for cancer patients. Biomarkers such as IGF-1 may facilitate assessment of differences in chemotherapy toxicity in subgroups achieving the physiologic fasting state. An onging randomized trial is studying the effect of 72 h of fasting. NCT00936364 , registered propectively on July 9, 2009.

  8. Safety and feasibility of fasting in combination with platinum-based chemotherapy

    International Nuclear Information System (INIS)

    Dorff, Tanya B.; Groshen, Susan; Garcia, Agustin; Shah, Manali; Tsao-Wei, Denice; Pham, Huyen; Cheng, Chia-Wei; Brandhorst, Sebastian; Cohen, Pinchas; Wei, Min; Longo, Valter; Quinn, David I.

    2016-01-01

    Short-term starvation prior to chemotherapy administration protects mice against toxicity. We undertook dose-escalation of fasting prior to platinum-based chemotherapy to determine safety and feasibility in cancer patients. 3 cohorts fasted before chemotherapy for 24, 48 and 72 h (divided as 48 pre-chemo and 24 post-chemo) and recorded all calories consumed. Feasibility was defined as ≥ 3/6 subjects in each cohort consuming ≤ 200 kcal per 24 h during the fast period without excess toxicity. Oxidative stress was evaluated in leukocytes using the COMET assay. Insulin, glucose, ketones, insulin-like growth factor-1 (IGF-1) and IGF binding proteins (IGFBPs) were measured as biomarkers of the fasting state. The median age of our 20 subjects was 61, and 85 % were women. Feasibility criteria were met. Fasting-related toxicities were limited to ≤ grade 2, most commonly fatigue, headache, and dizziness. The COMET assay indicated reduced DNA damage in leukocytes from subjects who fasted for ≥48 h (p = 0.08). There was a non-significant trend toward less grade 3 or 4 neutropenia in the 48 and 72 h cohorts compared to 24 h cohort (p = 0.17). IGF-1 levels decreased by 30, 33 and 8 % in the 24, 48 and 72 h fasting cohorts respectively after the first fasting period. Fasting for 72 h around chemotherapy administration is safe and feasible for cancer patients. Biomarkers such as IGF-1 may facilitate assessment of differences in chemotherapy toxicity in subgroups achieving the physiologic fasting state. An onging randomized trial is studying the effect of 72 h of fasting. Clinicaltrials.gov: NCT00936364, registered propectively on July 9, 2009. The online version of this article (doi:10.1186/s12885-016-2370-6) contains supplementary material, which is available to authorized users

  9. Doxorubicin Loaded Chitosan-W18 O49 Hybrid Nanoparticles for Combined Photothermal-Chemotherapy.

    Science.gov (United States)

    Yuan, Shanmei; Hua, Jisong; Zhou, Yinyin; Ding, Yin; Hu, Yong

    2017-08-01

    Combined treatment is more effective than single treatment against most forms of cancer. In this work, doxorubicin loaded chitosan-W 18 O 49 nanoparticles combined with the photothermal therapy and chemotherapy are fabricated through the electrostatic interaction between positively charged chitosan and negatively charged W 18 O 49 nanoparticles. The in vitro and in vivo behaviors of these nanoparticles are examined by dynamic light scattering, transmission electron microscopy, cytotoxicity, near-infrared fluorescence imaging, and tumor growth inhibition experiment. These nanoparticles have a mean size around 110 nm and show a pH sensitive drug release behavior. After irradiation by the 980 nm laser, these nanoparticles show more pronounced cytotoxicity against HeLa cells than that of free doxorubicin or photothermal therapy alone. The in vivo experiments confirm that their antitumor ability is significantly improved, resulting in superior efficiency in impeding tumor growth and extension of the lifetime of mice. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Radical resection for low rectal carcinoma combined with infusion pump chemotherapy via internal iliac artery

    Directory of Open Access Journals (Sweden)

    Bo YANG

    2011-10-01

    Full Text Available Objective To evaluate the effects and practicability of radical resection for low rectal carcinoma with infusion pump chemotherapy via internal iliac artery,and explore the correlation factors influencing the therapeutic effects.Methods Data of 316 patients with low rectal carcinoma,admitted from Oct.1997 to Mar.2008,were retrospectively analyzed and assigned into 2 groups according to the treatment: Patients received infusion pump chemotherapy via internal iliac artery to target area combined with intravenous systemic chemotherapy were assigned into group A(n=249,and those receiving systemic chemotherapy alone following radical resection were assigned to group B(n=67.The timing of pump chemotherapy to target area in group A was set at day 12 after recovery of digestive function,with regimen of 5-FU at 0.5g per dose plus hydroxycamptothecin at 10-15mg per dose,twice a week,four times as a treatment course for a total of 6 courses,and it was followed by intravenously systemic chemotherapy with a regimen of FOLFIRI or FOLFOX.In group B,at day 12 right after recovery of digestive function,the intravenous sytemic chemotherapy was started with the same regimen as in group A.The local recurrence rate,metastasis rate and survival rate after 1,3 and 5 years in the two groups were respectively observed and compared,and the correlation between the clinicopathological features and the 5 year local recurrence rates and survival rates was analyzed in patients of group A.Results In group A,the local recurrence rate at year 1,3 and 5 was 0,1.68%(4/238 and 3.79%(8/211,respectively,the metastasis rate was 0.80%(2/249,4.62%(11/238 and 10.90%(23/211,respectively,and the survival rate was 100%,77.73%(185/238 and 72.04%(152/211,respectively.In group B,the local recurrence rate at year 1,3 and 5 was 0,9.52%(6/63 and 16.36%(9/55,respectively,the metastasis rate was 1.49%(1/67,15.87%(10/63 and 27.27%(15/55,respectively,and the survival rate was 100

  11. Efficacy of intensity-modulated radiotherapy combined with chemotherapy or surgery in locally advanced squamous cell carcinoma of the head-and-neck

    Directory of Open Access Journals (Sweden)

    Yang H

    2013-10-01

    Full Text Available Hua Yang,* Li-Qiong Diao,* Mei Shi, Rui Ma, Jian-Hua Wang, Jian-Ping Li, Feng Xiao, Ying Xue, Man Xu, Bin ZhouDepartment of Radiotherapy Oncology, Xijing Hospital, Fourth Military Medical University, Xi'an, People's Republic of China*These authors contributed equally to this workObjectives: Long-term locoregional control following intensity-modulated radiotherapy (IMRT for locally advanced squamous cell carcinoma of the head-and-neck (SCCHN remains challenging. This study aimed to assess the efficacy and toxicity of IMRT with and without chemotherapy or surgery in locally advanced SCCHN.Materials and methods: Between January 2007 and January 2011, 61 patients with locally advanced SCCHN were treated with curative IMRT in the Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University; 28% underwent definitive IMRT and 72% postoperative IMRT, combined with simultaneous cisplatin-based chemotherapy in 58%. The mean doses of definitive and postoperative IMRT were 70.8 Gy (range, 66–74 Gy. Outcomes were analyzed using Kaplan–Meier curves. Acute and late toxicities were graded according to Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer radiation morbidity scoring criteria.Results: At a median follow-up of 35 months, 3-year local recurrence-free survival (LRFS, regional recurrence-free survival (RRFS, distant metastasis-free survival (DMFS, disease-free survival (DFS, and overall survival (OS were 83.8%, 86.1%, 82.4%, 53.2%, and 62%, respectively. Postoperative IMRT (n = 44, 72% had significantly higher LRFS/OS/DMFS than definitive IMRT (n = 17, 28%; P < 0.05. IMRT combined with chemotherapy (n = 35, 58% had significantly higher LRFS/OS/DMFS than IMRT alone (n = 26, 42%; P < 0.05. One year after radiotherapy, the incidence of xerostomia of grade 1, 2, or 3 was 13.1%, 19.7%, and 1.6%, respectively. No grade 4 acute or late toxicity was observed.Conclusion: IMRT combined with

  12. Utilization of special computerized tomography and nuclear medicine techniques for quality control and for the optimization of combined precision chemotherapy and precision radiation therapy

    International Nuclear Information System (INIS)

    Wiley, A.L. Jr.; Wirtanen, G.W.; Chien, I.-C.

    1984-01-01

    A combination of precision (selective, intra-arterial) chemotherapy and precision radiotherapy can be used for advanced pancreatic, biliary tract, and sarcomatous malignancies. There were some remarkable responses, but also a few poor responses and even some morbidity. Accordingly, methods are developed of pre-selecting those patients whose tumors are likely to respond to such therapy, as well as methods for improving the therapeutic ratio by the rational optimization of combined therapy. Specifically, clinical tumor blood flow characteristics (monitored with nuclear medicine techniques) may provide useful criteria for such selection. The authors also evaluate qualitatively the drug distribution or exposure space with specialized color-coded computerized tomography images, which demonstrate spatially dependent enhancement of intra-arterial contrast in tumor and in adjacent normal tissues. Such clinical data can improve the quality control aspects of intra-arterial chemotherapy administration, as well as the possibility of achievement of a significant therapeutic ratio by the integration of precision chemotherapy and precision radiation therapy. (Auth.)

  13. [A case report-advanced pancreas cancer with liver and lung metastases well controlled over one year by combination therapy with systemic chemotherapy, radiation and hepatic arterial infusion in an outpatient setting].

    Science.gov (United States)

    Hasuike, Yasunori; Tanigawa, Takahiko; Yamada, Masaharu; Minami, Yukiko; Ezumi, Koji; Kashiwazaki, Masaki; Fujimoto, Takayoshi

    2008-11-01

    We report a case of advanced pancreatic cancer with liver and lung metastases that was well controlled over one year by combination therapy with systemic chemotherapy, radiation and hepatic arterial infusion in an outpatient setting. The patient was a 74-year-old woman. Chief complaints were back pain and anorexia. She was diagnosed with pancreas cancer with liver and lung metastases at the time of first visit. We started systemic chemotherapy with gemcitabine 1 g/body and 5-FU 1 g/body alternately every other week on an outpatient basis. At 1.5 months (M) after initiation of chemotherapy, we started radiation therapy to the main tumor at a total dose of 40 Gy. After radiation, chemotherapy was resumed. As a result, the size of the main tumor decreased but metastatic liver tumors got larger. Then we changed to combination therapy with systemic chemotherapy (gemcitabine and 5-FU) and hepatic arterial infusion (5-FU weekly). Liver metastases almost disappeared after 7.5 M. Despite all these treatments, however, the number of metastatic lung tumors increased. The patient was hospitalized for 15 M and died after 17 M. We focused on and succeeded in the prolongation of lifetime and maintenance of QOL by combination therapy with systemic chemotherapy, radiation and hepatic arterial infusion therapy.

  14. The effects of hyperthermia on the immunomodulatory properties of human umbilical cord vein mesenchymal stem cells (MSCs).

    Science.gov (United States)

    Hesami, Shilan; Mohammadi, Mehdi; Rezaee, Mohamad Ali; Jalili, Ali; Rahmani, Mohammad Reza

    2017-11-01

    Hyperthermia can modulate inflammation and the immune response. Based on the recruitment of mesenchymal stem cells (MSCs) to inflamed tissues and the immunomodulatory properties of these cells, the aim of this study was to examine the effects of hyperthermia on the immunomodulatory properties of MSCs in a mixed lymphocyte reaction (MLR). Passages 4-6 of human umbilical cord vein mesenchymal stem cells were co-cultured in a two-way MLR. Cells in the hyperthermia groups were incubated at 41 °C for 45 min. A colorimetric assay was employed to examine the effects of MSCs on cell proliferation. The levels of IL-4 and TNF-α proteins in the cell culture supernatant were measured, and non-adherent cells were used for RNA extraction, which was then used for cDNA synthesis. RT-PCR was utilised to assess levels of IL-10, IL-17A, IL-4, TNF-α, TGF-β1, FOX P 3 , IFN-γ, CXCL12 and β-actin mRNA expression. UCV-MSCs co-cultured in an MLR reduced lymphocyte proliferation at 37 °C, whereas hyperthermia attenuated this effect. Hyperthermia increased expression of IL-10, TGF-β1 and FOXP3 mRNAs in co-culture; however, no effects on IL-17A and IFN-γ were observed, and it reduced CXCL12 expression. In co-culture, IL-4 mRNA and protein increased at 37 °C, an effect that was reduced by hyperthermia. No considerable change in TNF-α mRNA expression was found in hyperthermia-treated cells. Hyperthermia increases cell proliferation of the peripheral blood mononuclear cells and modifies the cytokine profile in the presence of UCV-MSCs.

  15. Immunohistochemical study on the fetal rat pituitary in hyperthermia-induced exencephaly

    OpenAIRE

    Watanabe, Yuichi G.; 渡辺, 勇一

    2002-01-01

    Hyperthermia of fetal rats is known to cause malformations of various organs including brain. The present study was carried out to investigate the effect of the hyperthermia-induced brain damages on the development of the adenohypophysis. Mother rats of Day 9.5 of pregnancy were anesthetized and immersed in hot water (43℃) for 15 min. At Day 21.5 of gestation, fetuses were removed by caesarian section and examined for exencephaly. Hyperthermal stress induced varying degrees of exencephaly in ...

  16. Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis.

    Science.gov (United States)

    Schuchmann, Sebastian; Schmitz, Dietmar; Rivera, Claudio; Vanhatalo, Sampsa; Salmen, Benedikt; Mackie, Ken; Sipilä, Sampsa T; Voipio, Juha; Kaila, Kai

    2006-07-01

    Febrile seizures are frequent during early childhood, and prolonged (complex) febrile seizures are associated with an increased susceptibility to temporal lobe epilepsy. The pathophysiological consequences of febrile seizures have been extensively studied in rat pups exposed to hyperthermia. The mechanisms that trigger these seizures are unknown, however. A rise in brain pH is known to enhance neuronal excitability. Here we show that hyperthermia causes respiratory alkalosis in the immature brain, with a threshold of 0.2-0.3 pH units for seizure induction. Suppressing alkalosis with 5% ambient CO2 abolished seizures within 20 s. CO2 also prevented two long-term effects of hyperthermic seizures in the hippocampus: the upregulation of the I(h) current and the upregulation of CB1 receptor expression. The effects of hyperthermia were closely mimicked by intraperitoneal injection of bicarbonate. Our work indicates a mechanism for triggering hyperthermic seizures and suggests new strategies in the research and therapy of fever-related epileptic syndromes.

  17. Dose concept of oncological hyperthermia: Heat-equation considering the cell destruction

    Directory of Open Access Journals (Sweden)

    Szasz A

    2006-01-01

    Full Text Available We shall assume, of course, that the objective of hyperthermia is to destroy the malignant cells. Destruction definitely needs energy. Description and quality assurance of hyperthermia use the Pennes heat equation to describe the processes. However the energy balance of the Pennes-equation does not contain the hyperthermic cell-destruction energy, which is a mandatory factor of the process. We propose a generalization of the Pennes-equation, inducing the entire energy balance. The new paradigm could be a theoretical basis of the till now empirical dose-construction for oncological hyperthermia. The cell destruction is a non-equilibrium thermodynamical process, described by the equations of chemical reactions. The dynamic behavior (time dependence has to be considered in this approach. We are going to define also a dose concept that can be objectively compared with other oncological methods. We show how such empirical dose as CEM43oC could be based theoretically as well.

  18. Interaction of hyperthermia and photoradiation therapy

    International Nuclear Information System (INIS)

    Waldow, S.M.; Dougherty, T.J.

    1984-01-01

    Local microwave hyperthermia (2450 MHz) was applied to auxillary implants of the SMT-F mammary carcinoma in mice in combination with photoradiation therapy (PRT) in an attempt to determine if the two modalities interact. When 40.5 0 C was applied for 30 min immediately prior to or immediately following PRT enhancement of tumor response over that of PRT alone was seen as judged by lack of tumor regrowth (35 days or longer after treatment). A temperature of 41.5 0 C applied for 30 min immediately following the 30-min PRT treatment produced a result slightly greater than that seen at 40.5 0 C. When a temperature of 44.5 0 C for 30 min was applied immediately following PRT, a substantial enhancement of tumor control at 35 days post-treatment was found. These results suggest that tumor response to PRT is enhanced by both a sublethal hyperthermic treatment (40.5 0 C, 41.5 0 C) and a moderately lethal heat treatment (44.5 0 C) given for a short duration, when applied immediately before or after photoradiation

  19. Hypoxic cell radiosensitization by moderate hyperthermia and glucose deprivation

    International Nuclear Information System (INIS)

    Kim, J.H.; Kim, S.H.; Hahn, E.W.

    1983-01-01

    Cell culture studies were carried out to determine whether moderate hyperthermia reduces the oxygen enhancement ratio of cells under well-defined cultural conditions. Using asynchronously growing HeLa cells, the OER of cells with and without glucose was determined following exposure of cells to moderate hyperthermia, 40.5omicronC for 1 hr, immediately after X irradiation. The OER of cells with 5 mM glucose was 3.2, whereas the OER of glucose-deprived cells was reduced to 2.0. The pH of the cell culture medium was kept at 7.4 throughtout the experiments. The present finding may provide a clue toward further enhancing the radiosensitization of hypoxic cells by heat

  20. Hypoxic cell radiosensitization by moderate hyperthermia and glucose deprivation

    International Nuclear Information System (INIS)

    Kim, J.H.; Kim, S.H.; Hahn, E.W.

    1983-01-01

    Cell culture studies were carried out to determine whether moderate hyperthermia reduces the oxygen enhancement ratio of cells under well-defined cultural conditions. Using asynchronously growing HeLa cells, the OER of cells with and without glucose was determined following exposure of cells to moderate hyperthermia, 40.5 degrees C for 1 hr, immediately after X irradiation. The OER of cells with 5 mM glucose was 3.2, whereas the OER of glucose-deprived cells was reduced to 2.0. The pH of the cell culture medium was kept at 7.4 throughout the experiments. The present finding may provide a clue toward further enhancing the radiosensitization of hypoxic cells by heat

  1. Effects of γ radiation and hyperthermia on DNA repair synthesis and the level of NAD+ in cultured human mononuclear leukocytes

    International Nuclear Information System (INIS)

    Jonsson, G.G.; Eriksson, G.; Pero, R.W.

    1984-01-01

    DNA repair has been investigated, estimated by unscheduled DNA synthesis (UDS) and the cellular NAD + pool, after exposing human mononuclear leukocytes to hyperthermia and γ radiation separately and in combination. It was found that γ radiation induced a decline in UDS with increasing temperature through the temperature region studied (37-45 0 C). At 42.5 0 C the γ-ray-induced UDS was reduced to about 70% of that at 37 0 C. Following γ-ray damage the NAD + pool dropped to about 20% of control values. Without hyperthermic treatment the cells completely recovered to the original level within 5 hr. Moderate hyperthermia (42.5 0 C for 45 min) followed by γ-ray damage altered the kinetics so that even after 8 hr the NAD + pool had recovered to only 70% of the original level. After heat treatment at 44 0 C for 45 min prior to γ radiation the cells did not recover at all, presumably because of the cytotoxic effects from the combined treatment

  2. Radiosensitization of tumors and normal tissues by combined treatment with misonidazole and heat

    International Nuclear Information System (INIS)

    Hofer, K.G.; MacKinnon, A.R.; Schubert, A.L.; Lehr, J.E.; Grimmett, E.V.

    1981-01-01

    Combination treatment of mice with misonidazole (0.5 mg/g body wt.) and hyperthermia (41.5/sup o/C for 45 mins.) produced dramatic radiosensitization in hypoxic BP-8 murine sarcoma cells. The dose modifying factor (DMF: 4.3) was such that hypoxic BP-8 cells subjected to combination therapy became more radiosensitive than untreated, fully oxygenated cell populations. In contrast, radiosensitization by combination treatment was comparatively minor or completely absent in normal body tissues such as skin (DMF: 1.57), intestine (DMF: 1.0), and bone marrow (DMF: 1.0). These results suggest that simultaneous administration of misonidazole and hyperthermia may prove an effective adjuvant to conventional clinical radiation therapy

  3. A thermocouple thermometry system for ultrasound hyperthermia

    International Nuclear Information System (INIS)

    Ozarka, M.; Gharakhani, A.; Magin, R.; Cain, C.

    1984-01-01

    A thermometry system designed to be used in the treatment of cancer by ultrasound hyperthermia is described. The system monitors tumor temperatures using 16 type T (copper-constantan) thermocouples and is controlled by a 12 MHz Intel 8031 microcomputer. An analog circuit board contains the thermocouple amplifiers, an analog multiplexer, scaling circuitry, and an analog to digital converter. A digital board contains the Intel 8031, program memory, data memory, as well as circuitry for control and data communications. Communication with the hyperthermia system control computer is serially by RS-232 with selectable baud rate. Since the thermocouple amplifiers may have slight differences in gain and offset, a calibrated offset is added to a lookup table value to obtain the proper display temperature to within +- 0.1 0 C. The calibration routine, implemented in software, loads a nonvolatile random access memory chip with the proper offset values based on the outputs of each thermocouple channel at known temperatures which bracket a range of interest

  4. Circulation of progenitor cells after intensive chemotherapy followed by combination G-CSF and EPO in breast carcinoma

    International Nuclear Information System (INIS)

    Filip, S.; Vanasek, J.; Blaha, M.; Vavrova, J.

    1997-01-01

    Hematologic effects of granulocyte colony-stimulating factor (G-CSF) and erythropoietic (EPO) combination after priming intensive chemotherapy in the treatment of female breast carcinoma are presented. In a previous group treated with G-CSF alone, 36% of patients became anemic and to be transfused for correction of their anemia. To the present study consecutive patients with different stages of breast carcinoma were admitted. All were given priming intensive chemotherapy (epirubicin 150 m/m 2 and cyclophosphamide 1300 mg/m 2 ) followed by subcutaneous application of G-CSF at a dose of 5 μg/kg/day and EPO 250 IU/kg/day. In cases where leucocyte counts dropped below 1 x 10 9 /dm 3 and hemoglobin level fell to 85 g/dm 3 administration of growth factors was started. The therapy was stopped when normal leukocyte count reached 4 x 10 9 /dm 3 for G-CSF and hemoglobin level rose to 115 g/dm 3 for EPO. Our results show significant difference between MNC/Tl (min.), CD34 + cells/μl (min.), CFU-GM/ml (min.), BFU-E/ml (min) and MNC/μl (max.), CD34 + cells/μl (max.), CFU-GM/ml (max.), BFU-E/ml (ml) p + cells/μl, 23.4-fold for CFU-GM/ml and 28.7-fold increase for BFU-E/ml. Side effects were minimal, no infectious complications occurred, body temperature did not rise over 3 grad C and no corrections of anemia were needed. It is concluded that the administration of G-CSF plus EPO combination following intensive chemotherapy reduces hematologic toxicity and induces large amount of hemopoietic progenitors suitable for autologous transplantation in women with breast carcinoma. (author)

  5. Therapeutic effects of microbubble added to combined high-intensity focused ultrasound and chemotherapy in a pancreatic cancer xenograft model

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Mi Hye [Dept. of Radiology, Konkuk University Medical Center, Seoul (Korea, Republic of); Lee, Jae Young; Kim, Bo Ram; Park, Eun Joo; Kim, Hoe Suk; Han, Joon Koo [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of); Kim, Hae Ri [Dept. of Pre-Dentistry, Gangneung-Wonju National University College of Dentistry, Gangneung (Korea, Republic of); Choi, Byung Ihn [Dept. of Radiology, Chung-Ang University Hospital, Seoul (Korea, Republic of)

    2016-09-15

    To investigate whether high-intensity focused ultrasound (HIFU) combined with microbubbles enhances the therapeutic effects of chemotherapy. A pancreatic cancer xenograft model was established using BALB/c nude mice and luciferase-expressing human pancreatic cancer cells. Mice were randomly assigned to five groups according to treatment: control (n = 10), gemcitabine alone (GEM; n = 12), HIFU with microbubbles (HIFU + MB, n = 11), combined HIFU and gemcitabine (HIGEM; n = 12), and HIGEM + MB (n = 13). After three weekly treatments, apoptosis rates were evaluated using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay in two mice per group. Tumor volume and bioluminescence were monitored using high-resolution 3D ultrasound imaging and in vivo bioluminescence imaging for eight weeks in the remaining mice. The HIGEM + MB group showed significantly higher apoptosis rates than the other groups (p < 0.05) and exhibited the slowest tumor growth. From week 5, the tumor-volume-ratio relative to the baseline tumor volume was significantly lower in the HIGEM + MB group than in the control, GEM, and HIFU + MB groups (p < 0.05). Despite visible distinction, the HIGEM and HIGEM + MB groups showed no significant differences. High-intensity focused ultrasound combined with microbubbles enhances the therapeutic effects of gemcitabine chemotherapy in a pancreatic cancer xenograft model.

  6. Therapeutic Effects of Microbubbles Added to Combined High-Intensity Focused Ultrasound and Chemotherapy in a Pancreatic Cancer Xenograft Model

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Mi Hye [Department of Radiology, Konkuk University Medical Center, Seoul 05030 (Korea, Republic of); Lee, Jae Young [Department of Radiology, Seoul National University Hospital, Seoul 03080 (Korea, Republic of); Kim, Hae Ri [Department of Pre-Dentistry, Gangneung-Wonju National University College of Dentistry, Gangneung 25457 (Korea, Republic of); Kim, Bo Ram; Park, Eun-Joo; Kim, Hoe Suk; Han, Joon Koo [Department of Radiology, Seoul National University Hospital, Seoul 03080 (Korea, Republic of); Choi, Byung Ihn [Department of Radiology, Chung-Ang University Hospital, Seoul 06973 (Korea, Republic of)

    2016-11-01

    To investigate whether high-intensity focused ultrasound (HIFU) combined with microbubbles enhances the therapeutic effects of chemotherapy. A pancreatic cancer xenograft model was established using BALB/c nude mice and luciferase-expressing human pancreatic cancer cells. Mice were randomly assigned to five groups according to treatment: control (n = 10), gemcitabine alone (GEM; n = 12), HIFU with microbubbles (HIFU + MB, n = 11), combined HIFU and gemcitabine (HIGEM; n = 12), and HIGEM + MB (n = 13). After three weekly treatments, apoptosis rates were evaluated using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay in two mice per group. Tumor volume and bioluminescence were monitored using high-resolution 3D ultrasound imaging and in vivo bioluminescence imaging for eight weeks in the remaining mice. The HIGEM + MB group showed significantly higher apoptosis rates than the other groups (p < 0.05) and exhibited the slowest tumor growth. From week 5, the tumor-volume-ratio relative to the baseline tumor volume was significantly lower in the HIGEM + MB group than in the control, GEM, and HIFU + MB groups (p < 0.05). Despite visible distinction, the HIGEM and HIGEM + MB groups showed no significant differences. High-intensity focused ultrasound combined with microbubbles enhances the therapeutic effects of gemcitabine chemotherapy in a pancreatic cancer xenograft model.

  7. Pregnancies and menstrual function before and after combined radiation (RT) and chemotherapy (TVPP) for Hodgkin's disease

    Energy Technology Data Exchange (ETDEWEB)

    Lacher, M.J.; Toner, K.

    1986-01-01

    The menstrual cycle, pregnancies, and offspring were evaluated before and after initial combined radiation (RT) and chemotherapy with thiotepa, vinblastine, vincristine, procarbazine, and prednisone (TVPP), in 34 women between the ages of 18 and 44 (median 26.5 years) treated for Stage II and Stage III Hodgkin's disease. The median range of follow-up is 83.1 months (range 40.5-140). After therapy 94.1% (32/34) continued to menstruate. Two of the four patients over the age of 35 ceased to menstruate. All patients under the age of 35 continued to menstruate (30/30). Age at the time of diagnosis was the only factor affecting change in menses with a significant probability (p = .001) that women greater than 30 years of age will experience some change in menstrual pattern. Seventeen pregnancies occurred in 12 women after therapy; 2 had 4 elective abortions; 10 delivered 12 children with normal physical development; 1 will deliver six months from now. Twelve of thirteen patients who wanted to become pregnant have conceived. The ability to become pregnant and deliver normal children after intensive treatment with combined radiation and chemotherapy (RT/TVPP) was comparable to the patients' pretreatment record.

  8. A numerical study on dual-phase-lag model of bio-heat transfer during hyperthermia treatment.

    Science.gov (United States)

    Kumar, P; Kumar, Dinesh; Rai, K N

    2015-01-01

    The success of hyperthermia in the treatment of cancer depends on the precise prediction and control of temperature. It was absolutely a necessity for hyperthermia treatment planning to understand the temperature distribution within living biological tissues. In this paper, dual-phase-lag model of bio-heat transfer has been studied using Gaussian distribution source term under most generalized boundary condition during hyperthermia treatment. An approximate analytical solution of the present problem has been done by Finite element wavelet Galerkin method which uses Legendre wavelet as a basis function. Multi-resolution analysis of Legendre wavelet in the present case localizes small scale variations of solution and fast switching of functional bases. The whole analysis is presented in dimensionless form. The dual-phase-lag model of bio-heat transfer has compared with Pennes and Thermal wave model of bio-heat transfer and it has been found that large differences in the temperature at the hyperthermia position and time to achieve the hyperthermia temperature exist, when we increase the value of τT. Particular cases when surface subjected to boundary condition of 1st, 2nd and 3rd kind are discussed in detail. The use of dual-phase-lag model of bio-heat transfer and finite element wavelet Galerkin method as a solution method helps in precise prediction of temperature. Gaussian distribution source term helps in control of temperature during hyperthermia treatment. So, it makes this study more useful for clinical applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Antiemetic therapy for non-anthracycline and cyclophosphamide moderately emetogenic chemotherapy.

    Science.gov (United States)

    Inui, Naoki

    2017-05-01

    Although antiemetic management in cancer therapy has improved, chemotherapy-induced nausea and vomiting remain common and troubling adverse events. Chemotherapeutic agents are classified based on their emetogenic effects, and appropriate antiemetics are recommended according to this categorization. Chemotherapy categorized as moderately emetogenic is associated with a wide spectrum of emetic risks. Combined anthracycline and cyclophosphamide regimens have been recently reclassified as highly emetogenic chemotherapy regimen. This review focuses on antiemetic pharmacotherapy in patients receiving non-anthracycline and cyclophosphamide-based moderately emetogenic chemotherapy regimens. Combination therapy with a 5-hydroxytryptamine-3 receptor agonist, preferably palonosetron, and dexamethasone is the standard therapy in moderately emetogenic chemotherapy, although triple therapy with add-on neurokinin-1 receptor antagonist is used as an alternative treatment strategy. Among moderately emetogenic chemotherapy regimens, carboplatin-containing chemotherapy has considerable emetic potential, particularly during the delayed phase. However, the additional of a neurokinin-1 receptor antagonist to the standard antiemetic therapy prevents carboplatin-induced nausea and vomiting. For regimens including oxaliplatin, the benefit of adding neurokinin-1 receptor antagonist requires further clarification.

  10. Stress-induced hyperthermia in translational stress research

    NARCIS (Netherlands)

    Vinkers, C.H.; Penning, R.; Ebbens, M.M.; Helhammer, J.; Verster, J.C.; Kalkman, C.J.; Olivier, B.

    2010-01-01

    The stress-induced hyperthermia (SIH) response is the transient change in body temperature in response to acute stress. This body temperature response is part of the autonomic stress response which also results in tachycardia and an increased blood pressure. So far, a SIH response has been found in

  11. First-line selective internal radiotherapy plus chemotherapy versus chemotherapy alone in patients with liver metastases from colorectal cancer (FOXFIRE, SIRFLOX, and FOXFIRE-Global): a combined analysis of three multicentre, randomised, phase 3 trials.

    Science.gov (United States)

    Wasan, Harpreet S; Gibbs, Peter; Sharma, Navesh K; Taieb, Julien; Heinemann, Volker; Ricke, Jens; Peeters, Marc; Findlay, Michael; Weaver, Andrew; Mills, Jamie; Wilson, Charles; Adams, Richard; Francis, Anne; Moschandreas, Joanna; Virdee, Pradeep S; Dutton, Peter; Love, Sharon; Gebski, Val; Gray, Alastair; van Hazel, Guy; Sharma, Ricky A

    2017-09-01

    Data suggest selective internal radiotherapy (SIRT) in third-line or subsequent therapy for metastatic colorectal cancer has clinical benefit in patients with colorectal liver metastases with liver-dominant disease after chemotherapy. The FOXFIRE, SIRFLOX, and FOXFIRE-Global randomised studies evaluated the efficacy of combining first-line chemotherapy with SIRT using yttrium-90 resin microspheres in patients with metastatic colorectal cancer with liver metastases. The studies were designed for combined analysis of overall survival. FOXFIRE, SIRFLOX, and FOXFIRE-Global were randomised, phase 3 trials done in hospitals and specialist liver centres in 14 countries worldwide (Australia, Belgium, France, Germany, Israel, Italy, New Zealand, Portugal, South Korea, Singapore, Spain, Taiwan, the UK, and the USA). Chemotherapy-naive patients with metastatic colorectal cancer (WHO performance status 0 or 1) with liver metastases not suitable for curative resection or ablation were randomly assigned (1:1) to either oxaliplatin-based chemotherapy (FOLFOX: leucovorin, fluorouracil, and oxaliplatin) or FOLFOX plus single treatment SIRT concurrent with cycle 1 or 2 of chemotherapy. In FOXFIRE, FOLFOX chemotherapy was OxMdG (oxaliplatin modified de Gramont chemotherapy; 85 mg/m 2 oxaliplatin infusion over 2 h, L-leucovorin 175 mg or D,L-leucovorin 350 mg infusion over 2 h, and 400 mg/m 2 bolus fluorouracil followed by a 2400 mg/m 2 continuous fluorouracil infusion over 46 h). In SIRFLOX and FOXFIRE-Global, FOLFOX chemotherapy was modified FOLFOX6 (85 mg/m 2 oxaliplatin infusion over 2 h, 200 mg leucovorin, and 400 mg/m 2 bolus fluorouracil followed by a 2400 mg/m 2 continuous fluorouracil infusion over 46 h). Randomisation was done by central minimisation with four factors: presence of extrahepatic metastases, tumour involvement of the liver, planned use of a biological agent, and investigational centre. Participants and investigators were not masked to treatment. The primary

  12. Late response to whole-lung irradiation alone and with whole-body hyperthermia in dogs

    International Nuclear Information System (INIS)

    Gillette, S.M.; Gillette, E.L.; Dawson, C.A.

    1997-01-01

    The late effects of whole-lung irradiation with and without whole-body hyperthermia were studied in beagle dogs. The reference doses ranged from 18 to 49.5 Gy given in 1.5-Gy fractions over 6 weeks. Whole-body hyperthermia was given in three 2-h treatments to a deep rectal temperature of 42.0 degrees C. Radiation was given simultaneously with hyperthermia on those days. Physiological and histopathological responses were evaluated. Physiological changes included decreases in cardiac output, systemic blood pressure, dynamic compliance and serotonin uptake. Early changes included an increase in extravascular water and total protein in the lavage. These changes were considered mild, were compensated for and occurred only in dogs receiving doses of 40.5 Gy or greater given in 1.5-Gy fractions over 6 weeks. Histopathological change were typical of irradiated lung and included pleural fibrosis, interstitial fibrosis, fibrotic foci, and peribronchial and perivascular fibrosis. There was no enhancement of late injury to lung by hyperthermia seen in this study. 17 refs., 3 figs., 2 tabs

  13. Metaplastic carcinoma. Breast. Relapse. Chemotherapy and Radiotherapy

    International Nuclear Information System (INIS)

    Marquez, A.; Terrasa, J.; Garcia, J.M.; Rifa, J.

    1996-01-01

    Metaplastic carcinoma of the breast is a rare tumor. The appearance of unexpected mesenchymal elements within the epithelial tumors is the squamous metaplasia. These tumors have a different clinical behaviour that classical breast carcinoma. We present a case of metaplastic mammary carcinoma with multiple relapses treated with a combination of chemotherapy and radiotherapy. The use of chemotherapy after local treatment has enhanced the relapse-free survival. The combined treatment modality seems to produce some benefit in the management of the local relapses of this neoplasms

  14. A case report of suspected malignant hyperthermia where patient survived the episode.

    Science.gov (United States)

    Iqbal, Asif; Badoo, Shoaib; Naqeeb, Ruqsana

    2017-01-01

    Malignant hyperthermia is rare inherited disorder in our part of the world; there are only few cases reported in literature in India who were suspected of having this condition. The overall incidence of malignant hyperthermia during general anesthesia is estimated to range from 1: 5000 to 1: 50,000-100,000 and mortality rate is estimated to be <5% in the presence of standard care. In India, there is no center where in vitro halothane caffeine contraction test is performed to confirm diagnosis in suspected cases. Second, dantrolene drug of choice for this condition is not freely available in market in India and is stored only in some hospitals in few major cities. Among the cases reported of suspected of malignant hyperthermia in India almost 50% have survived the condition despite nonavailability of dantrolene emphasizing role of early detection and aggressive management in these cases.

  15. A case report of suspected malignant hyperthermia where patient survived the episode

    Directory of Open Access Journals (Sweden)

    Asif Iqbal

    2017-01-01

    Full Text Available Malignant hyperthermia is rare inherited disorder in our part of the world; there are only few cases reported in literature in India who were suspected of having this condition. The overall incidence of malignant hyperthermia during general anesthesia is estimated to range from 1: 5000 to 1: 50,000–100,000 and mortality rate is estimated to be <5% in the presence of standard care. In India, there is no center where in vitro halothane caffeine contraction test is performed to confirm diagnosis in suspected cases. Second, dantrolene drug of choice for this condition is not freely available in market in India and is stored only in some hospitals in few major cities. Among the cases reported of suspected of malignant hyperthermia in India almost 50% have survived the condition despite nonavailability of dantrolene emphasizing role of early detection and aggressive management in these cases.

  16. Combination chemotherapy and radiotherapy of small cell lung cancer

    International Nuclear Information System (INIS)

    Saito, Yasuo; Chohtoh, Shuichi; Nishijima, Hiroshi; Kobayashi, Akihiko; Hirose, Jin-ichiro; Kamimura, Ryoichi; Takashima, Tsutomu; Konishi, Hideo; Miyata, Samon.

    1986-01-01

    Treatment results of 49 patients (25, limited disease, LD, 24, extensive disease, ED) with small cell lung cancer were retrospectively analyzed. Fifteen patients received chemotherapy with Cyclophosphamide (CPM) and Vincristine (VCR) following thoracic radiotherapy (RT). Twenty-two patients were given induction chemotherapy with CPM, Adriamycin (ADM), and VCR and were followed by thoracic RT. Other chemotherapy consisted of CPM, VCR, Methotrexate, and ADM in 2 patients, 5-FU, CPM, Mitomycin C, and Toyomycin in 1 patient. The remaining 9 patients (2, LD, 7, ED) were treated with RT alone. The response rate was 80 % (64 % CR; 16 % PR) for LD patients and 33 % (4 % CR; 29 % PR) for ED patients (P < 0.001). The three-year survival (Kaplan-Meier's product) of all patients was 14 %, with a median survival time (MST) of 8 months. For patients with LD, the 3-year survival was 27 % (MST 15 months). Survival of patients with ED was 14 % at 1 year, 0 % at 2 year (MST 5.5 months). The difference between these figures was statistically significant (P < 0.0003). The 3-year survival and relapse-free survival for complete responders with LD were 43 % (MST 21 months) and 36 % (median CR duration, 11.5 months) respectively. Six of 16 complete responders with LD are alive and well at over 2 years. Local recurrence rate of the complete responders with LD was 28.8 %. None of the 7 complete responders given more than 48 Gy relapsed within the radiation field. We believe that the addition of thoracic RT to patients with LD is necessary for the control of the primary tumors and for long-term disease-free survival. (author)

  17. Thermal Skin Damage During Reirradiation and Hyperthermia Is Time-Temperature Dependent

    Energy Technology Data Exchange (ETDEWEB)

    Bakker, Akke, E-mail: akke.bakker@amc.uva.nl [Department of Radiation Oncology, Academic Medical Center (AMC), Amsterdam (Netherlands); Kolff, M. Willemijn [Department of Radiation Oncology, Academic Medical Center (AMC), Amsterdam (Netherlands); Holman, Rebecca [Clinical Research Unit, Academic Medical Center (AMC), Amsterdam (Netherlands); Leeuwen, Caspar M. van; Korshuize-van Straten, Linda; Kroon-Oldenhof, Rianne de; Rasch, Coen R.N.; Tienhoven, Geertjan van; Crezee, Hans [Department of Radiation Oncology, Academic Medical Center (AMC), Amsterdam (Netherlands)

    2017-06-01

    Purpose: To investigate the relationship of thermal skin damage (TSD) to time–temperature isoeffect levels for patients with breast cancer recurrence treated with reirradiation plus hyperthermia (reRT + HT), and to investigate whether the treatment history of previous treatments (scar tissue) is a risk factor for TSD. Methods and Materials: In this observational study, temperature characteristics of hyperthermia sessions were analyzed in 262 patients with recurrent breast cancer treated in the AMC between 2010 and 2014 with reirradiation and weekly hyperthermia for 1 hour. Skin temperature was measured using a median of 42 (range, 29-82) measurement points per hyperthermia session. Results: Sixty-eight patients (26%) developed 79 sites of TSD, after the first (n=26), second (n=17), third (n=27), and fourth (n=9) hyperthermia session. Seventy percent of TSD occurred on or near scar tissue. Scar tissue reached higher temperatures than other skin tissue (0.4°C, P<.001). A total of 102 measurement points corresponded to actual TSD sites in 35 of 79 sessions in which TSD developed. Thermal skin damage sites had much higher maximum temperatures than non-TSD sites (2.8°C, P<.001). Generalized linear mixed models showed that the probability of TSD is related to temperature and thermal dose values (P<.001) and that scar tissue is more at risk (odds ratio 0.4, P<.001). Limiting the maximum temperature of a measurement point to 43.7°C would mean that the probability of observing TSD was at most 5%. Conclusion: Thermal skin damage during reRT + HT for recurrent breast cancer was related to higher local temperatures and time–temperature isoeffect levels. Scar tissue reached higher temperatures than other skin tissue, and TSD occurred at lower temperatures and thermal dose values in scar tissue compared with other skin tissue. Indeed, TSD developed often on and around scar tissue from previous surgical procedures.

  18. Evaluation of radiotherapy and chemotherapy treatment in patients of oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Sannomiya, Eduardo Kazuo; Medici Filho, Edmundo; Moraes, Luiz Cesar de; Castilho, Julio Cezar de Melo; Furukawa, Souhei

    2003-01-01

    We evaluated the effectiveness of radiotherapy combined with chemotherapy in patients with oral squamous cell carcinoma. Therefore, 1042 cases where reviewed in School Dentistry - Osaka Univ. Seven hundred and fifteen were male and three hundred and twenty-seven were female. Ora cancer was affected more male than female patients, with mean age of 582 years old. The tongue was the most common anatomic localization of oral cancer. In tongue, the use of external radiotherapy y combined with brachytherapy and brachytherapy isolated presented better results than chemotherapy combined with external radiotherapy. In buccal mucosa, there was not differences in the treatment's results using external radiotherapy and combined chemotherapy and external radiotherapy. In tongue's floor and upper and jaw gingiva the combined treatment with chemotherapy and external radiotherapy presented better results than isolated external radiotherapy. (author)

  19. Chemotherapy options for the elderly patient with advanced non-small cell lung cancer.

    LENUS (Irish Health Repository)

    Hennessy, B T

    2012-02-03

    Combination chemotherapy has been shown to improve overall survival compared with best supportive care in patients with advanced non-small cell lung cancer (NSCLC). The survival advantage is modest and was initially demonstrated with cisplatin-containing regimens in a large meta-analysis of randomized trials reported in 1995. Newer chemotherapy combinations have been shown to be better tolerated than older cisplatin-based combinations, and some trials have also shown greater efficacy and survival benefits with these newer combinations. Combination chemotherapy is, therefore, the currently accepted standard of care for patients with good performance statuses aged less than 70 years with advanced NSCLC. However, there are limited data from clinical trials to support the use of combination chemotherapy in elderly patients over 70 years of age with advanced NSCLC. Subgroup analyses of large randomized phase III trials suggest that elderly patients with good performance statuses do as well as younger patients treated with combination chemotherapy. There are few randomized trials reported that evaluate chemotherapy in patients aged greater than 70 years only. Based on data from trials performed by an Italian group, single-agent vinorelbine has been shown to have significant activity in elderly patients with advanced NSCLC and to be well tolerated by those patients with Eastern Cooperative Oncology Group performance statuses of two or less, with associated improvements in measures of global health.

  20. Cancer occurring after radiotherapy and chemotherapy

    International Nuclear Information System (INIS)

    Holm, L.E.

    1990-01-01

    Radiotherapy and chemotherapy can effectively control cancer but can also cause new cancers to develop as long-term complications. Almost all types of cancer have been associated with radiotherapy. The breast, thyroid, and bone marrow are the organs most susceptible to radiation carcinogenesis. The bone marrow is also most frequently involved by chemotherapy and the leukemia risk is much higher than after radiotherapy. The combination of intensive radiotherapy and chemotherapy is particularly leukemogenic. The latent period between radiotherapy/chemotherapy and the appearance of a second primary cancer ranges from a few years to several decades. The risk for a second primary cancer following radiotherapy or chemotherapy emphasizes the need for life long follow-up of patients receiving such treatments. This is particularly the case in individuals with long life expectancy, for example, patients treated for childhood neoplasms. The benefits of radiotherapy and chemotherapy in oncology exceed the risks for second primary cancers. Efforts should be directed towards identifying those patients who will benefit from the treatments so that only they are exposed to the risk. 33 references