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Sample records for cancer low-dose rate

  1. Low dose irradiation reduces cancer mortality rates

    International Nuclear Information System (INIS)

    Low doses of ionizing radiation stimulate development, growth, memory, sensual acuity, fecundity, and immunity (Luckey, T.D., ''Radiation Hormesis'', CRC Press, 1991). Increased immune competence reduces cancer mortality rates and provides increased average lifespan in animals. Decreased cancer mortality rates in atom bomb victims who received low dose irradiation makes it desirable to examine populations exposed to low dose irradiation. Studies with over 300,000 workers and 7 million person-years provide a valid comparison of radiation exposed and control unclear workers (Luckey, T.D., Nurture with Ionizing Radiation, Nutrition and Cancer, 34:1-11, 1999). Careful selection of controls eliminated any ''healthy worker effect''. The person-year corrected average indicated the cancer mortality rate of exposed workers was only 51% that of control workers. Lung cancer mortality rates showed a highly significant negative correlation with radon concentrations in 272,000 U.S. homes (Cohen, B.L., Health Physics 68:157-174, 1995). In contrast, radon concentrations showed no effect on lung cancer rates in miners from different countries (Lubin, J.H. Am. J. Epidemiology 140:323-332, 1994). This provides evidence that excessive lung cancer in miners is caused by particulates (the major factor) or toxic gases. The relative risk for cancer mortality was 3.7% in 10,000 Taiwanese exposed to low level of radiation from 60Co in their steel supported homes (Luan, Y.C. et al., Am. Nuclear Soc. Trans. Boston, 1999). This remarkable finding needs further study. A major mechanism for reduced cancer mortality rates is increased immune competence; this includes both cell and humoral components. Low dose irradiation increases circulating lymphocytes. Macrophage and ''natural killer'' cells can destroy altered (cancer) cells before the mass becomes too large. Low dose irradiation also kills suppressor T-cells; this allows helper T-cells to activate killer cells and antibody producing cells

  2. Low dose irradiation reduces cancer mortality rates

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    Luckey, T.D.

    2000-05-01

    Low doses of ionizing radiation stimulate development, growth, memory, sensual acuity, fecundity, and immunity (Luckey, T.D., ''Radiation Hormesis'', CRC Press, 1991). Increased immune competence reduces cancer mortality rates and provides increased average lifespan in animals. Decreased cancer mortality rates in atom bomb victims who received low dose irradiation makes it desirable to examine populations exposed to low dose irradiation. Studies with over 300,000 workers and 7 million person-years provide a valid comparison of radiation exposed and control unclear workers (Luckey, T.D., Nurture with Ionizing Radiation, Nutrition and Cancer, 34:1-11, 1999). Careful selection of controls eliminated any ''healthy worker effect''. The person-year corrected average indicated the cancer mortality rate of exposed workers was only 51% that of control workers. Lung cancer mortality rates showed a highly significant negative correlation with radon concentrations in 272,000 U.S. homes (Cohen, B.L., Health Physics 68:157-174, 1995). In contrast, radon concentrations showed no effect on hlumg cancer rates in miners from different countries (Lubin, J.H. Am. J. Epidemiology 140:323-332, 1994). This provides evidence that excessive lung cancer in miners is caused by particulates (the major factor) or toxic gases. The relative risk for cancer mortality was 3.7% in 10,000 Taiwanese exposed to low level of radiation from {sup 60}Co in their steel supported homes (Luan, Y.C. et al., Am. Nuclear Soc. Trans. Boston, 1999). This remarkable finding needs further study. A major mechanism for reduced cancer mortality rates is increased immune competence; this includes both cell and humoral components. Low dose irradiation increases circulating lymphocytes. Macrophage and ''natural killer'' cells can destroy altered (cancer) cells before the mass becomes too large. Low dose irradiation also kills suppressor T-cells; this allows

  3. Low dose rate Ir-192 interstitial brachytherapy for prostate cancer

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    Oki, Yosuke; Dokiya, Takushi; Yorozu, Atsunori; Suzuki, Takayuki; Saito, Shiro; Monma, Tetsuo; Ohki, Takahiro [National Tokyo Medical Center (Japan); Murai, Masaru; Kubo, Atsushi

    2000-04-01

    From December 1997 through January 1999, fifteen prostatic cancer patients were treated with low dose rate Ir-192 interstitial brachytherapy using TRUS and perineal template guidance without external radiotherapy. Up to now, as no apparent side effects were found, the safety of this treatment is suggested. In the future, in order to treat prostatic cancer patients with interstitial brachytherapy using I-125 or Pd-103, more investigation for this low dose rate Ir-192 interstitial brachytherapy is needed. (author)

  4. Outcomes of low-dose-rate brachytherapy for treatment of tongue cancer

    International Nuclear Information System (INIS)

    Between 1997 and 2006, 324 patients with T1-2 tongue cancer were treated with low-dose-rate brachytherapy at Tokyo Medical and Dental University Hospital. Their 5- and 10-year local control rates were 83% and 80%, respectively, and the occurrence rates of ≥ grade 3 mucositis and osteonecrosis were both 0.3%. During the study period, 9 other patients with tongue cancer underwent surgery and brachytherapy for positive surgical margins at our institution. Their 5- and 10-year local control rates were 76% and 64%. Moreover, 24 patients with tongue cancer received chemotherapy followed by brachytherapy, and their 5- and 10-year local control rates were both 100%. These outcomes are comparable to those of the patients who underwent low-dose-rate brachytherapy for T1-2 tongue cancer. In this study, 80% of patients treated by brachytherapy for T1-2 tongue cancer were cured with preserved function. However, for some patients with tumors unsuitable for treatment by brachytherapy alone, a combination of brachytherapy and surgery or chemotherapy may be a suitable treatment option. (author)

  5. Brachytherapy for early oral tongue cancer. Low dose rate to high dose rate

    International Nuclear Information System (INIS)

    To examine the compatibility of low dose rate (LDR) with high dose rate (HDR) brachytherapy, we reviewed 399 patients with early oral tongue cancer (T1-2N0M0) treated solely by brachytherapy at Osaka University Hospital between 1967 and 1999. For patients in the LDR group (n=341), the treatment sources consisted of Ir-192 pin for 227 patients (1973-1996; irradiated dose, 61-85 Gy; median, 70 Gy), Ra-226 needle for 113 patients (1967-1986; 55-93 Gy; median, 70 Gy). Ra-226 and Ir-192 were combined for one patient. Ir-192 HDR (microSelectron-HDR) was used for 58 patients in the HDR group (1991-present; 48-60 Gy; median, 60 Gy). LDR implantations were performed via oral and HDR via a submental/submandibular approach. The dose rates at the reference point for the LDR group were 0.30 to 0.8 Gy/h, and for the HDR group 1.0 to 3.4 Gy/min. The patients in the HDR group received a total dose of 48-60 Gy (8-10 fractions) during one week. Two fractions were administered per day (at least a 6-h interval). The 3- and 5-year local control rates for patients in the LDR group were 85% and 80%, respectively, and those in the HDR group were both 84%. HDR brachytherapy showed the same lymph-node control rate as did LDR brachytherapy (67% at 5 years). HDR brachytherapy achieved the same locoregional result as did LDR brachytherapy. A converting factor of 0.86 is applicable for HDR in the treatment of early oral tongue cancer. (author)

  6. Implications of effects ''adaptive response'', ''low-dose hypersensitivity'' und ''bystander effect'' for cancer risk at low doses and low dose rates

    International Nuclear Information System (INIS)

    A model for carcinogenesis (the TSCE model) was applied in order to examine the effects of ''Low-dose hypersensitivity (LDH)'' and the ''Bystander effect (BE)'' on the derivation of radiation related cancer mortality risks. LDH has been discovered to occur in the inactivation of cells after acute exposure to low LET radiation. A corresponding version of the TSCE model was applied to the mortality data on the Abomb survivors from Hiroshima and Nagasaki. The BE has been mainly observed in cells after exposure to high LET radiation. A Version of the TSCE model which included the BE was applied to the data on lung cancer mortality from the workers at the Mayak nuclear facilities who were exposed to Plutonium. In general an equally good description of the A-bomb survivor mortality data (for all solid, stomach and lung tumours) was found for the TSCE model and the (conventional) empirical models but fewer parameters were necessary for the TSCE model. The TSCE model which included the effects of radiation induced cell killing resulted in non-linear dose response curves with excess relative risks after exposure at young ages that were generally lower than in the models without cell killing. The main results from TSCE models which included cell killing described by either conventional survival curves or LDH were very similar. A sub multiplicative effect from the interaction of smoking and exposure to plutonium was found to result from the analysis of the Mayak lung cancer mortality data. All models examined resulted in the predominant number of Mayak lung cancer deaths being ascribed to smoking. The interaction between smoking and plutonium exposures was found to be the second largest effect. The TSCE model resulted in lower estimates for the lung cancer excess relative risk per unit plutonium dose than the empirical risk model, but this difference was not found to be statistically significant. The excess relative risk dose responses were linear in the empirical model and

  7. Low-dose-rate interstitial brachytherapy preserves good quality of life in buccal mucosa cancer patients

    International Nuclear Information System (INIS)

    The purpose of this study was to determine the results and long-term changes in radiation toxicity of stage I-II buccal mucosa cancer patients treated by low-dose-rate (LDR) brachytherapy with 198Au grains. A total of 133 stage I-II buccal mucosa carcinomas patients received 198Au grain implantation brachytherapy between January 1982 and July 2005: 75 of them were treated by 198Au grain implantation alone and 58 were treated by 198Au implantation in combination with external irradiation. The average 198Au-grain dose was 70 Gy in 7 days. Gross tumor areas ranged from 2.4 cm2 to 9 cm2, and the clinical target areas ranged from 6 cm2 to 15 cm2. The follow-up periods ranged from 3 months to 20 years (mean: 5 years 11 months and median: 5 years 1 months). Failure at the site of the primary lesion occurred in 17 patients. Post-treatment mucosal ulceration developed in 15 patients, and all were cured within 25 months by conservative treatment. Osteoradionecrosis was diagnosed in 8 patients, but only one patient required surgical treatment. No severe complications or aggravation of complications developed more than 10 years after treatment. The results of low-dose-rate (LDR)-brachytherapy (BT) alone and LDR-BT in combination with external irradiation at a total dose of 25 Gy were acceptable from the standpoint of cure rate and quality of life (QOL). (author)

  8. Radiotherapy for cancer of the maxillary sinus, with boost therapy by low dose rate intracavitary irradiation

    International Nuclear Information System (INIS)

    Prognosis of cancer of the maxillary sinus markedly depends on its local control. In order to increase the local control rate for cancer of the maxillary sinus, low dose rate intracavitary irradiation of the maxillary sinus was performed as boost therapy of external irradiation. During the period from January 1975 through September 1982, 87 patients with cancer of the maxillary sinus were treated by radiotherapy at the Department of Radiology, The Jikei University School of Medicine, and 43 out of these 87 cases were treated with intracavitary irradiation as boost therapy of external irradiation. The 3-year and 5-year cumulative survival rates of the 43 cases treated with intracavitary irradiation were 44% and 39%, respectively. The same two rates of the 44 cases without intracavitary irradiation were both 47%. Considering that tumor foci still persisted in the maxillary sinus in almost all of the 43 intracavitary irradiation cases and that 34 of them were of the postero-superior type (according to Oehngren's classification), which generally results in poor prognosis, intracavitary irradiation as boost therapy can be assumed to be one of the effective therapeutic techniques for cancer of the maxillary sinus. (author)

  9. Long-term results of breast cancer irradiation treatment with low-dose-rate external irradiation

    International Nuclear Information System (INIS)

    Purpose: The aim of this study was to assess beam therapy with low-dose-rate (LDR) external irradiation in a group of patients with breast cancer. Methods and Materials: This trial compared, from 1986 to 1989, patients with advanced breast cancer treated either by conventional fractionation or low-dose-rate (LDR) external radiotherapy (dose-rate 15 mGy/min, 5 sessions of 9 Gy delivered on 5 consecutive days). Results: A total of 21 patients were included in the fractionated therapy arm. At follow-up 15 years after treatment, 7 local recurrences had occurred, 3 patients had died of cancer, 18 patients were alive, 10 were without evidence of disease, and 6 had evidence of disease. A total of 22 patients had been included in the LDR arm of the study. Of these, 11 had received a dose of 45 Gy; thereafter, in view of severe local reactions, the dose was reduced to 35 Gy. There was no local recurrence in patients who had received 45 Gy, although there were 2 local recurrences among the 11 patients after 35 Gy. The sequelae were severe in patients who received 45 Gy but were comparable to those observed in patients treated by fractionated radiotherapy who received 35 Gy. The higher efficacy of tumor control in patients treated by LDR irradiation as well as the lower tolerance of normal tissue are probably related to the lack of repopulation. Conclusion: Although the patient numbers in this study are limited, based on our study results we conclude that the data for LDR irradiation are encouraging and that further investigation is warranted

  10. Quality of Life of Oral Cancer Patients After Low-Dose-Rate Interstitial Brachytherapy

    International Nuclear Information System (INIS)

    Purpose: To assess the quality of life (QOL) of oral cancer patients treated with low-dose-rate interstitial brachytherapy (LDR-BT) alone. Methods and Materials: Between June 2005 and July 2006, a total of 56 patients with oral cancer were enrolled in this prospective study. QOL was assessed by means of the core questionnaire and head and neck questionnaire module of the European Organization for Research and Treatment of Cancer (EORTC Quality of Life Questionnaire-Core 30 [QLQ-C30] and QLQ Head and Neck 35 [H and N35]). The questionnaires were distributed to the patients before the start of treatment and 3 months, 6 months, and 12 months after the start of LDR-BT. Results: It was possible to analyze the results for 20 of the initial 56 patients because they did not experience metastasis or recurrence during this study. No functions or symptoms asked about in the QLQ-C30 deteriorated during the first year. The emotional function score steadily and significantly increased. No symptoms in the QLQ-H and N35 significantly deteriorated. The scores for pain, trouble with social eating, and weight loss on the QLQ-H and N35 steadily and significantly decreased. Age, gender, and LDR-BT source had no effect on the change in QOL during the first year, but T-stage significantly affected the change in global health status, tumor site affected the changes in swallowing, sensory problems, sticky saliva, and complications affected the changes in pain, swallowing, and mouth opening. Conclusions: QOL of oral cancer patients treated with LDR-BT is high. However, tumor stage, tumor site, and complications affected the changes in a few functions and symptoms during the first year

  11. Low doses effects and gamma radiations low dose rates

    International Nuclear Information System (INIS)

    This expose wishes for bringing some definitions and base facts relative to the problematics of low doses effects and low dose rates effects. It shows some already used methods and some actual experimental approaches by focusing on the effects of ionizing radiations with a low linear energy transfer. (N.C.)

  12. Health effect of low dose/low dose rate radiation

    International Nuclear Information System (INIS)

    The clarified and non-clarified scientific knowledge is discussed to consider the cause of confusion of explanation of the title subject. The low dose is defined roughly lower than 200 mGy and low dose rate, 0.05 mGy/min. The health effect is evaluated from 2 aspects of clinical symptom/radiation hazard protection. In the clinical aspect, the effect is classified in physical (early and late) and genetic ones, and is classified in stochastic (no threshold value, TV) and deterministic (with TV) ones from the radioprotection aspect. Although the absence of TV in the carcinogenic and genetic effects has not been proved, ICRP employs the stochastic standpoint from the safety aspect for radioprotection. The lowest human TV known now is 100 mGy, meaning that human deterministic effect would not be generated below this dose. Genetic deterministic effect can be observable only in animal experiments. These facts suggest that the practical risk of exposure to <100 mGy in human is the carcinogenesis. The relationship between carcinogenic risk in A-bomb survivors and their exposed dose are found fitted to the linear no TV model, but the epidemiologic data, because of restriction of subject number analyzed, do not always mean that the model is applicable even below the dose <100 mGy. This would be one of confusing causes in explanation: no carcinogenic risk at <100 mGy or risk linear to dose even at <100 mGy, neither of which is scientifically conclusive at present. Also mentioned is the scarce risk of cancer in residents living in the high background radiation regions in the world in comparison with that in the A-bomb survivors exposed to the chronic or acute low dose/dose rate. Molecular events are explained for the low-dose radiation-induced DNA damage and its repair, gene mutation and chromosome aberration, hypothesis of carcinogenesis by mutation, and non-targeting effect of radiation (bystander effect and gene instability). Further researches to elucidate the low dose

  13. Treatment outcome with low-dose-rate interstitial brachytherapy in early-stage oral tongue cancers

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    Bhalavat Rajendra

    2009-01-01

    Full Text Available Purpose : Although radical radiotherapy is known to be equally effective for early-stage oral tongue cancers (T1-2 N0 with the added advantage of organ and function preservation, surgery remains the preferred treatment. We present outcome of patients treated with brachytherapy (BT either radical or boost. Materials and Methods : Fifty-seven patients (T1/T2 31/26 were studied. Seventeen patients (30% were treated with radical BT (50-67 Gy while 40 (70% with external beam radiation therapy (EBRT + BT (36-56 Gy + 15-38 Gy]. Low-dose-rate (LDR BT was delivered with 192 Ir wires, using plastic bead technique with varied dose rates (< 60 cGy/h in 29 patients, 60-90 cGy/h in 17, and> 90 cGy/h in 11. Results : The overall local control (LCR was achieved in 59.7% (34/57 patients. LCR for T1 and T2 was 67.8% and 50%, respectively. A total of 23 patients had failures [local: 20 (T1: 8; T2: 12 patients, node: 5 (T1:2; T2: 3, and local + nodal: 3]. Overall 5-year disease-free survival and overall survival (OAS were 51% and 67%, respectively and those for T1 and T2 was 64.5/77.4% and 38.5/54% respectively (P = 0.002. All 16 patients were salvaged. Median survival after salvage treatment was 13.5 months (6-100 months. Soft tissue necrosis was observed in 12.3% (7/57 and osteoradionecrosis in two patients. Conclusion : BT, as an integral part of radical radiation therapy in early-stage tongue cancers, appears to be an effective alternative treatment modality with preservation of the organ and function without jeopardizing the outcome.

  14. Phase III trial of high and low dose rate interstitial radiotherapy for early oral tongue cancer

    International Nuclear Information System (INIS)

    Purpose: Oral tongue carcinomas are highly curable with radiotherapy. In the past, patients with tongue carcinoma have usually been treated with low dose rate (LDR) interstitial radiation. This Phase III study was designed to compare the treatment results obtained with LDR with those obtained with high dose rate (HDR) interstitial radiotherapy for tongue carcinoma. Methods and Materials: The criteria for patient selection for the Phase III study were: (a) presence of a T1T2N0 tumor that could be treated with single-plane implantation, (b) localization of tumor at the lateral tongue border, (c) tumor thickness of 10 mm or less, (d) performance status between O and 3, and (e) absence of any severe concurrent disease. From April 1992 through December 1993, 15 patients in the LDR group (70 Gy/4 to 9 days) and 14 patients in the HDR group (60 Gy/10 fractions/6 days) were accrued. The time interval between two fractions of the HDR brachytherapy was more than 6 h. Results: Local recurrence occurred in two patients treated with LDR brachytherapy but in none of the patients treated with HDR. One- and 2-year local control rates for patients in the LDR group were both 86%, compared with 100% in the HDR group (p = 0.157). There were four patients with nodal metastasis in the LDR group and three in the HDR group. Local recurrence occurred in two of the four patients with nodal metastases in the LDR group. One- and 2-year nodal control rates for patients in the LDR group are were 85%, compared with 79% in the HDR group. Conclusion: HDR fractionated interstitial brachytherapy can be an alternative to traditional LDR brachytherapy for early tongue cancer and eliminate the radiation exposure for medical staffs

  15. Low dose rate irradiation of advanced head and neck cancers: present status

    International Nuclear Information System (INIS)

    A total of 46 patients with advanced epidermoid carcinomas of the head and neck were treated with semi-continuous low dose rate cobalt teletherapy with curative intent. The dose rate was 90 to 130 rad per hr, the patients were treated 6 to 8 hr per day, and received total doses of 6500 to 7000 rad in either single or split courses. Thirty-four of these patients had a minimum follow-up of one year and form the basis of this report. While the survival of these patients was poor (22% at 3 years), the local control rate of 58% was encouraging. The immediate tolerance of the mucosa frequently was exceeded in a single course treatment; furthermore, there was a high necrosis rate. Skin reactions, however, remained characteristically mild. Split course treatment succeeded in reducing mucosal reactions to a tolerable level without decreasing local control, but it did not reduce the high risk of necrosis (actually greater than 50% at 2 years). Residual tumor at 3 months carried a grave prognosis. All non-sterilizations and recurrences within the low dose rate treated volumes occurred with tumors 5 cm or more in greatest dimension; local control was obtained in all 10 patients who had less extensive primary lesions. Necroses occurred with equal frequencies in both the larger and relatively smaller tumors. Low dose rate treatment has been proven feasible and currently is being used in a randomized prospective trial to test its possible superiority over conventional fractionation

  16. LOW-DOSE RATE BRACHYTHERAPY FOR PROSTATE CANCER: DIFFERENT INDICATIONS – DIFFERENT RESULTS

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    V. A. Biryukov

    2014-07-01

    Full Text Available In Russia, there is presently a growing interest in low-dose intratissue radiotherapy (brachytherapy for locally advanced prostate cancer (PC. Since its inception, current brachytherapy has undergone a number of significant changes in terms of improved visualization and better treatment planning and monitoring, which is sure to have affected the higher quality of their performance and better long-term results. The main purpose of the given paper is to generalize the data of foreign investigators who have the greatest experience with brachytherapy for its further use in the treatment of patients with locally advanced PC under the conditions of Russian clinics.

  17. Radiation Leukemogenesis at Low Dose Rates

    International Nuclear Information System (INIS)

    The major goals of this program were to study the efficacy of low dose rate radiation exposures for the induction of acute myeloid leukemia (AML) and to characterize the leukemias that are caused by radiation exposures at low dose rate. An irradiator facility was designed and constructed that allows large numbers of mice to be irradiated at low dose rates for protracted periods (up to their life span). To the best of our knowledge this facility is unique in the US and it was subsequently used to study radioprotectors being developed for radiological defense (PLoS One. 7(3), e33044, 2012) and is currently being used to study the role of genetic background in susceptibility to radiation-induced lung cancer. One result of the irradiation was expected; low dose rate exposures are ineffective in inducing AML. However, another result was completely unexpected; the irradiated mice had a very high incidence of hepatocellular carcinoma (HCC), approximately 50%. It was unexpected because acute exposures are ineffective in increasing HCC incidence above background. This is a potential important finding for setting exposure limits because it supports the concept of an 'inverse dose rate effect' for some tumor types. That is, for the development of some tumor types low dose rate exposures carry greater risks than acute exposures

  18. Radiation Leukemogenesis at Low Dose Rates

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    Weil, Michael; Ullrich, Robert

    2013-09-25

    The major goals of this program were to study the efficacy of low dose rate radiation exposures for the induction of acute myeloid leukemia (AML) and to characterize the leukemias that are caused by radiation exposures at low dose rate. An irradiator facility was designed and constructed that allows large numbers of mice to be irradiated at low dose rates for protracted periods (up to their life span). To the best of our knowledge this facility is unique in the US and it was subsequently used to study radioprotectors being developed for radiological defense (PLoS One. 7(3), e33044, 2012) and is currently being used to study the role of genetic background in susceptibility to radiation-induced lung cancer. One result of the irradiation was expected; low dose rate exposures are ineffective in inducing AML. However, another result was completely unexpected; the irradiated mice had a very high incidence of hepatocellular carcinoma (HCC), approximately 50%. It was unexpected because acute exposures are ineffective in increasing HCC incidence above background. This is a potential important finding for setting exposure limits because it supports the concept of an 'inverse dose rate effect' for some tumor types. That is, for the development of some tumor types low dose rate exposures carry greater risks than acute exposures.

  19. The brachytherapy with low dose-rate iridium for prostate cancer

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    Momma, Tetsuo; Saito, Shiro; Ohki, Takahiro; Satoh, Hiroyuki; Toya, Kazuhito; Dokiya, Takushi [National Tokyo Medical Center (Japan); Murai, Masaru

    2000-11-01

    Brachytherapy as an option for the treatment of prostate cancer has been commonly performed in USA. As the permanent seeding of the radioactive materials is strictly restricted by the law in Japan, brachytherapy must be performed by the temporary implant. This treatment has been performed at a few facilities in Japan mostly using high dose-rate iridium. Only our facility has been using low dose-rate iridium (LDR-Ir) for prostate cancer. This study evaluates the clinical results of the treatment. Since December 1997 to December 1999, 26 patients with histologically diagnosed as prostate cancer (Stage B, 92%; Stage C, 8%) underwent brachytherapy. Twenty-two patients received brachytherapy alone, three were treated with a combination of brachytherapy and external beam radiotherapy (ERT) and one was treated with a combination of brachytherapy and neoadjuvant endocrine therapy. Patients ranged in age from 61 to 84 (median 76) years old. Treatment was initiated with perineal needle placement. From 10 to 14 needles were placed through the holes on the template which was fixed to the stabilizer of the transrectal ultrasound probe. After the needle placement, CT scan was performed to draw distribution curves for the treatment planning. LDR-Ir wires were introduced to the sheath and indwelled during the time calculated from dosimetry. Peripheral dose was 70 Gy for the monotherapy of brachytherapy. For the combination therapy, 40 Gy was given by brachytherapy and 36 Gy with ERT afterwards. LDR-Ir wires were removed after completion of the radiation and patients were followed with serum PSA level and annual biopsy. During 2 to 26 (median 12) months follow-up, 8 out of 9 patients with initial PSA level above 20 ng/ml showed PSA failure. All 13 patients with initial PSA level lower than 20 ng/ml were free from PSA failure. Eight out of 11 patients with Gleason's score 7 or higher showed PSA failure, and all 14 patients (including three patients with combined therapy) with

  20. The OER at low-dose rates

    International Nuclear Information System (INIS)

    There is increasing interest in the treatment of human cancers with multifraction beam therapy at low dose-rates, on the assumption that the OER at low dose-rates is smaller than that at high dose-rates. A comparison has therefore been made of various published values of OER as a function of γ dose-rate for Vicia faba, HeLa cells, P388 cells, hamster cells and chromosome aberrations. The mean value of the OER at low dose-rate was about 20% lower than the mean OER obtained at high dose-rate, although two OER values at low dose-rates were significantly lower than the other reported values. There are technical difficulties associated with maintaining the test systems under hypoxic conditions for long periods of time and the observed decrease in cloning efficiency of hypoxic control cells indicates that cells can be damaged by this treatment alone. It is therefore possible that the high dose-rate OER values would have been reduced if the cells irradiated at high dose-rates under oxic and anoxic conditions had had a pre-treatment period of storage under anoxic conditions. (U.K.)

  1. Study on the anti-cancer mechanisms of low dose-rate γ irradiation

    International Nuclear Information System (INIS)

    To investigate appropriate dose range in low-dose-rate γ irradiation and to establish a useful method for the research of radioactive biological effect produced by low does-rate γ irradiation, the authors have studied apoptosis of Hela carcinoma cells induced by different low dose rates of γ irradiation in vitro. The cultured cells were exposed to defined radiation doses from a 60Co therapy source. The radiation source delivered a dose rate of 1 Gy/min and gave total dose of 1, 2, 5, 10 and 15 Gy respectively. Using Annexin V labeled by fluorescein and PI, followed by flow cytometry and DNA ladder analysis and confocal microscope, apoptotic cells were detected and quantified. The results are as follows: (1) Determination of apoptosis by flow cytometry indicated that percentage of apoptotic cells was increasing with dose and time. When cells were cultured for 168 h after irradiation, the highest percentage of apoptosis was yielded in all groups. When the cells were irradiated with 1-2 Gy, no significant increase in the number of apoptotic cells could be seen. After a total dose of 5 Gy, however, a significant increase in the ratio of apoptotic/nonapoptotic cells was observed, and apoptosis reached a peak level of (72.57 ± 2.04)% (P60Co sources to Hela cells can induce a significant apoptosis rate, and a maximum level of apoptosis as high as (72.57±2.04)% for an irradiation dose of 5 Gy can be reached. (authors)

  2. Lung cancer incidence after exposure of rats to low doses of radon: influence of dose rate

    International Nuclear Information System (INIS)

    To study the effect on lung cancer incidence of a long exposure to low levels of radon, 500 male 3-months-old Sprague-Dawley rats, were exposed to a cumulative dose of 25 WLM of radon and its daughters, 6 hours a day, 5 days a week, during 18 months. Exposure conditions were controlled in order to maintain a defined PAEC: 42 x 106 J.m-3 (2 WL), in the range of domestic and environmental exposures. Animals were kept until they died or given euthanasia when moribund. Mean survival times were similar in both irradiated and control groups: 828 days (SD = 169) and 830 days (SD = 137), as well as lung cancer incidence, 0.60% at 25 WLM and 0.63% for controls. The incidence of lung lesions was compared statistically with controls and those previously obtained at cumulative exposures of 25 and 50 WLM delivered over a 4-6 month period, inducing a significant increase of lung cancer, 2.2% and 3.8% respectively. Such a comparison showed a decreased lung cancer incidence related to a decrease in the dose rate for low levels of radon exposure. (author)

  3. The different biological effects of single, fractioned and continuous low dose rate radiation on CL187 colorectal cancer cell line

    International Nuclear Information System (INIS)

    Objective: To investigate the effect and underlying mechanism of single, fractioned and continuous low dose rate radiation on CL187 colorectal cancer cell line. Methods: CL187 cells were exposed to 6 MV X-rays at a high dose rate of 4 Gy/min and 125I seed at a low dose rate of 2.77 cGy/h with three groups:single dose radiation group (SDR), fractioned dose radiation group (FDR) by 2 Gy/f, and continuous low dose rate radiation group (CLDR). The radiation doses were 0, 2, 4 and 8 Gy. Total cell number and cell viability were determined by trypan blue. Clone forming assay was used to evaluate the cell proliferation ability. The percentage of apoptosis cells was analyzed by flow cytometry. Western blot was used to detect the protein expression levels of PHLPP2, PTEN and Bax. Results: Compared with SDR and FDR groups, the total cell number and survival fraction of CLDR group decreased. The relative biological effect (RBE) for 125I seeds compared with 6 MV X-rays was 1.41. The percentage of apoptosis cells of CLDR group was significantly increased (t=-15.08, -11.99, P<0.05). The expression level of Bax increased in CLDR group, while no obvious changes were observed on PHLPP2 and PTEN among three groups. Conclusions: The expression level of PHLPP2 increases in SDR, FDR and CLDR group, while it seems that it was not influenced by dose rate. The expression level of Bax increased in three groups, while more colorectal CL187 cells in CLDR group may be killed due to the increase of Bax expression. (authors)

  4. Biological effects of low doses of radiation at low dose rate

    International Nuclear Information System (INIS)

    The purpose of this report was to examine available scientific data and models relevant to the hypothesis that induction of genetic changes and cancers by low doses of ionizing radiation at low dose rate is a stochastic process with no threshold or apparent threshold. Assessment of the effects of higher doses of radiation is based on a wealth of data from both humans and other organisms. 234 refs., 26 figs., 14 tabs

  5. The different biological effects of single, fractionated and continuous low dose rate irradiation on CL187 colorectal cancer cells

    International Nuclear Information System (INIS)

    To determine the biological effectiveness of single, fractionated and continuous low dose rate irradiation on the human colorectal cancer cell line CL187 in vitro and explore the cellular mechanisms. The CL187 cells were exposed to radiation of 6 MV X-ray at a high dose rate of 4Gy/min and 125I seed at a low dose rate of 2.77 cGy/h. Three groups were employed: single dose radiation group (SDR), fractionated dose radiation group (FDR) by 2Gy/f and continuous low dose rate radiation group (CLDR). Four radiation doses 2, 4, 6 and 8Gy were chosen and cells without irradiation as the control. The responses of CL187 cells to distinct modes of radiation were evaluated by the colony-forming assay, cell cycle progression as well as apoptosis analysis. In addition, we detected the expression patterns of DNA-PKcs, Ku70 and Ku80 by Western blotting. The relative biological effect for 125I seeds compared with 6 MV X-ray was 1.42. 48 hrs after 4Gy irradiation, the difference between proportions of cells at G2/M phase of SDR and CLDR groups were statistically significant (p = 0.026), so as the FDR and CLDR groups (p = 0.005). 48 hrs after 4Gy irradiation, the early apoptotic rate of CLDR group was remarkably higher than SDR and FDR groups (CLDR vs. SDR, p = 0.001; CLDR vs. FDR, p = 0.02), whereas the late apoptotic rate of CLDR group increased significantly compared with SDR and FDR group (CLDR vs. SDR, p = 0.004; CLDR vs. FDR, p = 0.007). Moreover, DNA-PKcs and Ku70 expression levels in CLDR-treated cells decreased compared with SDR and FDR groups. Compared with the X-ray high dose rate irradiation, 125I seeds CLDR showed more effective induction of cell apoptosis and G2/M cell cycle arrest. Furthermore, 125I seeds CLDR could impair the DNA repair capability by down-regulating DNA-PKcs and Ku70 expression

  6. Optimization strategies for pulsed low-dose-rate IMRT of recurrent lung and head and neck cancers.

    Science.gov (United States)

    Kang, Shengwei; Lang, Jinyi; Wang, Pei; Li, Jie; Lin, Muhan; Chen, Xiaoming; Guo, Ming; Chen, Fu; Chen, Lili; Ma, Charlie Ming

    2014-01-01

    Pulsed low-dose-rate radiotherapy (PLDR) has been proven to be a valid method of reirradiation. Previous studies of recurrent cancer radiotherapy were mainly based on conventional 3D CRT and VMAT delivery techniques. There are difficulties in IMRT planning using existing commercial treatment planning systems (TPS) to meet the PLDR protocol. This work focuses on PLDR using ten-field IMRT and a commercial TPS for two specific sites: recurrent lung cancers and head and neck cancers. Our PLDR protocol requires that the maximum dose to the PTV be less than 0.4 Gy and the mean dose to be 0.2 Gy per field. We investigated various planning strategies to meet the PLDR requirements for 20 lung and head and neck patients. The PTV volume for lung cases ranged from 101.7 to 919.4 cm3 and the maximum dose to the PTV ranged from 0.22 to 0.39 Gy. The PTV volume for head and neck cases ranged from 66.2 to 282.1 cm3 and the maximum dose to the PTV ranged from 0.21 to 0.39 Gy. With special beam arrangements and dosimetry parameters, it is feasible to use a commercial TPS to generate quality PLDR IMRT plans for lung and head and neck reirradiation. PMID:24892337

  7. Low-dose-rate brachytherapy for patients with transurethral resection before implantation in prostate cancer: long-term results

    Energy Technology Data Exchange (ETDEWEB)

    Prada, Pedro J.; Anchuelo, Javier; Blanco, Ana Garcia; Paya, Gema; Cardenal, Juan; Acuña, Enrique; Ferri, Maria [Department of Radiation Oncology, Hospital Universitario Marqués de Valdecilla, Santander, Cantabria (Spain); Vazquez, Andres; Pacheco, Maite; Sanchez, Jesica [Department of Radiation Physics, Hospital Universitario Marqués de Valdecilla, Santander, Cantabria (Spain)

    2016-01-15

    Objectives: We analyzed the long-term oncologic outcome for patients with prostate cancer and transurethral resection who were treated using low-dose-rate (LDR) prostate brachytherapy. Methods and Materials: From January 2001 to December 2005, 57 consecutive patients were treated with clinically localized prostate cancer. No patients received external beam radiation. All of them underwent LDR prostate brachytherapy. Biochemical failure was defined according to the 'Phoenix consensus'. Patients were stratified as low and intermediate risk based on The Memorial Sloan Kettering group definition. Results: The median follow-up time for these 57 patients was 104 months. The overall survival according to Kaplan-Meier estimates was 88% (±6%) at 5 years and 77% (±6%) at 12 years. The 5 and 10 years for failure in tumour-free survival (TFS) was 96% and respectively (±2%), whereas for biochemical control was 94% and respectively (±3%) at 5 and 10 years, 98% (±1%) of patients being free of local recurrence. A patient reported incontinence after treatment (1.7%). The chronic genitourinary complains grade I were 7% and grade II, 10%. At six months 94% of patients reported no change in bowel function. Conclusions: The excellent long-term results and low morbidity presented, as well as the many advantages of prostate brachytherapy over other treatments, demonstrates that brachytherapy is an effective treatment for patients with transurethral resection and clinical organ-confined prostate cancer. (author)

  8. Permanent interstitial low-dose-rate brachytherapy for patients with low risk prostate cancer. An interim analysis of 312 cases

    International Nuclear Information System (INIS)

    The biochemical relapse-free survival (bRFS) rate after treatment with permanent iodine-125 seed implantation (PSI) or combined seeds and external beam radiotherapy (COMB) for clinical stage T1-T2 localized prostate cancer is a clinically relevant endpoint. The goal of this work was to evaluate the influence of relevant patient- and treatment-related factors. The study population comprised 312 consecutive patients treated with permanent seed implantation. All patients were evaluable for analysis of overall survival (OS) and disease-specific survival (DSS), 230 for bRFS, of which 192 were in the PSI group and 38 in the COMB group. The prescribed minimum peripheral dose was 145 Gy for PSI, for COMB 110 Gy implant and external beam radiotherapy of 45 Gy. The median follow-up time was 33 months (range 8-66 months). bRFS was defined as a serum prostate-specific antigen (PSA) level ≤ 0.2 ng/ml at last follow-up. Overall, the actuarial bRFS at 50 months was 88.4 %. The 50-month bRFS rate for PSI and COMB was 90.9 %, and 77.2 %, respectively. In the univariate analysis, age in the categories ≤ 63 and > 63 years (p < 0.00), PSA nadir (≤ 0.5 ng/ml and > 0.5 ng/ml) and PSA bounce (yes/no) were the significant predicting factors for bRFS. None of the other patient and treatment variables (treatment modality, stage, PSA, Gleason score, risk group, number of risk factors, D90 and various other dose parameters) were found to be a statistically significant predictor of 50-month bRFS. The biochemical failure rates were low in this study. As a proof of principle, our large monocenteric analysis shows that low-dose-rate brachytherapy is an effective and safe procedure for patients with early stage prostate cancer. (orig.)

  9. Permanent interstitial low-dose-rate brachytherapy for patients with low risk prostate cancer. An interim analysis of 312 cases

    Energy Technology Data Exchange (ETDEWEB)

    Badakhshi, Harun; Graf, Reinhold; Budach, Volker; Wust, Peter [University Hospital Berlin, Department for Radiation Oncology of Charite School of Medicine, Berlin (Germany)

    2015-04-01

    The biochemical relapse-free survival (bRFS) rate after treatment with permanent iodine-125 seed implantation (PSI) or combined seeds and external beam radiotherapy (COMB) for clinical stage T1-T2 localized prostate cancer is a clinically relevant endpoint. The goal of this work was to evaluate the influence of relevant patient- and treatment-related factors. The study population comprised 312 consecutive patients treated with permanent seed implantation. All patients were evaluable for analysis of overall survival (OS) and disease-specific survival (DSS), 230 for bRFS, of which 192 were in the PSI group and 38 in the COMB group. The prescribed minimum peripheral dose was 145 Gy for PSI, for COMB 110 Gy implant and external beam radiotherapy of 45 Gy. The median follow-up time was 33 months (range 8-66 months). bRFS was defined as a serum prostate-specific antigen (PSA) level ≤ 0.2 ng/ml at last follow-up. Overall, the actuarial bRFS at 50 months was 88.4 %. The 50-month bRFS rate for PSI and COMB was 90.9 %, and 77.2 %, respectively. In the univariate analysis, age in the categories ≤ 63 and > 63 years (p < 0.00), PSA nadir (≤ 0.5 ng/ml and > 0.5 ng/ml) and PSA bounce (yes/no) were the significant predicting factors for bRFS. None of the other patient and treatment variables (treatment modality, stage, PSA, Gleason score, risk group, number of risk factors, D90 and various other dose parameters) were found to be a statistically significant predictor of 50-month bRFS. The biochemical failure rates were low in this study. As a proof of principle, our large monocenteric analysis shows that low-dose-rate brachytherapy is an effective and safe procedure for patients with early stage prostate cancer. (orig.) [German] Das biochemisch rezidivfreie Ueberleben (bRFS) nach der Brachytherapie mit permanenter Iod-125-Seed-Implantation (PSI) oder in Kombination mit externer Radiotherapie (COMB) ist beim Patienten mit fruehem Prostatakarzinom (T1/T2) ein relevanter

  10. The OER at low dose-rates

    International Nuclear Information System (INIS)

    The author comments on a letter (Kal, H.B., and Barendsen, G.W., 1976, Br. J. Radiol., vol. 49, 1049) reviewing published values of the OER for low dose-rate γ-rays. Artefacts of the system may have been responsible for one very low OER value taken from work carried out in the early 1960s, but later work in which these problems were eliminated still yielded OER values significantly lower than for acute X- or γ-ray exposures. Consideration is given to significance of this reduction in OER for γ-rays at the low dose-rates characteristic of interstitial implants. The performance of these interstitial implants may be comparable with the most sophisticated and expensive pion or heavy ion treatments. (U.K.)

  11. Mortality risk coefficients for radiation-induced cancer at high doses and dose-rates, and extrapolation to the low dose domain.

    Science.gov (United States)

    Liniecki, J

    1989-01-01

    Risk coefficients for life-long excessive mortality due to radiation-induced cancers are presented, as derived in 1988 by the U.N. Scientific Committee on the Effects of Atomic Radiation (UNSCEAR), principally on the basis of follow-up from A-bomb survivors in Japan, over the period from 1950 through 1985. The data are based on the new, revised dosimetry (DS 86) in the two cities, and reflect the effects of high and intermediate doses of basically low LET radiation delivered instantaneously. The author presents arguments relevant to the extrapolation of the risk to the low dose (dose rate) domain, as outlined by UNSCEAR in its 1986, and the NCRP (USA) in its 1980, (no 64), reports. The arguments are based on models and dose-response relationships for radiation action, derived from data on cellular radiobiology, animal experiments on radiation-induced cancers and life shortening, as well as the available limited human epidemiological evidence. The available information points to the lower effectiveness of sparsely ionizing radiation at low doses and low dose-rates, as compared with that observed for high, acutely delivered doses. The possible range of the reduction values (DREF) is presented. For high LET radiations, the evidence is less extensive and sometimes contradictory; however, it does not point to a reduction of the effectiveness at low doses/dose-rates, relative to the high dose domain. Practical consequences of these facts are considered. PMID:2489419

  12. Assessment of the expected harm from prenatal irradiation with low doses and low dose rates

    International Nuclear Information System (INIS)

    The validity of the coefficients, suggested by ICRP (Publication 45) for assessment of the risk from prenatal irradiation with low doses and low dose rates is discussed. This includes: development of lethal and curable cancer, severe genetic defects, death before implantation and retarded mental development. Summarizing the individual assessment, the total harm from prenatal irradiation with 1 mvSv have been estimated at 4,9.104 lost years. The expected harm from the additional irradiation of the Bulgarian population during the first year after the Chernobyl accident is evaluated on that basis, taking into account the number of expected pregnancies among Bulgarian women in reproductive age and the individual effective equivalent doses. 15 refs

  13. Advanced Computational Approaches for Characterizing Stochastic Cellular Responses to Low Dose, Low Dose Rate Exposures

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Bobby, R., Ph.D.

    2003-06-27

    applications of NEOTRANS2, indicate that nonlinear threshold-type, dose-response relationships for excess stochastic effects (problematic nonlethal mutations, neoplastic transformation) should be expected after exposure to low linear energy transfer (LET) gamma rays or gamma rays in combination with high-LET alpha radiation. Similar thresholds are expected for low-dose-rate low-LET beta irradiation. We attribute the thresholds to low-dose, low-LET radiation induced protection against spontaneous mutations and neoplastic transformations. The protection is presumed mainly to involve selective elimination of problematic cells via apoptosis. Low-dose, low-LET radiation is presumed to trigger wide-area cell signaling, which in turn leads to problematic bystander cells (e.g., mutants, neoplastically transformed cells) selectively undergoing apoptosis. Thus, this protective bystander effect leads to selective elimination of problematic cells (a tissue cleansing process in vivo). However, this protective bystander effects is a different process from low-dose stimulation of the immune system. Low-dose, low-LET radiation stimulation of the immune system may explain why thresholds for inducing excess cancer appear much larger (possibly more than 100-fold larger) than thresholds for inducing excess mutations and neoplastic transformations, when the dose rate is low. For ionizing radiation, the current risk assessment paradigm is such that the relative risk (RR) is always ¡Ý 1, no matter how small the dose. Our research results indicate that for low-dose or low-dose-rate, low-LET irradiation, RR < 1 may be more the rule than the exception. Directly tied to the current RR paradigm are the billion-dollar cleanup costs for radionuclide-contaminated DOE sites. Our research results suggest that continued use of the current RR paradigm for which RR ¡Ý 1 could cause more harm than benefit to society (e.g., by spreading unwarranted fear about phantom excess risks associated with low-dose low

  14. Analysis of risk factors for mandibular bone radionecrosis after exclusive low dose-rate brachytherapy for oral cancer

    International Nuclear Information System (INIS)

    Background: Brachytherapy is widely adopted as an exclusive treatment of T1/T2 oral cancer with a high probability of definitive cure. Therefore, any major complication, like mandibular bone necrosis, should be avoided. Many risk factors, either clinical or technical, have been considered in the literature. Materials and methods: One hundred consecutive interstitial iridium LDR treatments for early cancers of the tongue and floor of the mouth performed from January 1989 to November 1993 were reviewed. An analysis of some simple technical parameters (total dose, dose-rate, reference volume, linear activity, total reference kerma) was performed in order to identify the main physical risk factors. Moreover, total dose was recalculated as extrapolated responsive dose for normal tissue complications. Results: Bone necrosis was observed in 10 out of 100 patients with a median follow-up of 38 months. No significant incidence of this complication was observed when tumor site (mobile tongue versus floor of the mouth), dental status or total physical dose were considered. A significant correlation between the incidence of bone necrosis and two main parameters was found, i.e. dose-rate (P 3). Bone necrosis is clearly related to both these parameters since most cases (i.e. 80%) were observed in the subgroup over the volume and dose-rate threshold

  15. Ameliorative effects of low dose/low dose-rate irradiation on reactive oxygen species-related diseases model mice

    International Nuclear Information System (INIS)

    β-cells against superoxide generated by glycation reaction evoked by high glucose environment. Continuous irradiation at 0.63 mGy/hr from 28 days of age elongates life span, and recovers splenic inflammatory response in Klotho-mice bearing ageing syndrome. The radiation increases anti-oxidants in liver, implicating the prevention of ageing through the suppression of cellular oxidative damages. Our results suggest that low dose/low dose-rate radiation effectively ameliorates diseases related to reactive oxygen species, and elongates life span of animals, at least in part through the stimulation of protective responses against oxidative stress. These findings are important not only for clinical use of low dose/low dose-rate radiation for human diseases, but also for non-cancerous risk estimation at dose and dose rate range argued in legal restrictions. (author)

  16. Pulsed low dose rate brachytherapy for pelvic malignancies

    International Nuclear Information System (INIS)

    Purpose: The pulsed low dose rate remote afterloading unit was designed to combine the radiation safety and isodose optimization advantages of high dose rate technology with the radiobiologic advantages of continuous low dose rate brachytherapy. This is the first report of a prospective clinical trial evaluating the relative incidence of acute toxicity and local control in patients with pelvic malignancies who underwent interstitial or intracavitary brachytherapy with the pulsed low dose rate remote afterloader. Methods and Materials: From 5/11/92-6/21/95, 65 patients underwent 77 brachytherapy procedures as part of their treatment regimen for pelvic malignancies. Using the pulsed low dose rate Selectron, equipped with a single cable-driven 0.3-1.0 Ci Ir192 source, target volume doses of 0.40-0.85 Gy per pulse were prescribed to deliver the clinically determined dose. Forty-five intracavitary and 32 interstitial procedures were performed. Fifty-four patients had primary and 11 recurrent disease. Patients were followed closely to assess incidence of Grade 3-5 acute and delayed toxicity, local control, and survival. Results: With a median follow-up of 16.1 months (range 1-29), 33 patients are NED, 10 alive with disease, 13 dead with disease, 4 dead of intercurrent disease, and 5 lost to follow-up. Local control was maintained until last follow-up or death in 48 cases, local failure occurred in 11, unknown in 5. Grade 3-5 acute toxicities (requiring medical or surgical intervention) occurred in 5 out of 77 procedures (6.5%), delayed complications in 10 patients (15% actuarial incidence at 2 years). In the 52 procedures performed for 42 patients with cervix cancer, the acute toxicity incidence was 5.8%, with a 14% 2-year actuarial incidence of delayed complications. Of 32 interstitial templates performed on 30 patients for pelvic malignancies, there were three incidences of acute toxicity and five delayed toxicities. Conclusion: Using the parameters described for this

  17. Incidence of Second Malignancies in Prostate Cancer Patients Treated With Low-Dose-Rate Brachytherapy and Radical Prostatectomy

    International Nuclear Information System (INIS)

    Purpose: To compare the second malignancy incidence in prostate cancer patients treated with brachytherapy (BT) relative to radical prostatectomy (RP) and to compare both groups with the cancer incidence in the general population. Methods and Materials: From 1998 to 2010, 2418 patients were treated with Iodine 125 prostate BT monotherapy at the British Columbia Cancer Agency, and 4015 referred patients were treated with RP. Cancer incidence was compared with the age-matched general population using standardized incidence ratios (SIRs). Pelvic malignancies included invasive and noninvasive bladder cancer and rectal cancer. Cox multivariable analysis was performed with adjustment for covariates to determine whether treatment (RP vs BT) was associated with second malignancy risk. Results: The median age at BT was 66 years and at RP 62 years. The SIR comparing BT patients with the general population was 1.06 (95% confidence interval [CI] 0.91-1.22) for second malignancy and was 1.53 (95% CI 1.12-2.04) for pelvic malignancy. The SIR comparing RP patients with the general population was 1.11 (95% CI 0.98-1.25) for second malignancy and was 1.11 (95% CI 0.82-1.48) for pelvic malignancy. On multivariable analysis, older age (hazard ratio [HR] 1.05) and smoking (HR 1.65) were associated with increased second malignancy risk (P<.0001). Radical prostatectomy was not associated with a decreased second malignancy risk relative to BT (HR 0.90, P=.43), even when excluding patients who received postprostatectomy external beam radiation therapy (HR 1.13, P=.25). Older age (HR 1.09, P<.0001) and smoking (HR 2.17, P=.0009) were associated with increased pelvic malignancy risk. Radical prostatectomy was not associated with a decreased pelvic malignancy risk compared with BT (HR 0.57, P=.082), even when excluding postprostatectomy external beam radiation therapy patients (HR 0.87, P=.56). Conclusions: After adjustment for covariates, BT patients did not have an increased second

  18. Incidence of Second Malignancies in Prostate Cancer Patients Treated With Low-Dose-Rate Brachytherapy and Radical Prostatectomy

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, Sarah Nicole; Tyldesley, Scott [Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia (Canada); Department of Radiation Oncology, British Columbia Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Hamm, Jeremy [Department of Population Oncology, British Columbia Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Jiang, Wei Ning [Faculty of Medicine, University of British Columbia, Vancouver, British Columbia (Canada); Keyes, Mira; Pickles, Tom [Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia (Canada); Department of Radiation Oncology, British Columbia Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Lapointe, Vince [Department of Medical Physics, British Columbia Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Kahnamelli, Adam [Department of Radiation Oncology, British Columbia Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); McKenzie, Michael [Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia (Canada); Department of Radiation Oncology, British Columbia Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Miller, Stacy [Department of Radiation Oncology, British Columbia Cancer Agency–Centre for the North, Prince George, British Columbia (Canada); Morris, W. James, E-mail: jmorris@bccancer.bc.ca [Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia (Canada); Department of Radiation Oncology, British Columbia Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada)

    2014-11-15

    Purpose: To compare the second malignancy incidence in prostate cancer patients treated with brachytherapy (BT) relative to radical prostatectomy (RP) and to compare both groups with the cancer incidence in the general population. Methods and Materials: From 1998 to 2010, 2418 patients were treated with Iodine 125 prostate BT monotherapy at the British Columbia Cancer Agency, and 4015 referred patients were treated with RP. Cancer incidence was compared with the age-matched general population using standardized incidence ratios (SIRs). Pelvic malignancies included invasive and noninvasive bladder cancer and rectal cancer. Cox multivariable analysis was performed with adjustment for covariates to determine whether treatment (RP vs BT) was associated with second malignancy risk. Results: The median age at BT was 66 years and at RP 62 years. The SIR comparing BT patients with the general population was 1.06 (95% confidence interval [CI] 0.91-1.22) for second malignancy and was 1.53 (95% CI 1.12-2.04) for pelvic malignancy. The SIR comparing RP patients with the general population was 1.11 (95% CI 0.98-1.25) for second malignancy and was 1.11 (95% CI 0.82-1.48) for pelvic malignancy. On multivariable analysis, older age (hazard ratio [HR] 1.05) and smoking (HR 1.65) were associated with increased second malignancy risk (P<.0001). Radical prostatectomy was not associated with a decreased second malignancy risk relative to BT (HR 0.90, P=.43), even when excluding patients who received postprostatectomy external beam radiation therapy (HR 1.13, P=.25). Older age (HR 1.09, P<.0001) and smoking (HR 2.17, P=.0009) were associated with increased pelvic malignancy risk. Radical prostatectomy was not associated with a decreased pelvic malignancy risk compared with BT (HR 0.57, P=.082), even when excluding postprostatectomy external beam radiation therapy patients (HR 0.87, P=.56). Conclusions: After adjustment for covariates, BT patients did not have an increased second

  19. Long-term observation of 64 patients with roentgenographically occult lung cancer treated with external irradiation and intraluminal irradiation using low-dose-rate iridium

    International Nuclear Information System (INIS)

    Therapeutic results of intraluminal irradiation were analyzed in 64 patients with roentgenographically occult lung cancer (ROLC). The subjects were 64 patients who underwent intraluminal irradiation between 1987 and 2003. Radiotherapy was performed by combining external irradiation with intraluminal irradiation using low-dose-rate iridium (four 370-MBq wires) through a catheter with a spacer. The doses of radiation were 0-70 Gy (median value 46 Gy) by external irradiation and 10-60 Gy (median value 29.3 Gy) by intraluminal irradiation. The therapeutic effect was complete response (CR) in 63 patients and partial response (PR) in 1 patient, and local recurrence was observed in a PR case and in seven of the 63 patients who showed CR. The 5-year overall and relapse-free survival rates were 56 (95% confidence interval (CI), 43-69%) and 55% (95% CI, 43-68%), respectively. Fatal pulmonary hemorrhage was observed in one case. Considering the facts that ROLC often occurs as multiple cancers and that many patients with ROLC have reduced lung function, radiation therapy by a combination of intraluminal and external irradiation may replace surgery as the first choice for the treatment of this disease. (author)

  20. Genome instability induced by extreme low dose/low dose rate heavy ion radiation

    International Nuclear Information System (INIS)

    We irradiated normal human fibroblasts (HFL III) with carbon ions (290 MeV/u, 70 keV/um) at very low dose (1 mGy total dose) and low dose rate (1 mGy/6 h) and observed the growth kinetics for several months by continuous culturing. The growth of carbon irradiated cells started to slow down much earlier than that of non-irradiated control cells before reaching senescence. On the other hand, HFL III cells irradiated at the same dose and the dose rate of gamma-rays were slightly accelerated their growth. Our measurements on DNA double strand break (DSB) such as gamma-H2AX foci revealed a higher number of foci in carbon irradiated cells than in gamma-irradiated cells at a cell passage near senescence. Taken together, our results suggest that high linear energy transfer (LET) radiation causes different effects than low LET radiation even at very low doses and that the effect of single low dose irradiation can affect the stability of genome many generations after irradiation. (author)

  1. Bystander Effects Induced by Continuous Low-Dose-Rate 125I Seeds Potentiate the Killing Action of Irradiation on Human Lung Cancer Cells In Vitro

    International Nuclear Information System (INIS)

    Purpose: To investigate bystander effects of low-dose-rate (LDR) 125I seed irradiation on human lung cancer cells in vitro. Methods and Materials: A549 and NCI-H446 cell lines of differing radiosensitivity were directly exposed to LDR 125I seeds irradiation for 2 or 4 Gy and then cocultured with nonirradiated cells for 24 hours. Induction of micronucleus (MN), γH2AX foci, and apoptosis were assayed. Results: After 2 and 4 Gy irradiation, micronucleus formation rate (MFR) and apoptotic rate of A549 and NCI-H446 cells were increased, and the MFR and apoptotic rate of NCI-H446 cells was 2.1-2.8 times higher than that of A549 cells. After coculturing nonirradiated bystander cells with 125I seed irradiated cells for 24 hours, MFR and the mean number of γH2AX foci/cells of bystander A549 and NCI-H446 cells were similar and significantly higher than those of control (p 125I seeds could induce bystander effects, which potentiate the killing action on tumor cells and compensate for the influence of nonuniform distribution of radiation dosage on therapeutic outcomes

  2. Microdosimetric approach to the anlysis of cell responses at low dose and low dose rate

    International Nuclear Information System (INIS)

    An approach to the problem of radiation response is proposed and described by which effects produced at low doses and dose rates can be understood as the consequences of radiation absorption events in the nucleus of a single relevant cell and in its DNA. Radiation quality appears as the consequence of two related probabilities, that of energy deposition in the cell nucleus and that of energy deposition in DNA. The starting point is a ''gross sensitive volume'', GSV, identified with an average mammalian cell nucleus and composed of smaller sensitive volumes, identified with some critical parts of the DNA genome. The GSV leads to the definitions of an ''elemental dose'', the ''integral probability of responses of the GSV population'', and the smaller volumes lead to a ''relative local efficiency''. This approach is applied to various biological endpoints illustrating its merits. The level of dose below which the fraction of hit cells depends linearly on absorbed dose and is independent of dose rate, is delineated. Finally, guide lines for designing low dose and low dose rate experiments are proposed. (author)

  3. Prevalance rate of low-dose CT lung cancer screening. Results of a questionnaire survey of member facilities of Japan society of ningen dock with special concerns regarding the actual status and disincentives for implementing such screening

    International Nuclear Information System (INIS)

    We conducted a survey of member facilities of the Japan Society of Ningen Dock to elucidate the actual status of chest computed tomography (CT) screening and the reasons for not being able to change to low-dose CT. We sent a questionnaire consisting of 9 items to 531 member facilities in July 2010, response by facsimile to obtain an analysis. The prevalence rate of low-dose CT lung cancer screening slightly increased to 35% in comparison with the former survey done in November 2008. Some facilities indicated some shift in tube current to a lower range even though this was insufficient to meet the definition of low-dose CT. This reflects their thinking of ''Even with knowledge, there is strong hesitation to change to low-dose CT''. Among the reasons why they did not change to low-dose CT, a priority for high quality images was the top reason among problems of devices and performance. Informed consent was not yet adequate. It is necessary for manufactures to develop better technology to improve the image quality of low-dose CT and to report enough information to clinicians. On the medical side, perception of the necessity for appropriate reduction of radiation dose and the decision to move to low-dose CT would be of crucial significance for facility heads as well as radiologists and technicians. (author)

  4. External beam radiation therapy and a low-dose-rate brachytherapy boost without or with androgen deprivation therapy for prostate cancer

    International Nuclear Information System (INIS)

    Purpose: To assess outcomes with external beam radiation therapy (EBRT) and a low-dose-rate (LDR) brachytherapy boost without or with androgen deprivation therapy (ADT) for prostate cancer. Materials and Methods: From January 2001 through August 2011, 120 intermediate-risk or high-risk prostate cancer patients were treated with EBRT to a total dose of 4,500 cGy in 25 daily fractions and a palladium-103 LDR brachytherapy boost of 10,000 cGy (n = 90) or an iodine-125 LDR brachytherapy boost of 11,000 cGy (n = 30). ADT, consisting of a gonadotropin-releasing hormone agonist ± an anti-androgen, was administered to 29/92 (32%) intermediate-risk patients for a median duration of 4 months and 26/28 (93%) high-risk patients for a median duration of 28 months. Results: Median follow-up was 5.2 years (range, 1.1-12.8 years). There was no statistically-significant difference in biochemical disease-free survival (bDFS), distant metastasis-free survival (DMFS), or overall survival (OS) without or with ADT. Also, there was no statistically-significant difference in bDFS, DMFS, or OS with a palladium-103 vs. an iodine-125 LDR brachytherapy boost. Conclusions: There was no statistically-significant difference in outcomes with the addition of ADT, though the power of the current study was limited. The Radiation Therapy Oncology Group 0815 and 0924 phase III trials, which have accrual targets of more than 1,500 men, will help to clarify the role ADT in locally-advanced prostate cancer patients treated with EBRT and a brachytherapy boost. Palladium-103 and iodine-125 provide similar bDFS, DMFS, and OS. (author)

  5. External beam radiation therapy and a low-dose-rate brachytherapy boost without or with androgen deprivation therapy for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Strom, Tobin J.; Hutchinson, Sean Z.; Shrinath, Kushagra; Cruz, Alex A.; Figura, Nicholas B.; Nethers, Kevin; Biagioli, Matthew C.; Fernandez, Daniel C.; Heysek, Randy V.; Wilder, Richard B., E-mail: richard.wilder@moffitt.org [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (United States)

    2014-07-15

    Purpose: To assess outcomes with external beam radiation therapy (EBRT) and a low-dose-rate (LDR) brachytherapy boost without or with androgen deprivation therapy (ADT) for prostate cancer. Materials and Methods: From January 2001 through August 2011, 120 intermediate-risk or high-risk prostate cancer patients were treated with EBRT to a total dose of 4,500 cGy in 25 daily fractions and a palladium-103 LDR brachytherapy boost of 10,000 cGy (n = 90) or an iodine-125 LDR brachytherapy boost of 11,000 cGy (n = 30). ADT, consisting of a gonadotropin-releasing hormone agonist ± an anti-androgen, was administered to 29/92 (32%) intermediate-risk patients for a median duration of 4 months and 26/28 (93%) high-risk patients for a median duration of 28 months. Results: Median follow-up was 5.2 years (range, 1.1-12.8 years). There was no statistically-significant difference in biochemical disease-free survival (bDFS), distant metastasis-free survival (DMFS), or overall survival (OS) without or with ADT. Also, there was no statistically-significant difference in bDFS, DMFS, or OS with a palladium-103 vs. an iodine-125 LDR brachytherapy boost. Conclusions: There was no statistically-significant difference in outcomes with the addition of ADT, though the power of the current study was limited. The Radiation Therapy Oncology Group 0815 and 0924 phase III trials, which have accrual targets of more than 1,500 men, will help to clarify the role ADT in locally-advanced prostate cancer patients treated with EBRT and a brachytherapy boost. Palladium-103 and iodine-125 provide similar bDFS, DMFS, and OS. (author)

  6. Long-Term Efficacy and Toxicity of Low-Dose-Rate {sup 125}I Prostate Brachytherapy as Monotherapy in Low-, Intermediate-, and High-Risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kittel, Jeffrey A.; Reddy, Chandana A.; Smith, Kristin L.; Stephans, Kevin L.; Tendulkar, Rahul D. [Department of Radiation Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio (United States); Ulchaker, James; Angermeier, Kenneth; Campbell, Steven; Stephenson, Andrew; Klein, Eric A. [Department of Urology, Cleveland Clinic Glickman Urological and Kidney Institute, Cleveland, Ohio (United States); Wilkinson, D. Allan [Department of Radiation Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio (United States); Ciezki, Jay P., E-mail: ciezkij@ccf.org [Department of Radiation Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio (United States)

    2015-07-15

    Purpose/Objectives: To report long-term efficacy and toxicity for a single-institution cohort of patients treated with low-dose-rate prostate brachytherapy permanent implant (PI) monotherapy. Methods and Materials: From 1996 to 2007, 1989 patients with low-risk (61.3%), intermediate-risk (29.8%), high-intermediate-risk (4.5%), and high-risk prostate cancer (4.4%) were treated with PI and followed up prospectively in a registry. All patients were treated with {sup 125}I monotherapy to 144 Gy. Late toxicity was coded retrospectively according to a modified Common Terminology Criteria for Adverse Events 4.0 scale. The rates of biochemical relapse-free survival (bRFS), distant metastasis-free survival (DMFS), overall survival (OS), and prostate cancer–specific mortality (PCSM) were calculated. We identified factors associated with late grade ≥3 genitourinary (GU) and gastrointestinal (GI) toxicity, bRFS, DMFS, OS, PCSM, and incontinence. Results: The median age of the patients was 67 years, and the median overall and prostate-specific antigen follow-up times were 6.8 years and 5.8 years, respectively. The overall 5-year rates for bRFS, DMFS, OS, and PCSM were 91.9%, 97.8%, 93.7%, and 0.71%, respectively. The 10-year rates were 81.5%, 91.5%, 76.1%, and 2.5%, respectively. The overall rates of late grade ≥3 GU and GI toxicity were 7.6% and 0.8%, respectively. On multivariable analysis, age and prostate length were significantly associated with increased risk of late grade ≥3 GU toxicity. The risk of incontinence was highly correlated with both pre-PI and post-PI transurethral resection of the prostate. Conclusions: Prostate brachytherapy as monotherapy is an effective treatment for low-risk and low-intermediate-risk prostate cancer and appears promising as a treatment for high-intermediate-risk and high-risk prostate cancer. Significant long-term toxicities are rare when brachytherapy is performed as monotherapy.

  7. Long-Term Efficacy and Toxicity of Low-Dose-Rate 125I Prostate Brachytherapy as Monotherapy in Low-, Intermediate-, and High-Risk Prostate Cancer

    International Nuclear Information System (INIS)

    Purpose/Objectives: To report long-term efficacy and toxicity for a single-institution cohort of patients treated with low-dose-rate prostate brachytherapy permanent implant (PI) monotherapy. Methods and Materials: From 1996 to 2007, 1989 patients with low-risk (61.3%), intermediate-risk (29.8%), high-intermediate-risk (4.5%), and high-risk prostate cancer (4.4%) were treated with PI and followed up prospectively in a registry. All patients were treated with 125I monotherapy to 144 Gy. Late toxicity was coded retrospectively according to a modified Common Terminology Criteria for Adverse Events 4.0 scale. The rates of biochemical relapse-free survival (bRFS), distant metastasis-free survival (DMFS), overall survival (OS), and prostate cancer–specific mortality (PCSM) were calculated. We identified factors associated with late grade ≥3 genitourinary (GU) and gastrointestinal (GI) toxicity, bRFS, DMFS, OS, PCSM, and incontinence. Results: The median age of the patients was 67 years, and the median overall and prostate-specific antigen follow-up times were 6.8 years and 5.8 years, respectively. The overall 5-year rates for bRFS, DMFS, OS, and PCSM were 91.9%, 97.8%, 93.7%, and 0.71%, respectively. The 10-year rates were 81.5%, 91.5%, 76.1%, and 2.5%, respectively. The overall rates of late grade ≥3 GU and GI toxicity were 7.6% and 0.8%, respectively. On multivariable analysis, age and prostate length were significantly associated with increased risk of late grade ≥3 GU toxicity. The risk of incontinence was highly correlated with both pre-PI and post-PI transurethral resection of the prostate. Conclusions: Prostate brachytherapy as monotherapy is an effective treatment for low-risk and low-intermediate-risk prostate cancer and appears promising as a treatment for high-intermediate-risk and high-risk prostate cancer. Significant long-term toxicities are rare when brachytherapy is performed as monotherapy

  8. Low-dose radiation: a cause of breast cancer

    International Nuclear Information System (INIS)

    It is likely that the breast is the organ most sensitive to radiation carcinogenesis in postpubertal women. Studies of different exposed populations have yielded remarkably consistent results, in spite of wide differences in underlying breast cancer rates and conditions of exposure. Excess risk is approximately proportional to dose, and is relatively independent of ionization density and fractionization of dose. This implies that the risk associated with low-dose exposures to ionizing radiation can be estimated with some confidence from higher-dose data. Excess risk is heavily dependent on age at exposure but relatively independent of population differences in normal risk. The temporal patterns after exposure of both radiation-induced and naturally occurring breast cancer are similar, suggesting a strong influence of factors other than radiation on radiation-induced breast cancer. Uncertainties remain about risks from exposures before puberty and after menopause

  9. Dosimetric characterization of the GammaClip™169Yb low dose rate permanent implant brachytherapy source for the treatment of nonsmall cell lung cancer postwedge resection

    International Nuclear Information System (INIS)

    Purpose: A novel 169Yb low dose rate permanent implant brachytherapy source, the GammaClip™, was developed by Source Production and Equipment Co. (New Orleans, LA) which is designed similar to a surgical staple while delivering therapeutic radiation. In this report, the brachytherapy source was characterized in terms of “Dose calculation for photon-emitting brachytherapy sources with average energy higher than 50 keV: Report of the AAPM and ESTRO” by Perez-Calatayud et al. [Med. Phys. 39, 2904–2929 (2012)] using the updated AAPM Task Group Report No. 43 formalism.Methods: Monte Carlo calculations were performed using Monte Carlo N-Particle 5, version 1.6 in water and air, the in-air photon spectrum filtered to remove photon energies below 10 keV in accordance with TG-43U1 recommendations and previously reviewed 169Yb energy cutoff levels [D. C. Medich, M. A. Tries, and J. M. Munro, “Monte Carlo characterization of an Ytterbium-169 high dose rate brachytherapy source with analysis of statistical uncertainty,” Med. Phys. 33, 163–172 (2006)]. TG-43U1 dosimetric data, including SK, D-dot (r,θ), Λ, gL(r), F(r, θ), φan(r), and φan were calculated along with their statistical uncertainties. Since the source is not axially symmetric, an additional set of calculations were performed to assess the resulting axial anisotropy.Results: The brachytherapy source's dose rate constant was calculated to be (1.22 ± 0.03) cGy h−1 U−1. The uncertainty in the dose to water calculations, D-dot (r,θ), was determined to be 2.5%, dominated by the uncertainties in the cross sections. The anisotropy constant, φan, was calculated to be 0.960 ± 0.011 and was obtained by integrating the anisotropy factor between 1 and 10 cm using a weighting factor proportional to r−2. The radial dose function was calculated at distances between 0.5 and 12 cm, with a maximum value of 1.20 at 5.15 ± 0.03 cm. Radial dose values were fit to a fifth order polynomial and dual exponential

  10. Enhanced low dose rate sensitivity (ELDRS) in bipolar linear circuits

    International Nuclear Information System (INIS)

    Enhanced Low Dose Rate Sensitivity (ELDRS) in bipolar linear transistors was first identified in bipolar microcircuit transistors in 1991 and demonstrated in bipolar linear circuits in 1994. Since then it has been a major topic of research, characterization and analysis. Data compendia of low dose rate enhancement factors were presented in 1996, 2001 and 2008, identifying 30 unique widely used circuit types as susceptible to ELDRS. A space experiment has verified the phenomenon for ELDRS parts in space. Early work on ELDRS was directed toward identifying mechanisms, characterizing circuits and developing hardness assurance methods, concentrating on accelerated testing techniques. More recently the research has focused on the effects of pre-irradiation elevated temperature stress (PETS), final passivation layers and molecular hydrogen in the package on the ELDRS response, providing a basis for developing ELDRS-free parts. In this review paper the phenomena of ELDRS, its characteristics, the most recent modeling results and the latest hardness assurance techniques are discussed. (author)

  11. A database for a meta-analysis of cancer risk in animals at low doses and dose rates of ionising radiation

    International Nuclear Information System (INIS)

    Results of animal experiments listed in the International Radiobiology Archives (I.R.A.), complemented with data published in peer-reviewed literature since 1996 have been assembled in one data base and the induction of cancer at low doses has been analyzed. In total, approximately 100 separate, independent sets of experimental data have been studied. The main objective of this work is to provide information on radiation risk in the 0-500 mGy range. The data analyzed were those for which no significant reduction of life span was observed in exposed animals; or doses did not exceed 1 Gy; or no cancer was observed in exposed animals. With these criteria data sets with organ doses well in excess of 1 Gy were taken into account. In animals with a low natural incidence of cancer, the difference between the observed number of cancer cases and the prediction of the Linear No-threshold (LNT) hypothesis was compared in each experiment. Following intake of alpha emitters, the number of cancers observed is about 60% of the number of number predicted by the LNT, and only about 56% following intake of beta emitters. In some experiments, statistically weak protective effects were observed following the intake of alpha emitters, whereas apparently statistically strong protective effects were observed in some groups of animals exposed to beta radiation. In animals exposed to low LET radiation and neutrons, both clear excess cancer risk and clear cancer deficits were observed. In a second series of analysis, the several modeling approaches were used to model dose-response. Linear, logistic and probit regression models were examined. For all the data sets examined in this work, the analysis of the data using the LOGISTIC model seems to indicate surplus of negative slopes in the dose-response fits. Finer analyses are underway to determine what parameters are common to experiments which display similar dose-response relationships. If they exist in a sufficient number of experiments

  12. Spectrum of early lung cancer presentation in low-dose screening CT: a pictorial review.

    Science.gov (United States)

    Rampinelli, Cristiano; Calloni, Sonia Francesca; Minotti, Marta; Bellomi, Massimo

    2016-06-01

    The typical presentation of early stage lung cancers on low-dose CT screening are non-calcified pulmonary nodules. However, there is a wide spectrum of unusual focal abnormalities that can be early presentations of lung cancer. These abnormalities include, for example, cancers associated with 'cystic airspaces' or scar-like cancers. The detection of lung cancer with low-dose CT can be affected by the absence of intravenous contrast medium. As a consequence, endobronchial and central lesions can be difficult to recognize, raising the potential for missed cancers. Focal lesions arising within pre-existing lung disease, such as lung fibrosis or apical scars, can also be early lung cancer manifestations and deserve particular consideration as recognition of these lesions may be hindered by the underlying disease. Furthermore, the unpredictable growth rate of lung cancer, which ranges from indolent to aggressive cancers, necessitates attention to the wide spectrum of progression in lung cancer appearance on serial low-dose CT scans. In this pictorial review we discuss the spectrum of early lung cancer presentation in low-dose CT screening, highlighting typical as well as unusual radiological features and the varied growth rates of early lung cancer. Teaching Points • There is a wide spectrum of early presentations of lung cancer on LDCT. • Low radiation dose and the absence of contrast medium injection can affect lung cancer detection. • Lung cancer growth shows various behaviours, ranging from indolent to aggressive cancers. • Familiarity with LDCT technique can improve CT screening effectiveness and avoid missed diagnosis. PMID:27188380

  13. Influence of low-dose and low-dose-rate ionizing radiation on mutation induction in human cells

    Science.gov (United States)

    Yatagai, F.; Umebayashi, Y.; Suzuki, M.; Abe, T.; Suzuki, H.; Shimazu, T.; Ishioka, N.; Iwaki, M.; Honma, M.

    This is a review paper to introduce our recent studies on the genetic effects of low-dose and low-dose-rate ionizing radiation (IR). Human lymphoblastoid TK6 cells were exposed to γ-rays at a dose-rate of 1.2 mGy/h (total 30 mGy). The frequency of early mutations (EMs) in the thymidine kinase ( TK) gene locus was determined to be 1.7 × 10 -6, or 1.9-fold higher than the level seen in unirradated controls [Umebayashi, Y., Honma, M., Suzuki, M., Suzuki, H., Shimazu, T., Ishioka, N., Iwaki, M., Yatagai, F., Mutation induction in cultured human cells after low-dose and low-dose-rate γ-ray irradiation: detection by LOH analysis. J. Radiat. Res., 48, 7-11, 2007]. These mutants were then analyzed for loss of heterozygosity (LOH) events. Small interstitial-deletion events were restricted to the TK gene locus and were not observed in EMs in unirradated controls, but they comprised about half of the EMs (8/15) after IR exposure. Because of the low level of exposure to IR, this specific type of event cannot be considered to be the direct result of an IR-induced DNA double strand break (DSB). To better understand the effects of low-level IR exposure, the repair efficiency of site-specific chromosomal DSBs was also examined. The pre γ-irradiation under the same condition did not largely influence the efficiency of DSB repair via end-joining, but enhanced such efficiency via homologous recombination to an about 40% higher level (unpublished data). All these results suggest that DNA repair and mutagenesis can be indirectly influenced by low-dose/dose-rate IR.

  14. Theory and data for estimating the risk at low doses and dose rates

    International Nuclear Information System (INIS)

    Radiological protection bases the Linear Non-Threshold (LNT) model for estimating the risk at low doses and dose rates. Incorporation of risk concept into radiological protection brought the LNT model that implies that there is no wholly ''safe'' dose of radiation. Epidemiological studies have provided statistically reasonable basis for the LNT model for radiological protection. In estimating the cancer risk at low dose and dose rate using the atomic bomb survivor data, the dose and dose rate effectiveness factor (DDREF) is estimated. Theoretical and methodological issues on the DDREF emerged from the biological points of view. The International Commission of Radiological Protection (ICRP) indicated that uncertainty analysis of the risk suggests that the LNT model is more reasonable than the threshold model with uncertain threshold doses. The latest epidemiological studies at low dose rates support LNT models. The gap between biology and epidemiology is increasing although some issues already exist in risk estimation at low doses. To get more scientifically reliable risk estimate, the dialogue between biology and epidemiology is needed to construct the framework of risk estimation such as biologically-based carcinogenesis models. (author)

  15. Screening for lung cancer with low-dose computed tomography

    International Nuclear Information System (INIS)

    Lung cancer is the most common cause of death from malignancy. It is characterized by a favourable prognosis when treated in early stages and a poor prognosis in advanced stages. Populations at risk are relatively well defined, i.e. heavy smokers and workers exposed to asbestos and radon. Therefore, early detection using diagnostic techniques promises reduction of mortality from this tumor. Previous studies using chest radiography and sputum cytology were, however, disappointing due to poor sensitivity of these tests for early tumor stages. The new technique of low-dose computed tomography provides both high sensitivity for small tumors and a comfortable examination. As small benign pulmonary nodules are common reliable non-invasive diagnostic algorithms are required for classification of nodules. Preliminary studies using low-dose CT screening in smokers have provided promising results. Prior to a wide application of the technique in clinical routine more data are required as to inclusion criteria, examination intervals and the effect of screening on mortality reduction. (orig.)

  16. Use of alpha-1 adrenoceptor antagonists in patients who underwent low-dose-rate brachytherapy for prostate cancer - a randomized controlled trial of silodosin versus naftopidil -

    International Nuclear Information System (INIS)

    To evaluate the effect of two different alpha-1 adrenoceptor antagonists on lower urinary tract symptoms in patients who underwent LDR-brachytherapy. A total of 141 patients who had been clinically diagnosed with localized prostate cancer and underwent LDR-brachytherapy were enrolled. Patients were randomized and allocated to two groups (silodosin 8 mg vs. naftopidil 75 mg). The primary endpoint was a change in the international prostate symptom score (IPSS) at 3 months after seed implantation. Secondary endpoints included the recovery rate of IPSS at 12 months after seed implantation, the change in IPSS and overactive bladder symptom score, uroflowmetric parameters, and frequency volume chart (FVC). To determine independent variables that can predict IPSS recovery, logistic regression analysis was carried out. The mean change in the IPSS at 3 months after seed implantation in both groups was ⊿10.6 (naftopidil) and ⊿10.4 (silodosin), respectively. There was not a significant difference between the two groups (p=0.728). An increase in urinary frequency and a decrease in total urinated volume and mean voided volume were observed in FVC for 12 months after seed implantation. Multivariate analysis revealed that the urethral dose (UD30) was an independent predictive parameter of IPSS recovery. Patients with UD30 < 200Gy showed a higher recovery rate of IPSS at 12 months after seed implantation. There was no significant difference of serial change in IPSS between silodosin and naftopidil during the first year after seed implantation. A lower dose on the urethra was an independent predictor of IPSS recovery at 12 months after seed implantation

  17. Physics and quality assurance of low dose rate brachytherapy

    International Nuclear Information System (INIS)

    Purpose: The purpose of this course is to review the physical principles underlying design, clinical application and execution of interstitial and intracavitary implants in the classical low dose-rate (LDR) range. This year, the course will focus on quality assurance of sources, applicators and treatment planning software. In addition, development of procedures and QA checks designed optimize treatment delivery accuracy and patient safety during each individual procedure will be reviewed. The level of presentation will be designed to accommodate both physicists and physicians. Implementation of recently published AAPM Task Group reports (no. 40, 'Comprehensive Quality Assurance' and No. 43, 'Dosimetry of Interstitial Brachytherapy Sources') will be reviewed. Outline: (A) General Principles (1) QA endpoints: temporal accuracy, positional accuracy, dose delivery accuracy, and safety of the patient, personnel, and the institution (2) QA procedure development: forms, checklists, test development and design of treatment delivery procedures (B) QA of treatment delivery devices (1) Source acceptance testing and QA a) calibration and source strength specification standards b) leakage tests and source geometry verification (2) Applicator acceptance testing and QA (3) Remote afterloading devices (4) Treatment planning systems a) graphic input/output devices, implant geometry reconstruction, and graphical display b) dose calculation accuracy i) review of brachytherapy dose calculation algorithms ii) dosimetric benchmarks available: Task Group 43 report (C) Procedure-specific QA 1) Organization of treatment delivery team 2) Preplanning and preparation 3) Applicator insertion 4) Radiographic examination of the implant, prescription, and treatment calculation 5) Source insertion 6) Treatment planning and physicist review of treatment plans 7) QA during patient treatment and removal of sources and applicators

  18. Cancer risk at low doses of ionizing radiation: artificial neural networks inference from atomic bomb survivors.

    Science.gov (United States)

    Sasaki, Masao S; Tachibana, Akira; Takeda, Shunichi

    2014-05-01

    Cancer risk at low doses of ionizing radiation remains poorly defined because of ambiguity in the quantitative link to doses below 0.2 Sv in atomic bomb survivors in Hiroshima and Nagasaki arising from limitations in the statistical power and information available on overall radiation dose. To deal with these difficulties, a novel nonparametric statistics based on the 'integrate-and-fire' algorithm of artificial neural networks was developed and tested in cancer databases established by the Radiation Effects Research Foundation. The analysis revealed unique features at low doses that could not be accounted for by nominal exposure dose, including (i) the presence of a threshold that varied with organ, gender and age at exposure, and (ii) a small but significant bumping increase in cancer risk at low doses in Nagasaki that probably reflects internal exposure to (239)Pu. The threshold was distinct from the canonical definition of zero effect in that it was manifested as negative excess relative risk, or suppression of background cancer rates. Such a unique tissue response at low doses of radiation exposure has been implicated in the context of the molecular basis of radiation-environment interplay in favor of recently emerging experimental evidence on DNA double-strand break repair pathway choice and its epigenetic memory by histone marking. PMID:24366315

  19. Cancer risk at low doses of ionizing radiation. Artificial neural networks inference from atomic bomb survivors

    International Nuclear Information System (INIS)

    Cancer risk at low doses of ionizing radiation remains poorly defined because of ambiguity in the quantitative link to doses below 0.2 Sv in atomic bomb survivors in Hiroshima and Nagasaki arising from limitations in the statistical power and information available on overall radiation dose. To deal with these difficulties, a novel nonparametric statistics based on the ‘integrate-and-fire’ algorithm of artificial neural networks was developed and tested in cancer databases established by the Radiation Effects Research Foundation. The analysis revealed unique features at low doses that could not be accounted for by nominal exposure dose, including (1) the presence of a threshold that varied with organ, gender and age at exposure, and (2) a small but significant bumping increase in cancer risk at low doses in Nagasaki that probably reflects internal exposure to 239Pu. The threshold was distinct from the canonical definition of zero effect in that it was manifested as negative excess relative risk, or suppression of background cancer rates. Such a unique tissue response at low doses of radiation exposure has been implicated in the context of the molecular basis of radiation–environment interplay in favor of recently emerging experimental evidence on DNA double-strand break repair pathway choice and its epigenetic memory by histone marking. (author)

  20. Genetic Factors Affecting Susceptibility to Low Dose & Low Dose-Rate Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Bedford, Joel

    2014-04-18

    Our laboratory has, among other things, developed and used the gamma H2AX focus assay and other chromosomal and cell killing assays to show that differences in this DNA double strand break (dsb) related response can be clearly and distinctly demonstrated for cells which are mildly hyper-radiosensitive such as those associated with A-T heterozygosity. We have found this level of mild hypersensitivity for cells from some 20 to 30 % of apparently normal individuals and from apparently normal parents of Retinoblastoma patients. We found significant differences in gene expression in somatic cells from unaffected parents of Rb patients as compared with normal controls, suggesting that these parents may harbor some as yet unidentified genetic abnormality. In other experiments we sought to determine the extent of differences in normal human cellular reaponses to radiation depending on their irradiation in 2D monolayer vs 3D organized acinar growth conditions. We exmined cell reproductive death, chromosomal aberration induction, and the levels of γ-H2AX foci in cells after single acute gamma-ray doses and immediately after 20 hours of irradiation at a dose rate of 0.0017 Gy/min. We found no significant differences in the dose-responses of these cells under the 2D or 3D growth conditions. While this does not mean such differences cannot occur in other situations, it does mean that they do not generally or necessarily occur. In another series of studies in collaboration with Dr Chuan Li, with supprt from this current grant. We reported a role for apoptotic cell death in promoting wound healing and tissue regeneration in mice. Apoptotic cells released growth signals that stimulated the proliferation of progenitor or stem cells. In yet another collaboration with Dr, B. Chen with funds from this grant, the relative radiosensitivity to cell killing as well as chromosomal instability of 13 DNA-PKcs site-directed mutant cell lines (defective at phosphorylation sites or kinase

  1. Cancer and non-cancer risk at low doses of radiation: biological basis of radiation-environment interplay

    International Nuclear Information System (INIS)

    Cancer and non-cancer risk at low doses of ionizing radiation remains poorly defined due to ambiguity at low doses caused by limitations in statistical power and information available on interplay with environment. To deal with these problems, a novel non-parametric statistics was developed based on artificial neural networks theorem and applied to cancer and non-cancer risk in A-bomb survivors. The analysis revealed several unique features at low doses that could not be accounted for by nominal radiation dose alone. They include (1) threshold that varies with organ, gender and age, including cardiovascular diseases, (2) prevalence of infectious diseases, and (3) suppression of pathogenesis of HTLV1. The threshold is unique as it is manifested as negative excess relative risk, a reduction of spontaneous rate at low doses. The response is consistent with currently emerging laboratory data on DNA double-strand break (DSB) repair pathway choice and its sustainability as epigenetic memory in accordance with histone code theory. In response to DSB, of radiation or DNA replication arrest origin, distinct and competitively operating repair pathways are instigated. Activation by low doses of restitution-directed canonical non-homologous end-joining (C-NHEJ) suppresses both error-prone alternative end-joining (Alt-NHEJ) and homologous recombination (HR). The latter two present major pathways to mutagenesis at stalled replication folk associated with endogenous and exogenous genotoxin such as tobacco smoke metabolites and AID-associated somatic hypermutation and class switch recombination in Ig gene. Suppression of these error-prone pathways by low doses of low LET radiation is consistent with the reduction of cancer occurrence by environmental genotoxin, immunodiversity and stable integration of retrovirus DNA, providing a significant modulator of dose linearity at low doses. Whole picture may bring about a new landscape of cancer and non-cancer molecular epidemiology which

  2. Dosimetry Modeling for Focal Low-Dose-Rate Prostate Brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Al-Qaisieh, Bashar [Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, Leeds (United Kingdom); Mason, Josh, E-mail: joshua.mason@nhs.net [Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, Leeds (United Kingdom); Bownes, Peter; Henry, Ann [Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, Leeds (United Kingdom); Dickinson, Louise [Division of Surgery and Interventional Science, University College London, London (United Kingdom); Department of Radiology, Northwick Park Hospital, London North West NHS Trust, London (United Kingdom); Ahmed, Hashim U. [Division of Surgery and Interventional Science, University College London, London (United Kingdom); University College London Hospital, London (United Kingdom); Emberton, Mark [University College London Hospital, London (United Kingdom); Langley, Stephen [St Luke' s Cancer Centre, Guildford (United Kingdom)

    2015-07-15

    Purpose: Focal brachytherapy targeted to an individual lesion(s) within the prostate may reduce side effects experienced with whole-gland brachytherapy. The outcomes of a consensus meeting on focal prostate brachytherapy were used to investigate optimal dosimetry of focal low-dose-rate (LDR) prostate brachytherapy targeted using multiparametric magnetic resonance imaging (mp-MRI) and transperineal template prostate mapping (TPM) biopsy, including the effects of random and systematic seed displacements and interseed attenuation (ISA). Methods and Materials: Nine patients were selected according to clinical characteristics and concordance of TPM and mp-MRI. Retrospectively, 3 treatment plans were analyzed for each case: whole-gland (WG), hemi-gland (hemi), and ultra-focal (UF) plans, with 145-Gy prescription dose and identical dose constraints for each plan. Plan robustness to seed displacement and ISA were assessed using Monte Carlo simulations. Results: WG plans used a mean 28 needles and 81 seeds, hemi plans used 17 needles and 56 seeds, and UF plans used 12 needles and 25 seeds. Mean D90 (minimum dose received by 90% of the target) and V100 (percentage of the target that receives 100% dose) values were 181.3 Gy and 99.8% for the prostate in WG plans, 195.7 Gy and 97.8% for the hemi-prostate in hemi plans, and 218.3 Gy and 99.8% for the focal target in UF plans. Mean urethra D10 was 205.9 Gy, 191.4 Gy, and 92.4 Gy in WG, hemi, and UF plans, respectively. Mean rectum D2 cm{sup 3} was 107.5 Gy, 77.0 Gy, and 42.7 Gy in WG, hemi, and UF plans, respectively. Focal plans were more sensitive to seed displacement errors: random shifts with a standard deviation of 4 mm reduced mean target D90 by 14.0%, 20.5%, and 32.0% for WG, hemi, and UF plans, respectively. ISA has a similar impact on dose-volume histogram parameters for all plan types. Conclusions: Treatment planning for focal LDR brachytherapy is feasible. Dose constraints are easily met with a notable

  3. Dosimetry Modeling for Focal Low-Dose-Rate Prostate Brachytherapy

    International Nuclear Information System (INIS)

    Purpose: Focal brachytherapy targeted to an individual lesion(s) within the prostate may reduce side effects experienced with whole-gland brachytherapy. The outcomes of a consensus meeting on focal prostate brachytherapy were used to investigate optimal dosimetry of focal low-dose-rate (LDR) prostate brachytherapy targeted using multiparametric magnetic resonance imaging (mp-MRI) and transperineal template prostate mapping (TPM) biopsy, including the effects of random and systematic seed displacements and interseed attenuation (ISA). Methods and Materials: Nine patients were selected according to clinical characteristics and concordance of TPM and mp-MRI. Retrospectively, 3 treatment plans were analyzed for each case: whole-gland (WG), hemi-gland (hemi), and ultra-focal (UF) plans, with 145-Gy prescription dose and identical dose constraints for each plan. Plan robustness to seed displacement and ISA were assessed using Monte Carlo simulations. Results: WG plans used a mean 28 needles and 81 seeds, hemi plans used 17 needles and 56 seeds, and UF plans used 12 needles and 25 seeds. Mean D90 (minimum dose received by 90% of the target) and V100 (percentage of the target that receives 100% dose) values were 181.3 Gy and 99.8% for the prostate in WG plans, 195.7 Gy and 97.8% for the hemi-prostate in hemi plans, and 218.3 Gy and 99.8% for the focal target in UF plans. Mean urethra D10 was 205.9 Gy, 191.4 Gy, and 92.4 Gy in WG, hemi, and UF plans, respectively. Mean rectum D2 cm3 was 107.5 Gy, 77.0 Gy, and 42.7 Gy in WG, hemi, and UF plans, respectively. Focal plans were more sensitive to seed displacement errors: random shifts with a standard deviation of 4 mm reduced mean target D90 by 14.0%, 20.5%, and 32.0% for WG, hemi, and UF plans, respectively. ISA has a similar impact on dose-volume histogram parameters for all plan types. Conclusions: Treatment planning for focal LDR brachytherapy is feasible. Dose constraints are easily met with a notable reduction

  4. Dosimetric Considerations to Determine the Optimal Technique for Localized Prostate Cancer Among External Photon, Proton, or Carbon-Ion Therapy and High-Dose-Rate or Low-Dose-Rate Brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Georg, Dietmar, E-mail: Dietmar.Georg@akhwien.at [Department of Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Hopfgartner, Johannes [Department of Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Gòra, Joanna [Department of Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Kuess, Peter [Department of Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Kragl, Gabriele [Department of Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Berger, Daniel [Department of Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Hegazy, Neamat [Department of Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Goldner, Gregor; Georg, Petra [Department of Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria)

    2014-03-01

    Purpose: To assess the dosimetric differences among volumetric modulated arc therapy (VMAT), scanned proton therapy (intensity-modulated proton therapy, IMPT), scanned carbon-ion therapy (intensity-modulated carbon-ion therapy, IMIT), and low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy (BT) treatment of localized prostate cancer. Methods and Materials: Ten patients were considered for this planning study. For external beam radiation therapy (EBRT), planning target volume was created by adding a margin of 5 mm (lateral/anterior–posterior) and 8 mm (superior–inferior) to the clinical target volume. Bladder wall (BW), rectal wall (RW), femoral heads, urethra, and pelvic tissue were considered as organs at risk. For VMAT and IMPT, 78 Gy(relative biological effectiveness, RBE)/2 Gy were prescribed. The IMIT was based on 66 Gy(RBE)/20 fractions. The clinical target volume planning aims for HDR-BT ({sup 192}Ir) and LDR-BT ({sup 125}I) were D{sub 90%} ≥34 Gy in 8.5 Gy per fraction and D{sub 90%} ≥145 Gy. Both physical and RBE-weighted dose distributions for protons and carbon-ions were converted to dose distributions based on 2-Gy(IsoE) fractions. From these dose distributions various dose and dose–volume parameters were extracted. Results: Rectal wall exposure 30-70 Gy(IsoE) was reduced for IMIT, LDR-BT, and HDR-BT when compared with VMAT and IMPT. The high-dose region of the BW dose–volume histogram above 50 Gy(IsoE) of IMPT resembled the VMAT shape, whereas all other techniques showed a significantly lower high-dose region. For all 3 EBRT techniques similar urethra D{sub mean} around 74 Gy(IsoE) were obtained. The LDR-BT results were approximately 30 Gy(IsoE) higher, HDR-BT 10 Gy(IsoE) lower. Normal tissue and femoral head sparing was best with BT. Conclusion: Despite the different EBRT prescription and fractionation schemes, the high-dose regions of BW and RW expressed in Gy(IsoE) were on the same order of magnitude. Brachytherapy techniques

  5. Dosimetric Considerations to Determine the Optimal Technique for Localized Prostate Cancer Among External Photon, Proton, or Carbon-Ion Therapy and High-Dose-Rate or Low-Dose-Rate Brachytherapy

    International Nuclear Information System (INIS)

    Purpose: To assess the dosimetric differences among volumetric modulated arc therapy (VMAT), scanned proton therapy (intensity-modulated proton therapy, IMPT), scanned carbon-ion therapy (intensity-modulated carbon-ion therapy, IMIT), and low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy (BT) treatment of localized prostate cancer. Methods and Materials: Ten patients were considered for this planning study. For external beam radiation therapy (EBRT), planning target volume was created by adding a margin of 5 mm (lateral/anterior–posterior) and 8 mm (superior–inferior) to the clinical target volume. Bladder wall (BW), rectal wall (RW), femoral heads, urethra, and pelvic tissue were considered as organs at risk. For VMAT and IMPT, 78 Gy(relative biological effectiveness, RBE)/2 Gy were prescribed. The IMIT was based on 66 Gy(RBE)/20 fractions. The clinical target volume planning aims for HDR-BT (192Ir) and LDR-BT (125I) were D90% ≥34 Gy in 8.5 Gy per fraction and D90% ≥145 Gy. Both physical and RBE-weighted dose distributions for protons and carbon-ions were converted to dose distributions based on 2-Gy(IsoE) fractions. From these dose distributions various dose and dose–volume parameters were extracted. Results: Rectal wall exposure 30-70 Gy(IsoE) was reduced for IMIT, LDR-BT, and HDR-BT when compared with VMAT and IMPT. The high-dose region of the BW dose–volume histogram above 50 Gy(IsoE) of IMPT resembled the VMAT shape, whereas all other techniques showed a significantly lower high-dose region. For all 3 EBRT techniques similar urethra Dmean around 74 Gy(IsoE) were obtained. The LDR-BT results were approximately 30 Gy(IsoE) higher, HDR-BT 10 Gy(IsoE) lower. Normal tissue and femoral head sparing was best with BT. Conclusion: Despite the different EBRT prescription and fractionation schemes, the high-dose regions of BW and RW expressed in Gy(IsoE) were on the same order of magnitude. Brachytherapy techniques were clearly superior in terms of

  6. A comparison of the biological effects of 125I seeds continuous low-dose-rate radiation and 60Co high-dose-rate gamma radiation on non-small cell lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Zhongmin Wang

    Full Text Available To compare the biological effects of 125I seeds continuous low-dose-rate (CLDR radiation and 60Co γ-ray high-dose-rate (HDR radiation on non-small cell lung cancer (NSCLC cells.A549, H1299 and BEAS-2B cells were exposed to 125I seeds CLDR radiation or 60Co γ-ray HDR radiation. The survival fraction was determined using a colony-forming assay. The cell cycle progression and apoptosis were detected by flow cytometry (FCM. The expression of the apoptosis-related proteins caspase-3, cleaved-caspase-3, PARP, cleaved-PARP, BAX and Bcl-2 were detected by western blot assay.After irradiation with 125I seeds CLDR radiation, there was a lower survival fraction, more pronounced cell cycle arrest (G1 arrest and G2/M arrest in A549 and H1299 cells, respectively and a higher apoptotic ratio for A549 and H1299 cells than after 60Co γ-ray HDR radiation. Moreover, western blot assays revealed that 125I seeds CLDR radiation remarkably up-regulated the expression of Bax, cleaved-caspase-3 and cleaved-PARP proteins and down-regulated the expression of Bcl-2 proteins in A549 and H1299 cells compared with 60Co γ-ray HDR radiation. However, there was little change in the apoptotic ratio and expression of apoptosis-related proteins in normal BEAS-2B cells receiving the same treatment.125I seeds CLDR radiation led to remarkable growth inhibition of A549 and H1299 cells compared with 60Co HDR γ-ray radiation; A549 cells were the most sensitive to radiation, followed by H1299 cells. In contrast, normal BEAS-2B cells were relatively radio-resistant. The imbalance of the Bcl-2/Bax ratio and the activation of caspase-3 and PARP proteins might play a key role in the anti-proliferative effects induced by 125I seeds CLDR radiation, although other possibilities have not been excluded and will be investigated in future studies.

  7. DVH parameters and outcome for patients with early-stage cervical cancer treated with preoperative MRI-based low dose rate brachytherapy followed by surgery

    International Nuclear Information System (INIS)

    Background: To our knowledge no DVH data have so far been reported for MRI-guided BT in the preoperative setting of early-stage cervical cancer. We assessed DVH parameters and clinical outcome using 3D MRI-guided preoperative intracavitary LDR BT. Patients and methods: Thirty-nine patients with primary early cervical carcinoma (IB1 37, IIA 1 and IIB 1) were treated with preoperative MRI-based LDR BT, consisting of uterovaginal BT to a total dose of 60 Gy to the intermediate-risk CTV, followed 6 weeks later by bilateral salpingo-oophorectomy and extrafascial hysterectomy plus pelvic node dissection. Adjuvant chemoradiation was delivered to patients with pelvic lymph node involvement. Results: With a median follow-up of 4.4 years (range 2.6-6.6 years), local recurrence occurred in 1 patient (a lateropelvic relapse) (2.6%). The 4-year actuarial overall survival and disease-free survival were 94% (95% CI, 82-98), and 86% (95% CI, 67-95), respectively. The 2- and 4-year actuarial local relapse-free survival were 94 (95% CI, 86-100) and 91% (95% CI, 81-100), respectively. For intermediate-risk CTV, median D100 and D90 were 43 Gyα/β10 (range 2-74 Gyα/β10) and 75 Gyα/β10, respectively (range 29-129 Gyα/β10). For high-risk CTV, the median D100 and D90 were 69 Gyα/β10 (range 24-137 Gyα/β10) and 109 Gyα/β10 (range 37-198 Gyα/β10), respectively. Twenty grade 1-2 late complications were observed in 13 patients (33.3%): 10 bladder, 3 ureteral, 1 rectal, 1 small bowel, 1 vaginal, 1 pelvic fibrosis, 1 peripheral nerve, and 2 others. No grade 3 or 4 complication occurred. Conclusion: MRI-guided brachytherapy with adaptation of the time duration and/or the length of each radioactive source allows both high local control and low toxicity in the preoperative settings of early-stage cervical cancers.

  8. Chromosomal Aberrations in Normal and AT Cells Exposed to High Dose of Low Dose Rate Irradiation

    Science.gov (United States)

    Kawata, T.; Shigematsu, N.; Kawaguchi, O.; Liu, C.; Furusawa, Y.; Hirayama, R.; George, K.; Cucinotta, F.

    2011-01-01

    Ataxia telangiectasia (A-T) is a human autosomally recessive syndrome characterized by cerebellar ataxia, telangiectases, immune dysfunction, and genomic instability, and high rate of cancer incidence. A-T cell lines are abnormally sensitive to agents that induce DNA double strand breaks, including ionizing radiation. The diverse clinical features in individuals affected by A-T and the complex cellular phenotypes are all linked to the functional inactivation of a single gene (AT mutated). It is well known that cells deficient in ATM show increased yields of both simple and complex chromosomal aberrations after high-dose-rate irradiation, but, less is known on how cells respond to low-dose-rate irradiation. It has been shown that AT cells contain a large number of unrejoined breaks after both low-dose-rate irradiation and high-dose-rate irradiation, however sensitivity for chromosomal aberrations at low-dose-rate are less often studied. To study how AT cells respond to low-dose-rate irradiation, we exposed confluent normal and AT fibroblast cells to up to 3 Gy of gamma-irradiation at a dose rate of 0.5 Gy/day and analyzed chromosomal aberrations in G0 using fusion PCC (Premature Chromosomal Condensation) technique. Giemsa staining showed that 1 Gy induces around 0.36 unrejoined fragments per cell in normal cells and around 1.35 fragments in AT cells, whereas 3Gy induces around 0.65 fragments in normal cells and around 3.3 fragments in AT cells. This result indicates that AT cells can rejoin breaks less effectively in G0 phase of the cell cycle? compared to normal cells. We also analyzed chromosomal exchanges in normal and AT cells after exposure to 3 Gy of low-dose-rate rays using a combination of G0 PCC and FISH techniques. Misrejoining was detected in the AT cells only? When cells irradiated with 3 Gy were subcultured and G2 chromosomal aberrations were analyzed using calyculin-A induced PCC technique, the yield of unrejoined breaks decreased in both normal and AT

  9. Enhancement of tumor rejection in mice by low dose-rate gamma irradiation

    International Nuclear Information System (INIS)

    We reported a suppression effect of low dose-rate gamma irradiation on the appearance of a Methylcholanthrene (MC)-induced tumor (fibrosarcoma) in C57BL/6N mice in Int. J. Low Radiat. To elucidate the mechanism of the suppression effect, we studied the effect of low dose-rate irradiation on the rejective response against taking tumor cells. In this study the rejective response was analyzed by applying methods of TD50 assay. TD50 is the abbreviation for tumor dose 50 and indicates the number of cells required for successful transplantation to one half of an injected site in the recipient animals. We transplanted the tumor cells prepared from a MC-induced tumor in C57BL/6 mice. The increase of the TD 50 value suggests an enhancement of the rejective response against taking tumor cells. Irradiations were performed with Cs-137 gamma-rays at 1.2 mGy/hr or 0.35 mGy/hr for 1-8 weeks before tumor cell injection from six-week old mice, which were then injected with an appropriate number of single tumor cells. The value of TD 50 in mice irradiated at 0.35 mGy/hr for 5 weeks was 5 times higher than in the non-irradiated control mice. The total dose at 0.35 mGy/hr for 5 weeks was about 250mGy. At 1.2 mGy/hr or 0.7mGy/hr, an increase in TD 50 was observed when the total dose reached 250 mGy. These results suggest that low dose-rate radiation, under certain irradiation conditions, enhances immunological capacity against tumor cells in irradiated mice and thereby suppresses tumor incidence. For an estimation of risk of cancer incidence from low dose/dose-rate radiation, such protective effects as demonstrated in the present study should be taken into consideration. (author)

  10. Arsenic, mode of action at biologically plausible low doses: What are the implications for low dose cancer risk?

    International Nuclear Information System (INIS)

    Arsenic is an established human carcinogen. However, there has been much controversy about the shape of the arsenic response curve, particularly at low doses. This controversy has been exacerbated by the fact that the mechanism(s) of arsenic carcinogenesis are still unclear and because there are few satisfactory animal models for arsenic-induced carcinogenesis. Recent epidemiological studies have shown that the relative risk for cancer among populations exposed to ≤60 ppb As in their drinking water is often lower than the risk for the unexposed control population. We have found that treatment of human keratinocyte and fibroblast cells with 0.1 to 1 μM arsenite (AsIII) also produces a low dose protective effect against oxidative stress and DNA damage. This response includes increased transcription, protein levels and enzyme activity of several base excision repair genes, including DNA polymerase β and DNA ligase I. At higher concentrations (> 10 μM), As induces down-regulation of DNA repair, oxidative DNA damage and apoptosis. This low dose adaptive (protective) response by a toxic agent is known as hormesis and is characteristic of many agents that induce oxidative stress. A mechanistic model for arsenic carcinogenesis based on these data would predict that the low dose risk for carcinogenesis should be sub-linear. The threshold dose where toxicity outweighs protection is hard to predict based on in vitro dose response data, but might be estimated if one could determine the form (metabolite) and concentration of arsenic responsible for changes in gene regulation in the target tissues

  11. Risk of cancer subsequent to low-dose radiation

    International Nuclear Information System (INIS)

    The author puts low dose irradiation risks in perspective using average background radiation doses for standards. He assailed irresponsible media coverage during the height of public interest in the Three-Mile Island Reactor incident

  12. Genetic factors affecting radiosensitivity and cancer predisposition: application of a continuous low dose-rate irradiation colony formation assay to select radiosensitive retinoblastoma family members for correction with a cDNA library

    International Nuclear Information System (INIS)

    Full text: The aim of this study is to identify new or undescribed functions of radiosensitivity and genomic instability genes using a continuous low dose-rate colony formation assay. This assay expands on the standard colony formation assay, whereby colony formation ability (retention of proliferative capacity) is measured during continuous low dose-rate irradiation rather than 10-14 days following the completion of such exposures. This approach has previously employed by the Bedford laboratory to identify a Prkdc (DNA-PKcs) mutant of CHO cells, irs-20. In this study we examine the growth response of fibroblasts derived from recently identified radiosensitive retinoblastoma family members, both affected probands and their unaffected parents, and various apparently normal fibroblast lines obtained from the NIGMS Human Genetic Cell Repository (Coriell Medical Institute, Camden, NJ). Colony formation was assayed by plating single cells, exposing them at 37 deg C to continuous Cs-137 gamma irradiation at dose rates of 0.5-8.5 cGy/h, and scoring survivors as colonies with >100 viable cells. The retinoblastoma family members display severely limited growth (survival less than 10E-3) at dose rates greater than 2-2.5 cGy/h, while the apparently normal cell lines do not display such inhibited growth until 6-7 cGy/h. Two of the retinoblastoma family cell lines, MF-6F and MF-15F (both unaffected but radiosensitive parents), were selected as targets of transfection with a viral cDNA library (ViraPort human cDNA library, Stratagene Cloning Systems, La Jolla, CA) and subjected to a ∼3 cGy/h selection dose rate, where uncorrected survival relative to normal cells is lower by a factor of 50-150. Colonies recovered will provide valuable information regarding the genetic nature of their radiosensitivity (possibly involving chromosome stability, DNA repair, and/or cell cycle regulatory pathways), that may influence risks for cancer and heritable effects for a previously

  13. The effect for metastasis of urinary tract cancer by combination therapy with adriamycin and low dose radiation

    International Nuclear Information System (INIS)

    Thee were 12 cases (men 11 and 1 woman) with metastasis of urinary tract cancer. Average age was 65.3 years. Primary tumors were 7 bladder cancers, 3 pelvico-ureter cancers and 2 renal cell carcinomas. Treatment was mainly intravenous administration of 100 mg ADM and low dose of local radiation (2000 rad). Effective rate was 85.7% for metastasis of transitional cell carcinoma, but effective rate was 0% by treatment of administration of 30 mg ADM and local low dose radiation (2000 rad). No effect to metastasis of renal cell carcinoma was observed. (author)

  14. Determination of the survival curve of the cell irradiated with low dose rate neutrons

    International Nuclear Information System (INIS)

    The effect of the radiation in tissue and cells are a theme of extreme importance and that is receiving large attention more and more now. This work purposes to evaluate the deleterious effects of the neutrons radiation at low dose rate in lineages of human cancerous cells through the analysis of survival curves. Deleterious effects due to radiation of low dose rate (3.8 mSv/hr) were observed in cells of the lineage HeLa S3. Previous studies, in lineage HN5 of tongue carcinoma, showed survive level to 0.2Sv of 80%, compatible to the value of 88,57% 0.4 Sv obtained for HeLa S3. In a close future, with the molecular biology characterization of a great number or possibly all cancer types (that will be accelerated largely with the conclusion of the human genome project), studies like this, can be much more specific, and could determine the efficiency of the neutrons or any other radiation type for each one of those types. Those data would have of great value for the medicine and they would help to plan the treatments better. (author)

  15. Low doses effects and gamma radiations low dose rates; Les effets des faibles doses et des faibles debits de doses de rayons gamma

    Energy Technology Data Exchange (ETDEWEB)

    Averbeck, D. [Institut Curie, CNRS UMR 2027, 75 - Paris (France)

    1999-07-01

    This expose wishes for bringing some definitions and base facts relative to the problematics of low doses effects and low dose rates effects. It shows some already used methods and some actual experimental approaches by focusing on the effects of ionizing radiations with a low linear energy transfer. (N.C.)

  16. Non homologous end-rejoining pathway plays an important role in low dose-rate effects

    International Nuclear Information System (INIS)

    Full text: It has been generally accepted that low dose rate-effect results from the repair of sublethal damage. As the dose rate is lowered and the treatment time protracted, more and more sublethal damage can be repaired during the exposure. Recently we found that sublethal damage repair, Elkind recovery is due to double-strand break (DSB) repair mediated by homologous recombination (HR), and that these DNA DSBs constitute sublethal damage. To study the molecular mechanism of low dose-rate effect, we analyzed the knock-out mutants KU70-/-, RAD54-/-, and KU70-/-/RAD54-/-of the chicken B-cell line, DT40. Rad54 participates in the recombinational repair of DSBs, while Ku proteins are involved in non homologous end-rejoining (NHEJ). Survival enhancement by low dose-rate irradiation was observed in the parent DT40 and RAD54-/-cells but not in the NHEJ deficient KU70-/-and KU70-/-/RAD54-/-cells. In the low dose-rate effects, NHEJ pathway was more important than HR pathway. This suggests that low dose-rate effects are not directly attributable to the SLD repair because the SLD repair results from the HR pathway of DSBs. Under continuous low dose-rate irradiation, dividing chicken cells can progress through the cell cycle. NHEJ-deficient cells will be killed in G1 phase, since these cells show little activity of DSB repair in G1. NHEJ pathway plays an important role in low dose-rate effects

  17. Cohort studies on cancer mortality among nuclear workers exposed to low-dose ionizing radiation: a meta-analysis

    International Nuclear Information System (INIS)

    To provide direct estimates of risk of cancer after protracted low doses of ionising radiation and to strengthen the scientific basis of radiation protection standards for low-dose ionising radiation exposure. Published papers referring to 20 low-dose ionising radiation-exposed cohorts among nuclear industry workers with Standardized Mortality Ratios (SMR) were recta-analyzed in fixed and random effect models. The significantly deficient Meta-SMRs for all deaths (0.73; 95% CI: 0.66-0.80), all cancers (0.83; 95% CI: 0.77- 0.91), lung cancer (0.93; 95% CI: 0.90-0.95), non-Hodgkin lymphoma (0.88; 95% CI: 0.78- 0.99), esophagus cancer (0.83; 95% CI:0.76-0.91), colorectal cancer (0.88; 95% CI: 0.83-0.94), stomach cancer (0.81; 95% CI: 0.76-0.86) were observed. The Meta-SMRs for leukemia, multiple myeloma, Hodgkin's disease were found to be no significant difference with normal populations. There was no excessive risk of cancers among nuclear workers exposed to low-doses and low-dose rates ionizing radiation. (authors)

  18. Evaluation of Enhanced Low Dose Rate Sensitivity in Discrete Bipolar Junction Transistors

    Science.gov (United States)

    Chen, Dakai; Ladbury Raymond; LaBel, Kenneth; Topper, Alyson; Ladbury, Raymond; Triggs, Brian; Kazmakites, Tony

    2012-01-01

    We evaluate the low dose rate sensitivity in several families of discrete bipolar transistors across device parameter, quality assurance level, and irradiation bias configuration. The 2N2222 showed the most significant low dose rate sensitivity, with low dose rate enhancement factor of 3.91 after 100 krad(Si). The 2N2907 also showed critical degradation levels. The devices irradiated at 10 mrad(Si)/s exceeded specifications after 40 and 50 krad(Si) for the 2N2222 and 2N2907 devices, respectively.

  19. Health effects of low doses at low dose rates: dose-response relationship modeling in a cohort of workers of the nuclear industry

    International Nuclear Information System (INIS)

    The aim of this thesis is to contribute to a better understanding of the health effects of chronic external low doses of ionising radiation. This work is based on the French cohort of CEA-AREVA NC nuclear workers. The mains stages of this thesis were (1) conducting a review of epidemiological studies on nuclear workers, (2) completing the database and performing a descriptive analysis of the cohort, (3) quantifying risk by different statistical methods and (4) modelling the exposure-time-risk relationship. The cohort includes monitored workers employed more than one year between 1950 and 1994 at CEA or AREVA NC companies. Individual annual external exposure, history of work, vital status and causes of death were reconstructed for each worker. Standardized mortality ratios using French national mortality rates as external reference were computed. Exposure-risk analysis was conducted in the cohort using the linear excess relative risk model, based on both Poisson regression and Cox model. Time dependent modifying factors were investigated by adding an interaction term in the model or by using exposure time windows. The cohort includes 36, 769 workers, followed-up until age 60 in average. During the 1968- 2004 period, 5, 443 deaths, 2, 213 cancers, 62 leukemia and 1, 314 cardiovascular diseases were recorded. Among the 57% exposed workers, the mean cumulative dose was 21.5 milli-sieverts (mSv). A strong Healthy Worker Effect is observed in the cohort. Significant elevated risks of pleura cancer and melanoma deaths were observed in the cohort but not associated with dose. No significant association was observed with solid cancers, lung cancer and cardiovascular diseases. A significant dose-response relationship was observed for leukemia excluding chronic lymphatic leukemia, mainly for doses received less than 15 years before and for yearly dose rates higher than 10 mSv. This PhD work contributes to the evaluation of risks associated to chronic external radiation

  20. Health Risks From Low Doses and Low Dose-Rates of Ionizing Radiation. Session 5: Future of Radiation Protection Regulations.

    Science.gov (United States)

    Cool, Donald A

    2016-03-01

    The system of radiological protection is a prospective approach to protection of individuals in all exposure situations. It must be applied equitably across all age groups and all populations. This is a very different circumstance from dose assessment for a particular individual where the unique characteristics of the individual and the exposure can be taken into account. Notwithstanding the ongoing discussions on the possible shape of the dose response at low doses and dose rates, the prospective system of protection has therefore historically used a linear assumption as a pragmatic, prudent and protective approach. These radiation protection criteria are not intended to be a demarcation between "safe" and "unsafe" and are the product of a risk-informed judgement that includes inputs from science, ethics, and experience. There are significant implications for different dose response relationships. A linear model allows for equal treatment of an exposure, irrespective of the previously accumulated exposure. In contrast, other models would predict different implications. Great care is therefore needed in separating the thinking around risk assessment from risk management, and prospective protection for all age groups and genders from retrospective assessment for a particular individual. In the United States, the prospective regulatory structure functions effectively because of assumptions that facilitate independent treatment of different types of exposures, and which provide pragmatic and prudent protection. While the a linear assumption may, in fact, not be consistent with the biological reality, the implications of a different regulatory model must be considered carefully. PMID:26808877

  1. Low Dose Radiation Cancer Risks: Epidemiological and Toxicological Models

    Energy Technology Data Exchange (ETDEWEB)

    David G. Hoel, PhD

    2012-04-19

    The basic purpose of this one year research grant was to extend the two stage clonal expansion model (TSCE) of carcinogenesis to exposures other than the usual single acute exposure. The two-stage clonal expansion model of carcinogenesis incorporates the biological process of carcinogenesis, which involves two mutations and the clonal proliferation of the intermediate cells, in a stochastic, mathematical way. The current TSCE model serves a general purpose of acute exposure models but requires numerical computation of both the survival and hazard functions. The primary objective of this research project was to develop the analytical expressions for the survival function and the hazard function of the occurrence of the first cancer cell for acute, continuous and multiple exposure cases within the framework of the piece-wise constant parameter two-stage clonal expansion model of carcinogenesis. For acute exposure and multiple exposures of acute series, it is either only allowed to have the first mutation rate vary with the dose, or to have all the parameters be dose dependent; for multiple exposures of continuous exposures, all the parameters are allowed to vary with the dose. With these analytical functions, it becomes easy to evaluate the risks of cancer and allows one to deal with the various exposure patterns in cancer risk assessment. A second objective was to apply the TSCE model with varing continuous exposures from the cancer studies of inhaled plutonium in beagle dogs. Using step functions to estimate the retention functions of the pulmonary exposure of plutonium the multiple exposure versions of the TSCE model was to be used to estimate the beagle dog lung cancer risks. The mathematical equations of the multiple exposure versions of the TSCE model were developed. A draft manuscript which is attached provides the results of this mathematical work. The application work using the beagle dog data from plutonium exposure has not been completed due to the fact

  2. Effect of low-dose X-ray radiation on adaptive response in gastric cancer cell

    Institute of Scientific and Technical Information of China (English)

    Shukai Wang; Gang Jiang; Hongsheng Yu; Xiangping Liu; Chang Xu

    2013-01-01

    Objective: We aimed to study the effect and mechanism of low-dose radiation (LDR) on adaptive response of gastric cancer cell. Methods: SGC7901 cells were cultured in vitro, and divided into 4 groups: control group (D0 group), low-dose radiation group (D1 group, 75 mGy), high-dose radiation group (D2 group, 2 Gy), low-dose plus high-dose radiation group (D1 + D2 group, 75 mGy + 2 Gy, the interval of low and high-dose radiation being 8 h). Cell inhibition rate was detected by cytometry and CCK8 method; the proportion of cell cycle at different times after irradiation was determined by using a flow cytometry. The ATM mRNA levels were detected by using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Results: There was no significant different between groups D0 and D1, groups D2 and D1 + D2 cell inhibition rate (P > 0.05). There was a significant increase G2/M arrest in groups D2 and D1 + D2 than groups D0 and D1 after 6 h of radiation and did not recover at 48 h (P 0.05). Conclusion: LDR cannot induce adaptive response in SGC7901 cells in vitro, which may be associated the regulation of cell cycle, and its ATM mRNA expression cannot be affected by 75 mGy X-ray radiation.

  3. Mortality from diseases other than cancer following low doses of ionizing radiation

    DEFF Research Database (Denmark)

    Vrijheid, M; Cardis, E; Ashmore, P;

    2007-01-01

    BACKGROUND: Ionizing radiation at very high (radio-therapeutic) dose levels can cause diseases other than cancer, particularly heart diseases. There is increasing evidence that doses of the order of a few sievert (Sv) may also increase the risk of non-cancer diseases. It is not known, however......, whether such effects also occur following the lower doses and dose rates of public health concern. METHODS: We used data from an international (15-country) nuclear workers cohort study to evaluate whether mortality from diseases other than cancer is related to low doses of external ionizing radiation....... Analyses included 275 312 workers with adequate information on socioeconomic status, over 4 million person-years of follow-up and an average cumulative radiation dose of 20.7 mSv; 11 255 workers had died of non-cancer diseases. RESULTS: The excess relative risk (ERR) per Sv was 0.24 [95% CI (confidence...

  4. Impact of post-implant dosimetric parameters on the quality of life of patients treated with low-dose rate brachytherapy for localised prostate cancer: results of a single-institution study

    International Nuclear Information System (INIS)

    To assess the relationship between dosimetric parameters and the quality of life (QL) outcomes of patients with low-intermediate-risk localised prostate cancer (LPC) treated with low-dose-rate brachytherapy (LDR-BT). We evaluated the participants in two consecutive prospective studies of the QL of patients treated with LDR-BT for LPC. QL was evaluated by means of a patient-completed questionnaire assessing non functional [physical (PHY) and psychological (PSY) well-being, physical autonomy (POW), social relationships (REL)] and functional scales [urinary (URI), rectal (REC), and sexual (SEX) function]; a scale for erectile function (ERE) was included in the second study. Urethra (D10 ≤ 210 Gy) and rectal wall constraints (V100 ≤ 0.5 cc) were used for pre-planning dosimetry and were assessed with post planning computerized tomography one month later for each patient. QL was assessed in 251 LPC patients. Dosimetry did not influence the non-functional scales. As expected, a progressive impairment in sexual and erectile function was reported one month after LDR-BT, and became statistically significant after the third year. Rectal function significantly worsened after LDR-BT, but the differences progressively decreased after the 1-year assessment. Overall urinary function significantly worsened immediately after LDR-BT and then gradually improved over the next three years. Better outcomes were reported for V100 rectal wall volumes of ≤ 0.5 cc and D10 urethra values of ≤ 210 Gy. The findings of this study show that dosimetric parameters influence only functional QL outcomes while non-functional outcomes are only marginally influenced

  5. Low-dose CT scan screening for lung cancer: comparison of images and radiation doses between low-dose CT and follow-up standard diagnostic CT

    OpenAIRE

    ONO, KOJI; Hiraoka, Toru; Ono, Asami; Komatsu, Eiji; Shigenaga, Takehiko; Takaki, Hajime; Maeda, Toru; Ogusu, Hiroyuki; Yoshida, Shintaro; Fukushima, Kiyoyasu; Kai, Michiaki

    2013-01-01

    Objectives This study aim to compare image quality and radiation doses between low-dose CT and follow-up standard diagnostic CT for lung cancer screening. Methods In a single medical institution, 19 subjects who had been screened for lung cancer by low-dose CT before going through follow-up standard diagnostic CT were randomly selected. Both CT image sets for all subjects were independently evaluated by five specialized physicians. Results There were no significant differences between low-dos...

  6. ATM phosphorylation in HepG2 cells following continuous low dose-rate irradiation

    International Nuclear Information System (INIS)

    Objective: To investigate the change of ATM phosphorylation in HepG2 cells following a continuous low dose-rate irradiation. Methods: Cells were persistently exposed to low dose-rate (8.28 cGy/h) irradiation. Indirect immunofluorescence and Western blot were used to detect the expression of ATM phosphorylated proteins. Colony forming assay was used to observe the effect of a low dose-rate irradiation on HepG2 cell survival. Results: After 30 min of low dose-rate irradiation, the phosphorylation of ATM occurred. After 6 h persistent irradiation, the expression of ATM phosphorylated protein reached the peak value, then gradually decreased. After ATM phosphorylation was inhibited with Wortmannin, the surviving fraction of HepG2 cells was lower than that of the irradiation alone group at each time point (P<0.05). Conclusions: Continuous low dose-rate irradiation attenuated ATM phosphorylation, suggesting that continuous low dose-rate irradiation has a potential effect for increasing the radiosensitivity of HepG2 cells. (authors)

  7. Combined chemoradiotherapy with daily low-dose cisplatin in stage III non-small cell lung cancer. An interim report

    International Nuclear Information System (INIS)

    To improve the local control of stage III non-small cell lung cancer, we tried concurrent chemoradiotherapy with daily low-dose cisplatin during the first 5 weeks conventional radiotherapy. Ten consecutive patients with stage III non-small cell lung cancer were treated with chemoradiotherapy with 66 Gy in conventional fractionation and concurrent daily low-dose cisplatin (4 mg/m2), which was given 5 days per week (from Monday to Friday) for the first 5 weeks. There was no case with ≥grade 3 toxicity. The median survival was 14.6 months, and the 2-year local progression-free survival rate was 35%. Daily low-dose cisplatin combined with conventional radiotherapy was considered to be feasible and to have the possibility to offer better local control than radiotherapy alone in the treatment of stage III non-small cell lung cancer. (author)

  8. 20 percent lower lung cancer mortality with low-dose CT vs chest X-ray

    Science.gov (United States)

    Scientists have found a 20 percent reduction in deaths from lung cancer among current or former heavy smokers who were screened with low-dose helical computed tomography (CT) versus those screened by chest X-ray.

  9. Low-dose-rate brachytherapy as the sole radiation modality in the management of patients with early-stage breast cancer treated with breast-conserving therapy: preliminary results of a pilot trial

    International Nuclear Information System (INIS)

    Purpose: We present the preliminary findings of our in-house protocol treating the tumor bed alone after lumpectomy with low-dose-rate (LDR) interstitial brachytherapy in selected patients with early-stage breast cancer treated with breast-conserving therapy (BCT). Methods and Materials: Since March 1, 1993, 60 women with early-stage breast cancer were entered into a protocol of tumor bed irradiation only using an interstitial LDR implant with iodine-125. Patients were eligible if the tumor was ≤3 cm, margins were ≥2 mm, there was no extensive intraductal component, the axilla was surgically staged, and a postoperative mammogram was performed. Implants were placed using a standardized template either at the time of reexcision or shortly after lumpectomy. A total of 50 Gy was delivered at 0.52 Gy/h over a period of 96 h to the lumpectomy bed plus a 2-cm margin. Perioperative complications, cosmetic outcome, and local control were assessed. Results: The median follow-up for all patients is 20 months. Three patients experienced minimal perioperative pain that required temporary nonnarcotic analgesics. There have been four postoperative infections which resolved with oral antibiotics. No significant skin reactions related to the implant were noted and no patient experienced impaired would healing. Early cosmetic results reveal minimal changes consisting of transient hyperpigmentation of the skin at the puncture sites and temporary induration in the tumor bed. Good to excellent cosmetic results were noted in all 19 patients followed up a minimum of 24 months posttherapy. To date, 51 women have obtained 6-12-month follow-up mammograms and no recurrences have been noted. All patients currently have no physical signs of recurrence, and no patient has failed regionally or distantly. Conclusion: Treatment of the tumor bed alone with LDR interstitial brachytherapy appears to be well tolerated, and early results are promising. Long-term follow-up of these patients is

  10. Low-dose capecitabine (Xeloda) for treatment for gastrointestinal cancer

    OpenAIRE

    Miger, Jasmine; Holmqvist, Annica; Sun, Xiao-Feng; Albertsson, Maria

    2014-01-01

    The prodrug capecitabine (Xeloda) has been an important drug for treatment for gastrointestinal cancer (GI-cancer). This study explores the efficacy of continuous metronomic Xeloda, as well as tolerability and best response during treatment. Patients (n = 35) with stage IV GI-cancer were included in the study and were divided into two groups; upper (n = 13) and lower (n = 22) GI-cancer. All patients were given continuous metronomic Xeloda (500 mg × 2). Best response was measured by radiologic...

  11. The short term effects of Low-dose-rate Radiation on EL4 Lymphoma Cell

    Energy Technology Data Exchange (ETDEWEB)

    Bong, Jin Jong; Kang, Yu Mi; Shin, Suk Chull; Choi, Moo Hyun; Choi, Seung Jin; Kim, Hee Sun [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd, Seoul (Korea, Republic of); Lee, Kyung Mi [Global Research Lab, BAERI Institute, Dept. of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul (Korea, Republic of)

    2012-06-15

    To determine the biological effects of low-dose-rate radiation ({sup 137}Cs, 2.95 mGy/h) on EL4 lymphoma cells during 24 h, we investigated the expression of genes related to apoptosis, cell cycle arrest, DNA repair, iron transport, and ribonucleotide reductase. EL4 cells were continuously exposed to low-dose-rate radiation (total dose: 70.8 mGy) for 24 h. We analyzed cell proliferation and apoptosis by trypan blue exclusion and flow cytometry, gene expression by real-time PCR, and protein levels with the apoptosis ELISA kit. Apoptosis increased in the Low-dose-rate irradiated cells, but cell number did not differ between non- (Non-IR) and Low-dose-rate irradiated (LDR-IR) cells. In concordance with apoptotic rate, the transcriptional activity of ATM, p53, p21, and Parp was upregulated in the LDR-IR cells. Similarly, Phospho-p53 (Ser15), cleaved caspase 3 (Asp175), and cleaved Parp (Asp214) expression was upregulated in the LDR-IR cells. No difference was observed in the mRNA expression of DNA repair-related genes (Msh2, Msh3, Wrn, Lig4, Neil3, ERCC8, and ERCC6) between Non-IR and LDR-IR cells. Interestingly, the mRNA of Trfc was upregulated in the LDR-IR cells. Therefore, we suggest that short-term Low-dose-rate radiation activates apoptosis in EL4 lymphoma cells.

  12. The short term effects of Low-dose-rate Radiation on EL4 Lymphoma Cell

    International Nuclear Information System (INIS)

    To determine the biological effects of low-dose-rate radiation (137Cs, 2.95 mGy/h) on EL4 lymphoma cells during 24 h, we investigated the expression of genes related to apoptosis, cell cycle arrest, DNA repair, iron transport, and ribonucleotide reductase. EL4 cells were continuously exposed to low-dose-rate radiation (total dose: 70.8 mGy) for 24 h. We analyzed cell proliferation and apoptosis by trypan blue exclusion and flow cytometry, gene expression by real-time PCR, and protein levels with the apoptosis ELISA kit. Apoptosis increased in the Low-dose-rate irradiated cells, but cell number did not differ between non- (Non-IR) and Low-dose-rate irradiated (LDR-IR) cells. In concordance with apoptotic rate, the transcriptional activity of ATM, p53, p21, and Parp was upregulated in the LDR-IR cells. Similarly, Phospho-p53 (Ser15), cleaved caspase 3 (Asp175), and cleaved Parp (Asp214) expression was upregulated in the LDR-IR cells. No difference was observed in the mRNA expression of DNA repair-related genes (Msh2, Msh3, Wrn, Lig4, Neil3, ERCC8, and ERCC6) between Non-IR and LDR-IR cells. Interestingly, the mRNA of Trfc was upregulated in the LDR-IR cells. Therefore, we suggest that short-term Low-dose-rate radiation activates apoptosis in EL4 lymphoma cells.

  13. Review of low dose-rate epidemiological studies and biological mechanisms of dose-rate effects on radiation induced carcinogenesis

    International Nuclear Information System (INIS)

    Radiation protection system adopts the linear non-threshold model with using dose and dose-rate effectiveness factor (DDREF). The dose-rate range where DDREF is applied is below 100 mGy per hour, and it is regarded that there are no dose-rate effects at very low dose rate, less than of the order of 10 mGy per year, even from the biological risk evaluation model based on cellular and molecular level mechanisms for maintenance of genetic integrity. Among low dose-rate epidemiological studies, studies of residents in high natural background areas showed no increase of cancer risks at less than about 10 mGy per year. On the other hand, some studies include a study of the Techa River cohort suggested the increase of cancer risks to the similar degree of Atomic bomb survivor data. The difference of those results was supposed due to the difference of dose rate. In 2014, International Commission on Radiological Protection opened a draft report on stem cell biology for public consultations. The report proposed a hypothesis based on the new idea of stem cell competition as a tissue level quality control mechanism, and suggested that it could explain the dose-rate effects around a few milligray per year. To verify this hypothesis, it would be needed to clarify the existence and the lowest dose of radiation-induced stem cell competition, and to elucidate the rate of stem cell turnover and radiation effects on it. As for the turnover, replenishment of damaged stem cells would be the important biological process. It would be meaningful to collect the information to show the difference of dose rates where the competition and the replenishment would be the predominant processes. (author)

  14. Risk of Low Dose/Low Dose Rate Ionizing Radiation to Humans Symposium at the EMS 2009 Annual Meeting - September 2006

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, William F.; von Borstel, Robert C.; Brenner,; Redpath, J. Leslie; Erickson, Barbra E.; Brooks,

    2009-11-12

    The low dose symposium thoughtfully addressed controversy of risk from low dose radiation exposure, hormesis and radon therapy. The stem cell symposium cogently considered the role of DNA damage and repair in hematopoietic stem cells underlying aging and malignancy and provocatively presented evidence that stem cells may have distinct morphologies and replicative properties, as well as special roles in cancer initiation. In the epigenetics symposium, studies illustrated the long range interaction of epigenetic mechanisms, the roles of CTCF and BORIS in region/specific regulation of epigenetic processes, the impact of DNA damage on epigenetic processes as well as links between epigenetic mechanisms and early nutrition and bystander effects.

  15. Low-dose aspirin or other nonsteroidal anti-inflammatory drug use and prostate cancer risk

    DEFF Research Database (Denmark)

    Skriver, Charlotte; Dehlendorff, Christian; Borre, Michael;

    2016-01-01

    PURPOSE: Increasing evidence suggests that aspirin use may protect against prostate cancer. In a nationwide case-control study, using Danish high-quality registry data, we evaluated the association between the use of low-dose aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) and the...... risk of prostate cancer. METHODS: We identified 35,600 patients (cases) with histologically verified prostate cancer during 2000-2012. Cases were matched to 177,992 population controls on age and residence by risk-set sampling. Aspirin and nonaspirin NSAID exposure was defined by type, estimated dose......, duration, and consistency of use. We used conditional logistic regression to estimate odds ratios (ORs), with 95 % confidence intervals (CIs), for prostate cancer associated with low-dose aspirin (75-150 mg) or nonaspirin NSAID use, adjusted for potential confounders. RESULTS: Use of low-dose aspirin was...

  16. Calculations of cell survival at low dose rates using the LPL model

    International Nuclear Information System (INIS)

    The lethal potentially lethal (LPL) model is used to study the low dose rate problem. During irradiation, it is assumed that lesions are being created, repaired, and misrepaired. Two differential equations are used to describe the variations of the rates of production with time of potentially lethal (n/sub B/) and lethal (n/sub C/) lesions, respectively

  17. The variance-covariance method: Microdosimetry in time-varying low dose-rate radiation fields

    OpenAIRE

    Breckow, Joachim; Wenning, A.; Roos, H; Kellerer, Albrecht M.

    1988-01-01

    The variance-covariance method is employed at low doses and in radiation fields of low dose rates from an241Am (4 nGy/s) and a90Sr (300 nGy/s) source. The preliminary applications and results illustrate some of the potential of the method, and show that the dose average of lineal energy or energy imparted can be determined over a wide range of doses and dose rates. The dose averages obtained with the variance-covariance method in time-varying fields, for which the conventional variance method...

  18. Low-dose paclitaxel modulates tumour fibrosis in gastric cancer

    OpenAIRE

    TSUKADA, TOMOYA; Fushida, Sachio; Harada, Shinichi; Terai, Shiroh; Yagi, Yasumichi; Kinoshita, Jun; OYAMA, KATSUNOBU; Tajima, Hidehiro; NINOMIYA, ITASU; FUJIMURA, TAKASHI; Ohta, Tetsuo

    2013-01-01

    Various treatments have been used for peritoneal dissemination, which is the most common mode of metastasis in gastric cancer, but sufficiently good clinical outcomes have not yet been obtained because of the presence of rich fibrous components and acquired drug resistance. Epithelialmesenchymal transition (EMT) is one of the major causes of tissue fibrosis and transforming growth factor-β (TGF-β) has a pivotal function in the progression of EMT. Smad proteins play an important role in the TG...

  19. Risk of breast cancer following low-dose radiation exposure

    International Nuclear Information System (INIS)

    Risk of breast cancer following radiation exposure was studied, based on surveys of tuberculosis patients who had multiple fluoroscopic examinations of the chest, mastitis patients given radiotherapy, and atomic bomb survivors. Analysis suggests that the risk is greatest for persons exposed as adolescents, although exposure at all ages carries some risk. The dose-response relationship was consistent with linearity in all studies. Direct evidence of radiation risk at doses under 0.5 Gy (50 rad) is apparent among A-bomb survivors. Fractionation does not appear to diminish risk, nor does time since exposure (even after 45 years of observation). The interval between exposure and the clinical appearance of radiogenic breast cancer may be mediated by hormonal or other age-related factors but is unrelated to dose. Age-specific absolute risk estimtes for all studies are remarkably similar. The best estimate of risk among American women exposed after age 20 is 6.6 excess cancers/104 WY-Gy

  20. Cancer risk from low doses of ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Auvinen, A.

    1997-06-01

    The aim of the study was to estimate cancer risk from small doses of ionizing radiation from various sources, including both external and internal exposure. The types of radiation included alpha, gamma, and neutron radiation. A nationwide follow-up study covering the years up to 1992 revealed no significant association between fallout from the Chernobyl accident and incidence of childhood leukemia. An excess of eight cases or more per year could be excluded. However, some indication of an increase was evident in the most heavily affected areas. Furthermore, the risk estimates were in accordance with those reported from Hiroshima and Nagasaki, although the confidence intervals were wide. (282 refs.).

  1. Cancer risk from low doses of ionizing radiation

    International Nuclear Information System (INIS)

    The aim of the study was to estimate cancer risk from small doses of ionizing radiation from various sources, including both external and internal exposure. The types of radiation included alpha, gamma, and neutron radiation. A nationwide follow-up study covering the years up to 1992 revealed no significant association between fallout from the Chernobyl accident and incidence of childhood leukemia. An excess of eight cases or more per year could be excluded. However, some indication of an increase was evident in the most heavily affected areas. Furthermore, the risk estimates were in accordance with those reported from Hiroshima and Nagasaki, although the confidence intervals were wide. (282 refs.)

  2. Bioassay in BALB/c mice exposed to low dose rate radiation

    Energy Technology Data Exchange (ETDEWEB)

    Km, Sung Dae; Gong, Eun Ji; Bae, Min Ji; Yang, Kwang Mo; Kim, Joong Sun [Dongnam Institute of Radiological and Medical Sciences, Suwon (Korea, Republic of)

    2012-09-15

    The present study was performed to investigate the toxicity of low-dose-rate irradiation in BALB/c mice. Twenty mice of each sex were randomly assigned to four groups of five mice each and were exposed to 0 (sham), 0.02, 0.2, or 2 Gy, equivalents to low-dose-rate irradiation to 3.49 mGy{center_dot}h{sup -1}. Urine, blood, and blood biochemistry were analyzed, and organ weight was measured. The low-dose-rate irradiation did not induce any toxicologically significant changes in mortality, clinical signs, body weight, food and water consumption, urinalysis, and serum biochemistry. However, the weights of reproductive organs including the testis, ovary, and uterus decreased in a dose-dependent manner. Irradiation at 2 Gy significantly decreased the testis, ovary, and uterus weights, but did not change the weights of other organs. There were no adverse effects on hematology in any irradiated group and only the number of neutrophils increased dose dependently. The low-dose-rate irradiation exposure did not cause adverse effects in mice at dose levels of 2 Gy or less, but the reproductive systems of male and female mice showed toxic effects.

  3. Bioassay in BALB/c mice exposed to low dose rate radiation

    International Nuclear Information System (INIS)

    The present study was performed to investigate the toxicity of low-dose-rate irradiation in BALB/c mice. Twenty mice of each sex were randomly assigned to four groups of five mice each and were exposed to 0 (sham), 0.02, 0.2, or 2 Gy, equivalents to low-dose-rate irradiation to 3.49 mGy·h-1. Urine, blood, and blood biochemistry were analyzed, and organ weight was measured. The low-dose-rate irradiation did not induce any toxicologically significant changes in mortality, clinical signs, body weight, food and water consumption, urinalysis, and serum biochemistry. However, the weights of reproductive organs including the testis, ovary, and uterus decreased in a dose-dependent manner. Irradiation at 2 Gy significantly decreased the testis, ovary, and uterus weights, but did not change the weights of other organs. There were no adverse effects on hematology in any irradiated group and only the number of neutrophils increased dose dependently. The low-dose-rate irradiation exposure did not cause adverse effects in mice at dose levels of 2 Gy or less, but the reproductive systems of male and female mice showed toxic effects.

  4. Low-dose aspirin use and the risk of ovarian cancer in Denmark

    DEFF Research Database (Denmark)

    Baandrup, Lone; Kjaer, S K; Olsen, J H;

    2015-01-01

    BACKGROUND: A comprehensive body of evidence has shown that aspirin has cancer-preventive effects, particularly against gastrointestinal cancer, but its effects on the risk of ovarian cancer are less well established. This nationwide case-control study examined the association between low...... were seen for mucinous and endometrioid tumours. CONCLUSION: This nationwide case-control study indicates that low-dose aspirin use may be associated with a reduced risk of epithelial ovarian cancer....... regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for the association between low-dose aspirin use and the risk of epithelial ovarian cancer, both overall and for specific histological types. RESULTS: For 4103 ovarian cancer cases and 58 706 population controls, the...

  5. Concurrent chemoradiotherapy with daily low dose CDDP/5FU for locally unresectable head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kohno, Naoyuki; Kitahara, Satoshi; Tamura, Etsuyo; Tanabe, Tetsuya [Kyorin Univ., Mitaka, Tokyo (Japan). School of Medicine; Murata, Yasuhiro [National Defence Medical Coll., Tokorozawa, Saitama (Japan)

    2002-07-01

    To improve the local control rate and the prognosis of locally unresectable head and neck cancer patients, we studied the concurrent chemoradiotherapy. Between September 1996 and September 2000, thirty-eight patients with locally unresectable head and neck cancer were administered concurrent chemoradiotherapy consisting of low-dose and long-term treatment with cisplatin (CDDP) plus 5-fluorouracil (5FU), or (L-CF); the L-CF regimen consisted of CDDP, 3 mg/m{sup 2} on 5 days of the week and 5FU, 150 mg/m{sup 2} as a 24-hour infusion on 5 days of the week. Concurrently, conventional radiotherapy was given up to total dose of around 60 Gy. In the 36 patients evaluable for response, 19 complete and 10 partial responses were noted, with an overall response rate of 81%. Oral mucositis and myelosuppression were the major side effects and dose limiting toxicity. This study demonstrates increase in survival among the responders (complete+partial) in the concurrent chemoradiotherapy setting. We concluded that this treatment strategy was beneficial. Further studies for patients with locally unresectable head and neck cancer are warranted. (author)

  6. The American Brachytherapy Society recommendations for low-dose-rate brachytherapy for carcinoma of the cervix

    International Nuclear Information System (INIS)

    Purpose: This report presents guidelines for using low-dose-rate (LDR) brachytherapy in the management of patients with cervical cancer. Methods: Members of the American Brachytherapy Society (ABS) with expertise in LDR brachytherapy for cervical cancer performed a literature review, supplemented by their clinical experience, to formulate guidelines for LDR brachytherapy of cervical cancer. Results: The ABS strongly recommends that radiation treatment for cervical carcinoma (with or without chemotherapy) should include brachytherapy as a component. Precise applicator placement is essential for improved local control and reduced morbidity. The outcome of brachytherapy depends, in part, on the skill of the brachytherapist. Doses given by external beam radiotherapy and brachytherapy depend upon the initial volume of disease, the ability to displace the bladder and rectum, the degree of tumor regression during pelvic irradiation, and institutional practice. The ABS recognizes that intracavitary brachytherapy is the standard technique for brachytherapy for cervical carcinoma. Interstitial brachytherapy should be considered for patients with disease that cannot be optimally encompassed by intracavitary brachytherapy. The ABS recommends completion of treatment within 8 weeks, when possible. Prolonging total treatment duration can adversely affect local control and survival. Recommendations are made for definitive and postoperative therapy after hysterectomy. Although recognizing that many efficacious LDR dose schedules exist, the ABS presents suggested dose and fractionation schemes for combining external beam radiotherapy with LDR brachytherapy for each stage of disease. The dose prescription point (point A) is defined for intracavitary insertions. Dose rates of 0.50 to 0.65 Gy/h are suggested for intracavitary brachytherapy. Dose rates of 0.50 to 0.70 Gy/h to the periphery of the implant are suggested for interstitial implant. Use of differential source activity or

  7. Method of simulation of low dose rate for total dose effect in 0.18 {mu}m CMOS technology

    Energy Technology Data Exchange (ETDEWEB)

    He Baoping; Yao Zhibin; Guo Hongxia; Luo Yinhong; Zhang Fengqi; Wang Yuanming; Zhang Keying, E-mail: baopinghe@126.co [Northwest Institute of Nuclear Technology, Xi' an 710613 (China)

    2009-07-15

    Three methods for simulating low dose rate irradiation are presented and experimentally verified by using 0.18 {mu}m CMOS transistors. The results show that it is the best way to use a series of high dose rate irradiations, with 100 {sup 0}C annealing steps in-between irradiation steps, to simulate a continuous low dose rate irradiation. This approach can reduce the low dose rate testing time by as much as a factor of 45 with respect to the actual 0.5 rad (Si)/s dose rate irradiation. The procedure also provides detailed information on the behavior of the test devices in a low dose rate environment.

  8. Method of simulation of low dose rate for total dose effect in 0.18 μm CMOS technology

    International Nuclear Information System (INIS)

    Three methods for simulating low dose rate irradiation are presented and experimentally verified by using 0.18 μm CMOS transistors. The results show that it is the best way to use a series of high dose rate irradiations, with 100 0C annealing steps in-between irradiation steps, to simulate a continuous low dose rate irradiation. This approach can reduce the low dose rate testing time by as much as a factor of 45 with respect to the actual 0.5 rad (Si)/s dose rate irradiation. The procedure also provides detailed information on the behavior of the test devices in a low dose rate environment.

  9. Intracavitary after loading techniques, advantages and disadvantages with high and low dose-rate methods

    International Nuclear Information System (INIS)

    Even though suggested as early as 1903, it is only when suitable sealed gamma sources became available, afterloading methods could be developed for interstitial as well as intracavitary work. Manual afterloading technique can be used only for low dose rate irradiation, while remote controlled afterloading technique can be used for both low and high dose-rate irradiation. Afterloading units used at the Karolinska Institute, Stockholm, are described, and experience of their use is narrated briefly. (M.G.B.)

  10. Theoretical explanation of enhanced low dose rate sensitivity in erbium-doped optical fibers.

    Science.gov (United States)

    Gilard, Olivier; Thomas, Jérémie; Troussellier, Laurent; Myara, Mikhael; Signoret, Philippe; Burov, Ekaterina; Sotom, Michel

    2012-05-01

    A new theoretical framework is proposed to explain the dose and dose-rate dependence of radiation-induced absorption in optical fibers. A first-order dispersive kinetics model is used to simulate the growth of the density of color centers during an irradiation. This model succeeds in explaining the enhanced low dose rate sensitivity observed in certain kinds of erbium-doped optical fiber and provides some insight into the physical reasons behind this sensitivity. PMID:22614396

  11. Development and characterization of a novel variable low-dose rate irradiator for in vivo mouse studies

    OpenAIRE

    Olipitz, Werner; Hembrador, Sheena; Davidson, Matthew; Yanch, Jacquelyn C; Engelward, Bevin P.

    2010-01-01

    Radiation exposure of humans generally results in low doses delivered at low dose-rate. Our limited knowledge of the biological effects of low dose radiation is mainly based on data from the atomic bomb long-term survivor study (LSS) cohort. However, the total doses and dose-rates in the LSS cohort are still higher than most environmental and occupational exposures in humans. Importantly, the dose-rate is a critical determinant of health risks stemming from radiation exposure. Understanding t...

  12. Efficacy of a Low Dose of Estrogen on Antioxidant Defenses and Heart Rate Variability

    Directory of Open Access Journals (Sweden)

    Cristina Campos

    2014-01-01

    Full Text Available This study tested whether a low dose (40% less than the pharmacological dose of 17-β estradiol would be as effective as the pharmacological dose to improve cardiovascular parameters and decrease cardiac oxidative stress. Female Wistar rats (n=9/group were divided in three groups: (1 ovariectomized (Ovx, (2 ovariectomized animals treated for 21 days with low dose (LE; 0.2 mg, and (3 high dose (HE; 0.5 mg 17-β estradiol subcutaneously. Hemodynamic assessment and spectral analysis for evaluation of autonomic nervous system regulation were performed. Myocardial superoxide dismutase (SOD and catalase (CAT activities, redox ratio (GSH/GSSG, total radical-trapping antioxidant potential (TRAP, hydrogen peroxide, and superoxide anion concentrations were measured. HE and LE groups exhibited an improvement in hemodynamic function and heart rate variability. These changes were associated with an increase in the TRAP, GSH/GSSG, SOD, and CAT. A decrease in hydrogen peroxide and superoxide anion was also observed in the treated estrogen groups as compared to the Ovx group. Our results indicate that a low dose of estrogen is just as effective as a high dose into promoting cardiovascular function and reducing oxidative stress, thereby supporting the approach of using low dose of estrogen in clinical settings to minimize the risks associated with estrogen therapy.

  13. Oxygen enhancement ratio (OER) and therapeutic gain factor (GF) for californium-252 at low dose rate

    International Nuclear Information System (INIS)

    The potential benefit of the introduction of californium-252 in interstitial and intracavitary therapy is related to the greater efficiency of its neutron emission against anoxic cancer cells. In that respect, the oxygen enhancement ratio (OER) of the 252Cf emission has been determined for a continuous low dose rate irradiation. The biological system is growth inhibition in Vicia faba bean roots. A new Vicia faba ''BelB'' strain has been used, which better tolerates long periods (up to about 10 hours) of anoxia. In a first series of experiments, for a 252Cf (Dsub(n+γ)) dose rate of 0.11 Gy.h-1, an OER of 1.4+-0.1 was observed (the γ contribution Dγ to the total absorbed dose Dsub(n+γ) was 0.35 at the position of the root tips). In a second series of experiments, in somewhat different geometrical conditions with a 252Cf (Dsub(n+γ)) dose rate of 0.13 Gy.h-1, an OER of 1.5+-0.1 was observed (Dγ/Dsub(n+γ)=0.42). The OER values observed for similar irradiation times, with iridium-192 γ-rays, were 2.3+-0.2 and 2.6+-0.1 respectively, which leads to therapeutic gain factors (GF) of 1.6 and 1.7 respectively. These GF values are slightly lower than those previously obtained (GF=1.8) on the same system, with d(50)-Be p(75)-Be and 15 MeV neutron beams

  14. Cancer risk at low doses of ionizing radiation: artificial neural networks inference from atomic bomb survivors

    OpenAIRE

    Sasaki, Masao S.; Tachibana, Akira; Takeda, Shunichi

    2013-01-01

    Cancer risk at low doses of ionizing radiation remains poorly defined because of ambiguity in the quantitative link to doses below 0.2 Sv in atomic bomb survivors in Hiroshima and Nagasaki arising from limitations in the statistical power and information available on overall radiation dose. To deal with these difficulties, a novel nonparametric statistics based on the ‘integrate-and-fire’ algorithm of artificial neural networks was developed and tested in cancer databases established by the R...

  15. Cancer risk at low doses of ionizing radiation: artificial neural networks inference from atomic bomb survivors.

    OpenAIRE

    Sasaki, Masao S.; Tachibana, Akira; Takeda, Shunichi

    2014-01-01

    Cancer risk at low doses of ionizing radiation remains poorly defined because of ambiguity in the quantitative link to doses below 0.2 Sv in atomic bomb survivors in Hiroshima and Nagasaki arising from limitations in the statistical power and information available on overall radiation dose. To deal with these difficulties, a novel nonparametric statistics based on the 'integrate-and-fire' algorithm of artificial neural networks was developed and tested in cancer databases established by the R...

  16. Life span and tumorigenesis in mice exposed to continuous low dose-rate γ-rays

    International Nuclear Information System (INIS)

    To evaluate late biological effects of chronic low dose-rate radiation, we are conducting two experiments. Experiment 1 - Late effects of chronic low dose-rate γ-rays irradiation on SPF mice, using life-span and pathological changes as parameters. Continuous irradiation with γ-rays for 400 days was performed using 137Cs γ-rays at dose-rates of 20 mGy/day, 1 mGy/day and 0.05 mGy/day with accumulated doses equivalent to 8000 mGy, 400 mGy and 20 mGy, respectively. All mice were kept until they died a natural death. Statistical analyses show that the life spans of both sexes irradiated at 20mGy/day (p<0.0001) and of females irradiated at 1 mGy/day (p<0.05) were significantly shorter than that of the control group. Partial results show that the most common lethal neoplasms in the pooled data of non-irradiated control and irradiated make mice, in order of frequency, were neoplasms of the lymphohematopoietic system, liver, and lung. In female mice, neoplasms of the lymphohematopoietic system and soft tissue were common. Experiment 2 - Effects on the progeny of chronic low dose-rate γ-ray irradiated SPF mice: pilot study, was started in 1999 and is currently in progress. (author)

  17. Interstitial brachytherapy with Ir-192 low-dose-rate in the treatment of primary and recurrent cancer of the oral cavity and oropharynx. Review of 318 patients treated between 1985 and 1997

    International Nuclear Information System (INIS)

    To evaluate the impact of postoperative interstitial brachytherapy with and without external radiotherapy in the treatment of primary and recurrent squamous cell carcinoma of the oral cavity and oropharynx. Patients and Methods: Between 1985 and 1997, a total of 318 patients were treated by interstitial Ir-192 low-dose-rate brachytherapy as part of their primary (n = 236) or recurrent treatment (n = 82). There were 263 male (83%) and 55 (17%) female patients. The distribution of UICC (1997) stages was as follows: I (61 patients, 19%), II (71 patients, 22%), III (58 patients, 18%), IV (128 patients, 40%). The primary tumor site was located in the oral cavity in 201 patients (63%), in the oropharynx in 86 patients (27%), lower lip in 19 patients (6%) and other regions in twelve cases (4%). Treatment concepts did not vary over the time and were dictated by the initial tumor extension: a total of 175 patients (55%) received a combination of surgery, interstitial b brachytherapy (23-25 Gy) and external radiotherapy (50-60 Gy), 60 patients (19%) surgery and interstitial brachytherapy (45-55 Gy) alone. Advanced disease not amenable to primary surgery was either treated by radiochemotherapy and interstitial brachytherapy in 39 patients (12%) or a combination of interstitial brachytherapy, external radiotherapy and interstitial hyperthermia in 44 patients (14%). Results: Overall survival rates following primary and recurrent treatment were 50 ± 4% and 29 ± 5%, respectively, at 5 years (p < 0.0001). A significant impact on overall survival rate was noted for UICC stage: patients in stage I/II had survival rates of 64 ± 5% and 57 ± 10%, respectively, while patients in stage III/IV had survival rates of 39 ± 5% and 15 ± 5%, respectively, at 5 years (p < 0.0001). In addition, grading (p = 0.01) and hemoglobin levels (p = 0.05) had a significant influence on overall survival. Local tumor control rates for all patients were 74 ± 3% and 57 ± 7% at 5 years following primary

  18. Mitochondrial DNA deletion and aging induced by low dose rate of radiation in mice

    International Nuclear Information System (INIS)

    Mitochondrial DNA (mtDNA) is a closed circular DNA molecule and more than 100 copies are present in a cell. Deletion mutation of mtDNA accumulates with aging and can be a suitable marker for estimating biological effects on radiation-induced mutation in mice. The mice life span study in the Institute for Environmental Sciences suggests that low dose rate of radiation might accelerate aging in mice prolongly irradiated by 137Cs γ-rays (20 mGy/day for 400 days). To know the relationships between low dose rate irradiation, aging and mutation, we observed deletion mutations of mtDNA from mice irradiated by 137Cs γ-rays (20 mGy/day) for different dates. The real-time fluorescence PCR method was sensitive enough to determine the relative amount of deletion in several tissues. Age-dependent accumulations of deletion mutations were observed in aged mice (250-700 days). However, a significant increase of deletion mutation related to accumulated dose was not detected in 137Cs γ-ray irradiated mice for 4-12 Gy. These data suggest that the effect of the low dose rate irradiation on mtDNA is within a background level. (author)

  19. Relationship of HepG2 cell sensitivity to continuous low dose-rate irradiation with ATM phosphorylation

    Institute of Scientific and Technical Information of China (English)

    Quelin Mei; Jianyong Yang; Duanming Du; Zaizhong Cheng; Pengcheng liu

    2008-01-01

    Objective: To investigate the change of ATM phosphorylation in HepG2 cells and its effect on HepG2 cell survival under a continuous low dose-rate irradiation.Methods: HepG2 cells were exposed to equivalent doses of irradiation delivered at either a continuous low dose-rate (7.76 cGy/h) or a high dose-rate (4500 cGy/h).The ATM phosphorylated proteins and surviving fraction of HepG2 cell after low dose-rate irradiation were compared with that after equivalent doses of high dose-rate irradiation.Results: The phosphorylation of ATM protein was maximal at 0.5 Gy irradiation delivered at either a high dose-rate or a continuous low dose-rate.As the radiation dose increased, the phosphorylation of ATM protein decreased under continuous low dose-rate irradiation.However, the phosphorylation of ATM protein was remained stable under high dose-rate irradiation.When the phosphorylation of ATM protein under continuous low dose-rate irradiation was equal to that under high dose-rate irradiation, there was no significant difference in the surviving fraction of HepG2 cells between two ir-radiation methods (P>0.05).When the phosphorylation of ATM protein significantly decreased after continuous low dose-rate irradiation compared with that after high dose-rate irradiation, increased amounts of cell killing was found in low dose-rate irradiation (P<0.01).Conclusion: Continuous low dose-rate irradiation increases HepG2 cells radiosensitivity compared with high dose-rate irradiation.The increased amounts of cell killing following continuous low dose-rate exposures are associated with reduced ATM phosphorylated protein.

  20. Early detection of lung cancer using low-dose CT: an update

    International Nuclear Information System (INIS)

    Lung cancer is the leading cause of death from malignancy. Due to a lack of early symptoms patients usually undergo therapy at advanced tumor stages when prognosis is poor. Feasibility studies of low-dose spiral CT screening of heavy smokers have shown that many small, resectable lung cancers can be diagnosed at early stages using simple diagnostic algorithms based on size and attenuation of detected pulmonary nodules with a small proportion of invasive procedures for benign lesions. Preliminary results of repeat screening confirms small size and favourable stage distribution of detected cancers, using even simpler diagnostic algorithms: additional diagnostic procedures are only required in new or growing nodules whereas follow-up with low-dose CT is sufficient in nodules that appear unchanged to exclude slow growth. However, mortality reduction by lung cancer screening with low-dose CT has yet to be demonstrated. Several randomised controlled trials are under way to assess possible mortality reduction by comparison of mortalities in a screening group and a control group. It is hoped that through international cooperation data from these trials can be pooled to allow for statistically significant conclusions as early as possible. (orig.)

  1. Multi-level effects of low dose rate ionizing radiation on southern toad, Anaxyrus [Bufo] terrestris

    International Nuclear Information System (INIS)

    Despite their potential vulnerability to contaminants from exposure at multiple life stages, amphibians are one of the least studied groups of vertebrates in ecotoxicology, and research on radiation effects in amphibians is scarce. We used multiple endpoints to assess the radiosensitivity of the southern toad (Anaxyrus [Bufo] terrestris) during its pre-terrestrial stages of development -embryonic, larval, and metamorphic. Toads were exposed, from several hours after oviposition through metamorphosis (up to 77 days later), to four low dose rates of 137Cs at 0.13, 2.4, 21, and 222 mGy d-1, resulting in total doses up to 15.8 Gy. Radiation treatments did not affect hatching success of embryos, larval survival, or the length of the larval period. The individual family variation in hatching success of embryos was larger than the radiation response. In contrast, newly metamorphosed individuals from the higher dose-rate treatments had higher mass and mass/length body indices, a measure which may relate to higher post-metamorphic survival. The increased mass and index at higher dose rates may indicate that the chronic, low dose rate radiation exposures triggered secondary responses. Additionally, the increases in growth were linked to a decrease in DNA damage (as measured by the Comet Assay) in red blood cells at a dose rate of 21mGy d-1 and a total dose of 1.1 Gy. In conclusion, the complex effects of low dose rates of ionizing radiation may trigger growth and cellular repair mechanisms in amphibian larvae

  2. Multi-Level Effects of Low Dose Rate Ionizing Radiation on Southern Toad, Anaxyrus [Bufo] terrestris.

    Directory of Open Access Journals (Sweden)

    Karolina Stark

    Full Text Available Despite their potential vulnerability to contaminants from exposure at multiple life stages, amphibians are one of the least studied groups of vertebrates in ecotoxicology, and research on radiation effects in amphibians is scarce. We used multiple endpoints to assess the radiosensitivity of the southern toad (Anaxyrus [Bufo] terrestris during its pre-terrestrial stages of development -embryonic, larval, and metamorphic. Toads were exposed, from several hours after oviposition through metamorphosis (up to 77 days later, to four low dose rates of 137Cs at 0.13, 2.4, 21, and 222 mGy d-1, resulting in total doses up to 15.8 Gy. Radiation treatments did not affect hatching success of embryos, larval survival, or the length of the larval period. The individual family variation in hatching success of embryos was larger than the radiation response. In contrast, newly metamorphosed individuals from the higher dose-rate treatments had higher mass and mass/length body indices, a measure which may relate to higher post-metamorphic survival. The increased mass and index at higher dose rates may indicate that the chronic, low dose rate radiation exposures triggered secondary responses. Additionally, the increases in growth were linked to a decrease in DNA damage (as measured by the Comet Assay in red blood cells at a dose rate of 21 mGy d-1 and a total dose of 1.1 Gy. In conclusion, the complex effects of low dose rates of ionizing radiation may trigger growth and cellular repair mechanisms in amphibian larvae.

  3. Risk of prostate cancer in low-dose aspirin users: A retrospective cohort study.

    Science.gov (United States)

    Lapi, F; Levi, M; Simonetti, M; Cancian, M; Parretti, D; Cricelli, I; Sobrero, A; Cricelli, C

    2016-07-01

    A growing body of evidence indicates that use of low-dose aspirin (LDA) reduces the risk of certain adenocarcinomas. While there are several and consistent findings on the protective effect of LDA on colorectal and other cancers, few and conflicting evidence is available on prostate cancer (PCa). The aim of this study was to assess whether LDA reduces the incidence rate of PCa. We conducted a nationwide, population-based, retrospective cohort study by using Health Search IMS Health Longitudinal Patient Database (HSD). Patients with ischemic cardio- or cerebrovascular disease (index date) were identified. Time-dependent multivariable Cox proportional hazard models were adopted to estimate Hazard Ratios (HRs) and related 95% confidence intervals (95% CI) of PCa associated with use of LDA. The exposure was lagged by one year to consider the latency of drug effect on the outcome onset. Within a cohort 13,453 patients, the overall incidence rate of PCa was 2.5 per 1,000 person-years. Use of LDA was associated with a decreased incidence rate of PCa (HR = 0.64; 95% CI: 0.48-0.86), which was primarily driven by a frequency of LDA use equal to or higher than twice per week (HR = 0.60; 95% CI: 0.43-0.83). Such an association was more pronounced (HR = 0.43; 95% CI: 0.21-0.91) when LDA was used for five or more years. Our findings indicate that LDA use might be associated with a reduction of risk of PCa in patients with cardio- or cerebrovascular diseases. PMID:26915905

  4. Effects of emitter junction and passive base region on low dose rate effect in bipolar devices

    International Nuclear Information System (INIS)

    Low dose rate effect in bipolar devices consists in the increase of peripheral surface recombination current with dose rate decrease. This is due to the more rapid positive oxide charge and interface trap density build-up as the dose rate becomes lower. High dose rate elevated temperature irradiation is proposed for simulation if the low dose rate effect. In the present we tried to separate the effect of radiation-induced charge in the thick passivation oxide over the emitter junction and passive base regions of npn bipolar transistor. Its goal is to improve bipolar device design for use in space environments and nuclear installations. Three experiments were made during this work. 1. Experiment on radiation-induced charge neutralization (RICN) effect under elevated temperature was performed to show transistor degradation dependence on emitter-base bias. 2. High dose rate elevated and room temperature irradiation of bipolar transistors were performed to separate effects of emitter-junction and passive base regions. 3. Pre- and post- irradiation hydrogen ambient storage was used to investigate its effect on radiation-induced charge build-up over the passive base region. All experiments were performed with npn and pnp transistors. (authors)

  5. More than lung cancer: Automated analysis of low-dose screening CT scans

    OpenAIRE

    Mets, O.M.

    2012-01-01

    Smoking is a major health care problem and is projected to cause over 8 million deaths per year worldwide in the coming decades. To reduce lung cancer mortality in heavy smokers, several randomized screening trials were initiated in the past years using screening with low-dose Computed Tomography (CT). Recently, the National Lung Screening Trial (NLST), which was performed in the United States of America and compared about 25,000 participants screened with CT against 25,000 participants scree...

  6. Lung cancer screening with low-dose computed tomography: Canadian experience

    International Nuclear Information System (INIS)

    In 2003, the department of medical imaging at the University Health Network in Toronto, Ontario, became the first Canadian site of the International Early Lung Cancer Action Program (I-ELCAP). We report the results from the first 1000 baseline studies. Between June 2003 and December 2005, we enrolled 1000 high-risk smokers (that is, smokers with a history of a least 10 pack years, or the equivalent of one pack daily for 10 years), aged 55 years or older. A low-dose helical computed tomography (CT) (40 to 60 mA, 120 kV) was performed with 1.0mm to 1.25 collimation. Nodules found at baseline were followed according to the I-ELCAP protocol: 1) no noncalcified nodules (NCNs) or NCNs ≤ 4 mm or nonsolid nodules < 8 mm, annual repeat: 2) NCNs ≥ 5mm or nonsolid nodules ≥ 8 mm, 3-month follow up: or 3) nonsolid nodules ≥ 15 mm, antibiotics and 1-month follow-up. The first 100 study participants were aged 63 years, standard deviation (SD) 6 years, with a smoking history of 38 pack years, SD 22 pack years; 662 (66%) were former smokers, and 338 (34%) were current smokers; 453 (45%) were men, and 547 (55%) were women. Of the participants, 256 (26%) had a positive baseline low-dose computed tomography (LCDT) scan; 227 (23%) were followed after 3 months and 15 (1.6%) after 1 month; 7 (0.7%) received a contrast-enhanced CT and 6 (0.6%) an immediate CT-guided biopsy. Twenty-six invasive procedures were performed: 22 CT-guided biopsies, 1 ultrasound-guided lymph node metastasis biopsy, 1 bronchoscopic biopsy and 2 surgeries. The malignancy rate of the invasive procedures was 85%. Overall, the malignancy prevalence is 2.2%. Of the malignancies, 20 are lung carcinomas: 19 non-small-cell lung carcinomas (NSCLCs) (14 adenocarcinoma or bronchioalveolar carcinoma [BAC], 4 squamous carcinoma, and 1 large-cell carcinoma) and 1 small-cell carcinoma; 15 (78%) of the NSCLCs are Stage 1. Fourteen patients underwent surgery (1 pneumonectomy, 9 lobectomies, and 4 segmentectomies). Our

  7. The biochemical recurrence-free rate in patients who underwent prostate low-dose-rate brachytherapy, using two different definitions

    International Nuclear Information System (INIS)

    To assess the biochemical recurrence (BCR)-free rate in patients who underwent prostate low-dose-rate brachytherapy (LDR-brachytherapy), using two different definitions (Phoenix definition and PSA ≥ 0.2 ng/mL). Two hundreds and three patients who were clinically diagnosed with localized prostate cancer (cT1c-2cN0M0) and underwent LDR-brachytherapy between July 2004 and September 2008 were enrolled. The median follow-up period was 72 months. We evaluated the BCR-free rate using the Phoenix definition and the PSA cut-off value of 0.2 ng/mL, as in the definition for radical prostatectomy. To evaluate an independent variable that can predict BCR, Cox’s proportional hazard regression analysis was carried out. The BCR-free rate in patients using the Phoenix definition was acceptable (5-year: 92.8%). The 5- year BCR-free rate using the strict definition (PSA ≥ 0.2 ng/mL) was 74.1%. Cox’s proportional hazard regression analysis showed that a higher biological effective dose (BED) of ≥180 Gy2 was the only independent variable that could predict BCR (HR: 0.570, 95% C.I.: 0.327-0.994, p = 0.048). Patients with a higher BED (≥180 Gy2) had a significantly higher BCR-free rate than those with a lower BED (<180 Gy2) (5-year BCR-free rate: 80.5% vs. 67.4%). A higher BED ≥180 Gy2 promises a favorable BCR-free rate, even if the strict definition is adopted

  8. Suppression of carcinogenesis in mice by adaptive responses to low dose rate irradiation

    International Nuclear Information System (INIS)

    Effects of prolonged low-dose-rate irradiation on the process of carcinogenesis were examined in mice treated with chemical carcinogen or irradiated with high doses of X-rays. Female ICR mice, 5 week-old, 35 in each group, were exposed to gamma-rays from a 137Cs source in the long-term low dose rate irradiation facility at CRIEPI. The dose rate was 2.6 mGy/hr (A), 0.96 mGy/hr (B), or 0.30 mGy/hr (C). Thirty-five days later, the mice were injected into the groin with 0.5 mg of methylcholanthrene (MC) dissolved in olive oil and irradiation was continued. Cumulative tumor incidences after 216 days following MC injection were 89% in group A, 76% in group B, and 94% in group C. That in non-irradiated control group was 94%. The difference in the tumor incidence between the control and position B was statistically significant, indicating the suppressive effect of the low dose rate irradiation on the process of MC-induced carcinogenesis with an optimum dose rate around 1 mGy/hr. In B6C3F1 mice, although the suppression of tumor incidence was not observed, there was a significant delay in tumor appearance in the irradiated mice between 100-150 days after MC injection. A group of 20 female C57BL/6N mice, 5 weeks old, were exposed to gamma-rays at 0.95 mGy/hr for 5 weeks. Then, they were exposed weekly to 1.8 Gy whole body X-irradiation (300 kVp) for consecutive 4 weeks to induce thymic lymphoma. Another group received only the fractionated irradiation. The first mouse died from thymic lymphoma appeared 89 days after the last irradiation in the group received only the fractionated irradiation, while 110 days in the group combined with the low dose rate irradiation. (author)

  9. Comparison in vivo Study of Genotoxic Action of High- Versus Very Low Dose-Rate γ-Irradiation

    OpenAIRE

    A. N. Osipov; Klokov, D. Y.; Elakov, A. L.; Rozanova, O M; Zaichkina, S. I.; Aptikaeva, G. F.; Akhmadieva, A. Kh.

    2004-01-01

    The aim of the present study was to compare genotoxicity induced by high- versus very low dose-rate exposure of mice to γ-radiation within a dose range of 5 to 61 cGy using the single-cell gel electrophoresis (comet) assay and the micronucleus test. CBA/lac male mice were irradiated at a dose rate of 28.2 Gy/h (high dose rate) or 0.07 mGy/h (very low dose rate). The comet assay study on spleen lymphocytes showed that very low dose-rate irradiation resulted in a statistically significant incre...

  10. Radiotherapy combined with daily administration of low dose cisplatin for head and neck cancer

    International Nuclear Information System (INIS)

    Radiotherapy combined with daily administration of low-dose cisplatin (CDDP) was applied to 12 cases of head and neck cancer. They consisted of 12 carcinomas, occurring in the epipharynx (3 cases), mesopharynx (3), oral cavity (1), larynx (3), and parasinuses (2). The total response rate (CR+PR) was 83.3%. There was a remarkable effect in reducing tumor size, particularly on patients with laryngeal or epipharyngeal carcinoma. Severe mucositis with ulcers as a side effect was seen in eight cases after the irradiation of 20 to 30 Gy. Six of them tolerated a full dose of irradiation, but CDDP administration was stopped except in one case. To continue the CDDP administration in cases having irradiation of over 40 Gy, it is necessary to reduce the frequency of CDDP administration and/or to give post-irradiative hydration with 500 ml saline. When this combination therapy is used as a preoperative treatment, daily administration should be continued. Incidence of nausea or vomiting was not so frequent and they could be easily controlled by a serotonin-antagonist. Leukopenia was not severe. (author)

  11. OER and RBE for 125I and 192Ir at low dose rate on mammalian cells

    International Nuclear Information System (INIS)

    The oxygen enhancement ratio (OER) for 125I and 192Ir as well as the relative biological effectiveness (RBE) at low dose rates (40-80 cGy h-1) were determined for B16 melanoma cells in culture. The OER was found to be 2.1±0.03 for 125I and 2.7±0.04 for 192Ir. The RBE for 125I relative to 192Ir was determined as 1.8±0.03 under aerated conditions and as 2.4±0.03 under hypoxia. 18 refs.; 5 figs.; 1 table

  12. Whole-body low dose radiation promotes the efficiency of conventional radiotherapy of cancer

    International Nuclear Information System (INIS)

    Full text: Radiotherapy is the most commonly used local treatment of cancer. However, the large dose needed for local control often limits its successful use. In view of the stimulatory effect of low dose radiation (LDR) on anticancer immunity an experimental study of the effect of whole-body LDR on the outcome of conventional local radiotherapy of cancer was designed with an aim at reducing the total dose and promoting treatment efficiency. With a Lewis lung cancer model in mice it was observed that a regimen of 2 Gy x 3 per week for 2 weeks with a total local dose of 12 Gy resulted in only 23% reduction of tumor volume in 1 month as| compared with untreated control, while substitution of the second, third, fifth and sixth doses of 2 Gy with whole-body irradiation (WBI) of 0.075 Gy with a total local dose of 4 Gy plus 0.3 Gy WBI caused a 69% reduction of tumor volume in the same period. Since gene therapy with Egr-IL-18-B7.1 in combination with local X-rays showed better control of mouse I melanoma than local radiotherapy alone, a trial was made with this plasmid in the above Lewis lung cancer model. The results showed that in the 12 Gy protocol the tumor volume) reduction was 42% and in the 4 Gy local plus 0.3 Gy WBI protocol the tumor volume reduction was 77% in one month. This better control of cancer growth was apparently related to the stimulation of anticancer immunity by WBI with low doses and facilitation of IL-18) and B7.1 expression from the cancer cells in the gene therapy group resulting in up-regulation of immunity. It is concluded that WBI with low doses in combination with conventional radiotherapy exerts a significant promoting effect manifested in reduction in local radiation dose and improvement in tumor control

  13. Effects of low-dose rate irradiation on two types of type II diabetes model mice

    International Nuclear Information System (INIS)

    The effects of low-dose rate gamma-irradiation were investigated in two mouse strains - C57BL/KsJ-db/db (db mouse) and AKITA (AKITA mouse)-for type II diabetes mellitus. Both strains develop the developed type II diabetes by about 8 weeks of age due to dysfunction of the insulin/insulin receptor. The db Mouse' shows obese and exhibits hyperinsulinism, and the onset of Type II diabetes like resembles that for Westerners. On the other hand, the AKITA mouse has exhibits disordered insulin secretion, and the diabetes such as resembles that of Asians. Ten-week old female mice, in groups of 8 or 12, were irradiated at 0.65 mGy/hr in the low-dose rate irradiation facility in the Low Dose Radiation Research Center. The level of urine glucose was measured with test slips. The urine glucose levels of all of the mice were highly elevated the beginning of the irradiation. In the irradiated group of db mice, three mice showed decrease in glucose level compare to the level of non-irradiated diabetes mice after 35, 52 or 80 weeks of irradiation. All had maintained a normal level thereafter. No such improvement in diabetes was ever observed in the 12 mice of in the non-irradiated control group. The AKITA mice, however, did not decrease the glucose level regardless of the irradiation. Both the db mice and AKITA mice had their lives prolonged their life by the irradiation. The survival rate of db mice at the age of 90 weeks was 75% in the irradiated group, but 50% in the non-irradiated group. The average life span was 104 weeks in the irradiated group and 87 weeks in the control group. Furthermore, a marked difference was furthermore observed in the appearance of the coat hair, skin, and tail; appearances were well preserved in the irradiated group. The average life span in the irradiated AKITA mice was also longer than that for the non-irradiated mice, 51 weeks and 41 weeks in the irradiated and non-irradiated group respectively. These results suggest that the low-dose irradiation

  14. Low Dose Rate Radiosensitization of Hepatocellular Carcinoma In Vitro and in Patients

    Directory of Open Access Journals (Sweden)

    Kyle C. Cuneo

    2014-08-01

    Full Text Available Transarterial radioembolization (TARE with 90Y microspheres delivers low dose rate radiation (LDR to intrahepatic tumors. In the current study, we examined clonogenic survival, DNA damage, and cell cycle distribution in hepatocellular carcinoma (HCC cell lines treated with LDR in combination with varying doses and schedules of 5-fluorouracil (5-FU, gemcitabine, and sorafenib. Radiosensitization was seen with 1 to 3 μM 5-FU (enhancement ratio 2.2–13.9 and 30 to 100 nM gemcitabine (enhancement ratio 1.9–2.9 administered 24 hours before LDR (0.26 Gy/h to 4.2 Gy. Sorafenib radiosensitized only at high concentrations (3–10 μM when administered after LDR. For a given radiation dose, greater enhancement was seen with LDR compared to standard dose rate therapy. Summarizing our clinical experience with low dose rate radiosensitization, 13 patients (5 with HCC, 8 with liver metastases were treated a total of 16 times with TARE and concurrent gemcitabine. Six partial responses and one complete response were observed with a median time to local failure of 7.1 months for all patients and 9.9 months for patients with HCC. In summary, HCC is sensitized to LDR with clinically achievable concentrations of gemcitabine and 5-FU in vitro. Encouraging responses were seen in a small cohort of patients treated with TARE and concurrent gemcitabine. Future studies are needed to validate the safety and efficacy of this approach.

  15. Research on enhanced low dose rate sensitivity effect for PMOSFET used in space dosimeter

    International Nuclear Information System (INIS)

    In this paper, the ionizing damage effects and annealing behavior of foreign manufacturer production PMOSFET in 4007 circuit under different dose rates and bias conditions were investigated. The experiment results show that the PMOSFETs threshold voltage negative shift is more obvious with the dose rate reduction. It is thought that the PMOSFET of this kind of type has enhanced low dose rate sensitivity (ELDRS) effect. The PMOSFETs threshold voltage does not recover at room annealing after high dose rate exposure and continues the negative drifting, which is due to the radiation-induced interface traps buildup. The annealing temperature is higher, the threshold voltage return drift is more obvious. Zero bias is the worst bias condition. (authors)

  16. Relative biological effectiveness of 125I seeds for low-dose-rate irradiation of PANC-1

    International Nuclear Information System (INIS)

    Objective: To investigate the relative biological effectiveness(RBE) of National Model 6711 125I seeds and the response patterns of PANC-1 exposed to 125I seeds irradiation. Methods: PANC-1 cells in exponential growth were irradiated at initial dose rate of 2.59 cGy/h in vitro and exposed to 1, 2, 4, 6, 8 and 10 Gy. Meanwhile, the other part of cells were exposed to the same doses by 60Co at dose rate of 2.21 Gy/min. After irradiation, the cells were stained by trypan blue to measure the cellular mortality rate and to compare the changes along with plating times of 12, 24, 48 and 72 h after 4 Gy. The colonies were counted to obtain the plating efficiencies by colony-forming assay and the cell surviving faction was calculated to plot cell survival curves, and RBE of 125I seeds relative to 60Co was determined. Results: The cell death rate for continuous low- dose-rate (LDR) irradiation by 125I seeds was greater than 60Co at the same doses above or equal to 4 Gy. After 4 Gy irradiation, the cellular mortality rates were increased with times. The difference was significant between 125I seeds and 60Co. The survival fractions of 125I were lower than those of 60Co, and the RBE of 125I relative to 60Co was determined to be 1.45. Conclusion: The cell-killing effects for continuous low-dose-rate (LDR) irradiation by 125I seeds are greater than acute high-dose-rate of 60Co. (authors)

  17. Pre-irradiation with a low dose-rate depressed radiation-induced apoptosis in BALB/c mice spleens

    International Nuclear Information System (INIS)

    We aim to elucidate the effects of pre-irradiation to the whole-body with a low dose-rate on the acute radiation-induced apoptosis in the spleens of BALB/c mice. We found significant suppression of apoptosis induced by challenging irradiation at 2.0 Gy (1 Gy/min) immediately after chronic irradiation at 1.5 Gy with a low dose-rate (0.001 Gy/min). These findings suggest that chronic pre-irradiation with a low dose-rate induces some kind of radical detoxification systems and/or repair mechanisms against DNA damage which induces apoptosis. (author)

  18. Reviewing risks and benefits of low-dose computed tomography screening for lung cancer.

    Science.gov (United States)

    Chopra, Ishveen; Chopra, Avijeet; Bias, Thomas K

    2016-01-01

    Lung cancer is the third most common cancer among men and women and is one of the leading causes of cancer-related mortality. Diagnosis at an early stage has been suggested crucial for improving survival in individuals at high-risk of lung cancer. One potential facilitator to early diagnosis is low-dose computed tomography (LDCT). The United States Preventive Services Task Force guidelines call for annual LDCT screening for individuals at high-risk of lung cancer. This recommendation was based on the effectiveness of LDCT in early diagnosis of lung cancer, as indicated by the findings from the National Lung Screening Trial conducted in 2011. Although lung cancer accounts for more than a quarter of all cancer deaths in the United States and LDCT screening shows promising results regarding early lung cancer diagnosis, screening for lung cancer remains controversial. There is uncertainty about risks, cost-effectiveness, adequacy of evidence, and application of screening in a clinical setting. This narrative review provides an overview of risks and benefits of LDCT screening for lung cancer. Further, this review discusses the potential for implementation of LDCT in clinical setting. PMID:26680693

  19. Low-dose rate telecobalt therapy as a boost against esophageal carcinomas

    International Nuclear Information System (INIS)

    The results of treatment of 54 esophageal carcinomas managed with low-dose-rate telecobalt therapy (LDRT) as a boost were compared with those of 89 esophageal carcinomas treated with conventionally fractionated irradiation alone (CFI). The LDRT (1 Gy/hr, 5-7 Gy/day, to a total dose of 14-20 Gy) was boosted about 10 days after the CFI dose of 60 Gy. Although the LDRT group included more advanced cases than the CFI group, local effects and survival rate of the LDRT group, especially those with tumorous X-P and serrated types, were better than those of the CFI group. Late complications were more severe in the LDRT group. However, they were acceptable when the total dose in the LDRT group was brought under 80 Gy. (author)

  20. Evaluation of protracted low dose rate irradiation from an acute dose survival curve

    International Nuclear Information System (INIS)

    A method of transformation from an acute survival curve to a protracted low dose rate survival curve based on the concept of the dose equivalent sublethal damage advanced by Oliver is introduced. The transformation was done by solving a differential equation which was formulated between the slope of both survival curves and which was able to be applied to the situation where the dose rate might change with time, e.g., in using short-life radioisotopes or the complexity of the recovery of sub-lethal damage. The effects of the short-life radioisotopes (radon seeds and radiogold grains) in radiotherapy model; our data are compared with the data obtained by Orton

  1. Success rates for computed tomography-guided musculoskeletal biopsies performed using a low-dose technique

    Energy Technology Data Exchange (ETDEWEB)

    Motamedi, Kambiz; Levine, Benjamin D.; Seeger, Leanne L.; McNitt-Gray, Michael F. [UCLA Health System, Radiology, Los Angeles, CA (United States)

    2014-11-15

    To evaluate the success rate of a low-dose (50 % mAs reduction) computed tomography (CT) biopsy technique. This protocol was adopted based on other successful reduced-CT radiation dose protocols in our department, which were implemented in conjunction with quality improvement projects. The technique included a scout view and initial localizing scan with standard dose. Additional scans obtained for further guidance or needle adjustment were acquired by reducing the tube current-time product (mAs) by 50 %. The radiology billing data were searched for CT-guided musculoskeletal procedures performed over a period of 8 months following the initial implementation of the protocol. These were reviewed for the type of procedure and compliance with the implemented protocol. The compliant CT-guided biopsy cases were then retrospectively reviewed for patient demographics, tumor pathology, and lesion size. Pathology results were compared to the ultimate diagnoses and were categorized as diagnostic, accurate, or successful. Of 92 CT-guided procedures performed during this period, two were excluded as they were not biopsies (one joint injection and one drainage), 19 were excluded due to non-compliance (operators neglected to follow the protocol), and four were excluded due to lack of available follow-up in our electronic medical records. A total of 67 compliant biopsies were performed in 63 patients (two had two biopsies, and one had three biopsies). There were 32 males and 31 females with an average age of 50 (range, 15-84 years). Of the 67 biopsies, five were non-diagnostic and inaccurate and thus unsuccessful (7 %); five were diagnostic but inaccurate and thus unsuccessful (7 %); 57 were diagnostic and accurate thus successful (85 %). These results were comparable with results published in the radiology literature. The success rate of CT-guided biopsies using a low-dose protocol is comparable to published rates for conventional dose biopsies. The implemented low-dose protocol

  2. Emesis as a Screening Diagnostic for Low Dose Rate (LDR) Total Body Radiation Exposure.

    Science.gov (United States)

    Camarata, Andrew S; Switchenko, Jeffrey M; Demidenko, Eugene; Flood, Ann B; Swartz, Harold M; Ali, Arif N

    2016-04-01

    Current radiation disaster manuals list the time-to-emesis (TE) as the key triage indicator of radiation dose. The data used to support TE recommendations were derived primarily from nearly instantaneous, high dose-rate exposures as part of variable condition accident databases. To date, there has not been a systematic differentiation between triage dose estimates associated with high and low dose rate (LDR) exposures, even though it is likely that after a nuclear detonation or radiologic disaster, many surviving casualties would have received a significant portion of their total exposure from fallout (LDR exposure) rather than from the initial nuclear detonation or criticality event (high dose rate exposure). This commentary discusses the issues surrounding the use of emesis as a screening diagnostic for radiation dose after LDR exposure. As part of this discussion, previously published clinical data on emesis after LDR total body irradiation (TBI) is statistically re-analyzed as an illustration of the complexity of the issue and confounding factors. This previously published data includes 107 patients who underwent TBI up to 10.5 Gy in a single fraction delivered over several hours at 0.02 to 0.04 Gy min. Estimates based on these data for the sensitivity of emesis as a screening diagnostic for the low dose rate radiation exposure range from 57.1% to 76.6%, and the estimates for specificity range from 87.5% to 99.4%. Though the original data contain multiple confounding factors, the evidence regarding sensitivity suggests that emesis appears to be quite poor as a medical screening diagnostic for LDR exposures. PMID:26910032

  3. Effect of low doses of estradiol and tamoxifen on breast cancer cell karyotypes.

    Science.gov (United States)

    Rondón-Lagos, Milena; Rangel, Nelson; Di Cantogno, Ludovica Verdun; Annaratone, Laura; Castellano, Isabella; Russo, Rosalia; Manetta, Tilde; Marchiò, Caterina; Sapino, Anna

    2016-08-01

    Evidence supports a role of 17&-estradiol (E2) in carcinogenesis and the large majority of breast carcinomas are dependent on estrogen. The anti-estrogen tamoxifen (TAM) is widely used for both treatment and prevention of breast cancer; however, it is also carcinogenic in human uterus and rat liver, highlighting the profound complexity of its actions. The nature of E2- or TAM-induced chromosomal damage has been explored using relatively high concentrations of these agents, and only some numerical aberrations and chromosomal breaks have been analyzed. This study aimed to determine the effects of low doses of E2 and TAM (10(&8 )mol L(&1) and 10(&6 )mol L(&1) respectively) on karyotypes of MCF7, T47D, BT474, and SKBR3 breast cancer cells by comparing the results of conventional karyotyping and multi-FISH painting with cell proliferation. Estrogen receptor (ER)-positive (+) cells showed an increase in cell proliferation after E2 treatment (MCF7, T47D, and BT474) and a decrease after TAM treatment (MCF7 and T47D), whereas in ER& cells (SKBR3), no alterations in cell proliferation were observed, except for a small increase at 96 h. Karyotypes of both ER+ and ER& breast cancer cells increased in complexity after treatments with E2 and TAM leading to specific chromosomal abnormalities, some of which were consistent throughout the treatment duration. This genotoxic effect was higher in HER2+ cells. The ER&/HER2+ SKBR3 cells were found to be sensitive to TAM, exhibiting an increase in chromosomal aberrations. These in vitro results provide insights into the potential role of low doses of E2 and TAM in inducing chromosomal rearrangements in breast cancer cells. PMID:27357940

  4. Computer-aided detection of nodule in low-dose CT screening for lung cancer

    International Nuclear Information System (INIS)

    Objective: To evaluate the performance of computer-aided detection (CAD) system for detection of pulmonary nodules in 64-slice low-dose CT screening and to investigate whether CAD can improve the performance of radiologists in detecting pulmonary nodules. Methods: One hundred low-dose screening CT examinations were randomly selected from the database containing 578 consecutive cases between Jun 2007 and Jun 2008. All the examinations were performed on a 64-MSCT scanner with the exposure of 120 kVp, 30 or 40 mA, or automatic exposure control. Before the study started, the screening reports had been made with double reading by two radiologists. All the selected images were analyzed with the lung VCAR software from GE Healthcare with a nodule diameter threshold 3.0 mm. All discrepancies between the screening reports and the CAD results were reviewed and the true non-calcified nodules were determined in consensus by two experienced chest radiologists. Detected nodules were classified by density, size and location.The performance of the double reading and the CAD system were compared and analyzed statistically. McNemar-Bowker test was used for the statistical analysis. Results: A total of 257 true noncalcified nodules were determined in all 100 low-dose screening CT examinations. The detection rate of CAD system was 91.1% (234/257), with the missed rate of 8.9% (23/257). Twenty three nodules were missed by CAD, in which 10 were solid with the diameter ranged from 2.4 to 6.0 mm, and 13 were nonsolid with the diameter ranged from 2.1 to 8.6 mm.Of the 23 nodules, 17 were located in the outer zones of lungs and 6 in the inner zones. The double reading showed a detection rate of 59.1% (152/257) and a missed rate of 40.9% (105/257), which was significantly lower than CAD. The diameter of all the 105 missed nodules by radiologists were ranged from 2.4 to 11.8 mm, in which 94 nodules were solid, 10 were partly solid and 1 was nonsolid, with 69 located in outer zones of lungs

  5. Response to the argument on the risk of cancer with chest CT screening. Is low-dose chest CT safe?

    International Nuclear Information System (INIS)

    The steady increase in the annual number of chest CT screening has become a worldwide concern because of its associated risk of lung cancer. Epidemiological studies, however, have shown that repeated exposure to low-dose radiation does not increase the risk of lung cancer. In addition, a recent randomized controlled study on chest CT screening has shown its usefulness for reducing lung cancer mortality. We reviewed the risk of lung cancer after repeated exposure to low-dose radiation, the efficacy of chest CT screening, and device technology for reducing the irradiation dose. (author)

  6. Molecular alterations in childhood thyroid cancer after Chernobyl accident and low-dose radiation risk

    International Nuclear Information System (INIS)

    The linear no-threshold (LNT) model of radiation carcinogenesis has been used for evaluating the risk from radiation exposure. While the epidemiological studies have supported the LNT model at doses above 100 mGy, more uncertainties are still existed in the LNT model at low doses below 100 mGy. Thus, it is urged to clarify the molecular mechanisms underlying radiation carcinogenesis. After the Chernobyl accident in 1986, significant amount of childhood thyroid cancer has emerged in the children living in the contaminated area. As the incidence of sporadic childhood thyroid cancer is very low, it is quite evident that those cancer cases have been induced by radiation exposure caused mainly by the intake of contaminated foods, such as milk. Because genetic alterations in childhood thyroid cancers have extensively been studied, it should provide a unique chance to understand the molecular mechanisms of radiation carcinogenesis. In a current review, molecular signatures obtained from the molecular studies of childhood thyroid cancer after Chernobyl accident have been overviewed, and new roles of radiation exposure in thyroid carcinogenesis will be discussed. (author)

  7. Late effects of chronic low dose-rate γ-rays irradiation on mice

    International Nuclear Information System (INIS)

    To evaluate late biological effects of chronic low dose-rate radiation, the life-span and pathological changes were evaluated in mice which had been continuously irradiated with gamma-rays for 400 days. Two hundred (100 male and 100 female) specific-pathogen-free (SPF) B6C3F1 mice at six weeks of age were purchased every month. After a 2-week quarantine, they were divided into 4 groups (1 unirradiated control and 3 irradiated). Irradiation was performed using 137Cs gamma-rays at dose-rates of 20 mGy/day, 1 mGy/day and 0.05 mGy/day with accumulated doses equivalent to 8000 mGy, 400 mGy and 20 mGy, respectively. All mice were kept until they died a natural death. Results of the monthly microbiological examinations confirmed that the mice were maintained under SPF-conditions throughout the experimental period. A total of 4000 mice have been admitted into the experiment since it started in February 1996, all of which have received their predetermined doses and have been transferred to the animal room. Data on the 20 mGy/day group of both sexes suggested a shortened life span. The most common lethal neoplasms in pooled data of unirradiated control and irradiated male mice in order of frequency were neoplasms of the lymphohematopoietic system, liver, and lung. In female mice, neoplasms of the lymphohematopoietic system, soft tissue, and endocrine system were common. (author)

  8. OER of californium-252 at low dose rate for growth inhibition in Vicia faba

    International Nuclear Information System (INIS)

    OER of 252Cf, at low dose rate, has been determined for growth inhibition in Vicia faba roots. A new strain ''BelB'' was used; it was found to be more resistant to prolonged anoxia. Two sets of linear 252Cf sources were used (linear activity 0.31 and 0.47 (μg.cm-1)) in somewhat different geometrical arrangements. The (n+γ) 252Cf dose rates at the level of the root tips were 0.11 and 0.13 Gy.h-1 respectively. The relative contribution of the γ component Dsub(γ) to the total absorbed dose Dsub(n+γ) at the level of the root tips was evaluated Dsub(γ)/Dsub(n+γ)=0.35 for the first source-geometry and 0.42 for the second source-geometry. The reference radiation was the γ emission of 192Ir, used in the same geometrical conditions and for similar irradiation times. Irradiations performed in aerobic and anoxic conditions were alternated. OER values of 1.4 +- 0.1 and 1.5 +- 0.1 were observed for the 252Cf emission with the first and second source-geometry respectively. The corresponding OER values for 192Ir were 2.3 +- 0.2 and 2.6 +- 0.1; the derived oxygen gain factors were then equal to 1.6 and 1.7 repectively

  9. Pre-irradiation at a low dose-rate blunted p53 response

    International Nuclear Information System (INIS)

    We investigated whether chronic irradiation at a low dose-rate interferes with the p53-centered signal transduction pathyway induced by radiation in human cultured cells and C57BL/6N mice. In in vitro experiments, we found that a challenge with X-ray irradiation immediately after chronic irradiation resulted in lower levels of p53 than those observed after the challenge alone in glioblastoma cells (A-172). In addition, the levels of p53-centered apoptosis and its related proteins after the challenge were strongly correlated with the above-mentioned phenomena in squamous cell carcinoma cells (SAS/neo). In in vivo experiments, the accumulation of p53 and Bax, and the induction of apoptosis were observed dose-dependently in mouse spleen at 12 h after a challenge with X-rays (3.0 Gy). However, we found significant suppression of p53 and Bax accumulation and the induction of apoptosis 12 h after challenge irradiation at 3.0 Gy with a high doses-rate following chronic pre-irradiation (1.5 Gy, 0.001 Gy/min). These findings suggest that chronic pre-irradiation suppressed the p53 function through radiation-induced signaling and/or p53 stability. (author)

  10. Low dose radiation hypersensitivity and clustered DNA damages in human fibroblasts exposed to low dose and dose rate protons or 137CS y-rays

    Energy Technology Data Exchange (ETDEWEB)

    Bennett P. V.; Bennett, P.V.; Keszenman, D.J.; Johnson, A.M.; Sutherland, B.M.; Wilson, P.F.

    2013-05-14

    Effective radioprotection for human space travelers hinges upon understanding the individual properties of charged particles. A significant fraction of particle radiation astronauts will encounter in space exploratory missions will come from high energy protons in galactic cosmic radiation (GCR) and/or possible exposures to lower energy proton flux from solar particle events (SPEs). These potential exposures present major concerns for NASA and others, in planning and executing long term space exploratory missions. We recently reported cell survival and transformation (acquisition of anchorage-independent growth in soft agar) frequencies in apparently normal NFF-28 primary human fibroblasts exposed to 0-30 cGy of 50MeV, 100MeV (SPE-like), or 1000 MeV (GCR-like) monoenergetic protons. These were modeled after 1989 SPE energies at an SPE-like low dose-rate (LDR) of 1.65 cGy/min or high dose rate (HDR) of 33.3 cGy/min delivered at the NASA Space Radiation Laboratory (NSRL) at BNL.

  11. The bcl-2, bax gene expression and apoptosis of continuous low-dose-rate irradiation on PC-3 transplanting tumor

    International Nuclear Information System (INIS)

    Objective: The aim of this study was to investigate bcl-2, bax expression and apoptosis of continuous low-dose-rate irradiation on prostate cancer (PC)-3 transplanting tumor. Methods: The expression of bcl-2 and bax associated with apoptosis between experiment and control groups were analyzed using immunohistochemistry at 48, 96 and 192 h after two 125I seed sources implanting model. The correlation between apoptosis and the ratio of bax/bcl-2 was analyzed using Bi-variable linear correlation. SPSS 11.0 was used to analyse the data. Results: The bcl-2 expression in experiment group began to down-regulated significantly after 125I seed irradiation for 48 h as compared with control(t=2.500, P=0.067), though it was not reached to statistical significance. At 96 and 192 h after irradiation, significantly low expression of bcl- 2 were noted (t=4.950, 3.464; P=0.008 and 0.026). In contrast, significantly over expression of bax was noted at 48, 96 and 192 h after 12si irradiation (t=3.334,4.025,5.292;P=0.029, 0.016 and 0.006). The apoptotic index (AI) for PC-3 at 48, 96 and 192 h after 125I irradiation were 22.3%, 21.7% and 30.7%, which was significantly higher than controls when at 96 and 192 h after 125I irradiation (P= 0.016 and 0.036). Moreover, positive correlation was noted between AI and bax/bcl-2 ratio (r=0.784, P= 0.012). Conclusion: Low-dose-rate irradiation could down-regulate the expression of bcl-2, up-regulate the expression of bax and induced PC-3 cells apoptosis. (authors)

  12. Cancer and non-cancer brain and eye effects of chronic low-dose ionizing radiation exposure

    Directory of Open Access Journals (Sweden)

    Picano Eugenio

    2012-04-01

    Full Text Available Abstract Background According to a fundamental law of radiobiology (“Law of Bergonié and Tribondeau”, 1906, the brain is a paradigm of a highly differentiated organ with low mitotic activity, and is thus radio-resistant. This assumption has been challenged by recent evidence discussed in the present review. Results Ionizing radiation is an established environmental cause of brain cancer. Although direct evidence is lacking in contemporary fluoroscopy due to obvious sample size limitation, limited follow-up time and lack of focused research, anecdotal reports of clusters have appeared in the literature, raising the suspicion that brain cancer may be a professional disease of interventional cardiologists. In addition, although terminally differentiated neurons have reduced or mild proliferative capacity, and are therefore not regarded as critical radiation targets, adult neurogenesis occurs in the dentate gyrus of the hippocampus and the olfactory bulb, and is important for mood, learning/memory and normal olfactory function, whose impairment is a recognized early biomarker of neurodegenerative diseases. The head doses involved in radiotherapy are high, usually above 2 Sv, whereas the low-dose range of professional exposure typically involves lifetime cumulative whole-body exposure in the low-dose range of Conclusions At this point, a systematic assessment of brain (cancer and non-cancer effects of chronic low-dose radiation exposure in interventional cardiologists and staff is needed.

  13. Migration of a strand of four seeds in low-dose-rate brachytherapy

    Science.gov (United States)

    Dedic-Hagan, Jasmina; Teh, Amy Y M; Liang, Eisen; Collett, Nicholas; Woo, Henry H

    2014-01-01

    We report a case of stranded-seed migration (one strand of four seeds), via the prostatic venous plexus to the internal pudendal vein, in low-dose-rate (LDR) prostate brachytherapy. A 70-year-old man with low-risk prostate adenocarcinoma underwent transperineal permanent seed implantation. A total of 93 iodine-125 seeds were implanted (91 stranded seeds and 2 loose seeds). Immediate postimplantation fluoroscopic image and day 1 postimplantation CT scan indicated all implanted seeds to be within the vicinity of the prostate as planned. Day 30 pelvic X-ray and CT scan revealed migration of a strand of four seeds to the right pelvis (adjacent to ischial spine). At 2 years postimplantation, the patient continues to have good disease control with prostate specific antigen level of 0.69 μg/L, and asymptomatic. To the best of our knowledge, this is the first report of migration of an entire strand of seeds following LDR prostate brachytherapy. PMID:24879735

  14. Low Dose-Rate Effects on Chromosomal Aberrations in Workers Occupationally Exposed to Ionising Radiation

    International Nuclear Information System (INIS)

    Full text: Occupational exposure to ionising radiation can be assessed by chromosomal aberrations detected in peripheral blood lymphocytes. Blood samples were collected from 47 occupationally exposed individuals (X-ray diagnostic machines and industrial gamma defectoscopy). The chromosomal aberrations were analysed from at least 500 metaphases per person and their frequencies were compared with those obtained from 110 control individuals. It has been noticed the higher frequency of chromosomal aberrations in the exposed group related to the control. The increase was analysed according to the age groups (31-40, 41-50, and 51-60), sex and duration of employment. The higher frequency of dicentrics was not directly correlated with the age or duration of employment in the exposed group. The acentric fragments were encountered with much higher frequency in the exposed group. The chromosomal aberrations induced by low dose-rate in occupationally exposed people revealed the degree of individual sensitivity and the severity of the initial damage depending on the biological-pathological conditions. (author)

  15. Lifetime radiation risks from low-dose rate radionuclides in beagles

    International Nuclear Information System (INIS)

    One of the largest, long-term (25-yr) animal studies on the effects of low-dose internal irradiation is almost completed. Some 335 beagles were given continuous exposure to graded 90Sr [low linear energy transfer (LET)] in their diets (D-dogs) through adulthood. A second group (R-dogs) was given fractionated doses of 225Ra (high LET) as young adults. A third group of 44 was given a single injection of 90Sr as adults (S-dogs) to compare single to continuous dosages. All dogs were followed through their lifetimes. Only one of the 848 dogs is still alive. The animals were whole-body counted over their entire life span and were examined frequently for assessment of medical status. There were no acute radiation lethalities. Analyses of the large data base from these dogs have begun and preliminary indications are that 90Sr, which was tested over a 1500-fold skeletal dose rate range, does not cause significant life shortening at average accumulation skeletal doses of ∼2500 rads (25 Gy) and that a curvilinear dose response curve for life shortening was seen at higher accumulation doses. The data will be discussed in terms of modern epidemiological concepts and quantifications will be related to certain parameters of human risk from acute or chronic radiation exposures

  16. Preparation and determination of kerma for Iridium 192 sources of low dose rate for brachytherapy

    International Nuclear Information System (INIS)

    The practice of Brachytherapy with Iridium-192 sources of low dose rate (0.4 - 0.8 Gy/h) is a technique used in the treatment of diverse illnesses. in this work the preparation, quality control and calibration are presented in terms of kerma in air of Iridium-192 using as target these recycled Iridium-Platinum wires. The targets were obtained as decayed sources of different radio therapeutical centers in the country and they were characterized by Scanning electron microscopy in order to determine their chemical composition. Subsequently it was developed an experimental design to establish the effect of neutron flux, geometrical array and irradiation time over the activity and percentage of the sources homogeneity. The homogeneity was determined by auto radiography and by Gamma spectroscopy. Once the optimal irradiation conditions were established, it is determined the apparent activity and kerma in air using a well type ionization chamber with traceability to a primary laboratory. Iridium-192 sources were obtained with an average homogeneity 96 %, apparent activity 282.129 ± 0.531 M Bq and kerma in air 0.03200 ± 0.00006 m Gy m/h A. (Author)

  17. [Phantom Study on Dose Reduction Using Iterative Reconstruction in Low-dose Computed Tomography for Lung Cancer Screening].

    Science.gov (United States)

    Minehiro, Kaori; Takata, Tadanori; Hayashi, Hiroyuki; Sakuda, Keita; Nunome, Haruka; Kawashima, Hiroko; Sanada, Shigeru

    2015-12-01

    We investigated dose reduction ability of an iterative reconstruction technology for low-dose computed tomography (CT) for lung cancer screening. The Sinogram Affirmed Iterative Reconstruction (SAFIRE) provided in a multi slice CT system, Somatom Definition Flash (Siemens Healthcare) was used. An anthropomorphic chest phantom (N-1, Kyoto Kagaku) was scanned at volume CT dose index (CTDIvol) of 0.50-11.86 mGy with 120 kV. For noise (standard deviation) and contrast-to-noise ratio (CNR) measurements, CTP486 and CTP515 modules in the Catphan (The Phantom Laboratory) were scanned. Radiological technologists were participated in the perceptual comparison. SAFIRE reduced the SD values by approximately 50% compared with filter back projection (FBP). The estimated dose reduction rates by SAFIRE determined from the perceptual comparison was approximately 23%, while 75% dose reduction rate was expected from the SD value reduction of 50%. PMID:26685831

  18. Palliative low dose fortnightly methotrexate in oral cancers: Experience at a rural cancer centre from India

    Directory of Open Access Journals (Sweden)

    Santam Chakraborty

    2014-01-01

    Full Text Available Context: Palliative fortnightly chemotherapy in oral cancers. Aims: We present our experience with a regimen employing fortnightly (once in 2 weeks injectable methotrexate (MTX (40 mg/m 2 in a predominantly elderly cohort of patients with carcinoma of oral cavity and oropharynx. Settings and Design: Retrospective chart review conducted at a rural cancer center in India. Materials and Methods: All patients with oral cavity and oropharyngeal cancers started on treatment with fortnightly injectable MTX (40 mg/m 2 between 01/01/2011 and 31/12/2011. Statistical Analysis Used: The factors analyzed included the duration of disease control, pain control, overall survival and progression free survival which were evaluated using the Kaplan Meier method. Results: A total of 60 patients with a median age of 66.5 years were analyzed. Majority of the patients had poor nutritional status, performance status or co-morbidities. MTX was given for recurrent disease in 19 patients and after initial palliative radiotherapy in 41 patients. The median number of cycles delivered was nine. Grade 3/4 toxicities were seen in 2 patients only. Disease control rate at the end of treatment was seen in 33 (55% patients. Median overall survival was 34 weeks (interquartile range: 17-50 weeks. Conclusions: The fortnightly regimen of MTX was well-tolerated and showed a good clinical activity in this elderly cohort of patients with advanced oral cavity and oropharyngeal cancers.

  19. Late effects of chronic low dose-rate γ-rays irradiation on mice

    International Nuclear Information System (INIS)

    To evaluate late biological effects of chronic low dose-rate radiation, the life-span and pathological changes were evaluated in mice that were continuously irradiated with gamma-rays for 400 days. Two hundred (100 male and 100 female) specific-pathogen-free (SPF) B6C3F1 mice at six weeks of age were purchased every month. After a 2-week quarantine, they were divided into 4 groups (1 unirradiated control and 3 irradiated). Irradiation was performed using 137Cs gamma-rays at dose-rates of 20 mGy (22 h-day)-1, 1 mGy (22 h-day)-1 and 0.05 mGy (22 h-day)''-1 with accumulated doses equivalent to 8,000 mGy, 400 mGy and 20 mGy, respectively. All mice were kept until they died a natural death. Results of the monthly microbiological examinations confirmed that the mice were maintained under SPF-conditions throughout the experimental period. A total of 4,000 mice have been admitted into the experiment since it started in February 1996, all of which have received their predetermined doses and have been transferred to the animal room. Data on the 20 mGy (22 h-day)-1 group of both sexes suggested a shortened life span. The most common lethal neoplasms in pooled data of unirradiated control male mice and irradiated male mice in order of frequency were neoplasms of the lymphohematopoietic system, liver, lung, and soft tissue. In female mice, neoplasms of the lymphohematopoietic system, soft tissue, endocrine system, and liver were most common. (author)

  20. A brief measure of Smokers' knowledge of lung cancer screening with low-dose computed tomography.

    Science.gov (United States)

    Lowenstein, Lisa M; Richards, Vincent F; Leal, Viola B; Housten, Ashley J; Bevers, Therese B; Cantor, Scott B; Cinciripini, Paul M; Cofta-Woerpel, Ludmila M; Escoto, Kamisha H; Godoy, Myrna C B; Linder, Suzanne K; Munden, Reginald F; Volk, Robert J

    2016-12-01

    We describe the development and psychometric properties of a new, brief measure of smokers' knowledge of lung cancer screening with low-dose computed tomography (LDCT). Content experts identified key facts smokers should know in making an informed decision about lung cancer screening. Sample questions were drafted and iteratively refined based on feedback from content experts and cognitive testing with ten smokers. The resulting 16-item knowledge measure was completed by 108 heavy smokers in Houston, Texas, recruited from 12/2014 to 09/2015. Item difficulty, item discrimination, internal consistency and test-retest reliability were assessed. Group differences based upon education levels and smoking history were explored. Several items were dropped due to ceiling effects or overlapping constructs, resulting in a 12-item knowledge measure. Additional items with high item uncertainty were retained because of their importance in informed decision making about lung cancer screening. Internal consistency reliability of the final scale was acceptable (KR-20 = 0.66) and test-retest reliability of the overall scale was 0.84 (intraclass correlation). Knowledge scores differed across education levels (F = 3.36, p = 0.04), while no differences were observed between current and former smokers (F = 1.43, p = 0.24) or among participants who met or did not meet the 30-pack-year screening eligibility criterion (F = 0.57, p = 0.45). The new measure provides a brief, valid and reliable indicator of smokers' knowledge of key concepts central to making an informed decision about lung cancer screening with LDCT, and can be part of a broader assessment of the quality of smokers' decision making about lung cancer screening. PMID:27512650

  1. Long-term prognosis of patients with lung cancer detected on low-dose chest computed tomography screening.

    Science.gov (United States)

    Nawa, Takeshi; Nakagawa, Tohru; Mizoue, Tetsuya; Kusano, Suzushi; Chonan, Tatsuya; Fukai, Shimao; Endo, Katsuyuki

    2012-02-01

    The effectiveness of lung cancer screening using low-dose chest computed tomography (CT) remains elusive. The present study examined the prognosis of patients with lung cancer detected on CT screening in Japanese men and women. Subjects were 210 patients with primary lung cancer identified on CT screening at two medical facilities in Hitachi, Japan, where a total of 61,914 CT screenings were performed among 25,385 screenees between 1998 and 2006. Prognostic status of these patients was sought by examining medical records at local hospitals, supplemented by vital status information from local government. The 5-year survival rate was estimated according to the characteristics of patients and lung nodule. A total of 203 (97%) patients underwent surgery. During a 5.7-year mean follow-up period, 19 patients died from lung cancer and 6 died from other causes. The estimated 5-year survival rate for all patients and for those on stage IA was 90% and 97%, respectively. Besides cancer stage, smoking and nodule appearance were independent predictors of a poor survival; multivariable-adjusted hazard ratio (95% confidence interval) was 4.7 (1.3, 16.5) for current and past smokers versus nonsmokers and 4.6 (1.6, 13.9) for solid nodule versus others. Even patients with solid shadow had a 5-year survival of 82% if the lesion was 20mm or less in size. Results suggest that lung cancers detected on CT screening are mostly curative. The impact of CT screening on mortality at community level needs to be clarified by monitoring lung cancer deaths. PMID:21813201

  2. Injury to the blood-testis barrier after low-dose-rate chronic radiation exposure in mice

    International Nuclear Information System (INIS)

    Exposure to ionising radiation induces male infertility, accompanied by increasing permeability of the blood-testis barrier. However, the effect on male fertility by low-dose-rate chronic radiation has not been investigated. In this study, the effects of low-dose-rate chronic radiation on male mice were investigated by measuring the levels of tight-junction-associated proteins (ZO-1 and occludin-1), Niemann-Pick disease type 2 protein (NPC-2) and anti-sperm antibody (AsAb) in serum. BALB/c mice were exposed to low-dose-rate radiation (3.49 mGy h-1) for total exposures of 0.02 (6 h), 0.17 (2 d) and 1.7 Gy (21 d). Based on histological examination, the diameter and epithelial depth of seminiferous tubules were significantly decreased in 1.7-Gy-irradiated mice. Compared with those of the non-irradiated group, 1.7-Gy-irradiated mice showed significantly decreased ZO-1, occludin-1 and NPC-2 protein levels, accompanied with increased serum AsAb levels. These results suggest potential blood-testis barrier injury and immune infertility in male mice exposed to low-dose-rate chronic radiation. (authors)

  3. DNA damage-centered signaling pathways are effectively activated during low dose-rate Auger radioimmunotherapy

    International Nuclear Information System (INIS)

    Introduction: Low dose-rate radioimmunotherapy (RIT) using 125I-labelled monoclonal antibodies (125I-mAbs) is associated with unexpected high cytotoxicity per Gy. Methods: We investigated whether this hypersensitivity was due to lack of detection of DNA damage by the targeted cells. DNA damage was measured with the alkaline comet assay, gamma-H2AX foci and the micronucleus test in p53−/− and p53+/+ HCT116 cells exposed to increasing activities of internalizing anti-HER1 125I-mAbs or non-internalizing anti-CEA 125I-mAbs. The expression of proteins involved in radiation response and progression of cells through the cycle were determined. Results: Cell hypersensitivity to low absorbed doses of anti-CEA 125I-mAbs was not due to defect in DNA damage detection, since ATM (ataxia telangiectasia mutated gene), gamma-H2AX, p53 and p21 were activated in RIT-treated HCT116 cells and G2/M cell cycle arrest was observed. Moreover, the alkaline comet assay showed that DNA breaks accumulated when cells were placed at 4 °C during exposure but were repaired under standard RIT conditions (37 °C), suggesting that lesions detected under alkaline conditions (mostly DNA single strand breaks and alkali-labile sites) are efficiently repaired in treated cells. The level of gamma-H2AX protein corroborated by the level of foci measured in nuclei of treated cells was shown to accumulate with time thereby suggesting the continuous presence of DNA double strand breaks. This was accompanied by the formation of micronuclei. Conclusion: Hypersensitivity to non-internalizing 125I-mAbs is not due to lack of detection of DNA damage after low absorbed dose-rates. However, DNA double strand breaks accumulate in cells exposed both to internalizing and non-internalizing 125I-mAbs and lead to micronuclei formation. These results suggest impairment in DNA double strand breaks repair after low absorbed doses of 125I-mAbs

  4. Chloroquine Improves Survival and Hematopoietic Recovery After Lethal Low-Dose-Rate Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Lim Yiting [Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Hedayati, Mohammad; Merchant, Akil A.; Zhang Yonggang; Yu, Hsiang-Hsuan M. [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Kastan, Michael B. [Department of Oncology, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina (United States); Matsui, William, E-mail: matsuwi@jhmi.edu [Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); DeWeese, Theodore L., E-mail: deweete@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

    2012-11-01

    Purpose: We have previously shown that the antimalarial agent chloroquine can abrogate the lethal cellular effects of low-dose-rate (LDR) radiation in vitro, most likely by activating the ataxia-telangiectasia mutated (ATM) protein. Here, we demonstrate that chloroquine treatment also protects against lethal doses of LDR radiation in vivo. Methods and Materials: C57BL/6 mice were irradiated with a total of 12.8 Gy delivered at 9.4 cGy/hour. ATM null mice from the same background were used to determine the influence of ATM. Chloroquine was administered by two intraperitoneal injections of 59.4 {mu}g per 17 g of body weight, 24 hours and 4 hours before irradiation. Bone marrow cells isolated from tibia, fibula, and vertebral bones were transplanted into lethally irradiated CD45 congenic recipient mice by retroorbital injection. Chimerism was assessed by flow cytometry. In vitro methylcellulose colony-forming assay of whole bone marrow cells and fluorescence activated cell sorting analysis of lineage depleted cells were used to assess the effect of chloroquine on progenitor cells. Results: Mice pretreated with chloroquine before radiation exhibited a significantly higher survival rate than did mice treated with radiation alone (80% vs. 31%, p = 0.0026). Chloroquine administration before radiation did not affect the survival of ATM null mice (p = 0.86). Chloroquine also had a significant effect on the early engraftment of bone marrow cells from the irradiated donor mice 6 weeks after transplantation (4.2% vs. 0.4%, p = 0.015). Conclusion: Chloroquine administration before radiation had a significant effect on the survival of normal but not ATM null mice, strongly suggesting that the in vivo effect, like the in vitro effect, is also ATM dependent. Chloroquine improved the early engraftment of bone marrow cells from LDR-irradiated mice, presumably by protecting the progenitor cells from radiation injury. Chloroquine thus could serve as a very useful drug for protection

  5. Cancer and non-cancer brain and eye effects of chronic low-dose ionizing radiation exposure

    International Nuclear Information System (INIS)

    According to a fundamental law of radiobiology (“Law of Bergonié and Tribondeau”, 1906), the brain is a paradigm of a highly differentiated organ with low mitotic activity, and is thus radio-resistant. This assumption has been challenged by recent evidence discussed in the present review. Ionizing radiation is an established environmental cause of brain cancer. Although direct evidence is lacking in contemporary fluoroscopy due to obvious sample size limitation, limited follow-up time and lack of focused research, anecdotal reports of clusters have appeared in the literature, raising the suspicion that brain cancer may be a professional disease of interventional cardiologists. In addition, although terminally differentiated neurons have reduced or mild proliferative capacity, and are therefore not regarded as critical radiation targets, adult neurogenesis occurs in the dentate gyrus of the hippocampus and the olfactory bulb, and is important for mood, learning/memory and normal olfactory function, whose impairment is a recognized early biomarker of neurodegenerative diseases. The head doses involved in radiotherapy are high, usually above 2 Sv, whereas the low-dose range of professional exposure typically involves lifetime cumulative whole-body exposure in the low-dose range of < 200 mSv, but with head exposure which may (in absence of protection) arrive at a head equivalent dose of 1 to 3 Sv after a professional lifetime (corresponding to a brain equivalent dose around 500 mSv). At this point, a systematic assessment of brain (cancer and non-cancer) effects of chronic low-dose radiation exposure in interventional cardiologists and staff is needed

  6. Inhibition of subsequent nodal metastasis by low dose of elective neck irradiation for tongue cancers

    International Nuclear Information System (INIS)

    To study the influence of elective neck irradiation (ENI) with a dose of ≤30 Gy on subsequent nodal metastasis for tongue carcinomas. Forty-nine patients controlled at the primary site were evaluated. They were treated with interstitial irradiation and ENI of ≤30 Gy from 1979 to 1991. Subsequent nodal metastases developed in 14 patients (29%) 1 to 23 months after radiotherapy. The nodal recurrence rates were 4/10 (40%) for 0 Gy, 4/9 (44%) for 10-15 Gy, 6/22 (27%) for 16-20 Gy, and 0/8 (0%) for 21-30 Gy. The rates according to tumor thickness were 5/28 (18%) for superficial tumors and 9/21 (41%) for deeply invasive tumors. These factors were shown to be significant by multivariate analysis. The nodal recurrence from irradiated fields developed late compared with that from outside the fields. Successful salvage was obtained in 11/14 (79%), depending on the recurrent nodal stage. The five-year survival rate was significantly better in patients with irradiation of >15 Gy (96%) than those with 15 Gy or less (79%). ENI of low dose (15-30 Gy) significantly reduced nodal recurrence rate and prolonged survival. An elective dose of 30 Gy including the upper and middle neck was able to reduce subsequent nodal metastases about 10% (from 37% to 27% in our review). (author)

  7. Contamination and cancers: low-dose risks and standards of radioprotection

    International Nuclear Information System (INIS)

    Irradiation of the population due to the running of nuclear power stations represents less than 1% of the natural radioactivity today, and should amount to 3% at most by the year 2 000. The main effects of ionizing radiations are reviewed and their undetectability below 100 rems is underlined. Thus the evaluation of low-dose risks can only be speculative and the cautions hypothesis adopted is that of a linear relationship between dose and effect, together with the absence of threshold. According to calculations the worker, supposedly exposed to 500 mrem a year between ages 18 and 65, would run a 22.2% instead of the normal 22% risk of dying of cancer. As for the population, the risk would increase by only 1 per 10 000 in the year 2 000. This means that no other mutagenic and carcinogenic agent is as well regulated as radioactive pollution and efforts directed at a better control of harmful chemicals, for instance, are only taking an example from the ruling on radioprotection

  8. Transperineal low-dose rate iridium-192 interstitial brachytherapy in cervical carcinoma stage IIB

    Energy Technology Data Exchange (ETDEWEB)

    Budrukkar, A.N.; Shrivastava, S.K.; Jalali, R.; Agarwal, J.P.; Dinshaw, K.A. [Tata Memorial Hospital, Parel, Mumbai (India). Dept. of Radiation Oncology; Deshpande, D.D.; Nehru, R.M. [Tata Memorial Hospital, Parel, Mumbai (India). Dept. of Medical Physics

    2001-10-01

    Purpose: To assess local control, survival and complications in patients with cervical carcinoma Stage IIB treated radically with transperineal Iridium-192 low-dose rate interstitial brachytherapy following external beam radiotherapy. Patients and Methods: 65 women (age 25-70 years, mean 47 years) with cervical carcinoma Stage IIB were initially treated with external beam radiotherapy on a telecobalt or 6 MW linear accelerator to a dose of 50 Gy delivered in 5-6 weeks. After 2-3 weeks of completing external radiation, patients received interstitial brachytherapy with Iridium-192 (activity 0.5-1 mCi/cm) using a Syed-Neblett perineal template. The median dose delivered to the implant volume was 24 Gy (range 20-32 Gy) delivered at an average dose rate of 0.70 Gy/h (range 0.40-1.20 Gy/h). A point defined at 1.5 cm lateral to the central uterine tandem at the level of os was taken as a representative for assessing the dose to the cervix. Mean doses delivered by interstitial brachytherapy to point A, cervix, point B and rectum were 38 Gy, 34 Gy, 16 Gy and 16 Gy, respectively. Results: At a median follow-up of 53 months, the actuarial disease free survival and overall survival for 65 patients at both 5 and 10 years was 64% and 44%, respectively. Response to radiotherapy was a strong predictor of local control with 82% of patients continuing to have pelvic control after initial complete response. Overall, nine (14%) patients had persistent disease, ten (15%) developed a central recurrence after initial control and three patients developed distant metastasis on follow-up. No patient had any immediate treatment-related complication. Late toxicity included grade I-II rectal reactions in five patients and grade IV bladder complication (vesico-vaginal fistula) in two patients. 5 years after treatment, one patient developed intestinal obstruction, which was relieved after conservative management. Two patients developed vaginal stenosis. The 5- and 10-year disease free survival

  9. Expression of Genes Associated with DNA Damage Sensing in Human Fibroblasts Exposed to Low-dose-rate Gamma Rays

    Science.gov (United States)

    Zhang, Ye; Mehta, Satish; Hammond, Diane; Pierson, Duane; Jeevarajan, Antony; Cucinotta, Francis; Rohde, Larry; Wu, Honglu

    2007-01-01

    Understanding of the molecular response to low-dose and low-dose-rate radiation exposure is essential for the extrapolation of high-dose radiation risks to those at dose levels relevant to space and other environmental concerns. Most of the reported studies of gene expressions induced by low-dose or low-dose-rate radiation were carried out on exponentially growing cells. In the present study, we analyzed expressions of 84 genes associated with DNA damage sensing using real time PCR in human fibroblasts in mostly G1 phase of the cell cycle. The cells were exposed continuously to gamma rays at a dose rate of 0.8 cGy/hr for 1, 2, 6 or 24 hrs at 37 C throughout the exposure. The total RNA was isolated immediately after the exposure was terminated. Of the 84 genes, only a few showed significant changes of the expression level. Some of the genes (e.g. DDit3 and BTG2) were found to be up or down regulated only after a short period of exposure, while other genes (e.g. PRKDC) displayed a highest expression level at the 24 hr time point. The expression profiles for the exposed cells which had a smaller portion of G1 cells indicated more cell cycle signaling and DNA repair genes either up or down regulated. Interestingly, the panel of genes changed from radiation exposure in G1 cells is different from the panel in cells having less G1 arrest cells. The gene expression profile of the cells responding to low-dose-radiation insult apparently depends on the cell growth stage. The response pathway in G1 cells may differ from that in exponentially growing cells.

  10. Chemo-endocrine therapy with low-dose cisplatin, UFT, and dexamethasone for hormone-refractory prostate cancer patients

    International Nuclear Information System (INIS)

    Since September 2005, twenty-two patients with hormone-refractory prostate cancer (aged 55-81 years) were treated with LH-RH agonist and low-dose cisplatin, tegafur-uracil (UFT), and dexamethasone after proving resistant to estramustine phosphate therapy. The regimen of this therapy consists of 5 mg/body of cisplatin intravenously once a week, 300 mg/day of UFT and 1 mg/day of dexamethasone orally, every day. All patients suffered from clinical progression such as local recurrence in 11 patients who had already received radiation therapy, lymph node metastasis in 7 patients, and bone metastasis in 15 patients. Initial prostate specific antigen (PSA) value ranged from 1.7 ng/mL to 215.1 ng/mL. The PSA response rate, which decreased more than 50% in PSA values was 72.7% (16/22). The follow-up term ranged from 2 to 43 months, and nine patients died of cancer progression. The median time to progression was 11 months, and median overall survival was 19 months. There were no severe adverse effects, and stoppages of the therapy for 13 patients were all due to disease progression. Following this therapy, 9 patients received best supportive care and 4 patients received docetaxel chemotherapy. We considered this therapy to be effective for patients with hormone-refractory prostate cancer because it maintained their good quality of life (QOL). (author)

  11. Inhibition of Cellular Growth of Melanoma Cells Line by Heterogeneous Beta Chronic Irradiation at Very Low-Dose-Rate

    International Nuclear Information System (INIS)

    Radioisotopes that decay via beta emission are widely used in science and medicine. The main advantage of beta-emitters is the relatively long path length in biological tissue (in the mm range). The objective of this work was to determine the inhibition of cellular growth of melanoma cells (melanoma cells are one of the most radioresistant tumor cells) by beta irradiation at very low dose rate using a simple and economic device. This irradiation system represents a situation similar to radiodiagnostic, radioimmunotherapy and brachytherapy because there is a continuous emission of exponentially decreasing low-dose-rate irradiation with heterogeneous dose deposition. It permitted us to study different dose rates changing only the activity of beta emitter. We compare it with the high dose rate gamma irradiation. (authors)

  12. Conditioned instrumental behaviour in the rat: Effects of prenatal irradiation with various low dose-rate doses

    International Nuclear Information System (INIS)

    4 groups of rats of the Wistar-strain were subjected to γ-irradiation on the 16th day of gestation. 5 rats received 0,6 Gy low dose rate irradiation, 5 animals received 0,9 Gy low dose and 6 high dose irradiation, 3 females were shamirradiated. The male offspring of these 3 irradiation groups and 1 control group were tested for locomotor coordination on parallel bars and in a water maze. The female offspring were used in an operant conditioning test. The locomotor test showed slight impairment of locomotor coordination in those animals irradiated with 0,9 Gy high dose rate. Swimming ability was significantly impaired by irradiation with 0,9 Gy high dose rate. Performance in the operant conditioning task was improved by irradiation with 0,9 Gy both low and high dose rate. The 0,9 Gy high dose rate group learned faster than all the other groups. For the dose of 0,9 Gy a significant dose rate effect could be observed. For the dose of 0,6 Gy a similar tendency was observed, differences between 0,6 Gy high and low dose rate and controls not being significant. (orig./MG)

  13. Estimation of non-cancer stochastic effects of prolonged occupational exposure in low dose range

    International Nuclear Information System (INIS)

    This study is aimed at estimation of acute myocardial infarction (AMI) incidence and risk among persons exposed to prolonged low dose rate ionizing radiation. Prevalence and social and medical relevance, and available data on the increased cardio-vascular diseases mortality among nuclear workers determined the chosen clinical model (Howe G.R.,et. Al., 2004). A study was carried out into AMI incidence in closed population of Seversk in 1998-2004, the study was supported by the Federal Agency for Science and Innovations (grant MK-4931.2007.7). Siberian Group of Chemical Enterprises (SGCE) is a town-forming enterprise. Because of this the whole population was divided into residents and SGCE workers, of whom great majority was exposed to long term ionizing radiation in low doses (total cumulative external dose was up to 1 Sv). In the study period, increased incidence was found in both groups (from 5.12 up to 7.11 per 1 000 workers, and from 1.86 up to 2.44 per 1 000 residents). Cross-group analysis (SGCE workers - residents) revealed that general AMI incidence in SGCE employees was significantly greater (χ2 = 64.44-89.05-86.22-65.17-39.78-114.89-96.14; r 2 = 3.54-3.97-3.27-4.59-0.59-18.19-17.58; r = 0.0601-0.0462-0.0706-0.0322-0.4443-0.0000-0.0000 in 1998-2004 respectively). Analysis of standardized relative risk coefficients of developing AMI demonstrated their significant increase in the main group production (auxiliary production incidence was taken as the standard): 1.5 in 1999 (CI 95% 1.15-2.79), 1.8 in 2000 (CI 95% 1.07-2.47), 2.0 in 2001 (CI 95% 1.31-2.99), 2.1 in 2003 (CI 95% 1.42-3.11), 1.9 in 2004 (CI 95% 1.27-2.89). At present, there is data indicating close relationship between AMI development and dose accumulation rate; however, because of irradiation dose homogeneity of the study groups (great majority of AMI patients had doses up to 200 mSv) and limited number of cases in the sample, it was not possible to establish association between AMI development

  14. A comparative study of biological effects on tumor cells between low-dose-rate β-irradiation and high- dose-rate γ-irradiation

    International Nuclear Information System (INIS)

    Objective: To elucidate the radiobiological mechanism underlying cancer treatment with low-dose-rate β-irradiation of 32P, by comparing the cell-killing pattern with high-dose-rate γ-irradiation of 60Co. Methods: HeLa cells were exposed to low-dose-rate β-irradiation of 32P or high-dose-rate γ-irradiation of 60Co. Comparisons were made between these two types of radiations, focusing on the cell-killing patterns evaluated by radiation-induced reproductive cell death( senescence) and necrotic cell death through X-gal senescence staining and tRypan blue exclusion method respectively. Results: The results showed that there were different cell-killing patterns in HeLa cells between 32P radiation at dose-rate of 0.375 cGy/min and that of 60Co at dose-rate of 206 cGy/min at 72 h post irradiation. In exposure to 32P, more HeLa cells were lost due to reproductive cell death than to 60Co. X-gal staining showed that senescent cell ratio in HeLa cells after exposure of 32P was higher than after that of 60Co which caused more necrotic cell death. Conclusions: More reproductive and less necrotic cell death contribute to total cell loss in HeLa cells by radiation of 32P than by 60Co. Understanding the underlying mechanism of radiobiology in different radiations is helpful in radiotherapy of malignant tumor by choosing a more reasonable and effective procedure of treatment. (author)

  15. Low dose, radiation-induced adaptive response against cancer in high-dose-exposed, cancer-prone, Trp53 heterozygous mice

    International Nuclear Information System (INIS)

    Full text: Mice that are heterozygous for Trp53 are both cancer-prone and sensitive to high radiation doses. Groups of 7-8-week-old female Trp53 heterozygous mice were exposed to 4 Gy of 60Co-gamma radiation at either high (0.5 Gy/min) or low (0.5 mGy/min) dose rate. Other groups received a 10-mGy or 100-mGy dose, given at low dose rate (0.5 mGy/min) 24 h prior to the 4 Gy dose. Tumor frequency and latency were measured over the lifespan of the animals. Compared to animals receiving only 4 Gy at high dose rate, mice receiving a prior 10-mGy adapting exposure had significantly extended lifespan and increased latency for all malignant tumors taken together. However, the latency responses were tumor type specific. The prior 10-mGy exposure increased latency for lymphomas and hemangiosarcomas, but decreased latency for spinal osteosarcomas. Increasing the adapting dose to 100 mGy eliminated the tumor latency increase and significantly reduced lifespan. A 10-mGy adapting dose given prior to a 4 Gy exposure at low dose rate generally showed either a reduced effect or no effect. Adapting exposures had no significant effect on tumor frequency. We conclude that adaptive responses are induced by low doses of radiation in radiation sensitive, cancer prone Trp53 +/ - mice, and that these responses are expressed as an increase in tumor latency that reduces the carcinogenic effects of a subsequent large exposure. The dose at which protective effects give way to detrimental effects is tumor type specific

  16. Impacts of low dose rate irradiation on the fertility, fecundity and hatchling survival of Japanese rice fish (medaka, Oryzias latipes)

    International Nuclear Information System (INIS)

    A renewed international interest in the effects on biota from low dose rate irradiation has recently occurred. Much of that interest is centered on the relevance of previously accepted dose rate guidelines (e.g. 10 mGy d-1 for aquatic biota) suggested by the ICRP and IAEA. All parties concerned seem to agree that additional data are needed on population level impacts from chronic low-level exposures to radionuclides. Using a Low Dose Rate Irradiation Facility (LoDIF), we conducted an experiment on the fecundity, fertility and hatchling survival of Japanese Rice Fish (medaka, Oryzias latipes). Fish were exposed externally to 137Cs from juvenile through adulthood at mean dose rates of 3.5, 35 and 350 mGy d-1. Fish were bred at maturity and the following endpoints were examined: 1) the number of eggs produced; 2) the percent of eggs that hatched; and 3) the survival of hatchlings 20-days post hatch. The influence of gender was examined by breeding irradiated males with control females; control males with irradiated females; irradiated males with irradiated females; and control males with control females. The data contribute to our understanding the impacts of low dose rate irradiation. (author)

  17. Radiobiological responses for two cell lines following continuous low dose-rate (CLDR) and pulsed dose rate (PDR) brachytherapy

    International Nuclear Information System (INIS)

    The iso-effective irradiation of continuous low-dose-rate (CLDR) irradiation was compared with that of various schedules of pulsed dose rate (PDR) irradiation for cells of two established human lines, T-47D and NHIK 3025. Complete single-dose response curves were obtained for determination of parameters α and β by fitting of the linear quadratic formula. Sublethal damage repair constants μ and T1/2 were determined by split-dose recovery experiments. On basis of the acquired parameters of each cell type the relative effectiveness of the two regimens of irradiation (CLDR and PDR) was calculated by use of Fowler's radiobiological model for iso-effect irradiation for repeated fractions of dose delivered at medium dose rates. For both cell types the predicted and observed relative effectiveness was compared at low and high iso-effect levels. The results indicate that the effect of PDR irradiation predicted by Fowler's model is equal to that of CLDR irradiation for both small and large doses with T-47D cells. With NHIK 3025 cells PDR irradiation induces a larger effect than predicted by the model for small doses, while it induces the predicted effect for high doses. The underlying cause of this difference is unclear, but cell-cycle parameters, like G2-accumulation is tested and found to be the same for the two cell lines

  18. A model for inverse dose-rate effects - low dose-rate hyper-sensibility in response to targeted radionuclide therapy

    International Nuclear Information System (INIS)

    Full text of publication follows. The aim of this work was to test the hypothesis that the Linear-Quadratic (LQ) model of cell survival, developed for external beam radiotherapy (EBRT), could be extended to targeted radionuclide therapy (TRT) in order to predict dose-response relationships in a cell line exhibiting low dose hypersensitivity (LDH). Methods: aliquots of the PC-3 cancer cell line were treated with either EBRT or an in-vitro model of TRT (Irradiation of cell culture with Y-90 EDTA over 24, 48, 72 or 96 hours). Dosimetry for the TRT was calculated using radiation transport simulations with the Monte Carlo PENELOPE code. Clonogenic as well as functional biological assays were used to assess cell response. An extension of the LQ model was developed which incorporated a dose-rate threshold for activation of repair mechanisms. Results: accurate dosimetry for in-vitro exposures of cell cultures to radioactivity was established. LQ parameters of cell survival were established for the PC-3 cell line in response to EBRT. The standard LQ model did not predict survival in PC-3 cells exposed to Y90 irradiation over periods of up to 96 hours. In fact cells were more sensitive to the same dose when irradiation was carried out over 96 hours than 24 hours. I.e. at a lower dose-rate. Deviations from the LQ predictions were most pronounced below a threshold dose-rate of 0.5 Gy/hr. These results led to an extension of the LQ model based upon a dose-rate dependent sigmoid model of single strand DNA repair. This extension to the model resulted in predicted cell survival curves that closely matched the experimental data. Conclusion: the LQ model of cell survival to radiation has been shown to be largely predictive of response to low dose-rate irradiation. However, in cells displaying LDH, further adaptation of the model was required. (authors)

  19. Phase II Study of Chemoradiotherapy With S-1 and Low-Dose Cisplatin for Inoperable Advanced Gastric Cancer

    International Nuclear Information System (INIS)

    Purpose: The results of a pilot study using S-1/low-dose cisplatin/radiotherapy led us to hypothesize that the initial chemoradiotherapy regimen would induce a 70% efficacy rate with a 10% pathologic complete response rate. Patients and Methods: Only patients with unresectable or incurable advanced gastric cancer were eligible. The patients received induction S-1 and cisplatin therapy with radiotherapy followed by chemotherapy alone. Results: Of the 30 patients recruited and assessed, 29 were eligible for clinical evaluation of measurable lesions. The response rate was 65.5%, with 19 with a partial response, 8 with no change, and 2 with progressive disease of 29 patients. Of the 30 patients recruited, 10 (33.3%) underwent stomach resection and D2 LN dissections. The pathologic complete response rate was 13.3% (4 patients), and the R0 resection rate was 100% (10 patients). The survival analysis showed a median survival time of 25 months. Grade 3 toxicity occurred in 66.7% for leukocytopenia, 33.3% for thrombocytopenia, 23.3% for nausea and appetite loss, and 6.7% for anemia, diarrhea, and renal dysfunction. Although all the patients had been hospitalized with a poor performance status with a giant tumor, 97% (29 of 30) could be discharged after the first cycle, resulting in an improvement in quality of life. Conclusion: Chemoradiotherapy could be a powerful regimen for controlling tumor progression in advanced gastric cancer, improving patients' quality of life with tolerable toxicity. A complete histologic response rate of >10% would be expected, even for large tumors with metastatic lesions

  20. Enhanced Low Dose Rate Sensitivity (ELDRS) tests on advanced SiGe bipolar transistors for very high total dose applications

    International Nuclear Information System (INIS)

    A new comprehensive method for assessing Enhanced Low Dose Rate Sensitivity (ELDRS) in bipolar transistors to be used for very high total doses is applied to an advanced SiGe HBT technology for its use in the ATLAS Upgrade at CERN. Conventional ELDRS assessment methods are combined with switched experiments (high/low dose rate), providing a way to verify the presence of ELDRS at very high doses in reasonable irradiation time. Additionally, an anomalous damage recovery has been found in transistors with saturated damage after further low dose rate irradiations. -- Highlights: • It has been demonstrated that the bipolar technology under study does not show ELDRS in the whole range of total doses studied. • The previous radiation hardness tests of a SiGe HBT technology have been validated. • A new ELDRS test strategy is presented for ELDRS in very high total dose applications. • An anomalous damage recovery has been observed in switched dose rate experiments in the saturation region

  1. Influence to reject effect on tumor cells by pre-irradiation with low dose-rate gamma-rays

    International Nuclear Information System (INIS)

    Radiation has been supposed to be harmful no matter how low the dose is. We have, however, observed that low dose-rate irradiation increased the tumor cells rejecting ability in mice. The technique we used was TD50 (tumor dose 50) assay. The TD50 value indicates the number of cells required for successful transplantation to a half of injected site in the transplanted animals. We examined the rejective effect on tumor cell in pre-irradiated and non-irradiated mice using of TD50. Pre-irradiated groups were exposed 137Cs γ-rays at 0.4-1.2 mGy/hr. We found that TD50 values in mice irradiated with a total dose of 250 mGy were increased compared to non-irradiated mice. These results suggested that the low dose-rate irradiation increased, under certain conditions, the tumor cell rejecting ability in mice. (author)

  2. Dose-rate effects and chronological changes of chromosome aberration rates in spleen cells from mice that are chronically exposed to gamma-ray at low dose rates

    International Nuclear Information System (INIS)

    Dose-rate effects have not been examined in the low dose-rate regions of less than 60-600 mGy/h. Mice were chronically exposed to gamma-ray at 20 mGy/day (approximately 1 mGy/h) up to 700 days and at 1 mGy/day (approximately 0.05 mGy/h) for 500 days under SPF conditions. Chronological changes of chromosome aberration rates in spleen cells were observed along with accumulated doses at both low dose-rates. Unstable aberrations increased in a biphasic manner within 0-2 Gy and 4-14 Gy in 20 mGy/day irradiation. They slightly increased up to 0.5 Gy in 1 mGy/day irradiation. Chromosome aberration rates at 20 mGy/day and 1 mGy/day were compared at the same total doses of 0.5 Gy and 0.25 Gy. They were 2.0 vs. 0.53, and 1.0 vs. 0.47 respectively. Thus, dose-rate effects were observed in these low dose-rate regions. (author)

  3. Biological models and computed iso-effect tables for continuous low dose-rate and intermittent fractionated radiation therapy. Chapter 28

    International Nuclear Information System (INIS)

    Iso-effect tables for continuous low dose-rate radiotherapy and intermittent fractionated radiotherapy are computed using a cell population kinetic model and iso-effect programme. In this way equivalent tissue and tumour doses are estimated for varying fractionation schemes and treatment times. Iso-effect predictions are presented for human skin tolerance and human squamous cell carcinoma. Results are also presented for therapeutic ratios of skin tolerance:squamous cancer lethal dose for well-oxygenated tumours and tumours with 10% hypoxic cells. Using such iso-effect tables, optimal radiotherapy exposure times and a best choice of technique can be identified for different tissues and tumours. (U.K.)

  4. SU-E-T-546: Use of Implant Volume for Quality Assurance of Low Dose Rate Brachytherapy Treatment Plans

    Energy Technology Data Exchange (ETDEWEB)

    Wilkinson, D; Kolar, M [Radiation Oncology, Cleveland Clinic Foundation, Cleveland, OH (United States)

    2014-06-01

    Purpose: To analyze the application of volume implant (V100) data as a method for a global check of low dose rate (LDR) brachytherapy plans. Methods: Treatment plans for 335 consecutive patients undergoing permanent seed implants for prostate cancer and for 113 patients treated with plaque therapy for ocular melanoma were analyzed. Plaques used were 54 COMS (10 to 20 mm, notched and regular) and 59 Eye Physics EP917s with variable loading. Plots of treatment time x implanted activity per unit dose versus v100 ^.667 were made. V100 values were obtained using dose volume histograms calculated by the treatment planning systems (Variseed 8.02 and Plaque Simulator 5.4). Four different physicists were involved in planning the prostate seed cases; two physicists for the eye plaques. Results: Since the time and dose for the prostate cases did not vary, a plot of implanted activity vs V100 ^.667 was made. A linear fit with no intercept had an r{sup 2} = 0.978; more than 94% of the actual activities fell within 5% of the activities calculated from the linear fit. The greatest deviations were in cases where the implant volumes were large (> 100 cc). Both COMS and EP917 plaque linear fits were good (r{sup 2} = .967 and .957); the largest deviations were seen for large volumes. Conclusions: The method outlined here is effective for checking planning consistency and quality assurance of two types of LDR brachytherapy treatment plans (temporary and permanent). A spreadsheet for the calculations enables a quick check of the plan in situations were time is short (e.g. OR-based prostate planning)

  5. Health effects of prolonged low-dose rate gamma-irradiation of a human population in Taiwan, 1983-2003

    International Nuclear Information System (INIS)

    Health effects of low dose-rate , low LET irradiation on large numbers of human population have been rare and less well known and studied. However, the standards for safety and health regulation for radiation exposure depend on solid observations of related studies. during 1983 to mid 1990s, an unusual contamination occurred that was derived from several lost Co-60 orphan sources and un-intentionally recycled into thousands tons construction steels, eventually employed for construction in several cities in Taiwan. Continuous studies on the immediate and prolonged health effects of these 7,000 subjects, with more than 60% have been exposed during prenatal, childhood, and adolescents periods, have been able to form a stron scientific avenue to provide evidences for unusual observation on a human population in natural environments. Moreover, an exposure reconstruction program, co-joined with scientists in National Institute of Occupational Safety and Health and Oregan State University in the U. S.; were initiated and continued throughout the study program that critically provided dose response analysis feasible. These studies include bone marrow/hematological changes, lens opacities, thyroid function and thyroid glands abnormalities, growth and development in physical parameters, helper and suppressor T cell populations, serum p53 protein levels, and cancer incidences and risks. Moreover, several cytogenetic markers have been employed to analyze the subtle changes in the somatic tissues. These include frequencies of micronuclei formation, chromosomal aberrations and chromosomal translocations on circulating T-lymphocytes. Functional studies including IQ testing on prenatally exposed children and the reproductive potential as time-to-pregnancy, TTP, were also observed in married couples with offspring. The observations, published in more than 20 manuscripts, will be summarized and presented for future collaborative studies, based on the established database, case

  6. SU-E-T-546: Use of Implant Volume for Quality Assurance of Low Dose Rate Brachytherapy Treatment Plans

    International Nuclear Information System (INIS)

    Purpose: To analyze the application of volume implant (V100) data as a method for a global check of low dose rate (LDR) brachytherapy plans. Methods: Treatment plans for 335 consecutive patients undergoing permanent seed implants for prostate cancer and for 113 patients treated with plaque therapy for ocular melanoma were analyzed. Plaques used were 54 COMS (10 to 20 mm, notched and regular) and 59 Eye Physics EP917s with variable loading. Plots of treatment time x implanted activity per unit dose versus v100 ^.667 were made. V100 values were obtained using dose volume histograms calculated by the treatment planning systems (Variseed 8.02 and Plaque Simulator 5.4). Four different physicists were involved in planning the prostate seed cases; two physicists for the eye plaques. Results: Since the time and dose for the prostate cases did not vary, a plot of implanted activity vs V100 ^.667 was made. A linear fit with no intercept had an r2 = 0.978; more than 94% of the actual activities fell within 5% of the activities calculated from the linear fit. The greatest deviations were in cases where the implant volumes were large (> 100 cc). Both COMS and EP917 plaque linear fits were good (r2 = .967 and .957); the largest deviations were seen for large volumes. Conclusions: The method outlined here is effective for checking planning consistency and quality assurance of two types of LDR brachytherapy treatment plans (temporary and permanent). A spreadsheet for the calculations enables a quick check of the plan in situations were time is short (e.g. OR-based prostate planning)

  7. Assessment of I-125 seed implant accuracy when using the live-planning technique for low dose rate prostate brachytherapy

    International Nuclear Information System (INIS)

    Low risk prostate cancers are commonly treated with low dose rate (LDR) brachytherapy involving I-125 seeds. The implementation of a ‘live-planning’ technique at the Royal Adelaide Hospital (RAH) in 2007 enabled the completion of the whole procedure (i.e. scanning, planning and implant) in one sitting. ‘Live-planning’ has the advantage of a more reliable delivery of the planned treatment compared to the ‘traditional pre-plan’ technique (where patient is scanned and planned in the weeks prior to implant). During live planning, the actual implanted needle positions are updated real-time on the treatment planning system and the dosimetry is automatically recalculated. The aim of this investigation was to assess the differences and clinical relevance between the planned dosimetry and the updated real-time implant dosimetry. A number of 162 patients were included in this dosimetric study. A paired t-test was performed on the D90, V100, V150 and V200 target parameters and the differences between the planned and implanted dose distributions were analysed. Similarly, dosimetric differences for the organs at risk (OAR) were also evaluated. Small differences between the primary dosimetric parameters for the target were found. Still, the incidence of hotspots was increased with approximately 20% for V200. Statistically significant increases were observed in the doses delivered to the OAR between the planned and implanted data; however, these increases were consistently below 3% thus probably without clinical consequences. The current study assessed the accuracy of prostate implants with I-125 seeds when compared to initial plans. The results confirmed the precision of the implant technique which RAH has in place. Nevertheless, geographical misses, anatomical restrictions and needle displacements during implant can have repercussions for centres without live-planning option if dosimetric changes are not taken into consideration

  8. Low Dose Effects: Testing the Assumptions

    International Nuclear Information System (INIS)

    Our work is to investigate the biological responses of cells and animals to low doses and low dose rates of low linear energy transfer radiation and to compare the results to the predictions of the Linear No-Threshold (LNT) hypothesis. These experiments indicate that at low dose, none of the assumptions of the LNT hypothesis were supported by the data, either in cells or in animals. If these results from human and rodent cells, and from other animals, are applicable to humans, the data further indicate that the use of the LNT hypothesis for radiation protection purposes is not conservative but may actually increase the overall risk of cancer

  9. What physicians think about the need for informed consent for communicating the risk of cancer from low-dose radiation

    International Nuclear Information System (INIS)

    The National Institute of Environmental Health Sciences, a subsidiary of the Food and Drug Administration, has declared that X-ray radiation at low doses is a human carcinogen. The purpose of our study was to determine if informed consent should be obtained for communicating the risk of radiation-induced cancer from radiation-based imaging. Institutional review board approval was obtained for the prospective survey of 456 physicians affiliated with three tertiary hospitals by means of a written questionnaire. Physicians were asked to state their subspecialty, number of years in practice, frequency of referral for CT scanning, level of awareness about the risk of radiation-induced cancer associated with CT, knowledge of whether such information is provided to patients undergoing CT, and opinions about the need for obtaining informed consent as well as who should provide information about the radiation-induced cancer risk to patients. Physicians were also asked to specify their preference among different formats of informed consent for communicating the potential risk of radiation-induced cancer. Statistical analyses were performed using the chi-squared test. Most physicians stated that informed consent should be obtained from patients undergoing radiation-based imaging (71.3%, 325/456) and the radiology department should provide information about the risk of radiation-induced cancer to these patients (54.6%, 249/456). The informed consent format that most physicians agreed with included modifications to the National Institute of Environmental Health Services report on cancer risk from low-dose radiation (20.2%, 92/456) or included information on the risk of cancer from background radiation compared to that from low-dose radiation (39.5%, 180/456). Most physicians do not know if patients are informed about cancer risk from radiation-based imaging in their institutions. However, they believe that informed consent for communicating the risk of radiation-induced cancer

  10. Enhancement of viability of radiosensitive (PBMC) and resistant (MDA-MB-231) clones in low-dose-rate cobalt-60 radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Falcao, Patricia Lima, E-mail: patricialfalcao@gmail.com [Universidade Federal do Amazonas (UFAM), Manaus, AM (Brazil); Motta, Barbara Miranda; Lima, Fernanda Castro de; Lima, Celso Vieira; Campos, Tarcisio Passos Ribeiro [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil)

    2015-05-15

    Objective: in the present study, the authors investigated the in vitro behavior of radio-resistant breast adenocarcinoma (MDA-MB-231) cells line and radiosensitive peripheral blood mononuclear cells (PBMC), as a function of different radiation doses, dose rates and postirradiation time kinetics, with a view to the interest of clinical radiotherapy. Materials and methods: the cells were irradiated with Co-60, at 2 and 10 Gy and two different exposure rates, 339.56 cGy.min{sup -1} and the other corresponding to one fourth of the standard dose rates, present over a 10-year period of cobalt therapy. Post-irradiation sampling was performed at pre-established kinetics of 24, 48 and 72 hours. The optical density response in viability assay was evaluated and a morphological analysis was performed. Results: radiosensitive PBMC showed decrease in viability at 2 Gy, and a more significant decrease at 10 Gy for both dose rates. MDAMB-231 cells presented viability decrease only at higher dose and dose rate. The results showed MDA-MB-231 clone expansion at low dose rate after 48-72 hours post-radiation. Conclusion: low dose rate shows a possible potential clinical impact involving decrease in management of radio-resistant and radiosensitive tumor cell lines in cobalt therapy for breast cancer. (author)

  11. Enhancement of viability of radiosensitive (PBMC and resistant (MDA-MB-231 clones in low-dose-rate cobalt-60 radiation therapy

    Directory of Open Access Journals (Sweden)

    Patrícia Lima Falcão

    2015-06-01

    Full Text Available Abstract Objective: In the present study, the authors investigated the in vitro behavior of radio-resistant breast adenocarcinoma (MDA-MB-231 cells line and radiosensitive peripheral blood mononuclear cells (PBMC, as a function of different radiation doses, dose rates and postirradiation time kinetics, with a view to the interest of clinical radiotherapy. Materials and Methods: The cells were irradiated with Co-60, at 2 and 10 Gy and two different exposure rates, 339.56 cGy.min–1 and the other corresponding to one fourth of the standard dose rates, present over a 10-year period of cobalt therapy. Post-irradiation sampling was performed at pre-established kinetics of 24, 48 and 72 hours. The optical density response in viability assay was evaluated and a morphological analysis was performed. Results: Radiosensitive PBMC showed decrease in viability at 2 Gy, and a more significant decrease at 10 Gy for both dose rates. MDAMB- 231 cells presented viability decrease only at higher dose and dose rate. The results showed MDA-MB-231 clone expansion at low dose rate after 48–72 hours post-radiation. Conclusion: Low dose rate shows a possible potential clinical impact involving decrease in management of radio-resistant and radiosensitive tumor cell lines in cobalt therapy for breast cancer.

  12. Life span of mice continuously exposed to low dose rate radiation in long term and their pathological findings

    International Nuclear Information System (INIS)

    Findings in experimental animals exposed to low dose rate radiation are essential for elucidation of its biological effect because its epidemiological human studies performed in such population as the radiation handling personnel involve many unavoidable confounding factors. For the elucidation, authors have conducted an experiment with unusually low dose rate radiation in the specific-pathogen-free (SPF) mouse to see its effect on the life span and pathogenesis, of which outline is given here. All through under the SPF condition, 8 weeks old, male and female SPF mice of B6C3F1 strain were exposed to 137Cs gamma ray at 0, 0.05, 1.1 and 21 mGy/day for 400 days (a half of the average life span of the mouse) in total doses of 0, 20, 400, 800 mGy, respectively, and then maintained until death. Five hundred mice of each sex were included in one rate group, general status and body weight were checked every day, and organ weight measurement and histopathological examination were done at death. Significant shortening of life span was seen in males and females exposed at 21 and at 1.1 and 21 mGy/day, respectively, where 1.1 mGy/day is 400 times as high as the natural radiation dose rate. Major cause of death was malignant lymphoma in both sexes among 10 or more tumors observed. Between exposed and non-exposed groups, the significant increase of tumor incidence was detected in angiosarcoma and myelogenic leukemia of males at 21 mGy/day and ovarian tumor of females at the same rate. It was considered that the life span shortening was not due to the increase of specific tumor incidence by radiation but by early death by many lethal tumors. It was therefore concluded that the long-term continuous low dose rate radiation could induce the early tumorigenesis, tumor growth promotion or both. (K.T.)

  13. High-dose 5-fluorouracil plus low dose methotrexate plus or minus low-dose PALA in advanced colorectal cancer : a randomised phase II-III trial of the EORTC Gastrointestinal Group

    NARCIS (Netherlands)

    Wils, J; Blijham, GH; Wagener, T; De Greve, J; Jansen, RLH; Kok, TC; Nortier, JWR; Bleiberg, H; Couvreur, ML; Genicot, B; Baron, B

    2003-01-01

    The aim of this study was to investigate whether N-(phosphonacetyl)-L-aspartic acid (PALA) can enhance the activity of low-dose methotrexate (LD-MTX) modulated infusional 5-fluorouracil (5-FU) in patients with advanced colorectal cancer. 198 patients were randomised either to (i) 5-FU 60 mg/kg as a

  14. Responses of rat R-1 cells to low dose rate gamma radiation and multiple daily dose fractions

    International Nuclear Information System (INIS)

    Multifraction irradiation may offer the same therapeutic gain as continuous irradiation. Therefore, a comparison of the efficacy of low dose rate irradiation and multifraction irradiation was the main objective of the experiments to be described. Both regimens were tested on rat rhabdomyosarcoma (R-1) cells in vitro and in vivo. Exponentially growing R-1 cells were treated in vitro by a multifraction irradiation procedure with dose fractions of 2 Gy gamma radiation and time intervals of 1 to 3 h. The dose rate was 1.3 Gy.min-1. The results indicate that multifractionation of the total dose is more effective with respect to cell inactivation than continuous irradiation. (Auth.)

  15. [Early lung cancer detection in an occupational asbestos exposed population: clinical impact of low-dose computed tomography screening].

    Science.gov (United States)

    Pira, E; Coggiola, M; Bosio, D

    2010-01-01

    Lung cancer is the primary cause of cancer mortality in developed countries. Early detection and surgical resection is essential for the treatment of lung cancer. The introduction of low-dose spiral computed tomography (LDCT) is considered one of the most promising clinical research developments in early diagnosis of lung cancer. Our study is aimed at the evaluation of spiral CT in a cohort of subjects with a past occupational exposure to asbestos at high risk of developing lung cancer. 149 subjects were enrolled between 2007 and 2009 (the criteria for enrollment were date of birth between 1930-1961, no previous cancer and general good health, latency from the beginning of exposure > 10 years, exposure duration > 1 year, possibility to undergo to surgery). A helical low-dose CT (LDCT) of the chest was performed yearly and an evaluation protocol derived from IEO with a morphological analysis of nodules have been adopted. 13 nodules were diagnosed in the first CT, 7 in the second and 3 in the third but no invasive procedures have been taken and no lung cancer have been detected. Our early follow-up data aren't able yet to evaluate the effect of screening with LDCT on mortality but have do not confirm some of the literature initial results such as the Increase in cases of overdiagnosis (false positive) due to the high prevalence of benign lesions. PMID:21438306

  16. Low-Dose Chest Computed Tomography for Lung Cancer Screening Among Hodgkin Lymphoma Survivors: A Cost-Effectiveness Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Wattson, Daniel A., E-mail: dwattson@partners.org [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Hunink, M.G. Myriam [Departments of Radiology and Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands and Center for Health Decision Science, Harvard School of Public Health, Boston, Massachusetts (United States); DiPiro, Pamela J. [Department of Imaging, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Das, Prajnan [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hodgson, David C. [Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Mauch, Peter M.; Ng, Andrea K. [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts (United States)

    2014-10-01

    Purpose: Hodgkin lymphoma (HL) survivors face an increased risk of treatment-related lung cancer. Screening with low-dose computed tomography (LDCT) may allow detection of early stage, resectable cancers. We developed a Markov decision-analytic and cost-effectiveness model to estimate the merits of annual LDCT screening among HL survivors. Methods and Materials: Population databases and HL-specific literature informed key model parameters, including lung cancer rates and stage distribution, cause-specific survival estimates, and utilities. Relative risks accounted for radiation therapy (RT) technique, smoking status (>10 pack-years or current smokers vs not), age at HL diagnosis, time from HL treatment, and excess radiation from LDCTs. LDCT assumptions, including expected stage-shift, false-positive rates, and likely additional workup were derived from the National Lung Screening Trial and preliminary results from an internal phase 2 protocol that performed annual LDCTs in 53 HL survivors. We assumed a 3% discount rate and a willingness-to-pay (WTP) threshold of $50,000 per quality-adjusted life year (QALY). Results: Annual LDCT screening was cost effective for all smokers. A male smoker treated with mantle RT at age 25 achieved maximum QALYs by initiating screening 12 years post-HL, with a life expectancy benefit of 2.1 months and an incremental cost of $34,841/QALY. Among nonsmokers, annual screening produced a QALY benefit in some cases, but the incremental cost was not below the WTP threshold for any patient subsets. As age at HL diagnosis increased, earlier initiation of screening improved outcomes. Sensitivity analyses revealed that the model was most sensitive to the lung cancer incidence and mortality rates and expected stage-shift from screening. Conclusions: HL survivors are an important high-risk population that may benefit from screening, especially those treated in the past with large radiation fields including mantle or involved-field RT. Screening

  17. Low-Dose Chest Computed Tomography for Lung Cancer Screening Among Hodgkin Lymphoma Survivors: A Cost-Effectiveness Analysis

    International Nuclear Information System (INIS)

    Purpose: Hodgkin lymphoma (HL) survivors face an increased risk of treatment-related lung cancer. Screening with low-dose computed tomography (LDCT) may allow detection of early stage, resectable cancers. We developed a Markov decision-analytic and cost-effectiveness model to estimate the merits of annual LDCT screening among HL survivors. Methods and Materials: Population databases and HL-specific literature informed key model parameters, including lung cancer rates and stage distribution, cause-specific survival estimates, and utilities. Relative risks accounted for radiation therapy (RT) technique, smoking status (>10 pack-years or current smokers vs not), age at HL diagnosis, time from HL treatment, and excess radiation from LDCTs. LDCT assumptions, including expected stage-shift, false-positive rates, and likely additional workup were derived from the National Lung Screening Trial and preliminary results from an internal phase 2 protocol that performed annual LDCTs in 53 HL survivors. We assumed a 3% discount rate and a willingness-to-pay (WTP) threshold of $50,000 per quality-adjusted life year (QALY). Results: Annual LDCT screening was cost effective for all smokers. A male smoker treated with mantle RT at age 25 achieved maximum QALYs by initiating screening 12 years post-HL, with a life expectancy benefit of 2.1 months and an incremental cost of $34,841/QALY. Among nonsmokers, annual screening produced a QALY benefit in some cases, but the incremental cost was not below the WTP threshold for any patient subsets. As age at HL diagnosis increased, earlier initiation of screening improved outcomes. Sensitivity analyses revealed that the model was most sensitive to the lung cancer incidence and mortality rates and expected stage-shift from screening. Conclusions: HL survivors are an important high-risk population that may benefit from screening, especially those treated in the past with large radiation fields including mantle or involved-field RT. Screening

  18. Concurrent chemoradiotherapy with low dose weekly gemcitabine in stage III non-small cell lung cancer

    International Nuclear Information System (INIS)

    Combined chemoradiotherapy (CRT) is the treatment of choice for stage III NSCLC. Gemcitabine (G) is a novel deoxycitidine analogue that has been proven to be a potent radiosensitizer. Twenty-two consecutive patients were treated with concurrent CRT to demonstrate the tolerability and efficacy of low dose G given weekly as radiosensitizer in stage III NSCLC. Patients with KPS ≥70, adequate bone marrow reserve, with no prior radiotherapy (RT) and surgery were included. Eighteen patients had received prior induction chemotherapy (CT). G (75 mg/m2/week) was infused over 1 hour for 6 weeks. Thoracic RT was given two hours later over 6 weeks at 1.8 Gy/day fractions (total dose of 61.2 Gy). Pulmonary toxicity was evaluated with computed tomography scans in 6 weeks. Median age was 60 years (range, 48–75), median follow-up was 15 months (range, 2–40). Sixty-eight percent of patients were male and median KPS score was 90. Conformal 3D-RT planning was used in 64% of patients. G was given for a median of 5 weeks (range 1–9). Twelve patients (54.6%) received all planned CT. G was stopped because of intolerance in 6 and death in 2 patients. Seven patients (31.8%) had radiation pneumonitis. Twenty patients were evaluated for overall response, 1 patient (4.5%) had clinical CR, 81.8% had PR while 9.5% had SD. Median overall survival (OS) was 14 ± 5 months (95% CI 3–25). One- and 2-year OS rates were 55% and 38%. Sixteen patients died of disease-related events (6 with progression of primary tumor, 8 due to metastatic disease), 2 patients died of other causes. One- and 2-year progression-free survival and local control rates were 56%, 27% and 79%, 51%, respectively. G might be used as radiosensitizer for patients with stage III NSCLC who could not receive full doses CT with concurrent RT

  19. Treatment Outcome of Medium-Dose-Rate Intracavitary Brachytherapy for Carcinoma of the Uterine Cervix: Comparison With Low-Dose-Rate Intracavitary Brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Kaneyasu, Yuko, E-mail: kaneyasu@hiroshima-u.ac.jp [Department of Radiation Oncology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima (Japan); Department of Radiation Oncology, Tokyo Women' s Medical University, Tokyo (Japan); Kita, Midori [Department of Radiation Oncology, Tokyo Women' s Medical University, Tokyo (Japan); Department of Clinical Radiology, Tokyo Metropolitan Tama Medical Center, Tokyo (Japan); Okawa, Tomohiko [Evaluation and Promotion Center, Utsunomiya Memorial Hospital, Tochigi (Japan); Maebayashi, Katsuya [Department of Radiation Oncology, Tokyo Women' s Medical University, Tokyo (Japan); Kohno, Mari [Department of Diagnostic Imaging and Nuclear Medicine, Tokyo Women' s Medical University Hospital, Tokyo (Japan); Sonoda, Tatsuo; Hirabayashi, Hisae [Department of Radiology, Tokyo Women' s Medical University Hospital, Tokyo (Japan); Nagata, Yasushi [Department of Radiation Oncology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima (Japan); Mitsuhashi, Norio [Department of Radiation Oncology, Tokyo Women' s Medical University, Tokyo (Japan)

    2012-09-01

    Purpose: To evaluate and compare the efficacy of medium-dose-rate (MDR) and low-dose-rate (LDR) intracavitary brachytherapy (ICBT) for uterine cervical cancer. Methods and Materials: We evaluated 419 patients with squamous cell carcinoma of the cervix who were treated by radical radiotherapy with curative intent at Tokyo Women's Medical University from 1969 to 1999. LDR was used from 1969 to 1986, and MDR has been used since July 1987. When compared with LDR, fraction dose was decreased and fraction size was increased (1 or 2 fractions) for MDR to make the total dose of MDR equal to that of LDR. In general, the patients received a total dose of 60 to 70 Gy at Point A with external beam radiotherapy combined with brachytherapy according to the International Federation of Gynecology and Obstetrics stage. In the LDR group, 32 patients had Stage I disease, 81 had Stage II, 182 had Stage III, and 29 had Stage IVA; in the MDR group, 9 patients had Stage I disease, 19 had Stage II, 55 had Stage III, and 12 had Stage IVA. Results: The 5-year overall survival rates for Stages I, II, III, and IVA in the LDR group were 78%, 72%, 55%, and 34%, respectively. In the MDR group, the 5-year overall survival rates were 100%, 68%, 52%, and 42%, respectively. No significant statistical differences were seen between the two groups. The actuarial rates of late complications Grade 2 or greater at 5 years for the rectum, bladder, and small intestine in the LDR group were 11.1%, 5.8%, and 2.0%, respectively. The rates for the MDR group were 11.7%, 4.2%, and 2.6%, respectively, all of which were without statistical differences. Conclusion: These data suggest that MDR ICBT is effective, useful, and equally as good as LDR ICBT in daytime (about 5 hours) treatments of patients with cervical cancer.

  20. Treatment Outcome of Medium-Dose-Rate Intracavitary Brachytherapy for Carcinoma of the Uterine Cervix: Comparison With Low-Dose-Rate Intracavitary Brachytherapy

    International Nuclear Information System (INIS)

    Purpose: To evaluate and compare the efficacy of medium-dose-rate (MDR) and low-dose-rate (LDR) intracavitary brachytherapy (ICBT) for uterine cervical cancer. Methods and Materials: We evaluated 419 patients with squamous cell carcinoma of the cervix who were treated by radical radiotherapy with curative intent at Tokyo Women’s Medical University from 1969 to 1999. LDR was used from 1969 to 1986, and MDR has been used since July 1987. When compared with LDR, fraction dose was decreased and fraction size was increased (1 or 2 fractions) for MDR to make the total dose of MDR equal to that of LDR. In general, the patients received a total dose of 60 to 70 Gy at Point A with external beam radiotherapy combined with brachytherapy according to the International Federation of Gynecology and Obstetrics stage. In the LDR group, 32 patients had Stage I disease, 81 had Stage II, 182 had Stage III, and 29 had Stage IVA; in the MDR group, 9 patients had Stage I disease, 19 had Stage II, 55 had Stage III, and 12 had Stage IVA. Results: The 5-year overall survival rates for Stages I, II, III, and IVA in the LDR group were 78%, 72%, 55%, and 34%, respectively. In the MDR group, the 5-year overall survival rates were 100%, 68%, 52%, and 42%, respectively. No significant statistical differences were seen between the two groups. The actuarial rates of late complications Grade 2 or greater at 5 years for the rectum, bladder, and small intestine in the LDR group were 11.1%, 5.8%, and 2.0%, respectively. The rates for the MDR group were 11.7%, 4.2%, and 2.6%, respectively, all of which were without statistical differences. Conclusion: These data suggest that MDR ICBT is effective, useful, and equally as good as LDR ICBT in daytime (about 5 hours) treatments of patients with cervical cancer.

  1. [A comparative study between low-dose and high-dose medroxyprogesterone acetate (MPA) in the treatment of advanced and recurrent breast cancer--in relation to dose, serum concentration and response. Osaka Breast Cancer Research Group].

    Science.gov (United States)

    Furukawa, J; Yayoi, E; Takatsuka, Y; Aikawa, T; Maeura, Y; Kobayashi, T; Miyauchi, K; Kotsuma, Y

    1997-05-01

    A prospective randomized study was carried out to evaluate the effectiveness of MPA in the treatment of breast cancer by comparing low dose (600 mg/day) with high dose (1,200 mg/day) of MPA. In 35 evaluable cases, the response rate to treatment was 40.0% (8/20) with low dose MPA and 26.7% (4/15) with high dose MPA. There was no significant difference between the two groups. The serum MPA concentration measured by high-performance liquid chromatography (HPLC) assay was 23.2 +/- 17.6 ng/ml in the low-dose group and 89.5 +/- 56.7 ng/ml in the high-dose group. Intrapatient variability in serum MPA concentration was relatively stable, but interpatient variability was large. No correlation was found between the response rate and serum MPA concentration. The above results indicate that a low dose of MPA (600 mg/day) is a useful treatment with high effectiveness and safety in advanced and recurrent breast cancer patients. Though no exact data on the optimal serum concentration could not be obtained, it was obvious that a successful response cannot be expected from a serum MPA concentration of less than 17 ng/ml, which was the average serum concentration in NC and PD patients of the low-dose group. PMID:9170519

  2. Effects of long-term, low dose rate fission neutron irradiation on the peripheral hematological cells in rats

    International Nuclear Information System (INIS)

    Objective: To evaluate the effects of long-term, low dose rate fission neutron irradiation on the peripheral hematological cells in rats. Methods: 96 rats were randomly divided into the control group and the irradiation group with low dose rate fission neutron (252Cf, 0.35 mGy/h) irradiation 20.5 h every day. 8 rats of each group were killed at 14 d, 28 d, 42d, 56d, 70d after irradiation and 35d after the irradiation, and their peripheral hematological cells were tested respectively. Results: Compared with the control group, peripheral blood WBC was reduced significantly at the dose of 0.3Gy and 0.4Gy (P < 0.05), and was reduced remarkably at dose of 0.5Gy (P<0.01) and 35d after stopping irradiation(P<0.01). At dose of 0.2Gy, Peripheral blood RBC was abnormally higher comparing with the control group (P<0.01), accompanying with higher HCT and HGB, which suggests condensed blood. At the other point, RBC tend to become lower, but only at dose 0.5Gy, and the difference is significant comparing with control group(P <0.05). At dose of 0.3Gy, 0.4Gy and 0.5Gy, HCT were significantly lower comparing with control group. Comparing with control group, MCV was higher at 35d after stopping irradiation, and PLT was significantly lower in dose of 0.2Gy. Conclusion: Long-term irradiation with low dose rate fission neutron could significantly reduce peripheral blood WBC, with less effects on RBC and PLT. The reduced WBC could not recover at 35d after stopping irradiation. (authors)

  3. Rat skin carcinogenesis as a basis for estimating risks at low doses and dose rates of various types of radiation

    Energy Technology Data Exchange (ETDEWEB)

    Burns, F. J.; Vanderlaan, M.; Strickland, P.; Albert, R. E.

    1976-01-01

    The recovery rate, age dependence and latent period for tumor induction in rat skin were measured for single and split doses of radiation, and the data were analyzed in terms of a general model in an attempt to estimate the expected tumor response for various types of radiation given at low dose rates for long periods of time. The dorsal skin of male rats was exposed to electrons, x rays, or protons in either single or split doses for several doses and the tumor responses were compared during 80 weeks of observation. A two stage model incorporating a reversible or recoverable mode was developed and various parameters in the model, including recovery rate, dose-response coefficients, and indices of age sensitivity, were evaluated experimentally. The measured parameters were then utilized to calculate expected tumor responses for exposure periods extending for duration of life. The calculations indicated that low dose rates could be markedly (/sup 1///sub 100/ to /sup 1///sub 1000/) less effective in producing tumors than the same dose given in a short or acute exposure, although the magnitude of the reduction in effectiveness declines as the dose declines.

  4. The effects of environmental factors and experimental method on the results of low dose rate microprocessor irradiation tests

    International Nuclear Information System (INIS)

    As part of the safety studies of nuclear facilities, a series of experiments have been in progress over a number of years to determine the principal parameters for which allowance needs to be made in the testing of microprocessors in low dose rate nuclear irradiation environments. This paper contains a brief description of the results already published, followed by a review of the latest results obtained, specifically as concerns the effects of temperature, the origin of the batch, the angle of incidence of the radiation and the test routine used. (author)

  5. Clinical application of low-dose CT combined with computer-aided detection in lung cancer screening

    International Nuclear Information System (INIS)

    Objective: To investigate the clinical value of chest low-dose CT (LDCT) combined with computer-aided detection (CAD) system for lung cancer screening in high risk population. Methods: Two hundred and nineteen healthy candidates underwent 64-slice LDCT scan. All images were reviewed in consensus by two radiologists with 15 years of thoracic CT diagnosis experience. Then the image data were analyzed with CAD alone. Finally images were reviewed by two radiologists with 5 years of CT diagnosis experience with and without CT Viewer software. The sensitivity, false positive rate of CAD for pulmonary nodule detection were calculated. SPSS 11.5 software and Chi-square test were used for the statistics. Results: Of 219 candidates ,104(47.5% ) were detected with lung nodules. There were 366 true nodules confirmed by the senior radiologists. The CAD system detected 271 (74.0%) true nodules and 424 false-positive nodules. The false-positive rate was 1.94/per case. The two junior radiologists indentifid 292 (79.8%), 286(78.1%) nodules without CAD and 336 (91.8%), 333 (91.0%) nodules with CAD respectively. There were significant differences for radiologists in indentifying nodules with or without CAD system (P<0.01). Conclusions: CAD is more sensitive than radiologists for indentifying the nodules in the central area or in the hilar region of the lung. While radiologists are more sensitive for the peripheral and sub-pleural nodules,or ground glass opacity nodules, or nodules smaller than 4 mm. CAD can not be used alone. The detection rate can be improved with the combination of radiologist and CAD in LDCT screen. (authors)

  6. Formation of cytogenetic anomalies at the condition of prolonged exposure with low dose rate

    International Nuclear Information System (INIS)

    The properties of chromosomal aberration formation on condition of prolonged exposure had been investigated. It is demonstrated that risk of cytogenetic anomalies on condition of prolonged exposure may be in 1 - 2 order higher then one for the condition of acute exposure. Possible consequences of prolonged exposure for realization of cancer and genetic risks had been discussed

  7. Micronuclei induced by low dose rate irradiation in early spermatids of p53 null and wild mice

    Energy Technology Data Exchange (ETDEWEB)

    Kunugita, Naoki; Kakihara, Hiroyo; Kawamoto, Toshihiro; Norimura, Toshiyuki [Univ. of Occupational and Environmental Health, Kitakyushu, Fukuoka (Japan)

    2002-12-01

    To obtain evidence of the dose-rate effect on induction of micronuclei in early spermatids, we observed frequencies in wild-type p53(+/+), heterozygous p53(+/-) and null p53(-/-) mice 14 days after gamma rays irradiation at a high (1,020 mGy/min) or a low (1.2 mGy/min) dose-rate. A dose- and dose-rate-related increase in micronuclei was seen in early spermatids with no difference between the different p53 status. These data were found to be best fitted by a linear-quadratic dose-response model at a high dose-rate, and by a linear dose-response model at a low dose-rate. The yields at 1.2 mGy/min were significantly lower than those at 1,020 mGy/min in the same manner, independent of p53 status. Testis weight declined significantly after 3 Gy irradiation, but did not depend on dose-rates. In our other studies, we observed the complete elimination both of malformation in fetuses and CD3{sup -}4{sup +} mutant T-lymphocytes in p53(+/+) mice, but not in p53(-/-) mice after irradiation. This indicates that concerted DNA repair and p53-dependent apoptosis are likely to completely eliminate mutagenic damage from the irradiated tissues at low doses or dose-rates in teratogenesis and lymphocytes. In the germ cell, however, irradiation at 1.2 mGy/min was mutagenic, independent of p53 status. (author)

  8. Micronuclei induced by low dose rate irradiation in early spermatids of p53 null and wild mice

    International Nuclear Information System (INIS)

    To obtain evidence of the dose-rate effect on induction of micronuclei in early spermatids, we observed frequencies in wild-type p53(+/+), heterozygous p53(+/-) and null p53(-/-) mice 14 days after gamma rays irradiation at a high (1,020 mGy/min) or a low (1.2 mGy/min) dose-rate. A dose- and dose-rate-related increase in micronuclei was seen in early spermatids with no difference between the different p53 status. These data were found to be best fitted by a linear-quadratic dose-response model at a high dose-rate, and by a linear dose-response model at a low dose-rate. The yields at 1.2 mGy/min were significantly lower than those at 1,020 mGy/min in the same manner, independent of p53 status. Testis weight declined significantly after 3 Gy irradiation, but did not depend on dose-rates. In our other studies, we observed the complete elimination both of malformation in fetuses and CD3-4+ mutant T-lymphocytes in p53(+/+) mice, but not in p53(-/-) mice after irradiation. This indicates that concerted DNA repair and p53-dependent apoptosis are likely to completely eliminate mutagenic damage from the irradiated tissues at low doses or dose-rates in teratogenesis and lymphocytes. In the germ cell, however, irradiation at 1.2 mGy/min was mutagenic, independent of p53 status. (author)

  9. Radiation-induced cancer from low doses of ionizing radiation: risk analysis using the cell dose concept

    International Nuclear Information System (INIS)

    High doses of ionizing radiations are known to bear the risk of cancer to the exposed individual. In order to appreciate potential carcinogenesis from low doses also, the action of ionizing radiation in the human body has to be considered in holistic approach: energy depositions to individual cells trigger effects within a hierachical structure of interacting levels of biological systems, consisting consecutively of atoms, molecules, cells and organ tissue. The present paper describes the cell dose concept which is an essential factor in assessing the risk due to the ionizing radiation to the cells and tissues. Low dose of ionizing radiation induces adaptive response in individual cells which could be linked to the action of molecular radicals. Enzyme activities in bone marrow cells and bilayer lipid membranes and radicals are directly related to radiation effects. Temporary improvements of the detoxification of molecular radicals also improve the cellular defence. The risk analysis calls for more attention as it is important for radiation protection and other beneficial effects due to low doses of irradiation. (author). 18 refs

  10. Long-term results of concurrent chemoradiotherapy using low-dose continuous infusion of 5-fluorouracil for stage II-III esophageal cancer

    International Nuclear Information System (INIS)

    To improve the local control of stage II-III esophageal cancer, we tried concurrent chemoradiotherapy with low-dose continuous infusion of 5-fluorouracil (5-FU) during the entire course of conventional radiotherapy. Forty-three eligible patients with stage II-III esophageal cancer were treated with conventional radiotherapy up to 60-70 Gy concurrently with continuous infusion of 5-FU (300 mg/m2 per 24 hours) for 5 days per week given over 5 to 7 weeks. All patients were followed up more than 5 years after starting the treatments. Although there were two treatment-related deaths, 88% of the patients (38/43) could complete the planned course of chemoradiotherapy. Response rate was 90%. The median survival time was 12.2 months, and the 2- and 5-year overall survival rates were 33% and 15%, respectively. Low-dose continuous infusion of 5-FU given during the entire course of conventional radiotherapy is feasible and seems to offer better results than radiotherapy alone in the treatment of stage II-III esophageal cancer. (author)

  11. DoReMi workshop on multidisciplinary approaches to evaluating cancer risks associated with low-dose internal contamination

    International Nuclear Information System (INIS)

    A workshop dedicated to cancer risks associated with low-dose internal contamination was organised in March 2011, in Paris, in the framework of the DoReMi (Low Dose Research towards Multidisciplinary Integration) European Network of Excellence. The aim was to identify the best epidemiological studies that provide an opportunity to develop a multidisciplinary approach to improve the evaluation of the cancer risk associated with internal contamination. This workshop provided an opportunity for in-depth discussions between researchers working in different fields including (but not limited to) epidemiology, dosimetry, biology and toxicology. Discussions confirmed the importance of research on the health effects of internal contamination. Several existing epidemiological studies provide a real possibility to improve the quantification of cancer risk associated with internal emitters. Areas for future multidisciplinary collaborations were identified, that should allow feasibility studies to be carried out in the near future. The goal of this paper is to present an overview of the presentations and discussions that took place during this workshop. (authors)

  12. Radiation chemistry of water at low dose rates with emphasis on the energy balance

    International Nuclear Information System (INIS)

    There has been considerable interest in absorbed dose water calorimetry. In order to accurately relate the temperature change to the absorbed dose, the energy balance of the overall chemistry of the system must be known. The radiolytic products and their yields are affected by dose rate, dose and added solutes. The yields of the radiolytic products have been calculated using a computer program developed at Atomic Energy of Canada. The chemical energy balance was determined as a function of dose for various dose rates and initial concentrations of hydrogen (H2), oxygen (O2), and hydrogen peroxide (H2O2). In solutions containing H2O2 or O2 and H2 the chemical reactions were exothermic; in other cases they were endothermic. Approach to equilibrium and equilbrium conditions are discussed

  13. Experimental long-term exposures of fish to low dose rate gamma- or alpha-radiation

    International Nuclear Information System (INIS)

    While it is well known that α-radiation is much more damaging than γ-radiation (on an equal absorbed dose basis) to man and mammals, there are no data available to compare the effects of these radiations on fish. As many authorised disposals of radioactivity are made to sea or rivers and include α- and γ-emitters it is important that such data is obtained so that estimates of the combined biological damaging effects may be made. This paper describes experiments made to examine the comparative effects of chronic exposure to α- or γ-radiation on reproductive endpoints in a representative fish, the zebrafish Danio rerio. Fish were exposed to γ-radiation or α-radiation for approximately 1 year. The fish were allowed to breed once per week and for each breeding opportunity the total numbers of eggs, numbers of eggs viable at 24 hours and eggs hatching successfully were recorded. Dose rate groups were 300, 1000 or 7400μGy h-1 for γ-radiation and 9.6, 19, 84 and 214μGy h-1 for α-radiation. None of the α-radiation groups showed significant effects on any measure of egg production while among γ-radiation groups only the highest, 7400μGy h-1 group showed an effect. This was a rapid decrease in total number of eggs and viable eggs laid per opportunity, leading to a failure to lay any after 20 weekly opportunities. There was, however, no significant decrease in any group in the hatch rate of eggs which were viable at 24 hours. Comparison of the highest α-radiation dose rate which produced no effect (214μGy h-1) and the γ-radiation dose rate which had a significant effect (7400μGy h-1) gives a relative biological effect (RBEα) of <35. (author)

  14. Morbidity rate of nervous system among medical personnel occupationally exposed to chronic low dose irradiation

    International Nuclear Information System (INIS)

    The morbidity rate of the nervous system among 1190 subjects, medical personnel, working with sources and environment of ionizing radiation was studied by the personal analysis of the diseases, written down in the personal out-patient department cards as well as of a control group of 870 medical workers of various other specialities. The morbidity rate of the nervous system among the medical personnel, exposed to chronic occupational radiation effect, was established not to be higher than that of the other medical workers - 38.0 and 40.3% respectively. Neuroses and peripheral nervous diseases have the greatest relative share in the structure of morbidity rate of the nervous system in both groups examined, with no statistical significance in the differences of the indices. The significantly higher incidence of autonome dystonias, established among the personnel from the X-ray departments and consulting rooms could be discussed in connection with the great relative share of the subjects from that group with a length of service over 15 years and had received the possible maximum cumulative equivalent doses. 3 tabs., 21 refs

  15. Effect of low dose oxytocin treatment on the pregnancy rate of the dairy cows

    Directory of Open Access Journals (Sweden)

    H. Hamali,

    2011-02-01

    Full Text Available It is well known that during the natural mating, stimulation of the female genital system by the bull causes oxytocin release from the caudal part of the female pituitary gland and this hormone enhances the sperm transport in the genital tract. During the artificial insemination (A.I, this hormone dose not release perfectly. For determine of the oxytocin effect on the pregnancy rates of the cows, a total 100 cows were chosen in a dairy herd located in a suburb of Tabriz (North-west of Iran. These cows were randomly divided into two groups. In the group A, during the A.I, 30 IU oxytocin (3cc Vetocin was injected to the cows intramuscularly. In the group of B, 3cc saline was injected intramuscularly to the control cows. After 45 days of A.I, all of the cows were examined by rectal palpation for pregnancy detection. The pregnancy rates were 58% and 54% in the groups of oxytocin treated and control respectively. The difference between two groups did not differ significantly. These results indicated that oxytocin administration during the A.I had not significant effect on the cow's pregnancy rates.

  16. Low dose-rate intra-operative brachytherapy for soft tissue sarcomas: 85 cases report

    International Nuclear Information System (INIS)

    MATERIAL AND METHODS: Between May 1986 and January 1994, 85 patients with soft tissue sarcomas underwent intra-operative interstitial implants in conjunction with conservative tumor resections. Brachytherapy was part of the initial treatment in 62 cases, and was realized in 23 cases for recurrent tumor. 70/85 (82%) tumors were located in the limbs, 56/85 (66%) were T2 or T3. 38/85 (45%) were involving or close to neuro-vascular structures. The implant dose was 40 - 65 Gy when brachytherapy was the only treatment 31/85 p), mostly for recurrent sarcomas, and 12 - 25 Gy (mean 20 Gy) when combined with external irradiation ((54(85)) p). RESULTS: Median follow-up is 40 months. - 4 years actuarial survival rate is 70.8% for the whole series, 74.5% for previously untreated patients, 61.8 % for patients treated for recurrent tumors. - 4 years actuarial local control rate is respectively 86.4%, 95; 7% and 68.1%. Of the 8 patients with local relapse, 1 is alive without evolutive disease, 7 have developed pulmonary metastasis. Acute side-effects occurred in 18/85 patients (21 %) requiring surgical repair in 8 cases. Late side-effects were mostly fibrosis (30 p), lymphoedemas (8 p), neuropathies (5 p). As a result, functional impairment was observed in 13/85 (15 %) patients. No amputation was required for side-effects. CONCLUSION: This series emphasizes brachytherapy combined with external irradiation is a safe and efficient treatment technique in the treatment of soft tissue sarcomas. The local control rate appears satisfactory and the side-effects tolerable, with limited functional impairment

  17. Low doses of caffeine reduce heart rate during submaximal cycle ergometry

    Directory of Open Access Journals (Sweden)

    Wetter Thomas J

    2007-10-01

    Full Text Available Abstract Background The purpose of this study was to examine the cardiovascular effects of two low-levels of caffeine ingestion in non habitual caffeine users at various submaximal and maximal exercise intensities. Methods Nine male subjects (19–25 yr; 83.3 ± 3.1 kg; 184 ± 2 cm, underwent three testing sessions administered in a randomized and double-blind fashion. During each session, subjects were provided 4 oz of water and a gelatin capsule containing a placebo, 1.5 mg/kg caffeine, or 3.0 mg/kg caffeine. After thirty minutes of rest, a warm-up (30 Watts for 2 min the pedal rate of 60 rpm was maintained at a steady-state output of 60 watts for five minutes; increased to 120 watts for five minutes and to 180 watts for five minutes. After a 2 min rest the workload was 180 watts for one minute and increased by 30 watts every minute until exhaustion. Heart rate (HR was measured during the last 15-seconds of each minute of submaximal exercise. Systolic blood pressure (BP was measured at rest and during each of the three sub-maximal steady state power outputs. Minute ventilation (VE, Tidal volume (VT, Breathing frequency (Bf, Rating of perceived exertion (RPE, Respiratory exchange ratio (RER, and Oxygen consumption (VO2 were measured at rest and during each minute of exercise. Results Caffeine at 1.5 and 3.0 mg/kg body weight significantly lowered (p E, VT, VO2, RPE, maximal power output or time to exhaustion. Conclusion In non habitual caffeine users it appears that consuming a caffeine pill (1.5 & 3.0 mg/kg at a dose comparable to 1–3 cups of coffee lowers heart rate during submaximal exercise but not at near maximal and maximal exercise. In addition, this caffeine dose also only appears to affect systolic blood pressure at rest but not during cycling exercise.

  18. Mild oxidative stress induced by a low dose of cisplatin contributes to the escape of TRAIL-mediated apoptosis in the ovarian cancer SKOV3 cell line.

    Science.gov (United States)

    Lu, Jinzhi; Zhang, Lei; Xie, Fang; Zhu, Liya; Li, Xiaolan; Ouyang, Jingping; He, Xiaohua; Han, Song; Yi, Cunjian

    2016-06-01

    Tumor necrosis factor (TNF)-related apoptosis‑inducing ligand (TRAIL) is expressed in ovarian tissue and is widely thought to exhibit strong antitumor activity in a variety of tumor cell types. Therefore, we hypothesized that the cisplatin resistance of ovarian cancer is linked to the ability to escape from TRAIL-mediated apoptosis. We demonstrated that cisplatin-resistant ovarian cancer cell line SKOV3/DDP tolerated treatment with TRAIL, in contrast to the cisplatin‑sensitive ovarian cancer cell line SKOV3. SKOV3/DDP cells exhibited a much higher cell viability and a lower apoptosis rate than SKOV3 cells after treatment with TRAIL. To determine whether cisplatin induced the tolerance of TRAIL, we pretreated the SKOV3 cells with cisplatin in the presence of TRAIL. This revealed that a low dose of cisplatin (1 µM) increased the TRAIL tolerance of SKOV3 cells. Furthermore, cisplatin induced oxidative stress in both the SKOV3/DDP and SKOV3 cells, although the oxidative stress level of the SKOV3/DDP cells was generally much higher than that noted in the SKOV3 cells. Similarly, a low dose of hydrogen peroxide increased the TRAIL tolerance in SKOV3 cells. Notably, the TRAIL tolerance in the SKOV3 and SKOV3/DDP cells could be abrogated by the oxidative stress scavenger N-acetyl-cysteine. These results suggest that a low dose of cisplatin induces the tolerance of TRAIL in SKOV3 cells at least partly, depending on the oxidative stress signaling pathway. PMID:27035109

  19. Characterizing low dose and dose rate effects in rodent and human neural stem cells exposed to proton and gamma irradiation

    Directory of Open Access Journals (Sweden)

    Bertrand P. Tseng

    2013-01-01

    Full Text Available Past work has shown that exposure to gamma rays and protons elicit a persistent oxidative stress in rodent and human neural stem cells (hNSCs. We have now adapted these studies to more realistic exposure scenarios in space, using lower doses and dose rates of these radiation modalities, to further elucidate the role of radiation-induced oxidative stress in these cells. Rodent neural stem and precursor cells grown as neurospheres and human neural stem cells grown as monolayers were subjected to acute and multi-dosing paradigms at differing dose rates and analyzed for changes in reactive oxygen species (ROS, reactive nitrogen species (RNS, nitric oxide and superoxide for 2 days after irradiation. While acute exposures led to significant changes in both cell types, hNSCs in particular, exhibited marked and significant elevations in radiation-induced oxidative stress. Elevated oxidative stress was more significant in hNSCs as opposed to their rodent counterparts, and hNSCs were significantly more sensitive to low dose exposures in terms of survival. Combinations of protons and γ-rays delivered as lower priming or higher challenge doses elicited radioadaptive changes that were associated with improved survival, but in general, only under conditions where the levels of reactive species were suppressed compared to cells irradiated acutely. Protective radioadaptive effects on survival were eliminated in the presence of the antioxidant N-acetylcysteine, suggesting further that radiation-induced oxidative stress could activate pro-survival signaling pathways that were sensitive to redox state. Data corroborates much of our past work and shows that low dose and dose rate exposures elicit significant changes in oxidative stress that have functional consequences on survival.

  20. Fast radioactive seed localization in intraoperative cone beam CT for low-dose-rate prostate brachytherapy

    Science.gov (United States)

    Hu, Yu-chi; Xiong, Jian-ping; Cohan, Gilad; Zaider, Marco; Mageras, Gig; Zelefsky, Michael

    2013-03-01

    A fast knowledge-based radioactive seed localization method for brachytherapy was developed to automatically localize radioactive seeds in an intraoperative volumetric cone beam CT (CBCT) so that corrections, if needed, can be made during prostate implant surgery. A transrectal ultrasound (TRUS) scan is acquired for intraoperative treatment planning. Planned seed positions are transferred to intraoperative CBCT following TRUS-to-CBCT registration using a reference CBCT scan of the TRUS probe as a template, in which the probe and its external fiducial markers are pre-segmented and their positions in TRUS are known. The transferred planned seeds and probe serve as an atlas to reduce the search space in CBCT. Candidate seed voxels are identified based on image intensity. Regions are grown from candidate voxels and overlay regions are merged. Region volume and intensity variance is checked against known seed volume and intensity profile. Regions meeting the above criteria are flagged as detected seeds; otherwise they are flagged as likely seeds and sorted by a score that is based on volume, intensity profile and distance to the closest planned seed. A graphical interface allows users to review and accept or reject likely seeds. Likely seeds with approximately twice the seed volume are automatically split. Five clinical cases are tested. Without any manual correction in seed detection, the method performed the localization in 5 seconds (excluding registration time) for a CBCT scan with 512×512×192 voxels. The average precision rate per case is 99% and the recall rate is 96% for a total of 416 seeds. All false negative seeds are found with 15 in likely seeds and 1 included in a detected seed. With the new method, updating of calculations of dose distribution during the procedure is possible and thus facilitating evaluation and improvement of treatment quality.

  1. Low doses of radiation increase the latency of spontaneous lymphomas and spinal osteosarcomas in cancer-prone, radiation-sensitive Trp53 heterozygous mice

    International Nuclear Information System (INIS)

    Mice heterozygous for Trp53 are radiation-sensitive and cancer-prone, spontaneously developing a variety of cancer types. Osteosarcomas in the spine lead to paralysis, while lymphomas lead rapidly to death, distinct events that provide objective measures of latency. The effects of a single low-dose (10 or 100 mGy), low-dose-rate (0.5 mGy/min) 60Co γ irradiation on lymphoma or spinal osteosarcoma frequency and latency, defined as time of death or of onset of paralysis, respectively, were examined. Compared to spontaneous lymphomas or to spinal osteosarcomas leading to paralysis in unexposed mice, an exposure of 7-8-week-old Trp53+/- mice to 10 or 100 mGy had no significant effect on tumor frequency, indicating no effect on tumor initiation. All tumors are therefore assumed to be of spontaneous origin. However, a 10-mGy exposure reduced the risk of both lymphomas and spinal osteosarcomas by significantly increasing tumor latency, indicating that the main in vivo effect of a low-dose exposure is a reduction in the rate at which spontaneously initiated cells progress to malignancy. The effect of this adaptive response persisted for the entire life span of all the animals that developed these tumors. Exposure to 100 mGy delayed lymphoma latency longer than the 10-mGy exposure. However, the 100-mGy dose increased spinal osteosarcoma risk by decreasing overall latency compared to unexposed control mice. That result suggested that this higher dose was in a transition zone between reduced and increased risk, but that the dose at which the transition occurs varies with the tumor type. (author)

  2. Distributed optical fibre temperature measurements in a low dose rate radiation environment based on Rayleigh backscattering

    Science.gov (United States)

    Faustov, A.; Gussarov, A.; Wuilpart, M.; Fotiadi, A. A.; Liokumovich, L. B.; Kotov, O. I.; Zolotovskiy, I. O.; Tomashuk, A. L.; Deschoutheete, T.; Mégret, P.

    2012-04-01

    On-line monitoring of environmental conditions in nuclear facilities is becoming a more and more important problem. Standard electronic sensors are not the ideal solution due to radiation sensitivity and difficulties in installation of multiple sensors. In contrast, radiation-hard optical fibres can sustain very high radiation doses and also naturally offer multi-point or distributed monitoring of external perturbations. Multiple local electro-mechanical sensors can be replaced by just one measuring fibre. At present, there are over four hundred operational nuclear power plants (NPPs) in the world 1. Operating experience has shown that ineffective control of the ageing degradation of major NPP components can threaten plant safety and also plant life. Among those elements, cables are vital components of I&C systems in NPPs. To ensure their safe operation and predict remaining life, environmental monitoring is necessary. In particular, temperature and radiation dose are considered to be the two most important parameters. The aim of this paper is to assess experimentally the feasibility of optical fibre temperature measurements in a low doserate radiation environment, using a commercially available reflectometer based on Rayleigh backscattering. Four different fibres were installed in the Sub-Pile Room of the BR2 Material testing nuclear reactor in Mol, Belgium. This place is man-accessible during the reactor shut-down, allowing easy fibre installation. When the reactor operates, the dose-rates in the room are in a range 0.005-5 Gy/h with temperatures of 40-60 °C, depending on the location. Such a surrounding is not much different to some "hot" environments in NPPs, where I&C cables are located.

  3. Reductions in carotid chemoreceptor activity with low-dose dopamine improves baroreflex control of heart rate during hypoxia in humans.

    Science.gov (United States)

    Mozer, Michael T; Holbein, Walter W; Joyner, Michael J; Curry, Timothy B; Limberg, Jacqueline K

    2016-07-01

    The purpose of the present investigation was to examine the contribution of the carotid body chemoreceptors to changes in baroreflex control of heart rate with exposure to hypoxia. We hypothesized spontaneous cardiac baroreflex sensitivity (scBRS) would be reduced with hypoxia and this effect would be blunted when carotid chemoreceptor activity was reduced with low-dose dopamine. Fifteen healthy adults (11 M/4 F) completed two visits randomized to intravenous dopamine or placebo (saline). On each visit, subjects were exposed to 5-min normoxia (~99% SpO2), followed by 5-min hypoxia (~84% SpO2). Blood pressure (intra-arterial catheter) and heart rate (ECG) were measured continuously and scBRS was assessed by spectrum and sequence methodologies. scBRS was reduced with hypoxia (P dopamine (P dopamine (P dopamine did not attenuate the decrease in baroreflex sensitivity to falling pressures (scBRS "down-down"; P > 0.05). Present findings are consistent with a reduction in scBRS with systemic hypoxia. Furthermore, we show this effect is partially mediated by the carotid body chemoreceptors, given the fall in scBRS is attenuated when activity of the chemoreceptors is reduced with low-dose dopamine. However, the improvement in scBRS with dopamine appears to be specific to rising blood pressures. These results may have important implications for impairments in baroreflex function common in disease states of acute and/or chronic hypoxemia, as well as the experimental use of dopamine to assess such changes. PMID:27418545

  4. Stimulation effects of low dose-rate irradiation on pancreatic antioxidant activity in type II diabetes model mice

    International Nuclear Information System (INIS)

    The effects of low dose-rate gamma irradiation on the type II diabetes mellitus were investigated in BKS.Cg-+Leprdb/+Leprdb/Jcl (DB mice). Ten-week-old female DB mice (5 mice in each group) were irradiated with gamma ray at 0.35, 0.70, or 1.2 mGy/hr. During the course of the 12 weeks the glucose level slightly increased with little difference between the irradiated and the non-irradiated groups. The plasma insulin concentration decreased within the first 4 weeks in all groups. The level was kept low in the non-irradiated mice; while the insulin level in the irradiated groups showed a tendency to increase. In the 0.70 mGy/hr group the increase was statistically significant after 12 weeks of irradiation. Total activity of SOD, one of antioxidative enzymes, decreased both in non-irradiated and irradiated groups; however the decrease was less in the irradiated groups, especially 0.70 mGy/hr group. In the 0.70 mGy/hr group Mn-SOD activity, one of the components of total SOD activity, increased after 12-week irradiation. A pathological examination of the pancreas revealed that damage to β cells responsible for the secretion of insulin was much less in the 0.70 mGy/hr group compared to that in the non-irradiated group. These results indicated that the low dose-rate irradiation increase the antioxidative capacity in the pancreas to protect β cells from oxidative damage, and the to increase the insulin level. This mechanism would lead the mice to the recovery from the disease and the prolongation of the life span as is demonstrated in our previous report. (author)

  5. A comparison of larval density and low dose rate irradiation effects on amphibian body size at metamorphosis

    International Nuclear Information System (INIS)

    Amphibian larvae undergo substantial morphological and physiological changes as they metamorphose into adults. This period of rapid change and enhanced cell division could increase their sensitivity to external stressors. In this study, we were interested in possible differences between natural and anthropogenic stressor effects during the period just prior to metamorphosis. We studied this by exposing late-stage Scaphiopus holbrookii tadpoles in different larval densities to four irradiation dose rates (0.13, 2.4, 21, and 222 mGy d-1) from 137Cs. Life history traits important for population dynamics, such as body size at metamorphosis and development rate, were measured. Results suggest that the ecological factor larval density had a much more profound effect on juvenile body size at metamorphosis than low-dose rate radiation. The development rate measured as age at metamorphosis was not effected by the two stressors. Radiation had no impact on the endpoints we measured; giving credence to the IAEA guidance that a dose rate smaller than 10 mGy d-1 is protective of aquatic biota. (author)(tk)

  6. A comparison of larval density and low dose rate irradiation effects on amphibian body size at metamorphosis

    Energy Technology Data Exchange (ETDEWEB)

    Stark, K.; Scott, D.E.; Tsyusko, O.; Coughlin, D.P.; Hinton, T.G.

    2008-07-01

    Amphibian larvae undergo substantial morphological and physiological changes as they metamorphose into adults. This period of rapid change and enhanced cell division could increase their sensitivity to external stressors. In this study, we were interested in possible differences between natural and anthropogenic stressor effects during the period just prior to metamorphosis. We studied this by exposing late-stage Scaphiopus holbrookii tadpoles in different larval densities to four irradiation dose rates (0.13, 2.4, 21, and 222 mGy d-1) from 137Cs. Life history traits important for population dynamics, such as body size at metamorphosis and development rate, were measured. Results suggest that the ecological factor larval density had a much more profound effect on juvenile body size at metamorphosis than low-dose rate radiation. The development rate measured as age at metamorphosis was not effected by the two stressors. Radiation had no impact on the endpoints we measured; giving credence to the IAEA guidance that a dose rate smaller than 10 mGy d-1 is protective of aquatic biota. (author)(tk)

  7. Recovery Effect and Life Prolong Effect of Long Term Low-Dose Rate Irradiation on Type II Diabetes Model Mice

    Energy Technology Data Exchange (ETDEWEB)

    Nomura, T.; Makino, N.; Oda, T.; Suzuki, I.; Sakai, K

    2004-07-01

    The effects of low-dose rate gamma-irradiation were investigated on model mice for type II diabetes mellitus, C57BL/KsJ-db/db. The mice develop the type II diabetes by 10 weeks of age due to obesity and are characterized by hyperinsulinemia. Female 10-week old mice, a group of 12 mice, were irradiated at 0.65 mGy/hr from 137-Cs (370 GBq). The urine glucose levels of all of the mice were strongly positive at the beginning of the irradiation. In the irradiated group, the decrease in the glucose level was observed in 3 mice. Such recovery from the diabetes was never observed in 12 mice of non-irradiated control group. There is no systematic difference in the change of body weight, food assumption, and amount of drinking water, between the irradiated group and the non-irradiated group or between the recovered mice and the non-recovered mice. The survival was better in the irradiated group: the surviving fraction at the age of 90 weeks was 75% in the irradiated group, while 40% in the non-irradiated. Marked difference was also observed in the appearance of the coat hair, skin, and tail; better condition was kept in the irradiated group. In the irradiated mice mortality was delayed and the healthy appearance was prolonged in the irradiated mice by about 20 ? 30 weeks compared with the non-irradiated mice. These results suggest that the low-dose irradiation modified the condition of the diabetic mice, which lead not only to the recovery of the diabetes, but also to the suppression of the aging process. (Author)

  8. Genetic effect of low dose rate radiation on human cells immortalized with the hTERT gene

    International Nuclear Information System (INIS)

    We established immortal human cells by introducing the hTERT gene into skin fibroblast cells obtained from normal (SuSa) and ataxia telangiectasia (AT: AT1OS) individuals of Japanese origin. These immortalized cells showed the same characteristics as the original cells except expanded life span. We irradiated SuSa/T-n and AT1OS/T-n cells with low-dose-rate (LDR; 0.3 mGy/min) irradiation at confluent state in low-serum medium. Then, survival rate and micronucleus frequency of each cell line were analyzed. In SuSa/T-n cells, frequency of HPRT mutation induction was also determined by 6TG selection. In SuSa/T-n cells, survival rate and micronucleus frequency showed higher resistance after irradiation with LDR than high-dose-rate (HDR; 2 Gy/min) irradiation. In contrast, no significant difference was observed in survival and micronucleus induction in AT1OS/T-n cells between HDR and LDR irradiation, suggesting that AT1OS/T-n cells may have some defect in DNA repair activity. In SuSa/T-n cells, the frequency of HPRT mutation after LDR irradiation decreased to approximately one eighth that after HDR irradiation. (author)

  9. Dose-response relationships and risk estimates for the induction of cancer due to low doses of low-LET radiation

    International Nuclear Information System (INIS)

    Risk estimates for radiation-induced cancer at low doses can be obtained only by extrapolation from the known effects at high doses and high dose rates, using a suitable dose-response model. The applicability of three different models, linear, sublinear and supralinear, are discussed in this paper. Several experimental studies tend to favour a sublinear dose-response model (linear-quadratic model) for low-LET radiation. However, human epidemiological studies do not exclude any of the dose-response relationships. The risk estimates based on linear and linear quadratic dose-response models are compared and it is concluded that, for low-LET radiation, the linear dose-response model would probably over-estimate the actual risk of cancer by a factor of two or more. (author)

  10. High dose and low dose radiation exposure in the induction of breast cancer

    International Nuclear Information System (INIS)

    In today's modern practice of Radiation Oncology it is becoming increasingly common to follow many patients with breast cancer. There is a proven association between prior radiation and the development of breast cancer, although in many instances the available sources of data are confusing. Characteristic features of radiation induced breast cancer are the importance of age at first exposure to radiation and the long latency period. The risk of breast cancer is highest in women exposed in the first decade of life and lessens progressively with increased age at exposure. The latency period is typically 10 years or more; a time in which other age dependent factors may influence the expression of the malignant phenotype. Genetic factors may also (in theory) increase a particular patient's susceptibility. (author)

  11. Precipitate evolution in low-nickel austenitic stainless steels during neutron irradiation at very low dose rates

    Energy Technology Data Exchange (ETDEWEB)

    Isobe, Y.; Sagisaka, M. [Nuclear Fuel Industries, Osaka (Japan); Garner, F. [Pacific Northwest National Laboratory, Richland WA, AK (United States); Okita, T. [Tokyo Univ. (Japan)

    2007-07-01

    Full text of publication follows: Not all components of a fusion reactor will be subjected to high atomic displacement rates. Some components outside the plasma containment may experience relatively low displacement rates but data generated under long-term irradiation at low dpa rates is hard to obtain. In another study the neutron-induced microstructural evolution in response to long term irradiation at very low dose rates was studied for a Russian low-nickel austenitic stainless steel that is analogous to AISI 304. The irradiated samples were obtained from an out-of-core anti-crush support column for the BN-600 fast reactor with doses ranging from 1.5 to 22 dpa generated at 3x10{sup -9} to 4x10{sup -8} dpa/s. The irradiation temperatures were in a very narrow range of 370-375 deg. C. Microstructural observation showed that in addition to voids and dislocations, an unexpectedly high density of small carbide precipitates was formed that are not usually observed at higher dpa rates in this temperature range. These results required us to ask if such unexpected precipitation was anomalous or was a general feature of low-flux, long-term irradiation. It is shown in this paper that a similar behavior was observed in a western stainless steel, namely AISI 304 stainless steel, irradiated at similar temperatures and dpa rates in the EBR-II fast reactor, indicating that irradiation at low dpa rates for many years leads to a different precipitate microstructure and therefore different associated changes in matrix composition than are generated at higher dpa rates. One consequence of this precipitation is a reduced lattice parameter of the alloy matrix, leading to densification that increases in strength with increasing temperature and dose. A. non-destructive method to evaluate these precipitates is under development and is also discussed in this paper. (authors)

  12. Effects of low dose-rate radiation on sperm concentration and testicular volume in crab-eating monkeys (Macaca fascicularis)

    Energy Technology Data Exchange (ETDEWEB)

    Okamoto, M.; Kitazume, M.

    1986-05-01

    Mature male crab-eating monkeys over the age of 5 years were exposed to whole-body irradiation with 1.0 (3 monkeys), 1.5 (2 monkeys), 2.5 (3 monkeys) and 4.0 Gy (1 monkey) of /sup 137/Cs gamma-rays at the dose rate of 0.18 x 10/sup -4/ Gy/min (0.024 Gy/22h/day). Immediately after semen collection, sperm number was counted and the testicular volume (V) was measured. Sperm concentrations were continuously decreased after irradiation and reached the level of minimum sperm concentration, i.e., 0.4% for 1.0 Gy and 0.1% for 1.5 Gy. Testicular volume was also decreased to 59% of pre-irradiation at 18 weeks after irradiation with 1.5 Gy. However, after irradiation with 2.5 and 4.0 Gy, sperm concentrations were very low and these doses caused azoospermia. Testicular volume decreased to 48% of pre-irradiation at 16 weeks after 2.5 Gy irradiation. The spermatogenic activity had not recovered 18 and 27 months after irradiation with 2.5 and 4.0 Gy, respectively and the previous ones, the effects of low dose-rate radiation on spermatogenic activity seem to be different from those of high dose-rate radiation.

  13. Retrospective Analysis of Local Control and Cosmetic Outcome of 147 Periorificial Carcinomas of the Face Treated With Low-Dose Rate Interstitial Brachytherapy

    International Nuclear Information System (INIS)

    Purpose: Skin cancer is the most common malignancy in white populations. We evaluated the local cure rate and cosmetic outcome of patients with basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) of the face treated with low-dose rate brachytherapy. Methods and Materials: Between February 1990 and May 2000, 147 facial carcinomas in 132 patients were treated by 192Ir wire implantation. Side effects of brachytherapy were noted. Follow-up was 2 years or more. Locoregional recurrence-free survival (LRFS) and overall survival were recorded. Group A included patients treated by primary brachytherapy, and Group B included those treated after recurrence. Results: A total of 121 carcinomas were BCCs (82.3%) and 26 were SCCs (17.7%); the median tumor size was 10 mm. Of the tumors, 86 (58.5%) were in men and 61 (41.5%) were in women; the median age was 71 years. Group A comprised 116 lesions (78.9%), and Group B, 31 (21.1%). There were 17 relapses (11.6%) after a median follow-up of 72 months: 12 local, 4 nodal, and 1 local and nodal. Locoregional-free survival was 96.6% at 2 years and 87.3% at 5 years. Five-year LRFS was 82.6% in men and 93.3% in women (p = 0.027). After adjustment for gender, LRFS was better after primary treatment than after recurrence (hasard ratio HR, 2.91; 95% confidence interval, 1.06-8.03; p = 0.039). Five-year LRFS was 90.4% for BCC and 70.8% for SCC (p = 0.03). There were no Grade 3 complications. Conclusions: Low-dose rate brachytherapy offers good local control and cosmetic outcome in patients with periorificial skin carcinomas, with no Grade 3 complications. Brchytherapy is more efficient when used as primary treatment.

  14. Correlation between radon level and confounders of cancer. A note on epidemiological inference at low doses

    International Nuclear Information System (INIS)

    Complete text of publication follows. Objective. The aim of this study was to examine and further clarify the extent of radon and progeny induced carcinogenesis, both separated from and combined with other confounders and health risk factors. This work was financed by National Development Agency, Hungary, with GVOP-3.1.1.-2004-05-0384/3.0. Methods. A case-control study was conducted in a Hungarian countryside region where the proportion of houses with yearly average radon level above 200 Bq.m-3 was estimated to be higher than 20% by our preceding regional surveys. Radon levels were measured with CR39 closed etched detectors for three seasons separately yielding yearly average by estimating the low summer level. The detectors were placed in the bedrooms, where people were expected to spend one third of a day. 520 patients with diagnosed cancers were included in these measurements, amongst which 77 developed lung or respiratory cancers. The control group consisted 6333 individuals, above 30 years of age. Lifestyle risk factors of cancers were collected by surveys including social status, pollution from indoor heating, smoking and alcohol history, nutrition, exercise and mental health index 5. Except smoking and alcohol habits, these cofactors were only available for the control group. Comparing disease occurrences the authors selected the multivariate generalised linear models. The case and control proportions along a given factor are binomially distributed, thus the logit link function was used. For radon both log and linear terms were probed for. Results. Many known health confounders of cancers correlated with radon levels, with an estimated total net increase of 50-150 Bq m-3 with increased risks. For lung cancers the model with the terms radon, age, gender and smoking was found to have the lowest Akaike Information Criterion (AIC). Heavy dependency on age, gender and smoking contribute largely to observed lung cancer incidence. However log linear relationship

  15. Daily low-dose cisplatin and concurrent thoracic irradiation for poor-risk patients with unresectable non-small-cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Takata I

    2002-10-01

    Full Text Available A pilot study was conducted to assess the efficacy and feasibility of daily low-dose cisplatin with concurrent thoracic irradiation for clinically unresectable non-small-cell lung cancer (NSCLC. Patients with inoperable NSCLC who had poor risk factors such as advanced age, poor performance status, poor lung function, or concomitant active malignancy were entered into the study. Low-dose cisplatin (6 mg/m2 was administered daily before concurrent thoracic irradiation (2 Gy/day; total dose of 60 Gy was given. Twenty-five patients were registered. The majority of the patients had either stage IIIA (24.0% or stage IIIB (60.0% disease. Fifteen patients (60.0% completed the planned treatment. Both chemotherapy and radiotherapy were stopped in 3 patients (12.0% due to poor response, and 7 patients (28.0% partly received radiotherapy alone as a result of their toxicity response. The proportion of total administered dose to planned dose was 90.9% for chemotherapy and 99.3% for radiotherapy, which were comparable to those in previous studies for LA-NSCLC patients without poor risk factors. Grade 3 leukopenia and neutropenia developed in 14 patients (56.0% and 10 patients (40.0%, respectively, but grade 4 toxicity was not encountered. Grade 3 pneumonitis and esophagitis were observed in 4 patients (16.0% and 2 patients (8.0%, respectively. The overall response rate was 60.0%. The median survival time was 22 months, and the 2-year survival rate was 50.3%. Daily low-dose cisplatin and concurrent thoracic irradiation were well tolerated even by poor-risk patients with NSCLC, and showed a therapeutic efficacy similar to that for good-risk patients.

  16. In Vitro Cytotoxicity of Low-Dose-Rate Radioimmunotherapy by the Alpha-Emitting Radioimmunoconjugate Thorium-227-DOTA-Rituximab

    International Nuclear Information System (INIS)

    Purpose: To determine whether the low-dose-rate α-particle-emitting radioimmunoconjugate 227Th-1,4,7,10-p-isothiocyanato-benzyl-tetraazacyclododecane-1,4,7, 10-tetraacetic acid (DOTA)-rituximab can be used to inactivate lymphoma cells growing as single cells and small colonies. Methods and Materials: CD20-positive lymphoma cell lines were treated with 227Th-DOTA-rituximab for 1-5 weeks. To simulate the in vivo situation with continuous but decreasing supply of radioimmunoconjugates from the blood pool, the cells were not washed after incubation with 227Th-DOTA-rituximab, but half of the medium was replaced with fresh medium, and cell concentration and cell-bound activity were determined every other day after start of incubation. A microdosimetric model was established to estimate the average number of hits in the nucleus for different localizations of activity. Results: There was a specific targeted effect on cell growth of the 227Th-DOTA-rituximab treatment. Although the cells were not washed after incubation with 227Th-DOTA-rituximab, the average contribution of activity in the medium to the mean dose was only 6%, whereas the average contribution from activity on the cells' own surface was 78%. The mean dose rates after incubation with 800 Bq/mL 227Th-DOTA-rituximab varied from 0.01 to 0.03 cGy/min. The average delay in growing from 105 to 107 cells/mL was 15 days when the cells were treated with a mean absorbed radiation dose of 2 Gy α-particle radiation from 227Th-DOTA-rituximab, whereas it was 11 days when the cells were irradiated with 6 Gy of X-radiation. The relative biologic effect of the treatment was estimated to be 2.9-3.4. Conclusions: The low-dose-rate radioimmunoconjugate 227Th-DOTA-rituximab is suitable for inactivation of single lymphoma cells and small colonies of lymphoma cells.

  17. Biology responses to low dose radiation

    International Nuclear Information System (INIS)

    Biology responses to low dose radiation is the most important problem of medical radiation and radiation protection. The especial mechanism of low dose or low dose rate induced cell responses, has been found independent with linear no-threshold model. This article emphasize to introduce low dose or low dose rate induced biology responses of adaptive response, by-effect, super-sensitivity and genomic instability. (authors)

  18. To Screen or not to Screen: Low Dose Computed Tomography in Comparison to Chest Radiography or Usual Care in Reducing Morbidity and Mortality from Lung Cancer.

    Science.gov (United States)

    Dajac, Joshua; Kamdar, Jay; Moats, Austin; Nguyen, Brenda

    2016-01-01

    Lung cancer has the highest mortality rate of all cancers. This paper seeks to address the question: Can the mortality of lung cancer be decreased by screening with low-dose computerized tomography (LDCT) in higher risk patients compared to chest X-rays (CXR) or regular patient care? Currently, CXR screening is recommended for certain high-risk patients. Several recent trials have examined the effectiveness of LDCT versus chest radiography or usual care as a control. These trials include National Lung Screening Trial (NLST), Detection And screening of early lung cancer with Novel imaging TEchnology (DANTE), Lung Screening Study (LSS), Depiscan, Italian Lung (ITALUNG), and Dutch-Belgian Randomized Lung Cancer Screening Trial (Dutch acronym: NELSON study). NLST, the largest trial (n=53, 454), demonstrated a decrease in mortality from lung cancer in the LDCT group (RRR=20%, P=0.004). LSS demonstrated a greater sensitivity in detecting both early stage and any stage of lung cancer in comparison to traditional CXR. Although the DANTE trial yielded data consistent with findings in LSS, it also showed that via LDCT screening a greater proportion of patients were placed under unnecessary surgical procedures. The Depiscan trial yielded a high nodule detection rate at the cost of a high false-positive rate compared to CXR screening. The ITALUNG and NELSON trials demonstrated the early detection capabilities of LDCT for lung cancers compared to usual care without surveillance imaging. False-positive findings with unnecessary workup, intervention, and radiation exposure remain significant concerns for routine LDCT screening. However, current data suggests LDCT may provide a highly sensitive and specific means for detecting lung cancers and reducing mortality. PMID:27375974

  19. Experiences of low dose exposure mammography on the cancer mass screening of breast

    International Nuclear Information System (INIS)

    This paper summarizes experiences in the use of the mammograph for the mass screening of breast cancer. The exposure dose per experience was only 1/8.4 (0.21 mSv) that of conventional mammography. Application to 243 persons resulted in 95.6% (43/45 patients) of TPR, 57.1% (113/198 patients) of TNR and 1.7% (2/115 patients) of false negative. Although the authors consider that the mammograph has a bright future, a few points for improvement follow herein. To increase the accuracy of mass screening of breast cancer, photography techniques and decipherment of X-rays should be considered. (author)

  20. Lung cancer induced in hamsters by low doses of alpha radiation from 210Po

    International Nuclear Information System (INIS)

    Lung cancers have been induced in 9 to 53 percent of hamsters given multiple intratracheal instillations of polonium-210 in amounts yielding lifetime exposures of 15 to 300 rads to the lungs. Cigarette smokers have previously been estimated to receive 20 rads to areas of the bronchial epithelium from deposited polonium-210. This finding thus supports the hypothesis that alpha radiation resulting from the polonium-210 or lead-210 present in cigarette smoke may be a significant causative factor in human lung cancer. (U.S.)

  1. A cell based analysis on p53 response to low dose rate γ-ray irradiation in murine cells

    International Nuclear Information System (INIS)

    A derivative of murine immortal NIH/PG13Luc cells stably transfected with p53-dependent luciferase reporter plasmid was used to detect transcriptional activity of p53 in response to radiation. Microarray analysis revealed up-regulation of six p53-mediated genes (CDKN1A/p21, MDM2, SIP27, CCNG1/cyclin G1, EI24/PIG8 and Dinb/POLK) by exposure of cells to low dose rates (LDR) 60Co γ-ray for 72 h. Using real-time PCR, a significant elevation in expression of CCNG1/cyclinG1, MDM2 and CDKN1A/p21 was observed at dose rates of over 50 mGy/h. Dose rate dependency of these three p53-mediated genes was also observed. Expression of CCNG1/cyclinG1 at high dose rates (HDR) γ-rays was higher than that for LDR. However, expression of MDM2 for LDR γ-rays was higher than that for HDR. Cells irradiated at LDRs (1 mGy/h and 10 mGy/h) of γ-rays showed G1 phase arrest. Furthermore, G2 growth arrest was observed in cells irradiated at 50 mGy/h and 100 mGy/h, being correlated with p53-mediated CCNG1/cyclinG1 up-regulation. These results implicate that cellular response to radiation differs between the two LDRs of γ-rays used: (i) dose rates of 1-10mGy/h and (ii) dose rates over 50 mGy/h. (author)

  2. Hepatic intra-arterial chemotherapy (HIAC) of high dose mitomycin and epirubicin combined with caval chemofiltration versus prolonged low doses in liver metastases from colorectal cancer: a prospective randomized clinical study.

    Science.gov (United States)

    Fiorentini, G; Poddie, D B; Cantore, M; Rossi, S; Tumolo, S; Dentico, P; Bernardeschi, P; Guadagni, S; Rossi, G; Valori, V M; De Simone, M

    2004-11-01

    A multicenter randomized study comparing high dose of mitomycin and epirubicin given as hepatic intra-arterial chemotherapy (HIAC) combined with caval chemofiltration (CF) versus low doses of the same drugs in unresectable liver metastases from colorectal cancer showed a significant improvement in the survival rate of the 20 patients treated with high dose compared to the 22 patients treated with low doses with a 1 year survival of 69% vs 39%. The median survival was 17 vs 11 months and the responses were 65% vs 33%. Toxicity was colangitis in 50% of patients considered. The extrahepatic progression was similar in the two groups (7/20 vs 8/22). PMID:15675479

  3. Effects of low doses

    International Nuclear Information System (INIS)

    Actually, even though it is comfortable for the risk management, the hypothesis of the dose-effect relationship linearity is not confirmed for any model. In particular, in the area of low dose rate delivered by low let emitters. this hypothesis is debated at the light of recent observations, notably these ones relative to the mechanisms leading to genetic instability and induction eventuality of DNA repair. The problem of strong let emitters is still to solve. (N.C.)

  4. Case of ileal perforation during low dose irradiation for pelvic recurrence of rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hosokawa, Tetsuya; Kobatake, Toshio; Isomoto, Hiroharu; Shirouzu, Kazuo; Kakegawa, Teruo

    1989-01-01

    A 42-year-old man was evaluated for perineal pain. Computed tomography of the pelvis revealed recurrence of rectal cancer, which was impossible to treat sugically. Though irradiation therapy was started. As it had to be discontinued because of the appearance of inflammation in the perineal region and lower abdominal pain after 800 rad. Small intestinal gastrography revealed a perforation of the ileum, and intestinal resection was performed. Pathological studies showed cancer invasion, bleeding and edema due to acute radiation damage. The radiosensitive nature of the small intestine in this case led to a fatal outcome. Effective therapeutic and examination methods have not yes been established for cases such as this one. It is concluded that lowdose radiation may induce severe intestinal complications. (author).

  5. A case of ileal perforation during low dose irradiation for pelvic recurrence of rectal cancer

    International Nuclear Information System (INIS)

    A 42-year-old man was evaluated for perineal pain. Computed tomography of the pelvis revealed recurrence of rectal cancer, which was impossible to treat sugically. Though irradiation therapy was started. As it had to be discontinued because of the appearance of inflammation in the perineal region and lower abdominal pain after 800 rad. Small intestinal gastrography revealed a perforation of the ileum, and intestinal resection was performed. Pathological studies showed cancer invasion, bleeding and edema due to acute radiation damage. The radiosensitive nature of the small intestine in this case led to a fatal outcome. Effective therapeutic and examination methods have not yes been established for cases such as this one. It is concluded that lowdose radiation may induce severe intestinal complications. (author)

  6. The risk of childhood cancer from low doses of ionizing radiation received in utero

    International Nuclear Information System (INIS)

    Radiological protection is based upon the assumption that any additional exposure to ionising radiation leads to an increased risk of stochastic adverse health effects. The validity of this assumption is supported by the epidemiological association between childhood cancer and X-ray exposure of the fetus in utero for diagnostic purposes. Evidence for a direct causal interpretation of this association is compelling: the association has high statistical significance, it is consistent across many case-control studies carried out worldwide, and an appropriate dose-response relationship is indicated. Evidence against bias and confounding as alternative explanations is strong. Nonetheless, objections to causality have been raised. Four grounds for controversy are examined in detail, with the conclusion that they do not provide persuasive evidence against a cause and effect relationship. We conclude that acute doses of the order of 10 mGy received by the fetus in utero cause a subsequent increase in the risk of cancer in childhood, and that, in these circumstances, the excess absolute risk coefficient for childhood cancer incidence is 6-12% per Gy. (author)

  7. Radiation-related cancer risks at low doses among atomic bomb survivors.

    Science.gov (United States)

    Pierce, D A; Preston, D L

    2000-08-01

    To clarify the information in the Radiation Effects Research Foundation data regarding cancer risks of low radiation doses, we focus on survivors with doses less than 0.5 Sv. For reasons indicated, we also restrict attention mainly to survivors within 3, 000 m of the hypocenter of the bombs. Analysis is of solid cancer incidence from 1958-1994, involving 7,000 cancer cases among 50,000 survivors in that dose and distance range. The results provide useful risk estimates for doses as low as 0.05-0.1 Sv, which are not overestimated by linear risk estimates computed from the wider dose ranges 0-2 Sv or 0-4 Sv. There is a statistically significant risk in the range 0-0.1 Sv, and an upper confidence limit on any possible threshold is computed as 0.06 Sv. It is indicated that modification of the neutron dose estimates currently under consideration would not markedly change the conclusions. PMID:10931690

  8. Possible use of EPDM in radioactive waste disposal: Long term low dose rate and short term high dose rate irradiation in aquatic and atmospheric environment

    International Nuclear Information System (INIS)

    In this study, changes in the properties of ethylene propylene diene terpolymer (EPDM) irradiated with different dose rates in ambient atmosphere and aqueous environment were investigated. Irradiations were carried out both with low dose and high dose rate irradiation sources. EPDM samples which were differentiated from each other by peroxide type and 5-ethylidene 2-norbornene (ENB) contents were used. Long term low dose rate irradiations were carried out for the duration of up to 2.5 years (total dose of 1178 kGy) in two different irradiation environments. Dose rates (both high and low), irradiation environments (in aquatic and open to atmosphere), and peroxide types (aliphatic or aromatic) were the parameters studied. Characterization of irradiated EPDM samples were performed by hardness, compression, tensile, dynamic mechanical analysis (DMA), TGA–FTIR, ATR-FTIR, XRD and SEM tests. It was observed that the irradiation in water environment led to a lower degree of degradation when compared to that of irradiation open to atmosphere for the same irradiation dose. In addition, irradiation environment, peroxide type and dose rate had effects on the extent of change in the properties of EPDM. It was observed that EPDM is relatively radiation resistant and a candidate polymer for usage in radioactive waste management. - Highlights: ► Possible use of EPDM in radioactive waste management was studied. ► The low dose rate irradiations were carried out for duration of up to 2.5 years. ► Characterizations of irradiated samples were performed. ► EPDM could possibly be a candidate material to be used in the radioactive waste management.

  9. Effect of low-intensity low-dose rate irradiation on the incidence and the development of spontaneous leukosis in AKR mice

    International Nuclear Information System (INIS)

    Development of spontaneous leukosis in AKR mice is accelerated by irradiation with low doses of 1.2-2.4 cGy and low dose rate 0.06 cGy/day. The leukoses incidence rate increases. Deaths of the animals from leukosis occurs earlier, shortening the average and maximum life-spans of the animals. The dynamics of changes in the mass of organs of the immune systems (thymus and spleen) shows extrema. The moment of reaching the extremum correlates with the maximum rate of animals' deaths

  10. Erectile dysfunction following treatment with low-dose brachytherapy for prostate cancer

    International Nuclear Information System (INIS)

    Of 260 prostate cancer patients, 26% had potency before brachytherapy when defined as an sexual health inventory for men (SHIM) score of ≥12. Three years after brachytherapy, 44% patients had preserved erectile function (EF-pts) and 56% were erectile dysfunction (ED-pts). Between ED-pts and EF-pts, we compared the doses delivered to the penile bulb or neurovascular bundle using a dose-volume histogram obtained from brachytherapy postplan and patients' characteristics. The mean age and prostate volume of ED-pts were significantly higher than those of EF-pts. No difference was observed in the respective doses between the 2 groups.(author)

  11. Longitudinal follow-up study of smoking-induced emphysema progression in low-dose CT screening of lung cancer

    Science.gov (United States)

    Suzuki, H.; Matsuhiro, M.; Kawata, Y.; Niki, N.; Nakano, Y.; Ohmatsu, H.; Kusumoto, M.; Tsuchida, T.; Eguchi, K.; Kaneko, Masahiro; Moriyama, N.

    2014-03-01

    Chronic obstructive pulmonary disease is a major public health problem that is predicted to be third leading cause of death in 2030. Although spirometry is traditionally used to quantify emphysema progression, it is difficult to detect the loss of pulmonary function by emphysema in early stage, and to assess the susceptibility to smoking. This study presents quantification method of smoking-induced emphysema progression based on annual changes of low attenuation volume (LAV) by each lung lobe acquired from low-dose CT images in lung cancer screening. The method consists of three steps. First, lung lobes are segmented using extracted interlobar fissures by enhancement filter based on fourdimensional curvature. Second, LAV of each lung lobe is segmented. Finally, smoking-induced emphysema progression is assessed by statistical analysis of the annual changes represented by linear regression of LAV percentage in each lung lobe. This method was applied to 140 participants in lung cancer CT screening for six years. The results showed that LAV progressions of nonsmokers, past smokers, and current smokers are different in terms of pack-year and smoking cessation duration. This study demonstrates effectiveness in diagnosis and prognosis of early emphysema in lung cancer CT screening.

  12. Lung Cancer Screening With Low-Dose CT: Implementation Amid Changing Public Policy at One Health Care System.

    Science.gov (United States)

    Begnaud, Abbie; Hall, Thomas; Allen, Tadashi

    2016-01-01

    Screening for lung cancer with low-dose CT has evolved rapidly in recent years since the National Lung Screening Trial (NLST) results. Subsequent professional and governmental organization guidelines have shaped policy and reimbursement for the service. Increasingly available guidance describes eligible patients and components necessary for a high-quality lung cancer screening program; however, practical instruction and implementation experience is not widely reported. We launched a lung cancer screening program in the face of reimbursement and guideline uncertainties at a large academic health center. We report our experience with implementation, including challenges and proposed solutions. Initially, we saw less referrals than expected for screening, and many patients referred for screening did not clearly meet eligibility guidelines. We educated primary care providers and implemented system tools to encourage referral of eligible patients. Moreover, in response to the Centers for Medicare & Medicaid Services (CMS) final coverage determination, we report our programmatic adaptation to meet these requirements. In addition to the components common to all quality programs, individual health delivery systems will face unique barriers related to patient population, available resources, and referral patterns. PMID:27249755

  13. Concurrent pelvic radiation with weekly low-dose cisplatin and gemcitabine as primary treatment of locally advanced cervical cancer: A phase II study

    Directory of Open Access Journals (Sweden)

    Hend EL-Hadaad

    2015-09-01

    Full Text Available Purpose: This study was done to evaluate response, compliance and survival of weekly low dose cisplatin (20 mg/m2 and gemcitabine (125 mg/m2 concurrently with pelvic radiation as primary treatment of stage IIB-IIIB cervical cancer.Methods: External radiation consisted of 50 Gy/25 fractions using 6-10 MV photon followed by 600 cGy boost to parametrium if it was still felt thickened. Then, intracavitary radiotherapy to deliver 60 Gy at point A. Chemotherapy consisted of gemcitabine at a dose of 125 mg/ m2 was given by i.v infusion over 30 minutes immediately after cisplatin 20 mg/ m2 weekly for 5 weeks during EBRT. Forty–five eligible patients received the treatment protocol. Results: Toxicity was tolerable and manageable. No grade 4 toxicity while grade 3 was recorded in hematologic one only. In order of frequency; diarrhea, nausea and vomiting, and anemia (50%, 40%, 35.5% were most common adverse events. Overall clinical response rate was 93.4% with pathological complete response of 62.2%. After median follow-up of 20 months, 2-year survival and progression-free survival rates were 90.5% and 81% respectively. Conclusion: Weekly combination of low- dose cisplatin and gemcitabine given concurrently with pelvic radiotherapy in primary treatment of locally advanced cervical cancer resulted in a high response rate with a good compliance. Further exploration is needed for the use of this approach prior to incorporating it into routine clinical care through phase III clinical trial.

  14. Health benefits from low-dose irradiation

    International Nuclear Information System (INIS)

    Whole-body exposures of mice and humans show no harm from low doses of ionizing radiation. Forty reports show statistically significant, p < 0.01, beneficial effects when cancer and total mortality rates were examined in mice. In vitro experiments indicate that radiogenic metabolism, adaptive repair mechanisms, such as DNA repair enzymes, and the essential nature of ionizing radiation are responsible for part of this activity. However, overwhelming evidence shows that low-dose irradiation increases immune competence. Such data negate the linear concept, which has no reliable whole-animal data to support it in the low-dose range. Cell culture data are not pertinent; such cells do not have a complete immune system

  15. Concurrent chemoradiotherapy using protracted infusion of low-dose CDDP and 5-FU and radiotherapy for esophageal cancer

    International Nuclear Information System (INIS)

    We evaluated the effects and safety of concurrent chemoradiotherapy for patients with esophageal cancer. Between March 1994 and April 1998, concurrent chemoradiotherapy using protracted infusion of low-dose cisplatin (CDDP: 3-6 mg/m2/24 h), 5-fluorouracil (5-FU: 200 mg/m2/24 h) and radiotherapy was given to 26 patients. The median age was 70 yr, with a range from 58 to 86 yr. With regard to TNM classification (1987), 6 patients were stage II, 5 stage III, and 15 stage IV. Radiotherapy was performed by external irradiation alone in 23 patients and external irradiation plus brachytherapy in three patients. One patient underwent surgery after a dose of 40 Gy owing to the possibility of idiopathic bleeding from the stomach. Locally, primary effects resulted in complete response in 11 patients (42.3%) and partial response in 15 (57.7%). Acute toxicity was primarily hematologic. Leukopenia and thrombocytopenia of grade 3 of 4 occurred in eight (30.7%) and six (23.0%) of 26 patients, respectively. In patients administered CDDP at more than 5 mg/m2/day, hemotoxicity was severe because in five of the 10 patients administered 5 mg/m2 CDDP and one of the 2 patients administered 6 mg/m2 CDDP, thrombocytopenia of grade 3 or 4 occurred. Protracted infusion of low-dose CDDP and 5-FU with concomitant radiation therapy is effective, but from the point of acute toxicity, the optimal dose of CDDP and 5-FU needs further investigation. (author)

  16. Low-dose natural prostaglandin F2α (dinoprost) at timed insemination improves conception rate in dairy cattle.

    Science.gov (United States)

    Ambrose, Divakar J; Gobikrushanth, Mohanathas; Zuidhof, Sjoert; Kastelic, John P

    2015-03-01

    The primary objective was to determine if low doses of PGF2α (dinoprost) given intramuscularly (im) concurrent with timed artificial insemination (TAI) would improve conception rates in dairy cattle. A secondary objective was to determine if body condition score (BCS) and parity would influence conception rates, either independently or in interaction with PGF2α treatment. In experiment I, 307 lactating Holstein cows were randomly assigned to receive either 5-mg PGF2α im (PGF2α treated, n = 154) or 0-mg PGF2α (control, n = 153) at TAI (Day 0). Blood samples were obtained on Days -10, -3, 0, and 7 to determine plasma progesterone (P4) concentrations. Pregnancy was confirmed 30 to 32 days after insemination by transrectal ultrasonography. In experiment II, 451 cows were randomly assigned to receive either 10-mg PGF2α im (PGF2α treated, n = 226) or 0-mg PGF2α (control, n = 225) at TAI, and pregnancy was confirmed 45 to 50 days after TAI by palpation per rectum. Pregnancy data were analyzed by CATMOD (SAS). In experiment I, PGF2α treatment, BCS, and parity did not affect conception rate (35.7% vs. 37.0% for PGF2α treated vs. control; P > 0.05). However, in experiment II, conception rates were higher in cows given 10-mg PGF2α than those in control cows (45.8% vs. 36.0%; P < 0.05), in cows with high BCS than in cows with low BCS (52.1% vs. 30.4%; P < 0.01), and in primiparous than in multiparous cows (47.6% vs. 34.4%; P < 0.01), but their interaction with PGF2α treatment did not affect conception rates. In summary, 5 mg of PGF2α given im concurrent with TAI failed to enhance conception rate in lactating dairy cows, whereas 10 mg of PGF2α significantly increased conception rate. PMID:25434776

  17. Low-dose CT screening in an Asian population with diverse risk for lung cancer: A retrospective cohort study

    Energy Technology Data Exchange (ETDEWEB)

    Yi, Chin A. [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Seoul (Korea, Republic of); Lee, Kyung Soo [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Seoul (Korea, Republic of); Sungkyunkwan University School of Medicine, Department of Radiology, Samsung Medical Center, Seoul (Korea, Republic of); Shin, Myung-Hee; Cho, Yun Yung [Sungkyunkwan University School of Medicine, Department of Social and Preventive Medicine, Seoul (Korea, Republic of); Choi, Yoon-Ho [Sungkyunkwan University School of Medicine, Center for Health Promotion, Seoul (Korea, Republic of); Kwon, O. Jung [Sungkyunkwan University School of Medicine, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Seoul (Korea, Republic of); Shin, Kyung Eun [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Seoul (Korea, Republic of); Kyung Hee University Hospital, Department of Diagnostic Radiology, Seoul (Korea, Republic of)

    2015-08-15

    To evaluate the performance of low-dose CT (LDCT) screening for lung cancer (LCA) detection in an Asian population with diverse risks for LCA. LCA screening was performed in 12,427 symptomless Asian subjects using either LDCT (5,771) or chest radiography (CXR) (6,656) in a non-trial setting. Subjects were divided into high-risk and non-high-risk groups. Data were collected on the number of patients with screening-detected LCAs and their survival in order to compare outcomes between LDCT and CXR screening with the stratification of risks considering age, sex and smoking status. In the non-high-risk group, a significant difference was observed for the detection of lung cancer (adjusted OR, 5.07; 95 % CI, 2.72-9.45) and survival (adjusted HR of LCA survival between LDCT vs. CXR group, 0.08; 95 % CI, 0.01-0.62). No difference in detection or survival of LCA was noticed in the high-risk group. LCAs in the non-high-risk group were predominantly adenocarcinomas (96 %), and more likely to be part-solid or non-solid compared with those in the high-risk group (p = 0.023). In the non-high-risk group, LDCT helps detect more LCAs and offers better survival than CXR screening, due to better detection of part solid or non-solid lung adenocarcinomas. (orig.)

  18. Osteoporosis markers on low-dose lung cancer screening chest computed tomography scans predict all-cause mortality

    Energy Technology Data Exchange (ETDEWEB)

    Buckens, C.F. [University Medical Center Utrecht, Radiology Department, Utrecht (Netherlands); University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Utrecht (Netherlands); Graaf, Y. van der [University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Utrecht (Netherlands); Verkooijen, H.M.; Mali, W.P.; Jong, P.A. de [University Medical Center Utrecht, Radiology Department, Utrecht (Netherlands); Isgum, I.; Mol, C.P. [University Medical Center Utrecht, Image Sciences Institute, Utrecht (Netherlands); Verhaar, H.J. [University Medical Center Utrecht, Department of Geriatric Medicine, Utrecht (Netherlands); Vliegenthart, R.; Oudkerk, M. [Medical Center Groningen, Department of Radiology, Utrecht (Netherlands); Aalst, C.M. van; Koning, H.J. de [Erasmus MC Rotterdam, Department of Public Health, Rotterdam (Netherlands)

    2015-01-15

    Further survival benefits may be gained from low-dose chest computed tomography (CT) by assessing vertebral fractures and bone density. We sought to assess the association between CT-measured vertebral fractures and bone density with all-cause mortality in lung cancer screening participants. Following a case-cohort design, lung cancer screening trial participants (N = 3,673) who died (N = 196) during a median follow-up of 6 years (inter-quartile range: 5.7-6.3) were identified and added to a random sample of N = 383 from the trial. We assessed vertebral fractures using Genant and acute;s semiquantative method on sagittal reconstructions and measured bone density (Hounsfield Units (HU)) in vertebrae. Cox proportional hazards modelling was used to determine if vertebral fractures or bone density were independently predictive of mortality. The prevalence of vertebral fractures was 35 % (95 % confidence interval 30-40 %) among survivors and 51 % (44-58 %) amongst cases. After adjusting for age, gender, smoking status, pack years smoked, coronary and aortic calcium volume and pulmonary emphysema, the adjusted hazard ratio (HR) for vertebral fracture was 2.04 (1.43-2.92). For each 10 HU decline in trabecular bone density, the adjusted HR was 1.08 (1.02-1.15). Vertebral fractures and bone density are independently associated with all-cause mortality. (orig.)

  19. Low-dose CT screening in an Asian population with diverse risk for lung cancer: A retrospective cohort study

    International Nuclear Information System (INIS)

    To evaluate the performance of low-dose CT (LDCT) screening for lung cancer (LCA) detection in an Asian population with diverse risks for LCA. LCA screening was performed in 12,427 symptomless Asian subjects using either LDCT (5,771) or chest radiography (CXR) (6,656) in a non-trial setting. Subjects were divided into high-risk and non-high-risk groups. Data were collected on the number of patients with screening-detected LCAs and their survival in order to compare outcomes between LDCT and CXR screening with the stratification of risks considering age, sex and smoking status. In the non-high-risk group, a significant difference was observed for the detection of lung cancer (adjusted OR, 5.07; 95 % CI, 2.72-9.45) and survival (adjusted HR of LCA survival between LDCT vs. CXR group, 0.08; 95 % CI, 0.01-0.62). No difference in detection or survival of LCA was noticed in the high-risk group. LCAs in the non-high-risk group were predominantly adenocarcinomas (96 %), and more likely to be part-solid or non-solid compared with those in the high-risk group (p = 0.023). In the non-high-risk group, LDCT helps detect more LCAs and offers better survival than CXR screening, due to better detection of part solid or non-solid lung adenocarcinomas. (orig.)

  20. Involvement of immune system in enhanced tumor rejection in mice by chronic low dose-rate irradiation

    International Nuclear Information System (INIS)

    In the previous study, I found that low dose-rate radiation, under certain irradiation conditions, enhanced the rejective response against tumor cells in irradiated C57BL/6N mice. To elucidate the involvement of immune system, I studied the rejective response against taking tumor cells in C57BL/6 mice and scid mice. The C57BL/6N mice have normal immune system, but the scid mice lack a functional immune system. The rejective response was analyzed by applying methods of TD50 assay. TD50 is the abbreviation for tumor dose 50 and indicates the number of cells required for successful transplantation to 50% of injected sites in the recipient animals. I transplanted the tumor cells prepared from a Methylcholanthrene-induced tumor (fibrosarcoma) in mice. The increase in the TD50 value suggests an enhancement of the rejective response against taking tumor cells. The TD50 in non-irradiated scid mice was smaller than that of non-irradiated C57BL/6N mice and the values were 7.6 x 102 and 1.01 x 104, respectively. Furthermore, the TD50 value in C57BL/6N mice irradiated with 250 mGy increased to 3.5 x 104. On the other hand, that in scid mice irradiated with the same total dose remained at low level and did riot change. These results suggest that the increase in TD50 value in mice by irradiation with 250 mGy needs normal immune system. The immune system is stimulated by transplantated tumor cells and induced the enhancement of the rejective response against taking tumor cells. (author)

  1. Dose response relationship for unstable-type chromosome aberration rate of spleen cells from mice continuously exposed to low-dose-rate gamma-rays

    International Nuclear Information System (INIS)

    It has been reported that people who are chronically exposed to radiation such as nuclear facility workers and medical radiologists have slightly higher incidences of chromosome aberrations than non-exposed people. However, chronological changes of chromosome aberration rates related to accumulated doses and dose-rates for low dose-rate radiation exposures have not been well studied. Precise analyses of human populations are quite limited because confounding factors influence the results. For this reason, animal experiments are important for analyses. Mice were continuously exposed to gamma-rays at 400 mGy/22 hr/day for 10 days, 20 mGy/22 hr/day for about 400 days, and 1 mGy/22 hr/day for about 615 days under SPF conditions. Chronological changes of unstable-type chromosome aberration rates of spleen cells were observed along with accumulated doses at the middle dose rate and the two low-dose rates by conventional Giemsa-staining method. Aberrations such as dicentric chromosome, ring chromosome and fragment increased in a two-phase manner within 0-1.2 Gy and 2-8 Gy at 20 mGy/22 hr/day. They slightly increased up to 0.5 Gy at 1 mGy/22 hr/day. Aberration rates for 1, 2, 8 Gy at the 20 mGy/22 hr/day and for 0.5 Gy at 1 mGy/22 hr/day were 5.1, 9.6, 13.9 and 2.2 times higher than those of age-matched, non-irradiated control mice, respectively. Chromosome aberration rates at 400 mGy/22 hr/day were 2.7 times higher than that of 20 mGy/22 hr/day for the same total dose of 1.2 Gy. The results that unstable-type chromosome aberrations increased with accumulated dose of the low-dose rate radiation will be important to establish biological dosimetry for people who are chronically exposed to radiation. (author)

  2. Study of the radiation levels in low dose rate brachytherapy zones of the National Institute of Neoplastic Illnesses

    International Nuclear Information System (INIS)

    The present study has as objective to evaluate the radiation levels of the Brachytherapy work areas of low dose rate (Gammateque, nurses station and of hospitalization rooms of patients RIC of 4th, 5th Floor-East) and to estimate the effective dose of the occupationally exposed personnel and the public in general. The measurements of the dose rate in these areas, were registered with a radiations monitor Inspector trademark, during a period of 60 days, without altering the routinary work conditions. The more high levels of environmental dose equivalent rate registered in the different work areas its are of 1.41 and 47.78 μSv/h rooms 1 and 2 in the Gammateque environments, in the hospitalization rooms of the 4th and 5th floor in the point 1 are of 40.77 and 23.67, μSv/h respectively and in the point 2 are of 129.19 and 39.93, μSv/h respectively, and in the nurses station of the 4th and 5th floor its are respectively of 7.62 u Sv/h and 0.45 u Sv/h. According to the carried out measurements and the permanency in the work place is possible to estimate the effective dose involved to the occupationally exposed personnel. The personnel that works in Gammateque could be receiving respectively as maximum dose 0.61 mSv/month, and the personnel that works in the nurses station of 13.17 and 0.78 mSv/year in the 4th and 5th floor. These registered differences among the two floors are due to that the 5th floor counts with the shielding systems (screen) contrary to the 4th, another of the factors is the distribution form of the patient beds RIC. We should have present that the radiation levels although in some cases it is very high, however, they are below of the permissible limits according to standards, but it is still possible to reduce even more, the radiation levels in the critical points fulfilling with the ALARA principle. (Author)

  3. Accelerated Partial Breast Irradiation With Low-Dose-Rate Interstitial Implant Brachytherapy After Wide Local Excision: 12-Year Outcomes From a Prospective Trial

    International Nuclear Information System (INIS)

    Purpose: To evaluate the long-term toxicity, cosmesis, and local control of accelerated partial breast irradiation with implant brachytherapy after wide local excision for Stage T1N0 breast cancer (BCa). Materials and Methods: Between 1997 and 2001, 50 patients with Stage T1N0M0 BCa were treated in a Phase I-II protocol using low-dose-rate accelerated partial breast irradiation with implant brachytherapy after wide local excision and lymph node surgery. The total dose was escalated in three groups: 50 Gy (n = 20), 55 Gy (n = 17), and 60 Gy (n = 13). Patient- and physician-assessed breast cosmesis, patient satisfaction, toxicity, mammographic abnormalities, repeat biopsies, and disease status were prospectively evaluated at each visit. Kendall’s tau (τβ) and logistic regression analyses were used to correlate outcomes with dose, implant volume, patient age, and systemic therapy. Results: The median follow-up period was 11.2 years (range, 4–14). The patient satisfaction rate was 67%, 67% reported good-excellent cosmesis, and 54% had moderate-severe fibrosis. Higher dose was correlated with worse cosmetic outcome (τβ 0.6, p β 0.5, p β 0.4, p = .0024). Of the 50 patients, 35% had fat necrosis and 34% developed telangiectasias ≥1 cm2. Grade 3–4 late skin and subcutaneous toxicities were seen in 4 patients (9%) and 6 patients (13%), respectively, and both correlated with higher dose (τβ 0.3–0.5, p ≤ .01). One patient had Grade 4 skin ulceration and fat necrosis requiring surgery. Mammographic abnormalities were seen in 32% of the patients, and 30% underwent repeat biopsy, of which 73% were benign. Six patients had ipsilateral breast recurrence: five elsewhere in the breast, and one at the implant site. One patient died of metastatic BCa after recurrence. The 12-year actuarial local control, recurrence-free survival, and overall survival rate was 85% (95% confidence interval, 70–97%), 72% (95% confidence interval, 54–86%), and 87% (95% confidence

  4. Accelerated Partial Breast Irradiation With Low-Dose-Rate Interstitial Implant Brachytherapy After Wide Local Excision: 12-Year Outcomes From a Prospective Trial

    Energy Technology Data Exchange (ETDEWEB)

    Hattangadi, Jona A. [Harvard Radiation Oncology Program, Boston, MA (United States); Powell, Simon N. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); MacDonald, Shannon M.; Mauceri, Thomas; Ancukiewicz, Marek [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); Freer, Phoebe [Department of Radiology, Massachusetts General Hospital, Boston, MA (United States); Lawenda, Brian [21st Century Oncology, Las Vegas, NV (United States); Alm El-Din, Mohamed A. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Department of Clinical Oncology, Tanta University Hospital, Tanta (Egypt); Gadd, Michele A.; Smith, Barbara L. [Department of Surgical Oncology, Massachusetts General Hospital, Boston, MA (United States); Taghian, Alphonse G., E-mail: ataghian@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States)

    2012-07-01

    Purpose: To evaluate the long-term toxicity, cosmesis, and local control of accelerated partial breast irradiation with implant brachytherapy after wide local excision for Stage T1N0 breast cancer (BCa). Materials and Methods: Between 1997 and 2001, 50 patients with Stage T1N0M0 BCa were treated in a Phase I-II protocol using low-dose-rate accelerated partial breast irradiation with implant brachytherapy after wide local excision and lymph node surgery. The total dose was escalated in three groups: 50 Gy (n = 20), 55 Gy (n = 17), and 60 Gy (n = 13). Patient- and physician-assessed breast cosmesis, patient satisfaction, toxicity, mammographic abnormalities, repeat biopsies, and disease status were prospectively evaluated at each visit. Kendall's tau ({tau}{sub {beta}}) and logistic regression analyses were used to correlate outcomes with dose, implant volume, patient age, and systemic therapy. Results: The median follow-up period was 11.2 years (range, 4-14). The patient satisfaction rate was 67%, 67% reported good-excellent cosmesis, and 54% had moderate-severe fibrosis. Higher dose was correlated with worse cosmetic outcome ({tau}{sub {beta}} 0.6, p < .0001), lower patient satisfaction ({tau}{sub {beta}} 0.5, p < .001), and worse fibrosis ({tau}{sub {beta}} 0.4, p = .0024). Of the 50 patients, 35% had fat necrosis and 34% developed telangiectasias {>=}1 cm{sup 2}. Grade 3-4 late skin and subcutaneous toxicities were seen in 4 patients (9%) and 6 patients (13%), respectively, and both correlated with higher dose ({tau}{sub {beta}} 0.3-0.5, p {<=} .01). One patient had Grade 4 skin ulceration and fat necrosis requiring surgery. Mammographic abnormalities were seen in 32% of the patients, and 30% underwent repeat biopsy, of which 73% were benign. Six patients had ipsilateral breast recurrence: five elsewhere in the breast, and one at the implant site. One patient died of metastatic BCa after recurrence. The 12-year actuarial local control, recurrence

  5. Smoking cessation interventions within the context of Low-Dose Computed Tomography lung cancer screening: A systematic review.

    Science.gov (United States)

    Piñeiro, Bárbara; Simmons, Vani N; Palmer, Amanda M; Correa, John B; Brandon, Thomas H

    2016-08-01

    The integration of smoking cessation interventions (SCIs) within the context of lung cancer screening programs is strongly recommended by screening guidelines, and is a requirement for Medicare coverage of screening in the US. In Europe, there are no lung cancer screening guidelines, however, research trials are ongoing, and prominent professional societies have begun to recommend lung cancer screening. Little is known about the types and efficacy of SCIs among patients receiving low-dose computed tomography (LDCT) screening. This review addresses this gap. Based on a systematic search, we identified six empirical studies published prior to July 1, 2015, that met inclusion criteria for our review: English language, SCI for LDCT patients, and reported smoking-related outcomes. Three randomized studies and three single-arm studies were identified. Two randomized controlled trials (RCTs) evaluated self-help SCIs, whereas one pilot RCT evaluated the timing (before or after the LDCT scan) of a combined (counseling and pharmacotherapy) SCI. Among the single-arm trials, two observational studies evaluated the efficacy of combined SCI, and one retrospectively assessed the efficacy of clinician-delivered smoking assessment, advice, and assistance. Given the limited research to date, and particularly the lack of studies reporting results from RCTs, assumptions that SCIs would be effective among this population should be made with caution. Findings from this review suggest that participation in a lung screening trial promotes smoking cessation and may represent a teachable moment to quit smoking. Findings also suggest that providers can take advantage of this potentially teachable moment, and that SCIs have been successfully implemented in screening settings. Continued systematic and methodologically sound research in this area will help improve the knowledge base and implementation of interventions for this population of smokers at risk for chronic disease. PMID:27393513

  6. A comparative study of low dose weekly paclitaxel versus cisplatin with concurrent radiation in the treatment of locally advanced head and neck cancers

    Directory of Open Access Journals (Sweden)

    R K Jain

    2009-01-01

    Full Text Available Purpose: The purpose of this study was to compare low dose weekly paclitaxel versus cisplatin with concurrent radiation in locally advanced head and neck cancers. Materials and Methods: From August 2005 to July 2006, a total of 100 biopsy proven, locally advanced head and neck cancers were enrolled for the study. All the patients were stratified in two groups, study group A and control group B. Study group patients received injection Paclitaxel 20 mg/m 2 , I/V 1 hr infusion weekly for 6 weeks and control group patients received injection Cisplatin 30 mg/m 2 , I/V 2 hrs infusion weekly for 6 weeks. All patients received 66-70 Gy concurrent radiation at the rate of 2 Gy/day, 5 #/week, in 6-7 weeks by cobalt theratron phoenix - 80 teletherapy units. Result: Complete response achieved in 73% of patients in study group and 64% of patients in control group. There was no statistically significant difference observed between the study group and the control group (χ2 = 1.167, df = 1, level of significance 0.05. On 3-10 months of follow-up 59% of patients in the study group and 42% of patients in the control group are alive and disease free. Local toxicities including mucositis, dysphasia and skin reactions were more in the study group but tolerable. Conclusion: Efficacy of paclitaxel in low dose weekly schedule is comparable to cisplatin in locally advanced head and neck squamous cell carcinoma. Further analysis and follow-up are needed to evaluate if this benefit will translate into prolonged survival.

  7. Long-term results of low dose daily cisplatin chemotherapy used concurrently with modestly accelerated radiotherapy in locally advanced squamous cell carcinomas of the head neck cancer region

    Directory of Open Access Journals (Sweden)

    Pramod Kumar Gupta

    2014-01-01

    Full Text Available Introduction: Concurrent single agent cisplatin (CDDP with radiotherapy (RT improves outcomes in locally advanced squamous cell carcinomas of the head neck (LA-SCCHN. CDDP at 100 mg/m 2 at 3 weekly intervals raise compliance, hospitalization, and supportive care issues. Low dose daily CDDP was delivered with RT to evaluate its compliance, long-term safety and efficacy. Patients and Methods: During the period of month between November 2005 and May 2007, 52 patients of stage III/IV LA-SCCHN were given with conventional RT in a phased manner (dose-70 Gy/35 fractions/6 weeks along with daily CDDP (6 mg/m 2 ; capped 10 mg-30 cycles over 6 weeks. No hospitalization or antiemetic cover was planned. Compliance, acute and late toxicity were recorded as per Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer grading system and survival outcomes were evaluated. Results : The median follow-up was 63 months. 43 (83% cases complied with RT schedule and >28 cycles of CDDP was administered in 38 (73% cases. Confluent mucositis was seen in 65%, Grade III/IV dysphagia in 67%; 77% required enteral feed and hospitalization in 15%. There were four treatment related deaths. At 5 years, the loco-regional control was 25% (median-11 months and the overall survival was 31% (median-11 months. The 5 years actuarial rates of late Grade III/IV toxicity was 24%. Late swallowing difficulty/aspiration were seen in 17%; xerostomia-40%; ototoxicity-6%; nephrotoxicity-4%; and no second malignancy. Conclusion: Low dose cisplatin with moderately accelerated RT schedule appears feasible and logistically suitable "out-patient" option without increasing long-term toxicity in LA-SCCHN cancer region.

  8. Characterization of the neutron irradiation system for use in the Low-Dose-Rate Irradiation Facility at Sandia National Laboratories.

    Energy Technology Data Exchange (ETDEWEB)

    Franco, Manuel,

    2014-08-01

    The objective of this work was to characterize the neutron irradiation system consisting of americium-241 beryllium (241AmBe) neutron sources placed in a polyethylene shielding for use at Sandia National Laboratories (SNL) Low Dose Rate Irradiation Facility (LDRIF). With a total activity of 0.3 TBq (9 Ci), the source consisted of three recycled 241AmBe sources of different activities that had been combined into a single source. The source in its polyethylene shielding will be used in neutron irradiation testing of components. The characterization of the source-shielding system was necessary to evaluate the radiation environment for future experiments. Characterization of the source was also necessary because the documentation for the three component sources and their relative alignment within the Special Form Capsule (SFC) was inadequate. The system consisting of the source and shielding was modeled using Monte Carlo N-Particle transport code (MCNP). The model was validated by benchmarking it against measurements using multiple techniques. To characterize the radiation fields over the full spatial geometry of the irradiation system, it was necessary to use a number of instruments of varying sensitivities. First, the computed photon radiography assisted in determining orientation of the component sources. With the capsule properly oriented inside the shielding, the neutron spectra were measured using a variety of techniques. A N-probe Microspec and a neutron Bubble Dosimeter Spectrometer (BDS) set were used to characterize the neutron spectra/field in several locations. In the third technique, neutron foil activation was used to ascertain the neutron spectra. A high purity germanium (HPGe) detector was used to characterize the photon spectrum. The experimentally measured spectra and the MCNP results compared well. Once the MCNP model was validated to an adequate level of confidence, parametric analyses was performed on the model to optimize for potential

  9. Dose-response relationship for induction of reciprocal translocations in spermatogonia of the crab-eating monkey following gamma-irradiation at low dose-rate

    Energy Technology Data Exchange (ETDEWEB)

    Tobari, I.; Matsuda, Y.; Utsugi, T.; Yamagiwa, J.; Kitazume, M.; Okamoto, M.

    1986-05-01

    The frequency of reciprocal translocations induced by gamma-rays at low dose-rate was examined in the stem-spermatogonia of the crab-eating monkey (Macaca fascicularis) estimated and the dose-response relationship was estimated for induction of translocations at low dose-rate. Results a dose-rate of 0.18 x 10-4 By/min results show that the rate per Gy of translocation induction was estimated to be 0.0016/cell. Comparing this with results obtained in spermatogonia following acute irradiation at a dose-rate of 0.25 Gy/min, the dose-rate reduction factor is estimated to be 1/11.

  10. Low dose hyper-radiosensitivity in human lung cancer cell line A549 and its possible mechanisms

    International Nuclear Information System (INIS)

    Objective: To study the low dose hyper-radiosensitivity in human lung cancer cell line A549, and its possible mechanisms. Methods: Exponentially growing A549 cells were irradiated with 60Co γ-rays at doses of 0-2 Gy. Together with flow cytometry for precise cell sorting, cell survival fraction was measured by mean of conventional colony-formation assay. ATM1981 Ser-P protein expression was examined by Western blot. Apoptosis was identified by Hoechst 33258 fluorescent staining, and Annexin V-FITC and propidium iodide staining flow cytometry. Cell cycle distribution was observed by flow cytometry. Results: There was an excessive cell killing per unit dose when the doses were below about 0.3 Gy, and the cells exhibited more resistant response at the doses between 0.3 and 0.5 Gy, the cell survival fraction was decreased as the doses over 0.5 Gy. The expression of ATM1981Ser-P protein was first observed at 0.2 Gy, followed by an increase over 0.2 Gy, and reached the peak at 0.5 Gy (compared with 0.2 Gy group, t=7.96, P0.05). 24 hours after irradiation, part cells presented the characteristic morphological change of apoptosis, and the apoptosis curve was coincident with the dose-survival curve. Compared with the control group, the cell cycle had no change post-irradiation to 0.1 and 0.2 Gy. G2/M phase arrest was manifested at 6 and 12 hours post-irradiation to 0.3, 0.4 and 0.5 Gy (t=2.87, 2.88, 4.92 and 3.70, 3.12, 8.11, P2/M phase was decreased at 24 hours post-irradiation (t=3.87, 4.77, 3.01, P<0.05). Conclusions: A549 cells displays the phenomenon of hyper-radiosensitivity (HRS) /induced radioresistance (IRR). The model of cell death induced by low dose irradiation is mainly apoptosis. The activity of ATM and cell cycle change might play an important role in HRS/IRR. (authors)

  11. Extended continuous infusion low-dose recombinant interleukin-2 in advanced cancer: prolonged immunomodulation without significant toxicity.

    Science.gov (United States)

    Caligiuri, M A; Murray, C; Soiffer, R J; Klumpp, T R; Seiden, M; Cochran, K; Cameron, C; Ish, C; Buchanan, L; Perillo, D

    1991-12-01

    In previous clinical trials, recombinant interleukin-2 (rIL-2) has been infused at high doses over short periods of time to generate lymphokine-activated killer (LAK) cells in vivo. These trials have been limited by severe toxicities, and the immunologic effects of rIL-2 have been transient. The present study was designed to assess the toxicity and immunologic effects of prolonged administration of low doses of rIL-2. In this phase I study, patients with advanced cancer were scheduled to receive intravenous (IV) infusion of rIL-2 without interruption for 3 months in an outpatient setting. Twenty-one patients received rIL-2 at doses ranging from 0.5 x 10(5) to 6.0 x 10(5) U/m2/d. Treatment was extremely well tolerated, and no patient experienced grade 3 or grade 4 toxicity. The lowest dose level (0.5 x 10(5) U/m2/d) did not have demonstrable immunologic activity. At doses of 1.5 x 10(5) and 4.5 x 10(5) U/m2/d, rIL-2 infusion resulted in the specific expansion of natural-killer (NK) cells (sixfold and ninefold increases, respectively, at these two dose levels) without any changes in B cells, T cells, neutrophils, or monocytes. Grade 2 toxicity was observed at the dose of 6.0 x 10(5) U/m2/d, as three patients required interruption of therapy and two patients who completed therapy developed transient hypothyroidism. In patients with increased NK cells, enhancement of non-major histocompatibility complex (MHC)-restricted cytotoxicity and increased generation of LAK cells in vitro were also demonstrated. Therapy with low-dose rIL-2 can be given safely in an uninterrupted fashion for prolonged periods of time in an outpatient setting. This results in selective expansion of NK cells in vivo with minimal toxicity. Further investigation of this schedule for immunomodulation in vivo should be pursued in phase II studies of both malignant and immunodeficient disease states. PMID:1960552

  12. Fractionated Radioimmunotherapy With 90Y-Clivatuzumab Tetraxetan and Low-Dose Gemcitabine Is Active in Advanced Pancreatic Cancer

    Science.gov (United States)

    Ocean, Allyson J.; Pennington, Kenneth L.; Guarino, Michael J.; Sheikh, Arif; Bekaii-Saab, Tanios; Serafini, Aldo N.; Lee, Daniel; Sung, Max W.; Gulec, Seza A.; Goldsmith, Stanley J.; Manzone, Timothy; Holt, Michael; O’Neil, Bert H.; Hall, Nathan; Montero, Alberto J.; Kauh, John; Gold, David V.; Horne, Heather; Wegener, William A.; Goldenberg, David M.

    2014-01-01

    BACKGROUND It has been demonstrated that the humanized clivatuzumab tetraxetan (hPAM4) antibody targets pancreatic ductal carcinoma selectively. After a trial of radioimmunotherapy that determined the maximum tolerated dose of single-dose yttrium-90-labeled hPAM4 (90Y-hPAM4) and produced objective responses in patients with advanced pancreatic ductal carcinoma, the authors studied fractionated radioimmunotherapy combined with low-dose gemcitabine in this disease. METHODS Thirty-eight previously untreated patients (33 patients with stage IV disease and 5 patients with stage III disease) received gemcitabine 200 mg/m2 weekly for 4 weeks with 90Y-hPAM4 given weekly in Weeks 2, 3, and 4 (cycle 1), and the same cycle was repeated in 13 patients (cycles 2–4). In the first part of the study, 19 patients received escalating weekly 90Y doses of 6.5 mCi/m2, 9.0 mCi/m2, 12.0 mCi/m2, and 15.0 mCi/m2. In the second portion, 19 additional patients received weekly doses of 9.0 mCi/m2 or 12.0 mCi/m2. RESULTS Grade 3/4 thrombocytopenia or neutropenia (according to version 3.0 of the National Cancer Institute’s Common Terminology Criteria for Adverse Events) developed in 28 of 38 patients after cycle 1 and in all retreated patients; no grade >3 nonhematologic toxicities occurred. Fractionated dosing of cycle 1 allowed almost twice the radiation dose compared with single-dose radioimmunotherapy. The maximum tolerated dose of 90Y-hPAM4 was 12.0 mCi/m2 weekly for 3 weeks for cycle 1, with ≤9.0 mCi/m2 weekly for 3 weeks for subsequent cycles, and that dose will be used in future trials. Six patients (16%) had partial responses according to computed tomography-based Response Evaluation Criteria in Solid Tumors, and 16 patients (42%) had stabilization as their best response (58% disease control). The median overall survival was 7.7 months for all 38 patients, including 11.8 months for those who received repeated cycles (46% [6 of 13 patients] ≥1 year), with improved efficacy at

  13. SU-E-J-232: Feasibility of MRI-Based Preplan On Low Dose Rate Prostate Brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Y; Tward, J; Rassiah-Szegedi, P; Zhao, H; Sarkar, V; Huang, L; Szegedi, M; Kokeny, K; Salter, B [University of Utah Huntsman Cancer Institute, Salt Lake City, UT (United States)

    2015-06-15

    Purpose: To investigate the feasibility of using MRI-based preplan for low dose rate prostate brachytherapy. Methods: 12 patients who received transrectal ultrasound (TRUS) guided prostate brachytherapy with Pd-103 were retrospectively studied. Our care-standard of the TRUS-based preplan served as the control. One or more prostate T2-weighted wide and/or narrow-field of view MRIs obtained within the 3 months prior to the implant were imported into the MIM Symphony software v6.3 (MIM Software Inc., Cleveland, OH) for each patient. In total, 37 MRI preplans (10 different image sequences with average thickness of 4.8mm) were generated. The contoured prostate volume and the seed counts required to achieve adequate dosimetric coverage from TRUS and MRI preplans were compared for each patient. The effects of different MRI sequences and image thicknesses were also investigated statistically using Student’s t-test. Lastly, the nomogram from the MRI preplan and TRUS preplan from our historical treatment data were compared. Results: The average prostate volume contoured on the TRUS and MRI were 26.6cc (range: 12.6∼41.3cc), and 27.4 cc (range: 14.3∼50.0cc), respectively. Axial MRI thicknesses (range: 3.5∼8.1mm) did not significantly affect the contoured volume or the number of seeds required on the preplan (R2 = 0.0002 and 0.0012, respectively). Four of the MRI sequences (AX-T2, AX-T2-Whole-Pelvis, AX-T2-FSE, and AXIALT2- Hi-Res) showed statistically significant better prostate volume agreement with TRUS than the other seven sequences (P <0.01). Nomogram overlay between the MRI and TRUS preplans showed good agreement; indicating volumes contoured on MRI preplan scan reliably predict how many seeds are needed for implant. Conclusion: Although MRI does not allow for determination of the actual implant geometry, it can give reliable volumes for seed ordering purposes. Our future work will investigate if MRI is sufficient to reliably replace TRUS preplanning in patients

  14. SU-E-J-232: Feasibility of MRI-Based Preplan On Low Dose Rate Prostate Brachytherapy

    International Nuclear Information System (INIS)

    Purpose: To investigate the feasibility of using MRI-based preplan for low dose rate prostate brachytherapy. Methods: 12 patients who received transrectal ultrasound (TRUS) guided prostate brachytherapy with Pd-103 were retrospectively studied. Our care-standard of the TRUS-based preplan served as the control. One or more prostate T2-weighted wide and/or narrow-field of view MRIs obtained within the 3 months prior to the implant were imported into the MIM Symphony software v6.3 (MIM Software Inc., Cleveland, OH) for each patient. In total, 37 MRI preplans (10 different image sequences with average thickness of 4.8mm) were generated. The contoured prostate volume and the seed counts required to achieve adequate dosimetric coverage from TRUS and MRI preplans were compared for each patient. The effects of different MRI sequences and image thicknesses were also investigated statistically using Student’s t-test. Lastly, the nomogram from the MRI preplan and TRUS preplan from our historical treatment data were compared. Results: The average prostate volume contoured on the TRUS and MRI were 26.6cc (range: 12.6∼41.3cc), and 27.4 cc (range: 14.3∼50.0cc), respectively. Axial MRI thicknesses (range: 3.5∼8.1mm) did not significantly affect the contoured volume or the number of seeds required on the preplan (R2 = 0.0002 and 0.0012, respectively). Four of the MRI sequences (AX-T2, AX-T2-Whole-Pelvis, AX-T2-FSE, and AXIALT2- Hi-Res) showed statistically significant better prostate volume agreement with TRUS than the other seven sequences (P <0.01). Nomogram overlay between the MRI and TRUS preplans showed good agreement; indicating volumes contoured on MRI preplan scan reliably predict how many seeds are needed for implant. Conclusion: Although MRI does not allow for determination of the actual implant geometry, it can give reliable volumes for seed ordering purposes. Our future work will investigate if MRI is sufficient to reliably replace TRUS preplanning in patients

  15. Transcription factor-recognition sequences potentially involved in modulation of gene expression after exposure to low-dose-rate γ-rays in the mouse liver

    International Nuclear Information System (INIS)

    In vivo modulation of gene expression profiles after low-dose and low-dose-rate irradiation has been observed in a variety of experimental systems. However, few studies actually investigated the underlying mechanisms for these genetic responses. In this study, we used pre-existing microarray data and searched for gene modulations in response to long-term, low-dose-rate irradiation. Nucleotide sequences in the neighboring region of the up-regulated, down-regulated, and unaffected genes were retrieved from the Entrez Gene database, and recognition sequences for transcription factors (TFs) were searched using the TFSEARCH database. As a result, we suggested 21 potential TF-binding sites with significantly different incidence between the three gene groups (up-regulated, down-regulated and unaffected gene groups). The binding sites for sterol regulatory element-binding protein 1 (SREBP-1), aryl hydrocarbon receptor (AhR/Ar) and olfactory 1 (Olf-1) were suggested to be involved in up-regulation, while the binding sites for glucocorticoid receptor (GR(GGTACAANNT GTYCTK) ) and hepatocyte nuclear factor 1 (HNF-1) were suggested to be involved in down-regulation of the genes. In addition, the binding sites for activating enhancer-binding protein 4 (AP-4), nuclear factor-κB (NFκB), GR (NNNNNNCNNTNTGTNCTNN) and early growth response 3 (Egr-3) were correlated with modulation of gene expression regardless of the direction of modulation. Our results suggest that these TF-binding sites are involved in gene modulations after long-term continuous irradiation with low-dose-rate γ rays. GR and/or SREBP-1 might be associated with the altered metabolic process observed in liver after exposure to low-dose-rate irradiation. (author)

  16. Curcumin and epithelial-mesenchymal transition in breast cancer cells transformed by low doses of radiation and estrogen.

    Science.gov (United States)

    Gallardo, Marcela; Calaf, Gloria M

    2016-06-01

    Breast cancer is a major cause of global mortality in women. Curcumin exerts anti-proliferative, anti-migratory and apoptotic effects. The aim of this study was to evaluate gene expression involved in epithelial-mesenchymal transition (EMT). An in vitro model was developed with the MCF-10F immortalized breast epithelial cell line exposed to low radiation doses of high LET (linear energy transfer) α-particles (150 keV/µm) and cultured in the presence of 17β-estradiol (estrogen). The following cell lines were used: i) MCF-10F, normal; ii) Alpha5, pre-tumorigenic, and iii) Tumor2 derived from Alpha5 injected into the nude mice. Our previous results have shown that Alpha5 and Tumor2 increased cell proliferation, anchorage independency, invasive capabilities and tumor formation in nude mice in comparison to control. Results indicated that curcumin decreased expression of EMT-related genes in Tumor2 cell line when compared to its counterpart as E-cadherin, N-cadherin, ZEB2, Twist1, Slug, Axl, vimentin, STAT-3, fibronectin; and genes p53 and caveolin-1, as well as apoptotic genes caspase-3, caspase-8, and others such as cyclin D1 and NFκB. All these changes induced a decrease in migratory and invasive capabilities of such a cell line. Thus, it seems that curcumin may impinge upon apoptosis and metastatic properties of the malignant cells exerting antitumor activity in breast cancer cells transformed by low doses of α-particles and estrogen in vitro. PMID:27082017

  17. Quality of Life in Hematologic Cancer Patients: A Randomized Clinical Trial of Low Dose Naltrexone Versus Placebo

    Directory of Open Access Journals (Sweden)

    Mohammad A. Seifrabiei

    2008-01-01

    Full Text Available This study aimed to investigate its effect on hematologic cancer patients. This was a randomized controlled trial assessing quality of life in patients with hematologic malignancies from a single institute in Hamedan. Patients were allocated into two study arms and in addition to their routine treatment received either daily naltrexone 3 mg capsules (treatment group or 3 mg starch (placebo group and were followed up for 5 months. Quality of life was measured using the EORTC QLQ-C30 in four points in time (at admission, 1, 3 and 5 months follow-up. Data were analyzed to compare quality of life in two groups. Totally, 89 patients were studied (45 in treatment group and 44 in placebo group. There were no significant differences between two groups either in demographic and clinical characteristics or in baseline quality of life scores. However, at 1 month, 3 and 5-month follow-up assessments significant differences were observed. In one month follow-up two groups were significantly different in social functioning (p<0.05 indicating a better condition in the treatment group. In the 3-month follow-up, social functioning, role functioning, nausea and vomiting and appetite loss were better in the treatment group (all p-values <0.05. In the 5-month follow-up, physical functioning, social functioning, role functioning, global quality of life, nausea and vomiting and appetite loss were significantly better in the nalterxone group. Low dose naltrexone is an effective drug in improving quality of life in patients with hematologic cancers.

  18. SU-E-T-501: Normal Tissue Toxicities of Pulsed Low Dose Rate Radiotherapy and Conventional Radiotherapy: An in Vivo Total Body Irradiation Study

    International Nuclear Information System (INIS)

    Purpose: Pulsed low dose rate radiotherapy (PLDR) is a re-irradiation technique for therapy of recurrent cancers. We have previously shown a significant difference in the weight and survival time between the mice treated with conventional radiotherapy (CRT) and PLDR using total body irradiation (TBI). The purpose of this study was to investigate the in vivo effects of PLDR on normal mouse tissues.Materials and Methods: Twenty two male BALB/c nude mice, 4 months of age, were randomly assigned into a PLDR group (n=10), a CRT group (n=10), and a non-irradiated control group (n=2). The Siemens Artiste accelerator with 6 MV photon beams was used. The mice received a total of 18Gy in 3 fractions with a 20day interval. The CRT group received the 6Gy dose continuously at a dose rate of 300 MU/min. The PLDR group was irradiated with 0.2Gyx20 pulses with a 3min interval between the pulses. The mice were weighed thrice weekly and sacrificed 2 weeks after the last treatment. Brain, heart, lung, liver, spleen, gastrointestinal, urinary and reproductive organs, and sternal bone marrow were removed, formalin-fixed, paraffin-embedded and stained with H and E. Morphological changes were observed under a microscope. Results: Histopathological examination revealed atrophy in several irradiated organs. The degree of atrophy was mild to moderate in the PLDR group, but severe in the CRT group. The most pronounced morphological abnormalities were in the immune and hematopoietic systems, namely spleen and bone marrow. Brain hemorrhage was seen in the CRT group, but not in the PLDR group. Conclusions: Our results showed that PLDR induced less toxicity in the normal mouse tissues than conventional radiotherapy for the same dose and regimen. Considering that PLDR produces equivalent tumor control as conventional radiotherapy, it would be a good modality for treatment of recurrent cancers

  19. SU-E-T-501: Normal Tissue Toxicities of Pulsed Low Dose Rate Radiotherapy and Conventional Radiotherapy: An in Vivo Total Body Irradiation Study

    Energy Technology Data Exchange (ETDEWEB)

    Cvetkovic, D; Zhang, P; Wang, B; Chen, L; Ma, C [Fox Chase Cancer Center, Philadelphia, PA (United States)

    2014-06-01

    Purpose: Pulsed low dose rate radiotherapy (PLDR) is a re-irradiation technique for therapy of recurrent cancers. We have previously shown a significant difference in the weight and survival time between the mice treated with conventional radiotherapy (CRT) and PLDR using total body irradiation (TBI). The purpose of this study was to investigate the in vivo effects of PLDR on normal mouse tissues.Materials and Methods: Twenty two male BALB/c nude mice, 4 months of age, were randomly assigned into a PLDR group (n=10), a CRT group (n=10), and a non-irradiated control group (n=2). The Siemens Artiste accelerator with 6 MV photon beams was used. The mice received a total of 18Gy in 3 fractions with a 20day interval. The CRT group received the 6Gy dose continuously at a dose rate of 300 MU/min. The PLDR group was irradiated with 0.2Gyx20 pulses with a 3min interval between the pulses. The mice were weighed thrice weekly and sacrificed 2 weeks after the last treatment. Brain, heart, lung, liver, spleen, gastrointestinal, urinary and reproductive organs, and sternal bone marrow were removed, formalin-fixed, paraffin-embedded and stained with H and E. Morphological changes were observed under a microscope. Results: Histopathological examination revealed atrophy in several irradiated organs. The degree of atrophy was mild to moderate in the PLDR group, but severe in the CRT group. The most pronounced morphological abnormalities were in the immune and hematopoietic systems, namely spleen and bone marrow. Brain hemorrhage was seen in the CRT group, but not in the PLDR group. Conclusions: Our results showed that PLDR induced less toxicity in the normal mouse tissues than conventional radiotherapy for the same dose and regimen. Considering that PLDR produces equivalent tumor control as conventional radiotherapy, it would be a good modality for treatment of recurrent cancers.

  20. Low-dose radiation enhances susceptibility to cisplatin in resistant ovarian cancer cells via downregulation of ERCC1 and Bcl-2

    Institute of Scientific and Technical Information of China (English)

    Xiaoran Liu; Donghai Liang; Tao Jiang; Qing Dong; Hongsheng Yu 

    2016-01-01

    Objective Ovarian cancer is one of the leading causes of mortality in patients with malignant gyneco-logical tumors. After surgical intervention for ovarian cancer, cisplatin (DDP)-based chemotherapy is the first-line treatment. However, a major chal enge to treating ovarian cancer is the development of chemore-sistance. Thus, the first aim of this study was to determine whether low-dose radiation could enhance the susceptibility of resistant ovarian cancer cel s to DDP. The second aim was to provide new strategies for treating DDP-resistant ovarian cancer by examining its mechanism. Methods A cel counting kit-8 (CCK8) assay was performed to measure cel proliferation. Flow cytometry was utilized to quantify the apoptosis of DDP-resistant ovarian cancer cel s (SKOV3/DDP) using Annexin V and propidium iodide staining. Real-time quantitative (qPCR) was used to analyze the messenger RNA (mRNA) expression levels of excision repair cross complementing-group 1 (ERCC1) and B-cel lymphoma 2 (Bcl-2) in SKOV3/DDP. Results The IC50 values of the control, conventional-dose, and low-dose groups were 9.367 ± 0.16, 9.289 ± 0.16, and 3.847 ± 0.15, respectively (P Conclusion Low-dose radiation enhanced the sensitivity of resistant ovarian cancer cel s to DDP, pos-sibly by decreasing the DNA repair capacity of tumor cel s and promoting apoptosis.

  1. Estimation of radiation risks at low dose

    International Nuclear Information System (INIS)

    The report presents a review of the effects caused by radiation in low doses, or at low dose rates. For the inheritable (or ''genetic''), as well as for the cancer producing effects of radiation, present evidence is consistent with: (a) a non-linear relationship between the frequency of at least some forms of these effects, with comparing frequencies caused by doses many times those received annually from natural sources, with those caused by lower doses; (b) a probably linear relationship, however, between dose and frequency of effects for dose rates in the region of that received from natural sources, or at several times this rate; (c) no evidence to indicate the existence of a threshold dose below which such effects are not produced, and a strong inference from the mode of action of radiation on cells at low dose rates that no such thresholds are likely to apply to the detrimental, cancer-producing or inheritable, effects resulting from unrepaired damage to single cells. 19 refs

  2. Implementing low-dose computed tomography screening for lung cancer in Canada: implications of alternative at-risk populations, screening frequency, and duration

    Science.gov (United States)

    Evans, W.K.; Flanagan, W.M.; Miller, A.B.; Goffin, J.R.; Memon, S.; Fitzgerald, N.; Wolfson, M.C.

    2016-01-01

    Background Low-dose computed tomography (ldct) screening has been shown to reduce mortality from lung cancer; however, the optimal screening duration and “at risk” population are not known. Methods The Cancer Risk Management Model developed by Statistics Canada for the Canadian Partnership Against Cancer includes a lung screening module based on data from the U.S. National Lung Screening Trial (nlst). The base-case scenario reproduces nlst outcomes with high fidelity. The impact in Canada of annual screening on the number of incident cases and life-years gained, with a wider range of age and smoking history eligibility criteria and varied participation rates, was modelled to show the magnitude of clinical benefit nationally and by province. Life-years gained, costs (discounted and undiscounted), and resource requirements were also estimated. Results In 2014, 1.4 million Canadians were eligible for screening according to nlst criteria. Over 10 years, screening would detect 12,500 more lung cancers than the expected 268,300 and would gain 9200 life-years. The computed tomography imaging requirement of 24,000–30,000 at program initiation would rise to between 87,000 and 113,000 by the 5th year of an annual nlst-like screening program. Costs would increase from approximately $75 million to $128 million at 10 years, and the cumulative cost nationally over 10 years would approach $1 billion, partially offset by a reduction in the costs of managing advanced lung cancer. Conclusions Modelling various ways in which ldct might be implemented provides decision-makers with estimates of the effect on clinical benefit and on resource needs that clinical trial results are unable to provide.

  3. Metronomic Treatment with Low-Dose Trofosfamide Leads to a Long-Term Remission in a Patient with Docetaxel-Refractory Advanced Metastatic Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Jochen Greiner

    2010-01-01

    Full Text Available The treatment of metastatic prostate cancer patients refractory to androgen withdrawal and docetaxel therapy is currently discouraging and new therapeutic approaches are vastly needed. Here, we report a long-term remission over one year in a 68-year-old patient with metastatic docetaxel-refractory prostate cancer employing low-dose trofosfamide. The patient suffered from distant failure with several bone lesions and lymph node metastases depicted by a (11 C-Choline positron emission tomography/computerized tomography (PET/CT. After initiation of trofosfamide 100 mg taken orally once a day we observed a steadily decreasing PSA value from initial 46.6 down to 2.1 g/l. The Choline-PET/CT was repeated after 10 months of continuous therapy and demonstrated a partial remission of the bone lesions and a regression of all involved lymph nodes but one. Taken together we found an astonishing and durable activity of the alkylating agent trofosfamide given in a metronomic fashion. We rate the side effects as low and state an excellent therapeutic ratio of this drug in our patient.

  4. Mammography-oncogenecity at low doses

    International Nuclear Information System (INIS)

    Controversy exists regarding the biological effectiveness of low energy x-rays used for mammography breast screening. Recent radiobiology studies have provided compelling evidence that these low energy x-rays may be 4.42 ± 2.02 times more effective in causing mutational damage than higher energy x-rays. These data include a study involving in vitro irradiation of a human cell line using a mammography x-ray source and a high energy source which matches the spectrum of radiation observed in survivors from the Hiroshima atomic bomb. Current radiation risk estimates rely heavily on data from the atomic bomb survivors, and a direct comparison between the diagnostic energies used in the UK breast screening programme and those used for risk estimates can now be made. Evidence highlighting the increase in relative biological effectiveness (RBE) of mammography x-rays to a range of x-ray energies implies that the risks of radiation-induced breast cancers for mammography x-rays are potentially underestimated by a factor of four. A pooled analysis of three measurements gives a maximal RBE (for malignant transformation of human cells in vitro) of 4.02 ± 0.72 for 29 kVp (peak accelerating voltage) x-rays compared to high energy electrons and higher energy x-rays. For the majority of women in the UK NHS breast screening programme, it is shown that the benefit safely exceeds the risk of possible cancer induction even when this higher biological effectiveness factor is applied. The risk/benefit analysis, however, implies the need for caution for women screened under the age of 50, and particularly for those with a family history (and therefore a likely genetic susceptibility) of breast cancer. In vitro radiobiological data are generally acquired at high doses, and there are different extrapolation mechanisms to the low doses seen clinically. Recent low dose in vitro data have indicated a potential suppressive effect at very low dose rates and doses. Whilst mammography is a low

  5. Health effects of low doses at low dose rates: dose-response relationship modeling in a cohort of workers of the nuclear industry; Effets sanitaires des faibles doses a faibles debits de dose: modelisation de la relation dose-reponse dans une cohorte de travailleurs du nucleaire

    Energy Technology Data Exchange (ETDEWEB)

    Metz-Flamant, Camille

    2011-09-19

    The aim of this thesis is to contribute to a better understanding of the health effects of chronic external low doses of ionising radiation. This work is based on the French cohort of CEA-AREVA NC nuclear workers. The mains stages of this thesis were (1) conducting a review of epidemiological studies on nuclear workers, (2) completing the database and performing a descriptive analysis of the cohort, (3) quantifying risk by different statistical methods and (4) modelling the exposure-time-risk relationship. The cohort includes monitored workers employed more than one year between 1950 and 1994 at CEA or AREVA NC companies. Individual annual external exposure, history of work, vital status and causes of death were reconstructed for each worker. Standardized mortality ratios using French national mortality rates as external reference were computed. Exposure-risk analysis was conducted in the cohort using the linear excess relative risk model, based on both Poisson regression and Cox model. Time dependent modifying factors were investigated by adding an interaction term in the model or by using exposure time windows. The cohort includes 36, 769 workers, followed-up until age 60 in average. During the 1968- 2004 period, 5, 443 deaths, 2, 213 cancers, 62 leukemia and 1, 314 cardiovascular diseases were recorded. Among the 57% exposed workers, the mean cumulative dose was 21.5 milli-sieverts (mSv). A strong Healthy Worker Effect is observed in the cohort. Significant elevated risks of pleura cancer and melanoma deaths were observed in the cohort but not associated with dose. No significant association was observed with solid cancers, lung cancer and cardiovascular diseases. A significant dose-response relationship was observed for leukemia excluding chronic lymphatic leukemia, mainly for doses received less than 15 years before and for yearly dose rates higher than 10 mSv. This PhD work contributes to the evaluation of risks associated to chronic external radiation

  6. Differences in the level of DNA double-strand breaks in human tumour cell lines following low dose-rate irradiation

    International Nuclear Information System (INIS)

    In this study, levels of double-strand breaks (DSB) were measured by neutral filter elution under conditions of both repair inhibition and maximum recovery and compared with clonogenic survival curves for high (HDR) and low dose-rate (LDR) irradiation in human carcinoma lines of differing radiosensitivity. Data suggest that whatever the determinant, whether the degree of damage induction or repair, the level of DSB after LDR correlates well with cellular sensitivity in these four cell lines. Thus, DNA damage studies after low dose-rate irradiation may not only enable the examination of irreparable lesions which are important in cell killing but they may also provide a useful predictive test of cellular radiosensitivity. (Author)

  7. Radio-adaptive Response: An Implication for the Biological Consequences of Low Dose-rate Exposure to X-Ray

    International Nuclear Information System (INIS)

    Radiation induced adaptive response is described as the reduced damaging effect of a challenging radiation dose when induced by a previous low priming dose. To verify the radio-adaptive response that can be induced by occupationally (in vivo) received chronic low dose of X-ray, chromosomal aberration (CA) analysis, micronucleus test (MN), interleukin-1β (IL-1β) and nitric oxide (NO) concentrations were investigated for both the occupationally exposed and control groups before and after exposure to 2 Gy γ-rays as a challenge dose. The results showed that an elevated frequency of CA, MN and nucleoplasmic bridge (NPB) was recorded in radiation workers (exposed group) compared to control group. However, after 2Gy in vitro irradiation of lymphocytes of exposed and control groups, the exposed group was found to be lower than that of control group. On the other hand, IL-1β and NO concentrations in plasma were elevated in exposed group more than in control group. While, after 2Gy irradiation for both groups, there are higher increment in the concentrations of IL-1β and NO in exposed group than the increment difference observed for control group after in vitro irradiation as compared to the same group before irradiation. The present results suggested the existence of an in vivo cytogenetic adaptive response in individuals occupationally exposed to low dose of X-ray. In addition, the results showed that NO radicals and IL-1β have a role in the induction of radio-resistance due to in vivo exposure that may intermediate this radiation.

  8. Low Dose Hyper-radiosensitivity in Human Lung Cancer Cell Line A549 and Its Possible Mechanisms

    Institute of Scientific and Technical Information of China (English)

    Xiaofang DAI; Dan TAO; Hongge WU; Jing CHENG

    2009-01-01

    The low dose hyper-radiosensitivity (HRS) in human lung cancer cell line A549 was in-vestigated,the changes of ATM kinase,cell cycle and apoptosis of cells at different doses of radiation were observed,and the possible mechanisms were discussed.A549 cells in logarithmic growth phase were irradiated with 60Co γ-rays at doses of 0-2 Gy.Together with flow cytometry for precise cell sorting,cell survival fraction was measured by means of conventional colony-formation assay.The expression of ATM1981Ser-P protein was examined by Western blot 1 h after radiation.Apoptosis was detected by Hoechst 33258 fluorescent staining,and Annexin V-FITC/PI staining flow cytometry 24 h after radiation.Cell cycle distribution was observed by flow cytometly 6,12 and 24 h after ra-diation.The results showed that the expression of ATM1981Ser-P protein was observed at 0.2 Gy,followed by an increase at >0.2 Gy,and reached the peak at 0.5 Gy,with little further increase as the dose exceeded 0.5 Gy.Twenty-four h after radiation,partial cells presented the characteristic mor-phological changes of apoptosis,and the cell apoptosis curve was coincident with the survival curve.As compared with control group,the cell cycle almost had no changes after exposure to 0.1 and 0.2 Gy radiation (P>0.05).After exposure to 0.3,0.4 and 0.5 Cry radiation,G2/M phase arrest occurred 6 and 12 h after radiation (P<0.05),and the ratio of G2/M phase cells was decreased 24 h after radiation (P<0.05).It was concluded that A549 cells displayed the phenomenon of HRS/IRR.The mode of cell death was mainly apoptosis.The activity of ATM and cell cycle change may take an important role in HRS/IRR.

  9. Impact of learning curve and technical changes on dosimetry in low-dose brachytherapy for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Le Fur, E. [CHU Brest (France). Radiation Therapy Dept.; Universite de Bretagne Occidentale, Brest (France). Faculte de Medecine et des Sciences de la Sante; Malhaire, J.P.; Baverez, D.; Schlurmann, F. [CHU Brest (France). Radiation Therapy Dept.; Delage, F.; Perrouin-Verbe, M.A. [CHU Brest (France). Urology Dept.; Guerif, S. [University Hospital La Miletrie, Poitiers (France). Radiation Therapy Dept.; Poitiers Univ. (France); Fournier, G.; Valeri, A. [CHU Brest (France). Urology Dept.; Universite de Bretagne Occidentale, Brest (France). Faculte de Medecine et des Sciences de la Sante; Universite Europeenne de Bretagne, Rennes (France); APHP, Hopital Tenon, Paris (France). CeRe.PP; Pradier, O. [CHU Brest (France). Radiation Therapy Dept.; Universite de Bretagne Occidentale, Brest (France). Faculte de Medecine et des Sciences de la Sante; Universite Europeenne de Bretagne, Rennes (France); CHU Brest (France). LaTIM, INSERM U650

    2012-12-15

    Purpose: To assess the impact of experience and technical changes on peri- and postimplantation (1 month later) dosimetry for permanent prostate brachytherapy (PPB). Patients and methods: From July 2003 to May 2010, 150 prostate cancer patients underwent low-dose, loose-seed I{sup 125} PPB as monotherapy with intraoperative planning. Patients were divided into three groups - P1 (n = 64), P2 (n = 45), P3 (n = 41) - according to the technical changes that occurred during the study period: use of an automatic stepper at the beginning of P2 and a high-frequency ultrasound probe in P3. Peri- and postimplantation dosimetric parameters (on day 30) were reported: D90 (dose received by 90% of prostate volume), V100 and V150 (prostate volume receiving, respectively, 100% and 150% of the prescribed dose), D2 cc and D0.1 cc (doses received by 2 cc and 0.1 cc of the rectum), R100 (rectum volume that received 100% of the prescribed dose), and D10 and D30 (doses received by 10% and 30% of the urethra, only during peri-implantation). Results: We observed a decrease in the number of needles and seeds used over time. The mean peri-implantation D90 was 187.52 Gy without a significant difference between the three periods (p = 0.48). The postimplantation D90, V100, and V150 parameters were, respectively, 168.3 Gy, 91.9%, and 55% with no significant difference between the three periods. The peri-implantation and postimplantation D0.1 cc and R100 significantly decreased over time; on day 30: D0.1 cc P1 = 223.1 Gy vs. D0.1 cc P3 = 190.4 Gy (p = 8.10- 5) and R100 P1 = 1.06 cc vs. R100 P3 = 0.53 cc (p = 0.0008). Conclusion: We observed a learning curve for the implantation parameters, which led to a significant decrease in the rectal doses without having any impact on the prostate dosimetric parameters. (orig.)

  10. Impact of learning curve and technical changes on dosimetry in low-dose brachytherapy for prostate cancer

    International Nuclear Information System (INIS)

    Purpose: To assess the impact of experience and technical changes on peri- and postimplantation (1 month later) dosimetry for permanent prostate brachytherapy (PPB). Patients and methods: From July 2003 to May 2010, 150 prostate cancer patients underwent low-dose, loose-seed I125 PPB as monotherapy with intraoperative planning. Patients were divided into three groups - P1 (n = 64), P2 (n = 45), P3 (n = 41) - according to the technical changes that occurred during the study period: use of an automatic stepper at the beginning of P2 and a high-frequency ultrasound probe in P3. Peri- and postimplantation dosimetric parameters (on day 30) were reported: D90 (dose received by 90% of prostate volume), V100 and V150 (prostate volume receiving, respectively, 100% and 150% of the prescribed dose), D2 cc and D0.1 cc (doses received by 2 cc and 0.1 cc of the rectum), R100 (rectum volume that received 100% of the prescribed dose), and D10 and D30 (doses received by 10% and 30% of the urethra, only during peri-implantation). Results: We observed a decrease in the number of needles and seeds used over time. The mean peri-implantation D90 was 187.52 Gy without a significant difference between the three periods (p = 0.48). The postimplantation D90, V100, and V150 parameters were, respectively, 168.3 Gy, 91.9%, and 55% with no significant difference between the three periods. The peri-implantation and postimplantation D0.1 cc and R100 significantly decreased over time; on day 30: D0.1 cc P1 = 223.1 Gy vs. D0.1 cc P3 = 190.4 Gy (p = 8.10- 5) and R100 P1 = 1.06 cc vs. R100 P3 = 0.53 cc (p = 0.0008). Conclusion: We observed a learning curve for the implantation parameters, which led to a significant decrease in the rectal doses without having any impact on the prostate dosimetric parameters. (orig.)

  11. Phase I-II study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell cancer

    International Nuclear Information System (INIS)

    For patients with metastatic renal cell cancer (mRCC) who progressed on vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor therapy, the orally administered mammalian target of rapamycin (mTOR) inhibitor everolimus has been shown to prolong progression free survival. Intriguingly, inhibition of mTOR also promotes expansion of immunosuppressive regulatory T cells (Tregs) that can inhibit anti-tumor immune responses in a clinically relevant way in various tumor types including RCC. This study intends to investigate whether the antitumor efficacy of everolimus can be increased by preventing the detrimental everolimus induced expansion of Tregs using a metronomic schedule of cyclophosphamide. This phase I-II trial is a national multi-center study of different doses and schedules of low-dose oral cyclophosphamide in combination with a fixed dose of everolimus in patients with mRCC not amenable to or progressive after a VEGF-receptor tyrosine kinase inhibitor containing treatment regimen. In the phase I part of the study the optimal Treg-depleting dose and schedule of metronomic oral cyclophosphamide when given in combination with everolimus will be determined. In the phase II part of the study we will evaluate whether the percentage of patients progression free at 4 months of everolimus treatment can be increased from 50% to 70% by adding metronomic cyclophosphamide (in the dose and schedule determined in the phase I part). In addition to efficacy, we will perform extensive immune monitoring with a focus on the number, phenotype and function of Tregs, evaluate the safety and feasibility of the combination of everolimus and cyclophosphamide, perform monitoring of selected angiogenesis parameters and analyze everolimus and cyclophosphamide drug levels. This phase I-II study is designed to determine whether metronomic cyclophosphamide can be used to counter the mTOR inhibitor everolimus induced Treg expansion in patients with metastatic renal cell

  12. Comparison of low dose with standard dose abdominal/pelvic multidetector CT in patients with stage 1 testicular cancer under surveillance

    Energy Technology Data Exchange (ETDEWEB)

    O' Malley, Martin E. [Joint Department of Medical Imaging, Toronto, ON (Canada); Chung, Peter; Warde, Padraig [Princess Margaret Hospital, Department of Radiation Oncology, Toronto, ON (Canada); Haider, Masoom; Jhaveri, Kartik; Khalili, Korosh [Princess Margaret Hospital, Joint Department of Medical Imaging, Toronto, ON (Canada); Jang, Hyun-Jung [Toronto General Hospital, Joint Department of Medical Imaging, Toronto, ON (Canada); Panzarella, Tony [Princess Margaret Hospital, Department of Biostatistics, Toronto, ON (Canada)

    2010-07-15

    To compare the image quality and acceptability of a low dose with those of standard dose abdominal/pelvic multidetector CT in patients with stage 1 testicular cancer managed by surveillance. One hundred patients (median age 31 years; range 19-83 years), 79 with seminoma and 21 with non-seminoma, underwent abdominal/pelvic imaging with low and standard dose protocols on 64-slice multidetector CT. Three reviewers independently evaluated images for noise and diagnostic quality on a 5-point scale and for diagnostic acceptability. On average, each reader scored noise and diagnostic quality of standard dose images significantly better than corresponding low dose images (p < 0.0001). One reader found all CT examinations acceptable; two readers each found 1/100 (1%) low dose examinations unacceptable. Median and mean dose-length product for low and standard dose protocols were 416.0 and 452.2 (range 122.9-913.4) and 931.9 and 999.8 (range 283.8-1,987.7) mGy cm, respectively. The low dose protocol provided diagnostically acceptable images for at least 99% of patients and achieved mean dose reduction of 55% compared with the standard dose protocol. (orig.)

  13. The feasibility and safety of high-intensity focused ultrasound combined with low-dose external beam radiotherapy as supplemental therapy for advanced prostate cancer following hormonal therapy

    OpenAIRE

    Wu, Rui-Yi; Wang, Guo-Min; Xu, Lei; ZHANG, BO-HENG; Xu, Ye-Qing; Zeng, Zhao-Chong; Chen, Bing

    2011-01-01

    The aim of this study was to investigate the feasibility and safety of high-intensity focused ultrasound (HIFU) combined with (+) low-dose external beam radiotherapy (LRT) as supplemental therapy for advanced prostate cancer (PCa) following hormonal therapy (HT). Our definition of HIFU+LRT refers to treating primary tumour lesions with HIFU in place of reduced field boost irradiation to the prostate, while retaining four-field box irradiation to the pelvis in conventional-dose external beam r...

  14. Long term low dose rate irradiation causes recovery from type II diabetes and suppression of aging in type II diabetes-prone mice

    International Nuclear Information System (INIS)

    The effects of low dose rate gamma irradiation on model C57BL/KsJ-db/db mice with Type II diabetes mellitus was investigated. These mice develop Type II diabetes by 10 weeks of age, due to obesity, and are characterized by hyperinsulinemia. A group of 12 female 10-week old mice were irradiated at 0.65 mGy/hr in the low dose rate irradiation facility in the Low Dose Radiation Research Center. The urine glucose levels of all of the mice were strongly positive at the beginning of the irradiation. In the irradiated group, a decrease in the glucose level was observed in three mice, one in the 35th week, another in the 52nd week and the third in the 80th week. No recovery from the diabetes was observed in the 12 mice of non-irradiated control group. There was no systematic change of body weight or consumption of food and drinking water between the irradiated group and the non-irradiated group or between the recovered mice and the non-recovered mice. Survival was better in the irradiated group. The surviving fraction at the age of 90 weeks was 75 % in the irradiated group but only 40 % in the non-irradiated. A marked difference was also observed in the appearance of the coat hair, skin and tail. The irradiated group was in much better condition. Mortality was delayed and the healthy appearance was prolonged in the irradiated mice by about 20-30 weeks compared with the control mice. These results suggest that the low dose irradiation modified the condition of the diabetic mice, leading not only to recovery from diabetes, but also to suppression of the aging process

  15. TH-C-12A-07: Implementation of a Pulsed Low Dose Date Radiotherapy (PLRT) Protocol for Recurrent Cancers Using Advanced Beam Delivery

    International Nuclear Information System (INIS)

    Purpose: Recent in vitro and in vivo experimental findings provided strong evidence that pulsed low-dose-rate radiotherapy (PLDR) produced equivalent tumor control as conventional radiotherapy with significantly reduced normal tissue toxicities. This work aimed to implement a PLDR clinical protocol for the management of recurrent cancers utilizing IMRT and VMAT. Methods: Our PLDR protocol requires that the daily 2Gy dose be delivered in 0.2Gy×10 pulses with a 3min interval between the pulses. To take advantage of low-dose hyper-radiosensitivity the mean dose to the target is set at 0.2Gy and the maximum dose is limited to 0.4Gy per pulse. Practical planning strategies were developed for IMRT and VMAT: (1) set 10 ports for IMRT and 10 arcs for VMAT with each angle/arc as a pulse; (2) set the mean dose (0.2Gy) and maximum dose (0.4Gy) to the target per pulse as hard constraints (no constraints to OARs); (3) select optimal port/arc angles to avoid OARs; and (4) use reference structures in or around target/OARs to reduce maximum dose to the target/OARs. IMRT, VMAT and 3DCRT plans were generated for 60 H and N, breast, lung, pancreas and prostate patients and compared. Results: All PLDR treatment plans using IMRT and VMAT met the dosimetry requirements of the PLDR protocol (mean target dose: 0.20Gy±0.01Gy; maximum target dose < 0.4Gy). In comparison with 3DCRT, IMRT and VMAT exhibited improved target dose conformity and OAR dose sparing. A single arc can minimize the difference in the target dose due to multi-angle incidence although the delivery time is longer than 3DCRT and IMRT. Conclusion: IMRT and VMAT are better modalities for PLDR treatment of recurrent cancers with superior target dose conformity and critical structure sparing. The planning strategies/guidelines developed in this work are practical for IMRT/VMAT treatment planning to meet the dosimetry requirements of the PLDR protocol

  16. TH-C-12A-07: Implementation of a Pulsed Low Dose Date Radiotherapy (PLRT) Protocol for Recurrent Cancers Using Advanced Beam Delivery

    Energy Technology Data Exchange (ETDEWEB)

    Ma, C; Lin, M; Chen, L; Price, R [Fox Chase Cancer Center, Philadelphia, PA (United States); Li, J; Kang, S; Wang, P; Lang, J [Sichuan Provincial Cancer Hospital, Chengdu (China)

    2014-06-15

    Purpose: Recent in vitro and in vivo experimental findings provided strong evidence that pulsed low-dose-rate radiotherapy (PLDR) produced equivalent tumor control as conventional radiotherapy with significantly reduced normal tissue toxicities. This work aimed to implement a PLDR clinical protocol for the management of recurrent cancers utilizing IMRT and VMAT. Methods: Our PLDR protocol requires that the daily 2Gy dose be delivered in 0.2Gy×10 pulses with a 3min interval between the pulses. To take advantage of low-dose hyper-radiosensitivity the mean dose to the target is set at 0.2Gy and the maximum dose is limited to 0.4Gy per pulse. Practical planning strategies were developed for IMRT and VMAT: (1) set 10 ports for IMRT and 10 arcs for VMAT with each angle/arc as a pulse; (2) set the mean dose (0.2Gy) and maximum dose (0.4Gy) to the target per pulse as hard constraints (no constraints to OARs); (3) select optimal port/arc angles to avoid OARs; and (4) use reference structures in or around target/OARs to reduce maximum dose to the target/OARs. IMRT, VMAT and 3DCRT plans were generated for 60 H and N, breast, lung, pancreas and prostate patients and compared. Results: All PLDR treatment plans using IMRT and VMAT met the dosimetry requirements of the PLDR protocol (mean target dose: 0.20Gy±0.01Gy; maximum target dose < 0.4Gy). In comparison with 3DCRT, IMRT and VMAT exhibited improved target dose conformity and OAR dose sparing. A single arc can minimize the difference in the target dose due to multi-angle incidence although the delivery time is longer than 3DCRT and IMRT. Conclusion: IMRT and VMAT are better modalities for PLDR treatment of recurrent cancers with superior target dose conformity and critical structure sparing. The planning strategies/guidelines developed in this work are practical for IMRT/VMAT treatment planning to meet the dosimetry requirements of the PLDR protocol.

  17. USE OF A COMBINATION OF АVASTIN AND LOW-DOSE INTERFERON- α IN THE FIRST-LINE TREATMENT OF METASTATIC RENAL-CELL CANCER

    Directory of Open Access Journals (Sweden)

    A. S. Kalpinsky

    2014-07-01

    Full Text Available Background. The registered AVOREN Phase III trial demonstrated the efficacy of a combination of bevacizumab and interferon-α (IFN-α as first-line targeted therapy in patients with metastatic renal-cell cancer (mRCC. The median progression-free survival (PFS was significantly higher in the bevacizumab + IFN-α group, amounting to 10.2 months versus 5.4 months in the IFN-α group (p < 0.0001. The most common grade 3 and 4 side effects in the AVOREN study included the adverse events due to IFN-α use; this initiated a prospective multicenter BEVLiN (Bevacizumab and Low-Dose Interferon Phase II trial in 2008 to evaluate the efficacy and tolerability of a combination of bevacizumab and low-dose IFN-α in patients with mRCC to diminish the toxicity of treatment.Subjects and methods. The trial enrolled 146 patients having good and moderate prognosis according to the MSKCC scale. The patients received Avastin 10 mg/kg every 2 weeks and IFN-α 3,000,000 IU thrice weekly. The historical control group was taken from the AVOREN trial as a control group. The main purposes of the trial were to evaluate the tolerability of treatment (the frequency of adverse events due to IFN-α use, grade 3 or more toxicity and PFS. The additional goals were to estimate overall survival (OS, objective response rates, and the incidence of any adverse events of grade 3–4 toxicity.Results. The median follow-up was 29.4 months (range 1.5–35.4 months. The rate of objective responses was 28.8 % (95 % confidence interval (CI 21.4–37.1. The median PFS was 15.3 months (95 % CI 11.7–18.0 and PFS was 58.2 and 28.9 % at 12 and 24 months of treatment, respectively. The median OS was 30.7 months (95 % CI 25.7 was unachieved. In the IFN-α group, all grades of adverse reactions and their grade 3 or more were recorded in 53.4 and 10.3 % of the patients, respectively. The adverse events that were a reason for IFN-α discontinuation were recorded in 24.0 % of the patients

  18. The relative contributions of different organ sites to the total cancer mortality associated with low-dose radiation exposure

    International Nuclear Information System (INIS)

    In this paper, the factors involved in the assessment of the relative contributions of mortality from cancer of individual organs are explored, thus providing a basis for new estimates of weighting factors to be made by the ICRP in assessing the total detriment for a given radiation dose. Systems of site-specific relative weights for cancer mortality risk due to radiation exposure were examined with respect to the effects of age, sex, projection model, population characteristics as represented by baseline, cause-specific mortality rates and choice between probability of untimely death and expected loss of life span as a measure of health detriment. (UK)

  19. Frequency of chromosome aberration and dose/dose rate effects in the mouse exposed to long-term low dose radiation

    International Nuclear Information System (INIS)

    Authors have been conducting long term irradiation experiments in the mouse with the dose rate as low as unreported hitherto and have shown with highly sensitive methods to detect chromosomal aberration, that there is the positive dose rate effect under even such a condition, of which details are described herein. According to the definition of United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCER) (1993), the low dose rate is 137Cs-gamma-ray at the low dose rate of 1 or 20 mGy/22 h/day (total, 125-615 or 100-8000 mGy, respectively). Other groups received radiations of 0 Gy (non-irradiated, age-matched control), 200-8000 mGy at 200 mGy/22 h/day, 400-8000 mGy at 400 mGy/22 h/day, or 250-2000 mGy at 890 mGy/min. At the defined days after exposure, mice were sacrificed, their spleens were dissected out, splenic cells were cultured for 48 hr, and their chromosome specimens were prepared to be stained with Giemsa or FISH (fluorescence in situ hybridization). Dicentric (dic) and translocation chromosomal aberrations were found to increase even with the lowest total (accumulated) dose, where the frequency was significantly higher than that in control. Comparison of the regression slopes at each dose rate of the relation between dose and aberration revealed the difference dependent on the rate, thus demonstrating the presence of dose rate effect. Dose/dose rate effect factor (DDREF) calculated by authors' procedure (at 1000-100 mGy: DDREF=17.8-4.5 for dic by FISH; 24.5-5.2 for dic+ring chromosome by Giemsa) was thought important in the risk assessment of low dose radiation and also revealed a problem in International Commission on Radiological Protection (ICRP) (1991) calculation of the factor. (K.T.)

  20. Reliable categorisation of visual scoring of coronary artery calcification on low-dose CT for lung cancer screening: validation with the standard Agatston score

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Yi-Luan; Wu, Fu-Zong; Wang, Yen-Chi [Kaohsiung Veterans General Hospital, Department of Radiology, Kaohsiung 813 (China); National Yang Ming University, Faculty of Medicine, School of Medicine, Taipei (China); Ju, Yu-Jeng [National Taiwan University, Department of Psychology, Taipei (China); Mar, Guang-Yuan [Kaohsiung Veterans General Hospital, Division of Cardiology, Department of Medicine, Kaohsiung 813 (China); Chuo, Chiung-Chen [Kaohsiung Veterans General Hospital, Department of Radiology, Kaohsiung 813 (China); Lin, Huey-Shyan [Fooyin University, School of Nursing, Kaohsiung (China); Wu, Ming-Ting [Kaohsiung Veterans General Hospital, Department of Radiology, Kaohsiung 813 (China); National Yang Ming University, Faculty of Medicine, School of Medicine, Taipei (China); National Yang Ming University, Institute of Clinical Medicine, Taipei (China)

    2013-05-15

    To validate the reliability of the visual coronary artery calcification score (VCACS) on low-dose CT (LDCT) for concurrent screening of CAC and lung cancer. We enrolled 401 subjects receiving LDCT for lung cancer screening and ECG-gated CT for the Agatston score (AS). LDCT was reconstructed with 3- and 5-mm slice thickness (LDCT-3mm and LDCT-5mm respectively) for VCACS to obtain VCACS-3mm and VCACS-5mm respectively. After a training session comprising 32 cases, two observers performed four-scale VCACS (absent, mild, moderate, severe) of 369 data sets independently, the results were compared with four-scale AS (0, 1-100, 101-400, >400). CACs were present in 39.6 % (146/369) of subjects. The sensitivity of VCACS-3mm was higher than for VCACS-5mm (83.6 % versus 74.0 %). The median of AS of the 24 false-negative cases in VCACS-3mm was 2.3 (range 1.1-21.1). The false-negative rate for detecting AS {>=} 10 on LDCT-3mm was 1.9 %. VCACS-3mm had higher concordance with AS than VCACS-5mm (k = 0.813 versus k = 0.685). An extended test of VCACS-3mm for four junior observers showed high inter-observer reliability (intra-class correlation = 0.90) and good concordance with AS (k = 0.662-0.747). This study validated the reliability of VCACS on LDCT for lung cancer screening and showed that LDCT-3mm was more feasible than LDCT-5mm for CAD risk stratification. (orig.)

  1. Ionizing radiation decreases human cancer mortality rates

    International Nuclear Information System (INIS)

    Information from nine studies with exposed nuclear workers and military observers of atmospheric bomb explosions confirms the results from animal studies which showed that low doses of ionizing radiation are beneficial. The usual ''healthy worker effect'' was eliminated by using carefully selected control populations. The results from 13 million person-years show the cancer mortality rate of exposed persons is only 65.6% that of carefully selected unexposed controls. This overwhelming evidence makes it politically untenable and morally wrong to withhold public health benefits of low dose irradiation. Safe supplementation of ionizing radiation should become a public health service. (author)

  2. Marked increase in the rate of ocular lens and forelimb regeneration in the newt. Cynops pyrrhogaster, following partial body exposure to low dose X-rays

    Energy Technology Data Exchange (ETDEWEB)

    Okamoto, T.; Kanao, T.; Miyachi, Y.

    2004-07-01

    In recent years, concern over the stimulating effects of low-dose X-rays has been growing. Therefore the effects of low-dose X-irradiation on lens and forelimb regeneration in the newt were examined. Newts were subjected to s harm or whole-body X-ray exposure at a dose of 0.05, 0.2 or 0.4Gy, delivered at a rate of 0.43Gy/min. The eyeballs were fixed in formalin solution, embedded in paraffin and assessed histologically. On day 14 after lens removal, unexposed animals showed the formation of a hollow epithelial vesicle of depigmented cells continuous with the laminae of the iris corresponding to the expected regeneration stage (Reyer's regeneration stage II). In contrast, lenses from newts exposed to a 0.2Gy dose X-ray showed some formation of the primary lens fiber nucleus corresponding to the fiber differentiation stage (Reyer's regeneration stage III-early). Thus, low-dose X-irradiation induced well regeneration compared to the unexposed groups. However, when newts were injected with N-nitro-L-arginine, nitric oxide inhibitor, no radiation-induced effect could be observed. Furthermore, an acceleration from Reyer's stage II to III-early was also found on day 14 following irradiation of only the upper belly, including the spleen. Interestingly, well regeneration could be observed on forelimb stage. On 6 weeks after amputation, unexposed animal was showed the assembly of the condrogenesis of the radius and ulna. In contrast, forelimb from newts exposed to a 0.2Gy spleen portion was showed the onset of digit formation. The effects of low-dose X-irradiation on regeneration may be mediated by changes in immune activity. (Author)

  3. Screening for early lung cancer with low-dose spiral computed tomography: results of annual follow-up examinations in asymptomatic smokers

    International Nuclear Information System (INIS)

    The aim of this study was analysis of incidence results in a prospective one-arm feasibility study of lung cancer screening with low-radiation-dose spiral computed tomography in heavy smokers. Eight hundred seventeen smokers (≥40 years, ≥20 pack years of smoking history) underwent baseline low-dose CT. Biopsy was recommended in nodules >10 mm with CT morphology suggesting malignancy. In all other lesions follow-up with low-dose CT was recommended. Annual repeat CT was offered to all study participants. Six hundred sixty-eight (81.8%) of the 817 subjects underwent annual repeat CT with a total of 1735 follow-up years. Follow-up of non-calcified nodules present at baseline CT demonstrated growth in 11 of 792 subjects. Biopsy was performed in 8 of 11 growing nodules 7 of which represented lung cancer. Of 174 new nodules, 3 represented lung cancer. The 10 screen-detected lung cancers were all non-small cell cancer (6 stage IA, 1 stage IB, 1 stage IIIA, 2 stage IV). Five symptom-diagnosed cancers (2 small cell lung cancer: 1 limited disease, 1 extensive disease, 3 central/endobronchial non-small cell lung cancer, 2 stage IIIA, 1 stage IIIB) were diagnosed because of symptoms in the 12-month interval between two annual CT scans. Incidence of lung cancer was lower than prevalence, screen-detected cancers were smaller, and stage I was found in 70% (7 of 10) of screen-detected tumors. Only 27% (4 of 15) of invasive procedures was performed for benign lesions; however, 33% (5 of 15) of all cancers diagnosed in the population were symptom-diagnosed cancers (3 central NSCLC, all stage III, 2 SCLC) demonstrating the limitations of CT screening. (orig.)

  4. Low-dose effects of Bisphenol A on human primary vascular endothelial cells and colon cancer cells

    OpenAIRE

    Varandas, Edna Soraia Gregório Ribeiro Varandas

    2014-01-01

    Bisphenol A (BPA) is an extensively utilized endocrine disruptor for which human exposure is considered generalized through ingestion. Information regarding BPA effects on vascular and digestive tract tissues is scarce. Therefore, in this work primary Human Umbilical Vein Endothelial Cells (HUVEC) and human colon adenocarcinona cell line HT29 were used to evaluate BPA effects at two distinct low-dose concentrations relevant in terms of human health risk assessment. BPA di...

  5. Hearing loss due to concurrent daily low-dose cisplatin chemoradiation for locally advanced head and neck cancer

    International Nuclear Information System (INIS)

    Background and purpose: Cisplatin-based chemo-irradiation (CRT) is increasingly used for head and neck squamous cell carcinoma (HNSCC). We aimed to assess hearing deterioration due to low-dose cisplatin chemoradiation and to compare the observed hearing loss with hearing loss in our previously described high-dose cisplatin CRT cohort. Materials and methods: A prospective analysis of hearing thresholds at low and (ultra)-high frequencies obtained before and after treatment in 60 patients. Patients received low-dose cisplatin (6 mg/m2, daily infusions, 20-25 days) with concomitant accelerated radiotherapy (70 Gy). Results: Audiometry up to 16 kHz was performed before therapy and 31 days (median) post-treatment. The total incidence of ototoxicity in CTCAEv3.0 was 31% in audiograms up to 8 kHz, and 5% of ears tested qualified for HAs due to treatment. The mean hearing loss at speech frequencies was 2.6 dB (SD 5.7) and 2.3 dB (SD 9.2) at PTA 1-2-4 kHz air-conduction and bone-conduction, respectively. The mean hearing loss at ultra-high frequencies (PTA AC 8-10-12.5 kHz) was 9.0 dB (SD 8.1). Low-dose cisplatin CRT caused less acute hearing loss (CTCAE 31%), compared to high-dose cisplatin CRT (CTCAE 78%). Conclusions: Low-dose cisplatin chemo-irradiation for HNSCC is a relatively safe treatment protocol with respect to ototoxicity

  6. Prostate-Specific Antigen at 4 to 5 Years After Low-Dose-Rate Prostate Brachytherapy Is a Strong Predictor of Disease-Free Survival

    Energy Technology Data Exchange (ETDEWEB)

    Lo, Andrea C. [Department of Radiation Oncology, British Columbia Cancer Agency Vancouver Centre, Vancouver, British Columbia (Canada); Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia (Canada); Morris, W. James, E-mail: JMorris@bccancer.bc.ca [Department of Radiation Oncology, British Columbia Cancer Agency Vancouver Centre, Vancouver, British Columbia (Canada); Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia (Canada); Lapointe, Vincent [Department of Medical Physics, British Columbia Cancer Agency Vancouver Centre, Vancouver, British Columbia (Canada); Hamm, Jeremy [Department of Population Oncology, British Columbia Cancer Agency Vancouver Centre, Vancouver, British Columbia (Canada); Keyes, Mira; Pickles, Tom; McKenzie, Michael [Department of Radiation Oncology, British Columbia Cancer Agency Vancouver Centre, Vancouver, British Columbia (Canada); Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia (Canada); Spadinger, Ingrid [Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia (Canada); Department of Medical Physics, British Columbia Cancer Agency Vancouver Centre, Vancouver, British Columbia (Canada)

    2014-01-01

    Purpose: To determine (1) the prognostic utility of prostate-specific antigen (PSA) concentration at 45 to 60 months (48mPSA) after low-dose-rate prostate brachytherapy (LDR-PB); (2) the predictors of 48mPSA; and (3) the prognostic utility of directional trends between PSA levels at 24, 36, and 48 months after LDR-PB. Methods and Materials: Between 1998 and 2008, 2223 patients with low- and intermediate-risk prostate cancer received LDR-PB monotherapy. A cohort of 1434 of these patients was identified with a documented 48mPSA and no evidence of disease relapse prior to the 48mPSA. In addition, a subset of this cohort (n=585) was identified with ≥72 months of follow-up and documented PSA values at both 24 and 36 months after implantation. Results: Median follow-up time was 76 months. Eight-year Kaplan-Meier disease-free survival (DFS) rates were 100% vs 73.4% for patients with 48mPSA ≤0.2 vs those with >0.2 ng/mL; 99.1% versus 53.8% for a 48mPSA threshold of ≤0.4 versus >0.4 ng/mL, respectively; and 97.3% versus 0% for a threshold of ≤1.0 versus >1.0 ng/mL, respectively. On multivariate analysis, the only factor predictive of DFS was 48mPSA (P<.0001). On subset analysis (n=585), 29 patients had a PSA rise (defined as >0.2 ng/mL) between 24 and 36 months, 24 patients had a rise between 36 and 48 months, and 11 patients had rises over both intervals. Failure rates in these patients were 52%, 79%, and 100%, respectively. On multivariate analysis, initial PSA, androgen deprivation therapy, and dose to 90% of the prostate significantly correlated with 48mPSA but together accounted for only ∼5% of its total variance. Conclusions: The 48mPSA after LDR-PB is highly predictive of long-term DFS. Patients with 48mPSA ≤0.4 ng/mL had a <1% risk of disease relapse at 8 years, whereas all patients with 48mPSA >1.0 ng/mL relapsed. Consecutive PSA rises of >0.2 ng/mL from 24 to 36 months and from 36 to 48 months were also highly predictive of subsequent failure.

  7. An evaluation of a Low-Dose-Rate (LDR) brachytherapy procedure using a systems engineering & error analysis methodology for health care (SEABH) - (SAVE)

    LENUS (Irish Health Repository)

    Chadwick, Liam

    2012-03-12

    Health Care Failure Modes and Effects Analysis (HFMEA®) is an established tool for risk assessment in health care. A number of deficiencies have been identified in the method. A new method called Systems and Error Analysis Bundle for Health Care (SEABH) was developed to address these deficiencies. SEABH has been applied to a number of medical processes as part of its validation and testing. One of these, Low Dose Rate (LDR) prostate Brachytherapy is reported in this paper. The case study supported the validity of SEABH with respect to its capacity to address the weaknesses of (HFMEA®).

  8. Low-dose prednisolone in first-line docetaxel for patients with metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Kongsted, Per; Svane, Inge Marie; Lindberg, Henriette;

    2015-01-01

    incidence of peripheral edema (32% vs. 15%, P<0.001) and grade 3 nonhematological toxicity (56% vs. 43%, P = 0.022). Patients treated with D alone were also more frequently hospitalized (53% vs. 41%, P = 0.035), mainly owing to a higher incidence of febrile neutropenia in this group (25% vs. 10%, P<0......% CI: 0.76-1.26, P = 0.89, Cox proportional hazard regression model). CONCLUSIONS: Coadministration of low-dose P reduced the incidence of peripheral edema, grade 3 nonhematological toxicity, and the risk of being admitted owing to febrile neutropenia during treatment with D. Adjusted survival analysis...

  9. Differential effects of repeated low dose treatment with the cannabinoid agonist WIN 55,212-2 in experimental models of bone cancer pain and neuropathic pain

    DEFF Research Database (Denmark)

    Hald, Andreas; Ding, Ming; Egerod, Kristoffer Lihme;

    2008-01-01

    Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment with....... Furthermore, this treatment strategy was not found to induce measurable CNS related side effects or tolerance. Cancer cell viability assays and bone volume fraction assessed by micro computed tomography (microCT) demonstrated that these effects were not due to changes in cancer progression. The difference in...... cannabinoid agonists. However, the use of cannabinoid agonists in humans may be hampered by CNS related side effects and development of tolerance. In the present study, we investigated the effect of repeated low dose administration of the synthetic cannabinoid agonist WIN 55,212-2 on bone cancer pain and...

  10. Low-Dose Hyper-Radiosensitivity Is Not a Common Effect in Normal Asynchronous and G2-Phase Fibroblasts of Cancer Patients

    International Nuclear Information System (INIS)

    Purpose: In our previous study, using the micronucleus assay, a low-dose hyper-radiosensitivity (HRS)-like phenomenon was observed for normal fibroblasts of 2 of the 40 cancer patients investigated. In this article we report, for the first time, the survival response of primary fibroblasts from 25 of these patients to low-dose irradiation and answer the question regarding the effect of G2-phase enrichment on HRS elicitation. Methods and Materials: The clonogenic survival of asynchronous as well as G2-phase enriched fibroblast populations was measured. Separation of G2-phase cells and precise cell counting was performed using a fluorescence-activated cell sorter. Sorted and plated cells were irradiated with single doses (0.1-4 Gy) of 6-MV x-rays. For each patient, at least 4 independent experiments were performed, and the induced-repair model was fitted over the whole data set to confirm the presence of HRS effect. Results: The HRS response was demonstrated for the asynchronous and G2-phase enriched cell populations of 4 patients. For the rest of patients, HRS was not defined in either of the 2 fibroblast populations. Thus, G2-phase enrichment had no effect on HRS elicitation. Conclusions: The fact that low-dose hyper-radiosensitivity is not a common effect in normal human fibroblasts implies that HRS may be of little consequence in late-responding connective tissues with regard to radiation fibrosis

  11. The investigation of prostatic calcifications using μ-PIXE analysis and their dosimetric effect in low dose rate brachytherapy treatments using Geant4

    Science.gov (United States)

    Pope, D. J.; Cutajar, D. L.; George, S. P.; Guatelli, S.; Bucci, J. A.; Enari, K. E.; Miller, S.; Siegele, R.; Rosenfeld, A. B.

    2015-06-01

    Low dose rate brachytherapy is a widely used modality for the treatment of prostate cancer. Most clinical treatment planning systems currently in use approximate all tissue to water, neglecting the existence of inhomogeneities, such as calcifications. The presence of prostatic calcifications may perturb the dose due to the higher photoelectric effect cross section in comparison to water. This study quantitatively evaluates the effect of prostatic calcifications on the dosimetric outcome of brachytherapy treatments by means of Monte Carlo simulations and its potential clinical consequences. Four pathological calcification samples were characterised with micro-particle induced x-ray emission (μ-PIXE) to determine their heavy elemental composition. Calcium, phosphorus and zinc were found to be the predominant heavy elements in the calcification composition. Four clinical patient brachytherapy treatments were modelled using Geant4 based Monte Carlo simulations, in terms of the distribution of brachytherapy seeds and calcifications in the prostate. Dose reductions were observed to be up to 30% locally to the calcification boundary, calcification size dependent. Single large calcifications and closely placed calculi caused local dose reductions of between 30-60%. Individual calculi smaller than 0.5 mm in diameter showed minimal dosimetric impact, however, the effects of small or diffuse calcifications within the prostatic tissue could not be determined using the methods employed in the study. The simulation study showed a varying reduction on common dosimetric parameters. D90 showed a reduction of 2-5%, regardless of calcification surface area and volume. The parameters V100, V150 and V200 were also reduced by as much as 3% and on average by 1%. These reductions were also found to relate to the surface area and volume of calcifications, which may have a significant dosimetric impact on brachytherapy treatment, however, such impacts depend strongly on specific factors

  12. The investigation of prostatic calcifications using μ-PIXE analysis and their dosimetric effect in low dose rate brachytherapy treatments using Geant4

    International Nuclear Information System (INIS)

    Low dose rate brachytherapy is a widely used modality for the treatment of prostate cancer. Most clinical treatment planning systems currently in use approximate all tissue to water, neglecting the existence of inhomogeneities, such as calcifications. The presence of prostatic calcifications may perturb the dose due to the higher photoelectric effect cross section in comparison to water. This study quantitatively evaluates the effect of prostatic calcifications on the dosimetric outcome of brachytherapy treatments by means of Monte Carlo simulations and its potential clinical consequences.Four pathological calcification samples were characterised with micro-particle induced x-ray emission (μ-PIXE) to determine their heavy elemental composition. Calcium, phosphorus and zinc were found to be the predominant heavy elements in the calcification composition. Four clinical patient brachytherapy treatments were modelled using Geant4 based Monte Carlo simulations, in terms of the distribution of brachytherapy seeds and calcifications in the prostate. Dose reductions were observed to be up to 30% locally to the calcification boundary, calcification size dependent. Single large calcifications and closely placed calculi caused local dose reductions of between 30–60%. Individual calculi smaller than 0.5 mm in diameter showed minimal dosimetric impact, however, the effects of small or diffuse calcifications within the prostatic tissue could not be determined using the methods employed in the study. The simulation study showed a varying reduction on common dosimetric parameters. D90 showed a reduction of 2–5%, regardless of calcification surface area and volume. The parameters V100, V150 and V200 were also reduced by as much as 3% and on average by 1%. These reductions were also found to relate to the surface area and volume of calcifications, which may have a significant dosimetric impact on brachytherapy treatment, however, such impacts depend strongly on specific

  13. Plasma levels of a low-dose constant-rate-infusion of ketamine and its effect on single and repeated nociceptive stimuli in conscious dogs.

    Science.gov (United States)

    Bergadano, Alessandra; Andersen, Ole K; Arendt-Nielsen, Lars; Theurillat, Regula; Thormann, Wolfgang; Spadavecchia, Claudia

    2009-11-01

    This study quantitatively investigated the analgesic action of a low-dose constant-rate-infusion (CRI) of racemic ketamine (as a 0.5 mg kg(-1) bolus and at a dose rate of 10 microg kg(-1) min(-1)) in conscious dogs using a nociceptive withdrawal reflex (NWR) and with enantioselective measurement of plasma levels of ketamine and norketamine. Withdrawal reflexes evoked by transcutaneous single and repeated electrical stimulation (10 pulses, 5 Hz) of the digital plantar nerve were recorded from the biceps femoris muscle using surface electromyography. Ketamine did not affect NWR thresholds or the recruitment curves after a single nociceptive stimulation. Temporal summation (as evaluated by repeated stimuli) and the evoked behavioural response scores were however reduced compared to baseline demonstrating the antinociceptive activity of ketamine correlated with the peak plasma concentrations. Thereafter the plasma levels at pseudo-steady-state did not modulate temporal summation. Based on these experimental findings low-dose ketamine CRI cannot be recommended for use as a sole analgesic in the dog. PMID:18706837

  14. Low-dose rate prostate brachytherapy is well tolerated in patients with a history of inflammatory bowel disease

    International Nuclear Information System (INIS)

    Purpose: We report on the follow-up of 24 patients with a prior history of inflammatory bowel disease (IBD) treated with brachytherapy for early-stage prostate cancer. Methods and Materials: Twenty-four patients with a history of inflammatory bowel disease (17 with ulcerative colitis (UC), 7 with Crohn's disease [CD]) underwent prostate brachytherapy between 1992 and 2004. Fifteen patients were treated with I-125 implantation and 6 patients were treated with Pd-103 alone or in combination with 45 Gy external beam radiation. Charts were reviewed for all patients, and all living patients were contacted by phone. National Cancer Institute common toxicity scores for proctitis were assigned to all patients. Actuarial risk of late toxicity was calculated by the Kaplan-Meier method. Statistical analysis was performed using SPSS software. Follow-up ranged from 3 to 126 months (median, 48.5 months; mean, 56.8 months). Results: None of the patients experienced Grade 3 or 4 rectal toxicity. Four patients experienced Grade 2 late rectal toxicity. The 5-year actuarial freedom from developing late Grade 2 rectal toxicity was 81%. At a median follow-up of 48.5 months, 23 patients were alive and had no evidence of disease with a median prostate-specific antigen for the sample of 0.1 ng/mL (range, <0.05-0.88 ng/mL). One patient died of other causes unrelated to his prostate cancer. Conclusions: Prostate brachytherapy is well tolerated in patients with a history of controlled IBD. Therefore, brachytherapy should be considered a viable therapeutic option in this patient population

  15. Phase Ⅱ study of protracted irinotecan infusion and a low-dose cisplatin for metastatic gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Hiroshi Imamura; Arimichi Takabayashi; Hideaki Tsukuma; Masataka Ikeda; Hiroshi Furukawa; Toshimasa Tsujinaka; Kazumasa Fujitani; Kenji Kobayashi; Hiroyuki Narahara; Michio Kato; Haruhiko Imamoto

    2006-01-01

    AIM: To test protracted irinotecan infusion plus a lowdose cisplatin in this Phase Ⅱ trial to decrease its toxicity.METHODS: The eligibility criteria were: (1) histologically proven measurable gastric cancer; (2) performance status of 0 or 1; (3) no prior chemotherapy or completion of prior therapy at least 4 wk before enrollment; (4)adequate function of major organs; (5) no other active malignancy; and (6) written informed consent. The regimen consisted of irinotecan (60 mg/m2) on d 1 and 15 by 24-h infusion and cisplatin (10 mg/m2) on d 12 2, 3,15, 16, and 17. Treatment was repeated every 4 wk.RESULTS: Thirty-one patients were registered between April 2000 and January 2001. The response rate for all 31 patients, 20 patients without prior chemotherapy, and 11 patients with prior chemotherapy was 52% (16/31),60% (12/20), and 36% (4/11), respectively. The median survival time was 378 d. The median number of courses given to all patients was 2. Grade 4 neutropenia occurred in 11 (35%) patients, while grade 3 to 4 diarrhea or nausea occurred in 1 (3%) and 3 (10%) patients,respectively. Fatigue was minimal as grade 1 fatigue was found only in 3 (10%) patients. Other adverse events were mild and no treatment-related deaths occurred.CONCLUSION: This regimen showed a high level of activity and acceptable toxicity in patients with metastatic gastric cancer.

  16. Microarray analysis of differentially expressed genes in the kidneys and testes of mice after long-term irradiation with low-dose-rate γ-rays

    International Nuclear Information System (INIS)

    Measuring global gene expression using cDNA or oligonucleotide microarrays is an effective approach to understanding the complex mechanisms of the effects of radiation. However, few studies have been carried out that investigate gene expression in vivo after prolonged exposure to low-dose-rate radiation. In this study, C57BL/6J mice were continuously irradiated with γ-rays for 485 days at dose-rates of 0.032-13 μGy/min. Gene expression profiles in the kidney and testis from irradiated and unirradiated mice were analyzed, and differentially expressed genes were identified. A combination of pathway analysis and hierarchical clustering of differentially expressed genes revealed that expression of genes involved in mitochondrial oxidative phosphorylation was elevated in the kidney after irradiation at the dose-rates of 0.65 μGy/min and 13 μGy/min. Expression of cell cycle-associated genes was not profoundly modulated in the kidney, in contrast to the response to acute irradiation, suggesting a threshold in the dose-rate for modulation of the expression of cell cycle-related genes in vivo following exposure to radiation. We demonstrated that changes to the gene expression profile in the testis were largely different from those in the kidney. The Gene Ontology categories 'DNA metabolism', 'response to DNA damage' and 'DNA replication' overlapped significantly with the clusters of genes whose expression decreased with an increase in the dose-rate to the testis. These observations provide a fundamental insight into the organ-specific responses to low-dose-rate radiation. (author)

  17. Low-dose-rate high-let radiation cytogenetic effects on mice in vivo as model of space radiation action on mammalian

    Science.gov (United States)

    Sorokina, Svetlana; Zaichkina, Svetlana; Rozanova, Olga; Aptikaeva, Gella; Romanchenko, Sergei; Smirnova, Helene; Dyukina, Alsu; Peleshko, Vladimir

    At present time little is known concerning the biological effects of low-dose-rate high-LET radiation exposure in space. The currently available experimental data on the biological effect of low doses of chronic radiation with high-LET values, which occur under the conditions of aircraft and space flights, have been primarily obtained in the examinations of pilots and astronauts after flights. Another way of obtaining this kind of evidence is the simulation of irradiation conditions during aircraft and space flights on high-energy accelerators and the conduction of large-scale experiments on animals under these conditions on Earth. In the present work, we investigated the cytogenetic effects of low-dose-rate high-LET radiation in the dose ranges of 0.2-30 cGy (1 cGy/day) and 0.5-16 cGy (0.43 cGy/day) in the radiation field behind the concrete shield of the Serpukhov accelerator of 70 GeV protons that simulates the spectral and component composition of radiation fields formed in the conditions of high-altitude flights on SHK mice in vivo. The dose dependence, adaptive response (AR) and the growth of solid tumor were examined. For induction of AR, two groups of mice were exposed to adapting doses of 0.2-30 cGy and the doses of 0.5-16 cGy of high-LET radiation. For comparison, third group of mice from unirradiated males was chronically irradiated with X-rays at adapting doses of 10 cGy (1 cGy/day). After a day, the mice of all groups were exposed to a challenging dose of 1.5 Gy of X-rays (1 Gy/min). After 28 h, the animals of all groups were killed by the method of cervical dislocation. Bone marrow specimens for calculating micronuclei (MN) in polychromatic erythrocytes (PCE) were prepared by a conventional method with minor modifications. The influence of adapting dose of 16 cGy on the growth of solid tumor of Ehrlich ascite carcinoma was estimated by measuring the size of the tumor at different times after the inoculation of ascitic cells s.c. into the femur. It was

  18. Low-dose radiation epidemiology studies: status and issues.

    Science.gov (United States)

    Shore, Roy E

    2009-11-01

    Although the Japanese atomic bomb study and radiotherapy studies have clearly documented cancer risks from high-dose radiation exposures, radiation risk assessment groups have long recognized that protracted or low exposures to low-linear energy transfer radiations are key radiation protection concerns because these are far more common than high-exposure scenarios. Epidemiologic studies of human populations with low-dose or low dose-rate exposures are one approach to addressing those concerns. A number of large studies of radiation workers (Chernobyl clean-up workers, U.S. and Chinese radiological technologists, and the 15-country worker study) or of persons exposed to environmental radiation at moderate to low levels (residents near Techa River, Semipalatinsk, Chernobyl, or nuclear facilities) have been conducted. A variety of studies of medical radiation exposures (multiple-fluoroscopy, diagnostic (131)I, scatter radiation doses from radiotherapy, etc.) also are of interest. Key results from these studies are summarized and compared with risk estimates from the Japanese atomic bomb study. Ideally, one would like the low-dose and low dose-rate studies to guide radiation risk estimation regarding the shape of the dose-response curve, DDREF (dose and dose-rate effectiveness factor), and risk at low doses. However, the degree to which low-dose studies can do so is subject to various limitations, especially those pertaining to dosimetric uncertainties and limited statistical power. The identification of individuals who are particularly susceptible to radiation cancer induction also is of high interest in terms of occupational and medical radiation protection. Several examples of studies of radiation-related cancer susceptibility are discussed, but none thus far have clearly identified radiation-susceptible genotypes. PMID:19820457

  19. Solar Variability and the Near-Earth Environment: Mining Enhanced Low Dose Rate Sensitivity Data From the Microelectronics and Photonics Test Bed Space Experiment

    Science.gov (United States)

    Turflinger, T.; Schmeichel, W.; Krieg, J.; Titus, J.; Campbell, A.; Reeves, M.; Marshall (P.); Hardage, Donna (Technical Monitor)

    2004-01-01

    This effort is a detailed analysis of existing microelectronics and photonics test bed satellite data from one experiment, the bipolar test board, looking to improve our understanding of the enhanced low dose rate sensitivity (ELDRS) phenomenon. Over the past several years, extensive total dose irradiations of bipolar devices have demonstrated that many of these devices exhibited ELDRS. In sensitive bipolar transistors, ELDRS produced enhanced degradation of base current, resulting in enhanced gain degradation at dose rates 1 rd(Si)/s. This Technical Publication provides updated information about the test devices, the in-flight experiment, and both flight-and ground-based observations. Flight data are presented for the past 5 yr of the mission. These data are compared to ground-based data taken on devices from the same date code lots. Information about temperature fluctuations, power shutdowns, and other variables encountered during the space flight are documented.

  20. Correlation between the rate of bioreduction of nitroxide spin label by human tumor cells and their low-dose radiation response

    International Nuclear Information System (INIS)

    The authors discuss a correlation observed between the bioreduction of nitroxide spin label by four human tumor cell lines and a normal tissue fibroblast clone and their low-dose radiation response, specifically their DQ. In measurements of the bioreduction rate of several other cell lines, this correlation appears to persist. In order to define the mechanism of this correlation, they have begun by subtly altering the measurement conditions. The original conditions for measurement involved adding the spin label to cells whose culture medium had been changed (the label was added to the new medium). By delaying the addition of the label to the culture medium, they substantially reduced the variation of the bioreduction rate between the cell lines. This implies that the fresh medium provides a nonspecific irritant or disequilibrium to the cultured cell system to which they response variably by accelerating, among other things, the metabolic process responsible for spin label bioreduction

  1. Dosimetry TL 'in vivo' for the quality control in radiotherapy with Co-60 and brachytherapy of low dose rate

    International Nuclear Information System (INIS)

    Full text: The dosimetry 'in vivo' is used frequently as a valuable tool for the quality control in radiotherapy. Measurements of the entry and exit doses provide us of information on the precision of the technique or the procedure of used treatment; the measurement of the doses in rectal or bladder in gynecological implants contribute to perfect or to adjust the procedures in brachytherapy. Also systematic errors can be identified in particular situations that allow to optimize the treatment and to minimize errors. A study in the service of Radiotherapy of the San Roque Hospital, was realized for to control the procedures used in the treatment of different cancer therapy. Patients were selected, to which were carried out a routine planning with the system of planning of on line treatment Prowess 3000 that then were controlled with thermoluminescent dosemeters 'in vivo' using the Ceprocor Services. Skin doses were measurement in treatment of breast, pelvis, thorax, head and neck, and doses was measured in cavities of the body as oral cavity, rectal, esophagus, etc., placing the TLD inside special catheters. In the case of doses in skin, the dosimeters was placed in acrylic badges. A very good agreement was found between the measurements 'in vivo' and the plans of the planner. In some cases the control allowed to modify the doses to avoid organs damage for the radiation fields. (author)

  2. In vivo dosimetry using electron paramagnetic resonance in L-alanine in gynecological low dose rate brachytherapy

    International Nuclear Information System (INIS)

    To present the results of in vivo dosimetry performed on 15 patients treated for gynecological cancer with the aim of optimizing the detector design and its application in body cavities and comparing the doses measured in vivo with those calculated by the Plato (Nucletron) system of brachytherapy treatment planning. Electron paramagnetic resonance (EPR) is, as a dosimetric method, based on the detection of free radicals generated by ionizing radiation in L-alanine. The concentration of free radicals is proportional to the absorbed dose and is determined by the EPR technique. The detectors appear as small cellulose capsules (outer diameter 5 mm, length 15 mm), tightly filled with crystalline L-alanine powder. The doses from 137Cs brachytherapy sources were measured in selected points inside the rectum and vagina. The relative deviations of measured doses from those calculated by the treatment planning system ranged from -28% to +40%. The mean deviations from the prescribed doses were relatively low (+1% for detectors placed in the rectum, - 10% for detectors placed in the vagina). However, due to a low number of samples and large standard deviations of the mean values (±23% and ±11% for detectors placed in the rectum and the vagina, respectively), the deviations of the mean values are of low statistical significance. The accuracy of the measurements was analyzed and is hereby discussed. The main sources of the differences between the measured and calculated dose should, generally, be attributed to uncertainties in the determination of the detector position inside the body as ascertained from the radiographs and to uncontrollable motion of detectors during treatment. (author)

  3. 低剂量螺旋CT扫描在周围型肺癌诊断中的临床应用价值%Low Dose Spiral CT Scanning in the Diagnosis of Peripheral Lung Cancer Clinical Application Value

    Institute of Scientific and Technical Information of China (English)

    何揆

    2014-01-01

    , Ye Zheng sign, blood vessels, cluster sign, pleural sag and obstructive pneumonia or atelectasis rate of peripheral lung cancer signs show no significant decrease, the dif erence is not statistical y significant ( > 0. 05). Conclusion Low-dose spiral CT scanning in reducing radiation dose of at the same time, also can clearly show various signs of peripheral lung cancer, in the diagnosis of peripheral lung cancer has high clinical value.

  4. Screenings of lung cancer with low dose spiral CT: results of a three year pilot study and design of the randomised controlled trial Italung-CT

    International Nuclear Information System (INIS)

    Purpose: To report the results of a three-year observational pilot study of lung cancer screening with low dose computed tomography (CT) and to present the study design of a randomised clinical trial named as Italung CT. Materials and methods: Sixty (47 males and 13 females, mean age 64±4.5 years) heavy smokers (at least 20 packs-year) underwent three low-dose spiral CT screening tests one year apart on a single slice or multislice CT scanner. Indeterminate nodules were managed according to the recommendations of the Early Lung Cancer Action Project. Results: Indeterminate nodules were observed in 33 (55%) of the subjects (60% at the baseline screening test, 24% at the first annual test and 16% at the second annual test). The size of the largest indeterminate nodule was <5mm in diameter in 20 subjects. 10 of whom showed the nodule at the baseline test. Forty-five subjects (75%) completed the first annual test and 42 (70%) the second annual test. One (1.6%) prevalent lung cancer (adenosquamous carcinoma) and one (2.2%) incident lung cancer (small cell cancer at the first annual examination) were observed, as well as pulmonary localisation of Hodgkin's lymphoma (at the second annual test). In addition, one subject underwent lung surgery for a chondromatous hamartoma. Conclusions: The results of the pilot study are substantially in line with those of other observational studies of greater sample size. This justifies optimism about the reliability of the results in the screened arm of the Italung Ct trial which hast just began

  5. Hair medullary cell counts following low-dose-rate γ-and high-energy neutron irradiation

    International Nuclear Information System (INIS)

    Young adult Balb/c mice with hair follicles synchronously in the middle of the hair growth cycle received whole-body or partial-body doses of γ-radiation or neutron radiation. The follicles were analysed 3 days after irradiation in dose-response experiments, or at various times after a constant dose in time-course experiments, for changes in the number of cells in the forming medulla of the hair in the region just above the germinal matrix of the growing (anagen) hair follicle. Time-course experiments showed that 3 days after irradiating growing follicles (2 or 4 Gy of γ-rays or 1 or 2 Gy of neutrons), maximum reduction in the hair medullary cell count (HMCC) was observed. Survival curves were obtained for γ-rays over a range of dose-rates (4.0-0.0023 Gy/min) using total doses between 0.5 and 5.0 Gy. A survival curve was also obtained for 62 MeV neutrons at a dose-rate of 0.31 Gy/min and doses of 0.1-2.0 Gy. (author)

  6. Nutrient intake and nutrient patterns and risk of lung cancer among heavy smokers: results from the COSMOS screening study with annual low-dose CT

    International Nuclear Information System (INIS)

    The role of nutrients in lung cancer aetiology remains controversial and has never been evaluated in the context of screening. Our aim was to investigate the role of single nutrients and nutrient patterns in the aetiology of lung cancer in heavy smokers. Asymptomatic heavy smokers (≥20 pack-years) were invited to undergo annual low-dose computed tomography. We assessed diet using a self-administered food frequency questionnaire and collected information on multivitamin supplement use. We performed principal component analysis identifying four nutrient patterns and used Cox proportional Hazards regression to assess the association between nutrients and nutrients patterns and lung cancer risk. During a mean follow-up of 5.7 years, 178 of 4,336 participants were diagnosed with lung cancer by screening. We found a significant risk reduction of lung cancer with increasing vegetable fat consumption (HR for highest vs. lowest quartile = 0.50, 95 % CI = 0.31–0.80; P-trend = 0.02). Participants classified in the high “vitamins and fiber” pattern score had a significant risk reduction of lung cancer (HR = 0.57; 95 % CI = 0.36–0.90, P-trend = 0.01). Among heavy smokers enrolled in a screening trial, high vegetable fat intake and adherence to the “vitamin and fiber” nutrient pattern were associated with reduced lung cancer incidence.

  7. Array-CGH analysis of mouse malignant lymphomas. Effects of chronic exposure to low-dose-rate γ-radiation on tumorigenesis

    International Nuclear Information System (INIS)

    We previously reported that mice that were chronically irradiated with γ-rays at low dose rates had significantly shorter life spans than unirradiated controls. The major cause of this life-shortening is considered to be the earlier onset and/or the faster progression of malignant lymphomas in the irradiated groups. In this study, chromosomal aberrations in a total of 54 malignant lymphomas from mice irradiated with a dose rate of 21 mGy/day and nonirradiated mice were precisely compared by microarray-based comparative genomic hybridization (array-CGH) analysis. Array-CGH profiles showed that about two-thirds of the tumors had aneuploidy genotypes, in which numeric aberrations of chromosomes 12, 14, 15, 16, and X were observed frequently in the unirradiated group while that of chromosome 15 predominated in the irradiated group. In addition, copy-number alterations were frequently identified on partial chromosomal regions harboring the following oncogenes and tumor suppressor genes: c-myc, N-myc, notch-1, notch-2, hes-1, akt-1, akt-2, akt-3, bcl-6, bcl-10, bcl-11a, bcl-11b, pim-2, BCoR, XIAP, rhoE, p16INK4a, p15INK4b, p73, p27Kip1, RB, and pten. If aberrations extending across whole-chromosomal and partial-chromsomal regions are counted together, gains on chromosomes 3, 12, 13, 14, 16 and X can be associated preferentially with the unirradiated group, whereas gains on chromosome 15, along with losses on chromosomes 4 and 14, were detected more frequently in the irradiated group. These observations offer insights into how low-dose-rate irradiation caused the earlier onset and/or the faster progression of tumors, as well as into the molecular pathogenesis of murine lymphomas. (author)

  8. Effect of irradiation temperature and strain rate on the mechanical properties of V-4Cr-4Ti irradiated to low doses in fission reactors

    Energy Technology Data Exchange (ETDEWEB)

    Zinkle, S.J.; Snead, L.L.; Rowcliffe, A.F.; Alexander, D.J.; Gibson, L.T. [Oak Ridge National Lab., TN (United States)

    1998-09-01

    Tensile tests performed on irradiated V-(3-6%)Cr-(3-6%)Ti alloys indicate that pronounced hardening and loss of strain hardening capacity occurs for doses of 0.1--20 dpa at irradiation temperatures below {approximately}330 C. The amount of radiation hardening decreases rapidly for irradiation temperatures above 400 C, with a concomitant increase in strain hardening capacity. Low-dose (0.1--0.5 dpa) irradiation shifts the dynamic strain aging regime to higher temperatures and lower strain rates compared to unirradiated specimens. Very low fracture toughness values were observed in miniature disk compact specimens irradiated at 200--320 C to {approximately}1.5--15 dpa and tested at 200 C.

  9. Comparative response of dogs and monkeys to sublethal acute and continuous low dose-rate gamma-ray exposure

    International Nuclear Information System (INIS)

    Monkeys (Macaca mulatta) and dogs (beagle) were given thirteen 100-rad gamma-ray doses at 28-day intervals. The comparative response (injury and recovery) of the hematopoietic system of the two species was observed at 7-day intervals during the exposure regime. At 84 days after the thirteenth gamma-ray dose, the 1300-rad conditioned and control dogs and monkeys were challenged continuously with 35 R/day until death to determine the amount of radiation-induced injury remaining in conditioned animals as a reduction in mean survival time. Dogs (50 percent) and monkeys (8 percent) died from injury incurred during the conditioning exposures. Thus, the comparative response of dogs and monkeys to dose protraction by acute dose fractionation was similar to what might be expected from a single acute dose. Mean survival times for nonconditioned dogs and monkeys during continuous exposure at 35 R/day were the same (approximately 1400 h). Thus, hematopoietic response of the two species by this method of dose protraction was not significantly different. Mean survival times of conditioned dogs and monkeys during the continuous 35 R/day gamma-ray challenge exposure were greater than for their control counterparts. Thus, the long-term radiation-induced injury was not measurable by this method. Conditioning doses of more than four times the acute LD50-30 in dogs and approximately two times that of monkeys served only to increase both mean survival time and variance in a gamma-ray stress environment with a dose rate of 35 R/day

  10. Adaptive response and genetic instability induced by a low-dose rate radiation simulating the high-altitude flight conditions on mice in vivo

    International Nuclear Information System (INIS)

    Complete text of publication follows. In the present work, we investigated the effect of a low-dose rate of high-LET radiation that simulates the spectral and component composition of radiation fields formed in the conditions of high-altitude flights on mice in vivo. The dose dependence, adaptive response, and genetic instability in generation F1 born from males irradiated under these conditions were examined in polychromatic erythrocytes of bone marrow using the micronucleus test. Two-month-old males of SHK white mongrel mice were used. Irradiation was performed for 24 h a day in the radiation field behind the concrete shield of the U-70 accelerator of 70 GeV protons (Serpukhov), which adequately simulates radiation field formed in the atmosphere at a height of about 10 km, to accumulate doses of 11.5, 21.5 and 31.5 cGy (1 cGy/day). The experiments demonstrated that: 1) irradiation of mice in vivo with these doses of low dose rate high-LET radiation leads to an increase in cytogenetic damage in polychromatic erythrocytes; 2) irradiation of mice with these doses induces no adaptive response in polychromatic erythrocytes as opposite to γ-radiation; and 3) in mice of the F1 generation born from males irradiated with doses of 11.5, 21.5 and 31.5 cGy, an increase in sensitivity to additional irradiation with a dose of 1.5 Gy of γ-radiation and the absence of adaptive response compared with the descendants of unirradiated males occur. These data indicate a genetic instability in generation F1 born from irradiated males.

  11. Combined use of positron emission tomography and volume doubling time in lung cancer screening with low-dose CT scanning

    DEFF Research Database (Denmark)

    Ashraf, H; Dirksen, A; Jakobsen, Annika Loft;

    2011-01-01

    In lung cancer screening the ability to distinguish malignant from benign nodules is a key issue. This study evaluates the ability of positron emission tomography (PET) and volume doubling time (VDT) to discriminate between benign and malignant nodules....

  12. Influence of dose rate on leukemogenesis in mice irradiated by gamma rays at a high dose rate or low dose rates

    International Nuclear Information System (INIS)

    The purpose of this study was to assess the extent of the effect of dose rate on tumorigenesis, focusing on myeloid leukemia, one of the typical neoplasias induced by radiation. In the experiment, C3H/He male mice were irradiated with gamma-rays at various doses at a dose rate of 0.88Gy/min, or 0.30mGy/min or 0.016mGy/min, and equations of dose response curves for leukemia were derived from data on the incidence in each group by the least square method. Each equation fitted well with the linear quadratic equation by coefficiency of more than 90%. The extent of the dose rate effect was expressed as dose and dose rate effectiveness factor (DDREF) based on the definition by ICRP-Publication 60. We obtained DDREF by dividing the slope factor of the tangential line of group H (0.88Gy/min) by that of group L-1 (0.30mGy/min) or L-2 (0.016mGy/min), the tangential lines being drawn from the value of the incidence of the control group on the dose response curve. The value of group H to group L-1 was 12.00/1.71=7.022, and that of group H to group L-2 was 12.00/2.56=4.69. These values indicated that reduction of the dose rate caused a decrease in the induction of leukemia, ranging between the values 2 and 10 in the NCRP 1990 report. (author)

  13. Reanalysis of cancer mortality in Japanese A-bomb survivors exposed to low doses of radiation: bootstrap and simulation methods

    Directory of Open Access Journals (Sweden)

    Dropkin Greg

    2009-12-01

    Full Text Available Abstract Background The International Commission on Radiological Protection (ICRP recommended annual occupational dose limit is 20 mSv. Cancer mortality in Japanese A-bomb survivors exposed to less than 20 mSv external radiation in 1945 was analysed previously, using a latency model with non-linear dose response. Questions were raised regarding statistical inference with this model. Methods Cancers with over 100 deaths in the 0 - 20 mSv subcohort of the 1950-1990 Life Span Study are analysed with Poisson regression models incorporating latency, allowing linear and non-linear dose response. Bootstrap percentile and Bias-corrected accelerated (BCa methods and simulation of the Likelihood Ratio Test lead to Confidence Intervals for Excess Relative Risk (ERR and tests against the linear model. Results The linear model shows significant large, positive values of ERR for liver and urinary cancers at latencies from 37 - 43 years. Dose response below 20 mSv is strongly non-linear at the optimal latencies for the stomach (11.89 years, liver (36.9, lung (13.6, leukaemia (23.66, and pancreas (11.86 and across broad latency ranges. Confidence Intervals for ERR are comparable using Bootstrap and Likelihood Ratio Test methods and BCa 95% Confidence Intervals are strictly positive across latency ranges for all 5 cancers. Similar risk estimates for 10 mSv (lagged dose are obtained from the 0 - 20 mSv and 5 - 500 mSv data for the stomach, liver, lung and leukaemia. Dose response for the latter 3 cancers is significantly non-linear in the 5 - 500 mSv range. Conclusion Liver and urinary cancer mortality risk is significantly raised using a latency model with linear dose response. A non-linear model is strongly superior for the stomach, liver, lung, pancreas and leukaemia. Bootstrap and Likelihood-based confidence intervals are broadly comparable and ERR is strictly positive by bootstrap methods for all 5 cancers. Except for the pancreas, similar estimates of

  14. Comparison of two low-dose rates in vaginal prophylactic pre-operative (PO) brachytherapy (BT) for stage I-II endometrial carcinoma: results of a randomized trial

    International Nuclear Information System (INIS)

    Purpose: Local control, survival, prognostic factors and complications in a prospective randomized trial comparing two vaginal low-dose rates PO BT in early stage endometrial carcinoma are evaluated. Materials and methods: From 1985 to 1988, 107 with stage I-II endometrial carcinoma were randomized to receive a vaginal prophylactic PO BT with a low-dose rate of 0.4 Gy/h or 0.8 Gy/h with a total dose of 50 Gy to 5 mm depth from the surface of the vagina. Patients underwent surgery immediately after the end of PO BT. Surgery consisted of hysterosalpingoophorectomy and pelvic node sampling. External radiotherapy was performed when histological examination evidenced a deep invasion of the myometrium (> (1(2))), or a grade III tumor or a lymph node involvement. Patients were regularly followed up and complications were reported using a common glossary. Results: Patients characteristics were equally distributed in both groups with a median age of 60 (range = 26-82). Previous surgery had been performed in 30 % of the patients. There were 12 % stage II and 93 % adenocarcinomas. Tumour invasion to more than one half of myometrium was found in 25 %. The median duration of PO BT was 7 and 4 days in the 0.4 Gy/h group and 0.8 Gy/h group respectively. Estimated 3-year -event-free survival was 91 % in the 0.4 Gy/h group and 80 % in the 0.8 Gy/h group (p = 0.1). Relapses were observed in 12 patients: 3 in the 0.4 Gy/h group and 9 in the 0.8 Gy/h group. Eight patients presented metastases as a first relapse (1 in the 0.4 Gy/h group and 7 in the 0.8 Gy/h group) and 4 patients a local failure as a first relapse (2 in each group). Prognostic factors for event-free survival included isthmic involvement (3-year event-free survival: 73 %, p = 0.01) and pelvic node involvement (3-year event-free: 20 %, p < 0.0001). A total of 52 complications in 26 patients was observed in the 0.4 Gy/h group and 51 complications in 31 patients in the 0.8 Gy/h group. The most frequent complications were

  15. Increased risk for small cell lung cancer following residential exposure to low-dose radon: A pilot study

    International Nuclear Information System (INIS)

    Alpha track radon detectors were placed in the homes of 35 lung cancer patients and 35 matched controls for a period of 8 to 10 mo. Twenty lung cancer patients had small cell lung carcinoma; 11 had adenocarcinoma, 2 had squamous cell carcinoma, and 2 had unclassified carcinoma among 15 nonsmokers. Mean overall living on ground level was significantly higher in the group with small cell lung carcinoma (50 y ± 15) than among controls (33 y ± 19); the adjusted odds ratio for lung cancer was 5.2 (90% confidence interval [90% CI] = 1.1--24.9) per decade of living on the ground floor for the group with small cell lung carcinoma. Radon exposure of more than 1.0 pci/l in the group with small cell lung carcinoma was associated with increased risk of lung cancer, although it did not reach statistical significance [odds ratio = 1.5 (90% CI = 0.4--5.4)], adjusting for differences in smoking habits. The study supports the presence of a differentially increased risk for small cell lung carcinoma following long-term radon exposure. 12 refs., 2 tabs

  16. Influence of low doses of radiation due to 222Rn on proliferation of fibroblasts and MCF-7 human breast cancer cells in vitro

    International Nuclear Information System (INIS)

    The aim of the present study is to analyze the effects of low doses of radiation due to radon (within the range present in the environment) in the proliferation of normal (fibroblasts) and tumoral (MCF-7 human breast cancer cells) mammalian cells. Both fibroblast and MCF-7 cells were incubated in culture media with different levels of radon (doses of 10-15,000 μGy), or non-radon (control). After incubation the number of cells per plate was measured with a hemocytometer. The dissolution of radon in the culture media decreased the proliferation of MCF-7 cells (not the fibroblasts). Within the range of doses used in this experiment, the lowest as well as the highest doses of radiation had the lowest antiproliferative effects. Intermediate doses strongly decreased the number of final cells with respect to those in the control population

  17. Targeting heat shock protein 70 using gold nanorods enhances cancer cell apoptosis in low dose plasmonic photothermal therapy.

    Science.gov (United States)

    Ali, Moustafa R K; Ali, Hala R; Rankin, Carl R; El-Sayed, Mostafa A

    2016-09-01

    Plasmonic photothermal therapy (PPTT) is a promising cancer treatment where plasmonic nanoparticles are used to convert near infrared light to localized heat to cause cell death, mainly via apoptosis and necrosis. Modulating PPTT to induce cell apoptosis is more favorable than necrosis. Herein, we used a mild treatment condition using gold nanorods (AuNRs) to trigger apoptosis and tested how different cell lines responded to it. Three different cancer cell lines of epithelial origin: HSC (oral), MCF-7 (breast) and Huh7.5 (liver) had comparable AuNRs uptake and were heated to same environmental temperature (under 50 °C). However, Huh7.5 cells displayed a significant increase in cell apoptosis after PPTT as compared to the other two cell lines. As HSP70 is known to increase cellular resistance to heat, we determined relative HSP70 levels in these cells and results indicated that Huh7.5 cells had ten-fold decreased levels of HSP70 as compared with HSC and MCF-7 cells. We then down-regulated HSP70 with a siRNA and observed that all three cell lines displayed significant reduction in viability and an increase in apoptosis after PPTT. As an enhancement to PPTT, we conjugated AuNRs with Quercetin, an inhibitor of HSP70 which displayed anti-cancer effects via apoptosis. PMID:27318931

  18. Late Urinary Side Effects 10 Years After Low-Dose-Rate Prostate Brachytherapy: Population-Based Results From a Multiphysician Practice Treating With a Standardized Protocol and Uniform Dosimetric Goals

    Energy Technology Data Exchange (ETDEWEB)

    Keyes, Mira, E-mail: mkeyes@bccancer.bc.ca; Miller, Stacy; Pickles, Tom; Halperin, Ross; Kwan, Winkle; Lapointe, Vincent; McKenzie, Michael; Spadinger, Ingrid; Pai, Howard; Chan, Elisa K.; Morris, W. James

    2014-11-01

    Purpose: To determine late urinary toxicity (>12 months) in a large cohort of uniformly treated low-dose-rate prostate brachytherapy patients. Methods and Materials: From 1998 to 2009, 2709 patients with National Comprehensive Cancer Network–defined low-risk and low-tier intermediate-risk prostate cancer were treated with Iodine 125 ({sup 125}I) low-dose-rate prostate brachytherapy; 2011 patients with a minimum of 25 months of follow-up were included in the study. Baseline patients, treatment, implant factors, and late urinary toxicity (Radiation Therapy Oncology Group [RTOG] grading system and International Prostate Symptom Score [IPSS]) were recorded prospectively. Time to IPSS resolution, late RTOG genitourinary toxicity was examined with Kaplan-Meier and log-rank tests. Cox proportional hazards regression was done for individual covariates and multivariable models. Results: Median follow-up was 54.5 months (range, 2-13 years). Actuarial toxicity rates reached 27% and 10% (RTOG ≥2 and ≥3, respectively) at 9-13 years. Symptoms resolved quickly in the majority of patients (88% in 6-12 months). The prevalence of RTOG 0, 1, 2, 3, and 4 toxicity with a minimum of 7 years' follow-up was 70%, 21%, 6.4%, 2.3%, and 0.08%, respectively. Patients with a larger prostate volume, higher baseline IPSS, higher D90, acute toxicity, and age >70 years had more late RTOG ≥2 toxicity (all P≤.02). The IPSS resolved slower in patients with lower baseline IPSS and larger ultrasound prostate volume, those not receiving androgen deprivation therapy, and those with higher D90. The crude rate of RTOG 3 toxicity was 6%. Overall the rate of transurethral resection of the prostate was 1.9%; strictures, 2%; incontinence, 1.3%; severe symptoms, 1.8%; late catheterization, 1.3%; and hematuria, 0.8%. The majority (80%) resolved their symptoms in 6-12 months. Conclusion: Long-term urinary toxicity after brachytherapy is low. Although actuarial rates increase with longer

  19. Late Urinary Side Effects 10 Years After Low-Dose-Rate Prostate Brachytherapy: Population-Based Results From a Multiphysician Practice Treating With a Standardized Protocol and Uniform Dosimetric Goals

    International Nuclear Information System (INIS)

    Purpose: To determine late urinary toxicity (>12 months) in a large cohort of uniformly treated low-dose-rate prostate brachytherapy patients. Methods and Materials: From 1998 to 2009, 2709 patients with National Comprehensive Cancer Network–defined low-risk and low-tier intermediate-risk prostate cancer were treated with Iodine 125 (125I) low-dose-rate prostate brachytherapy; 2011 patients with a minimum of 25 months of follow-up were included in the study. Baseline patients, treatment, implant factors, and late urinary toxicity (Radiation Therapy Oncology Group [RTOG] grading system and International Prostate Symptom Score [IPSS]) were recorded prospectively. Time to IPSS resolution, late RTOG genitourinary toxicity was examined with Kaplan-Meier and log-rank tests. Cox proportional hazards regression was done for individual covariates and multivariable models. Results: Median follow-up was 54.5 months (range, 2-13 years). Actuarial toxicity rates reached 27% and 10% (RTOG ≥2 and ≥3, respectively) at 9-13 years. Symptoms resolved quickly in the majority of patients (88% in 6-12 months). The prevalence of RTOG 0, 1, 2, 3, and 4 toxicity with a minimum of 7 years' follow-up was 70%, 21%, 6.4%, 2.3%, and 0.08%, respectively. Patients with a larger prostate volume, higher baseline IPSS, higher D90, acute toxicity, and age >70 years had more late RTOG ≥2 toxicity (all P≤.02). The IPSS resolved slower in patients with lower baseline IPSS and larger ultrasound prostate volume, those not receiving androgen deprivation therapy, and those with higher D90. The crude rate of RTOG 3 toxicity was 6%. Overall the rate of transurethral resection of the prostate was 1.9%; strictures, 2%; incontinence, 1.3%; severe symptoms, 1.8%; late catheterization, 1.3%; and hematuria, 0.8%. The majority (80%) resolved their symptoms in 6-12 months. Conclusion: Long-term urinary toxicity after brachytherapy is low. Although actuarial rates increase with longer follow

  20. Low-dose computed tomography screening for lung cancer in a clinical setting: essential elements of a screening program.

    Science.gov (United States)

    McKee, Brady J; McKee, Andrea B; Kitts, Andrea Borondy; Regis, Shawn M; Wald, Christoph

    2015-03-01

    The purpose of this article is to review clinical computed tomography (CT) lung screening program elements essential to safely and effectively manage the millions of Americans at high risk for lung cancer expected to enroll in lung cancer screening programs over the next 3 to 5 years. To optimize the potential net benefit of CT lung screening and facilitate medical audits benchmarked to national quality standards, radiologists should interpret these examinations using a validated structured reporting system such as Lung-RADS. Patient and physician educational outreach should be enacted to support an informed and shared decision-making process without creating barriers to screening access. Programs must integrate smoking cessation interventions to maximize the clinical efficacy and cost-effectiveness of screening. At an institutional level, budgets should account for the necessary expense of hiring and/or training qualified support staff and equipping them with information technology resources adequate to enroll and track patients accurately over decades of future screening evaluation. At a national level, planning should begin on ways to accommodate the upcoming increased demand for physician services in fields critical to the success of CT lung screening such as diagnostic radiology and thoracic surgery. Institutions with programs that follow these specifications will be well equipped to meet the significant oncoming demand for CT lung screening services and bestow clinical benefits on their patients equal to or beyond what was observed in the National Lung Screening Trial. PMID:25658476

  1. Acute dose and low dose-rate irradiation of carcinoma cells expressing human papillomavirus E6 and E7 oncoproteins - the significance of p53, Rb and G1 arrest status

    International Nuclear Information System (INIS)

    Purpose: The development of carcinomas in a number of sites including the cervix, vulva and anus have been associated with cellular infection by human papillomaviruses (HPV), including HPV 16 and HPV 18. The mechanism by which these viruses contribute to tumor development or progression seems in part to be related to the integration of the viral genome into the host cells DNA, and the binding of p53 protein by the HPV E6 oncoprotein as well as the binding of the retinoblastoma (Rb) protein and Rb-like proteins by the HPV E7 oncoprotein. These interactions lead to loss of p53 and Rb function including loss of the G1 cell cycle checkpoint. Although it is believed that both p53 and Rb play a role in the radiosensitivity of the cell, whether alteration in either protein enhances or diminishes cellular radiation response is not clear from the literature. Because HPV-associated tumors such as cervical cancer are often treated with acute dose and/or low dose-rate radiation, we set out to evaluate the radiation response of several carcinoma cell sublines expressing either oncogenic E6 or E7 to both types of radiation, and to determine if p53/Rb dependent G1 arrest is an important determinant of cell fate after irradiation. Materials and Methods: We have previously developed a series of RKO colorectal carcinoma cell sublines expressing both low-risk (HPV 11) and high-risk (HPV 16) E6 and E7 genes. p53-dependent G1 arrest is intact in RKO parental cells and cells expressing low-risk E6 proteins, while the G1 arrest is abrogated in cells expressing high-risk E6 or E7. Clonogenic survival was assessed after exposure to acute dose (1 Gy/min) and low dose-rate (0.25 Gy/hour) radiation. The radiobiologic parameters α, β and the surviving fraction at 2 Gy (SF2) were determined. SDS-PAGE/immunoblotting was carried out to assess both p53 and p21WAF1/CIP1 levels after exposure to radiation. Flow cytometry was performed before and after exposure to low dose-rate radiation to confirm

  2. M-BAND Analysis of Chromosome Aberration In Human Epithelial Cells exposed to Gamma-ray and Secondary Neutrons of Low Dose Rate

    Science.gov (United States)

    Hada, M.; Saganti, P. B.; Gersey, B.; Wilkins, R.; Cucinotta, F. A.; Wu, H.

    2007-01-01

    High-energy secondary neutrons, produced by the interaction of galactic cosmic rays with the atmosphere, spacecraft structure and planetary surfaces, contribute to a significant fraction to the dose equivalent in crew members and passengers during commercial aviation travel, and astronauts in space missions. The Los Alamos Nuclear Science Center (LANSCE) neutron facility's "30L" beam line is known to generate neutrons that simulate the secondary neutron spectrum of the Earth's atmosphere at high altitude. The neutron spectrum is also similar to that measured onboard spacecraft like the MIR and the International Space Station (ISS). To evaluate the biological damage, we exposed human epithelial cells in vitro to the LANSCE neutron beams at an entrance dose rate of 2.5 cGy/hr or gamma-ray at 1.7cGy/hr, and assessed the induction of chromosome aberrations that were identified with mBAND. With this technique, individually painted chromosomal bands on one chromosome allowed the identification of inter-chromosomal aberrations (translocation to unpainted chromosomes) and intra-chromosomal aberrations (inversions and deletions within a single painted chromosome). Compared to our previous results for gamma-rays and 600 MeV/nucleon Fe ions of high dose rate, the neutron data showed a higher frequency of chromosome aberrations. However, detailed analysis of the inversion type revealed that all of the three radiation types in the study induced a low incidence of simple inversions. The low dose rate gamma-rays induced a lower frequency of chromosome aberrations than high dose rate gamma-rays, but the inversion spectrum was similar for the same cytotoxic effect. The distribution of damage sites on chromosome 3 for different radiation types will also be discussed.

  3. Semicontinuous Low-Dose-Rate Teletherapy for the Treatment of Recurrent Glial Brain Tumors: Final Report of a Phase I/II Study

    International Nuclear Information System (INIS)

    Purpose: Semicontinuous low-dose-rate teletherapy (SLDR) is a novel irradiation strategy that exploits the increased radiosensitivity of glial cells in a narrow range of reduced dose rate. We present the final report of a prospective Phase I/II study testing the feasibility of SLDR for the treatment of recurrent gliomas. Methods and Materials: Patients with previously irradiated recurrent gliomas were enrolled from November 1993 to March 1998. Patients received SLDR, delivered 6 to 8 hours/day at a dose rate of 40 to 50 cGy/hour for a total dose of 30 to 35 Gy given over 12 days using a modified cobalt-60 treatment unit. Acute central nervous system toxicity after SLDR treatment was the primary endpoint. Overall survival was a secondary endpoint. Results: Twenty patients were enrolled (14 World Health Organization Grade 4 glioma, 5 Grade 2 glioma, 1 ependymoma). No patients developed ≥Grade 3 central nervous system toxicity at 3 months without radiographic evidence of tumor progression. Overall survival after SLDR was 56% at 6 months, 28% at 12 months, and 17% at 24 months. One patient survived >48 months, and 1 patient survived >60 months after SLDR treatment. Re-resection before SLDR treatment significantly improved 1-year overall survival for all patients and patients with Grade 4 glioma. Conclusion: The delivery of SLDR is feasible in patients with recurrent gliomas and resulted in improved outcomes for patients who underwent re-resection. There were 2 long-term survivors (>48 months). This pilot study supports the notion that reduced dose rate influences the efficacy and tolerance of reirradiation in the treatment of recurrent gliomas.

  4. Effect of a vitamin D3-based nutritional supplement ('Videchol') on carbohydrate metabolism of rats following chronic low dose-rate irradiation

    International Nuclear Information System (INIS)

    In this study we evaluated the effects of the administration of a vitamin D3 preparation 'Videchol' to chronically irradiated rats (1 cGy day-1) by the assessment of the activities of several glycolytic enzymes: lactic dehydrogenase (LDH) (EC 1.1.1.28), pyruvate kinase (PK) (EC 2.7.1.40) and hexokinase (HK) (EC 2.7.1.1), in populations of erythroid and myeloid bone marrow cells. Videchol treatment of irradiated rats led to the normalisation of HK and LDH activity at cumulative doses of around 30 cGy in granulocyte-monocyte cells and to normalisation of LDH and PK activities in erythroid cells starting at 20 cGy in comparison with irradiated rats who did not receive Videchol. The reaction kinetic parameters of LDH in erythrocytes changed according to the redistribution pattern of the isozymes throughout the different stages of the experiment. The administration of Videchol to irradiated rats led to a rearrangement of the LDH isozymes ratio characterised by kinetic properties more comparable to those of the controls. Thus, vitamin D3 appears to induce a normalisation of carbohydrate metabolism in rats chronically irradiated with low dose-rate ionising radiation. (author)

  5. Behavior and awareness of thyroid cancer patients in Korea having non-hospitalized low-dose radioiodine treatment with regard to radiation safety

    International Nuclear Information System (INIS)

    With the recent increase in incidence of thyroid cancer, non-hospitalized low-dose (NH-LD) radioiodine treatment (RIT) has also increased rapidly. The radioactivity limit that is allowed to be administered without hospitalization depends on individual calculation, based partly on patients' behavior. In this study, Korean patients' behavior in relation to radiation safety in NHLD RIT was surveyed. A total of 218 patients who underwent NH-LD RIT of 1.1 GBq 131I in a single center were surveyed. The patients underwent RIT with a standard protocol and the survey was performed by interview when they visited subsequently for a whole-body scan. The survey questionnaire included three parts of questions: general information, behavior relating to isolation during RIT, and awareness of radiation safety. After administration of radioiodine, 40% of patients who returned home used mass transportation, and another 47% went home by taxi or in car driven by another person. Isolation at home was generally sufficient. However, 7% of patients did not stay in a separate room. Among the 218 patients, 34% did not go home and chose self-isolation away from home, mostly due to concerns about radiation safety of family members. However, the places were mostly public places, including hotels, resorts, and hospitals. About half of the patients replied that access to radiation safety information was not easy and their awareness of radiation safety was not satisfactory. As a result, 45% of patients wanted hospitalized RIT. In many countries, including Korea, RIT is continuously increasing. Considering the radiation safety of patients' family members or the public and the convenience of patients, the pretreatment education of patients should be enhanced. In addition, the hospitalization of patients having low-dose therapy is recommended to be seriously considered and expanded, with the expansion of dedicated treatment facilities

  6. A randomized phase II clinical trial of personalized peptide vaccination with metronomic low-dose cyclophosphamide in patients with metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Noguchi, Masanori; Moriya, Fukuko; Koga, Noriko; Matsueda, Satoko; Sasada, Tetsuro; Yamada, Akira; Kakuma, Tatsuyuki; Itoh, Kyogo

    2016-02-01

    This study investigated the effect of metronomic cyclophosphamide (CPA) in combination with personalized peptide vaccination (PPV) on regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC), and whether it could improve the antitumor effect of PPV. Seventy patients with metastatic castration-resistant prostate cancer were randomly assigned (1:1) to receive PPV plus oral low-dose CPA (50 mg/day), or PPV alone. PPV treatment used a maximum of four peptides chosen from 31 pooled peptides according to human leukocyte antigen types and antigen-specific humoral immune responses before PPV, for 8 subcutaneous weekly injections. Peptide-specific cytotoxic T lymphocyte (CTL) and immunoglobulin G responses were measured before and after PPV. The incidence of grade 3 or 4 hematologic adverse events was higher in the PPV plus CPA arm than in the PPV alone arm. Decrease in Treg and increase in MDSC were more pronounced in PPV plus CPA treatment than in PPV alone (p = 0.036 and p = 0.048, respectively). There was no correlation between the changes in Treg or MDSC and CTL response. There was no difference in positive immune responses between the two arms, although overall survival in patients with positive immune responses was longer than in those with negative immune responses (p = 0.001). Significant differences in neither progression-free survival nor overall survival were observed between the two arms. Low-dose CPA showed no change in the antitumor effect of PPV, possibly due to the simultaneous decrease in Treg and increase in MDSC, in patients under PPV. PMID:26728480

  7. A randomized controlled trial to investigate the influence of low dose radiotherapy on immune stimulatory effects in liver metastases of colorectal cancer

    International Nuclear Information System (INIS)

    Insufficient migration and activation of tumor specific effector T cells in the tumor is one of the main reasons for inadequate host anti-tumor immune response. External radiation seems to induce inflammation and activate the immune response. This phase I/II clinical trial aims to evaluate whether low dose single fraction radiotherapy can improve T cell associated antitumor immune response in patients with colorectal liver metastases. This is an investigator-initiated, prospective randomised, 4-armed, controlled Phase I/II trial. Patients undergoing elective hepatic resection due to colorectal cancer liver metastasis will be enrolled in the study. Patients will receive 0 Gy, 0.5 Gy, 2 Gy or 5 Gy radiation targeted to their liver metastasis. Radiation will be applied by external beam radiotherapy using a 6 MV linear accelerator (Linac) with intensity modulated radiotherapy (IMRT) technique two days prior to surgical resection. All patients admitted to the Department of General-, Visceral-, and Transplantion Surgery, University of Heidelberg for elective hepatic resection are consecutively screened for eligibility into this trial, and written informed consent is obtained before inclusion. The primary objective is to assess the effect of active local external beam radiation dose on, tumor infiltrating T cells as a surrogate parameter for antitumor activity. Secondary objectives include radiogenic treatment toxicity, postoperative morbidity and mortality, local tumor control and recurrence patterns, survival and quality of life. Furthermore, frequencies of systemic tumor reactive T cells in blood and bone marrow will be correlated with clinical outcome. This is a randomized controlled patient blinded trial to assess the safety and efficiency of low dose radiotherapy on metastasis infiltrating T cells and thus potentially enhance the antitumor immune response. ClinicalTrials.gov: http://www.clinicaltrials.gov/ct2/show/NCT01191632

  8. How to understand low dose risks

    International Nuclear Information System (INIS)

    It is well established that those who were exposed to ionizing radiation have increased risks of developing malignancies. The magnitude of the risk varies depending on not only the dose but also age at the time of exposure, gender, background incidence rate etc. In the case of atomic bomb survivors, the relative risk of cancer is linearly related to the dose, and the sex averaged relative risk (exposure age is 30, risk calculation is when they reached age 70) is 1.5 at 1 Gy. Because the increased risks below 100 to 200 mGy are too small and not statistically significant, there are arguments in interpreting the risks at the low dose range. (author)

  9. Low-dose computed tomography screening for lung cancer in populations highly exposed to tobacco: A systematic methodological appraisal of published randomised controlled trials.

    Science.gov (United States)

    Coureau, Gaëlle; Salmi, L Rachid; Etard, Cécile; Sancho-Garnier, Hélène; Sauvaget, Catherine; Mathoulin-Pélissier, Simone

    2016-07-01

    Low-dose computed tomography (LDCT) screening recommendations for lung cancer are contradictory. The French National Authority for Health commissioned experts to carry a systematic review on the effectiveness, acceptability and safety of lung cancer screening with LDCT in subjects highly exposed to tobacco. We used MEDLINE and Embase databases (2003-2014) and identified 83 publications representing ten randomised control trials. Control arms and methodology varied considerably, precluding a full comparison and questioning reproducibility of the findings. From five trials reporting mortality results, only the National Lung Screening Trial found a significant decrease of disease-specific and all-cause mortality with LDCT screening compared to chest X-ray screening. None of the studies provided all information needed to document the risk-benefit balance. The lack of statistical power and the methodological heterogeneity of European trials question on the possibility of obtaining valid results separately or by pooling. We conclude, in regard to the lack of strong scientific evidence, that LDCT screening should not be recommended in subjects highly exposed to tobacco. PMID:27211572

  10. Long-term follow-up of non-calcified pulmonary nodules (<10 mm) identified during low-dose CT screening for lung cancer

    International Nuclear Information System (INIS)

    To assess the long-term stability of small (<10 mm) non-calcified pulmonary nodules (NCNs) in high-risk subjects initially screened for lung cancer using low-dose chest computed tomography (LDCCT). A total of 449 subjects initially underwent screening with serial LDCCT over a 2-year period. Participants identified as having NCNs ≥10 mm were referred for formal lung cancer workup. NCNs <10 mm diameter were followed in accordance with the study protocol. Seven years after baseline screening, subjects with previously documented NCNs <10 mm, which were unchanged in size after the 2-year follow-up period, were re-imaged using LDCCT to assess for interval nodule growth. Eighty-three subjects with previously documented stable NCNs <10 mm underwent LDCCT at 7 years. NCNs were unchanged in 78 subjects and had decreased in size in 4 subjects. There was interval growth of an NCN (from 6 mm to 9 mm) in one subject re-imaged at 7 years, but this nodule has remained stable in size over a further 2-year follow-up period. Non-calcified pulmonary nodules <10 mm in size that are unchanged in size or smaller after 2 years of follow-up with LDCCT are most likely benign. (orig.)

  11. Low-dose Photofrin-induced PDT offers excellent clinical response with minimal morbidity in chest wall recurrence of breast cancer

    Science.gov (United States)

    Allison, Ron; Mang, Thomas S.

    2000-03-01

    Limited therapeutic options exist when chest wall recurrence form breast cancer progresses despite standard salvage treatment. As photodynamic therapy offers excellent response for cutaneous lesions this may be a possible indication for PDT. A total of 102 treatment fields were illuminated on 9 women with biopsy proven chest wall recurrence of breast cancer which was progressing despite salvage surgery, radiation, and chemi-hormonal therapy. PDT consisted of outpatient IV infusion of Photofrin at 0.8 mg/kg followed 48 hours laser by illumination at 140-170 J/cm2 via a KTP Yag laser coupled to a dye unit. No patient was lost to follow up. At 6 months post PDT; complete response, defined as total lesion elimination was 89 percent, partial response 8 percent, and no response 3 percent. No photosensitivity was seen and no patient developed scarring, fibrosis, or healing difficulties. Low dose Photofrin induced PDT is very active against chest wall lesions. Despite fragile and heavily pre-treated tissues, excellent clinical and cosmetic outcome was obtained. PDT is an underutilized modality for this indication.

  12. [Low dose ionising radiation and cancer: findings and methods. Report of a meeting and consequences for Switzerland].

    Science.gov (United States)

    Schüler, G; Gutzwiller, F

    1991-01-01

    Today's society is concerned about the dangers of ionising radiation, especially in the aftermath of Chernobyl. On the other hand, there exists a widespread lack of understanding radiation biology and radioepidemiology--the very sciences which provide the data from which today's risk estimates have been derived. The papers in this issue of the Journal were presented at a workshop on "Low level radiation and cancer: data and methods" held on 10th-11th December in Feuisberg, near Zurich. The meeting was organised by the Institute of Social and Preventive Medicine of the University of Zurich under the auspices of the Swiss Federal Office of Public Health. Its aims were threefold. First, to give an introduction to some basic facts and methodological issues in radiation physics, biology and epidemiology. Secondly, to give an overview of the availability of data for radioepidemiological research in Switzerland and, thirdly, to evaluate possible research strategies in this country. A list of some notions and units commonly used in the radiation sciences serves an an introduction to the field (G. Schüler et al.). In using units and notions it is important to distinguish the description of biological experiments and epidemiological observations from definitions and risk projections proposed by international reports and consensus bodies for radioprotection purposes. The next papers deal more specifically with selected aspects of the basic sciences. Dosimetry means quantifying the physical effects of ionizing radiation in human tissue; this is not a straight-forward procedure (I. Cordt). The foundations of general radiation biology are succinctly summarised by C. Michel. An account of our present knowledge and theories of radiation carcinogenesis is provided by W. Burkart. W Lutz compares dose-response models of chemical carcinogenesis with those used in radiation carcinogenesis. During the last decade the epidemiological foundations of radioprotection have changed

  13. mBAND analysis of chromosome aberrations in human epithelial cells induced by gamma-rays and secondary neutrons of low dose rate.

    Science.gov (United States)

    Hada, M; Gersey, B; Saganti, P B; Wilkins, R; Cucinotta, F A; Wu, H

    2010-08-14

    Human risks from chronic exposures to both low- and high-LET radiation are of intensive research interest in recent years. In the present study, human epithelial cells were exposed in vitro to gamma-rays at a dose rate of 17 mGy/h or secondary neutrons of 25 mGy/h. The secondary neutrons have a broad energy spectrum that simulates the Earth's atmosphere at high altitude, as well as the environment inside spacecrafts like the Russian MIR station and the International Space Station (ISS). Chromosome aberrations in the exposed cells were analyzed using the multicolor banding in situ hybridization (mBAND) technique with chromosome 3 painted in 23 colored bands that allows identification of both inter- and intrachromosome exchanges including inversions. Comparison of present dose responses between gamma-rays and neutron irradiations for the fraction of cells with damaged chromosome 3 yielded a relative biological effectiveness (RBE) value of 26+/-4 for the secondary neutrons. Our results also revealed that secondary neutrons of low dose rate induced a higher fraction of intrachromosome exchanges than gamma-rays, but the fractions of inversions observed between these two radiation types were indistinguishable. Similar to the previous findings after acute radiation exposures, most of the inversions observed in the present study were accompanied by other aberrations. The fractions of complex type aberrations and of unrejoined chromosomal breakages were also found to be higher in the neutron-exposed cells than after gamma-rays. We further analyzed the location of the breaks involved in chromosome aberrations along chromosome 3, and observed hot spots after gamma-ray, but not neutron, exposures. PMID:20338263

  14. Radiation cancer analysis and low dose risk estimation: new developments and perspectives - conference to be held Feb 2002. Final technical report for period November 1, 2001--October 31, 2002

    International Nuclear Information System (INIS)

    The Proceedings of the 20th LH Gray Conference on Radiation Cancer Analysis and Low Dose Risk Estimation: New Developments and Perspectives (17-21 February 2002, Ede, the Netherlands) comprises 32 peer-reviewed papers on invited and proffered contributions to the conference with a preface by the guest editors. The on-going discussion of low dose radiation risk; the issue of the linear, non-threshold extrapolation; and the anticipated new recommendations, e.g. from BEIR and ICRP, provided the back-drop for the conference. The meeting dealt with topics such as basic mechanisms and bystander effects, cancer modeling, cancer genetics, radon exposure and lung cancer risk, cancer after medical exposure, cancer risk estimation, dose-effect relationships, and application to radiation protection

  15. Pathogenic effects of low dose irradiation: dose-effect relationships

    International Nuclear Information System (INIS)

    There is no evidence of pathogenic effects in human groups exposed to less than 100 mSv at low dose-rate. The attributed effects are therefore the result of extrapolations from higher doses. The validity of such extrapolations is discussed from the point of view of epidemiology as well as cellular and molecular biology. The Chernobyl accident resulted in large excess of thyroid cancers in children; it also raised the point that some actual sanitary effects among distressed populations might be a direct consequence of low doses. Studies under the control of UN have not confirmed this point identifying no dose-effect relationship and 'severe socio-economic and psychological pressures... poverty, poor diet and living conditions, and lifestyle factors' as the main cause for depressed health. Some hypothesis are considered for explaining the dose-dependence and high prevalence of non-cancer causes of death among human groups exposed to more than 300 mSv. (author)

  16. Randomized controlled phase I/II study to investigate immune stimulatory effects by low dose radiotherapy in primarily operable pancreatic cancer

    International Nuclear Information System (INIS)

    The efficiencies of T cell based immunotherapies are affected by insufficient migration and activation of tumor specific effector T cells in the tumor. Accumulating evidence exists on the ability of ionizing radiation to modify the tumor microenvironment and generate inflammation. The aim of this phase I/II clinical trial is to evaluate whether low dose single fraction radiotherapy can improve T cell associated antitumor immune response in patients with pancreatic cancer. This trial has been designed as an investigator initiated; prospective randomised, 4-armed, controlled Phase I/II trial. Patients who are candidates for resection of pancreatic cancer will be randomized into 4 arms. A total of 40 patients will be enrolled. The patients receive 0 Gy, 0.5 Gy, 2 Gy or 5 Gy radiation precisely targeted to their pancreatic carcinoma. Radiation will be delivered by external beam radiotherapy using a 6 MV Linac with IMRT technique 48 h prior to the surgical resection. The primary objective is the determination of an active local external beam radiation dose, leading to tumor infiltrating T cells as a surrogate parameter for antitumor activity. Secondary objectives include local tumor control and recurrence patterns, survival, radiogenic treatment toxicity and postoperative morbidity and mortality, as well as quality of life. Further, frequencies of tumor reactive T cells in blood and bone marrow as well as whole blood cell transcriptomics and plasma-proteomics will be correlated with clinical outcome. An interim analysis will be performed after the enrolment of 20 patients for safety reasons. The evaluation of the primary endpoint will start four weeks after the last patient's enrolment. This trial will answer the question whether a low dose radiotherapy localized to the pancreatic tumor only can increase the number of tumor infiltrating T cells and thus potentially enhance the antitumor immune response. The study will also investigate the prognostic and predictive

  17. A review of data on the effects of low and low dose-rate radiation with special reference to the dose limit problem

    International Nuclear Information System (INIS)

    This is a review of data pertaining to detection and quantification of the effects after exposure to low LET radiations delivered at low and low dose-rate, i.e., at a level of maximum permissible dose for the radiation workers, on experimental materials ranging from plant to rodents and on some human populations. Irradiation at a dose of a few rad is reported to induce mutation or malignant transformation in some selected model systems, with a linear dose-effect relationship. Moreover, the incidence of the chromosome aberrations in spermatocytes is reported to be elevated in the scorpiones (Tityus bahiensis) collected in a region of high natural background radiations (several rem/year). An increase in the incidence of childhood malignancies is reported among children exposed in utero to diagnostic X-rays. Appreciable increase in the incidence of genetic diseases due possibly to chromosome aberrations is also reported among population living in a region of high natural background radiations. Points are raised and discussed as to the interpretation and particularly application of these data to the estimation of somatic and genetic risks of human population from man-made radiations. Recent attempts of risk-benefit analysis with populations subjected to mass X-ray examination of the chest and stomac are referred to. Since we are unaware of the actual injuries due to the exposure even at the level of radiation workers (5 rem/year), it is out of the capacity of a biologist to afford the basis for the decision of limiting the exposure of general population due to the light water reactor operation to 5 mrem/year. (auth.)

  18. Age and sex dependence in tumorigenesis in mice by continuous low-dose-rate gamma-ray whole-body irradiation

    International Nuclear Information System (INIS)

    We investigated the dependency of sex and age in mice in the induction of neoplasms by gamma-rays from cesium-137 at a low dose rate of 0.375Gy/22h/day. Thymic lymphomas occurred significantly at the same incidence in both sexes, and more frequently when younger mice were exposed to radiation. Strain C57BL/6J mice were divided into 8 groups, which were whole-body irradiated with a total dose of 39Gy for 105 days each. The exposure was begun at 28 days of age (male:AM1, female:AF1), and then stepwise increasing the starting age by 105 days, i.e., from 133 days (AM2 and AF2), from 238 days (AM3 and AF3), and from 343 days (AM4 and AF4), respectively. Unirradiated mice served as control (UM and UF). The incidence of thymic lymphomas was about 60 % in AM1, AM2, AF1 and AF2, 40 % in AM3 and AF3 and 20 % in AF4 and AF4, demonstrating no sex dependency, but a distinct age dependency, for lymphomogenesis. It was proven that mice showed a tendency to become less susceptible to radiation induced thymic lymphoma with increasing age. Concomitantly, life-shortening also was caused, and the greater the degree of life-shortening was, the younger the mice were the start of exposure. Life-shortening was attributed to thymic lymphoma, and hemorrhage and infectious diseases due to the depletion of bone marrow cells. (author)

  19. Naltrexone at low doses upregulates a unique gene expression not seen with normal doses: Implications for its use in cancer therapy.

    Science.gov (United States)

    Liu, Wai M; Scott, Katherine A; Dennis, Jayne L; Kaminska, Elwira; Levett, Alan J; Dalgleish, Angus G

    2016-08-01

    It has been reported that lower doses of the opioid antagonist naltrexone are able to reduce tumour growth by interfering with cell signalling as well as by modifying the immune system. We have evaluated the gene expression profile of a cancer cell line after treatment with low-dose naltrexone (LDN), and assessed the effect that adapting treatment schedules with LDN may have on enhancing efficacy. LDN had a selective impact on genes involved with cell cycle regulation and immune modulation. Similarly, the pro-apoptotic genes BAD and BIK1 were increased only after LDN. Continuous treatment with LDN had little effect on growth in different cell lines; however, altering the treatment schedule to include a phase of culture in the absence of drug following an initial round of LDN treatment, resulted in enhanced cell killing. Furthermore, cells pre-treated with LDN were more sensitive to the cytotoxic effects of a number of common chemotherapy agents. For example, priming HCT116 with LDN before treatment with oxaliplatin significantly increased cell killing to 49±7.0 vs. 14±2.4% in cultures where priming was not used. Interestingly, priming with NTX before oxaliplatin resulted in just 32±1.8% cell killing. Our data support further the idea that LDN possesses anticancer activity, which can be improved by modifying the treatment schedule. PMID:27279602

  20. Radiation biology of low doses

    International Nuclear Information System (INIS)

    Present risk assessments and standards in radiation protection are based on the so-called linear no-threshold (LNT) dose - effect hypothesis, i.e., on a linear, proportional relationship between radiation doses and their effects on biological systems. This concept presupposes that any dose, irrespective of its level and time of occurrence, carries the same risk coefficient and, moreover, that no individual biological effects are taken into account. This contribution presents studies of low energy transfer (LET) radiation which deal with the risk of cancer to individual cells. According to the LNT hypothesis, the relationship for the occurrence of these potential effects should be constant over the dose range: successful repair, cell death, mutation with potential carcinogenesis. The results of the studies presented here indicate more differentiated effects as a function of dose application as far as damage to cellular DNA by ionizing radiation is concerned. At the same overall dose level, multiple exposures to low doses sometimes give rise to much smaller effects than those arising from one single exposure to the total dose. These adaptive effects of cells are known from other studies. The results of the study allow the conclusion to be drawn that non-linear relationships must be assumed to exist for the LET radiation considered. Correspondingly, the linear no-threshold hypothesis model should at least be reconsidered with respect to the low dose range in the light of recent biological findings. The inclusion of other topical research findings also could give rise to a new, revised, risk-oriented approach in radiological protection. (orig.)

  1. Effects of very low dose-rate 90Sr/90Y exposure on the acute moist desquamation response of pig skin

    International Nuclear Information System (INIS)

    Background and objectives: Previous data, predominantly involving high dose-rate fractionated irradiation with incomplete repair intervals, had indicated that the kinetics of repair of sublethal damage for acute radiation reactions in pig skin could best be defined by a biphasic repair model with half-times for repair of 0.2 and 5.4 h, partition coefficient 0.5. To further test the validity of this finding and obtain a better estimate of the repair rate of the slow component of repair, the acute response of pig skin to very low dose-rates (VLDR), originally estimated to be 0.0067-0.0244 Gy/min, was investigated as part of a 4 fraction irradiation protocol involving an overall treatment time of 90Sr/90Y plaques. Irradiation with a 4 fraction protocol included 3 equal, high dose-rate, fractions with full repair, followed by a fourth VLDR fraction. The total doses administered were originally planned to represent the dose associated with the predicted ED20, ED50 and ED80 (75% of total biological dose given at high dose-rate and 25% at VLDR) calculated on the basis of the repair kinetic parameters obtained from earlier studies. However, during the analysis a revision to the physical dosimetry was identified; this had been overlooked prior to the start of the study. Following completion of irradiation the irradiated sites were examined weekly and the presence or absence of moist desquamation recorded. Results: The incidence of moist desquamation was slightly higher than expected on the basis of the parameters used to calculate iso-effective doses, at least in part as a consequence of the change to the dosimetry. Using likelihood methods and the original dose estimates, the best model based estimate of the dose-rate correction factor for the LDR and VLDR plaques was 1.29. This was comparable with the physical calibration factor, median value 1.23. The VLDR fraction associated with a 50% incidence of moist desquamation, based on experimental observation, was 23.2 ± 0

  2. Total body irradiation (TBI) in pediatric patients. A single-center experience after 30 years of low-dose rate irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Linsenmeier, Claudia; Thoennessen, Daniel; Negretti, Laura; Streller, Tino; Luetolf, Urs Martin [University Hospital Zurich (Switzerland). Dept. of Radiation-Oncology; Bourquin, Jean-Pierre [University Children' s Hospital Zurich (Switzerland). Dept. of Hemato-Oncology; Oertel, Susanne [University Hospital Zurich (Switzerland). Dept. of Radiation-Oncology; Heidelberg Univ. (Germany). Dept. of Radiation Oncology

    2010-11-15

    TBI at the low-dose rate that was generally used here. Conditioning for bone marrow transplantation without radiation is an attractive option, but is not sufficiently effective to completely replace TBI for the most common pediatric indications. (orig.)

  3. Total body irradiation (TBI) in pediatric patients. A single-center experience after 30 years of low-dose rate irradiation

    International Nuclear Information System (INIS)

    TBI at the low-dose rate that was generally used here. Conditioning for bone marrow transplantation without radiation is an attractive option, but is not sufficiently effective to completely replace TBI for the most common pediatric indications. (orig.)

  4. Breast Cancer Rates by State

    Science.gov (United States)

    ... Associated Lung Ovarian Prostate Skin Uterine Cancer Home Breast Cancer Rates by State Language: English Español (Spanish) Recommend ... from breast cancer each year. Rates of Getting Breast Cancer by State The number of people who get ...

  5. Radiochemotherapy with short daily infusion of low-dose oxaliplatin, leucovorin, and 5-FU in T3-T4 unresectable rectal cancer: a phase II IATTGI study

    International Nuclear Information System (INIS)

    survival was 19.5 months (CI 95%, 18.0, 21). Conclusions: Outpatient treatment with low-dose, 30-min daily OXA infusion was feasible and very active, with acceptable toxicity

  6. [{sup 131}I]Iodoazomycin arabinoside for low-dose-rate isotope radiotherapy: radiolabeling, stability, long-term whole-body clearance and radiation dosimetry estimates in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Piyush [Department of Oncologic Imaging, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, T6G 2N8 (Canada); McQuarrie, Steven A. [Department of Oncologic Imaging, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, T6G 2N8 (Canada); Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, T6G 2N8 (Canada); Zhou, Aihya [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, T6G 2N8 (Canada); McEwan, Alexander J.B. [Department of Oncologic Imaging, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, T6G 2N8 (Canada); Wiebe, Leonard I. [Department of Oncologic Imaging, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, T6G 2N8 (Canada) and Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, T6G 2N8 (Canada)]. E-mail: leonard.wiebe@ualberta.ca

    2005-08-01

    activities. Based on measured radioactivity burdens during the week following injection and on published animal ([{sup 125}I]IAZA) and clinical ([{sup 123}I]IAZA) dosimetry data, the current dose estimates point to selective tumor irradiation at low dose rates.

  7. BrachyView: Proof-of-principle of a novel in-body gamma camera for low dose-rate prostate brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Petasecca, M.; Loo, K. J.; Safavi-Naeini, M.; Han, Z.; Metcalfe, P. E.; Lerch, M. L. F.; Qi, Y.; Rosenfeld, A. B. [Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522 (Australia); Meikle, S. [Brain and Mind Research Institute, University of Sydney, NSW 2006, Australia and Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522 (Australia); Pospisil, S.; Jakubek, J. [Institute of Experimental and Applied Physics, Czech Technical University of Prague, Prague (Czech Republic); Bucci, J. A. [St George Cancer Care Centre, St George Hospital, Kogarah, NSW 2217 (Australia); Zaider, M. [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021 (United States)

    2013-04-15

    Purpose: The conformity of the achieved dose distribution to the treatment plan strongly correlates with the accuracy of seed implantation in a prostate brachytherapy treatment procedure. Incorrect seed placement leads to both short and long term complications, including urethral and rectal toxicity. The authors present BrachyView, a novel concept of a fast intraoperative treatment planning system, to provide real-time seed placement information based on in-body gamma camera data. BrachyView combines the high spatial resolution of a pixellated silicon detector (Medipix2) with the volumetric information acquired by a transrectal ultrasound (TRUS). The two systems will be embedded in the same probe so as to provide anatomically correct seed positions for intraoperative planning and postimplant dosimetry. Dosimetric calculations are based on the TG-43 method using the real position of the seeds. The purpose of this paper is to demonstrate the feasibility of BrachyView using the Medipix2 pixel detector and a pinhole collimator to reconstruct the real-time 3D position of low dose-rate brachytherapy seeds in a phantom. Methods: BrachyView incorporates three Medipix2 detectors coupled to a multipinhole collimator. Three-dimensionally triangulated seed positions from multiple planar images are used to determine the seed placement in a PMMA prostate phantom in real time. MATLAB codes were used to test the reconstruction method and to optimize the device geometry. Results: The results presented in this paper show a 3D position reconstruction accuracy of the seed in the range of 0.5-3 mm for a 10-60 mm seed-to-detector distance interval (Z direction), respectively. The BrachyView system also demonstrates a spatial resolution of 0.25 mm in the XY plane for sources at 10 mm distance from Medipix2 detector plane, comparable to the theoretical value calculated for an equivalent gamma camera arrangement. The authors successfully demonstrated the capability of BrachyView for real

  8. BrachyView: Proof-of-principle of a novel in-body gamma camera for low dose-rate prostate brachytherapy

    International Nuclear Information System (INIS)

    Purpose: The conformity of the achieved dose distribution to the treatment plan strongly correlates with the accuracy of seed implantation in a prostate brachytherapy treatment procedure. Incorrect seed placement leads to both short and long term complications, including urethral and rectal toxicity. The authors present BrachyView, a novel concept of a fast intraoperative treatment planning system, to provide real-time seed placement information based on in-body gamma camera data. BrachyView combines the high spatial resolution of a pixellated silicon detector (Medipix2) with the volumetric information acquired by a transrectal ultrasound (TRUS). The two systems will be embedded in the same probe so as to provide anatomically correct seed positions for intraoperative planning and postimplant dosimetry. Dosimetric calculations are based on the TG-43 method using the real position of the seeds. The purpose of this paper is to demonstrate the feasibility of BrachyView using the Medipix2 pixel detector and a pinhole collimator to reconstruct the real-time 3D position of low dose-rate brachytherapy seeds in a phantom. Methods: BrachyView incorporates three Medipix2 detectors coupled to a multipinhole collimator. Three-dimensionally triangulated seed positions from multiple planar images are used to determine the seed placement in a PMMA prostate phantom in real time. MATLAB codes were used to test the reconstruction method and to optimize the device geometry. Results: The results presented in this paper show a 3D position reconstruction accuracy of the seed in the range of 0.5–3 mm for a 10–60 mm seed-to-detector distance interval (Z direction), respectively. The BrachyView system also demonstrates a spatial resolution of 0.25 mm in the XY plane for sources at 10 mm distance from Medipix2 detector plane, comparable to the theoretical value calculated for an equivalent gamma camera arrangement. The authors successfully demonstrated the capability of BrachyView for

  9. Asbestos Surveillance Program Aachen (ASPA): initial results from baseline screening for lung cancer in asbestos-exposed high-risk individuals using low-dose multidetector-row CT

    International Nuclear Information System (INIS)

    The purpose of this study was to assess the prevalence of lung cancer in a high-risk asbestos-exposed cohort using low-dose MDCT. Of a population of 5,389 former power-plant workers, 316 were characterized as individuals at highest risk for lung cancer according to a lung-cancer risk model including age, asbestos exposure and smoking habits. Of these 316, 187 (mean age: 66.6 years) individuals were included in a prospective trial. Mean asbestos exposure time was 29.65 years and 89% were smokers. Screening was performed on a 16-slice MDCT (Siemens) with low-dose technique (10/20 mAseff.; 1 mm/0.5 mm increment). In addition to soft copy PACS reading analysis on a workstation with a dedicated lung analysis software (LungCARE; Siemens) was performed. One strongly suspicious mass and eight cases of histologically proven lung cancer were found plus 491 additional pulmonary nodules (average volume: 40.72 ml, average diameter 4.62 mm). Asbestos-related changes (pleural plaques, fibrosis) were visible in 80 individuals. Lung cancer screening in this high-risk cohort showed a prevalence of lung cancer of 4.28% (8/187) at baseline screening with an additional large number of indeterminate pulmonary nodules. Low-dose MDCT proved to be feasible in this highly selected population. (orig.)

  10. Low dose effects. Adaptive response

    International Nuclear Information System (INIS)

    The purpose of this work was to evaluate if there are disturbancies in adaptive response when lymphocytes of people living on the polluted with radionuclides area after Chernobyl disaster and liquidators suffered from accident have been investigated. The level of lymphocytes with micronuclei have been scored in Moscow donors and people living in Bryansk region with the degree of contamination 15 - 40 Ci/km. The doses that liquidators have been obtained were not higher then 25 cGy. The mean spontaneous level of MN in control people and people from Chernobyl zones does't differ significantly but the individual variability in the mean value between two populations does not differ significantly too. And in this case it seems that persons of exposed areas. Then another important fact in lymphocytes of people living on polluted areas the chronic low dose irradiation does not induce the adaptive response. In Moscow people in most cases (≅ 59 %) the adaptive response is observed and in some cases the demonstration of adaptive response is not significant (≅1%). In Chernobyl population exposed to chronic low level, low dose rate irradiation there are fewer people here with distinct adaptive response (≅38%). And there appear beings with increased radiosensitivity after conditioned dose. Such population with enhanced radiosensitivity have not observed in Moscow. In liquidators the same types of effects have been registered. These results have been obtained on adults. Adaptive response in children 8 - 14 old population living in Moscow and in Chernobyl zone have been investigated too. In this case the spontaneous level of MN is higher in children living in polluted areas, after the 1.0 Gy irradiation the individual variability is very large. Only 5 % of children have distinct is very large. Only 5 % of children have distinct adaptive response, the enhancement of radiosensitivity after conditioned dose is observed. (authors)

  11. Low-dose non-enhanced CT versus full-dose contrast-enhanced CT in integrated PET/CT studies for the diagnosis of uterine cancer recurrence

    Energy Technology Data Exchange (ETDEWEB)

    Kitajima, Kazuhiro [Institute of Biomedical Research and Innovation, Department of PET Diagnosis, Kobe (Japan); Kobe University Graduate School of Medicine, Department of Radiology, Kobe (Japan); Suzuki, Kayo [Institute of Biomedical Research and Innovation, Department of PET Diagnosis, Kobe (Japan); Nakamoto, Yuji [Kyoto University Hospital, Department of Diagnostic Radiology, Kyoto (Japan); Onishi, Yumiko; Sakamoto, Setsu; Sugimura, Kazuro [Kobe University Graduate School of Medicine, Department of Radiology, Kobe (Japan); Senda, Michio [Institute of Biomedical Research and Innovation, Department of Molecular Imaging, Kobe (Japan); Kita, Masato [Kobe City Medical Center General Hospital, Department of Obstetrics and Gynecology, Kobe (Japan)

    2010-08-15

    To evaluate low-dose non-enhanced CT (ldCT) and full-dose contrast-enhanced CT (ceCT) in integrated {sup 18}F-fluorodeoxyglucose (FDG) PET/CT studies for restaging of uterine cancer. A group of 100 women who had undergone treatment for uterine cervical (n=55) or endometrial cancer (n=45) underwent a conventional PET/CT scans with ldCT, and then a ceCT scan. Two observers retrospectively reviewed and interpreted the PET/ldCT and PET/ceCT images in consensus using a three-point grading scale (negative, equivocal, or positive) per patient and per lesion. Final diagnoses were obtained by histopathological examination, or clinical follow-up for at least 6 months. Patient-based analysis showed that the sensitivity, specificity and accuracy of PET/ceCT were 90% (27/30), 97% (68/70) and 95% (95/100), respectively, whereas those of PET/ldCT were 83% (25/30), 94% (66/70) and 91% (91/100), respectively. Sensitivity, specificity and accuracy did not significantly differ between two methods (McNemar test, p=0.48, p=0.48, and p=0.13, respectively). There were 52 sites of lesion recurrence: 12 pelvic lymph node (LN), 11 local recurrence, 8 peritoneum, 7 abdominal LN, 5 lung, 3 supraclavicular LN, 3 liver, 2 mediastinal LN, and 1 muscle and bone. The grading results for the 52 sites of recurrence were: negative 5, equivocal 0 and positive 47 for PET/ceCT, and negative 5, equivocal 4 and positive 43 for PET/ldCT, respectively. Four equivocal regions by PET/ldCT (local recurrence, pelvic LN metastasis, liver metastasis and muscle metastasis) were correctly interpreted as positive by PET/ceCT. PET/ceCT is an accurate imaging modality for the assessment of uterine cancer recurrence. Its use reduces the frequency of equivocal interpretations. (orig.)

  12. The feasibility and safety of high-intensity focused ultrasound combined with low-dose external beam radiotherapy as supplemental therapy for advanced prostate cancer following hormonal therapy

    Institute of Scientific and Technical Information of China (English)

    Rui-Yi Wu; Guo-Min Wang; Lei Xu; Bo-Heng Zhang; Ye-Qing Xu; Zhao-Chong Zeng; Bing Chen

    2011-01-01

    The aim of this study was to investigate the feasibility and safety of high-intensity focused ultrasound (HIFU) combined with (+) low-dose external beam radiotherapy (LRT) as supplemental therapy for advanced prostate cancer (PCa) following hormonal therapy (HT). Our definition of HIFU+LRT refers to treating primary tumour lesions with HIFU in place of reduced field boost irradiation to the prostate, while retaining four-field box irradiation to the pelvis in conventional-dose external beam radiotherapy (CRT). We performed a prospective, controlled and non-randomized study on 120 patients with advanced PCa after HT who received HIFU, CRT, HIFU+LRT and HT alone, respectively. CT/MR imaging showed the primary tumours and pelvic lymph node metastases visibly shrank or even disappeared after HIFU+LRT treatment. There were significant differences among four groups with regard to overall survival (OS) and disease-specific survival (DSS) curves (P=0.018 and 0.015). Further comparison between each pair of groups suggested that the long-term DSS of the HIFU+LRT group was higher than those of the other three groups, but there was no significant difference between the HIFU+LRT group and the CRT group. Multivariable Cox's proportional hazard model showed that both HIFU+LRT and CRT were independently associated with DSS (P=0.001 and 0.035) and had protective effects with regard to the risk of death. Compared with CRT, HIFU+LRT significantly decreased incidences of radiation-related late gastrointestinal (GI) and genitourinary (GU) toxicity grade ≥II. In conclusion, long-term survival of patients with advanced PCa benefited from strengthening local control of primary tumour and regional lymph node metastases after HT. As an alternative to CRT, HIFU+LRT showed good efficacy and better safety.

  13. Normal tissue response to low doses of radiotherapy assessed by molecular markers - A study of skin in patients treated for prostate cancer

    International Nuclear Information System (INIS)

    The aim of this study was to evaluate normal tissue response by molecular markers to multi fraction low doses of ionizing radiation, with the focus on changes in repopulation, estimated using Ki-67 as the proliferation marker, and on expressions of the p53 and p21 proteins, identified as key proteins in the DNA damage checkpoint. Repeated skin biopsies were taken from patients treated for prostate cancer with radiotherapy. The expressions of Ki-67, p53 and p21 of the keratinocytes in the basal cell layer of the epidermis were quantified immunohistochemically. The dose to the basal layer was 1.1 Gy per fraction, given five times per week for seven weeks. The indices of the three markers were determined over the whole period. A significant suppression of the Ki-67 index was observed during the first weeks, followed by a significant gradual increase in the Ki-67 index over the last weeks. The p53 and p21 protein levels were almost zero in the unirradiated skin. Upon irradiation, both the p53 and p21 index increased in a pattern very congruent to the Ki-67 index. In conclusion, daily fractions of about 1 Gy to the skin resulted in, for the keratinocytes in the basal layer, a cell growth arrest for a couple of weeks and a subsequent acceleration in repopulation during the following weeks of irradiation. The present findings also provided novel insights into the role of the p53/p21 pathway in the response of a normal epithelium to ionizing radiation as it is applied in radiotherapy

  14. Biologically based analysis of lung cancer incidence in a large Canadian occupational cohort with low-LET low-dose radiation exposure, and comparison with Japanese atomic bomb survivors

    International Nuclear Information System (INIS)

    Lung cancer incidence is analyzed in a large Canadian National Dose Registry (CNDR) cohort with individual annual dosimetry for low-dose occupational exposure to gamma and tritium radiation using several types of multistage models. The primary analysis utilizes the two-stage clonal expansion model (TSCE), with sensitivity analyses using extensions of this model incorporating additional stages. Characteristic and distinct temporal patterns of risk are found for dose-response affecting early, middle, or late stages of carcinogenesis, e.g. initiation with one or more stages, clonal expansion, or malignant conversion. Fixed lag or lag distributions are used to model time from first malignant cell to incidence. Background rates are analyzed by gender, job classification and birth cohort. Lacking individual smoking data, surrogate doses based on US annual per capita cigarette consumption appear to account for much of the birth cohort effect. Males, with mean cumulative exposure for gamma and tritium of 11.5 mSv and 322 incident lung cancer cases have a significant dose-response with 33 cases attributable to radiation. Female dose-response, with mean cumulative exposure of 1.7 mSv and 78 incident cases, appears similar but is not statistically significant. Findings for males include an inverse-dose-rate effect (increased risk with protraction of a given dose) and dose-response effects on initiation, promotion and malignant conversion, although the effect on initiation is not statistically significant. The excess relative risk (ERR) and excess absolute risk (EAR) depend on age at exposure, duration, dose, and age at follow-up. The ERR increases with dose, tapering off at higher doses, making a plot of ERR against dose concave-downward, similar to apparent low-dose results seen below 1 Sv for solid tumor mortality of atomic bomb survivors. The concave-downward trend of ERR and the inverse-dose-rate effect are both counter to prevailing beliefs about effects of low

  15. Long-term results of exclusive low-dose rate curie-therapy for a high-grade vaginal intraepithelial neoplasia; Resultats a long terme de la curietherapie exclusive de bas debit de dose pour neoplasie vaginale intraepitheliale de haut grade

    Energy Technology Data Exchange (ETDEWEB)

    Blanchard, P.; Monnier, L.; Dumas, I.; Azoury, F.; Mazeron, R.; Haie-Meder, C. [Institut Gustave-Roussy, 94 - Villejuif (France)

    2010-10-15

    The authors report the results of an exclusive low dose rate curie therapy for female patients treated for a grade 3 vaginal intraepithelial neoplasia. They reviewed the medical files of patients treated since 1983, i.e. 28 women. They analysed demographic characteristics, the clinic description of lesions, possible treatments which occurred before this high-grade vaginal intraepithelial neoplasia, possible previous history of cervical or endometrial cancer, curie therapy detailed data, presence of tumorous relapse. According to that, they conclude that a 60 Gy exclusive low- vaginal dose-rate curie-therapy is an efficient and well tolerated treatment for high-grade vaginal intraepithelial neoplasia. Short communication

  16. Role of low-dose spiral CT scan in early lung cancer screeing of high risk population: a systematic review of the literature with a Meta-analysis

    International Nuclear Information System (INIS)

    Objective: To assess the overall diagnostic value of low-dose spiral computed tomography (LDSCT) screening trials for early lung cancer of high risk population. Methods: A search in PubMed, Cancerlit, Embase bank, Cochrane Library, CBMdisc and CNKI was performed to identify relevant English and Chinese-language articles from January 1, 1995 to June 1,2005. Quality evaluation and heterogeneity test were performed to the included researches. Consistency analysis was executed. Pooled weighted sensitivity and specificity were calculated. Receiver operating characteristic (ROC) curve was performed and area under the curve (AUC) was calculated. Test of odds ratio(OR)was performed to these results of base screening and annual follow-up screening at least two years. Finally, sensitivity analysis was performed. Results: Fifteen articles were included, with 9 independent researches and a total of 8168 subjects. Heterogeneity existed. Base screening was undertaken in high risk population in the grade of BO (discovering nodule), B5 (discovering nodule of diameter more than 5 mm), B10 (discovering nodule of diameter more than 10 mm) and corresponding Kappa value was 0.061, 0.134 and 0.460, pooled weighted sensitivity was 0.686, 0.721 and 0.640, pooled weighted specificity was 0.708, 0.815 and 0.959. Area under the ROC was 0.778, 0.949 and 0.539 respectively. Statistically significant difference did not exist between the AUC of BO and B5 (P>0.05), but existed between B0 and B10, B5 and B10 (P<0.05). With the fixed effect model, the pooled OR in the grade of B5 and B10 were 1.11 and 1.66 respectively. Conclusion: The articles entered into this Meta-analysis were of high quality. The pooled weighted sensitivity and specificity of LDSCT screening for early lung cancer of high risk population was moderate. The method was affected by chance factors easily. It was relatively reasonable to define the positive standard as the discovered nodule's diameter was more than 5 mm. Close flow

  17. Fibroblasts from ataxia telangiectasia (AT) and AT heterozygotes show an enhanced level of residual DNA double-strand breaks after low dose-rate γ-irradiation as assayed by pulsed field gel electrophoresis

    International Nuclear Information System (INIS)

    Skin fibroblasts from ataxia telangiectasia (AT) patients, obligate AT heterozygotes (ATH) and normal individuals were studied for colony-forming ability and repair of DNA double-strand breaks (dsb) after γ-irradiation. AT cells were three to four times more radiosensitive than normal cells at high and low dose-rate exposures; ATH cells, however, showed a marginally increased radiosensitivity after high dose-rate γ-irradiation and an intermediate response after low dose-rate exposure. The repair of DNA dsb was studied by pulsed field gel electrophoresis. After high dose-rate γ-irradiation the repair time constant (t1/2) was around 1h for normal, ATH and AT cells. After low dose-rate γ-irradiation the fraction of residual dsb was 1.4% for normal, 2.1% for ATH and 5.2% for AT cells, demonstrating a deficiency in the repair of a small fraction of dsb in AT. (author)

  18. Performance evaluation and dose verification of the low dose rate permanent prostrate brachytherapy system at the korle-bu Teaching Hospital

    International Nuclear Information System (INIS)

    Low dose rate prostate brachytherapy equipment that is newly acquired or substantially upgraded requires acceptance testing before being put into clinical service as well as Quality control after installation and when in use. Thus, quality control tests typically are periodic repetitions, partial or full, of acceptance and commissioning tests. The ultrasound system is the most important equipment used in LDR prostate brachytherapy. The AAPM TG 128 provides a set of instructions for quality control testing of an ultrasound system with a specific focus on those tests applicable to image guidance during a prostate implant procedure. Following the AAPM TG 128 protocol and CIRS 045 brachytherapy QA phantom as well as other protocols, eight experiments were performed to evaluate the performance of the system. The overall average axial distance in the B and F columns were found to be 10.12 ± 0.1 mm and 10.10 ± 0.11 mm respectively deviating by approximately 1.2 % and 1.0 % respectively from a standard inter- target distance of 10 mm. Also the lateral distance measured along the rows 1, 2, 3 and 4 resulted in an average distance of 10.07 ± 0.06 mm along rows B4 – C4, deviating from the standard inter- target distance of 10 mm by approximately 0.07 mm or ± 0.7 %, that of B3 – D3 also was 20.01 ± 0.07, deviating from 20 mm standard inter- target distance by 0.01 mm or 0.05 %, targets along B2 – E2 recorded an average distance of 29.56 ± 0.33 mm deviating from 30 mm standard inter- target distance by approximately -0.44 mm or -1.47 % and the last which is B1 – F1 also recorded an average distance of 39.54 ± 0.38 mm deviating from 40 mm standard inter- target distance by approximately -0.46 mm or – 1.15 %. Volume measurement accuracy of the three standard volumes, 4 cm3, 9 cm3 and 20 cm3 produced average measurements of 3.97 ± 0.16 cm3, 8.86 ± 0.29 cm3 and 20.11 ± 1.04 cm3 resulting in approximate deviations of -0.75 %, -1.56 % and 0.55 % respectively. That

  19. High dose rate interstitial radiation for tongue cancer

    International Nuclear Information System (INIS)

    From April 1992 through March 1995, 38 patients with T1-2N0 tongue cancer were treated with high dose rate (HDR) or low dose rate (LDR) brachytherapy alone. Three year local control rates of HDR and LDR groups were 94% and 90%, respectively. Treatment results and complication of HDR brachytherapy were almost the same as those of LDR brachytherapy. At the same period, 11 patients with T1-2N0-2 tongue cancer were treated with external radiation and HDR brachytherapy. Three year local control rate was 90%. HDR brachytherapy have some advantages compared with LDR brachytherapy. (author)

  20. Effects of low doses of ionizing radiation

    International Nuclear Information System (INIS)

    Several groups of human have been irradiated by accidental or medical exposure, if no gene defect has been associated to these exposures, some radioinduced cancers interesting several organs are observed among persons exposed over 100 to 200 mSv delivered at high dose rate. Numerous steps are now identified between the initial energy deposit in tissue and the aberrations of cell that lead to tumors but the sequence of events and the specific character of some of them are the subject of controversy. The stake of this controversy is the risk assessment. From the hypothesis called linear relationship without threshold is developed an approach that leads to predict cancers at any tiny dose without real scientific foundation. The nature and the intensity of biological effects depend on the quantity of energy absorbed in tissue and the modality of its distribution in space and time. The probability to reach a target (a gene) associated to the cancerating of tissue is directly proportional to the dose without any other threshold than the quantity of energy necessary to the effect, its probability of effect can be a more complex function and depends on the quality of the damage produced as well as the ability of the cell to repair the damage. These two parameters are influenced by the concentration of initial injuries in the target so by the quality of radiation and by the dose rate. The mechanisms of defence explain the low efficiency of radiation as carcinogen and then the linearity of effects in the area of low doses is certainly the least defensible scientific hypothesis for the prediction of the risks. (N.C.)

  1. Patterns of Recurrence After Low-Dose-Rate Prostate Brachytherapy: A Population-Based Study of 2223 Consecutive Low- and Intermediate-Risk Patients

    Energy Technology Data Exchange (ETDEWEB)

    Lo, Andrea C.; Morris, W. James, E-mail: JMorris@bccancer.bc.ca; Pickles, Tom; Keyes, Mira; McKenzie, Michael; Tyldesley, Scott

    2015-03-15

    Objectives: This study examined patterns of recurrence after low–dose-rate prostate brachytherapy (LDR-PB), estimated local recurrence rate and compared that rate to the estimated local recurrence rate after radical prostatectomy (RP). Methods and Materials: A prospective database was maintained with clinical, dosimetric, and outcome data for all LDR-PB implantation procedures performed at our institution. From 1998 to 2008, 2223 patients with prostate cancer received LDR-PB without supplemental external beam radiation therapy. Patients who developed Phoenix-defined biochemical failure were reviewed for sites of relapse and investigations completed. Results: At a median follow-up of 5 years, 108 of 2223 patients (4.8%) developed biochemical relapse. In 1 additional patient, local relapse was found on transurethral prostate resection, but his prostate-specific antigen concentration was well short of triggering Phoenix-defined failure. Of the 109 patients with disease relapse, 18 of 2223 (0.8%) had a proven local recurrence, and 30 of 2223 (1.3%) had a proven distant recurrence. The remaining 61 of 2223 patients (2.7%) had unidentified sites of recurrence; of these, 57 patients (93%) had digital rectal examinations (DREs), 18 (30%) had post-treatment biopsies, 45 (74%) had bone scans, and 34 (56%) had computed tomography imaging of the abdomen and pelvis. If every biochemical failure were local, the local recurrence rate would be as high as 4.9%; however, by excluding those with proven distant failure and those with both a negative DRE and biopsy, we estimate that the local recurrence rate is 2.7% or less. Conclusions: In the context of limitations of the study design, our population-based analysis indicates that the local recurrence rate after LDR-PB is as low or lower than that after RP in our jurisdiction.

  2. Does the cell radioresistance acquired by low dose-rate gamma irradiation depend on genetic factors or physiological changes. Study carried out on inactive cells of the unicellular green alga Chlorella pyrenoidosa CHICK

    International Nuclear Information System (INIS)

    Inactive cells of the unicellular green alga Chlorella pyrenoidosa CHICK were used to test the following hypothesis: the radioresistance acquired by these cells after irradiation at low dose rate (0.06 Gy/mn) is due to the selection or induction of radioresistant clones. Clone cultures were grown mainly from colonies exhibiting defects (high cell loss, slowed growth, pigment deficiency). Of thirty clones studied, three only of second and third separations possessed the radioresistance of their original population. On the basis of these results, backed up by a first experiment which shows the loss of cell radioresistance when continuous irradiation is stopped, the initial hypothesis may be dismissed and research directed towards changes relative to cell restoration processes by irradiation at low dose rates

  3. Lung Cancer Rates by State

    Science.gov (United States)

    ... HPV-Associated Ovarian Prostate Skin Uterine Cancer Home Lung Cancer Rates by State Language: English Español (Spanish) Recommend ... incidence data are currently available. Rates of Getting Lung Cancer by State The number of people who get ...

  4. Ovarian Cancer Rates by State

    Science.gov (United States)

    ... HPV-Associated Lung Prostate Skin Uterine Cancer Home Ovarian Cancer Rates by State Language: English Español (Spanish) Recommend ... for which statistics are available. Rates of Getting Ovarian Cancer by State The number of women who get ...

  5. New risk estimates at low doses

    International Nuclear Information System (INIS)

    The age of molecular radiation epidemiology may be at hand. The techniques are available to establish with the degree of precision required to determine whether agent-specific mutations can be identified consistently. A concerted effort to examine radiation-induced changes in as many relevant genes as possible appears to be justified. Cancers in those exposed to low doses of ionizing radiation should be chosen for the investigation. Parallel studies of radiation-induced cancers in experimental animals would not only complement the human studies, but perhaps reveal approaches to extrapolation of risk estimates across species. A caveat should be added to this optimistic view of what molecular studies might contribute to the knotty problem of risk estimates at low doses. The suggestions are made by one with no expertise in the field of molecular biology

  6. The 20th L H Gray Conference - Radiation Cancer Analysis and Low Dose Risk Assessment: New Developments and Perspectives (Ede, the Netherlands, February 2002)

    International Nuclear Information System (INIS)

    There are few international venues where scientists in vastly different fields working on a common problem, or on a number of closely related problems, can get together in an intimate setting to present the results of their research and to discuss their approaches and views in a collegial atmosphere, and without the trappings of a huge convention with its conflicting parallel sessions and distracting events. Over the years, the L H Gray Conferences have provided an ideal setting for such intimate gatherings. This year the 20th L H Gray Conference, held in Ede, the Netherlands, was no exception. Convened for the first time outside the United Kingdom and hosted by the Dutch National Institute for Public Health and the Environment (RIVM). Paramount in all the participants' minds was the emerging information from molecular radiation biology on the recently recognised 'new' processes such as genomic instability, bystander effects, hypersensitivity, and the adaptive response. A novel aspect this year was the introduction of the opportunity, both at the beginning and at the end of the meeting, to participate in a 'vote' on controversial subjects by answering electronically such questions as: 'does radiation hormesis occur at low doses?' and 'should an age-dependence of radiological risk be incorporated into recommendations for radiation protectionThere appears to be no evidence for radiation-induced genomic instability, at least in this tumour. If this model holds for other tumour types, it would suggest that there is no 'radiation fingerprint' and that no special mechanism lies behind radiation-induced cancer. The major social event of the meeting was an afternoon devoted to a delightful excursion to the renowned Kroeller-Mueller Museum in the nearby national park (De Hoge Veluwe). Our Dutch hosts were even able to order up some sunshine for the day. After an afternoon of strolling through the museum and surrounding park, we were bussed to a hotel on the precipitous

  7. AB139. Low-dose versus standard dose of bacillus Calmette-Guerin in the treatment of non-muscle invasive bladder cancer

    Science.gov (United States)

    Xu, Chuanliang

    2016-01-01

    Objective To investigate whether low-dose BCG treatment can reduce the side effects while maintaining efficacy for patients with NMIBC when compared with standard dose BCG treatment. Methods A comprehensive literature search of PubMed, EMBASE, CINAHL, LILACS and CENTRAL databases was conducted to identify relevant randomized controlled trials (RCT) or quasi-randomized controlled trials (qRCT) that have assessed the efficacy of low and standard dose BCG therapy for patients with NMIBC. Systematic review and meta-analysis were performed according to preferred reporting items for systematic reviews and meta-analysis criteria. Results Six RCTs and two qRCTs were eligible for meta-analysis. Low-dose BCG instillation was not inferior to reduce the risk of bladder tumor recurrence [hazard ratio (HR), 1.15; 95% confidence interval (CI), 1.00–1.31; P=0.05], meanwhile no difference was found regarding tumor progression (HR =1.08; 95% CI, 0.83–1.42; P=0.57). However, low-dose BCG provided a significantly lower incidence of overall side effects (RR =0.75; 95% CI, 0.60–0.94; P=0.01), systemic side effects (RR =0.57; 95% CI, 0.34–0.97; P=0.04), severe side effects (RR =0.52; 95% CI, 0.36–0.74; P=0.0003) and withdrawal due to BCG toxicity (RR =0.49; 95% CI, 0.26–0.91; P=0.02). In contrast, local side effects were comparable between low-dose and standard dose arms (RR =0.89; 95% CI, 0.73–1.08; P=0.24). Conclusions Low-dose BCG instillation significantly reduces the incidence of overall side effects, especially severe and systemic symptoms in patients with NMIBC, while the oncological control efficacy of low-dose BCG is not inferior to standard dose BCG. Further studies with stratification using different risk factors at randomization are required to assess whether the efficacy of low-dose BCG is comparable to standard dose BCG for different risk of patients.

  8. High dose rate brachytherapy for oral cancer

    International Nuclear Information System (INIS)

    Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer. (author)

  9. EFFECT OF LOW DOSES OF THE MYCOTOXIN FUMONISIN B1 ON THE BODY MASS GAIN, FEED INTAKE AND FEED CONVERSION RATE OF PIGS

    Directory of Open Access Journals (Sweden)

    Akos Toth

    2000-06-01

    Full Text Available The fumonisin group of mycotoxins produced by Fusariun moniliforme is a rather newly discovered contaminant of some agricultural products, especially maize based food and animal feed. Fumonisin was discovered in 1988 of mouldy maize inspected since 1993 has shown FB1 contamination, the degree of this contamination increasing from year to year. Problems of mycotoxins cause significant economic losses due to the reduced feed intake, body weight gain and feed efficiency. We have very few informations about the effect of FB1 on these in South Africa, where high evidence was found between the occurrence of human oesophageal cancer and the rate of FB1 contamination. The discovery of this toxin lead to the explanation of equine leucoencephalomalacia (ELEM, porcine pulmonary oedema (PPC and possibly liver cancer in rats. In Hungary almost 70 % parameters – especially in farm animals. Three experiments were carried out with weaned piglets, in order to study the dose and time dependent effect of FB1. Fungal culture of Fusariun moniliforme was added to the diet so that the FB1 exposure was: 0, 10, 20 and 40 ppm for 4 weeks, 0, 1, 5 and 10 ppm for 8 weeks and 0, 1, 5 and 10 ppm for 5 months. In none of the experiments and the periods examined had FB1 any significant effect on feed consumption, body weight gain and feed conversion of weaned pigs. In spite of these findings mild or severe pulmonary oedema caused by the toxin was found in the animals by dissection carried out at the end of the experiment. Our results draw the attention to human health concerns of FB1. The toxin consumed by the animals without any clinical signs can cumulate in the animals and then enter the human organism by means of products of animal origin (meat, milk, etc..

  10. Endometrial safety of ultra-low-dose estradiol vaginal tablets

    DEFF Research Database (Denmark)

    Simon, James; Nachtigall, Lila; Ulrich, Lian G; Eugster-Hausmann, Michaela; Gut, Robert

    2010-01-01

    To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17ß-estradiol vaginal tablets in postmenopausal women with vaginal atrophy.......To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17ß-estradiol vaginal tablets in postmenopausal women with vaginal atrophy....

  11. Endometrial safety of ultra-low-dose estradiol vaginal tablets

    DEFF Research Database (Denmark)

    Simon, James; Nachtigall, Lila; Ulrich, Lian G; Eugster-Hausmann, Michaela; Gut, Robert

    2010-01-01

    To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17β-estradiol vaginal tablets in postmenopausal women with vaginal atrophy.......To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17β-estradiol vaginal tablets in postmenopausal women with vaginal atrophy....

  12. Harderian Gland Tumorigenesis: Low-Dose and LET Response.

    Science.gov (United States)

    Chang, Polly Y; Cucinotta, Francis A; Bjornstad, Kathleen A; Bakke, James; Rosen, Chris J; Du, Nicholas; Fairchild, David G; Cacao, Eliedonna; Blakely, Eleanor A

    2016-05-01

    Increased cancer risk remains a primary concern for travel into deep space and may preclude manned missions to Mars due to large uncertainties that currently exist in estimating cancer risk from the spectrum of radiations found in space with the very limited available human epidemiological radiation-induced cancer data. Existing data on human risk of cancer from X-ray and gamma-ray exposure must be scaled to the many types and fluences of radiations found in space using radiation quality factors and dose-rate modification factors, and assuming linearity of response since the shapes of the dose responses at low doses below 100 mSv are unknown. The goal of this work was to reduce uncertainties in the relative biological effect (RBE) and linear energy transfer (LET) relationship for space-relevant doses of charged-particle radiation-induced carcinogenesis. The historical data from the studies of Fry et al. and Alpen et al. for Harderian gland (HG) tumors in the female CB6F1 strain of mouse represent the most complete set of experimental observations, including dose dependence, available on a specific radiation-induced tumor in an experimental animal using heavy ion beams that are found in the cosmic radiation spectrum. However, these data lack complete information on low-dose responses below 0.1 Gy, and for chronic low-dose-rate exposures, and there are gaps in the LET region between 25 and 190 keV/μm. In this study, we used the historical HG tumorigenesis data as reference, and obtained HG tumor data for 260 MeV/u silicon (LET ∼70 keV/μm) and 1,000 MeV/u titanium (LET ∼100 keV/μm) to fill existing gaps of data in this LET range to improve our understanding of the dose-response curve at low doses, to test for deviations from linearity and to provide RBE estimates. Animals were also exposed to five daily fractions of 0.026 or 0.052 Gy of 1,000 MeV/u titanium ions to simulate chronic exposure, and HG tumorigenesis from this fractionated study were compared to the

  13. Radon Exposure and the Definition of Low Doses-The Problem of Spatial Dose Distribution.

    Science.gov (United States)

    Madas, Balázs G

    2016-07-01

    Investigating the health effects of low doses of ionizing radiation is considered to be one of the most important fields in radiological protection research. Although the definition of low dose given by a dose range seems to be clear, it leaves some open questions. For example, the time frame and the target volume in which absorbed dose is measured have to be defined. While dose rate is considered in the current system of radiological protection, the same cancer risk is associated with all exposures, resulting in a given amount of energy absorbed by a single target cell or distributed among all the target cells of a given organ. However, the biological effects and so the health consequences of these extreme exposure scenarios are unlikely to be the same. Due to the heterogeneous deposition of radon progeny within the lungs, heterogeneous radiation exposure becomes a practical issue in radiological protection. While the macroscopic dose is still within the low dose range, local tissue doses on the order of Grays can be reached in the most exposed parts of the bronchial airways. It can be concluded that progress in low dose research needs not only low dose but also high dose experiments where small parts of a biological sample receive doses on the order of Grays, while the average dose over the whole sample remains low. A narrow interpretation of low dose research might exclude investigations with high relevance to radiological protection. Therefore, studies important to radiological protection should be performed in the frame of low dose research even if the applied doses do not fit in the dose range used for the definition of low doses. PMID:27218294

  14. Dose to the Bladder Neck Is the Most Important Predictor for Acute and Late Toxicity After Low-Dose-Rate Prostate Brachytherapy: Implications for Establishing New Dose Constraints for Treatment Planning

    International Nuclear Information System (INIS)

    Purpose: To identify an anatomic structure predictive for acute (AUT) and late (LUT) urinary toxicity in patients with prostate cancer treated with low-dose-rate brachytherapy (LDR) with or without external beam radiation therapy (EBRT). Methods and Materials: From July 2002 to January 2013, 927 patients with prostate cancer (median age, 66 years) underwent LDR brachytherapy with Iodine 125 (n=753) or Palladium 103 (n=174) as definitive treatment (n=478) and as a boost (n=449) followed by supplemental EBRT (median dose, 50.4 Gy). Structures contoured on the computed tomographic (CT) scan on day 0 after implantation included prostate, urethra, bladder, and the bladder neck, defined as 5 mm around the urethra between the catheter balloon and the prostatic urethra. AUT and LUT were assessed with the Common Terminology Criteria for Adverse Events, version4. Clinical and dosimetric factors associated with AUT and LUT were analyzed with Cox regression and receiver operating characteristic analysis to calculate area under the receiver operator curve (ROC) (AUC). Results: Grade ≥2 AUT and grade ≥2 LUT occurred in 520 patients (56%) and 154 patients (20%), respectively. No grade 4 toxicities were observed. Bladder neck D2cc retained a significant association with AUT (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.03-1.04; P<.0001) and LUT (HR, 1.01; 95% CI, 1.00-1.03; P=.014) on multivariable analysis. In a comparison of bladder neck with the standard dosimetric variables by use of ROC analysis (prostate V100 >90%, D90 >100%, V150 >60%, urethra D20 >130%), bladder neck D2cc >50% was shown to have the strongest prognostic power for AUT (AUC, 0.697; P<.0001) and LUT (AUC, 0.620; P<.001). Conclusions: Bladder neck D2cc >50% was the strongest predictor for grade ≥2 AUT and LUT in patients treated with LDR brachytherapy. These data support inclusion of bladder neck constraints into brachytherapy planning to decrease urinary toxicity

  15. Investigating the influence of drug aggregation on the percutaneous penetration rate of tetracaine when applying low doses of the agent topically to the skin.

    Science.gov (United States)

    Cai, X J; Patel, T; Woods, A; Mesquida, P; Jones, S A

    2016-04-11

    Understanding the molecular aggregation of therapeutic agents is particularly important when applying low doses of a drug to the surface of the skin. The aim of this study was to understand how the concentration of a drug influenced its molecular aggregation and its subsequent percutaneous penetration after topical application. A model drug tetracaine was shown to form a series of different aggregates across the μM (fluorescence spectroscopy) to mM (light scattering analysis) concentration range. The aggregate formation process was sensitive to the pH of the vehicle in which the drug was dissolved (pH 4, critical aggregation concentration (CAC) - 11μM; pH 8, CAC - 7μM) and it appeared to have an impact upon the drug's percutaneous penetration. At pH 4, increasing the concentration of the drug in the donor solution decreased the skin permeability coefficient (Kp) of tetracaine (13.7±4.3×10(-3)cm/h to0.06±0.02×10(-3)cm/h), whilst at pH 8, it increased the Kp (29.9±9.9×10(-3)cm/h to 75.1±41.7×10(-3)cm/h). These data trends were reproduced in a silicone membrane and this supported the notion that the more polar aggregates formed at pH 4 acted to decrease the proportion of species available to pass through the skin, whilst the more hydrophobic aggregates formed in pH 8 increased the membrane diffusing species. PMID:26854427

  16. Cytogenetic effects of low-dose radiation

    International Nuclear Information System (INIS)

    The effects of ionizing radiation on chromosomes have been known for several decades and dose-effect relationships are also fairly well established in the mid- and high-dose and dose-rate range for chromosomes of mammalian cells. In the range of low doses and dose rates of different types of radiation few data are available for direct analysis of the dose-effect relationships, and extrapolation from high to low doses is still the unavoidable approach in many cases of interest for risk assessment. A review is presented of the data actually available and of the attempts that have been made to obtain possible generalizations. Attention is focused on some specific chromosomal anomalies experimentally induced by radiation (such as reciprocal translocations and aneuploidies in germinal cells) and on their relevance for the human situation. (author)

  17. Association between absolute volumes of lung spared from low-dose irradiation and radiation-induced lung injury after intensity-modulated radiotherapy in lung cancer: a retrospective analysis

    OpenAIRE

    Chen, Jinmei; Hong, Jinsheng; Zou, Xi; Lv, Wenlong; Guo, Feibao; Hong, Hualan; Zhang, Weijian

    2015-01-01

    The aim of this study was to investigate the association between absolute volumes of lung spared from low-dose irradiation and radiation-induced lung injury (RILI) after intensity-modulated radiotherapy (IMRT) for lung cancer. The normal lung relative volumes receiving greater than 5, 10, 20 and 30 Gy (V5–30) mean lung dose (MLD), and absolute volumes spared from greater than 5, 10, 20 and 30 Gy (AVS5–30) for the bilateral and ipsilateral lungs of 83 patients were recorded. Any association of...

  18. Alterations in p53-specific T cells and other lymphocyte subsets in breast cancer patients during vaccination with p53-peptide loaded dendritic cells and low-dose interleukin-2

    DEFF Research Database (Denmark)

    Svane, Inge Marie; Pedersen, Anders E; Nikolajsen, Kirsten;

    2008-01-01

    We have previously established a cancer vaccine using autologous DCs, generated by in vitro stimulation with IL-4 and GM-CSF, and pulsed with six HLA-A*0201 binding wild-type p53 derived peptides. This vaccine was used in combination with low-dose interleukin-2 in a recently published clinical...... Phase II trial where 26 HLA-A2+ patients with progressive late-stage metastatic breast cancer (BC) were included. Almost 1/3rd of the patients obtained stable disease or minor regression during treatment with a positive correlation to tumour over-expression of p53. In the present study, we performed a...... (CD44high, CCR-7low and CD62Llow). Furthermore, fresh blood from 18 cancer patients included in the vaccination trial were prospectively examined for more general treatment associated quantitative and qualitative changes in T cell subpopulations. We found that the frequency of CD4+ CD25high regulatory...

  19. Second-line treatment of non small cell lung cancer by biweekly gemcitabine and docetaxel +/- granulocyte-macrophage colony stimulating factor and low dose aldesleukine.

    Science.gov (United States)

    Correale, Pierpaolo; Tindara Miano, Salvatora; Remondo, Cinzia; Migali, Cristina; Rotundo, Maria Saveria; Macrì, Paolo; Tagliaferri, Pierosandro; Caraglia, Michele; Gotti, Giuseppe; Francini, Guido

    2009-03-15

    Background. The antitumor activity of a novel biweekly gemcitabine (G) + docetaxel (D) regimen +/- granulocyte-macrophage colony stimulating factor (GM-CSF) and aldesleukine (IL-2) has been evaluated in a phase II trial in advanced pretreated non-small-cell lung cancer (NSCLC). Results. The treatment was well tolerated. The 42.3% response rate exceeded the predefined target activity, while time to progression (TTP) and overall survival (OS) were 7 and 11.2 months, respectively. A greater objective response rate (58.3% vs 28.6%) and an increased number of eosinophils, basophils and activated mononuclear blood cells were observed in those patients who also received cytokine administration. Methods. Twenty-six NSCLC patients received second line G (1000 mg/m2) and D (75 mg/m2) every 15 days. 12/26 patients also received s.c. GM-CSF (100µg, days 2-6) and s.c. IL-2 (0.5MIU/ twice daily, days 7-14 and 16-29) by random selection. Conclusion. The biweekly GD regimen is a safe and active second-line treatment in NSCLC. Addition of immune-adjuvant cytokines' may enhance the activity of this therapeutic combination. PMID:19242101

  20. Rescue treatment with interstitial brachytherapy irradiation re very low dose rate iridium-192 (UBT) in inoperable tumors of the oral cavity, oropharynx and nodal: experience of 28 cases in the Gustave-Roussy Institute in Paris

    International Nuclear Information System (INIS)

    Purpose: A retrospective analysis of the evolution of 28 patients was performed local recurrences, second tumors and advanced disease in neck nodes in territory previously irradiated, which were re-irradiated using interstitial brachytherapy Ir-192 at very low dose rate (UBT) in the Gustave-Roussy Institute in Paris. Material and Methods: A series of 28 who had received radiation therapy is reported as part of heir initial treatment. 17 patients were treated for local recurrences or second tumors while 11 patients had presented nodal disease. All of them were inoperable. So were treated with interstitial brachytherapy with Ir-192 wires at very low rate dose (UBT), plastic tube technique, re-irradiation regime between 1978 and 1988 Gustave Roussy Institute. Two groups were considered. Group 1 included 17 patients with local recurrences, lesion progression and second tumors. Group 2 included 11 patients with metastatic nodal disease. The mean treatment volume was 45.25 cc, the average dose was 65 Gy, and the average treatment time between the first treatment and re irradiation was 56 months. The average duration of treatment was 14.6 days with a average dose rate of 0.18 Gy / h. After loading technique was used in plastic tubes. They were previously performed to load the simulation with orthogonal plates, false sources and provisional dosimetry. Late toxicity was assessed according to the RTOG score. Local control rates were studied complications and survive on some factors of possible prognostic significance. The statistical analysis of significance was performed by the method and log rank test were prepared survival curves and disease-free survival by Kaplan-Meier. Results: 2 groups were analyzed separately. In group 1, procedures were performed 17 UBTD and method of low dose rate (LDR). 10 of 17 patients achieved complete responses. The patient that the procedure was performed at low dose rate also achieved a complete response. In 3 cases, no response is not

  1. Health risks associated with low dose diagnostic or therapeutic radiation exposures

    International Nuclear Information System (INIS)

    The health risks to humans associated with exposure to low doses of ionizing radiation have been extrapolated from effects observed at high doses, dose rates, and mixed radiation qualities using a linear no threshold model. Based on this approach, it has been argued that human exposure to low doses of diagnostics X-rays and gamma-rays increase an individual's risk of developing cancer throughout their life-time. Also, repeated medical diagnostic procedures involving low dose exposures will have an additive effect and consequently further increase health risk. The specific aim of this seminar will be to address the relative risk associated with diagnostic X-rays from CT scans and gamma-rays from positron emission tomography (PET) scans. Objectives of the talk will include: 1) Defining low dose exposures at a cellular level and relate that to diagnostic or therapeutic exposures, 2) Describing modern tools in molecular cytogenetics to estimate radiation exposure and assess radiation risk, 3) Identifying the different cellular mechanisms that influence radiation risk at high and low dose exposures and relate that to individual radiation risk. (author)

  2. Statistical and low dose response

    International Nuclear Information System (INIS)

    The low dose response and the lower limit of detection of the Hanford dosimeter depend upon may factors, including the energy of the radiation, whether the exposure is to be a single radiation or mixed fields, annealing cycles, environmental factors, and how well various batches of TLD materials are matched in the system. A careful statistical study and sensitivity analysis were performed to determine how these factors influence the response of the dosimeter system. Estimates have been included in this study of the standard deviation of calculated dose for various mixed field exposures from 0 to 1000 mrem

  3. Effect of ultra-low-dose estriol and lactobacilli vaginal tablets (Gynoflor®) on inflammatory and infectious markers of the vaginal ecosystem in postmenopausal women with breast cancer on aromatase inhibitors.

    Science.gov (United States)

    Donders, G; Bellen, G; Neven, P; Grob, P; Prasauskas, V; Buchholz, S; Ortmann, O

    2015-10-01

    This study was a detailed microscopic analysis of the changes of vaginal microflora characteristics after application of 0.03 mg estriol-lactobacilli combination on the vaginal ecosystem in postmenopausal breast cancer (BC) survivors on aromatase inhibitors (AI) with severe atrophic vaginitis. A total of 16 BC women on AI applied daily one vaginal tablet of Gynoflor® for 28 days followed by a maintenance therapy of three tablets weekly for 8 weeks. During four follow up visits a smear from the upper lateral vaginal wall was analysed by phase contrast microscopy at 400 times magnification in order to classify the lactobacillary grades(LBG), bacterial vaginosis (BV), aerobic vaginitis (AV), vulvovaginal candidosis (VVC), proportional number of leukocytes and evidence of parabasal cells and epitheliolysis. LBG improved from 81% LBG-III at entry to 88% LBG-I&IIa after 2 weeks of initial therapy, which further improved upon follow up (p treatment (p < 0.01). While at entry most patients had moderate or severe AV, after maintenance therapy no patient except one had AV. The number of leukocytes dropped dramatically from a score of 1.78 ± 0.70 to 1.06 ± 0.25 which was consistent till the end of the study (p < 0.01). Parabasal cells dropped from a score of 3.4 ± 0.64 at entry to 1.3 ± 0.60 at the final visit (p trend < 0.01). Starting from a low rate of Candida colonisation of 2/14 (14%), a sudden rise to 7/16 (44%) occurred after 2 weeks, to return back to base levels at subsequent visits. The vaginal use of ultra-low dose estriol and lactobacilli results in rapid and enduring improvement of all markers of the vaginal microflora and epithelial vaginal cell quality in women with breast cancer on AI with dyspareunia. Candida may develop soon after its use, but rapidly disappears again upon their prolonged use. Due to its excellent safety profiles and clinical efficacy we recommend this product as first choice in women on AI with severe dyspareunia. PMID:26223323

  4. Complex damage, low doses and Bystander effects

    International Nuclear Information System (INIS)

    , there has been a wealth of new data showing that there are also 'untargeted' intracellular and extracellular processes that can be observed as high frequencies of delayed cellular effects (eg genomic instability) or effects in cells that have not themselves been irradiated ('bystander' effects). In considering risks from low doses and/or low dose rates of radiation, what are the relative contributions from untargeted mechanisms and how should this balance be applied to guide extrapolations of robust epidemiological data to the low exposure levels of practical relevance?

  5. [The functional state of the mitochondrial respiratory chain of the small intestine enterocytes of the rats under the low dose rate X-ray total external exposure].

    Science.gov (United States)

    2013-01-01

    The influence of the low-rate ionizing radiation (0.055 Gy/min) at the doses of 0.1; 0.5 and 1.0 Gy on the functional state of the mitochondria respiratory chain of the rat small intestine enterocytes was investigated. The dysfunction of the electron transport chain enzymes andchanges in the content of cytochromes b, c, a in themitochondrial inner membrane were revealed 1, 12 and 24 hours after exposure to radiation. The re- vealed disorders indicate early membrane sensitivity to the radiation effect. The inhibition of the H+ -ATPase activity in the studied dose range indicates the decrease of the mitochondrial energy capacity. PMID:25508872

  6. Effect of low frequency magnetic field at reproductive system state and peroxidation processes in liver of male rates after low dose chronic irradiation

    International Nuclear Information System (INIS)

    Low frequency magnetic field (power 3.5 wt, tension 8v, amplitude 15 Tl, frequency of followed impulses 10 Hz, frequency of exposure 70-90 Hz) significantly modified the morphofunctional state of the reproductive system and peroxidation processes in liver of male rates. It concluded in a partial restoration of testicular weight, a recovery of the blood serum testosterone levels and of the molecular characteristics of the androgen receptor system in liver and testes, a normalization of peroxidation processes in liver and a stimulation of some biochemical and bioenergetic processes in testes (authors)

  7. Dosimetric characterization of low dose rate Iridium 192 wires used in interstitial brachytherapy, produced by Brachytherapy Sources Laboratory the CTRS/IPEN/CNEN-SP, Brazil

    International Nuclear Information System (INIS)

    In this work they were some dosimetric parameters established by the dosimetry protocol AAPM TG-43 for the thread of 192Ir with the purpose of complementing the dosimetric specifications of an original source produced at the country. For so much quantities such as the constant of dose rate, A , function of radial dose, g(r), and anisotropy function, F(r,θ), they were experimentally determined and the geometry function, G(r,θ), it was calculated. Measurements with TLD of LiF, with dimensions of 1 mm X 1 mm X 1 mm, was made in a phantom made of 5 plates of solid water RW3 material with dimensions of 300 mm X 300 mm X 10 mm, where it was obtained values of dose rate for some radial distances of the source, between 10 and 100 mm, to for an angle of 90 deg, for g(r), and also for other angles between 0 deg and 180 deg for F(r,θ). Threads of 192Ir were studied in the lengths of 10 mm, 20 mm, 30 mm, 50 mm and 100 mm. The stored energy on the thermoluminescent dosimeters was integrated by means of a TLD reader Harshaw 2000 meantime into a cycle of thermal treatment to which the thermoluminescent dosimeters was submitted being, 400 C in an interval of time of 1 hour proceeded immediately for more 2 hours to 105 C, after this treatment the thermoluminescent dosimeters was irradiated; even so, before the reading the detectors was still warm to 105 deg C for 10 minutes. The constant of dose rate for the threads of 192Ir of 10 mm, 20 mm, 30 mm, 50 mm and 100 mm are (1,076 =- 3,7%); (0,931 =- 3,7%); (0,714 =- 3,7%); (0,589 =-3,7%) and (0,271 =- 3,7%) cGyh-1 U-1, respectively (1U = unit of kerma intensity in the air = 1mGy m2 h-1 = 1cGy cm2 h-1). The results obtained for g(r) and F(r,θ) have uncertainties of (=- 4,5%) and they are compared with values obtained by Monte Carlo simulation and also for other values presented in the literature. (author)

  8. Long-term stability of liquid ionization chambers with regard to their qualification as local reference dosimeters for low dose-rate absorbed dose measurements in water

    International Nuclear Information System (INIS)

    The long-term sensitivity and calibration stability of liquid ionization chambers (LICs) has been studied at a local and a secondary standards dosimetry laboratory over a period of 3 years. The chambers were transported several times by mail between the two laboratories for measurements. The LICs used in this work are designed for absorbed dose measurements in the dose rate region of 0.1-100 mGy min-1 and have a liquid layer thickness of 1 mm and a sensitive volume of 16.2 mm3. The liquids used as sensitive media in the chambers are mixtures of isooctane (C8H18) and tetramethylsilane (Si(CH3)4) in different proportions (about 2 to 1). Operating at a polarizing voltage of 300 V the leakage current of the chambers was stable and never exceeded 3% of the observable current at a dose rate of about 1 mGy min-1. The volume sensitivity of the chambers was measured to be of the order of 10-9 C Gy-1 mm-3. No systematic changes in the absorbed dose to water calibration was observed for any of the chambers during the test period (σ<0.2%). Variations in chamber dose response with small changes in the polarizing voltage as well as sensitivity changes with accumulated absorbed dose were also investigated. Measurements showed that the LIC response varies by 0.15% per 1% change in applied voltage around 300 V. No significant change could be observed in the LIC sensitivity after a single absorbed dose of 15 kGy. The results indicate that the LIC can be made to serve as a calibration transfer instrument and a reference detector for absorbed dose to water determinations providing good precision and long-term reproducibility. (author)

  9. Pre-irradiation with low-dose 12C6+ beam significantly enhances the efficacy of AdCMV-p53 gene therapy in human non-small lung cancer

    Science.gov (United States)

    Liu, Bing; Zhang, Hong; Li, Wenjian; Li, Qiang; Zhou, Guangming; Xie, Yi; Hao, Jifang; Min, Fengling; Zhou, Qingming; Duan, Xin

    2007-04-01

    The combination of ionizing radiation and gene therapy has been investigated. However, there are very few reports about the combination of heavy-ion irradiation and gene therapy. To determine if the pre-exposure to low-dose heavy ion beam enhances the suppression of AdCMV-p53 on non-small lung cancer (NSLC), the cells pre-irradiated or non-irradiated were infected with 20, 40 MOI of AdCMV-p53. Survival fraction and the relative biology effect (RBE) were determined by clonogenic assay. The results showed that the proportions of p53 positive cells in 12C6+ beam induced AdCMV-p53 infected cells were more than 90%, which were significantly more than those in γ-ray induced AdCMV-p53 infected cells. The pre-exposure to low-dose 12C6+ beam significantly prevented the G0/G1 arrest and activated G2/M checkpoints. The pre-exposure to 12C6+ beam significantly improved cell to apoptosis. RBEs for the 12C6+ + AdCMV-p53 infection groups were 30% 60%, 20% 130% and 30% 70% more than those for the 12C6+-irradiated only, AdCMV-p53 infected only, and γ-irradiation induced AdCMVp53 infected groups, respectively. The data suggested that the pre-exposure to low-dose 12C6+ beam significantly promotes exogenous p53 expression in NSLC, and the suppression of AdCMV-p53 gene therapy on NSLC.

  10. Pre-irradiation with low-dose 12C6+beam significantly enhances the efficacy of AdCMV-p53 gene therapy in human non-small lung cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The combination of ionizing radiation and gene therapy has been investigated. However, there are very few reports about the combination of heavy-ion irradiation and gene therapy. To determine if the pre-exposure to low-dose heavy ion beam enhances the suppression of AdCMV-p53 on non-small lung cancer (NSLC), the cells pre-irradiated or non-irradiated were infected with 20, 40 MOI of AdCMV-p53. Survival fraction and the relative biology effect (RBE) were determined by clonogenic assay. The results showed that the proportions of p53 positive cells in 12C6+ beam induced AdCMV-p53 infected cells were more than 90%, which were signifi-cantly more than those in γ-ray induced AdCMV-p53 infected cells. The pre-exposure to low-dose 12C6+ beam significantly prevented the G0/G1 arrest and activated G2/M checkpoints. The pre-exposure to 12C6+ beam significantly improved cell to apoptosis. RBEs for the 12C6+ + AdCMV-p53 infection groups were 30%-60%, 20%-130% and 30%-70% more than those for the 12C6+-irradiated only, AdCMV-p53 infected only, and γ-irradiation induced AdCMVp53 infected groups, respectively. The data suggested that the pre-exposure to low-dose 12C6+ beam significantly promotes exogenous p53 expression in NSLC, and the suppression of AdCMV-p53 gene therapy on NSLC.

  11. Genes activated by low dose radiation

    International Nuclear Information System (INIS)

    Gene expression profiles were examined in the mouse kidney and testis in order to investigate the molecular mechanisms of the life span-shortening effect of low dose-rate radiation. C57BL/6J male mice (7-8 wks old) were irradiated by cesium-137 gamma-rays for 485 days at rates of 0, 32, 650 and 13,000 nGy/min and organs were excised out. Gene expression was analyzed with cDNA microarray Illumina Sentrix Mouse-6. In the kidney, 4 genes concerning mitochondrial respiration (oxidative phosphorylation) were found to be up-regulated at the middle and high dose rates (expression level changed in >1.6 folds by irradiation). Significantly modulated genes were in 16 clusters, which exerted elevated expression level dose rate-dependently and found to be categorized in cytoplasm/mitochondria/energy pathways by the database ''Gene Ontology''. In the testis, gene expression pattern was different from that in kidney. Clustering analysis and database revealed that up-regulated genes belonged to ''DNA repair'', ''response to DNA damage'', DNA replication'' and ''Mitotic cell cycles''. Thus low dose radiation can cause the cellular oxidative stress by elevated respiratory activity in the kidney, and a type of emergent biological response in the testis. (R.T.)

  12. Are radiosensitivity data derived from natural field conditions consistent with data from controlled exposures? A case study of Chernobyl wildlife chronically exposed to low dose rates

    International Nuclear Information System (INIS)

    The discrepancy between laboratory or controlled conditions ecotoxicity tests and field data on wildlife chronically exposed to ionising radiation is presented for the first time. We reviewed the available chronic radiotoxicity data acquired in contaminated fields and used a statistical methodology to support the comparison with knowledge on inter-species variation of sensitivity to controlled external γ irradiation. We focus on the Chernobyl Exclusion Zone and effects data on terrestrial wildlife reported in the literature corresponding to chronic dose rate exposure situations (from background∼100 nGy/h up to ∼10 mGy/h). When needed, we reconstructed the dose rate to organisms and obtained consistent unbiased data sets necessary to establish the dose rate–effect relationship for a number of different species and endpoints. Then, we compared the range of variation of radiosensitivity of species from the Chernobyl-Exclusion Zone with the statistical distribution established for terrestrial species chronically exposed to purely gamma external irradiation (or chronic Species radioSensitivity Distribution – SSD). We found that the best estimate of the median value (HDR50) of the distribution established for field conditions at Chernobyl (about 100 μGy/h) was eight times lower than the one from controlled experiments (about 850 μGy/h), suggesting that organisms in their natural environmental were more sensitive to radiation. This first comparison highlights the lack of mechanistic understanding and the potential confusion coming from sampling strategies in the field. To confirm the apparent higher sensitive of wildlife in the Chernobyl Exclusion Zone, we call for more a robust strategy in field, with adequate design to deal with confounding factors. -- Highlights: ► Discrepancy between controlled tests and Chernobyl effects data on wildlife was examined. ► We proposed a method to correct the dosimetry used for Chernobyl wildlife. ► Wildlife from the

  13. Near-term and late biological effects of acute and low-dose-rate continuous gamma-ray exposure in dogs and monkeys

    International Nuclear Information System (INIS)

    Monkeys (Macaca mulatta) and dogs (beagle) were given thirteen 100-rad gamma-ray doses at 28-day intervals. The comparative response (inury and recovery) of the hematopoietic system of the two species was observed at 7-day intervals during the exposure regime. At 84 days after the thirteenth gamma-ray dose, the 1300-rad conditioned and control dogs and monkeys were challenged continuously with gamma rays at 35 r/day until death to determine the amount of radiation-induced injry remaining in conditioned animals as a reduction in mean survival time. Dogs (50%) and monkeys (8%) died from injury incurred during conditioning exposures. Thus, the comparative response (in terms of lethality) of dogs and monkeys to dose protraction by acute dose fractionation was similar to what we would expect from a single acute dose. The mean survival times for nonconditioned dogs and monkeys during continuous exposure at 35 R/day were the same (approx. 1400 h). Thus, the hematopoietic response of the two species by this method of dose protraction was not significantly different. Mean survival times of conditioned dogs and monkeys during the continuous 35-R/day gamma-ray challenge exposure were greater (significant in dogs but not in monkeys) than for their control counterparts. Thus, long-term radiation-induced injury was not measurable by this method. Conditioning doses of more than 4 times the acute LD5030 in dogs and approximately 2 times that in monkeys served only to increase both mean survival time and variance in a gamma-ray stress environment with a dose rate of 35 Rat/day

  14. There Is No Correlation Between Erectile Dysfunction and Dose to Penile Bulb and Neurovascular Bundles Following Real-Time Low-Dose-Rate Prostate Brachytherapy

    International Nuclear Information System (INIS)

    Purpose: We evaluated the relationship between the onset of erectile dysfunction and dose to the penile bulb and neurovascular bundles (NVBs) after real-time ultrasound-guided prostate brachytherapy. Methods and Materials: One hundred forty-seven patients who underwent prostate brachytherapy met the following eligibility criteria: (1) treatment with 125I brachytherapy to a prescribed dose of 160 Gy with or without hormones without supplemental external beam radiation therapy, (2) identification as potent before the time of implantation based on a score of 2 or higher on the physician-assigned Mount Sinai Erectile Function Score and a score of 16 or higher on the abbreviated International Index of Erectile Function patient assessment, and (3) minimum follow-up of 12 months. Median follow-up was 25.7 months (range, 12-47 months). Results: The 3-year actuarial rate of impotence was 23% (34 of 147 patients). An additional 43% of potent patients (49 of 113 patients) were using a potency aid at last follow-up. The penile bulb volume receiving 100% of the prescription dose (V100) ranged from 0-0.05 cc (median, 0 cc), with a dose to the hottest 5% (D5) range of 12.5-97.9 Gy (median, 40.8 Gy). There was no correlation between penile bulb D5 or V100 and postimplantation impotency on actuarial analysis. For the combined right and left NVB structures, V100 range was 0.3-5.1 cc (median, 1.8 cc), and V150 range was 0-1.5 cc (median, 0.31 cc). There was no association between NVB V100 or V150 and postimplantation impotency on actuarial analysis. Conclusion: Penile bulb doses are low after real-time ultrasound-guided prostate brachytherapy. We found no correlation between dose to either the penile bulb or NVBs and the development of postimplantation impotency.

  15. Low dose rate 137Cs Brachytherapy source calibration with farmer type ionisation chamber and specialised fabricated jig in Korle-Bu Teaching Hospital

    International Nuclear Information System (INIS)

    An important part of a general quality assurance (QA) program for brachytherapy dosimetry is the source calibration because wide ranges of uncertainties are quoted by manufactures. This research is aimed at calibrating LDR 137Cs brachytherapy source in the Korle-Bu Teaching Hospital by multiple-distance air kerma measurement technique using a specialized designed jig and a calibrated therapy ionization chamber. Specialized jig was fabricated with source holder positions and ionization chamber positions on the jig. Farmer type ionization chamber of volume 0.6cm3 was used with and without build up cap. The results were validated using well type ionization chamber on channels on 1 and 5 taking into account decay correction. Air Kerma rates were determined at multiple distances between 8cm to 12cm from measured charges recorded by Max 4000 electrometer. The scatter dose relationship described by Ezzell [1992] was used to determine scattered radiation. The analytical method of determining air kerma calibration factor of 137Cs described by Sharma et.al [2011] was used to determine beam quality correction factor for the 137Cs. Beam attenuation was determined. Experimental data were compared with manufacturer's quoted source strength for verification. Well type ionization chamber results and experimental results on channel V1 and V5 deviated by 2.39% and 1.58% respectively. Experimental data deviated by 4.73% and 1.24% from theoretical data on channels V1 and V5 respectively. The mean of the experimental data deviated from the theoretical data by ±3.1% and from the well type measurements data by ±1.98%. The well type chamber results compared well with the experimental data. This is an indication that the method used for source calibration is a reliable alternative method of source calibration. The method used in this work has proven to be an efficient way of determining the actual source strength of the LDR brachytherapy 137Cs source in Korle-Bu Radiotherapy Centre

  16. Intradermal vaccination of adults with three low doses (2 µg of recombinant hepatitis B vaccine. I. Seroconversion rate and adverse effects

    Directory of Open Access Journals (Sweden)

    Baldy José Luís da S

    2003-01-01

    Full Text Available A total of 250 dentists (53.6% men and 46.4% women, with a mean age of 35.1 ± 9.8 years, were submitted to serological tests for the diagnosis of hepatitis B (HB - HBsAg, anti-HBs, anti-HBc, HBeAg, and anti-HBe - using a radioimmunoassay. One or more of these markers were detected in 78 individuals (31.2% who were excluded from the group to be vaccinated. Of the 172 HB-susceptible individuals, 135 (78.5% responded to the call and were intradermally injected with three 2 µg doses of the Belgian HB recombinant vaccine, applied at an interval of one month between the 1st and 2nd dose and of five months between the 2nd and 3rd dose. A new determination of HB markers carried out 50 days after the 3rd dose showed that 110 (81.5% individuals had become anti-HBs positive (65.5% good responders and 34.5% poor responders. Mean serum anti-HBs titer of these 110 dentists was 42.4 U S/N, similar in both sexes. The adverse effects analyzed in 106 dentists were: (a local: pain (12.3%, burning sensation (14.1%, pruritus (25.5%, erythema (28.3%, local heat (18.9%, and a hypochromic spot (32.1%; (b systemic (4.7%: discomfort in two patients, and fever, anorexia, and asthenia in one patient each. Intradermal administration of a fourth 2 µg vaccine dose to 39 dentists (poor or non-responders increased the total number of anti-HBs-positive individuals from 110 (81.5% to 114 (84.4%, with the number of good responders increasing from 72 (65.5% to 85 (74.6%. We conclude that the Belgian recombinant vaccine applied in the scheme used here induces a high rate of seroconversion and causes only mild and transitory adverse effects.

  17. Enhancement of the Immunostimulatory Functions of Ex Vivo–Generated Dendritic Cells from Early-Stage Colon Cancer Patients by Consecutive Exposure to Low Doses of Sequential-Kinetic-Activated IL-4 and IL-12. A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Elisabetta Radice

    2015-08-01

    Full Text Available Dendritic cells (DCs, specialized antigen-presenting cells bridging innate and adaptive immunity, play a crucial role in determining specific immune response to tumors. Because of their potent immunoregulatory capacities, DCs have been exploited in anticancer vaccination, with limited success thus far. This pilot study compared low-dose interleukin (IL-4 and IL-12 prepared by sequential kinetic activation (SKA with standard doses of the same recombinant human cytokines on functional activity of ex vivo–generated monocyte-derived (Mo DCs from colon carcinoma patients and normal subjects. MoDCs were exposed to medium alone, SKA-IL-4 (0.5 fg/ml, or SKA-IL-12 (2 fg/ml, alone or consecutively combined, in parallel with rhIL-4 (50 ng/ml and rhIL-12 (1 ng/ml. Primary allogeneic one-way mixed lymphocyte reaction (MLR was the end point to assess in vitro T-lymphocyte proliferation in response to MoDCs, and secreted IL-12p70 and interferon-γ in MLR supernatants measured by ELISA to assay for T-helper 1–promoting MoDC phenotype. No single agent enhanced the compromised allostimulatory activity of MoDCs from colon cancer patients, unlike healthy donors. However, MoDCs from nonmetastatic colon cancer patients, after sequential exposure to SKA-IL-4 (48 hours and SKA-IL-12 (24 hours, displayed increased T-cell stimulatory capacity by MLR and acquired driving T-helper 1 polarization activity, although less markedly than the effects induced by recombinant human cytokines or found in normal subjects. These results point to an immunomodulatory capacity of low-dose SKA-IL-4 and SKA-IL-12 and encourage further investigation to provide clues for the rational development of new and more effective immunotherapeutic strategies against cancer.

  18. Breast cancer risk from low-dose exposures to ionizing radiation: results of parallel analysis of three exposed populations of women

    International Nuclear Information System (INIS)

    Breast cancer incidence data were analyzed from three populations of women exposed to ionizing radiation: survivors of the Hiroshima and Nagasaki atomic bombs, patients in Massachusetts tuberculosis sanitoria who were exposed to multiple chest fluoroscopies, and patients treated by X-rays for acute postpartum mastitis in Rochester, New York. Parallel analyses by radiation dose, age at exposure, and time after exposure suggested that risk of radiation-induced cancer increased approximately linearly with increasing dose and was heavily dependent on age at exposure; however, the risk was otherwise remarkably similar among the three populations, at least for ages 10 to 40 years at exposure, and followed the same temporal pattern of occurrence as did breast cancer incidence in nonexposed women of similar ages

  19. Myeloid Sarcoma of the Uterine Cervix as Presentation of Acute Myeloid Leukaemia after Treatment with Low-Dose Radioiodine for Thyroid Cancer: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Anne Sophie Weingertner

    2009-01-01

    Full Text Available The development of acute myeloid leukaemia after low-dose radioiodine therapy and its presentation as a myeloid sarcoma of the uterine cervix are both rare events. We report a case of acute myeloid leukaemia revealed by a myeloid sarcoma of the uterine cervix in a 48-year-old woman, 17 months after receiving a total dose of 100 mCi 131I for papillary thyroid cancer. A strict hematological follow-up of patients treated with any dose of 131I is recommended to accurately detect any hematological complications which might have been underestimated. Unusual presentations, such as chloroma of the uterine cervix, may reveal myeloid malignancy and should be kept in mind.

  20. Lung Cancer Rates by Race and Ethnicity

    Science.gov (United States)

    ... HPV-Associated Ovarian Prostate Skin Uterine Cancer Home Lung Cancer Rates by Race and Ethnicity Language: English Español ( ... Tweet Share Compartir The rate of people getting lung cancer or dying from lung cancer varies by race ...

  1. Prostate Cancer Rates by Race and Ethnicity

    Science.gov (United States)

    ... HPV-Associated Lung Ovarian Skin Uterine Cancer Home Prostate Cancer Rates by Race and Ethnicity Language: English Español ( ... Tweet Share Compartir The rate of men getting prostate cancer or dying from prostate cancer varies by race ...

  2. Cervical Cancer Rates by Race and Ethnicity

    Science.gov (United States)

    ... Associated Lung Ovarian Prostate Skin Uterine Cancer Home Cervical Cancer Rates by Race and Ethnicity Language: English Español ( ... Tweet Share Compartir The rate of women getting cervical cancer or dying from cervical cancer varies by race ...

  3. Ovarian Cancer Rates by Race and Ethnicity

    Science.gov (United States)

    ... HPV-Associated Lung Prostate Skin Uterine Cancer Home Ovarian Cancer Rates by Race and Ethnicity Language: English Español ( ... Tweet Share Compartir The rate of women getting ovarian cancer or dying from ovarian cancer varies by race ...

  4. Colorectal Cancer Rates by Race and Ethnicity

    Science.gov (United States)

    ... Associated Lung Ovarian Prostate Skin Uterine Cancer Home Colorectal Cancer Rates by Race and Ethnicity Language: English Español ( ... Tweet Share Compartir The rate of people getting colorectal cancer or dying from colorectal cancer varies by race ...

  5. Human health effects of low doses of ionizing radiation: the BEIR III controversy

    International Nuclear Information System (INIS)

    Controversy in the BEIR III Subcommittee on Somatic Effects concerning human health effects of low doses of low-LET radiation has centered on (a) the appropriate dose-response relationship by which extrapolation to low doses of data obtained at relatively high doses should be governed, and (b) the appropriate human evidence which should be the basis of estimation of lifetime cancer risk from radiation exposure. It is shown that the use of the linear no-threshold dose-response relationship for extrapolation purposes is an excellent approximation that is in agreement with widely accepted fundamental radiobiological principles. The appropriate human data for derivation of cancer risks are the composite age-specific risks derived from all epidemiologic studies of human cancer resulting from partial-body and whole-body radiation exposure; this composite is in good agreement with the currently available cancer incidence dose-response data obtained from the Nagasaki Tumor Registry. The current version of BEIR III significantly underestimates the radiation-induced cancer risk because it ignores the effect of high-dose-rate, low-LET radiation on cell survival in relation to cancer induction probability, and because it emphasizes cancer mortality rather than cancer incidence. The controversy and the way in which it was resolved raises important questions about how the public and its representatives can in the future obtain objective scientific evaluations of issues that may have significant economic, social, and political implications

  6. Sustained platelet-sparing effect of weekly low dose paclitaxel allows effective, tolerable delivery of extended dose dense weekly carboplatin in platinum resistant/refractory epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Blagden Sarah

    2011-07-01

    Full Text Available Abstract Background Platinum agents have shown demonstrable activity in the treatment of patients with platinum resistant, recurrent ovarian cancer when delivered in a "dose-dense" fashion. However, the development of thrombocytopenia limits the weekly administration of carboplatin to no greater than AUC 2. Paclitaxel has a well-described platelet sparing effect however its use to explicitly provide thromboprotection in the context of dose dense carboplatin has not been explored. Methods We treated seven patients with platinum resistant ovarian cancer who had previously received paclitaxel or who had developed significant peripheral neuropathy precluding the use of further full dose weekly paclitaxel. Results We were able to deliver carboplatin AUC 3 and paclitaxel 20 mg/m2 with no thrombocytopenia or worsening of neuropathic side-effects, and with good activity. Conclusions We conclude that this regimen may be feasible and active, and could be formally developed as a "platinum-focussed dose-dense scaffold" into which targeted therapies that reverse platinum resistance can be incorporated, and merits further evaluation.

  7. Low-dose cyclophosphamide-induced acute hepatotoxicity

    OpenAIRE

    Subramaniam, S. Ravih; Cader, Rizna Abdul; Mohd, Rozita; Yen, Kong Wei; Ghafor, Halim Abdul

    2013-01-01

    Patient: Male, 48 Final Diagnosis: Low dose cyclophosphamide-induced acute hepatotoxicity Symptoms: Epigastric pain Medication: Withdrawal of cyclophosphamide Clinical Procedure: — Specialty: Nephrology • Hepatology • Gastroenterology • Toxicology Objective: Unexpected drug reaction Background: Cyclophosphamide is commonly used to treat cancers, systemic vasculitides, and kidney diseases (e.g., lupus nephritis and focal segmental glomerulosclerosis). Acute adverse effects include bone marrow ...

  8. Transcriptome profiling of mice testes following low dose irradiation

    DEFF Research Database (Denmark)

    Belling, Kirstine C.; Tanaka, Masami; Dalgaard, Marlene Danner; Nielsen, John Erik; Nielsen, Henrik Bjørn; Brunak, Søren; Almstrup, Kristian; Leffers, Henrik

    2013-01-01

    ABSTRACT: BACKGROUND: Radiotherapy is used routinely to treat testicular cancer. Testicular cells vary in radio-sensitivity and the aim of this study was to investigate cellular and molecular changes caused by low dose irradiation of mice testis and to identify transcripts from different cell types...

  9. Fludarabine Phosphate, Low-Dose Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies or Kidney Cancer

    Science.gov (United States)

    2015-10-13

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); B-cell Chronic Lymphocytic Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Childhood Renal Cell Carcinoma; Chronic Phase Chronic Myelogenous Leukemia; Clear Cell Renal Cell Carcinoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Splenic Marginal Zone Lymphoma; Stage III Renal Cell Cancer; Stage IV Renal Cell Cancer; T-cell Large Granular Lymphocyte Leukemia; Type 1 Papillary Renal Cell Carcinoma; Type 2 Papillary Renal Cell Carcinoma; Waldenström Macroglobulinemia

  10. Low dose irradiation creep of pure nickel

    International Nuclear Information System (INIS)

    A detailed climb-controlled glide model of low dose irradiation creep has been developed to rationalize irradiation creep data of pure nickel irradiated in a light ion irradiation creep apparatus. Experimental irradiation creep data were obtained to study the effects of initial microstructure and stress on low dose irradiation creep in pure nickel. Pure nickel specimens (99.992% Ni), with three different microstructures, were irradiated with 17 or 15 MeV deuterons at 473 K and stresses ranging from 0.35 to 0.9 of the unirradiated yield stress. Transmission electron microscopy revealed that the microstructure following irradiation to 0.05 dpa consisted of a high density of small dislocation loops, some small voids and network dislocations. The creep model predicted creep rates proportional to the mobile dislocation density and a comparison of experimental irradiation creep rates as a function of homologous stress revealed a dependence on initial microstructure of the magnitude predicted by the measured dislocation densities. The three microstructures that were irradiated consisted of 85% and 25% cold-worked Ni specimens and well-annealed Ni specimens. A weak stress dependence of irradiation creep was observed in 85% cold-worked Ni in agreement with experimental determinations of the stress dependence of irradiation creep by others. The weak stress dependence was shown to be a consequence of the stress independence of the dislocation climb velocity and the weak stress dependence of the barrier removal process. The irradiation creep rate was observed to be proportional to the applied stress. This linear stress dependence was suggested to be due to the stress dependence of the mobile dislocation density. 101 references, 27 figures, 11 tables

  11. Fludarabine Phosphate, Low-Dose Total-Body Irradiation, and Donor Stem Cell Transplant Followed by Cyclosporine, Mycophenolate Mofetil, Donor Lymphocyte Infusion in Treating Patients With Hematopoietic Cancer

    Science.gov (United States)

    2016-08-01

    ; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Renal Cell Cancer; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage II Multiple Myeloma; Stage III Multiple Myeloma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  12. Preparation and determination of kerma for Iridium 192 sources of low dose rate for brachytherapy; Preparacion y determinacion del kerma de fuentes de iridio-192 de baja tasa de dosis para braquiterapia

    Energy Technology Data Exchange (ETDEWEB)

    Tendilla, J.I.; Tovar M, V.; Mitsoura, E.; Aguilar H, F.; Alanis M, J. [Instituto Nacional de Investigaciones Nucleares, C.P. 52045-1, Salazar, Esrado de Mexico, D.F. (Mexico)

    2000-07-01

    The practice of Brachytherapy with Iridium-192 sources of low dose rate (0.4 - 0.8 Gy/h) is a technique used in the treatment of diverse illnesses. in this work the preparation, quality control and calibration are presented in terms of kerma in air of Iridium-192 using as target these recycled Iridium-Platinum wires. The targets were obtained as decayed sources of different radio therapeutical centers in the country and they were characterized by Scanning electron microscopy in order to determine their chemical composition. Subsequently it was developed an experimental design to establish the effect of neutron flux, geometrical array and irradiation time over the activity and percentage of the sources homogeneity. The homogeneity was determined by auto radiography and by Gamma spectroscopy. Once the optimal irradiation conditions were established, it is determined the apparent activity and kerma in air using a well type ionization chamber with traceability to a primary laboratory. Iridium-192 sources were obtained with an average homogeneity 96 %, apparent activity 282.129 {+-} 0.531 M Bq and kerma in air 0.03200 {+-} 0.00006 m Gy m/h A. (Author)

  13. Low doses of arsenic, via perturbing p53, promotes tumorigenesis.

    Science.gov (United States)

    Ganapathy, Suthakar; Li, Ping; Fagman, Johan; Yu, Tianqi; Lafontant, Jean; Zhang, Guojun; Chen, Changyan

    2016-09-01

    In drinking water and in workplace or living environments, low doses of arsenic can exist and operate as a potent carcinogen. Due to insufficient understanding and information on the pervasiveness of environmental exposures to arsenic, there is an urgent need to elucidate the underlying molecular mechanisms of arsenic regarding its carcinogenic effect on human health. In this study, we demonstrate that low doses of arsenic exposure mitigate or mask p53 function and further perturb intracellular redox state, which triggers persistent endoplasmic reticulum (ER) stress and activates UPR (unfolded protein response), leading to transformation or tumorigenesis. Thus, the results suggest that low doses of arsenic exposure, through attenuating p53-regulated tumor suppressive function, change the state of intracellular redox and create a microenvironment for tumorigenesis. Our study also provides the information for designing more effective strategies to prevent or treat human cancers initiated by arsenic exposure. PMID:27425828

  14. Low Dose Risk, Decisions, and Risk Communication

    International Nuclear Information System (INIS)

    The overall research objective was to establish new levels of information about how people, groups, and communities respond to low dose radiation exposure. This is basic research into the social psychology of individual, group, and community responses to radiation exposures. The results of this research are directed to improving risk communication and public participation in management of environmental problems resulting from low dose radiation

  15. Effect of low-dose ionizing radiation on immune system in mice

    Energy Technology Data Exchange (ETDEWEB)

    Hoshi, Y.; Sakai, K. [Central Research Institute of Electric Power Industry, Tokyo (Japan)

    2002-07-01

    Low-dose irradiation induces a number of biological functions in mice. Nomura et al. have demonstrated that the low-dose irradiation elevates the level of antioxidants and gives suppressive effects on some chemically induced reactive oxygen species (ROS)-related disease models. We paid attention to this stimulated immunological function by low dose irradiation and started the study that by low dose irradiation and started the study that by low-dose rate irradiation. The enhancement of immune response in mice under various conditions will be discussed.

  16. Effect of low-dose ionizing radiation on immune system in mice

    International Nuclear Information System (INIS)

    Low-dose irradiation induces a number of biological functions in mice. Nomura et al. have demonstrated that the low-dose irradiation elevates the level of antioxidants and gives suppressive effects on some chemically induced reactive oxygen species (ROS)-related disease models. We paid attention to this stimulated immunological function by low dose irradiation and started the study that by low dose irradiation and started the study that by low-dose rate irradiation. The enhancement of immune response in mice under various conditions will be discussed

  17. The effect of low-dose β-blocker on heart rate and heart rate variability in health subjects wth a resting heart rate of less than 65 beats per minute: Effect on the quality of prospective electrocardiography-gated coronary CT angiography

    International Nuclear Information System (INIS)

    We assessed the effect of a low-dose β-blocker on heart rate (HR), HR variability (HRV) and image quality of prospective electrocardiography-gated coronary CT angiography (CCTA) in healthy subjects with low HR. CCTA was performed with a 64-slice CT in 75 subjects with a HR of less than 65 beats per minute (bpm). Subjects were divided into 2 groups: Group 1 (G1), 35 with a low dose β-blocker; and Group 2 (G2), 40 without pre-medication. The image quality (IQ) of the CCTA was assessed on a 4-point grading scale (1, poor; 4, excellent). Initial HR (bpm) was not different between the 2 groups. HR during CCTA was lower in G1 than G2 (50.3 ± 5.6 vs. 53.3 ± 4.8, p = 0.016). HRV was not different between the 2 groups. Per-segment analysis showed better IQ at the mid-segment of the right coronary artery (3.0 ± 0.9 vs. 2.5 ± 1.1, p = 0.039) and the first diagonal branch (3.4 ± 0.6 vs. 3.1 ± 0.7, p = 0.024), in the G1 than the G2 group, respectively. The IQ was negatively correlated with HR, but no correlation was found between HRV and IQ. The IQs in the per-vessel analysis were not different between the 2 groups. Low-dose β-blocker reduced HR and improved the IQ of CCTA in a few segments, even at a HR of less than 65 bpm. However the effect was limited.

  18. Low dose irradiation and biological defense mechanisms

    International Nuclear Information System (INIS)

    It has been generally accepted in the context of radiation protection that ionizing radiation has some adverse effect even at low doses. However, epidemiological studies of human populations cannot definitively show its existence or absence. Furthermore, recent studies of populations living in areas of different background radiation levels reported some decrease in adverse health effects at high background levels. Genetic studies of atomic bomb survivors failed to produce statistically significant findings on the mutagenic effects of ionizing radiation. A British study however, suggests that a father's exposure to low dose radiation on the job may increase his children's risk of leukemia. On the other hand, many experimental studies have raised the possibility that low doses of ionizing radiation may not be harmful or may even produce stimulating or adaptive responses. The term 'hormesis' has come to be used to describe these phenomena produced by low doses of ionizing radiation when they were beneficial for the organisms studied. At the end of the International Conference on Low Dose Irradiation one conclusion appeared to be justified: radiation produces an adaptive response, though it is not universally detected yet. The conference failed to obtain any consensus on risk assessment at low doses, but raised many problems to be dealt with by future studies. The editors therefore believe that the Proceedings will be useful for all scientists and people concerned with radiation protection and the biological effects of low-dose irradiation

  19. Low-Dose-Rate Computed Tomography System Utilizing 25 mm/s-Scan Silicon X-ray Diode and Its Application to Iodine K-Edge Imaging Using Filtered Bremsstrahlung Photons

    Science.gov (United States)

    Matsushita, Ryo; Sato, Eiichi; Yanbe, Yutaka; Chiba, Hiraku; Maeda, Tomoko; Hagiwara, Osahiko; Matsukiyo, Hiroshi; Osawa, Akihiro; Enomoto, Toshiyuki; Watanabe, Manabu; Kusachi, Shinya; Sato, Shigehiro; Ogawa, Akira; Onagawa, Jun

    2013-03-01

    A low-dose-rate X-ray computed tomography (CT) system is useful for reducing absorbed dose for patients. The CT system with a tube current of sub-mA was developed using a silicon X-ray diode (Si-XD). The Si-XD is a high-sensitivity Si photodiode (PD) selected for detecting X-ray photons, and the X-ray sensitivity of the Si-XD was twice as high as that of Si-PD cerium-doped yttrium aluminum perovskite [YAP(Ce)]. X-ray photons are directly detected using the Si-XD without a scintillator, and the photocurrent from the diode is amplified using current-voltage and voltage-voltage amplifiers. The output voltage is converted into logical pulses using a voltage-frequency converter with a maximum frequency of 500 kHz, and the frequency is proportional to the voltage. The pulses from the converter are sent to the differentiator with a time constant of 500 ns to generate short positive pulses for counting, and the pulses are counted using a counter card. Tomography is accomplished by repeated linear scans and rotations of an object, and projection curves of the object are obtained by the linear scan. The exposure time for obtaining a tomogram was 5 min at a scan step of 0.5 mm and a rotation step of 3.0°. The tube current and voltage were 0.55 mA and 60 kV, respectively, and iodine K-edge CT was carried out using filtered bremsstrahlung X-ray spectra with a peak energy of 38 keV.

  20. Potentiation of T cell-mediated immunity by low dose radiation

    International Nuclear Information System (INIS)

    Full text: Low dose radiation is reported to have beneficial effect on organisms in some cases, though high dose radiation is harmful. Attenuation of diabetes, auto-immune diseases and cancer is the example of this beneficial effect of radiation, i.e. radiation hormesis. Because the disorder of accommodation in immune system is involved in such diseases, immunological network is assumed to be one of the targets for radiation hormesis. In this study, we utilized mice immunized with allogeneic tumor cells to evaluate the hormetic effect of continuous irradiation with low dose rate gamma-ray on the host immune system. C57BL/6 mice (H-2b) were exposed to gamma-ray in an irradiation room bearing 50,000 Ci 60Co at 97 μGy/h, the dose rate where no significant effect on life span is detected by continuous whole body irradiation. Ninety-eight hour after the initiation of the irradiation, they were intraperitoneally immunized with an allogeneic mastocytoma, P815 (H-2b), and further irradiated for 335 h. We found that antigen-specific killer T cell activity was significantly enhanced by the irradiation. Ability of spleen cells to produce T cell lymphokines such as IL-2, IL-4 and IL-10 was also significantly elevated. Antigen-specific IgG1 titer in serum which is highly dependent on T cells, increased, while IgM titer was not marginally affected. In addition, T cell population in spleen was increased and B cell population decreased in naive mice irradiated with the same schedule, while natural killer activity decreased. These results suggest that the continuous whole body exposure to low dose rate gamma-ray potentiates T cell mediated immunity and shifts the immunological balance from humoral immunity to cellular immunity. Modulation of such immunological balance might be involved in the beneficial effect of low dose rate radiation

  1. Effect of low doses of gamma radiation in tomato seeds

    International Nuclear Information System (INIS)

    Tomato dry seeds of the hybrid 'Gladiador' Fl were exposed to low doses of gamma radiation from 60Co source at 0. 509 kGy tax rate in order to study stimulation effects of radiation on germination and plant growth. Eight treatments of different radiation doses were applied as follows: 0 (control); 2.5, 5.0, 7.5, 10.0, 12.5, 15.0, 20.0 Gy. Seed germination as well as green fruits number, harvested fruit number, fruit weight and total production were assessed to identify occurrence of stimulation. Tomato seeds and plants were handled as for usual tomato production in Brazil. Low doses of gamma radiation treatment in the seeds stimulate germination and substantially increase fruit number and total production up to 86% at 10 Gy dose. There are evidences that the use of low doses of gamma radiation can stimulate germination and plant production thus, showing hormetic effects. (author)

  2. Association between absolute volumes of lung spared from low-dose irradiation and radiation-induced lung injury after intensity-modulated radiotherapy in lung cancer: a retrospective analysis.

    Science.gov (United States)

    Chen, Jinmei; Hong, Jinsheng; Zou, Xi; Lv, Wenlong; Guo, Feibao; Hong, Hualan; Zhang, Weijian

    2015-11-01

    The aim of this study was to investigate the association between absolute volumes of lung spared from low-dose irradiation and radiation-induced lung injury (RILI) after intensity-modulated radiotherapy (IMRT) for lung cancer. The normal lung relative volumes receiving greater than 5, 10, 20 and 30 Gy (V5-30) mean lung dose (MLD), and absolute volumes spared from greater than 5, 10, 20 and 30 Gy (AVS5-30) for the bilateral and ipsilateral lungs of 83 patients were recorded. Any association of clinical factors and dose-volume parameters with Grade ≥2 RILI was analyzed. The median follow-up was 12.3 months; 18 (21.7%) cases of Grade 2 RILI, seven (8.4%) of Grade 3 and two (2.4%) of Grade 4 were observed. Univariate analysis revealed the located lobe of the primary tumor. V5, V10, V20, MLD of the ipsilateral lung, V5, V10, V20, V30 and MLD of the bilateral lung, and AVS5 and AVS10 of the ipsilateral lung were associated with Grade ≥2 RILI (P lung was prognostic for Grade ≥2 RILI (P = 0.010, OR = 0.272, 95% CI: 0.102-0.729). Receiver operating characteristic curves indicated Grade ≥2 RILI could be predicted using AVS5 of the ipsilateral lung (area under curve, 0.668; cutoff value, 564.9 cm(3); sensitivity, 60.7%; specificity, 70.4%). The incidence of Grade ≥2 RILI was significantly lower with AVS5 of the ipsilateral lung ≥564.9 cm(3) than with AVS5 lung were associated with Grade ≥2 RILI, and AVS5 of the ipsilateral lung was prognostic for Grade ≥2 RILI for lung cancer after IMRT. PMID:26454068

  3. Study of the radiation levels in low dose rate brachytherapy zones of the National Institute of Neoplastic Illnesses; Estudio de los Niveles de Radiacion en Zonas de Braquiterapia de Baja Tasa de Dosis del Instituto Nacional de Enfermedades Neoplasicas

    Energy Technology Data Exchange (ETDEWEB)

    Figueroa J, N.; Mora Y, B. [Instituto Nacional de Enfermedades Neoplasicas, Lima (Peru)]. e-mail: navorf01@yahoo.es

    2006-07-01

    The present study has as objective to evaluate the radiation levels of the Brachytherapy work areas of low dose rate (Gammateque, nurses station and of hospitalization rooms of patients RIC of 4th, 5th Floor-East) and to estimate the effective dose of the occupationally exposed personnel and the public in general. The measurements of the dose rate in these areas, were registered with a radiations monitor Inspector trademark, during a period of 60 days, without altering the routinary work conditions. The more high levels of environmental dose equivalent rate registered in the different work areas its are of 1.41 and 47.78 {mu}Sv/h rooms 1 and 2 in the Gammateque environments, in the hospitalization rooms of the 4th and 5th floor in the point 1 are of 40.77 and 23.67, {mu}Sv/h respectively and in the point 2 are of 129.19 and 39.93, {mu}Sv/h respectively, and in the nurses station of the 4th and 5th floor its are respectively of 7.62 u Sv/h and 0.45 u Sv/h. According to the carried out measurements and the permanency in the work place is possible to estimate the effective dose involved to the occupationally exposed personnel. The personnel that works in Gammateque could be receiving respectively as maximum dose 0.61 mSv/month, and the personnel that works in the nurses station of 13.17 and 0.78 mSv/year in the 4th and 5th floor. These registered differences among the two floors are due to that the 5th floor counts with the shielding systems (screen) contrary to the 4th, another of the factors is the distribution form of the patient beds RIC. We should have present that the radiation levels although in some cases it is very high, however, they are below of the permissible limits according to standards, but it is still possible to reduce even more, the radiation levels in the critical points fulfilling with the ALARA principle. (Author)

  4. Characteristics of repair following very low doses

    International Nuclear Information System (INIS)

    The effects of ionizing radiation on living systems being with the physical processes of energy deposition and develop through many stages of chemical reaction and biological response. The modeling effort attempts to organize the available data and theories of all of these stages into self-consistent models that can be compared and tested. In some cases, important differences among models result in only small differences in cell survival within the ranges of dose and dose rate that are normally investigated. To overcome this limitation, new ways of irradiating cells at extremes of dose rate, or ways of evaluating the effects of very small doses, are developed. Mathematical modeling and cellular studies complement each other. It has recently been found that some mechanisms are not adequate to account for the interaction of dose and repair time as they affect the reproductive survival of plateau-phase Chinese hamster ovary (CHO) cells. Repair of radiation-induced cellular damage plays a central role in the survival of cells exposed to doses of 1 Gy or more. This repair is responsible for the dose rate, split-dose and delayed plating effect and can be evaluated. Because split-dose and dose-rate experiments involve repair during irradiation and delayed plating experiments involve repair after irradiation is completed, it was originally thought that different repair processes were involved. It is now clear that this is not necessarily the case. Appropriately designed models can account for observed effects at conventional doses (1 Gy or more) whether they assume all damage is lethal unless repaired or some damage is innocuous unless it interacts with additional damage. The fact that the survival following a plating delay is always less than the survival following immediate plating at low doses indicates that the damage produced is probably not potentially lethal

  5. Effects of low doses: Proof and inferences

    International Nuclear Information System (INIS)

    It is essential to discuss the plausibility of 'low-dose' effects from environmental exposures. The question, nonetheless, is wrongly labelled, for it is not the magnitude of the dose that matters, but rather the effect. The question thus concerns 'doses with low effects'. More precisely, because the low effects on large populations are not that small, even when epidemiological tools fail to detect them, it would be more accurate to talk about 'doses with undetectable or barely detectable effects'. Hereafter, we describe this 'low-effect dose' concept from the viewpoint of toxicology and epidemiology and discuss the fragile boundary line for these low-effect doses. Next, we review the different types of inference from observed situations (i.e., with high effects) to situations relevant to public health, to characterize the level of confidence to be accorded them. The first type is extrapolation - from higher to lower doses or from higher to lower dose rates. The second type is transposition - from humans to other humans or from animals to humans. The third type can be called 'analogy' as in 'read across' approaches, where QSAR (Quantitative Structure Activity Relationship) methodology can be used. These three types of inferences can be based on an estimate of the 'distance' between observed and predicted areas, but can also rely on knowledge and theories of the relevant mechanisms. The new tools of predictive toxicology are helpful both in deriving quantitative estimates and grounding inferences on sound bases. (author)

  6. Skin Cancer Rates by Race and Ethnicity

    Science.gov (United States)

    ... Search The CDC Cancel Submit Search The CDC Skin Cancer Note: Javascript is disabled or is not supported ... HPV-Associated Lung Ovarian Prostate Uterine Cancer Home Skin Cancer Rates by Race and Ethnicity Language: English Español ( ...

  7. Chromosome instability and global gene expression patterns in proliferating human T-lymphocytes after low dose rate γ-irradiation, and genetic instability in cells from in vivo radiation-exposed persons

    International Nuclear Information System (INIS)

    Chromosomal instability (Cl), and radiation induced Cl in particular, as well as in a wider sense, genomic instability, has been of great interest lately, as it provides an explanation for the occurrence of multiple mutations during transformation of a normal cell to a malignant tumor cell. To explore this phenomenon, we developed an in vitro system to study the long term, cytogenetic effects of ionizing radiation in human T-lymphocytes. Irradiated or non-irradiated T-cells were grown for up to two months as monoclonal or bulk cell cultures in medium enriched with T-cell growth factors. Analysis of G-banded karyotypes at different time intervals demonstrated clonal aberrations in 65% of the clones derived from irradiated cells, and in only 5% of the clones from non-irradiated cells. Delayed occurrence of de novo aberrations, and a progressive development of subclones with karyotypic abnormalities of increasing complexity, was observed many cell generations after the radiation exposure. Moreover, cells exposed to γ-radiation at a low dose rate (LDR, 0.024 Gy h-1) for 5 days in G0-phase, e.g. a dose that gives the cells time to repair between subsequent hits, also demonstrated CI. Following a radiological accident in Estonia 1994, we studied the possible induction of CI in vivo. Both long term bulk cultures and single cell clones were established from one high and three low exposed persons, as well as control individuals from Estonia. Compared to our historical Swedish controls, we found CI to occur in both bulk cultures and clones, and the aberrations were more complex in the exposed individuals than in the controls, indicating that the aberrations were caused by the irradiation. However, due to the high frequency of CI in the Estonian controls, no conclusion with regard to chromosomal instability in vivo could be drawn from the study. In order to trace factors that induce and maintain the chromosomal instability, and clarify which steps are affected in the

  8. Health hazards of low doses of ionizing radiations. Vo. 1

    International Nuclear Information System (INIS)

    Exposure to high doses of ionizing radiation results in clinical manifestations of several disease entities that may be fatal. The onset and severity of these acute radiation syndromes are deterministic in relation to dose magnitude. Exposure to ionizing radiations at low doses and low dose rates could initiate certain damage in critical molecules of the cell, that may develop in time into serious health effects. The incidence of such delayed effects in low, and is only detectable through sophisticated epidemiological models carried out on large populations. The radiation damage induced in critical molecules of cells may develop by stochastic biochemical mechanisms of repair, residual damage, adaptive response, cellular transformation, promotion and progression into delayed health effects, the most important of which is carcinogenesis. The dose response relationship of probabilistic stochastic delayed effects of radiation at low doses and low dose rates, is very complex indeed. The purpose of this review is to provide a comprehensive understanding of the underlying mechanisms, the factors involved, and the uncertainties encountered. Contrary to acute deterministic effects, the occurrence of probabilistic delayed effects of radiation remains to be enigmatic. 7 figs

  9. LOW DOSE MAGNESIUM SULPHATE REGIME FOR ECLAMPSIA

    Directory of Open Access Journals (Sweden)

    Bangal V

    2009-09-01

    Full Text Available Pre- eclampsia is one of the commonest medical complications seen during pregnancy. It contributes significantly to maternal and perinatal morbidity and mortality. Dr.J.A.Pritchard in 1955, introduced magnesium sulphate for control of convulsions in eclampsia and is used worldwide. Considering the low body mass index of indian women, a low dose magnesium sulphate regime has been introduced by some authors. Present study was carried out at tertiary care centre in rural area. Fifty cases of eclampsia were randomly selected to find out the efficacy of low dose magnesium sulphate regime to control eclamptic convulsions. Maternal and perinatal outcome and magnesium toxicity were analyzed. It was observed that 86% cases responded to initial intravenous dose of 4 grams of 20% magnesium sulphate . Eight percent cases, who got recurrence of convulsion, were controlled by additional 2 grams of 20% magnesium sulphate. Six percent cases required shifting to standard Pritchard regime, as they did not respond to low dose magnesium sulphate regime. The average total dose of magnesium sulphate required for control of convulsions was 20 grams ie. 54.4% less than that of standard Pritchard regime. The maternal and perinatal morbidity and mortality in the present study werecomparable to those of standard Pritchard regime. The study did not find a single case of magnesium related toxicity with low dose magnesium sulphate regime. Low dose magnesium sulphate regime was found to be safe and effective in eclampsia.

  10. Low dose rapamycin exacerbates autoimmune experimental uveitis.

    Directory of Open Access Journals (Sweden)

    Zili Zhang

    Full Text Available BACKGROUND: Rapamycin, a potent immune modulator, is used to treat transplant rejection and some autoimmune diseases. Uveitis is a potentially severe inflammatory eye disease, and 2 clinical trials of treating uveitis with rapamycin are under way. Unexpectedly, recent research has demonstrated that low dose rapamycin enhances the memory T cell population and function. However, it is unclear how low dose rapamycin influences the immune response in the setting of uveitis. DESIGN AND METHODS: B10.RIII mice were immunized to induce experimental autoimmune uveitis (EAU. Ocular inflammation of control and rapamycin-treated mice was compared based on histological change. ELISPOT and T cell proliferation assays were performed to assess splenocyte response to ocular antigen. In addition, we examined the effect of rapamycin on activation-induced cell death (AICD using the MitoCapture assay and Annexin V staining. RESULTS: Administration of low dose rapamycin exacerbated EAU, whereas treating mice with high dose rapamycin attenuated ocular inflammation. The progression of EAU by low dose rapamycin coincided with the increased frequency of antigen-reactive lymphocytes. Lastly, fewer rapamycin-treated T cells underwent AICD, which might contribute to exaggerated ocular inflammation and the uveitogenic immune response. CONCLUSION: These data reveal a paradoxical role for rapamycin in uveitis in a dose-dependent manner. This study has a potentially important clinical implication as rapamycin might cause unwanted consequences dependent on dosing and pharmacokinetics. Thus, more research is needed to further define the mechanism by which low dose rapamycin augments the immune response.

  11. Dual effect of low dose of irradiation on wheat x Leymus angustus: enhancement and damage

    International Nuclear Information System (INIS)

    The effects of low dose of γ-irradiation on wheat x Leymus angustus were studied. The results showed that appropriate low dose of irradiation can overcome the cross incompatibility and enhance seed setting, on the other hand, restrain the development of hybrid embryos and make rate of seed containing embryos decrease. When irradiation is used to enhance wide hybridization, the damage of low dose of γ-irradiation should be considered

  12. Mechanisms of Low Dose Radio-Suppression of Genomic Instability

    Energy Technology Data Exchange (ETDEWEB)

    Engelward, Bevin P

    2009-09-16

    The major goal of this project is to contribute toward the elucidation of the impact of long term low dose radiation on genomic stability. We have created and characterized novel technologies for delivering long term low dose radiation to animals, and we have studied genomic stability by applying cutting edge molecular analysis technologies. Remarkably, we have found that a dose rate that is 300X higher than background radiation does not lead to any detectable genomic damage, nor is there any significant change in gene expression for genes pertinent to the DNA damage response. These results point to the critical importance of dose rate, rather than just total dose, when evaluating public health risks and when creating regulatory guidelines. In addition to these studies, we have also further developed a mouse model for quantifying cells that have undergone a large scale DNA sequence rearrangement via homologous recombination, and we have applied these mice in studies of both low dose radiation and space radiation. In addition to more traditional approaches for assessing genomic stability, we have also explored radiation and possible beneficial effects (adaptive response), long term effects (persistent effects) and effects on communication among cells (bystander effects), both in vitro and in vivo. In terms of the adaptive response, we have not observed any significant induction of an adaptive response following long term low dose radiation in vivo, delivered at 300X background. In terms of persistent and bystander effects, we have revealed evidence of a bystander effect in vivo and with researchers at and demonstrated for the first time the molecular mechanism by which cells “remember” radiation exposure. Understanding the underlying molecular mechanisms by which radiation can induce genomic instability is fundamental to our ability to assess the biological impact of low dose radiation. Finally, in a parallel set of studies we have explored the effects of heavy

  13. LOW DOSE RISK, DECISIONS, and RISK COMMUNICATION

    International Nuclear Information System (INIS)

    The objective of this project is to conduct basic research on how people receive, evaluate, and form positions on scientific information and its relationship to low-dose radiation exposure. There are three major areas of study in our research program. First is the development of theories, frameworks and concepts essential to guiding data collection and analysis. The second area is a program of experimental studies on risk perception, evaluation of science information, and the structure of individual positions regarding low-dose exposures. Third is the community-level studies to examine and record how the social conditions, under which science communications take place, influence the development of attitudes and opinions about: low-dose exposures, the available management options, control of radiation risks, and preferences for program and policy goals

  14. A graphical review of radiogenic animal cancer data using the 'dose and dose-rate map'

    International Nuclear Information System (INIS)

    We have been investigating the effects of low dose or low dose rate irradiation on mice, using our low dose-rate irradiation facilities. In these studies, we found that the effects were highly dependent on both total dose and dose rate. To show this visually, we proposed the 'dose/dose rate map', and plotted the results of our laboratory and our co-workers. The map demonstrated that dose/dose rate plane could be divided into three areas; 1) An area where harmful effects are observed, 2) An area where no harmful effects are observed, and 3) Another area, between previous two areas, where certain protective functions are enhanced. As this map would be a powerful tool to find some trend among the vast numbers of data relating the biological effects of ionizing radiation, we have developed a computer program which plots the collected data on the dose/dose rate map sorting by experimental conditions. In this study, we graphically reviewed and analyzed the data relating to the lifespan studies of animals with a view to determining the relationships between doses and dose rates of ionizing radiation and cancer incidence. The data contains about 800 sets of experiments, which concerns 187,000 animals exposed to gamma ray or X-ray and their 112,000 controls, and total of about 30,000 cancers in exposed animals and 14,000 cancers in controls. About 800 points of data were plotted on the dose/dose rate map. The plot showed that 1) The divided three areas in the dose/dose rate map were generally confirmed by these 800 points of data, and 2) In some particular conditions, e.g. sarcoma by X-rays, the biologically effective area is extended to relatively high dose/dose rate area. (author)

  15. Exposure to low dose radiation and its effect

    International Nuclear Information System (INIS)

    The title subjects are easily explained. As an introduction, the concept of the ICRP Recommendation (2007) is explained briefly on its use of radiation protection and management. Natural radiation dose to ordinary Japanese is said to be the average 1.5 mSv/y in contrast to the whole world people, 2.4. Medical radiation dose to Japanese is estimated to amount to 2.3 mSv/y, to American, 3.0, and to people of medically advanced nations, 1.92. There are areas always exposed to the natural high dose radiation like Ramsar 10.2 mSv/y (Iran). The effect of such natural low dose has been shown to be all insignificant on cancer mortality in Yangjian area (3.3 mSv/y) in China, on lung cancer risk due to radon in Japan Misasa spa area (>10 mSv/y), and on cancer mortality among 176 thousands nuclear industry workers in Japan (average accumulated dose 12 mSv), etc. There have been such reports as increased bladder cancer in Chernobyl, increased leukemic relative risk of infants whose fathers worked in Sellafield nuclear facility, and acute death/health-injury of residents in the past Lou-Lan area where Chinese nuclear bombs were tested. Fallout data from 1955 to 2011 shows the process of radioactive materials fallen and peaks were due to nuclear tests and Chernobyl/Fukushima Accidents. Basic studies on low dose effect involve those of the radioadoptive response, radiation hormesis, bystander effect and cluster injury of DNA. In low dose-carcinogenesis relationship, presented are models of linear non-threhold (LNT), those estimating lower risk than LNT like linear quadratic (LQ) model, and higher risk like supra-linear model. Risks leading to cancer formation include the occupation and others like medical doctors, tobacco smoking and various anxieties/stresses. (T.T.)

  16. Features of action of low doses of γ-radiation on yeast cells

    International Nuclear Information System (INIS)

    Lethal effect of low doses and adaptive response to low doses of chronic irradiation were investigated in experiments on yeast cells. It was shown that the phenomenon of hypersensitivity at low doses of γ-irradiation was not found in yeast cells. Adaptive response the degree of which depends on radiation dose rate was observed after exposure to low doses of chronic irradiation. Adaptive reaction was kept for some time after the treatment of adaptive irradiation then the sensitivity of cells increased even in comparison with unirradiated ones

  17. Evaluation of a combination of low-dose ketamine and low-dose midazolam in terminal dyspnea-attenuation of "double-effect"

    Directory of Open Access Journals (Sweden)

    Abhijit Kanti Dam

    2008-01-01

    Full Text Available Aim: Of all symptoms in palliative medicine those concerning respiration are most excruciating and difficult to treat. Reticence about the use of morphine for palliation of dyspnea is common, especially in nonmalignant diseases, as there is a fear of causing respiratory depression, particularly where Chronic Obstructive Pulmonary Disease (COPD exists. This factor is also compounded by the lack of availability of morphine in parts of developing countries. Ketamine has excellent anesthetic and analgesic effects in addition to being easily available. It produces bronchodilatation and does not produce respiratory or cardiovascular depression. The author seeks to evaluate the role of low-dose (0.2 mg/kg ketamine and midazolam (0.02 mg/kg in the attenuation of terminal dyspnea. Methods: Sixteen patients with terminal dyspnea, admitted to the Critical Care Unit (CCU with cancer and other noncancer diagnoses were recruited. The subjective component of dyspnea was assessed using the Graphic Rating Scale (GRS, which has values from 0 - 10, 10 being maximum dyspnea. Each patient received a low-dose of ketamine and midazolam for relief of dyspnea. All the patients received low-flow (2 L/min. oxygen therapy via nasal cannula. Immediately after admission, all the patients were reassured and nursed in a decubitus position of their choice. The GRS was recorded at the point of admission, 10 minutes after starting oxygen therapy, and ten minutes after administration of low-dose ketamine and midazolam. Hemodynamic parameters were also recorded at these three points. Result: All the patients who enrolled in our study had significant dyspnea at admission, as was evident from the GRS scores of 8.250 (SD 0.91, respiratory rate of 28.56 (SD 5.0, mean arterial blood pressure (MABP of 102.7 (SD 14.63, pulse rate of 115.62 (SD 23.3, and SpO2 of 92.43 (SD 2.38. All the patients benefited from the combination of ketamine and midazolam, as evidenced by the statistically

  18. Stimulation of seeds by low dose irradiation

    International Nuclear Information System (INIS)

    The first section of the bibliography lists materials on the stimulation of seeds by low dose irradiation, with particular reference to stimulation of germination and yield. The second section contains a small number of selected references on seed irradiation facilities. (author)

  19. DoReMi workshop on multidisciplinary approaches to evaluating cancer risks associated with low-dose internal contamination; Approches multidisciplinaires pour l'evaluation du risque de cancer associe aux contaminations internes aux faibles doses: synthese du seminaire scientifique organise dans le cadre du projet europeen DoReMi

    Energy Technology Data Exchange (ETDEWEB)

    Laurier, D.; Guseva Canu, I.; Bertho, J.M.; Blanchardon, E.; Rage, E. [Institut de radioprotection et de surete nucleaire, IRSN, Fontenay-aux-Roses Cedex (France); Baatout, S. [Belgian Nuclear Research Centre, SCK-CEN, Mol (Belgium); Bouffler, S. [Health Protection Agency, Centre for Radiation Chemical and Environmental Hazards, HPA-CRCE, Chilton (United Kingdom); Cardis, E. [Centre for Research in Environmental Epidemiology, CREAL, Barcelona (Spain); Gomolka, M.; Kreuzer, M. [Federal Office for Radiation Protection, Department of Radiation Protection and Health, BfS, Neuherberg (Germany); Hall, J. [Inserm U612, Institut Curie, Orsay (France); Kesminiene, A. [International Agency for Research on Cancer, Section of Environment and Radiation, IARC, Lyon (France)

    2012-01-15

    A workshop dedicated to cancer risks associated with low-dose internal contamination was organised in March 2011, in Paris, in the framework of the DoReMi (Low Dose Research towards Multidisciplinary Integration) European Network of Excellence. The aim was to identify the best epidemiological studies that provide an opportunity to develop a multidisciplinary approach to improve the evaluation of the cancer risk associated with internal contamination. This workshop provided an opportunity for in-depth discussions between researchers working in different fields including (but not limited to) epidemiology, dosimetry, biology and toxicology. Discussions confirmed the importance of research on the health effects of internal contamination. Several existing epidemiological studies provide a real possibility to improve the quantification of cancer risk associated with internal emitters. Areas for future multidisciplinary collaborations were identified, that should allow feasibility studies to be carried out in the near future. The goal of this paper is to present an overview of the presentations and discussions that took place during this workshop. (authors)

  20. Activated T-cell Therapy, Low-Dose Aldesleukin, and Sargramostim in Treating Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer That is Stage III-IV, Refractory, or Recurrent

    Science.gov (United States)

    2016-02-15

    Malignant Ovarian Clear Cell Tumor; Malignant Ovarian Serous Tumor; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  1. Effect of low dose of gamma radiation on the induction and signalling of complex damages of DNA in the mammals cells

    International Nuclear Information System (INIS)

    The work presented in the frame of this thesis are in line with the studies on the radioinduced damages of DNA in order to better understand their genotoxic effects and the associated risks. The different radioinduced damages of DNA are given, the complex damages, double strand-break and multiple damages are particularly detailed as well as their methods of detection. Are presented the systems implemented in the cell in order to point the radioinduced damages and to implement the repair systems of these lesions. Then, are presented the knowledge on the effects of low doses and low dose rates. The whole of this work has for objective to highlight the mechanisms by which the reduction of dose rate allows an increase of cell survival. By a better knowledge of the system implemented in response to a low dose rate irradiation, it is possible to valid or not the linear without threshold model of low doses effects and consequently to better understand the eventual risks of cancer linked to exposures of low dose