Brachytherapy for cervix cancer: low-dose rate or high-dose rate brachytherapy – a meta-analysis of clinical trials

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Stefano Eduardo J

2009-04-01

Full Text Available Abstract Background The literature supporting high-dose rate brachytherapy (HDR in the treatment of cervical carcinoma derives primarily from retrospective series. However, controversy still persists regarding the efficacy and safety of HDR brachytherapy compared to low-dose rate (LDR brachytherapy, in particular, due to inadequate tumor coverage for stage III patients. Whether LDR or HDR brachytherapy produces better results for these patients in terms of survival rate, local control rate and the treatment complications remain controversial. Methods A meta-analysis of RCT was performed comparing LDR to HDR brachytherapy for cervix cancer treated for radiotherapy alone. The MEDLINE, EMBASE, CANCERLIT and Cochrane Library databases, as well as abstracts published in the annual proceedings were systematically searched. We assessed methodological quality for each outcome by grading the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE methodology. We used "recommend" for strong recommendations, and "suggest" for weak recommendations. Results Pooled results from five randomized trials (2,065 patients of HDR brachytherapy in cervix cancer showed no significant increase of mortality (p = 0.52, local recurrence (p = 0.68, or late complications (rectal; p = 0.7, bladder; p = 0.95 or small intestine; p = 0.06 rates as compared to LDR brachytherapy. In the subgroup analysis no difference was observed for overall mortality and local recurrence in patients with clinical stages I, II and III. The quality of evidence was low for mortality and local recurrence in patients with clinical stage I, and moderate for other clinical stages. Conclusion Our meta-analysis shows that there are no differences between HDR and LDR for overall survival, local recurrence and late complications for clinical stages I, II and III. By means of the GRADE system, we recommend the use of HDR for all clinical stages of cervix

Brachytherapy for cervix cancer: low-dose rate or high-dose rate brachytherapy – a meta-analysis of clinical trials

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Viani, Gustavo A; Manta, Gustavo B; Stefano, Eduardo J; de Fendi, Ligia I

2009-01-01

Background The literature supporting high-dose rate brachytherapy (HDR) in the treatment of cervical carcinoma derives primarily from retrospective series. However, controversy still persists regarding the efficacy and safety of HDR brachytherapy compared to low-dose rate (LDR) brachytherapy, in particular, due to inadequate tumor coverage for stage III patients. Whether LDR or HDR brachytherapy produces better results for these patients in terms of survival rate, local control rate and the treatment complications remain controversial. Methods A meta-analysis of RCT was performed comparing LDR to HDR brachytherapy for cervix cancer treated for radiotherapy alone. The MEDLINE, EMBASE, CANCERLIT and Cochrane Library databases, as well as abstracts published in the annual proceedings were systematically searched. We assessed methodological quality for each outcome by grading the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. We used "recommend" for strong recommendations, and "suggest" for weak recommendations. Results Pooled results from five randomized trials (2,065 patients) of HDR brachytherapy in cervix cancer showed no significant increase of mortality (p = 0.52), local recurrence (p = 0.68), or late complications (rectal; p = 0.7, bladder; p = 0.95 or small intestine; p = 0.06) rates as compared to LDR brachytherapy. In the subgroup analysis no difference was observed for overall mortality and local recurrence in patients with clinical stages I, II and III. The quality of evidence was low for mortality and local recurrence in patients with clinical stage I, and moderate for other clinical stages. Conclusion Our meta-analysis shows that there are no differences between HDR and LDR for overall survival, local recurrence and late complications for clinical stages I, II and III. By means of the GRADE system, we recommend the use of HDR for all clinical stages of cervix cancer. PMID:19344527

High dose rate brachytherapy for oral cancer.

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Yamazaki, Hideya; Yoshida, Ken; Yoshioka, Yasuo; Shimizutani, Kimishige; Furukawa, Souhei; Koizumi, Masahiko; Ogawa, Kazuhiko

2013-01-01

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.

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

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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

Post-operative high dose rate brachytherapy in patients with low to intermediate risk endometrial cancer

International Nuclear Information System (INIS)

Pearcey, R.G.; Petereit, D.G.

2000-01-01

This paper investigates the outcome using different dose/fractionation schedules in high dose rate (HDR) post-operative vaginal vault radiotherapy in patients with low to intermediate risk endometrial cancer. The world literature was reviewed and thirteen series were analyzed representing 1800 cases. A total of 12 vaginal vault recurrences were identified representing an overall vaginal control rate of 99.3%. A wide range of dose fractionation schedules and techniques have been reported. In order to analyze a dose response relationship for tumor control and complications, the biologically effective doses to the tumor and late responding tissues were calculated using the linear quadratic model. A threshold was identified for complications, but not vaginal control. While dose fractionation schedules that delivered a biologically effective dose to the late responding tissues in excess of 100 Gy 3 (LQED = 60 Gy) predicted for late complications, dose fractionation schedules that delivered a modest dose to the vaginal surface (50 Gy 10 or LQED = 30 Gy) appeared tumoricidal with vaginal control rates of at least 98%. By using convenient, modest dose fractionation schedules, HDR vaginal vault - brachytherapy yields very high local control and extremely low morbidity rates. (author)

Low-Dose-Rate Brachytherapy Versus Cryotherapy in Low- and Intermediate-Risk Prostate Cancer.

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Gestaut, Matthew M; Cai, Wendi; Vyas, Shilpa; Patel, Belur J; Hasan, Salman A; MunozMaldonado, Yolanda; Deb, Niloyjyoti; Swanson, Gregory

2017-05-01

Cryotherapy and brachytherapy are definitive local treatment options for low- to intermediate-risk prostate cancer. There are both prospective and retrospective data for brachytherapy, but the use of cryotherapy has been limited primarily to single-institution retrospective studies. Currently, no published evidence has compared low-dose-rate brachytherapy versus cryotherapy. Institutional review board approval was obtained to conduct a retrospective chart review of consecutive patients treated at our institution from 1990 to 2012. For inclusion, patients must have received a prostate cancer diagnosis and have been considered to have low- to intermediate-risk disease according to the National Comprehensive Cancer Network criteria. All patients received brachytherapy or cryotherapy treatment. Disease specifics and failure details were collected for all patients. Failure was defined as prostate-specific antigen nadir +2 ng/mL. A total of 359 patients were analyzed. The groups comprised 50 low-risk cryotherapy (LRC), 92 intermediate-risk cryotherapy (IRC), 133 low-risk brachytherapy (LRB), and 84 intermediate-risk brachytherapy (IRB) patients. The median prostate-specific antigen follow-up periods were 85.6 months (LRC), 59.2 months (IRC), 74.9 months (LRB), and 59.8 months (IRB). The 5-year biochemical progression-free survival (bPFS) rate was 57.9% in the cryotherapy group versus 89.6% in the brachytherapy group (Pcryotherapy for low- and intermediate-risk groups (Pcryotherapy patients was -35°C (range, -96°C to -6°C). Cryotherapy used a median of 2 freeze-thaw cycles (range, 2-4 freeze-thaw cycles). Results from this study suggest that cryotherapy is inferior to brachytherapy for patients with low- to intermediate-risk prostate cancer. Patient selection criteria for consideration of cryotherapy and brachytherapy are similar in terms of anesthesia candidacy. Therefore, cryotherapy would not be recommended as a first-line local therapy for this particular

A graphical review of radiogenic animal cancer data using the 'dose and dose-rate map'

International Nuclear Information System (INIS)

Yoshida, Kazuo; Hoshi, Yuko; Sakai, Kazuo

2008-01-01

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)

High dose rate brachytherapy for oral cancer

International Nuclear Information System (INIS)

Yamazaki, Hideya; Yoshida, Ken; Yoshioka, Yasuo; Shimizutani, Kimishige; Koizumi, Masahiko; Ogawa, Kazuhiko; Furukawa, Souhei

2013-01-01

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)

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

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Iwasaki, Toshiyasu; Otsuka, Kensuke; Yoshida, Kazuo

2015-01-01

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)

Dose escalation using conformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer.

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Martinez, Alvaro A; Gustafson, Gary; Gonzalez, José; Armour, Elwood; Mitchell, Chris; Edmundson, Gregory; Spencer, William; Stromberg, Jannifer; Huang, Raywin; Vicini, Frank

2002-06-01

To overcome radioresistance for patients with unfavorable prostate cancer, a prospective trial of pelvic external beam irradiation (EBRT) interdigitated with dose-escalating conformal high-dose-rate (HDR) prostate brachytherapy was performed. Between November 1991 and August 2000, 207 patients were treated with 46 Gy pelvic EBRT and increasing HDR brachytherapy boost doses (5.50-11.5 Gy/fraction) during 5 weeks. The eligibility criteria were pretreatment prostate-specific antigen level >or=10.0 ng/mL, Gleason score >or=7, or clinical Stage T2b or higher. Patients were divided into 2 dose levels, low-dose biologically effective dose 93 Gy (149 patients). No patient received hormones. We used the American Society for Therapeutic Radiology and Oncology definition for biochemical failure. The median age was 69 years. The mean follow-up for the group was 4.4 years, and for the low and high-dose levels, it was 7.0 and 3.4 years, respectively. The actuarial 5-year biochemical control rate was 74%, and the overall, cause-specific, and disease-free survival rate was 92%, 98%, and 68%, respectively. The 5-year biochemical control rate for the low-dose group was 52%; the rate for the high-dose group was 87% (p failure. The Radiation Therapy Oncology Group Grade 3 gastrointestinal/genitourinary complications ranged from 0.5% to 9%. The actuarial 5-year impotency rate was 51%. Pelvic EBRT interdigitated with transrectal ultrasound-guided real-time conformal HDR prostate brachytherapy boost is both a precise dose delivery system and a very effective treatment for unfavorable prostate cancer. We demonstrated an incremental beneficial effect on biochemical control and cause-specific survival with higher doses. These results, coupled with the low risk of complications, the advantage of not being radioactive after implantation, and the real-time interactive planning, define a new standard for treatment.

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

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Elaguppillai, V.

1981-01-01

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)

Phase III trial of high- vs. low-dose-rate interstitial radiotherapy for early mobile tongue cancer

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Inoue, Takehiro; Inoue, Toshihiko; Yoshida, Ken; Yoshioka, Yasuo; Shimamoto, Shigetoshi; Tanaka, Eiichi; Yamazaki, Hideya; Shimizutani, Kimishige; Teshima, Teruki; Furukawa, Souhei

2001-01-01

Purpose: Early mobile tongue cancer can be controlled with interstitial radiotherapy (ISRT). We carried out a Phase III trial to compare the treatment results of low-dose-rate (Ld) ISRT and high-dose-rate (HDR) ISRT for early mobile tongue cancer. Methods and Materials: From April 1992 through October 1996, 59 patients with cancer of the early mobile tongue were registered in this Phase III study. Eight patients were excluded from the evaluation because of violations of the requirements for this study. Of 51 eligible patients, 26 patients were treated with LDR-ISRT (70 Gy/4-9 days) and 25 patients with HDR-ISRT (60 Gy/10 fractions/1 week). For the hyperfractionated HDR-ISRT, the time interval between 2 fractions was more than 6 h. Results: Five-year local control rates of the LDR and HDR groups were 84% and 87% respectively. Nodal metastasis occurred in 6 patients in each group. Five-year nodal control rates of the LDR and HDR groups were 77% and 76%, respectively. Conclusion: Hyperfractionated HDR-ISRT for early mobile tongue cancer has the same local control compared with continuous LDR-ISRT. Hyperfractionated HDR-ISRT is an alternative treatment for continuous LDR-ISRT

High dose rate versus low dose rate interstitial radiotherapy for carcinoma of the floor of mouth

International Nuclear Information System (INIS)

Inoue, Takehiro; Inoue, Toshihiko; Yamazaki, Hideya; Koizumi, Masahiko; Kagawa, Kazufumi; Yoshida, Ken; Shiomi, Hiroya; Imai, Atsushi; Shimizutani, Kimishige; Tanaka, Eichii; Nose, Takayuki; Teshima, Teruki; Furukawa, Souhei; Fuchihata, Hajime

1998-01-01

Purpose: Patients with cancer of the floor of mouth are treated with radiation because of functional and cosmetic reasons. We evaluate the treatment results of high dose rate (HDR) and low dose rate (LDR) interstitial radiation for cancer of the floor of mouth. Methods and Materials: From January 1980 through March 1996, 41 patients with cancer of the floor of mouth were treated with LDR interstitial radiation using 198 Au grains, and from April 1992 through March 1996 16 patients with HDR interstitial radiation. There were 26 T1 tumors, 30 T2 tumors, and 1 T3 tumor. For 21 patients treated with interstitial radiation alone, a total radiation dose of interstitial therapy was 60 Gy/10 fractions/6-7 days in HDR and 85 Gy within 1 week in LDR. For 36 patients treated with a combination therapy, a total dose of 30 to 40 Gy of external radiation and a total dose of 48 Gy/8 fractions/5-6 days in HDR or 65 Gy within 1 week in LDR were delivered. Results: Two- and 5-year local control rates of patients treated with HDR interstitial radiation were 94% and 94%, and those with LDR were 75% and 69%, respectively. Local control rate of patients treated with HDR brachytherapy was slightly higher than that with 198 Au grains (p = 0.113). For late complication, bone exposure or ulcer occurred in 6 of 16 (38%) patients treated with HDR and 13 of 41 (32%) patients treated with LDR. Conclusion: HDR fractionated interstitial brachytherapy can be an alternative to LDR brachytherapy for cancer of the floor of mouth and eliminate radiation exposure for the medical staff

High versus low-dose rate brachytherapy for cervical cancer.

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Patankar, Sonali S; Tergas, Ana I; Deutsch, Israel; Burke, William M; Hou, June Y; Ananth, Cande V; Huang, Yongmei; Neugut, Alfred I; Hershman, Dawn L; Wright, Jason D

2015-03-01

Brachytherapy plays an important role in the treatment of cervical cancer. While small trials have shown comparable survival outcomes between high (HDR) and low-dose rate (LDR) brachytherapy, little data is available in the US. We examined the utilization of HDR brachytherapy and analyzed the impact of type of brachytherapy on survival for cervical cancer. Women with stages IB2-IVA cervical cancer treated with primary (external beam and brachytherapy) radiotherapy between 2003-2011 and recorded in the National Cancer Database (NCDB) were analyzed. Generalized linear mixed models and Cox proportional hazards regression were used to examine predictors of HDR brachytherapy use and the association between HDR use and survival. A total of 10,564 women including 2681 (25.4%) who received LDR and 7883 (74.6%) that received HDR were identified. Use of HDR increased from 50.2% in 2003 to 83.9% in 2011 (Puse of HDR. While patients in the Northeast were more likely to receive HDR therapy, there were no other clinical or socioeconomic characteristics associated with receipt of HDR. In a multivariable Cox model, survival was similar between the HDR and LDR groups (HR=0.93; 95% CI 0.83-1.03). Similar findings were noted in analyses stratified by stage and histology. Kaplan-Meier analyses demonstrated no difference in survival based on type of brachytherapy for stage IIB (P=0.68), IIIB (P=0.17), or IVA (P=0.16) tumors. The use of HDR therapy has increased rapidly. Overall survival is similar for LDR and HDR brachytherapy. Copyright © 2015 Elsevier Inc. All rights reserved.

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)

Jacob, P

2006-01-01

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

Time-driven activity-based costing of low-dose-rate and high-dose-rate brachytherapy for low-risk prostate cancer.

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Ilg, Annette M; Laviana, Aaron A; Kamrava, Mitchell; Veruttipong, Darlene; Steinberg, Michael; Park, Sang-June; Burke, Michael A; Niedzwiecki, Douglas; Kupelian, Patrick A; Saigal, Christopher

Cost estimates through traditional hospital accounting systems are often arbitrary and ambiguous. We used time-driven activity-based costing (TDABC) to determine the true cost of low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy for prostate cancer and demonstrate opportunities for cost containment at an academic referral center. We implemented TDABC for patients treated with I-125, preplanned LDR and computed tomography based HDR brachytherapy with two implants from initial consultation through 12-month followup. We constructed detailed process maps for provision of both HDR and LDR. Personnel, space, equipment, and material costs of each step were identified and used to derive capacity cost rates, defined as price per minute. Each capacity cost rate was then multiplied by the relevant process time and products were summed to determine total cost of care. The calculated cost to deliver HDR was greater than LDR by $2,668.86 ($9,538 vs. $6,869). The first and second HDR treatment day cost $3,999.67 and $3,955.67, whereas LDR was delivered on one treatment day and cost $3,887.55. The greatest overall cost driver for both LDR and HDR was personnel at 65.6% ($4,506.82) and 67.0% ($6,387.27) of the total cost. After personnel costs, disposable materials contributed the second most for LDR ($1,920.66, 28.0%) and for HDR ($2,295.94, 24.0%). With TDABC, the true costs to deliver LDR and HDR from the health system perspective were derived. Analysis by physicians and hospital administrators regarding the cost of care afforded redesign opportunities including delivering HDR as one implant. Our work underscores the need to assess clinical outcomes to understand the true difference in value between these modalities. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Low doses effects and gamma radiations low dose rates

International Nuclear Information System (INIS)

Averbeck, D.

1999-01-01

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.)

Incidental renal tumours on low-dose CT lung cancer screening exams.

Science.gov (United States)

Pinsky, Paul F; Dunn, Barbara; Gierada, David; Nath, P Hrudaya; Munden, Reginald; Berland, Lincoln; Kramer, Barnett S

2017-06-01

Introduction Renal cancer incidence has increased markedly in the United States in recent decades, largely due to incidentally detected tumours from computed tomography imaging. Here, we analyze the potential for low-dose computed tomography lung cancer screening to detect renal cancer. Methods The National Lung Screening Trial randomized subjects to three annual screens with either low-dose computed tomography or chest X-ray. Eligibility criteria included 30 + pack-years, current smoking or quit within 15 years, and age 55-74. Subjects were followed for seven years. Low-dose computed tomography screening forms collected information on lung cancer and non-lung cancer abnormalities, including abnormalities below the diaphragm. A reader study was performed on a sample of National Lung Screening Trial low-dose computed tomography images assessing presence of abnormalities below the diaphragms and abnormalities suspicious for renal cancer. Results There were 26,722 and 26,732 subjects enrolled in the low-dose computed tomography and chest X-ray arms, respectively, and there were 104 and 85 renal cancer cases diagnosed, respectively (relative risk = 1.22, 95% CI: 0.9-1.5). From 75,126 low-dose computed tomography screens, there were 46 renal cancer diagnoses within one year. Abnormalities below the diaphragm rates were 39.1% in screens with renal cancer versus 4.1% in screens without (P cancer cases versus 13% of non-cases had abnormalities below the diaphragms; 55% of cases and 0.8% of non-cases had a finding suspicious for renal cancer (P cancers. The benefits to harms tradeoff of incidental detection of renal tumours on low-dose computed tomography is unknown.

Dose escalation using conformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer

International Nuclear Information System (INIS)

Martinez, Alvaro A.; Gustafson, Gary; Gonzalez, Jose; Armour, Elwood; Mitchell, Chris; Edmundson, Gregory; Spencer, William; Stromberg, Jannifer; Huang, Raywin; Vicini, Frank

2002-01-01

Purpose: To overcome radioresistance for patients with unfavorable prostate cancer, a prospective trial of pelvic external beam irradiation (EBRT) interdigitated with dose-escalating conformal high-dose-rate (HDR) prostate brachytherapy was performed. Methods and Materials: Between November 1991 and August 2000, 207 patients were treated with 46 Gy pelvic EBRT and increasing HDR brachytherapy boost doses (5.50-11.5 Gy/fraction) during 5 weeks. The eligibility criteria were pretreatment prostate-specific antigen level ≥10.0 ng/mL, Gleason score ≥7, or clinical Stage T2b or higher. Patients were divided into 2 dose levels, low-dose biologically effective dose 93 Gy (149 patients). No patient received hormones. We used the American Society for Therapeutic Radiology and Oncology definition for biochemical failure. Results: The median age was 69 years. The mean follow-up for the group was 4.4 years, and for the low and high-dose levels, it was 7.0 and 3.4 years, respectively. The actuarial 5-year biochemical control rate was 74%, and the overall, cause-specific, and disease-free survival rate was 92%, 98%, and 68%, respectively. The 5-year biochemical control rate for the low-dose group was 52%; the rate for the high-dose group was 87% (p<0.001). Improvement occurred in the cause-specific survival in favor of the brachytherapy high-dose level (p=0.014). On multivariate analysis, a low-dose level, higher Gleason score, and higher nadir value were associated with increased biochemical failure. The Radiation Therapy Oncology Group Grade 3 gastrointestinal/genitourinary complications ranged from 0.5% to 9%. The actuarial 5-year impotency rate was 51%. Conclusion: Pelvic EBRT interdigitated with transrectal ultrasound-guided real-time conformal HDR prostate brachytherapy boost is both a precise dose delivery system and a very effective treatment for unfavorable prostate cancer. We demonstrated an incremental beneficial effect on biochemical control and cause

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

International Nuclear Information System (INIS)

Nomura, Takaharu

2008-01-01

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)

Dosimetric and radiobiological comparison of volumetric modulated arc therapy, high-dose rate brachytherapy, and low-dose rate permanent seeds implant for localized prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Yang, Ruijie, E-mail: ruijyang@yahoo.com; Zhao, Nan; Liao, Anyan; Wang, Hao; Qu, Ang

2016-10-01

To investigate the dosimetric and radiobiological differences among volumetric modulated arc therapy (VMAT), high-dose rate (HDR) brachytherapy, and low-dose rate (LDR) permanent seeds implant for localized prostate cancer. A total of 10 patients with localized prostate cancer were selected for this study. VMAT, HDR brachytherapy, and LDR permanent seeds implant plans were created for each patient. For VMAT, planning target volume (PTV) was defined as the clinical target volume plus a margin of 5 mm. Rectum, bladder, urethra, and femoral heads were considered as organs at risk. A 78 Gy in 39 fractions were prescribed for PTV. For HDR and LDR plans, the dose prescription was D{sub 90} of 34 Gy in 8.5 Gy per fraction, and 145 Gy to clinical target volume, respectively. The dose and dose volume parameters were evaluated for target, organs at risk, and normal tissue. Physical dose was converted to dose based on 2-Gy fractions (equivalent dose in 2 Gy per fraction, EQD{sub 2}) for comparison of 3 techniques. HDR and LDR significantly reduced the dose to rectum and bladder compared with VMAT. The D{sub mean} (EQD{sub 2}) of rectum decreased 22.36 Gy in HDR and 17.01 Gy in LDR from 30.24 Gy in VMAT, respectively. The D{sub mean} (EQD{sub 2}) of bladder decreased 6.91 Gy in HDR and 2.53 Gy in LDR from 13.46 Gy in VMAT. For the femoral heads and normal tissue, the mean doses were also significantly reduced in both HDR and LDR compared with VMAT. For the urethra, the mean dose (EQD{sub 2}) was 80.26, 70.23, and 104.91 Gy in VMAT, HDR, and LDR brachytherapy, respectively. For localized prostate cancer, both HDR and LDR brachytherapy were clearly superior in the sparing of rectum, bladder, femoral heads, and normal tissue compared with VMAT. HDR provided the advantage in sparing of urethra compared with VMAT and LDR.

Dosimetric and radiobiological comparison of volumetric modulated arc therapy, high-dose rate brachytherapy, and low-dose rate permanent seeds implant for localized prostate cancer

International Nuclear Information System (INIS)

Yang, Ruijie; Zhao, Nan; Liao, Anyan; Wang, Hao; Qu, Ang

2016-01-01

To investigate the dosimetric and radiobiological differences among volumetric modulated arc therapy (VMAT), high-dose rate (HDR) brachytherapy, and low-dose rate (LDR) permanent seeds implant for localized prostate cancer. A total of 10 patients with localized prostate cancer were selected for this study. VMAT, HDR brachytherapy, and LDR permanent seeds implant plans were created for each patient. For VMAT, planning target volume (PTV) was defined as the clinical target volume plus a margin of 5 mm. Rectum, bladder, urethra, and femoral heads were considered as organs at risk. A 78 Gy in 39 fractions were prescribed for PTV. For HDR and LDR plans, the dose prescription was D 90 of 34 Gy in 8.5 Gy per fraction, and 145 Gy to clinical target volume, respectively. The dose and dose volume parameters were evaluated for target, organs at risk, and normal tissue. Physical dose was converted to dose based on 2-Gy fractions (equivalent dose in 2 Gy per fraction, EQD 2 ) for comparison of 3 techniques. HDR and LDR significantly reduced the dose to rectum and bladder compared with VMAT. The D mean (EQD 2 ) of rectum decreased 22.36 Gy in HDR and 17.01 Gy in LDR from 30.24 Gy in VMAT, respectively. The D mean (EQD 2 ) of bladder decreased 6.91 Gy in HDR and 2.53 Gy in LDR from 13.46 Gy in VMAT. For the femoral heads and normal tissue, the mean doses were also significantly reduced in both HDR and LDR compared with VMAT. For the urethra, the mean dose (EQD 2 ) was 80.26, 70.23, and 104.91 Gy in VMAT, HDR, and LDR brachytherapy, respectively. For localized prostate cancer, both HDR and LDR brachytherapy were clearly superior in the sparing of rectum, bladder, femoral heads, and normal tissue compared with VMAT. HDR provided the advantage in sparing of urethra compared with VMAT and LDR.

SU-E-T-34: An in Vivo Study On Pulsed Low Dose-Rate Radiotherapy for Prostate Cancer

International Nuclear Information System (INIS)

Wang, B; Cvetkovic, D; Chen, L; Ma, C; Chen, X; Zhang, P; Zhang, C

2014-01-01

Purpose: Re-irradiation with conventional radiotherapy techniques (CRT) may pose significant risks due to high accumulative radiation doses. Pulsed low dose-rate radiotherapy (PLDR) has been used in clinical trials for recurrent cancer treatment. In our previous studies, PLDR irradiation showed significantly lower toxicity than CRT, resulting in much longer survival of mice after PLDR total body irradiation (TBI) than conventional TBI. The purpose of this study was to investigate tumor control efficacy of PLDR treatment for prostate cancer with an animal model of prostate cancer LNCaP. Methods: We used an orthotopic murine model of LNCaP cell line for this study. LNCaP cells were implanted into immune-suppressed male nude mice via surgery. We monitored the tumor growth with MRI. The tumor-bearing mice were allocated into a PLDR(n=9), CRT(n=7), and control group(n=7) randomly. The mice in the PLDR and CRT groups were irradiated with 2Gy dose for one time. For the CRT treatment, the mice received 2Gy at a dose-rate of 300 MU/minute. For the PLDR treatment, the 2Gy dose was further divided into ten pulses of 0.2Gy at the same dose-rate with an interval of 3 minutes between the pulses. Results: Sizable tumor growth delays were observed for the PLDR and CRT groups through weekly MRI scans. The mean values of the normalized tumor volumes (± standard deviation of the mean) were 1.53±0.07, 1.53±0.14, and 1.81±0.09 at one week after treatment, 2.28±0.13, 2.19±0.16, and 3.04±0.25 at two weeks after treatment, and 3.31±0.23, 3.14±0.24 and 4.62±0.49 at three weeks after treatment, for the PLDR, CRT, and control groups, respectively. Conclusion: The PLDR and CRT treatments showed comparable tumor control rates in this study. Our in vivo results indicate that PLDR may be a viable option for treating recurrent prostate cancer due to its equivalent tumor control but low normal tissue toxocities

Use of BEIR V and UNSCEAR 1988 in radiation risk assessment: Lifetime total cancer mortality risk estimates at low doses and low dose rates for low-LET radiation

International Nuclear Information System (INIS)

1992-12-01

In November 1986, the Department of Defense (DoD) asked the Committee on Interagency Radiation Research and Policy Coordination (CIRRPC) to develop a coordinated Federal position on risk assessment for low levels of ionizing radiation. Since Federal risk assessment activities are based primarily on the scientific data and analyses in authoritative review documents prepared by groups like the National Academy of Sciences' Committee on the Biological Effects of Ionizing Radiation (BEIR), the National Council on Radiation Protection and Measurements (NCRP) and the United Nations' Scientific Committee on the Effects of Atomic Radiation (UNSCEAR), DoD proposed that the CIRRPC Science Panel undertake the task of providing coordinated interagency positions on the use of information in the reports of such groups. The practice has been for individual Federal agencies to interpret and decide independently how to use the information provided in such reports. As a result of its deliberations, the Subpanel recommends two nominal risk estimates for lifetime total cancer mortality following whole-body exposure to low levels of low-LET ionizing radiation, one for the general population and one for the working-age population (see Section II). The recommended risk estimates reflect the general agreement of information in BEIR V and UNSCEAR 1988 for total cancer mortality. The Subpanel's risk estimates and associated statements are intended to meet the needs of the Federal agencies for: (a) values that are current; (b) values that are relevant to the low-dose and low dose-rate ionizing radiation exposures principally encountered in carrying out Federal responsibilities; (c) a statement of the change in the estimates of lifetime total cancer mortality relative to estimates in previous authoritative review documents; and (d) a practical statement on the scientific uncertainty associated with applying the lifetime total cancer mortality values at very low doses

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)

Metz-Flamant, Camille

2011-01-01

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

Biological responses to low dose rate gamma radiation

International Nuclear Information System (INIS)

Magae, Junji; Ogata, Hiromitsu

2003-01-01

Linear non-threshold (LNT) theory is a basic theory for radioprotection. While LNT dose not consider irradiation time or dose-rate, biological responses to radiation are complex processes dependent on irradiation time as well as total dose. Moreover, experimental and epidemiological studies that can evaluate LNT at low dose/low dose-rate are not sufficiently accumulated. Here we analyzed quantitative relationship among dose, dose-rate and irradiation time using chromosomal breakage and proliferation inhibition of human cells as indicators of biological responses. We also acquired quantitative data at low doses that can evaluate adaptability of LNT with statistically sufficient accuracy. Our results demonstrate that biological responses at low dose-rate are remarkably affected by exposure time, and they are dependent on dose-rate rather than total dose in long-term irradiation. We also found that change of biological responses at low dose was not linearly correlated to dose. These results suggest that it is necessary for us to create a new model which sufficiently includes dose-rate effect and correctly fits of actual experimental and epidemiological results to evaluate risk of radiation at low dose/low dose-rate. (author)

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

International Nuclear Information System (INIS)

Sasaki, Masao S.

2013-01-01

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

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

International Nuclear Information System (INIS)

Tayier, A.; Hayashi, Keiji; Yoshimura, Ryoichi

2011-01-01

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 198 Au grains. A total of 133 stage I-II buccal mucosa carcinomas patients received 198 Au grain implantation brachytherapy between January 1982 and July 2005: 75 of them were treated by 198 Au grain implantation alone and 58 were treated by 198 Au implantation in combination with external irradiation. The average 198 Au-grain dose was 70 Gy in 7 days. Gross tumor areas ranged from 2.4 cm 2 to 9 cm 2 , and the clinical target areas ranged from 6 cm 2 to 15 cm 2 . 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)

The brachytherapy with low dose-rate iridium for prostate cancer

International Nuclear Information System (INIS)

Momma, Tetsuo; Saito, Shiro; Ohki, Takahiro; Satoh, Hiroyuki; Toya, Kazuhito; Dokiya, Takushi; Murai, Masaru

2000-01-01

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

Effects of dose, dose-rate and fraction on radiation-induced breast and lung cancers

International Nuclear Information System (INIS)

Howe, G.R.

1992-01-01

Recent results from a large Canadian epidemiologic cohort study of low-LET radiation and cancer will be described. This is a study of 64,172 tuberculosis patients first treated in Canada between 1930 and 1952, of whom many received substantial doses to breast and lung tissue from repeated chest fluoroscopies. The mortality of the cohort between 1950 and 1987 has been determined by computerized record linkage to the National Mortality Data Base. There is a strong positive association between radiation and breast cancer risk among the females in the cohort, but in contrast very little evidence of any increased risk in lung cancer. The results of this and other studies suggest that the effect of dose-rate and/or fractionation on cancer risk may will differ depending upon the particular cancer being considered. (author)

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

International Nuclear Information System (INIS)

Takahashi, A.; Ohnishi, K.; Asakawa, I.; Tamamoto, T.; Yasumoto, J.; Yuki, K.; Ohnishi, T.; Tachibana, A.

2003-01-01

Full text: We have studied whether the p53-centered signal transduction pathway induced by acute radiation is interfered with chronic pre-irradiation at a low dose-rate in human cultured cells and whole body of mice. In squamous cell carcinoma cells, we found that a challenge irradiation with X-ray immediately after chronic irradiation resulted in lower levels of p53 than those observed after the challenge irradiation alone. In addition, the induction of p53-centered apoptosis and the accumulation of its related proteins after the challenge irradiation were strongly correlated with the above-mentioned phenomena. In mouse spleen, the induction of apoptosis and the accumulation of p53 and Bax were observed dose-dependently at 12 h after a challenge irradiation. In contrast, we found significant suppression of them induced by challenge irradiation at a high dose-rate when mice were pre-irradiated with chronic irradiation at a low dose-rate. These findings suggest that chronic pre-irradiation suppressed the p53 function through radiation-induced p53-dependent signal transduction processes. There are numerous papers about p53 functions in apoptosis, radiosensitivity, genomic instability and cancer incidence in cultured cells or animals. According to our data and other findings, since p53 can prevent carcinogenesis, pre-irradiation at a low dose-rate might enhance the predisposition to cancer. Therefore, it is possible that different maximal permissible dose equivalents for the public populations are appropriate. Furthermore, concerning health of human beings, studies of the adaptive responses to radiation are quite important, because the radiation response strongly depends on experience of prior exposure to radiation

Medium-dose-rate intracavitary brachytherapy for cervical cancer

International Nuclear Information System (INIS)

Tanaka, Eiichi; Isohashi, Fumiaki; Oh, Ryoong-Jin

2003-01-01

due to pelvic necrosis without local recurrence 6 years after radiotherapy (Grade 5). Another patient developed perforation of sigmoid colon 9 years after radiotherapy (Grade 4). Minor late complications (Grade 1-2) occurred in 7 patients (9%). MDR-ICRT for cervical cancer can be used as effectively as low-dose-late (LDR) and high-dose-rate (HDR) ICRT. (author)

Relative implications of protective responses versus damage induction at low dose and low-dose-rate exposures, using the microdose approach

Energy Technology Data Exchange (ETDEWEB)

Feinendegen, L.E

2003-07-01

In reviewing tissue effects of low-dose radiation (1) absorbed dose to tissue is replaced by the sum of energy deposited with track events in cell-equivalent tissue micromasses, i.e. with microdose hits, in the number of exposed micromasses and (2) induced cell damage and adaptive protection are related to microdose hits in exposed micromasses for a given radiation quality. DNA damage increases with the number of microdose hits. They also can induce adaptive protection, mainly against endogenous DNA damage. This protection involves cellular defenses, DNA repair and damage removal. With increasing numbers of low linear energy transfer (LET) microdose hits in exposed micromasses, adaptive protection first tends to outweigh damage and then (above 200 mGy) fails and largely disappears. These experimental data predict that cancer risk coefficients derived by epidemiology at high-dose irradiation decline at low doses and dose rates when adaptive protection outdoes DNA damage. The dose-risk function should include both linear and non-linear terms at low doses. (author)

Relative implications of protective responses versus damage induction at low dose and low-dose-rate exposures, using the microdose approach

International Nuclear Information System (INIS)

Feinendegen, L.E.

2003-01-01

In reviewing tissue effects of low-dose radiation (1) absorbed dose to tissue is replaced by the sum of energy deposited with track events in cell-equivalent tissue micromasses, i.e. with microdose hits, in the number of exposed micromasses and (2) induced cell damage and adaptive protection are related to microdose hits in exposed micromasses for a given radiation quality. DNA damage increases with the number of microdose hits. They also can induce adaptive protection, mainly against endogenous DNA damage. This protection involves cellular defenses, DNA repair and damage removal. With increasing numbers of low linear energy transfer (LET) microdose hits in exposed micromasses, adaptive protection first tends to outweigh damage and then (above 200 mGy) fails and largely disappears. These experimental data predict that cancer risk coefficients derived by epidemiology at high-dose irradiation decline at low doses and dose rates when adaptive protection outdoes DNA damage. The dose-risk function should include both linear and non-linear terms at low doses. (author)

A comparison of anti-tumor effects of high dose rate fractionated and low dose rate continuous irradiation in multicellular spheroids

International Nuclear Information System (INIS)

Kubota, Nobuo; Omura, Motoko; Matsubara, Sho.

1997-01-01

In a clinical experience, high dose rate (HDR) fractionated interstitial radiotherapy can be an alternative to traditional low dose rate (LDR) continuous interstitial radiotherapy for head and neck cancers. To investigate biological effect of HDR, compared to LDR, comparisons have been made using spheroids of human squamous carcinoma cells. Both LDR and HDR were delivered by 137 Cs at 37degC. Dose rate of LDR was 8 Gy/day and HDR irradiations of fraction size of 4, 5 or 6 Gy were applied twice a day with an interval time of more than 6 hr. We estimated HDR fractionated dose of 31 Gy with 4 Gy/fr to give the same biological effects of 38 Gy by continuous LDR for spheroids. The ratio of HDR/LDR doses to control 50% spheroids was 0.82. (author)

Low dose diagnostic radiation does not increase cancer risk in cancer prone mice

Energy Technology Data Exchange (ETDEWEB)

Boreham, D., E-mail: dboreham@nosm.ca [Northern Ontario School of Medicine, ON (Canada); Phan, N., E-mail: nghiphan13@yahoo.com [Univ. of Ottawa, Ottawa, ON (Canada); Lemon, J., E-mail: lemonja@mcmaster.ca [McMaster Univ., Hamilton, ON (Canada)

2014-07-01

The increased exposure of patients to low dose diagnostic ionizing radiation has created concern that these procedures will result in greater risk of carcinogenesis. However, there is substantial evidence that shows in many cases that low dose exposure has the opposite effect. We have investigated whether CT scans can modify mechanisms associated with carcinogenesis in cancer-prone mice. Cancer was induced in Trp53+/- mice with an acute high dose whole-body 4 Gy γ-radiation exposure. Four weeks following the cancer-inducing dose, weekly whole-body CT scans (10 mGy/scan, 75 kVp X-rays) were given for ten consecutive weeks adding an additional radiation burden of 0.1 Gy. Short-term biological responses and subsequent lifetime cancer risk were investigated. Five days following the last CT scan, there were no detectable differences in the spontaneous levels of DNA damage in blood cells (reticulocytes). In fact, CT scanned mice had significantly lower constitutive levels of oxidative DNA damage and cell death (apoptosis), compared to non-CT scanned mice. This shows that multiple low dose radiation exposures modified the radio response and indicates protective processes were induced in mice. In mice treated with the multiple CT scans following the high cancer-inducing 4 Gy dose, tumour latency was increased, significantly prolonging lifespan. We conclude that repeated CT scans can reduce the cancer risk of a prior high-dose radiation exposure, and delay the progression of specific types of radiation-induced cancers in Trp53+/-mice. This research shows for the first time that low dose exposure long after cancer initiation events alter risk and reduce cancer morbidity. Cancer induction following low doses does not follow a linear non-threshold model of risk and this model should not be used to extrapolate risk to humans following low dose exposure to ionizing radiation. (author)

High-dose-rate brachytherapy alone post-hysterectomy for endometrial cancer

International Nuclear Information System (INIS)

MacLeod, Craig; Fowler, Allan; Duval, Peter; D'Costa, Ieta; Dalrymple, Chris; Firth, Ian; Elliott, Peter; Atkinson, Ken; Carter, Jonathan

1998-01-01

Purpose: To evaluate the outcome of post-hysterectomy adjuvant vaginal high-dose-rate (HDR) brachytherapy. Methods and Materials: A retrospective analysis was performed on a series of 143 patients with endometrial cancer treated with HDR brachytherapy alone post-hysterectomy from 1985 to June 1993. Of these patients, 141 received 34 Gy in four fractions prescribed to the vaginal mucosa in a 2-week period. The median follow-up was 6.9 years. Patients were analyzed for treatment parameters, survival, local recurrence, distant relapse, and toxicity. Results: Five-year relapse free survival and overall survival was 100% and 88% for Stage 1A, 98% and 94% for Stage IB, 100% and 86% for Stage IC, and 92% and 92% for Stage IIA. The overall vaginal recurrence rate was 1.4%. The overall late-toxicity rate was low, and no RTOG grade 3, 4, or 5 complications were recorded. Conclusion: These results are similar to reported international series that have used either low-dose-rate or HDR brachytherapy. The biological effective dose was low for both acute and late responding tissues compared with some of the HDR brachytherapy series, and supports using this lower dose and possibly decreasing late side-effects with no apparent increased risk of vaginal recurrence

Quantitative analysis of biological responses to low dose-rate γ-radiation, including dose, irradiation time, and dose-rate

International Nuclear Information System (INIS)

Magae, J.; Furukawa, C.; Kawakami, Y.; Hoshi, Y.; Ogata, H.

2003-01-01

Full text: Because biological responses to radiation are complex processes dependent on irradiation time as well as total dose, it is necessary to include dose, dose-rate and irradiation time simultaneously to predict the risk of low dose-rate irradiation. In this study, we analyzed quantitative relationship among dose, irradiation time and dose-rate, using chromosomal breakage and proliferation inhibition of human cells. For evaluation of chromosome breakage we assessed micronuclei induced by radiation. U2OS cells, a human osteosarcoma cell line, were exposed to gamma-ray in irradiation room bearing 50,000 Ci 60 Co. After the irradiation, they were cultured for 24 h in the presence of cytochalasin B to block cytokinesis, cytoplasm and nucleus were stained with DAPI and propidium iodide, and the number of binuclear cells bearing micronuclei was determined by fluorescent microscopy. For proliferation inhibition, cells were cultured for 48 h after the irradiation and [3H] thymidine was pulsed for 4 h before harvesting. Dose-rate in the irradiation room was measured with photoluminescence dosimeter. While irradiation time less than 24 h did not affect dose-response curves for both biological responses, they were remarkably attenuated as exposure time increased to more than 7 days. These biological responses were dependent on dose-rate rather than dose when cells were irradiated for 30 days. Moreover, percentage of micronucleus-forming cells cultured continuously for more than 60 days at the constant dose-rate, was gradually decreased in spite of the total dose accumulation. These results suggest that biological responses at low dose-rate, are remarkably affected by exposure time, that they are dependent on dose-rate rather than total dose in the case of long-term irradiation, and that cells are getting resistant to radiation after the continuous irradiation for 2 months. It is necessary to include effect of irradiation time and dose-rate sufficiently to evaluate risk

Investigation of the dose rate dependency of the PAGAT gel dosimeter at low dose rates

International Nuclear Information System (INIS)

Zehtabian, M.; Faghihi, R.; Zahmatkesh, M.H.; Meigooni, A.S.; Mosleh-Shirazi, M.A.; Mehdizadeh, S.; Sina, S.; Bagheri, S.

2012-01-01

Medical physicists need dosimeters such as gel dosimeters capable of determining three-dimensional dose distributions with high spatial resolution. To date, in combination with magnetic resonance imaging (MRI), polyacrylamide gel (PAG) polymers are the most promising gel dosimetry systems. The purpose of this work was to investigate the dose rate dependency of the PAGAT gel dosimeter at low dose rates. The gel dosimeter was used for measurement of the dose distribution around a Cs-137 source from a brachytherapy LDR source to have a range of dose rates from 0.97 Gy h −1 to 0.06 Gy h −1 . After irradiation of the PAGAT gel, it was observed that the dose measured by gel dosimetry was almost the same at different distances (different dose rates) from the source, although the points nearer the source had been expected to receive greater doses. Therefore, it was suspected that the PAGAT gel is dose rate dependent at low dose rates. To test this further, three other sets of measurements were performed by placing vials containing gel at different distances from a Cs-137 source. In the first two measurements, several plastic vials were exposed to equal doses at different dose rates. An ionization chamber was used to measure the dose rate at each distance. In addition, three TLD chips were simultaneously irradiated in order to verify the dose to each vial. In the third measurement, to test the oxygen diffusion through plastic vials, the experiment was repeated again using plastic vials in a nitrogen box and glass vials. The study indicates that oxygen diffusion through plastic vials for dose rates lower than 2 Gy h −1 would affect the gel dosimeter response and it is suggested that the plastic vials or (phantoms) in an oxygen free environment or glass vials should be used for the dosimetry of low dose rate sources using PAGAT gel to avoid oxygen diffusion through the vials.

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...

Dose rate effect on low-dose hyper-radiosensitivity with cells in vitro

Energy Technology Data Exchange (ETDEWEB)

Kim, Geon-Min; Kim, Eun-Hee [Seoul National University, Seoul (Korea, Republic of)

2016-10-15

Low-dose hyper-radiosensitivity (HRS) is the phenomenon that mammalian cells exhibit higher sensitivity to radiation at low doses (< 0.5 Gy) than expected by the linear-quadratic model. At doses above 0.5Gy, the cellular response is recovered to the level expected by the linear-quadratic model. This transition is called the increased radio-resistance (IRR). HRS was first verified using Chinese hamster V79 cells in vitro by Marples and has been confirmed in studies with other cell lines including human normal and tumor cells. HRS is known to be induced by inactivation of ataxia telangiectasia-mutated (ATM), which plays a key role in repairing DNA damages. Considering the connection between ATM and HRS, one can infer that dose rate may affect cellular response regarding HRS at low doses. In this study, we quantitated the effect of dose rate on HRS by clonogenic assay with normal and tumor cells. The HRS of cells at low dose exposures is a phenomenon already known. In this study, we observed HRS of rat normal diencephalon cells and rat gliosarcoma cells at doses below 1 Gy. In addition, we found that dose rate mattered. HRS occurred at low doses, but only when total dose was delivered at a rate below certain level.

Radiobiological aspects of continuous low dose-rate irradiation and fractionated high dose-rate irradiation

International Nuclear Information System (INIS)

Turesson, I.

1990-01-01

The biological effects of continuous low dose-rate irradiation and fractionated high dose-rate irradiation in interstitial and intracavitary radiotherapy and total body irradiation are discussed in terms of dose-rate fractionation sensitivity for various tissues. A scaling between dose-rate and fraction size was established for acute and late normal-tissue effects which can serve as a guideline for local treatment in the range of dose rates between 0.02 and 0.005 Gy/min and fraction sizes between 8.5 and 2.5 Gy. This is valid provided cell-cycle progression and proliferation can be ignored. Assuming that the acute and late tissue responses are characterized by α/β values of about 10 and 3 Gy and a mono-exponential repair half-time of about 3 h, the same total doses given with either of the two methods are approximately equivalent. The equivalence for acute and late non-hemopoietic normal tissue damage is 0.02 Gy/min and 8.5 Gy per fraction; 0.01 Gy/min and 5.5 Gy per fraction; and 0.005 Gy/min and 2.5Gy per fraction. A very low dose rate, below 0.005 Gy/min, is thus necessary to simulate high dose-rate radiotherapy with fraction sizes of about 2Gy. The scaling factor is, however, dependent on the repair half-time of the tissue. A review of published data on dose-rate effects for normal tissue response showed a significantly stronger dose-rate dependence for late than for acute effects below 0.02 Gy/min. There was no significant difference in dose-rate dependence between various acute non-hemopoietic effects or between various late effects. The consistent dose-rate dependence, which justifies the use of a general scaling factor between fraction size and dose rate, contrasts with the wide range of values for repair half-time calculated for various normal-tissue effects. This indicates that the model currently used for repair kinetics is not satisfactory. There are also few experimental data in the clinical dose-rate range, below 0.02 Gy/min. It is therefore

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

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Murray, I.; Mather, S.J.

2015-01-01

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 Y 90 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)

Ageing effects of polymers at very low dose-rates

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Chenion, J.; Armand, X.; Berthet, J.; Carlin, F.; Gaussens, G.; Le Meur, M.

1987-10-01

The equipment irradiation dose-rate into the containment is variable from 10 -6 to 10 -4 gray per second for the most exposed materials. During qualification, safety equipments are submitted in France to dose-rates around 0.28 gray per second. This study purpose is to now if a so large irradiation dose-rate increase is reasonable. Three elastomeric materials used in electrical cables, o'rings seals and connectors, are exposed to a very large dose-rates scale between 2.1.10 -4 and 1.4 gray per second, to 49 KGy dose. This work was carried out during 3.5 years. Oxygen consumption measurement of the air in contact with polymer materials, as mechanical properties measurement show that: - at very low dose-rate, oxygen consumption is maximum at the same time (1.4 year) for the three elastomeric samples. Also, mechanical properties simultaneously change with oxygen consumption. At very low dose-rate, for the low irradiation doses, oxygen consumption is at least 10 times more important that it is showed when irradiation is carried out with usual material qualification dose-rate. At very low dose-rate, oxygen consumption decreases when absorbed irradiation dose by samples increases. The polymer samples irradiation dose is not still sufficient (49 KGy) to certainly determine, for the three chosen polymer materials, the reasonable irradiation acceleration boundary during nuclear qualification tests [fr

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

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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

The biological effect of 125I seed continuous low dose rate irradiation in CL187 cells

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Zhuang Hong-Qing

2009-01-01

Full Text Available Abstract Background To investigate the effectiveness and mechanism of 125I seed continuous low-dose-rate irradiation on colonic cell line CL187 in vitro. Methods The CL187 cell line was exposed to radiation of 60Coγ ray at high dose rate of 2 Gy/min and 125I seed at low dose rate of 2.77 cGy/h. Radiation responses to different doses and dose rates were evaluated by colony-forming assay. Under 125I seed low dose rate irradiation, a total of 12 culture dishes were randomly divided into 4 groups: Control group, and 2, 5, and 10 Gy irradiation groups. At 48 h after irradiation, apoptosis was detected by Annexin and Propidium iodide (PI staining. Cell cycle arrests were detected by PI staining. In order to investigate the influence of low dose rate irradiation on the MAPK signal transduction, the expression changes of epidermal growth factor receptor (EGFR and Raf under continuous low dose rate irradiation (CLDR and/or EGFR monoclonal antibodies were determined by indirect immunofluorescence. Results The relative biological effect (RBE for 125I seeds compared with 60Co γ ray was 1.41. Apoptosis rates of CL187 cancer cells were 13.74% ± 1.63%, 32.58% ± 3.61%, and 46.27% ± 3.82% after 2 Gy, 5 Gy, and 10 Gy irradiation, respectively; however, the control group apoptosis rate was 1.67% ± 0.19%. G2/M cell cycle arrests of CL187 cancer cells were 42.59% ± 3.21%, 59.84% ± 4.96%, and 34.61% ± 2.79% after 2 Gy, 5 Gy, and 10 Gy irradiation, respectively; however, the control group apoptosis rate was 26.44% ± 2.53%. P 2/M cell cycle arrest. After low dose rate irradiation, EGFR and Raf expression increased, but when EGFR was blocked by a monoclonal antibody, EGFR and Raf expression did not change. Conclusion 125I seeds resulted in more effective inhibition than 60Co γ ray high dose rate irradiation in CL187 cells. Apoptosis following G2/M cell cycle arrest was the main mechanism of cell-killing effects under low dose rate irradiation. CLDR could

Genotoxic effects of high dose rate X-ray and low dose rate gamma radiation in ApcMin/+ mice.

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Graupner, Anne; Eide, Dag M; Brede, Dag A; Ellender, Michele; Lindbo Hansen, Elisabeth; Oughton, Deborah H; Bouffler, Simon D; Brunborg, Gunnar; Olsen, Ann Karin

2017-10-01

Risk estimates for radiation-induced cancer in humans are based on epidemiological data largely drawn from the Japanese atomic bomb survivor studies, which received an acute high dose rate (HDR) ionising radiation. Limited knowledge exists about the effects of chronic low dose rate (LDR) exposure, particularly with respect to the application of the dose and dose rate effectiveness factor. As part of a study to investigate the development of colon cancer following chronic LDR vs. acute HDR radiation, this study presents the results of genotoxic effects in blood of exposed mice. CBAB6 F1 Apc +/+ (wild type) and Apc Min/+ mice were chronically exposed to estimated whole body absorbed doses of 1.7 or 3.2 Gy 60 Co-γ-rays at a LDR (2.2 mGy h -1 ) or acutely exposed to 2.6 Gy HDR X-rays (1.3 Gy min -1 ). Genotoxic endpoints assessed in blood included chromosomal damage (flow cytometry based micronuclei (MN) assay), mutation analyses (Pig-a gene mutation assay), and levels of DNA lesions (Comet assay, single-strand breaks (ssb), alkali labile sites (als), oxidized DNA bases). Ionising radiation (ca. 3 Gy) induced genotoxic effects dependent on the dose rate. Chromosomal aberrations (MN assay) increased 3- and 10-fold after chronic LDR and acute HDR, respectively. Phenotypic mutation frequencies as well as DNA lesions (ssb/als) were modulated after acute HDR but not after chronic LDR. The Apc Min/+ genotype did not influence the outcome in any of the investigated endpoints. The results herein will add to the scant data available on genotoxic effects following chronic LDR of ionising radiation. Environ. Mol. Mutagen. 58:560-569, 2017. © 2017 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society. © 2017 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.

Consequences of the exposure at low dose rates-contribution of animal experimentation

International Nuclear Information System (INIS)

Masse, R.

1990-01-01

The exposure of laboratory animals to the various types of radiations will induce cancers in relation with the tissue absorbed doses. The shape of the dose-effet relationship is most variable. It is important to distinguish which tumours are comparable to human tumours. Those showing more analogies answer but seldom to the classical lineo-quadratic relationship; however, a strong attenuation of induction is demonstrated at low dose rates. Quasi-threshold relationships are seen after the exposure of some tissues to high-LET radiations. These observations question the validity of generalizing the radiobiologists' dual action theory, setting the origin of the dose-effect relationship in the induction of events within the DNA molecule. There is an alternative in the cellular collaboration events; it assumes that the effectiveness per dose unit decreases constantly as an inverse function of the dose rate [fr

Bystander effects of exposure to low-dose-rate 125I seeds on human lung cancers cells in vitro

International Nuclear Information System (INIS)

Jia Rongfei; Chen Honghong; Yu Lei; Zhao Meijia; Shao Chunlin; Cheng Wenying

2007-01-01

The bystander effects induced by continuous low-dose-rate (LDR) 125 I seeds radiation on damage of human lung cancer cells were investigated. Human adenocarcinoma cell line A549 and human small cell lung cancer cell line NCI-H446, which have different sensitivities to high-dose rate (HDR) external irradiation, were exposed directly to 125 I seeds in vitro and co-cultured with unirradiated cells for 24 h. Using cytokinesis-blocking micronucleus method and γ H2AX fluorescence immunoassay, bystander effects induced by 2Gy and 4Gy 125 I seed irradiation on micronucleus formation and DNA double-strand breaks (DSBs) of human lung cancer cells were detected and evaluated. The results showed that irradiation with 125 I seeds can induce medium-mediated bystander effects in A549 cells and NCI-H446 cells, exhibiting that both micronuclei formation and γ H2AX focus formation in bystander cells were increased significantly compared with non-irradiated cells. The extent of DNA damage induced by bystander effects was correlated with accumulated radiation dose and radiosensitive of tumor cells. NCI-H446 cells that were sensitive to HDR γ irradiation were more sensitive to continuous LDR irradiation and bystander effects than A549. However, a comparison between the bystander effects and direct effects elicits the intensity of bystander responses of A549 cells was higher than that of NCI-H446 cells. A dose-related reduction in bystander responses was observed both in A549 cells and NCI-H446 cells, suggesting that the signaling factors involved in the bystander signaling pathways may decrease with the increase of cell damages. (authors)

Low dose CT in early lung cancer diagnosis: prevalence data

International Nuclear Information System (INIS)

Cardinale, Luciano; Cortese, Giancarlo; Ferraris, Fabrizio; Perotto, Fabio; Fava, Cesare; Borasio, Piero; Dogliotti, Luigi; Novello, Silvia; Scagliotti, Giorgio

2005-01-01

Purpose. Lung cancer has a high mortality rate and its prognosis largely depends on early detection. We report the prevalence data of the study on early detection of lung cancer with low-dose spiral CT underway at our hospital. Materials and methods. Since the beginning of 2001, 519 asymptomatic volunteers have undergone annual blood tests, sputum tests, urinalyses and low-dose spiral CT. The inclusion criteria were age (55 years old), a history of cigarette smoking and a negative history for previous neoplastic disease. The diagnostic workup varied depending on the size and CT features of the nodules detected. Results. At baseline, the CT scan detected nodules> 5 mm in 22% of subjects; the nodules were single in 42 and multiple in 71. In 53% of cases the findings were completely negative, while in 122 (23.4%) nodules with a diameter [it

Retrospective Dosimetric Comparison of Low-Dose-Rate and Pulsed-Dose-Rate Intracavitary Brachytherapy Using a Tandem and Mini-Ovoids

International Nuclear Information System (INIS)

Mourtada, Firas; Gifford, Kent A.; Berner, Paula A.; Horton, John L.; Price, Michael J.; Lawyer, Ann A.; Eifel, Patricia J.

2007-01-01

The purpose of this study was to compare the dose distribution of Iridium-192 ( 192 Ir) pulsed-dose-rate (PDR) brachytherapy to that of Cesium-137 ( 137 Cs) low-dose-rate (LDR) brachytherapy around mini-ovoids and an intrauterine tandem. Ten patient treatment plans were selected from our clinical database, all of which used mini-ovoids and an intrauterine tandem. A commercial treatment planning system using AAPM TG43 formalism was used to calculate the dose in water for both the 137 Cs and 192 Ir sources. For equivalent system loadings, we compared the dose distributions in relevant clinical planes, points A and B, and to the ICRU bladder and rectal reference points. The mean PDR doses to points A and B were 3% ± 1% and 6% ± 1% higher than the LDR doses, respectively. For the rectum point, the PDR dose was 4% ± 3% lower than the LDR dose, mainly because of the 192 Ir PDR source anisotropy. For the bladder point, the PDR dose was 1% ± 4% higher than the LDR dose. We conclude that the PDR and LDR dose distributions are equivalent for intracavitary brachytherapy with a tandem and mini-ovoids. These findings will aid in the transfer from the current practice of LDR intracavitary brachytherapy to PDR for the treatment of gynecologic cancers

High-dose-rate versus low-dose-rate brachytherapy in the treatment of cervical cancer: analysis of tumor recurrence - the University of Wisconsin experience

International Nuclear Information System (INIS)

Petereit, Daniel G.; Sarkaria, Jann N.; Potter, David M.; Schink, Julian C.

1999-01-01

Purpose: To retrospectively compare the clinical outcome for cervical cancer patients treated with high-dose-rate (HDR) vs. low-dose-rate (LDR) brachytherapy. Methods and Materials: One hundred ninety-one LDR patients were treated from 1977 to 1988 and compared to 173 HDR patients treated from 1989 to 1996. Patients of similar stage and tumor volumes were treated with identical external beam fractionation schedules. Brachytherapy was given in either 1 or 2 LDR implants for the earlier patient cohort, and 5 HDR implants for the latter cohort. For both patient groups, Point A received a minimum total dose of 80 Gy. The linear-quadratic formula was used to calculate the LDR dose-equivalent contribution to Point A for the HDR treatments. The primary endpoints assessed were survival, pelvic control, relapse-free survival, and distant metastases. Endpoints were estimated using the Kaplan-Meier method. Comparisons between treatment groups were performed using the log-rank test and Cox proportional hazards models. Results: The median follow-up was 65 months (2 to 208 months) in the LDR group and 22 months (1 to 85 months) in the HDR group. For all stages combined there was no difference in survival, pelvic control, relapse-free survival, or distant metastases between LDR and HDR patients. For Stage IB and II HDR patients, the pelvic control rates were 85% and 80% with survival rates of 86% and 65% at 3 years, respectively. In the LDR group, Stage IB and II patients had 91% and 78% pelvic control rates, with 82% and 58% survival rates at 3 years, respectively. No difference was seen in survival or pelvic control for bulky Stage I and II patients combined (> 5 cm). Pelvic control at 3 years was 44% (HDR) versus 75% (LDR) for Stage IIIB patients (p = 0.002). This difference in pelvic control was associated with a lower survival rate in the Stage IIIB HDR versus LDR population (33% versus 58%, p = 0.004). The only major difference, with regard to patient characteristics

Estimation of radiation risks at low dose

International Nuclear Information System (INIS)

1990-04-01

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

Late effects of low doses and dose rates

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Paretzke, H.G.

1980-01-01

This paper outlines the spectrum of problems and approaches used in work on the derivation of quantitative prognoses of late effects in man of low doses and dose rates. The origins of principal problems encountered in radiation risks assessments, definitions and explanations of useful quantities, methods of deriving risk factors from biological and epidemiological data, and concepts of risk evaluation and problems of acceptance are individually discussed

Low and high dose rate heavy ion radiation-induced intestinal and colonic tumorigenesis in APC1638N/+ mice

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Suman, Shubhankar; Kumar, Santosh; Moon, Bo-Hyun; Fornace, Albert J.; Datta, Kamal

2017-05-01

Ionizing radiation (IR) is a recognized risk factor for colorectal cancer (CRC) and astronauts undertaking long duration space missions are expected to receive IR doses in excess of permissible limits with implications for colorectal carcinogenesis. Exposure to IR in outer space occurs at low doses and dose rates, and energetic heavy ions due to their high linear energy transfer (high-LET) characteristics remain a major concern for CRC risk in astronauts. Previously, we have demonstrated that intestinal tumorigenesis in a mouse model (APC1638N/+) of human colorectal cancer was significantly higher after exposure to high dose rate energetic heavy ions relative to low-LET γ radiation. The purpose of the current study was to compare intestinal tumorigenesis in APC1638N/+ mice after exposure to energetic heavy ions at high (50 cGy/min) and relatively low (0.33 cGy/min) dose rate. Male and female mice (6-8 weeks old) were exposed to either 10 or 50 cGy of 28Si (energy: 300 MeV/n; LET: 70 keV/μm) or 56Fe (energy: 1000 MeV/n; LET: 148 keV/μm) ions at NASA Space Radiation Laboratory in Brookhaven National Laboratory. Mice (n = 20 mice/group) were euthanized and intestinal and colon tumor frequency and size were counted 150 days after radiation exposure. Intestinal tumorigenesis in male mice exposed to 56Fe was similar for high and low dose rate exposures. Although male mice showed a decreasing trend at low dose rate relative to high dose rate exposures, the differences in tumor frequency between the two types of exposures were not statistically significant after 28Si radiation. In female mice, intestinal tumor frequency was similar for both radiation type and dose rates tested. In both male and female mice intestinal tumor size was not different after high and low dose rate radiation exposures. Colon tumor frequency in male and female mice after high and low dose rate energetic heavy ions was also not significantly different. In conclusion, intestinal and colonic tumor

Rectal dose assessment in patients submitted to high-dose-rate brachytherapy for uterine cervix cancer

International Nuclear Information System (INIS)

Oliveira, Jetro Pereira de; Batista, Delano Valdivino Santos; Bardella, Lucia Helena; Carvalho, Arnaldo Rangel

2009-01-01

Objective: The present study was aimed at developing a thermoluminescent dosimetric system capable of assessing the doses delivered to the rectum of patients submitted to high-dose-rate brachytherapy for uterine cervix cancer. Materials and methods: LiF:Mg,Ti,Na powder was the thermoluminescent material utilized for evaluating the rectal dose. The powder was divided into small portions (34 mg) which were accommodated in a capillary tube. This tube was placed into a rectal probe that was introduced into the patient's rectum. Results: The doses delivered to the rectum of six patients submitted to high-dose-rate brachytherapy for uterine cervix cancer evaluated by means of thermoluminescent dosimeters presented a good agreement with the planned values based on two orthogonal (anteroposterior and lateral) radiographic images of the patients. Conclusion: The thermoluminescent dosimetric system developed in the present study is simple and easy to be utilized as compared to other rectal dosimetry methods. The system has shown to be effective in the evaluation of rectal doses in patients submitted to high-dose-rate brachytherapy for uterine cervix cancer. (author)

Carcinogenesis induced by low-dose radiation

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Piotrowski Igor

2017-11-01

Full Text Available Although the effects of high dose radiation on human cells and tissues are relatively well defined, there is no consensus regarding the effects of low and very low radiation doses on the organism. Ionizing radiation has been shown to induce gene mutations and chromosome aberrations which are known to be involved in the process of carcinogenesis. The induction of secondary cancers is a challenging long-term side effect in oncologic patients treated with radiation. Medical sources of radiation like intensity modulated radiotherapy used in cancer treatment and computed tomography used in diagnostics, deliver very low doses of radiation to large volumes of healthy tissue, which might contribute to increased cancer rates in long surviving patients and in the general population. Research shows that because of the phenomena characteristic for low dose radiation the risk of cancer induction from exposure of healthy tissues to low dose radiation can be greater than the risk calculated from linear no-threshold model. Epidemiological data collected from radiation workers and atomic bomb survivors confirms that exposure to low dose radiation can contribute to increased cancer risk and also that the risk might correlate with the age at exposure.

DuraSeal® as a spacer to reduce rectal doses in low-dose rate brachytherapy for prostate cancer

International Nuclear Information System (INIS)

Heikkilä, Vesa-Pekka; Kärnä, Aarno; Vaarala, Markku H.

2014-01-01

The purpose of this study was to evaluate the utility of off-label use of DuraSeal® polyethylene glycol (PEG) gel in low-dose rate (LDR) prostate brachytherapy seed implantation to reduce rectal doses. Diluted DuraSeal® was easy to use and, in spite of a clearance effect, useful in decreasing D 2cc rectal doses

Human papillomavirus E6 and E7 oncoproteins alter cell cycle progression but not radiosensitivity of carcinoma cells treated with low-dose-rate radiation

International Nuclear Information System (INIS)

DeWeese, Theodore L.; Walsh, Jonathan C.; Dillehay, Larry E.; Kessis, Theodore D.; Hedrick, Lora; Cho, Kathleen R.; Nelson, William G.

1997-01-01

Purpose: Low-dose-rate radiation therapy has been widely used in the treatment of urogenital malignancies. When continuously exposed to low-dose-rate ionizing radiation, target cancer cells typically exhibit abnormalities in replicative cell-cycle progression. Cancer cells that arrest in the G2 phase of the cell cycle when irradiated may become exquisitely sensitive to killing by further low-dose-rate radiation treatment. Oncogenic human papillomaviruses (HPVs), which play a major role in the pathogenesis of uterine cervix cancers and other urogenital cancers, encode E6 and E7 transforming proteins known to abrogate a p53-dependent G1 cell-cycle checkpoint activated by conventional acute-dose radiation exposure. This study examined whether expression of HPV E6 and E7 oncoproteins by cancer cells alters the cell-cycle redistribution patterns accompanying low-dose-rate radiation treatment, and whether such alterations in cell-cycle redistribution affect cancer cell killing. Methods and Materials: RKO carcinoma cells, which contain wild-type P53 alleles, and RKO cell sublines genetically engineered to express HPV E6 and E7 oncoproteins, were treated with low-dose-rate (0.25-Gy/h) radiation and then assessed for p53 and p21WAF1/CIP1 polypeptide induction by immunoblot analysis, for cell-cycle redistribution by flow cytometry, and for cytotoxicity by clonogenic survival assay. Results: Low-dose-rate radiation of RKO carcinoma cells triggered p53 polypeptide elevations, p21WAF1/CIP1 induction, and arrest in the G1 and G2 phases of the cell cycle. In contrast, RKO cells expressing E6 and E7 transforming proteins from high-risk oncogenic HPVs (HPV 16) arrested in G2, but failed to arrest in G1, when treated with low-dose-rate ionizing radiation. Abrogation of the G1 cell-cycle checkpoint activated by low-dose-rate radiation exposure appeared to be a characteristic feature of transforming proteins from high-risk oncogenic HPVs: RKO cells expressing E6 from a low

Breast cancer incidence following low-dose rate environmental exposure: Techa River Cohort, 1956–2004

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Ostroumova, E; Preston, D L; Ron, E; Krestinina, L; Davis, F G; Kossenko, M; Akleyev, A

2008-01-01

In the 1950s, the Mayak nuclear weapons facility in Russia discharged liquid radioactive wastes into the Techa River causing exposure of riverside residents to protracted low-to-moderate doses of radiation. Almost 10 000 women received estimated doses to the stomach of up to 0.47 Gray (Gy) (mean dose=0.04 Gy) from external γ-exposure and 137Cs incorporation. We have been following this population for cancer incidence and mortality and as in the general Russian population, we found a significant temporal trend of breast cancer incidence. A significant linear radiation dose–response relationship was observed (P=0.01) with an estimated excess relative risk per Gray (ERR/Gy) of 5.00 (95% confidence interval (CI), 0.80, 12.76). We estimated that approximately 12% of the 109 observed cases could be attributed to radiation. PMID:19002173

Comparison of high dose rate (HDR) and low dose rate (LDR) brachytherapy in the treatment of stage IIIB cervix cancer with radiation therapy alone. The preliminary results

International Nuclear Information System (INIS)

Trippe, Nivaldo; Novaes, P.E.; Ferrigno, R.; Pellizzon, A.C.; Salvajoli, J.V.; Fogaroli, R.C.; Maia, M.A.C.; Baraldi, H.E.

1996-01-01

Purpose/Objective: To compare the results between HDR and LDR brachytherapy in the treatment of stage IIIB cervix cancer with radiation therapy alone through a prospective and randomized trial. Materials and Methods: From September 1992 to December 1993, 65 patients with stage IIIB cervical cancer were randomized to one of the following treatment schedule according to the brachytherapy used to complement the dose of external beam radiotherapy (EBRT): 1 - High dose rate (HDR) - 36 patients - 4 weekly insertions of 6,0 Gy at point A 2 - Low dose rate (LDR) - 29 patients - 2 insertions two weeks apart of 17,5 Gy at point A The External Beam radiotherapy was performed through a Linac 4MV, in box arrangement for whole pelvis and in AP-PA fields for parametrial complementation of dose. The dose at the whole pelvis was 45 Gy in 25 fractions of 1,8 Gy and the parametrial dose was 16 Gy. The brachytherapy was realized with Fletcher colpostats and intrauterine tandem, in both arms. The HDR brachytherapy was realized through a Micro-Selectron device, working with Iridium-192 with initial activity of 10 Ci and started ten days after the beginning of EBRT. The total treatment time was shortened in two weeks for this group. The LDR brachytherapy started only after the end of EBRT. Results: With the minimum follow up of 24 months and medium of 31 months, the disease free survival was 50% among the 36 patients in HDR group and 47,8% among the 29 patients in LDR group. Local failures occurred in 50% and 52,8% respectively. Grade I and II complications were restricted to rectites and cistites and the incidence of them was 8,3% for HDR group and 13% for LDR group. Until the time of evaluation there were no grade III complications in any group. Conclusions: Although the number of patients is small and the time of follow up still short, these preliminary results suggest that the HDR brachytherapy has an equivalent efficiency in local control as the LDR in the treatment of stage IIIB

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.

Salvage high-dose-rate brachytherapy for local prostate cancer recurrence after radical radiotherapy

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V. A. Solodkiy

2016-01-01

Full Text Available Studies salvage interstitial radiation therapy for recurrent prostate cancer, launched at the end of the XX century. In recent years, more and more attention is paid to high-dose-rate brachytherapy (HDR-BT as a method of treating local recurrence.The purpose of research – preliminary clinical results of salvage high-dose-rate brachytherapy applied in cases of suspected local recurrence or of residual tumour after radiotherapy.Preliminary findings indicate the possibility of using HDR-BT, achieving local tumor control with low genitourinary toxicity.

Estimates of Health Detriments and Tissue Weighting Factors for Hong Kong Populations from Low Dose, Low Dose Rate and Low LET Ionising Radiation Exposure

International Nuclear Information System (INIS)

Lee, S.K.

1998-01-01

The total health detriments and the tissue weighting factors for the Hong Kong populations from low dose, low dose rate and low LET ionising radiation exposure are obtained according to the methodology recommended in ICRP Publication 60. The probabilities of fatal cancers for the general (ages 0-90) and working (ages 20-64) populations due to lifetime exposure at low dose and low dose rate are 4.9 x 10 -2 Sv -1 and 3.6 x 10 -2 Sv -1 respectively, comparing with the ICRP 60 estimates of 5.0 x 10 -2 Sv -1 and 4.0 x 10 -2 Sv -1 . The corresponding total health detriments for the general and working populations are 6.9 x 10 -2 Sv -1 and 4.9 x 10 -2 Sv -1 respectively comparing with the ICRP 60 estimates of 7.3 x 10 -2 Sv -1 and 5.6 x 10 -2 Sv -1 . Tissue weighting factors for the general population are 0.01 (bone surface and skin), 0.02 (liver, oesophagus and thyroid), 0.04 (bladder and breast), 0.08 (remainder), 0.10 (stomach), 0.11 (bone marrow), 0.15 (colon), 0.19 (lung) and 0.21 (gonads) and for the working population are 0.01 (bone surface and skin), 0.03 (liver, oesophagus and thyroid), 0.04 (breast), 0.06 (remainder), 0.07 (bladder), 0.08 (colon), 0.14 (bone marrow and stomach), 0.16 (lung) and 0.20 (gonads). (author)

Lung cancer screening with low-dose CT

International Nuclear Information System (INIS)

Diederich, S.; Wormanns, D.; Heindel, W.

2003-01-01

Screening for lung cancer is hoped to reduce mortality from this common tumour, which is characterised by a dismal overall survival, relatively well defined risk groups (mainly heavy cigarette smokers and workers exposed to asbestos) and a lack of early symptoms. In the past studies using sputum cytology and chest radiography have failed to demonstrate any reduction in lung cancer mortality through screening. One of the reasons is probably the relatively poor sensitivity of both these tests in early tumours. Low radiation dose computed tomography (CT) has been shown to have a much higher sensitivity for small pulmonary nodules, which are believed to be the most common presentation of early lung cancer. As, however, small pulmonary nodules are common and most are not malignant, non-invasive diagnostic algorithms are required to correctly classify the detected lesions and avoid invasive procedures in benign nodules. Nodule density, size and the demonstration of growth at follow-up have been shown to be useful in this respect and may in the future be supplemented by contrast-enhanced CT and positron emission tomography. Based on these diagnostic algorithms preliminary studies of low-dose CT in heavy smokers have demonstrated a high proportion of asymptomatic, early, resectable cancers with good survival. As, however, several biases could explain these findings in the absence of the ultimate goal of cancer screening, i.e. mortality reduction, most researchers believe that randomised controlled trials including several 10000 subjects are required to demonstrate a possible mortality reduction. Only then general recommendations to screen individuals at risk of lung cancer with low-dose CT should be made. It can be hoped that international cooperation will succeed in providing results as early as possible

Interstitial high-dose rate brachytherapy as boost for anal canal cancer

International Nuclear Information System (INIS)

Falk, Alexander Tuan; Claren, Audrey; Benezery, Karen; François, Eric; Gautier, Mathieu; Gerard, Jean-Pierre; Hannoun-Levi, Jean-Michel

2014-01-01

To assess clinical outcomes of patients treated with a high-dose rate brachytherapy boost for anal canal cancer (ACC). From August 2005 to February 2013, 28 patients presenting an ACC treated by split-course external beam radiotherapy (EBRT) and HDR brachytherapy with or without chemotherapy in a French regional cancer center in Nice were retrospectively analyzed. Median age was 60.6 years [34 – 83], 25 patients presented a squamous cell carcinoma and 3 an adenocarcinoma; 21 received chemotherapy. Median dose of EBRT was 45 Gy [43.2 – 52]. Median dose of HDR brachytherapy was 12 Gy [10 - 15] with a median duration of 2 days. Median overall treatment time was 63 days and median delay between EBRT and brachytherapy was 20 days. Two-year local relapse free, metastatic free, disease free and overall survivals were 83%, 81.9%, 71.8% and 87.7% respectively. Acute toxicities were frequent but not severe with mostly grade 1 toxicities: 37% of genito-urinary, 40.7% of gastro-intestinal and 3.7% of cutaneous toxicities. Late toxicities were mainly G1 (43.1%) and G2 (22%). Two-year colostomy-free survival was 75.1%, one patient had a definitive sphincter amputation. High-dose rate brachytherapy for anal canal carcinoma as boost represents a feasible technique compared to low or pulsed-dose rate brachytherapy. This technique remains an excellent approach to precisely boost the tumor in reducing the overall treatment time

Carcinogenesis in mice after low doses and dose rates

International Nuclear Information System (INIS)

Ullrich, R.L.

1979-01-01

The results from the experimental systems reported here indicate that the dose-response curves for tumor induction in various tissues cannot be described by a single model. Furthermore, although the understanding of the mechanisms involved in different systems is incomplete, it is clear that very different mechanisms for induction are involved. For some tumors the mechanism of carcinogenesis may be mainly a result of direct effects on the target cell, perhaps involving one or more mutations. While induction may occur, in many instances, through such direct effects, the eventual expression of the tumor can be influenced by a variety of host factors including endocrine status, competence of the immune system, and kinetics of target and interacting cell populations. In other tumors, indirect effects may play a major role in the initiation or expression of tumors. Some of the hormone-modulated tumors would fall into this class. Despite the complexities of the experimental systems and the lack of understanding of the types of mechanisms involved, in nearly every example the tumorigenic effectiveness per rad of low-LET radiation tends to decrease with decreasing dose rate. For some tumor types the differences may be small or may appear only with very low dose rates, while for others the dose-rate effects may be large

Gynecological brachytherapy - from low-dose-rate to high-tech. Gynaekologische Brachytherapie - von Low-dose-rate zu High-tech

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Herrmann, T. (Abt. Strahlenthgerapie, Klinik und Poliklinik fuer Radiologie, Medizinische Akademie ' Carl Gustav Carus' , Dresden (Germany)); Christen, N. (Abt. Strahlenthgerapie, Klinik und Poliklinik fuer Radiologie, Medizinische Akademie ' Carl Gustav Carus' , Dresden (Germany)); Alheit, H.D. (Abt. Strahlenthgerapie, Klinik und Poliklinik fuer Radiologie, Medizinische Akademie ' Carl Gustav Carus' , Dresden (Germany))

1993-03-01

The transition from low-dose-rate (LDR) brachytherapy to high-dose-rate (HDR) afterloading treatment is in progress in most centres of radiation therapy. First reports of studies comparing HDR and LDR treatment in cervix cancer demonstrate nearly equal local control. In our own investigations on 319 patients with primary irradiated carcinoma of the cervix (125 HDR/194 LDR) we found the following control rates: Stage FIGO I 95.4%/82.9% (HDR versus LDR), stage FIGO II 71.4%/73.7%, stage FIGO III 57.9%/38.5%. The results are not significant. The side effects - scored after EORT/RTOG criteria - showed no significant differences between both therapies for serious radiogenic late effects on intestine, bladder and vagina. The study and findings from the literature confirm the advantage of the HDR-procedure for patient and radiooncologist and for radiation protection showing at least the same results as in the LDR-area. As for radiobiolgical point of view it is important to consider that the use of fractionation in the HDR-treatment is essential for the sparing of normal tissues and therefore a greater number of small fractionation doses in the brachytherapy should be desirable too. On the other hand the rules, which are true for fractionated percutaneous irradiation therapy (overall treatment time as short as possible to avoid reppopulation of tumor cells) should be taken into consideration in combined brachy-teletherapy regime in gynecologic tumors. The first step in this direction may be accelerated regime with a daily application of both treatment procedures. The central blocking of the brachytherapy region from the whole percutaneous treatment target volume should be critically reflected, especially in the case of advanced tumors. (orig.)

Toxicity bioassay in mice exposed to low dose-rate radiation

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Kim, Joog Sun; Gong, Eun Ji; Heo, Kyu; Yang, Kwang Mo [Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan (Korea, Republic of)

2013-04-15

The systemic effect of radiation increases in proportion to the dose amount and rate. The association between accumulated radiation dose and adverse effects, which is derived according to continuous low dose-rate radiation exposure, is not clearly elucidated. Our previous study showed that low dose-rate radiation exposure did not cause adverse effects in BALB/c mice at dose levels of ≤2 Gy, but the testis weight decreased at a dose of 2 Gy. In this study, we studied the effects of irradiation at the low dose rate (3.49 mGy/h) in the testes of C57BL/6 mice. Mice exposed to a total dose of 0.02, 0.2, and 2 Gy were found to be healthy and did not show any significant changes in body weight and peripheral blood components. However, mice irradiated with a dose of 2 Gy had significantly decreased testis weight. Further, histological studies and sperm evaluation also demonstrated changes consistent with the findings of decreased testis weight. In fertile patients found to have arrest of sperm maturation, the seminiferous tubules lack the DNMT1 and HDAC1 protein. The decrease of DNMT1 and HDAC1 in irradiated testis may be the part of the mechanism via which low dose-rate irradiation results in teticular injury. In conclusion, despite a low dose-rate radiation, our study found that when mice testis were irradiated with 2 Gy at 3.49 mGy/h dose rate, there was significant testicular and sperm damage with decreased DNMT1 and HDAC1 expression.

Low-dose irradiation for controlling prostate cancer

International Nuclear Information System (INIS)

Cuttler, J.M.

2003-01-01

Prostate cancer is the second most commonly diagnosed cancer among North American men and the second leading cause of death in those aged 65 and over. The American Cancer Society recommends testing those over age 50 who are expected to live at least 10 years, even though the ability of early detection to decrease prostate cancer mortality has not been demonstrated. So controversy exists about the appropriateness of screening because of the considerable economic and social burden of diagnosing and treating prostate cancer, coupled with the projected large increase in the number of new cases as the population ages. This very important public health issue could be addressed at low cost by total-body low-dose irradiation therapy to stimulate the patient's own defences to prevent and control most cancers, including prostate cancer, with no symptomatic side effects. (author)

LDR brachytherapy: can low dose rate hypersensitivity from the "inverse" dose rate effect cause excessive cell killing to peripherial connective tissues and organs?

Science.gov (United States)

Leonard, B E; Lucas, A C

2009-02-01

Examined here are the possible effects of the "inverse" dose rate effect (IDRE) on low dose rate (LDR) brachytherapy. The hyper-radiosensitivity and induced radioresistance (HRS/IRR) effect benefits cell killing in radiotherapy, and IDRE and HRS/IRR seem to be generated from the same radioprotective mechanisms. We have computed the IDRE excess cell killing experienced in LDR brachytherapy using permanent seed implants. We conclude, firstly, that IDRE is a dose rate-dependent manifestation of HRS/IRR. Secondly, the presence of HRS/IRR or IDRE in a cell species or tissue must be determined by direct dose-response measurements. Thirdly, a reasonable estimate is that 50-80% of human adjoining connective and organ tissues experience IDRE from permanent implanted LDR brachytherapy. If IDRE occurs for tissues at point A for cervical cancer, the excess cell killing will be about a factor of 3.5-4.0 if the initial dose rate is 50-70 cGy h(-1). It is greater for adjacent tissues at lower dose rates and higher for lower initial dose rates at point A. Finally, higher post-treatment complications are observed in LDR brachytherapy, often for unknown reasons. Some of these are probably a result of IDRE excess cell killing. Measurements of IDRE need be performed for connective and adjacent organ tissues, i.e. bladder, rectum, urinary tract and small bowels. The measured dose rate-dependent dose responses should extended to tissues and organs remain above IDRE thresholds).

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

International Nuclear Information System (INIS)

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 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 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. (author)

Dose-rate effects of low-dropout voltage regulator at various biases

International Nuclear Information System (INIS)

Wang Yiyuan; Zheng Yuzhan; Gao Bo; Chen Rui; Fei Wuxiong; Lu Wu; Ren Diyuan

2010-01-01

A low-dropout voltage regulator, LM2941, was irradiated by 60 Co γ-rays at various dose rates and biases for investigating the total dose and dose rate effects. The radiation responses show that the key electrical parameters, including its output and dropout voltage, and the maximum output current, are sensitive to total dose and dose rates, and are significantly degraded at low dose rate and zero bias. The integrated circuits damage change with the dose rates and biases, and the dose-rate effects are relative to its electric field. (authors)

Dose Response Model of Biological Reaction to Low Dose Rate Gamma Radiation

International Nuclear Information System (INIS)

Magae, J.; Furikawa, C.; Hoshi, Y.; Kawakami, Y.; Ogata, H.

2004-01-01

It is necessary to use reproducible and stable indicators to evaluate biological responses to long term irradiation at low dose-rate. They should be simple and quantitative enough to produce the results statistically accurate, because we have to analyze the subtle changes of biological responses around background level at low dose. For these purposes we chose micronucleus formation of U2OS, a human osteosarcoma cell line, as indicators of biological responses. Cells were exposed to gamma ray in irradiation rom bearing 50,000 Ci 60Co. After irradiation, they were cultured for 24 h in the presence of cytochalasin B to block cytokinesis, and cytoplasm and nucleus were stained with DAPI and prospidium iodide, respectively. the number of binuclear cells bearing micronuclei was counted under a fluorescence microscope. Dose rate in the irradiation room was measured with PLD. Dose response of PLD is linear between 1 mGy to 10 Gy, and standard deviation of triplicate count was several percent of mean value. We fitted statistically dose response curves to the data, and they were plotted on the coordinate of linearly scale response and dose. The results followed to the straight line passing through the origin of the coordinate axes between 0.1-5 Gy, and dose and does rate effectiveness factor (DDREF) was less than 2 when cells were irradiated for 1-10 min. Difference of the percent binuclear cells bearing micronucleus between irradiated cells and control cells was not statistically significant at the dose above 0.1 Gy when 5,000 binuclear cells were analyzed. In contrast, dose response curves never followed LNT, when cells were irradiated for 7 to 124 days. Difference of the percent binuclear cells bearing micronucleus between irradiated cells and control cells was not statistically significant at the dose below 6 Gy, when cells were continuously irradiated for 124 days. These results suggest that dose response curve of biological reaction is remarkably affected by exposure

Risks to health from radiation at low dose rates

International Nuclear Information System (INIS)

Gentner, N.E.; Osborne, R.V.

1997-01-01

Our focus is on whether, using a balance-of-evidence approach, it is possible to say that at a low enough dose, or at a sufficiently low dose rate, radiation risk reduces to zero in a population. We conclude that insufficient evidence exists at present to support such a conclusion. In part this reflects statistical limitations at low doses, and in part (although mechanisms unquestionably exist to protect us against much of the damage induced by ionizing radiation) the biological heterogeneity of human populations, which means these mechanisms do not act in all members of the population at all times. If it is going to be possible to demonstrate that low doses are less dangerous than we presently assume, the evidence, paradoxically, will likely come from studies of higher dose and dose rate scenarios than are encountered occupationally. (author)

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

International Nuclear Information System (INIS)

Yoshimura, Ryo-ichi; Shibuya, Hitoshi; Miura, Masahiko; Watanabe, Hiroshi; Ayukawa, Fumio; Hayashi, Keiji; Toda, Kazuma

2009-01-01

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

Recent international regulations: low dose-low rate radiation protection and the demise of reason.

Science.gov (United States)

Okkalides, Demetrios

2008-01-01

The radiation protection measures suggested by the International Committee for Radiation Protection (ICRP), national regulating bodies and experts, have been becoming ever more strict despite the decrease of any information supporting the existence of the Linear no Threshold model (LNT) and of any adverse effects of Low Dose Low Rate (LDLR) irradiation. This tendency arises from the disproportionate response of human society to hazards that are currently in fashion and is unreasonable. The 1 mSv/year dose limit for the public suggested by the ICRP corresponds to a 1/18,181 detriment-adjusted cancer risk and is much lower than other hazards that are faced by modern societies such as e.g. driving and smoking which carry corresponding rate risks of 1/2,100 and 1/2,000. Even worldwide deadly work accidents rate is higher at 1/ 8,065. Such excessive safety measures against minimal risks from man made radiation sources divert resources from very real and much greater hazards. In addition they undermine research and development of radiation technology and tend to subjugate science and the quest for understanding nature to phobic practices.

High-Dose-Rate Monotherapy: Safe and Effective Brachytherapy for Patients With Localized Prostate Cancer

International Nuclear Information System (INIS)

Demanes, D. Jeffrey; Martinez, Alvaro A.; Ghilezan, Michel; Hill, Dennis R.; Schour, Lionel; Brandt, David; Gustafson, Gary

2011-01-01

Purpose: High-dose-rate (HDR) brachytherapy used as the only treatment (monotherapy) for early prostate cancer is consistent with current concepts in prostate radiobiology, and the dose is reliably delivered in a prospectively defined anatomic distribution that meets all the requirements for safe and effective therapy. We report the disease control and toxicity of HDR monotherapy from California Endocurietherapy (CET) and William Beaumont Hospital (WBH) in low- and intermediate-risk prostate cancer patients. Methods and Materials: There were 298 patients with localized prostate cancer treated with HDR monotherapy between 1996 and 2005. Two biologically equivalent hypofractionation protocols were used. At CET the dose was 42 Gy in six fractions (two implantations 1 week apart) delivered to a computed tomography–defined planning treatment volume. At WBH the dose was 38 Gy in four fractions (one implantation) based on intraoperative transrectal ultrasound real-time treatment planning. The bladder, urethral, and rectal dose constraints were similar. Toxicity was scored with the National Cancer Institute Common Toxicity Criteria for Adverse Events version 3. Results: The median follow-up time was 5.2 years. The median age of the patients was 63 years, and the median value of the pretreatment prostate-specific antigen was 6.0 ng/mL. The 8-year results were 99% local control, 97% biochemical control (nadir +2), 99% distant metastasis–free survival, 99% cause-specific survival, and 95% overall survival. Toxicity was scored per event, meaning that an individual patient with more than one symptom was represented repeatedly in the morbidity data table. Genitourinary toxicity consisted of 10% transient Grade 2 urinary frequency or urgency and 3% Grade 3 episode of urinary retention. Gastrointestinal toxicity was <1%. Conclusions: High disease control rates and low morbidity demonstrate that HDR monotherapy is safe and effective for patients with localized prostate cancer.

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

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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

Cancer radiotherapy based on femtosecond IR laser-beam filamentation yielding ultra-high dose rates and zero entrance dose.

Science.gov (United States)

Meesat, Ridthee; Belmouaddine, Hakim; Allard, Jean-François; Tanguay-Renaud, Catherine; Lemay, Rosalie; Brastaviceanu, Tiberius; Tremblay, Luc; Paquette, Benoit; Wagner, J Richard; Jay-Gerin, Jean-Paul; Lepage, Martin; Huels, Michael A; Houde, Daniel

2012-09-18

Since the invention of cancer radiotherapy, its primary goal has been to maximize lethal radiation doses to the tumor volume while keeping the dose to surrounding healthy tissues at zero. Sadly, conventional radiation sources (γ or X rays, electrons) used for decades, including multiple or modulated beams, inevitably deposit the majority of their dose in front or behind the tumor, thus damaging healthy tissue and causing secondary cancers years after treatment. Even the most recent pioneering advances in costly proton or carbon ion therapies can not completely avoid dose buildup in front of the tumor volume. Here we show that this ultimate goal of radiotherapy is yet within our reach: Using intense ultra-short infrared laser pulses we can now deposit a very large energy dose at unprecedented microscopic dose rates (up to 10(11) Gy/s) deep inside an adjustable, well-controlled macroscopic volume, without any dose deposit in front or behind the target volume. Our infrared laser pulses produce high density avalanches of low energy electrons via laser filamentation, a phenomenon that results in a spatial energy density and temporal dose rate that both exceed by orders of magnitude any values previously reported even for the most intense clinical radiotherapy systems. Moreover, we show that (i) the type of final damage and its mechanisms in aqueous media, at the molecular and biomolecular level, is comparable to that of conventional ionizing radiation, and (ii) at the tumor tissue level in an animal cancer model, the laser irradiation method shows clear therapeutic benefits.

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)

Kaneyasu, Yuko; Kita, Midori; Okawa, Tomohiko; Maebayashi, Katsuya; Kohno, Mari; Sonoda, Tatsuo; Hirabayashi, Hisae; Nagata, Yasushi; Mitsuhashi, Norio

2012-01-01

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.

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

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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.

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

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

International Nuclear Information System (INIS)

Klug, H.

1986-01-01

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) [de

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

International Nuclear Information System (INIS)

Nag, Subir; Chao, Clifford; Erickson, Beth; Fowler, Jeffery; Gupta, Nilendu; Martinez, Alvaro; Thomadsen, Bruce

2002-01-01

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

Exposure to low doses of ionizing radiations

International Nuclear Information System (INIS)

Le Guen, B.

2008-01-01

The author discusses the knowledge about the effects of ionizing radiations on mankind. Some of them have been well documented (skin cancer and leukaemia for the pioneer scientists who worked on radiations, some other types of cancer for workers who handled luminescent paints, rock miners, nuclear explosion survivors, patients submitted to radiological treatments). He also evokes the issue of hereditary cancers, and discusses the issue of low dose irradiation where some surveys can now be performed on workers. He discusses the biological effects of these low doses. He outlines that many questions remain about these effects, notably the influence of dose level and of dose rate level on the biological reaction

Low-dose-rate total lymphoid irradiation: a new method of rapid immunosuppression

International Nuclear Information System (INIS)

Blum, J.E.; de Silva, S.M.; Rachman, D.B.; Order, S.E.

1988-01-01

Total Lymphoid Irradiation (TLI) has been successful in inducing immunosuppression in experimental and clinical applications. However, both the experimental and clinical utility of TLI are hampered by the prolonged treatment courses required (23 days in rats and 30-60 days in humans). Low-dose-rate TLI has the potential of reducing overall treatment time while achieving comparable immunosuppression. This study examines the immunosuppressive activity and treatment toxicity of conventional-dose-rate (23 days) vs low-dose-rate (2-7 days) TLI. Seven groups of Lewis rats were given TLI with 60Co. One group was treated at conventional-dose-rates (80-110 cGy/min) and received 3400 cGy in 17 fractions over 23 days. Six groups were treated at low-dose-rate (7 cGy/min) and received total doses of 800, 1200, 1800, 2400, 3000, and 3400 cGy over 2-7 days. Rats treated at conventional-dose-rates over 23 days and at low-dose-rate over 2-7 days tolerated radiation with minimal toxicity. The level of immunosuppression was tested using allogeneic (Brown-Norway) skin graft survival. Control animals retained allogeneic skin grafts for a mean of 14 days (range 8-21 days). Conventional-dose-rate treated animals (3400 cGy in 23 days) kept their grafts 60 days (range 50-66 days) (p less than .001). Low-dose-rate treated rats (800 to 3400 cGy total dose over 2-7 days) also had prolongation of allogeneic graft survival times following TLI with a dose-response curve established. The graft survival time for the 3400 cGy low-dose-rate group (66 days, range 52-78 days) was not significantly different from the 3400 cGy conventional-dose-rate group (p less than 0.10). When the total dose given was equivalent, low-dose-rate TLI demonstrated an advantage of reduced overall treatment time compared to conventional-dose-rate TLI (7 days vs. 23 days) with no increase in toxicity

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

International Nuclear Information System (INIS)

Prada, Pedro J.; Anchuelo, Javier; Blanco, Ana Garcia; Paya, Gema; Cardenal, Juan; Acuña, Enrique; Ferri, Maria; Vazquez, Andres; Pacheco, Maite; Sanchez, Jesica

2016-01-01

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)

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)

Modeling low-dose-rate effects in irradiated bipolar-base oxides

International Nuclear Information System (INIS)

Graves, R.J.; Cirba, C.R.; Schrimpf, R.D.; Milanowski, R.J.; Saigne, F.; Michez, A.; Fleetwood, D.M.; Witczak, S.C.

1997-02-01

A physical model is developed to quantify the contribution of oxide-trapped charge to enhanced low-dose-rate gain degradation in BJTs. Simulations show that space charge limited transport is partially responsible for the low-dose-rate enhancement

Lung cancer risk at low doses of alpha particles

International Nuclear Information System (INIS)

Hofmann, W.; Katz, R.; Zhang, C.X.

1986-01-01

A survey of inhabitant exposures arising from the inhalation of 222 Rn and 220 Rn progeny, and lung cancer mortality has been carried out in two adjacent areas in Guangdong Province, People's Republic of China, designated as the high background and the control area. Annual exposure rates are 0.38 working level months (WLM) per year in the high background, and 0.16 WLM/yr in the control area. In 14 yr of continuous study, from 1970 to 1983, age-adjusted mortality rates were found to be 2.7 per 10(5) living persons of all ages in the high background area, and 2.9 per 10(5) living persons in the control area. From this data, we conclude that we are unable to determine excess lung cancers over the normal fluctuations below a cumulative exposure of 15 WLM. This conclusion is supported by lung cancer mortality data from Austrian and Finnish high-background areas. A theoretical analysis of epidemiological data on human lung cancer incidence from inhaled 2 ]2'' 2 Rn and 220 Rn progeny, which takes into account cell killing as competitive with malignant transformation, leads to the evaluation of a risk factor which is either a linear-exponential or a quadratic-exponential function of the alpha-particle dose. Animal lung cancer data and theoretical considerations can be supplied to support either hypothesis. Thus we conclude that at our current stage of knowledge both the linear-exponential and the quadratic-exponential extrapolation to low doses seem to be equally acceptable for Rn-induced lung cancer risk, possibly suggesting a linear-quadratic transformation function with an exponential cell-killing term, or the influence of risk-modifying factors such as repair or proliferation stimuli

Response of human fibroblasts to low dose rate gamma irradiation

International Nuclear Information System (INIS)

Dritschilo, A.; Brennan, T.; Weichselbaum, R.R.; Mossman, K.L.

1984-01-01

Cells from 11 human strains, including fibroblasts from patients with the genetic diseases of ataxia telangiectasia (AT), xeroderma pigmentosum (XP), and Fanconi's anemia (FA), were exposed to γ radiation at high (1.6-2.2 Gy/min) and at low (0.03-0.07 Gy/min) dose rates. Survival curves reveal an increase inthe terminal slope (D 0 ) when cells are irradiated at low dose rates compared to high dose rates. This was true for all cell lines tested, although the AT, FA, and XP cells are reported or postulated to have radiation repair deficiencies. From the response of these cells, it is apparent that radiation sensitivities differ; however, at low dose rate, all tested human cells are able to repair injury

Lung cancer screening with low-dose helical CT in Korea: experiences at the Samsung Medical Center.

Science.gov (United States)

Chong, Semin; Lee, Kyung Soo; Chung, Myung Jin; Kim, Tae Sung; Kim, Hojoong; Kwon, O Jung; Choi, Yoon-Ho; Rhee, Chong H

2005-06-01

To determine overall detection rates of lung cancer by low-dose CT (LDCT) screening and to compare histopathologic and imaging differences of detected cancers between high- and low-risk groups, this study included 6,406 asymptomatic Korean adults with >or=45 yr of age who underwent LDCT for lung cancer screening. All were classified into high- (>or=20 pack-year smoking; 3,353) and low-risk (3,053; <20 pack-yr smoking and non-smokers) groups. We compared CT findings of detected cancers and detection rates between high- and low-risk. At initial CT, 35% (2,255 of 6,406) had at least one or more non-calcified nodule. Lung cancer detection rates were 0.36% (23 of 6,406). Twenty-one non-small cell lung cancers appeared as solid (n=14) or ground-glass opacity (GGO) (n=7) nodules. Cancer likelihood was higher in GGO nodules than in solid nodules (p<0.01). Fifteen of 23 cancers occurred in high-risk group and 8 in low-risk group (p=0.215). Therefore, LDCT screening help detect early stage of lung cancer in asymptomatic Korean population with detection rate of 0.36% on a population basis and may be useful for discovering early lung cancer in low-risk group as well as in high-risk group.

Low-dose CT: new tool for screening lung cancer?

International Nuclear Information System (INIS)

Diederich, S.; Wormanns, D.; Heindel, W.

2001-01-01

Lung cancer is the leading cause of death from malignant tumours as it is very common and has a poor prognosis at advanced tumour stages. Prognosis could be improved by treatment at early stages. As these stages are usually asymptomatic, a diagnostic test that would allow detection of early tumour stages in a population at risk could potentially reduce mortality from lung cancer. Previous approaches using chest radiography and sputum cytology in smokers have been disappointing. Fluorescent bronchoscopy and molecular markers are not yet applicable in clinical routine. Because of its high sensitivity for small pulmonary nodules, which are the most common manifestation of early lung cancer, CT appears suitable as a screening test. Low-dose examination parameters can and should be used for this purpose. From clinical practice it is well known that chest CT often demonstrates small pulmonary nodules, which do not represent lung cancer. Therefore, non-invasive diagnostic algorithms are required to avoid unnecessary biopsies in benign lesions. In preliminary studies of low-dose CT using algorithms based on size and density of detected nodules a large proportion of asymptomatic lung cancers and a large proportion of early, resectable tumour stages were found with a small proportion of invasive procedures for benign nodules. Before this technology can be recommended for broad application, however, further information is required regarding appropriate inclusion criteria (smoking habits, age groups) and screening intervals. Most importantly, further data are required to clarify whether lung cancer screening using low-dose CT can actually reduce mortality from lung cancer. (orig.)

Up-regulation of calreticulin in mouse liver tissues after long-term irradiation with low-dose-rate gamma rays.

Science.gov (United States)

Yi, Lan; Hu, Nan; Yin, Jie; Sun, Jing; Mu, Hongxiang; Dai, Keren; Ding, Dexin

2017-01-01

The biological effects of low-dose or low-dose-rate ionizing radiation on normal tissues has attracted attention. Based on previous research, we observed the morphology of liver tissues of C57BL/6J mice that received irradiation dose rates increased. Additionally, differential protein expression in liver tissues was analyzed using a proteomics approach. Compared with the matched group in the 2D gel analysis of the irradiated groups, 69 proteins had ≥ 1.5-fold changes in expression. Twenty-three proteins were selected based on ≥2.5-fold change in expression, and 22 of them were meaningful for bioinformatics and protein fingerprinting analysis. These molecules were relevant to cytoskeleton processes, cell metabolism, biological defense, mitochondrial damage, detoxification and tumorigenesis. The results from real-time PCR and western blot (WB) analyses showed that calreticulin (CRT) was up-regulated in the irradiated groups, which indicates that CRT may be relevant to stress reactions when mouse livers are exposed to low-dose irradiation and that low-dose-rate ionizing radiation may pose a cancer risk. The CRT protein can be a potential candidate for low-dose or low-dose-rate ionizing radiation early-warning biomarkers. However, the underlying mechanism requires further investigation.

Low Dose Suppression of Neoplastic Transformation in Vitro

Energy Technology Data Exchange (ETDEWEB)

John Leslie Redpath

2012-05-01

This grant was to study the low dose suppression of neoplastic transformation in vitro and the shape of the dose-response curve at low doses and dose-rates of ionizing radiation. Previous findings had indicated a suppression of transformation at dose <10cGy of low-LET radiation when delivered at high dose-rate. The present study indicates that such suppression extends out to doses in excess of 100cGy when the dose (from I-125 photons) is delivered at dose-rates as low as 0.2 mGy/min and out to in excess of {approx}25cGy the highest dose studied at the very low dose-rate of 0.5 mGy/day. We also examined dose-rate effects for high energy protons (which are a low-LET radiation) and suppression was evident below {approx}10cGy for high dose-rate delivery and at least out to 50cGy for low dose-rate (20cGy/h) delivery. Finally, we also examined the effect of low doses of 1 GeV/n iron ions (a high-LET radiation) delivered at high dose-rate on transformation at low doses and found a suppression below {approx}10cGy that could be attributable to an adaptive response in bystander cells induced by the associated low-LET delta rays. These results have implications for cancer risk assessment at low doses.

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.)

After low and high dose-rate interstitial brachytherapy followed by IMRT radiotherapy for intermediate and high risk prostate cancer

International Nuclear Information System (INIS)

Nakamura, Satoshi; Murakami, Naoya; Inaba, Koji; Wakita, Akihisa; Kobayashi, Kazuma; Takahashi, Kana; Okamoto, Hiroyuki; Umezawa, Rei; Morota, Madoka; Sumi, Minako; Igaki, Hiroshi; Ito, Yoshinori; Itami, Jun

2016-01-01

The study aimed to compare urinary symptoms in patients with clinically localized prostate cancer after a combination of either low-dose-rate or high-dose-rate interstitial brachytherapy along with intensity-modulated radiation therapy (LDR-ISBT + IMRT or HDR-ISBT + IMRT). From June 2009 to April 2014, 16 and 22 patients were treated with LDR-ISBT + IMRT and HDR-ISBT + IMRT, respectively. No patient from these groups was excluded from this study. The prescribed dose of LDR-ISBT, HDR-ISBT, and IMRT was 115 Gy, 20 Gy in 2 fractions, and 46 Gy in 23 fractions, respectively. Obstructive and irritative urinary symptoms were assessed by the International Prostate Symptom Score (IPSS) examined before and after treatments. After ISBT, IPSS was evaluated in the 1st and 4th weeks, then every 2–3 months for the 1st year, and every 6 months thereafter. The median follow-up of the patients treated with LDR-ISBT + IMRT and HDR-ISBT + IMRT was 1070.5 days and 1048.5 days, respectively (p = 0.321). The IPSS-increment in the LDR-ISBT + IMRT group was greater than that in the HDR-ISBT + IMRT between 91 and 180 days after ISBT (p = 0.015). In the LDR-ISBT + IMRT group, the IPSS took longer time to return to the initial level than in the HDR-ISBT + IMRT group (in LDR-ISBT + IMRT group, the recovery time was 90 days later). The dose to urethra showed a statistically significant association with the IPSS-increment in the irritative urinary symptoms (p = 0.011). Clinical outcomes were comparable between both the groups. Both therapeutic modalities are safe and well suited for patients with clinically localized prostate cancer; however, it took patients longer to recover from LDR-ISBT + IMRT than from HDR-ISBT + IMRT. It is possible that fast dose delivery induced early symptoms and early recovery, while gradual dose delivery induced late symptoms and late recovery. Urethral dose reductions were associated with small increments in IPSS

Mathematical model for evaluation of dose-rate effect on biological responses to low dose γ-radiation

International Nuclear Information System (INIS)

Ogata, H.; Kawakami, Y.; Magae, J.

2003-01-01

Full text: To evaluate quantitative dose-response relationship on the biological response to radiation, it is necessary to consider a model including cumulative dose, dose-rate and irradiation time. In this study, we measured micronucleus formation and [ 3 H] thymidine uptake in human cells as indices of biological response to gamma radiation, and analyzed mathematically and statistically the data for quantitative evaluation of radiation risk at low dose/low dose-rate. Effective dose (ED x ) was mathematically estimated by fitting a general function of logistic model to the dose-response relationship. Assuming that biological response depends on not only cumulative dose but also dose-rate and irradiation time, a multiple logistic function was applied to express the relationship of the three variables. Moreover, to estimate the effect of radiation at very low dose, we proposed a modified exponential model. From the results of fitting curves to the inhibition of [ 3 H] thymidine uptake and micronucleus formation, it was obvious that ED 50 in proportion of inhibition of [ 3 H] thymidine uptake increased with longer irradiation time. As for the micronuclei, ED 30 also increased with longer irradiation times. These results suggest that the biological response depends on not only total dose but also irradiation time. The estimated response surface using the three variables showed that the biological response declined sharply when the dose-rate was less than 0.01 Gy/h. These results suggest that the response does not depend on total cumulative dose at very low dose-rates. Further, to investigate the effect of dose-rate within a wider range, we analyzed the relationship between ED x and dose-rate. Fitted curves indicated that ED x increased sharply when dose-rate was less than 10 -2 Gy/h. The increase of ED x signifies the decline of the response or the risk and suggests that the risk approaches to 0 at infinitely low dose-rate

Pulsed dose rate and fractionated high dose rate brachytherapy: choice of brachytherapy schedules to replace low dose rate treatments

International Nuclear Information System (INIS)

Visser, Andries G.; Aardweg, Gerard J.M.J. van den; Levendag, Peter C.

1996-01-01

Purpose: Pulsed dose rate (PDR) brachytherapy is a new type of afterloading brachytherapy (BT) in which a continuous low dose rate (LDR) treatment is simulated by a series of 'pulses,' i.e., fractions of short duration (less than 0.5 h) with intervals between fractions of 1 to a few hours. At the Dr. Daniel den Hoed Cancer Center, the term 'PDR brachytherapy' is used for treatment schedules with a large number of fractions (at least four per day), while the term 'fractionated high dose rate (HDR) brachytherapy' is used for treatment schedules with just one or two brachytherapy fractions per day. Both treatments can be applied as alternatives for LDR BT. This article deals with the choice between PDR and fractionated HDR schedules and proposes possible fractionation schedules. Methods and Materials: To calculate HDR and PDR fractionation schedules with the intention of being equivalent to LDR BT, the linear-quadratic (LQ) model has been used in an incomplete repair formulation as given by Brenner and Hall, and by Thames. In contrast to earlier applications of this model, both the total physical dose and the overall time were not kept identical for LDR and HDR/PDR schedules. A range of possible PDR treatment schedules is presented, both for booster applications (in combination with external radiotherapy (ERT) and for BT applications as a single treatment. Because the knowledge of both α/β values and the half time for repair of sublethal damage (T (1(2)) ), which are required for these calculations, is quite limited, calculations regarding the equivalence of LDR and PDR treatments have been performed for a wide range of values of α/β and T (1(2)) . The results are presented graphically as PDR/LDR dose ratios and as ratios of the PDR/LDR tumor control probabilities. Results: If the condition that total physical dose and overall time of a PDR treatment must be exactly identical to the values for the corresponding LDR treatment regimen is not applied, there appears

Synergistic cancer growth-inhibitory effect of emodin and low-dose ...

African Journals Online (AJOL)

Purpose: To investigate the anti-cancer activity of emodin and its combination with low-dose cisplatin against human gastric cancer (SNU-5), including their effects on cell cycle phase distribution, apoptosis and cancer cell morphology. Methods: The anti-cancer activity of emodin, cisplatin and their combination against ...

Enhanced low dose rate radiation effect test on typical bipolar devices

International Nuclear Information System (INIS)

Liu Minbo; Chen Wei; Yao Zhibin; He Baoping; Huang Shaoyan; Sheng Jiangkun; Xiao Zhigang; Wang Zujun

2014-01-01

Two types of bipolar transistors and nine types bipolar integrated circuit were selected in the irradiation experiment at different "6"0Co γ dose rate. The base current of bipolar transistor and input bias current of amplifier and comparator was measured, low dose enhance factor of test device was obtained. The results show that bipolar device have enhanced low dose rate sensitivity, enhancement factor of bipolar integrated circuit was bigger than that of transistor, and enhanced low dose rate sensitivity greatly varied with different structure and process of bipolar device. (authors)

CANCER RISKS ATTRIBUTABLE TO LOW DOSES OF IONIZING RADIATION - ASSESSING WHAT WE REALLY KNOW?

Science.gov (United States)

Cancer Risks Attributable to Low Doses of Ionizing Radiation - What Do We Really Know?AbstractHigh doses of ionizing radiation clearly produce deleterious consequences in humans including, but not exclusively, cancer induction. At very low radiation doses the situatio...

SU-E-T-620: Planning and Dosimetry for Pulsed Low Dose Rate RT for Recurrent Lung, Spine, GYN and Head and Neck Cancers

Energy Technology Data Exchange (ETDEWEB)

Tong, X; Luo, F; Liu, Y; Zhang, W; Xu, Q; Zhang, T; Li, J [3rd Affiliated Hospital of Qiqihar Medical University, Qiqihar (China); Chen, L; Ma, C [Fox Chase Cancer Center, Philadelphia, PA (United States)

2015-06-15

Purpose: Extensive in vitro and in vivo studies have shown that pulsed low dose rate (PLDR) radiotherapy has potential to provide significant local tumor control and to reduce normal tissue toxicities. This work investigated the planning and dosimetry of PLDR re-irradiation for recurrent cancers. Methods: We analyzed the treatment plans and dosimetry for 13 recurrent patients who were treated with the PLDR technique in this study. All cases were planned with the 3DCRT technique with optimal beam angle selection. The treatment was performed on a Siemens accelerator using 6MV beams. The target volume ranged between 161 and 703cc. The previous RT dose was 40–60Gy while the re-irradiation dose was 16–60Gy. The interval between previous RT and re-irradiation was 13–336 months, and the follow-up time was up to 27months. The total prescription dose was administered in 2Gy/day fractions with the daily dose delivered in 10 sub-fractions (pulses) of 20cGy with a 3min interval between the pulses to achieve an effective dose rate of 6.7cGy/min. Results: The clinical outcome was analyzed based on the treatment plans. All pulses were kept with Dmax<40cGy. The PLDR treatments were effective (CR: 3 patients, PR: 10 patients). The acute and late toxicities were all acceptable (generally grade II or under). Two patients died three months after the PLDR re-irradiation, one due to massive cerebral infarction and the other due to acute cardiac failure. All others survived more than 8 months. Five patients showed good conditions at the last follow-up. Among them two recurrent lung cancer patients had survived 23 months and one nasopharyngeal cancer patient had survived 27 months. Conclusion: The PLDR technique was effective for the palliative treatment of head and neck, lung, spine and GYN cancers. Further phase II and III studies are warranted to quantify the efficacy of PLDR for recurrent cancers.

Injury of the blood-testies barrier after low-dose-rate chronic radiation exposure

Energy Technology Data Exchange (ETDEWEB)

Sohn, Young Hoon; Bae Min Ji; Lee, Chang Geun; Yang, Kwang Mo; Jur, Kyu; Kim, Jong Sun [Dongnam Institute of Radiological and Medical Science, Busan (Korea, Republic of)

2014-04-15

The systemic effect of radiation increases in proportionally with the dose and dose rate. Little is known concerning the relationships between harmful effects and accumulated dose, which is derived from continuous low-dose rate radiation exposure. Recent our studies show that low-dose-rate chronic radiation exposure (3.49 mGy/h) causes adverse effects in the testis at a dose of 2 Gy (6 mGy/h). However, the mechanism of the low-dose-rate 2 Gy irradiation induced testicular injury remains unclear. The present results indicate that low-dose rate chronic radiation might affect the BTB permeability, possibly by decreasing levels of ZO-1, Occludin-1, and NPC-2. Furthermore, our results suggest that there is a risk of male infertility through BTB impairment even with low-dose-rate radiation if exposure is continuous.

Comparison of radiosensitization by 41 deg. C hyperthermia during low dose rate irradiation and during pulsed simulated low dose rate irradiation in human glioma cells

International Nuclear Information System (INIS)

Raaphorst, G. Peter; Ng, Cheng E.; Shahine, Bilal

1999-01-01

Purpose: Long duration mild hyperthermia has been shown to be an effective radiosensitizer when given concurrently with low dose rate irradiation. Pulsed simulated low dose rate (PSLDR) is now being used clinically, and we have set out to determine whether concurrent mild hyperthermia can be an effective radiosensitizer for the PSLDR protocol. Materials and Methods: Human glioma cells (U-87MG) were grown to plateau phase and treated in plateau phase in order to minimize cell cycle redistribution during protracted treatments. Low dose rate (LDR) irradiation and 41 deg. C hyperthermia were delivered by having a radium irradiator inside a temperature-controlled incubator. PSLDR was given using a 150 kVp X-ray unit and maintaining the cells at 41 deg. C between irradiations. The duration of irradiation and concurrent heating depended on total dose and extended up to 48 h. Results: When 41 deg. C hyperthermia was given currently with LDR or PSLDR, the thermal enhancement ratios (TER) were about the same if the average dose rate for PSLDR was the same as for LDR. At higher average dose rates for PSLDR the TERs became less. Conclusions: Our data show that concurrent mild hyperthermia can be an effective sensitizer for PSLDR. This sensitization can be as effective as for LDR if the same average dose rate is used and the TER increases with decreasing dose rate. Thus mild hyperthermia combined with PSLDR may be an effective clinical protocol

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......-dose aspirin and the risk of ovarian cancer. PATIENTS AND METHODS: We identified all patients in the Danish Cancer Registry aged 30-84 years old with a histologically verified first diagnosis of epithelial ovarian cancer during 2000-2011. Each patient was sex- and age-matched to 15 population controls using...... risk-set sampling. Prescription use, comorbidity, reproductive history, and demographic characteristics data were obtained from nationwide registries. The use of low-dose (75-150 mg) aspirin was defined according to the dose as well as the duration and consistency of use. Conditional logistic...

Impact of point A asymmetry on local control and survival for low dose-rate (LDR) brachytherapy in cervical cancer.

Science.gov (United States)

Opfermann, Krisha J; Wahlquist, Amy; Watkins, John; Kohler, Matthew; Jenrette, Joseph

2012-03-01

To evaluate whether Point A asymmetry in low dose-rate (LDR) brachytherapy is associated with local control (LC), disease-free survival (DFS) and/or overall survival (OS). A retrospective analysis of disease control and survival outcomes was conducted for patients who underwent LDR brachytherapy for advanced cervical cancer. Institutional protocol entailed concurrent chemotherapy and whole pelvis radiotherapy (WPRT) over 5 weeks, followed by placement of Fletcher-Suit tandem and colpostat applicators at weeks 6 and 8. Objective Point A doses, 80-85 Gy, were accomplished by placement of Cesium-137 (Cs-137) sources. Cox proportional hazards regression models were used to assess associations between disease control and survival endpoints with variables of interest. The records of 50 patients with FIGO stage IB1-IVA cervical cancer undergoing LDR brachytherapy at our institution were identified. Thirty of these patients had asymmetry > 2.5%, and 11 patients had asymmetry > 5%. At a median survivor follow-up of 20.25 months, 15 patients had experienced disease failure (including 5 cervical/vaginal apex only failures and 2 failures encompassing the local site). Right/left dose asymmetry at Point A was associated with statistically significantly inferior LC (p = 0.035) and inferior DFS (p = 0.011) for patients with mean Point A dose of > 80 Gy. Insufficient evidence existed to conclude an association with OS. LDR brachytherapy may be associated with clinically significant dose asymmetry. The present study demonstrates that patients with Point A asymmetry have a higher risk of failure for DFS and LC.

Positional variation of applicators during low dose rate intracavitary brachytherapy for cervical cancer: a prospective study

Directory of Open Access Journals (Sweden)

Arul Ponni

2010-10-01

Full Text Available Purpose: In order to know the effect of variation in position of applicators to the dose received by the tumor volume, critical organs such as rectum and bladder and the correlation of variation on the clinical outcome.Material and methods: 36 patients with histologically proven cervical cancer, undergoing intracavitary brachythe - rapy (ICBT from October 2005 to December 2006 were the subjects of the study. Two pairs of orthogonal X-ray films were taken: one prior to loading of sources and the other after removal of sources. These patients were followed up as per the RTOG criteria.Results: The median duration of insertion was 25 hours with a median follow up period of 6.7 months. The translational variation of the applicator position for all patients was 3 mm and 1 mm (2 SD, respectively, in the patient’s lateral and antero-posterior direction. The rotational variation was 3 and 4 degrees (2 SD in the patient’s transverse and sagittal planes. Detailed analysis of source movement showed following changes in median dose: point A: 14%, point B: 2%, point P: 1%, Rectum 1: 3.5%, Rectum 2: 4% and Bladder: 9.1%. The incidence of rectal toxicity was 6/36(16.7% and that of bladder was 1/36 (2.8%. When the variables were grouped to evaluate the relationship, our study showed statistically significant relationship between: R2 and rectal toxicity (p value: 0.002, point A and rectal toxicity (Pearson: 0.792, lateral displacement/anteroposterior displacement and rectal toxicity (p value: 0.012/0.003, beta angle and R2 (p value: 0.002.Conclusions: The geometric relationships between the ICBT applicators and the critical structures vary during the course of low dose rate brachytherapy. Source movement does result in significant dose alterations in terms of increased rate of complications, but its impact on cure rates needs to be studied in the future.

Biological effective doses in the intracavitary high dose rate brachytherapy of cervical cancer

Directory of Open Access Journals (Sweden)

Y. Sobita Devi

2011-12-01

Full Text Available Purpose: The aim of this study is to evaluate the decrease of biological equivalent dose and its correlation withlocal/loco-regional control of tumour in the treatment of cervical cancer when the strength of the Ir-192 high dose rate(HDR brachytherapy (BT source is reduced to single, double and triple half life in relation to original strength of10 Ci (~ 4.081 cGy x m2 x h–1. Material and methods: A retrospective study was carried out on 52 cervical cancer patients with stage II and IIItreated with fractionated HDR-BT following external beam radiation therapy (EBRT. International Commission onRadiation Units and Measurement (ICRU points were defined according to ICRU Report 38, using two orthogonal radiographimages taken by Simulator (Simulix HQ. Biologically effective dose (BED was calculated at point A for diffe -rent Ir-192 source strength and its possible correlation with local/loco-regional tumour control was discussed. Result: The increase of treatment time per fraction of dose due to the fall of dose rate especially in HDR-BT of cervicalcancer results in reduction in BED of 2.59%, 7.02% and 13.68% with single, double and triple half life reduction ofsource strength, respectively. The probabilities of disease recurrence (local/loco-regional within 26 months are expectedas 0.12, 0.12, 0.16, 0.39 and 0.80 for source strength of 4.081, 2.041, 1.020, 0.510 and 0.347 cGy x m2 x h–1, respectively.The percentages of dose increase required to maintain the same BED with respect to initial BED were estimated as1.71, 5.00, 11.00 and 15.86 for the dose rate of 24.7, 12.4, 6.2 and 4.2 Gy/hr at point A, respectively. Conclusions: This retrospective study of cervical cancer patients treated with HDR-BT at different Ir-192 sourcestrength shows reduction in disease free survival according to the increase in treatment time duration per fraction.The probable result could be associated with the decrease of biological equivalent dose to point A. Clinical

Brachytherapy for Buccal Cancer: From Conventional Low Dose Rate (LDR) or Mold Technique to High Dose Rate Interstitial Brachytherapy (HDR-ISBT).

Science.gov (United States)

Kotsuma, Tadayuki; Yamazaki, Hideya; Masui, Koji; Yoshida, Ken; Shimizutani, Kimishige; Akiyama, Hironori; Murakami, Shumei; Isohashi, Fumiaki; Yoshioka, Yasuo; Ogawa, Kazuhiko; Tanaka, Eiichi

2017-12-01

To examine the effectiveness of newly-installed high-dose-rate interstitial brachytherapy (HDR-ISBT) for buccal cancer. We retrospectively reviewed 36 patients (25 men and 11 women) with buccal cancer treated with curative brachytherapy with or without external radiotherapy with a median follow-up of 99 months. A total of 15 HDR-ISBT (median 48 Gy/ 8 fractions, range=24-60 Gy) patients were compared to conventional 15 cases LDR-ISBT (70 Gy, range=42.8-110 Gy) and 7 molds techniques (15 Gy, range=9-74 Gy). A total of 31 patients also underwent external radiotherapy (30 Gy, range=24-48 Gy). They comprised of 3T1, 23 T2, 8 T3, 3 T4 including 11 node positive cases. HDR-ISBT provided 82% of local control rate at 5 years, whereas conventional brachytherapy showed 72% [p=0.44; LDR-ISBT (65%), mold therapy (85.7%)]. Patients with early lesions (T1-2 or stage I-II) showed better local control rates than those with advanced lesions (T3-4 or stage III-IV). Severe late grade 3 complications developed in two patients treated with LDR-ISBT and EBRT. There is no significant difference in toxicity grade ≤2 between conventional brachytherapy (5/15=33%) and HDR-ISBT (7/32=32%, p=0.92). HDR-ISBT achieved good and comparable local control rates to conventional brachytherapy without elevating the toxicity. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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.

Multidisciplinary European Low Dose Initiative (MELODI). Strategic research agenda for low dose radiation risk research

Energy Technology Data Exchange (ETDEWEB)

Kreuzer, M. [Federal Office for Radiation Protection, BfS, Department of Radiation Protection and Health, Neuherberg (Germany); Auvinen, A. [University of Tampere, Tampere (Finland); STUK, Helsinki (Finland); Cardis, E. [ISGlobal, Barcelona Institute for Global Health, Barcelona (Spain); Durante, M. [Institute for Fundamental Physics and Applications, TIFPA, Trento (Italy); Harms-Ringdahl, M. [Stockholm University, Centre for Radiation Protection Research, Stockholm (Sweden); Jourdain, J.R. [Institute for Radiological Protection and Nuclear Safety, IRSN, Fontenay-aux-roses (France); Madas, B.G. [MTA Centre for Energy Research, Environmental Physics Department, Budapest (Hungary); Ottolenghi, A. [University of Pavia, Physics Department, Pavia (Italy); Pazzaglia, S. [Italian National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), Rome (Italy); Prise, K.M. [Queens University Belfast, Belfast (United Kingdom); Quintens, R. [Belgian Nuclear Research Centre, SCK-CEN, Mol (Belgium); Sabatier, L. [French Atomic Energy Commission, CEA, Paris (France); Bouffler, S. [Public Health England, PHE, Chilton (United Kingdom)

2018-03-15

MELODI (Multidisciplinary European Low Dose Initiative) is a European radiation protection research platform with focus on research on health risks after exposure to low-dose ionising radiation. It was founded in 2010 and currently includes 44 members from 18 countries. A major activity of MELODI is the continuous development of a long-term European Strategic Research Agenda (SRA) on low-dose risk for radiation protection. The SRA is intended to identify priorities for national and European radiation protection research programs as a basis for the preparation of competitive calls at the European level. Among those key priorities is the improvement of health risk estimates for exposures close to the dose limits for workers and to reference levels for the population in emergency situations. Another activity of MELODI is to ensure the availability of European key infrastructures for research activities, and the long-term maintenance of competences in radiation research via an integrated European approach for training and education. The MELODI SRA identifies three key research topics in low dose or low dose-rate radiation risk research: (1) dose and dose rate dependence of cancer risk, (2) radiation-induced non-cancer effects and (3) individual radiation sensitivity. The research required to improve the evidence base for each of the three key topics relates to three research lines: (1) research to improve understanding of the mechanisms contributing to radiogenic diseases, (2) epidemiological research to improve health risk evaluation of radiation exposure and (3) research to address the effects and risks associated with internal exposures, differing radiation qualities and inhomogeneous exposures. The full SRA and associated documents can be downloaded from the MELODI website (http://www.melodi-online.eu/sra.html). (orig.)

Mammography-oncogenecity at low doses

International Nuclear Information System (INIS)

Heyes, G J; Mill, A J; Charles, M W

2009-01-01

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

High-Dose-Rate Monotherapy for Localized Prostate Cancer: 10-Year Results

Energy Technology Data Exchange (ETDEWEB)

Hauswald, Henrik; Kamrava, Mitchell R.; Fallon, Julia M.; Wang, Pin-Chieh; Park, Sang-June; Van, Thanh; Borja, Lalaine; Steinberg, Michael L.; Demanes, D. Jeffrey, E-mail: JDemanes@mednet.ucla.edu

2016-03-15

Purpose: High-dose-rate (HDR) brachytherapy was originally used with external beam radiation therapy (EBRT) to increase the dose to the prostate without injuring the bladder or rectum. Numerous studies have reported HDR brachytherapy is safe and effective. We adapted it for use without EBRT for cases not requiring lymph node treatment. Patients and Methods: We entered the patient demographics, disease characteristics, and treatment parameters into a prospective registry and serially added follow-up data for 448 men with low-risk (n=288) and intermediate-risk (n=160) prostate cancer treated from 1996 to 2009. Their median age was 64 years (range 42-90). The median prostate-specific antigen (PSA) level was 6.0 ng/mL (range 0.2-18.2). The Gleason score was ≤6 in 76% and 7 in 24%. The median dose was 43.5 Gy in 6 fractions. The clinical and biochemical disease control and survival rates were calculated. Adverse events were graded according to the Common Toxicity Criteria of Adverse Events. Results: The median follow-up period was 6.5 years (range 0.3-15.3). The actuarial 6- and 10-year PSA progression-free survival was 98.6% (95% confidence interval [CI] 96.9%-99.4%) and 97.8% (95% CI 95.5%-98.9%). Overall survival at 10 years was 76.7% (95% CI 69.9%-82.2%). The local control, distant metastasis-free survival, and cause-specific survival were 99.7% (95% CI 97.9%-99.9%), 98.9% (95% CI 96.3%-99.7%), and 99.1% (95% CI 95.8%-99.8%). T stage, initial PSA level, Gleason score, National Comprehensive Cancer Network risk group, patient age, and androgen deprivation therapy did not significantly correlate with disease control or survival. No late grade 3 to 4 rectal toxicities developed. Late grade 3 to 4 genitourinary toxicity occurred in 4.9% (grade 3 in 4.7%). Conclusions: HDR monotherapy is a safe and highly effective treatment of low- and intermediate-risk prostate cancer.

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)

Tanaka, Kimio; Kohda, Atsushi; Ichinohe, Kazuaki; Matsumoto, Tsuneya; Oghiso, Yoichi

2006-01-01

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)

High-dose preoperative radiation for cancer of the rectum: Impact of radiation dose on patterns of failure and survival

International Nuclear Information System (INIS)

Ahmad, N.R.; Mohiuddin, M.; Marks, G.

1993-01-01

A variety of dose-time schedules are currently used for preoperative radiation therapy of rectal cancer. An analysis of patients treated with high-dose preoperative radiation therapy was undertaken to determine the influence of radiation dose on the patterns of failure, survival, and complications. Two hundred seventy-five patients with localized rectal cancer were treated with high-dose preoperative radiation therapy. One hundred fifty-six patients received 45 Gy (low-dose group). Since 1985, 119 patients with clinically unfavorable cancers were given a higher dose, 55 Gy using a shrinking field technique (high-dose group). All patients underwent curative resection. Median follow-up was 66 months in the low-dose group and 28 months in the high-dose group. Patterns of failure, survival, and complications were analyzed as a function of radiation dose. Fourteen percent of the total group developed a local recurrence; 20% in the low-dose group as compared with 6% in the high-dose group. The actuarial local recurrence rate at 5 years was 20% for the low-dose group and 8% for the high-dose group, and approached statistical significance with p = .057. For tethered/fixed tumors the actuarial local recurrence rates at 5 years were 28% and 9%, respectively, with p = .05. Similarly, for low-lying tumors (less than 6 cm from the anorectal junction) the rates were 24% and 9%, respectively, with p = .04. The actuarial rate of distant metastasis was 28% in the low-dose group and 20% in the high-dose group and was not significantly different. Overall actuarial 5-year survival for the total group of patients was 66%. No significant difference in survival was observed between the two groups, despite the higher proportion of unfavorable cancers in the high-dose group. The incidence of complications was 2%, equally distributed between the two groups. High-dose preoperative radiation therapy for rectal cancer results in excellent local control rates. 27 refs., 2 figs., 8 tabs

Tumour alpha/beta ratios and dose-rate selection in brachytherapy

International Nuclear Information System (INIS)

Duchesne, G.M.

2003-01-01

Traditionally brachytherapy employed low dose rate (LDR) techniques. Recent adoption of high dose rate (HDR) applications, addressing radiation protection concerns, has sparked debate over possible reductions in therapeutic ratio. The radiobiological characteristics of two contrasting examples, prostate cancer and cervical cancer, are examined. Both in-vitro and clinical observations of prostate cancer suggest a low α/β ratio. Labelling indices are below 2.5%, translating into long potential doubling times (Tpot ) of 16 to 61 days or more. Clinical PSA doubling times are in the order of years. Analysis of clinical endpoints in prostate cancer treated with either LDR or HDR techniques indicates that its α/β ratio may lie between 1 - 4 Gy, similar to slowly proliferating late reacting tissues. As such, therapeutic gain may arise from the use of hypofractionated HDR treatments, exploiting the sensitivity to large fraction sizes, effectively escalating dose. The slow proliferative rate also gives credence to the use of LDR, although several tumour doublings may occur during the effective treatment time, and analysis of the clinical data using a low α/β ratio suggests that LDR doses are only equivalent to 70 Gy with conventional fractionation. Cervical carcinoma is a rapidly proliferating tumour with Tpot values of 3-6 days. LDR implants were delivered over relatively short treatment times, negating repopulation effects, and the 'hyperfractionation' effect of LDR was suited to the high α/β ratio. HDR, although also preventing significant repopulation, has the potential to decrease the therapeutic ratio if low α/β , late-reacting tissues are not protected. Clinical data however show improved outcomes and reduced morbidity with HDR through reduced doses to normal tissues. Choosing the optimal dose rate in brachytherapy depends on tumour behaviour and achievable accuracy. HDR offers some advantages even for high α/β ratio tumours, and may be the technique of

Nationwide, Multicenter, Retrospective Study on High-Dose-Rate Brachytherapy as Monotherapy for Prostate Cancer

International Nuclear Information System (INIS)

Yoshioka, Yasuo; Kotsuma, Tadayuki; Komiya, Akira; Kariya, Shinji; Konishi, Koji; Nonomura, Norio; Ogawa, Kazuhiko; Tanaka, Eiichi; Nishimura, Kensaku; Fujiuchi, Yasuyoshi; Kitamura, Hiroshi; Yamagami, Takuji; Yamasaki, Ichiro; Nishimura, Kazuo; Teshima, Teruki; Nakamura, Katsumasa; Itami, Jun

2017-01-01

Purpose: To present, analyze, and discuss results of a nationwide, multicenter, retrospective study on high-dose-rate brachytherapy (HDR-BT) as monotherapy for low-, intermediate-, and high-risk prostate cancer. Methods and Materials: From 1995 through 2013, 524 patients, 73 (14%) with low-risk, 207 (40%) with intermediate-risk, and 244 (47%) with high-risk prostate cancer, were treated with HDR-BT as monotherapy at 5 institutions in Japan. Dose fractionations were 27 Gy/2 fractions for 69 patients (13%), 45.5 Gy/7 fractions for 168 (32%), 49 Gy/7 fractions for 149 (28%), 54 Gy/9 fractions for 130 (25%), and others for 8 (2%). Of these patients, 156 (30%) did not receive androgen deprivation therapy, and 202 patients (39%) did receive androgen deprivation therapy 3 years. Median follow-up time was 5.9 years (range, 0.4-18.1 years), with a minimum of 2 years for surviving patients. Results: After 5 years, respective actuarial rates of no biochemical evidence of disease, overall survival, cause-specific survival, and metastasis-free survival for all patients were 92%, 97%, 99%, and 94%. For low/intermediate/high-risk patients, the 5-year no biochemical evidence of disease rates were 95%/94%/89%, the 5-year overall survival rates were 98%/98%/94%, the 5-year cause-specific survival rates were 98%/100%/98%, and the 5-year metastasis-free survival rates were 98%/95%/90%, respectively. The cumulative incidence of late grade 2 to 3 genitourinary toxicity at 5 years was 19%, and that of late grade 3 was 1%. The corresponding incidences of gastrointestinal toxicity were 3% and 0% (0.2%). No grade 4 or 5 of either type of toxicity was detected. Conclusions: The findings of this nationwide, multicenter, retrospective study demonstrate that HDR-BT as monotherapy was safe and effective for all patients with low-, intermediate-, and high-risk prostate cancer.

Nationwide, Multicenter, Retrospective Study on High-Dose-Rate Brachytherapy as Monotherapy for Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Yoshioka, Yasuo, E-mail: yoshioka@radonc.med.osaka-u.ac.jp [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Osaka (Japan); Kotsuma, Tadayuki [Department of Radiation Oncology, Osaka National Hospital, Osaka (Japan); Komiya, Akira [Department of Urology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama (Japan); Department of Urology, Chiba University Hospital, Chiba (Japan); Kariya, Shinji [Department of Radiology, Kochi Medical School, Kochi (Japan); Konishi, Koji [Department of Radiation Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan); Nonomura, Norio [Department of Urology, Osaka University Graduate School of Medicine, Osaka (Japan); Ogawa, Kazuhiko [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Osaka (Japan); Tanaka, Eiichi [Department of Radiation Oncology, Osaka National Hospital, Osaka (Japan); Nishimura, Kensaku [Department of Urology, Osaka National Hospital, Osaka (Japan); Fujiuchi, Yasuyoshi; Kitamura, Hiroshi [Department of Urology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama (Japan); Yamagami, Takuji [Department of Radiology, Kochi Medical School, Kochi (Japan); Yamasaki, Ichiro [Department of Urology, Kochi Medical School, Kochi (Japan); Nishimura, Kazuo [Department of Urology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan); Teshima, Teruki [Department of Radiation Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan); Nakamura, Katsumasa [Department of Radiation Oncology, Hamamatsu University School of Medicine, Shizuoka (Japan); Itami, Jun [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan)

2017-04-01

Purpose: To present, analyze, and discuss results of a nationwide, multicenter, retrospective study on high-dose-rate brachytherapy (HDR-BT) as monotherapy for low-, intermediate-, and high-risk prostate cancer. Methods and Materials: From 1995 through 2013, 524 patients, 73 (14%) with low-risk, 207 (40%) with intermediate-risk, and 244 (47%) with high-risk prostate cancer, were treated with HDR-BT as monotherapy at 5 institutions in Japan. Dose fractionations were 27 Gy/2 fractions for 69 patients (13%), 45.5 Gy/7 fractions for 168 (32%), 49 Gy/7 fractions for 149 (28%), 54 Gy/9 fractions for 130 (25%), and others for 8 (2%). Of these patients, 156 (30%) did not receive androgen deprivation therapy, and 202 patients (39%) did receive androgen deprivation therapy <1 year, 112 (21%) for 1-3 years, and 54 (10%) for >3 years. Median follow-up time was 5.9 years (range, 0.4-18.1 years), with a minimum of 2 years for surviving patients. Results: After 5 years, respective actuarial rates of no biochemical evidence of disease, overall survival, cause-specific survival, and metastasis-free survival for all patients were 92%, 97%, 99%, and 94%. For low/intermediate/high-risk patients, the 5-year no biochemical evidence of disease rates were 95%/94%/89%, the 5-year overall survival rates were 98%/98%/94%, the 5-year cause-specific survival rates were 98%/100%/98%, and the 5-year metastasis-free survival rates were 98%/95%/90%, respectively. The cumulative incidence of late grade 2 to 3 genitourinary toxicity at 5 years was 19%, and that of late grade 3 was 1%. The corresponding incidences of gastrointestinal toxicity were 3% and 0% (0.2%). No grade 4 or 5 of either type of toxicity was detected. Conclusions: The findings of this nationwide, multicenter, retrospective study demonstrate that HDR-BT as monotherapy was safe and effective for all patients with low-, intermediate-, and high-risk prostate cancer.

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

International Nuclear Information System (INIS)

Picano, Eugenio; Vano, Eliseo; Domenici, Luciano; Bottai, Matteo; Thierry-Chef, Isabelle

2012-01-01

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

Long-term results of exclusive low-dose rate curie-therapy for a high-grade vaginal intraepithelial neoplasia

International Nuclear Information System (INIS)

Blanchard, P.; Monnier, L.; Dumas, I.; Azoury, F.; Mazeron, R.; Haie-Meder, C.

2010-01-01

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

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

International Nuclear Information System (INIS)

Mei Quelin; Du Duanming; Chen Zaizhong; Liu Pengcheng; Yang Jianyong; Li Yanhao

2008-01-01

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)

Occupational radiation exposure to low doses of ionizing radiation and female breast cancer

International Nuclear Information System (INIS)

Adelina, P.; Bliznakov, V.; Bairacova, A.

2003-01-01

The aim of this study is to examine the relationship between past occupational radiation exposure to low doses of ionizing radiation and cases of diagnosed and registered breast cancer [probability of causation - PC] among Bulgarian women who have used different ionizing radiation sources during their working experience. The National Institute of Health (NIH) in US has developed a method for estimating the probability of causation (PC) between past occupational radiation exposure to low doses of ionizing radiation and cases of diagnosed cancer. We have used this method. A group of 27 women with diagnosed breast cancer has been studied. 11 of them are former workers in NPP - 'Kozloduy', and 16 are from other sites using different sources of ionizing radiation. Analysis was performed for 14 women, for whom full personal data were available. The individual radiation dose for each of them is below 1/10 of the annual dose limit, and the highest cumulative dose for a period of 14 years of occupational exposure is 50,21 mSv. The probability of causation (PC) values in all analyzed cases are below 1%, which confirms the extremely low probability of causation (PC) between past occupational radiation exposure to low doses of ionizing radiation and occurring cases of breast cancer. (orig.)

Estimation of radiation exposure from lung cancer screening program with low-dose computed tomography

Energy Technology Data Exchange (ETDEWEB)

Kim, Su Yeon; Jun, Jae Kwan [Graduate School of Cancer Science and Policy, National Cancer Center, Seoul (Korea, Republic of)

2016-12-15

The National Lung Screening Trial (NLST) demonstrated that screening with Low-dose Computed Tomography (LDCT) screening reduced lung cancer mortality in a high-risk population. Recently, the United States Preventive Services Task Force (USPSTF) gave a B recommendation for annual LDCT screening for individuals at high-risk. With the promising results, Korea developed lung cancer screening guideline and is planning a pilot study for implementation of national lung cancer screening. With widespread adoption of lung cancer screening with LDCT, there are concerns about harms of screening, including high false-positive rates and radiation exposure. Over the 3 rounds of screening in the NLST, 96.4% of positive results were false-positives. Although the initial screening is performed at low dose, subsequent diagnostic examinations following positive results additively contribute to patient's lifetime exposure. As with implementing a large-scale screening program, there is a lack of established risk assessment about the effect of radiation exposure from long-term screening program. Thus, the purpose of this study was to estimate cumulative radiation exposure of annual LDCT lung cancer screening program over 20-year period.

Research on low radiation doses - A better understanding of low doses

International Nuclear Information System (INIS)

2016-01-01

Radiation doses below 100 mSv are called low doses. Epidemiological research on the health hazards of low doses are difficult to do because numerous pathologies, particularly cancer, appear lifelong for genetical or environmental causes without any link with irradiation and it is very difficult to identify the real cause of a cancer. Another concern is that the impact on human health is weak and are observed only after a long period after irradiation. These features make epidemiological studies cumbersome to implement since they require vast cohorts and a very long-term follow-up. The extrapolation of the effects of higher doses to the domain of low doses does not meet reality and it is why the European Union takes part into the financing of such research. In order to gain efficiency, scientists work together through various European networks among them: HLEG (High Level Expert Group On European Low Dose Risk Research) or MELODI (Multidisciplinary European Low Dose Initiative). Several programs are underway or have been recently launched: -) the impact of Cesium contamination on children's health (Epice program), -) the study of the impact of medical imaging on children, -) the study of the health of children living near nuclear facilities, -) the relationship between radon and lung cancer, -) the effect of occupational low radiation doses, -) the effect of uranium dissolved in water on living organisms (Envirhom program). (A.C.)

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...

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

International Nuclear Information System (INIS)

Hanisch, Per Henrik; Furre, Torbjoern; Olsen, Dag Rune; Pettersen, Erik O.

2007-01-01

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 T 1/2 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

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

International Nuclear Information System (INIS)

Inoue, Takehiro; Inoue, Toshihiko; Teshima, Teruki; Murayama, Shigeyuki; Shimizutani, Kimishige; Fuchihata, Hajime; Furukawa, Souhei

1996-01-01

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

Low- and high-dose radioiodine therapy for low-/intermediate-risk differentiated thyroid cancer. A preliminary clinical trial

International Nuclear Information System (INIS)

Qu Yuan; Huang Rui; Li Lin

2017-01-01

To compare the ablation results, therapeutic responses and adverse reactions between a low dose (1.1 GBq) or high dose (3.7 GBq) of 131 I in low-/intermediate-risk differentiated thyroid cancer (DTC) patients. The factors influencing the ablation result and therapeutic response were also analyzed. The researchers used a random number table to randomly assign the enrolled patients to the low-dose group or high-dose group at a 1:1 ratio, and assessment of ablation result, therapeutic response, and adverse reactions evaluated 6 ± 3 months after therapy. A total of 140 patients were enrolled in the study through October 2014-June 2015. Until February 2016, 132 patients completed the trial. 99 patients were re-examined under thyroid-stimulating hormone (TSH) stimulation 3-9 months after 131 I therapy. For the low-dose and high-dose groups, the success rates of ablation were 52.7% (29/55) and 59.1% (26/44), respectively. The ablation results did not differ significantly between the two groups (P = 0.548). One hundred and thirty two patients were re-examined 2-9 months after 131 I therapy. The low-dose group had an excellent response rate of ∼80% (53/66), an indeterminate response rate of ∼ 20% (13/66), and no cases with a biochemical incomplete response. The high-dose group had an excellent response rate of ∼85% (36/66), an indeterminate response rate of ∼11% (7/66), and a biochemical incomplete response rate of ∼4% (3/66). No significant differences in the therapeutic response were observed between the two groups (P = 0.087). Patients in stage N1b had a significantly lower success rate of ablation than those in stage N0 (P = 0.000). The success rate of ablation increased significantly with lower thyroglobulin (Tg) levels (P = 0.000). A pre-treatment Tg level was significantly associated with a higher excellent response rate (P = 0.002). Pre-treatment-stimulated Tg of 0.47 and 3.09 μg/L were identified as cut-off values for predicting the ablation result and

Towards a new dose and dose-rate effectiveness factor (DDREF)? Some comments.

Science.gov (United States)

Chadwick, K H

2017-06-26

The aim of this article is to offer a broader, mechanism-based, analytical tool than that used by (Rühm et al 2016 Ann. ICRP 45 262-79) for the interpretation of cancer induction relationships. The article explains the limitations of this broader analytical tool and the implications of its use in view of the publications by Leuraud et al 2015 (Lancet Haematol. 2 e276-81) and Richardson et al 2015 (Br. Med. J. 351 h5359). The publication by Rühm et al 2016 (Ann. ICRP 45 262-79), which is clearly work in progress, reviews the current status of the dose and dose-rate effectiveness factor (DDREF) as recommended by the ICRP. It also considers the issues which might influence a reassessment of both the value of the DDREF as well as its application in radiological protection. In this article, the problem is approached from a different perspective and starts by commenting on the limited scientific data used by Rühm et al 2016 (Ann. ICRP 45 262-79) to develop their analysis which ultimately leads them to use a linear-quadratic dose effect relationship to fit solid cancer mortality data from the Japanese life span study of atomic bomb survivors. The approach taken here includes more data on the induction of DNA double strand breaks and, using experimental data taken from the literature, directly relates the breaks to cell killing, chromosomal aberrations and somatic mutations. The relationships are expanded to describe the induction of cancer as arising from radiation induced cytological damage coupled to cell killing since the cancer mutated cell has to survive to express its malignant nature. Equations are derived for the induction of cancer after both acute and chronic exposure to sparsely ionising radiation. The equations are fitted to the induction of cancer in mice to illustrate a dose effect relationship over the total dose range. The 'DDREF' derived from the two equations varies with dose and the DDREF concept is called into question. Although the equation for

Mutation induction in cultured human cells after low-dose and low-dose-rate γ-ray irradiation. Detection by LOH analysis

International Nuclear Information System (INIS)

Umebayashi, Yukihiro; Iwaki, Masaya; Yatagai, Fumio; Honma, Masamitsu; Suzuki, Masao; Suzuki, Hiromi; Shimazu, Toru; Ishioka, Noriaki

2007-01-01

To study the genetic effects of low-doses and low-dose-rate ionizing radiation (IR), human lymphoblastoid TK6 cells were exposed to 30 mGy of γ-rays at a dose-rate of 1.2 mGy/hr. The frequency of early mutations (EMs) in the thymidine kinase (TK) gene locus was determined to be 1.7 x 10 -6 , or 1.9-fold higher than the level seen in unirradiated controls. These mutations were analyzed with a loss of heterozygosity (LOH) detection system, a methodology which has been shown to be sensitive to the effects of radiation. Among the 15 EMs observed after IR exposure, 8 were small interstitial-deletion events restricted to the TK gene locus. However, this specific type of event was not found in unirradiated controls. Although these results were observed under the limited conditions, they strongly suggest that the LOH detection system can be used for estimating the genetic effects of a low-dose IR exposure delivered at a low-dose-rate. (author)

The Cancer of the Prostate Risk Assessment (CAPRA) score predicts biochemical recurrence in intermediate-risk prostate cancer treated with external beam radiotherapy (EBRT) dose escalation or low-dose rate (LDR) brachytherapy.

Science.gov (United States)

Krishnan, Vimal; Delouya, Guila; Bahary, Jean-Paul; Larrivée, Sandra; Taussky, Daniel

2014-12-01

To study the prognostic value of the University of California, San Francisco Cancer of the Prostate Risk Assessment (CAPRA) score to predict biochemical failure (bF) after various doses of external beam radiotherapy (EBRT) and/or permanent seed low-dose rate (LDR) prostate brachytherapy (PB). We retrospectively analysed 345 patients with intermediate-risk prostate cancer, with PSA levels of 10-20 ng/mL and/or Gleason 7 including 244 EBRT patients (70.2-79.2 Gy) and 101 patients treated with LDR PB. The minimum follow-up was 3 years. No patient received primary androgen-deprivation therapy. bF was defined according to the Phoenix definition. Cox regression analysis was used to estimate the differences between CAPRA groups. The overall bF rate was 13% (45/345). The CAPRA score, as a continuous variable, was statistically significant in multivariate analysis for predicting bF (hazard ratio [HR] 1.37, 95% confidence interval [CI] 1.10-1.72, P = 0.006). There was a trend for a lower bF rate in patients treated with LDR PB when compared with those treated by EBRT ≤ 74 Gy (HR 0.234, 95% CI 0.05-1.03, P = 0.055) in multivariate analysis. In the subgroup of patients with a CAPRA score of 3-5, CAPRA remained predictive of bF as a continuous variable (HR 1.51, 95% CI 1.01-2.27, P = 0.047) in multivariate analysis. The CAPRA score is useful for predicting biochemical recurrence in patients treated for intermediate-risk prostate cancer with EBRT or LDR PB. It could help in treatment decisions. © 2013 The Authors. BJU International © 2013 BJU International.

High dose rate versus low dose rate brachytherapy in the treatment of stage IIIB cervical cancer, and the importance of brachytherapy timing

International Nuclear Information System (INIS)

Petereit, Daniel G.; Sarkaria, Jann N.; Czyzewski, Ann; Buchler, Dolores A.

1996-01-01

Purpose/Objective: To determine the efficacy of HDR versus LDR brachytherapy for Stage IIIB cervical cancer patients. Material and Methods: Forty-four HDR patients were retrospectively compared to 51 LDR patients treated at the same institution from 1977 to 1988 (LDR) and from 1989 to 1995 (HDR). A tumor burden score (TBS) of 2-9 was calculated for both groups of patients to assess volume of disease (2-4 low tumor burden, 5-9 high tumor burden). LDR and HDR patients received 60 Gy to the whole pelvis at 1.7 Gy/Fx. The majority of LDR patients were treated after completion of external beam radiation (EBR) with one 25 Gy implant to Point A (55 cGy/h). The HDR patients were treated with 4-5 HDR fractions of 3.7 Gy to 5.8 Gy/Fx for an LDR equivalence of 20-25 Gy (median dose/Fx 4.3 Gy, median insertion number 5). Clinical endpoints were calculated actuarially with significance determined by the log rank test and the relative risk (RR). Results: The median follow-up for the HDR and LDR groups was 1.8 and 5 years, respectively. Pelvic control and survival was better in the LDR group than the HDR group, 51%, 73%, 32%, 44% (p = 0.004, RR = 0.4), with grade III and above RTOG complications of 19% and 15%, respectively. The median age and performance status were similar between the two groups; however, a TBS score ≥7 was present in 23% of the HDR patients and in 9% of the LDR patients. Pelvic control in the HDR group was 58% with a TBS ≤4, and 17% with a TBS >4 (p = 0.01, RR = 0.4). The median EBR dose at the first HDR insertion was 31 Gy while all the LDR patients received 60 Gy before the insertion. Pelvic control rates in Table 1 indicate a trend towards improved outcome within the HDR group and same TBS if more external beam radiation was given prior to the first HDR insertion. Pelvic control was also higher within the HDR group when Point A received a BED Gy 10≥100 versus <100: 62%, 40%, respectively (RR 0.6). Conclusion: These retrospective results of HDR versus

Publication of new results from the INWORKS epidemiological study about the risk of cancer among nuclear industry workers chronically exposed to low ionizing radiation doses

International Nuclear Information System (INIS)

2015-01-01

In this cohort study, 308297 workers in the nuclear industry from France, the United Kingdom, and the United States with detailed monitoring data for external exposure to ionising radiation were linked to death registries. Excess relative rate per Gy of radiation dose for mortality from cancer was estimated. Follow-up encompassed 8.2 million person years. Of 66632 known deaths by the end of follow-up, 17?957 were due to solid cancers. Results suggest a linear increase in the rate of cancer with increasing radiation exposure. The average cumulative colon dose estimated among exposed workers was 20.9 mGy (median 4.1 mGy). The estimated rate of mortality from all cancers excluding leukaemia increased with cumulative dose by 48% per Gy (90% confidence interval 20% to 79%), lagged by 10 years. Similar associations were seen for mortality from all solid cancers (47% (18% to 79%)), and within each country. The estimated association over the dose range of 0-100 mGy was similar in magnitude to that obtained over the entire dose range but less precise. Smoking and occupational asbestos exposure are potential confounders; however, exclusion of deaths from lung cancer and pleural cancer did not affect the estimated association. Despite substantial efforts to characterise the performance of the radiation dosimeters used, the possibility of measurement error remains. The study provides a direct estimate of the association between protracted low dose exposure to ionising radiation and solid cancer mortality. Although high dose rate exposures are thought to be more dangerous than low dose rate exposures, the risk per unit of radiation dose for cancer among radiation workers was similar to estimates derived from studies of Japanese atomic bomb survivors. Quantifying the cancer risks associated with protracted radiation exposures can help strengthen the foundation for radiation protection standards

Results in patients treated with high-dose-rate interstitial brachytherapy for oral tongue cancer

International Nuclear Information System (INIS)

Yamamoto, Michinori; Shirane, Makoto; Ueda, Tsutomu; Miyahara, Nobuyuki

2006-01-01

Eight patients were treated with high-dose-rate interstitial brachytherapy for oral tongue cancer between September 2000 and August 2004. The patient distribution was 1 T1, 5 T2, 1 T3, and 1 T4a. Patients received 50-60 Gy in 10 fractions over seven days with high-dose-rate brachytherapy. Six of the eight patients were treated with a combination of external beam radiotherapy (20-30 Gy) and interstitial brachytherapy. The two-year primary local control rate was 83% for initial case. High-dose-rate brachytherapy was performed safely even for an aged person, and was a useful treatment modality for oral tongue cancer. (author)

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.

Early quality of life outcomes in patients with prostate cancer managed by high-dose-rate brachytherapy as monotherapy

International Nuclear Information System (INIS)

Komiya, Akira; Fujiuchi, Yasuyoshi; Ito, Takatoshi

2013-01-01

The purpose of this study was to evaluate the early quality of life outcomes in prostate cancer patients managed by high-dose-rate brachytherapy as monotherapy. A total of 51 patients with cT1c-T3aN0M0 prostate cancer treated between July 2007 and January 2010 were included in this study. The average age was 69?years, and the average initial serum prostate-specific antigen was 10.98?ng/mL. A total of 25, 18 and eight patients were considered to be low, intermediate and high risk, respectively. All patients received one implant of Ir-192 and seven fractions of 6.5?Gy within 3.5?days for a total prescribed dose of 45.5?Gy. For high-risk prostate cancer, neoadjuvant androgen deprivation therapy was carried out for at least 6?months, and continued after high-dose-rate brachytherapy. Quality of life outcomes were measured by using the International Prostate Symptom Score, the Functional Assessment of Cancer Therapy-Prostate and the International Index of Erectile Function Questionnaire. The oncological outcome was assessed by serum prostate-specific antigen and diagnostic imaging. Adverse events were also recorded. The Functional Assessment of Cancer Therapy-Prostate scores decreased for a few months after high-dose-rate brachytherapy, and recovered to pretreatment condition thereafter. The International Prostate Symptom Score significantly increased 2?weeks after treatment for each of its items and their sum, and it returned to baseline after 12?weeks. Sexual function decreased at 2 and 4?weeks, and recovered after 12?weeks. Severe complications were rare. Within a median follow up of 17.2?months, two patients showed a prostate-specific antigen recurrence. High-dose-rate brachytherapy for prostate cancer is a feasible treatment modality with acceptable toxicity and only a limited impact on the quality of life. (author)

Measuring the absorbed dose in critical organs during low rate dose brachytherapy with 137 Cs using thermoluminescent dosemeters

International Nuclear Information System (INIS)

Torres, A.; Gonzalez, P.R.; Furetta, C.; Azorin, J.; Andres, U.; Mendez, G.

2003-01-01

Intracavitary Brachytherapy is one of the most used methods for the treatment of the cervical-uterine cancer. This treatment consists in the insertion of low rate dose 137 Cs sources into the patient. The most used system for the treatment dose planning is that of Manchester. This planning is based on sources, which are considered fixed during the treatment. However, the experience has shown that, during the treatment, the sources could be displaced from its initial position, changing the dose from that previously prescribed. For this reason, it is necessary to make measurements of the absorbed dose to the surrounding organs (mainly bladder and rectum). This paper presents the results of measuring the absorbed dose using home-made LiF: Mg, Cu, P + Ptfe thermoluminescent dosimeters (TLD). Measurements were carried out in-vivo during 20 minutes at the beginning and at the end of the treatments. Results showed that the absorbed dose to the critical organs vary significantly due to the movement of the patient during the treatment. (Author)

Physiological and immunological changes following exposure to low versus high-dose ionizing irradiation; comparative analysis with dose rate and cumulative dose

International Nuclear Information System (INIS)

Heesun, Kim; Heewon, Jang; Soungyeon, Song; Shinhye, Oh; Cukcheul, Shin; Meeseon, Jeong; Chasoon, Kim; Kwnaghee, Yang; Seonyoung, Nam; Jiyoung, Kim; Youngwoo, Jin; Changyoung, Cha

2008-01-01

Full text: While high-dose of ionizing radiation is generally harmful and causes damage to living organisms some reports suggest low-dose of radiation may not be as damaging as previously thought. Despite increasing evidence regarding the protective effect of low-dose radiation, no studies have directly compared the exact dose-response pattern by high- and low-dose of radiation exposed at high-and low-dose rate. This study aims to explore the cellular and molecular changes in mice exposed to low- and high-dose of radiation exposed at low- and high-dose rate. When C57BL/6 mice (Female, 6 weeks) were exposed at high-dose rate, 0.8 Gy/min, no significant change on the level of WBC, RBC, or platelets was observed up to total dose of 0.5 Gy. However, 2 Gy of radiation caused dramatic reduction in the level of white blood cells (WBC) and platelets. This reduction was accompanied by increased DNA damage in hematopoietic environments. The reduction of WBC was mainly due to the reduction in the number of CD4+ T cells and CD19+ B cells. CD8+ T cells and NK cells appeared to be relatively resistant to high-dose of radiation. This change was also accompanied by the reduction of T- and B- progenitor cells in the bone marrow. In contrast, no significant changes of the number of CD4+ T, CD8+ T, NK, and B cells were observed in the spleen of mice exposed at low-dose-rate (0.7 m Gy/h or 3.95 mGy/h) for up to 2 Gy, suggesting that low-dose radiation does not alter cellular distribution in the spleen. Nevertheless, mice exposed to low-dose radiation exhibited elevation of VEGF, MCP-1, IL-4, Leptin, IL-3, and Tpo in the peripheral blood and slight increases in MIP-2, RANTES, and IL-2 in the spleen. This suggests that chronic γ-radiation can stimulate immune function without causing damage to the immune components of the body. Taken together, these data indicate hormesis of low-dose radiation, which could be attributed to the stimulation of immune function. Dose rate rather than total

Smoking habits in the randomised Danish Lung Cancer Screening Trial with low-dose CT

DEFF Research Database (Denmark)

Ashraf, Haseem; Saghir, Zaigham; Dirksen, Asger

2014-01-01

BACKGROUND: We present the final results of the effect of lung cancer screening with low-dose CT on the smoking habits of participants in a 5-year screening trial. METHODS: The Danish Lung Cancer Screening Trial (DLCST) was a 5-year screening trial that enrolled 4104 subjects; 2052 were randomised...... to annual low-dose CT (CT group) and 2052 received no intervention (control group). Participants were current and ex-smokers (≥4 weeks abstinence from smoking) with a tobacco consumption of ≥20 pack years. Smoking habits were determined annually. Missing values for smoking status at the final screening...... round were handled using two different models. RESULTS: There were no statistically significant differences in annual smoking status between the CT group and control group. Overall the ex-smoker rates (CT + control group) significantly increased from 24% (baseline) to 37% at year 5 of screening (p

The Effect of Dose and Quality Assurance in Early Prostate Cancer Treated with Low Dose Rate Brachytherapy as Monotherapy.

Science.gov (United States)

Henry, A M; Rodda, S L; Mason, M; Musunuru, H; Al-Qaisieh, B; Bownes, P; Smith, J; Franks, K; Carey, B; Bottomley, D

2015-07-01

To examine the relationship between post-implant computed tomography dosimetry and long-term prostate-specific antigen relapse-free survival in patients treated with iodine 125 (I-125) low dose rate prostate brachytherapy as monotherapy and, second, to audit recent practice against Royal College of Radiologists' (RCR) guidelines after the re-introduction of post-implant dosimetry for all patients in our centre. Between March 1995 and September 2007, 2157 consecutive patients with localised prostate cancer underwent I-125 permanent prostate brachytherapy as monotherapy in a single UK centre. All patients were transrectal ultrasound planned delivering a 145 Gy (TG 43) minimum peripheral dose. None received supplemental external beam radiotherapy. Post-implant computed tomography-based dosimetry was undertaken between 4 and 6 weeks after treatment and was available for 711 (33%). Outcomes were analysed in terms of the relationship of D90 to prostate-specific antigen relapse-free survival (nadir 2+ definition) and all patients had a minimum follow-up of 5 years. For contemporary patients from 2011, quality metrics from post-implant computed tomography as defined by RCR guidelines are presented. A mean D90 of 138.7 Gy (standard deviation 24.7) was achieved for the historic cohort. Biochemical control at 10 years was 76% in patients with D90 > 140 Gy and 68% in those with D90 standard deviation) D90 has increased from 154 (15.3) Gy in 2011 to 164 (13.5) Gy in 2013. Similarly, an increase in the mean (standard deviation) V100 from 92 (4.4) to 95 (3.2) % is noted over time. No difference between clinicians was noted. D90 values of less than 140 Gy continue to be predictive of increased risk of recurrence of prostate cancer across risk groups with longer follow-up. Quality assurance can be used to ensure improved and consistent implant quality in a team with multiple clinicians. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights

Treatment of the prostate cancer with high dose rate brachytherapy

International Nuclear Information System (INIS)

Martinez, Alvaro; Torres Silva, Felipe

2002-01-01

The prostate cancer treatment in early stages is controversial. The high dose rate brachytherapy has been used like monotherapy or boost with external beam radiotherapy in advanced disease. This paper describes the technique and the advantages over other modalities

Cancer Control Related to Stimulation of Immunity by Low-Dose Radiation

OpenAIRE

Liu, Shu-Zheng

2006-01-01

Previous studies showed that low dose radiation (LDR) could stimulate the immune system in both animal and human populations. This paper reviews the present status of relevant research as support to the use of LDR in clinical practice for cancer prevention and treatment. It has been demonstrated that radiation-induced changes in immune activity follows an inverse J-shaped curve, i.e., low dose stimulation and high dose suppression. The stimulation of immunity by LDR concerns most anticancer p...

Enhanced response rates in pancreatic cancer with concurrent continuous infusion(CI) low dose chemotherapy and hyperfractionated radiotherapy

International Nuclear Information System (INIS)

Bronn, Donald G.; Franklin, Roman; Krishnan, Rajan S.; Richardson, Ralph W.; Conlin, Christopher

1996-01-01

radiographic responses were achieved within 1-3 months after completion of the radiotherapy portion of the concurrent treatment regimen. One year survival was achieved in 78% of patients treated ((7(9))). These response and survival rates were achieved with minimal complications and side-effects and patients predominantly maintained ambulatory status throughout the entire course of treatment and follow-up. Conclusions: Concurrent CI combination chemotherapy in low daily doses with BID hyperfractionated radiotherapy is effective in achieving dramatic local response and improved survival with minimal side-effects. These results suggest that a significant synergistic effect exists with concurrent chemoradiotherapy in complimentary low dose regimens for the treatment of pancreatic cancer. Additional studies are suggested for further exploration of the optimal integration of well tolerated concurrent chemoradiation combinations

Radiobiological modelling of dose-gradient effects in low dose rate, high dose rate and pulsed brachytherapy

International Nuclear Information System (INIS)

Armpilia, C; Dale, R G; Sandilos, P; Vlachos, L

2006-01-01

This paper presents a generalization of a previously published methodology which quantified the radiobiological consequences of dose-gradient effects in brachytherapy applications. The methodology uses the linear-quadratic (LQ) formulation to identify an equivalent biologically effective dose (BED eq ) which, if applied uniformly to a specified tissue volume, would produce the same net cell survival as that achieved by a given non-uniform brachytherapy application. Multiplying factors (MFs), which enable the equivalent BED for an enclosed volume to be estimated from the BED calculated at the dose reference surface, have been calculated and tabulated for both spherical and cylindrical geometries. The main types of brachytherapy (high dose rate (HDR), low dose rate (LDR) and pulsed (PB)) have been examined for a range of radiobiological parameters/dimensions. Equivalent BEDs are consistently higher than the BEDs calculated at the reference surface by an amount which depends on the treatment prescription (magnitude of the prescribed dose) at the reference point. MFs are closely related to the numerical BED values, irrespective of how the original BED was attained (e.g., via HDR, LDR or PB). Thus, an average MF can be used for a given prescribed BED as it will be largely independent of the assumed radiobiological parameters (radiosensitivity and α/β) and standardized look-up tables may be applicable to all types of brachytherapy treatment. This analysis opens the way to more systematic approaches for correlating physical and biological effects in several types of brachytherapy and for the improved quantitative assessment and ranking of clinical treatments which involve a brachytherapy component

Lung cancer mortality between 1950 and 1987 after exposure to fractionated moderate-dose-rate ionizing radiation in the Canadian fluoroscopy cohort study and a comparison with lung cancer mortality in the atomic bomb survivors study

International Nuclear Information System (INIS)

Howe, G.R.

1995-01-01

Current lung cancer risk estimates after exposure to low-linear energy transfer radiation such as X rays are based on studies of people exposed to such radiation at high dose rates, for example the atomic bomb survivors. Radiobiology and animal experiments suggest that risks from exposure at low to moderate dose rates, for example medical diagnostic procedures, may be overestimated by such risk models, but data for humans to examine this issue are limited. In this paper we report on lung cancer mortality between 1950 and 1987 in a cohort of 64,172 Canadian tuberculosis patients, of whom 39% were exposed to highly fractionated multiple chest fluoroscopies leading to a mean lung radiation dose of 1.02 Sv received at moderate dose rates. These data have been used to estimate the excess relative risk per sievert of lung cancer mortality, and this is compared directly to estimates derived from 75,991 atomic bomb survivors. Based on 1,178 lung cancer deaths in the fluoroscopy study, there was no evidence of any positive association between risk and dose, with the relative risk at 1 Sv being 1.00 (95% confidence interval 0.94, 1.07), which contrasts with that based on the atomic bomb survivors, 1.60 (1.27, 1.99). The difference in effect between the two studies almost certainly did not arise by chance (P = 0.0001). This study provides strong support from data for humans for a substantial fractionation/dose-rate effect for low-linear energy transfer radiation and lung cancer risk. This implies that lung cancer risk from exposures to such radiation at present-day dose rates is likely to be lower than would be predicted by current radiation risk models based on studies of high-dose-rate exposures. 25 refs., 8 tabs

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

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)

Georg, Dietmar; Hopfgartner, Johannes; Gòra, Joanna; Kuess, Peter; Kragl, Gabriele; Berger, Daniel; Hegazy, Neamat; Goldner, Gregor; Georg, Petra

2014-01-01

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 ( 192 Ir) and LDR-BT ( 125 I) were D 90% ≥34 Gy in 8.5 Gy per fraction and D 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 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 were clearly superior in

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.

High dose rate (HDR) and low dose rate (LDR) interstitial irradiation (IRT) of the rat spinal cord

International Nuclear Information System (INIS)

Pop, Lucas A.M.; Plas, Mirjam van der; Skwarchuk, Mark W.; Hanssen, Alex E.J.; Kogel, Albert J. van der

1997-01-01

Purpose: To describe a newly developed technique to study radiation tolerance of rat spinal cord to continuous interstitial irradiation (IRT) at different dose rates. Material and methods: Two parallel catheters are inserted just laterally on each side of the vertebral bodies from the level of Th 10 to L 4 . These catheters are afterloaded with two 192 Ir wires of 4 cm length each (activity 1-2.3 mCi/cm) for the low dose rate (LDR) IRT or connected to the HDR micro-Selectron for the high dose rate (HDR) IRT. Spinal cord target volume is located at the level of Th 12 -L 2 . Due to the rapid dose fall-off around the implanted sources, a dose inhomogeneity across the spinal cord thickness is obtained in the dorso-ventral direction. Using the 100% reference dose (rate) at the ventral side of the spinal cord to prescribe the dose, experiments have been carried out to obtain complete dose response curves at average dose rates of 0.49, 0.96 and 120 Gy/h. Paralysis of the hind-legs after 5-6 months and histopathological examination of the spinal cord of each irradiated rat are used as experimental endpoints. Results: The histopathological damage seen after irradiation is clearly reflected the inhomogeneous dose distribution around the implanted catheters, with the damage predominantly located in the dorsal tract of the cord or dorsal roots. With each reduction in average dose rate, spinal cord radiation tolerance is significantly increased. When the dose is prescribed at the 100% reference dose rate, the ED 50 (induction of paresis in 50% of the animals) for the HDR-IRT is 17.3 Gy. If the average dose rate is reduced from 120 Gy/h to 0.96 or 0.49 Gy/h, a 2.9- or 4.7-fold increase in the ED 50 values to 50.3 Gy and 80.9 Gy is observed; for the dose prescribed at the 150% reference dose rate (dorsal side of cord) ED 50 values are 26.0, 75.5 and 121.4 Gy, respectively. Using different types of analysis and in dependence of the dose prescription and reference dose rate, the �

Physics and quality assurance for brachytherapy - Part II: Low dose rate and pulsed dose rate

International Nuclear Information System (INIS)

Williamson, Jeffrey F.

1997-01-01

Purpose: A number of recent developments have revitalized brachytherapy including remote afterloading, implant optimization, increasing use of 3D imaging, and advances in dose specification and basic dosimetry. However, the core physical principles underlying the classical methods of dose calculation and arrangement of multiple sources remain unchanged. The purpose of this course is to review these principles and their applications to low dose-rate interstitial and intracavitary brachytherapy. Emphasis will be placed upon the classical implant systems along with classical and modern methods of dose specification. The level of presentation is designed for radiation oncology residents and beginning clinical physicists. A. Basic Principles (1) Radium-substitute vs. low-energy sealed sources (2) Dose calculation principles (3) The mysteries of source strength specification revealed: mgRaEq, mCi and air-kerma strength B. Interstitial Brachytherapy (1) Target volume, implanted volume, dose specification in implants and implant optimization criteria (2) Classical implant systems: Manchester Quimby and Paris a) Application of the Manchester system to modern brachytherapy b) Comparison of classical systems (3) Permanent interstitial implants a) Photon energy and half life b) Dose specification and pre-operative planning (4) The alphabet soup of dose specification: MCD (mean central dose), minimum dose, MPD (matched peripheral dose), MPD' (minimum peripheral dose) and DVH (dose-volume histogram) quality indices C. Intracavitary Brachytherapy for Carcinoma of the Cervix (1) Basic principles a) Manchester System: historical foundation of U.S. practice patterns b) Principles of applicator design (2) Dose specification and treatment prescription a) mg-hrs, reference points, ICRU Report 38 reference volume -- Point A dose vs mg-hrs and IRAK (Integrated Reference Air Kerma) -- Tissue volume treated vs mg-hrs and IRAK b) Practical methods of treatment specification and prescription

Physics and quality assurance for brachytherapy - Part II: Low dose rate and pulsed dose rate

International Nuclear Information System (INIS)

Williamson, Jeffrey F.

1996-01-01

Purpose: A number of recent developments have revitalized brachytherapy including remote afterloading, implant optimization, increasing use of 3D imaging, and advances in dose specification and basic dosimetry. However, the core physical principles underlying the classical methods of dose calculation and arrangement of multiple sources remain unchanged. The purpose of this course is to review these principles and their applications to low dose-rate interstitial and intracavitary brachytherapy. Emphasis will be placed upon the classical implant systems along with classical and modern methods of dose specification. The level of presentation is designed for radiation oncology residents and beginning clinical physicists. A. Basic Principles (1) Radium-substitute vs. low-energy sealed sources (2) Dose calculation principles (3) The mysteries of source strength specification revealed: mgRaEq, mCi and air-kerma strength B. Interstitial Brachytherapy (1) Target volume, implanted volume, dose specification in implants and implant optimization criteria (2) Classical implant systems: Manchester Quimby and Paris a) Application of the Manchester system to modern brachytherapy b) Comparison of classical systems (3) Permanent interstitial implants a) Photon energy and half life b) Dose specification and pre-operative planning (4) The alphabet soup of dose specification: MCD (mean central dose), minimum dose, MPD (matched peripheral dose), MPD' (minimum peripheral dose) and DVH (dose-volume histogram) quality indices C. Intracavitary Brachytherapy for Carcinoma of the Cervix (1) Basic principles a) Manchester System: historical foundation of U.S. practice patterns b) Principles of applicator design (2) Dose specification and treatment prescription a) mg-hrs, reference points, ICRU Report 38 reference volume --Point A dose vs mg-hrs and IRAK (Integrated Reference Air Kerma) --Tissue volume treated vs mg-hrs and IRAK b) Practical methods of treatment specification and prescription

Rectal dose assessment in patients submitted to high-dose-rate brachytherapy for uterine cervix cancer; Avaliacao da dose no reto em pacientes submetidas a braquiterapia de alta taxa de dose para o tratamento do cancer do colo uterino

Energy Technology Data Exchange (ETDEWEB)

Oliveira, Jetro Pereira de [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Faculdade de Medicina; Rosa, Luiz Antonio Ribeiro da [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)], e-mail: lrosa@ird.gov.br; Batista, Delano Valdivino Santos; Bardella, Lucia Helena [Instituto Nacional de Cancer (INCA), Rio de Janeiro, RJ (Brazil). Unit of Medical Physics; Carvalho, Arnaldo Rangel [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil). Lab. of Thermoluminescent Dosimetry

2009-03-15

Objective: The present study was aimed at developing a thermoluminescent dosimetric system capable of assessing the doses delivered to the rectum of patients submitted to high-dose-rate brachytherapy for uterine cervix cancer. Materials and methods: LiF:Mg,Ti,Na powder was the thermoluminescent material utilized for evaluating the rectal dose. The powder was divided into small portions (34 mg) which were accommodated in a capillary tube. This tube was placed into a rectal probe that was introduced into the patient's rectum. Results: The doses delivered to the rectum of six patients submitted to high-dose-rate brachytherapy for uterine cervix cancer evaluated by means of thermoluminescent dosimeters presented a good agreement with the planned values based on two orthogonal (anteroposterior and lateral) radiographic images of the patients. Conclusion: The thermoluminescent dosimetric system developed in the present study is simple and easy to be utilized as compared to other rectal dosimetry methods. The system has shown to be effective in the evaluation of rectal doses in patients submitted to high-dose-rate brachytherapy for uterine cervix cancer. (author)

Epistemological problems in assessing cancer risks at low radiation doses

International Nuclear Information System (INIS)

Walinder, G.

1987-01-01

Historically, biology has not been subjected to any epistemological analysis as has been the case with mathematics and physics. Our knowledge of the effects in biological systems of various stimuli proves to be dualistic in a complementary (although not mutually exclusive) way, which bears resemblance to the knowledge of phenomena in quantum physics. The dualistic limbs of biological knowledge are the action of stimuli and the response of the exposed, biological system. With regard to radiogenic cancer, this corresponds to the action of the ionizations and the response of the exposed mammal to that action, respectively. The following conclusions can be drawn from the present analysis: Predictions as to radiogenic cancer seem often if not always to have neglected the response variability (variations in radiosensitivity) in individuals or among individuals in populations, i.e. the predictions have been based exclusively on radiation doses and exposure conditions. The exposed individual or population, however, must be considered an open statistical system, i.e. a system in which predictions as to the effect of an agent are only conditionally possible. The knowledge is inverse to the size of the dose or concentration of the active agent. On epistemological grounds, we can not gain knowledge about the carcinogenic capacity of very low (non-dominant) radiation doses. Based on the same principle, we can not predict cancer risks at very low (non-dominant) radiation doses merely on the basis of models, or otherwise interpolated or extrapolated high-dose effects, observed under special exposure conditions

Joint analysis of French and Czech uranium miners: lung cancer risk at low radon exposure rates and modifying effects of time since exposure and age at exposure

International Nuclear Information System (INIS)

Ladislav Tomasek; Agnes Rogel; Margot Tirmarche; Dominique Laurier

2006-01-01

The present analysis was conducted in the frame of European project 'Quantification of lung cancer risk after low radon exposure and low exposure rate: synthesis from epidemiologic and experimental data'. The overall goal of the project related to uranium miners was the evaluation of lung cancer dose-response relationship and of dose rate effects among European uranium miners exposed to low doses and low dose rates of radon decay products. In addition, modifying factors like attained age, age at exposure and time since exposure were investigated. The joint analysis of French and Czech uranium miners was conducted mainly in order to increase the statistical power and to allow a more detailed description of the variation of dose-response relationship in time. (N.C.)

Joint analysis of French and Czech uranium miners: lung cancer risk at low radon exposure rates and modifying effects of time since exposure and age at exposure

Energy Technology Data Exchange (ETDEWEB)

Ladislav Tomasek [National Radiation Protection Institute, Prague (Czech Republic); Agnes Rogel; Margot Tirmarche; Dominique Laurier [Institut de Radioprotection et de Surete Nucleaire, Fontenay-aux-Roses (France)

2006-07-01

The present analysis was conducted in the frame of European project 'Quantification of lung cancer risk after low radon exposure and low exposure rate: synthesis from epidemiologic and experimental data'. The overall goal of the project related to uranium miners was the evaluation of lung cancer dose-response relationship and of dose rate effects among European uranium miners exposed to low doses and low dose rates of radon decay products. In addition, modifying factors like attained age, age at exposure and time since exposure were investigated. The joint analysis of French and Czech uranium miners was conducted mainly in order to increase the statistical power and to allow a more detailed description of the variation of dose-response relationship in time. (N.C.)

Successful Treatment of Opioid-Refractory Cancer Pain with Short-Course, Low-Dose Ketamine.

Science.gov (United States)

Waldfogel, Julie M; Nesbit, Suzanne; Cohen, Steven P; Dy, Sydney M

2016-12-01

Opioids remain the mainstay of treatment for severe cancer pain, but up to 20% of patients have persistent or refractory pain despite rapid and aggressive opioid titration, or develop refractory pain after long-term opioid use. In these scenarios, alternative agents and mechanisms for analgesia should be considered. This case report describes a 28-year-old man with metastatic pancreatic neuroendocrine cancer with severe, intractable pain despite high-dose opioids including methadone and a hydromorphone patient-controlled analgesia (PCA). After treatment with short-course, low-dose ketamine, his opioid requirements decreased by 99% and pain ratings by 50%, with the majority of this decrease occurring in the first 48 hours. As this patient's pain and opioid regimen escalated, he likely experienced some component of central sensitization and hyperalgesia. Administration of ketamine reduced opioid consumption by 99% and potentially "reset" neuronal hyperexcitability and reduced pain signaling, allowing for improved pain control.

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)

Tanaka, Kimio; Khoda, Atsushi; Ichinohe, Kazuaki; Oghiso, Yoichi

2007-01-01

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)

Salvage high-dose-rate interstitial brachytherapy for locally recurrent rectal cancer

Energy Technology Data Exchange (ETDEWEB)

Pellizzon, Antonio Cassio Assis, E-mail: acapellizzon@hcancer.org.br [A.C. Camargo Cancer Center, Sao Paulo, SP (Brazil). Departamento de Radioterapia

2016-05-15

For tumors of the lower third of the rectum, the only safe surgical procedure is abdominal-perineal resection. High-dose-rate interstitial brachytherapy is a promising treatment for local recurrence of previously irradiated lower rectal cancer, due to the extremely high concentrated dose delivered to the tumor and the sparing of normal tissue, when compared with a course of external beam radiation therapy. (author)

Dosimetric accuracy at low monitor unit setting in electron beams at different dose rates

International Nuclear Information System (INIS)

Ravikumar, M.; Ravichandran, R.; Supe, Sanjay S.; Sharma, Anil K.

1999-01-01

As electron beam with low monitor unit (LMU) settings are used in some dosimetric studies, better understanding of accuracy in dose delivery at LMU setting is necessary. The dose measurements were carried out with 0.6 cm 3 farmer type ion chamber at d max in a polystyrene phantom. Measurements at different MUs show that the dose linearity ratio (DLR) increases as the MU setting decreases below 20 MU and DLRs are found to increase when the incident electron beams have higher energies. The increase in DLR is minimum for low dose rate setting for all five electron beam energies (6, 9, 12, 16 and 20 MeV). As the variation in dose delivery is machine-specific, a detailed study should be conducted before the low MU setting is implemented. Since errors in dose delivery are high at higher dose rates, low dose rate may be better at low MU unit setting. (author)

Low- and high-dose laser irradiation effects on cell migration and destruction

Science.gov (United States)

Layton, Elivia; Gallagher, Kyra A.; Zukerman, Sara; Stevens, Brianna; Zhou, Feifan; Liu, Hong; Chen, Wei R.

2018-02-01

Metastases are the cause of more than 90 percent of cancer-related deaths. Current treatment methods, including chemotherapy, radiation, and surgery, fail to target the metastases effectively. One potential treatment for metastatic cancer is laser immunotherapy (LIT). LIT combines the use of a photothermal laser with an immunoadjuvant, Glycated Chitosan (GC). GC combined with single-walled carbon nanotubes (SWNTs) has proven to be a viable alternative to traditional cancer treatment methods, when under irradiation of laser with appropriate wavelength. In this study, the effects of low dose and high dose laser irradiation on metastatic pancreatic cancer cell migration were observed. It was found that low dose irradiation increased the migration rate, but the high dose irradiation significantly decreased the migration rate of the cancer cells. When using LIT, the goal is to kill tumor cells and to prompt the correct immune response. If the tumor were irradiated with a low dose, it would promote metastasis. If the dose of irradiation were too high, it would destroy the entire tumor and the immune response would not recognize the tumor. Therefore, the laser dose plays an important role in LIT, particularly when using SWNT as light absorbing agent. Our results from this study will delineate the optimal laser irradiation dose for destroying tumor cells and at the same time preserve and release tumor antigens as a precursor of antitumor immune response.

Assessment of the feasibility of using transrectal ultrasound for postimplant dosimetry in low-dose-rate prostate brachytherapy

Energy Technology Data Exchange (ETDEWEB)

Davies, Rhian Siân, E-mail: rhian.s.davies@wales.nhs.uk; Perrett, Teresa; Powell, Jane; Barber, Jim; Tanguay, Jacob; Button, Michael; Cochlin, Dennis; Smith, Christian; Lester, Jason Francis

2016-01-01

A study was performed to establish whether transrectal ultrasound (TRUS)-based postimplant dosimetry (PID) is both practically feasible and comparable to computed tomography (CT)-based PID, recommended in current published guidelines. In total, 22 patients treated consecutively at a single cancer center with low-dose-rate (LDR) brachytherapy for early-stage prostate cancer had a transrectal ultrasound performed immediately after implant (d0-TRUS) and computed tomography scan 30 days after implant (d30-CT). Postimplant dosimetry planning was performed on both image sets and the results were compared. The interobserver reproducibility of the transrectal ultrasound postimplant dosimetry planning technique was also assessed. It was noticed that there was no significant difference in mean prostate D{sub 90} (136.5 Gy and 144.4 Gy, p = 0.2197), V{sub 100} (86.4% and 89.1%, p = 0.1480) and V{sub 150} (52.0% and 47.8%, p = 0.1657) for d30-CT and d0-TRUS, respectively. Rectal doses were significantly higher for d0-TRUS than d30-CT. Urethral doses were available with d0-TRUS only. We have shown that d0-TRUS PID is a useful tool for assessing the quality of an implant after low-dose-rate prostate brachytherapy and is comparable to d30-CT PID. There are clear advantages to its use in terms of resource and time efficiency both for the clinical team and the patient.

Early detection of lung cancer using ultra-low-dose computed tomography in coronary CT angiography scans among patients with suspected coronary heart disease.

Science.gov (United States)

Zanon, Matheus; Pacini, Gabriel Sartori; de Souza, Vinicius Valério Silveiro; Marchiori, Edson; Meirelles, Gustavo Souza Portes; Szarf, Gilberto; Torres, Felipe Soares; Hochhegger, Bruno

2017-12-01

To assess whether an additional chest ultra-low-dose CT scan to the coronary CT angiography protocol can be used for lung cancer screening among patients with suspected coronary artery disease. 175 patients underwent coronary CT angiography for assessment of coronary artery disease, additionally undergoing ultra-low-dose CT screening to early diagnosis of lung cancer in the same scanner (80kVp and 15mAs). Patients presenting pulmonary nodules were followed-up for two years, repeating low-dose CTs in intervals of 3, 6, or 12 months based on nodule size and growth rate in accordance with National Comprehensive Cancer Network guidelines. Ultra-low-dose CT identified 71 patients with solitary pulmonary nodules (41%), with a mean diameter of 5.50±4.00mm. Twenty-eight were >6mm, and in 79% (n=22) of these cases they were false positive findings, further confirmed by follow-up (n=20), resection (n=1), or biopsy (n=1). Lung cancer was detected in six patients due to CT screening (diagnostic yield: 3%). Among these, four cases could not be detected in the cardiac field of view. Most patients were in early stages of the disease. Two patients diagnosed at advanced stages died due to cancer complications. The addition of the ultra-low-dose CT scan represented a radiation dose increment of 1.22±0.53% (effective dose, 0.11±0.03mSv). Lung cancer might be detected using additional ultra-low-dose protocols in coronary CT angiography scans among patients with suspected coronary artery disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Second salvage high-dose-rate brachytherapy for radiorecurrent prostate cancer

Directory of Open Access Journals (Sweden)

Metha Maenhout

2017-04-01

Full Text Available Purpose : Salvage treatments for localized radiorecurrent prostate cancer can be performed safely when a focal and image guided approach is used. Due to the low toxicity, the opportunity exists to investigate a second salvage treatment when a second locally recurrent prostate cancer occurs. Here, we describe a second salvage treatment procedure of 4 patients. Material and methods : Four patients with a pathologically proven second local recurrence were treated in an outpatient magnetic resonance imaging (MRI-guided setting with a single fraction of 19 Gy focal high-dose-rate brachytherapy (HDR-BT. Delineation was performed using choline-PET-CT or a 68Ga-PSMA PET in combination with multiparametric 3 Tesla MRI in all four patients. Toxicity was measured using common toxicity criteria for adverse events (CTCAE version 4.0. Results : With a median follow-up of 12 months (range, 6-15, there were 2 patients with biochemical recurrence as defined by the Phoenix-definition. There were no patients with grade 3 or more toxicity. In all second salvage HDR-BT treatments, the constraints for rectum, bladder, and urethra were met. Median treatment volume (GTV was 4.8 cc (range, 1.9-6.6 cc. A median of 8 catheters (range, 6-9 were used, and the median dose to the treatment volume (GTV was a D95: 19.3 Gy (SD 15.5-19.4 Gy. Conclusions : Second focal salvage MRI-guided HDR-BT for a select group of patients with a second locally recurrent prostate cancer is feasible. There was no grade 3 or more acute toxicity for these four patients.

Dose-Time Relations for Induction of Lung Cancer in Uranium Miners

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Blair, H. A. [University of Rochester School of Medicine and Dentistry, Rochester, NY (United States)

1969-11-15

Lack of data on the concentration of radon and daughters in the air inhaled by uranium miners has made it difficult in the past to establish radiation dose and time factors for induction of lung cancer. Recent determinations by others of {sup 210}Pb in the bones of miners who died of cancer provide, however, a new approach. Because {sup 210}Pb, a decay product of radon, accumulates in bone but is also excreted, its concentration, after prolonged exposure, will approach an equilibrium which is a measure of the rate of exposure. It is shown that the {sup 210}Pb. levels in bone at the end of mining are as closely proportional to existing measured and estimated exposure rates to radon as can be expected. It is reasonable, therefore, to use {sup 210}Pb levels in bone as measures of prior exposure rates. When this is done a graph of survival times from beginning of exposures against reciprocal of {sup 210}Pb shows that lung cancer in man exhibits the two types, early and late, previously revealed in bone cancer in dogs and skin cancer in rats. When the dose is high, death follows initiation of cancer in about 7 years. When the dose is low, the usual case, there is an additional latency of 16 years so the time from attainment of initiating dose to death is 23 years. The initiating dose for the high dose type is about 65 pCi {sup 210}Pb per gram years and for the low dose type about 10 pCi per gram years which, in terms of exposure, is about 400 working level months, WLM, as working level, WL, is currently defined. Of the derived parameters the total low dose development time of 23 years is fairly accurate. The high dose development time of 7 years is less certain. The initiating low dose of 10 pCi per gram years is probably moderately accurate, but its counterpart of 400 WLM less certain. The high initiating dose is poorly determined. Twenty three lung cancer cases were involved in this study. Additional cases along with additional environmental and other measurements

Nonrandomized study comparing the effects of preoperative radiotherapy and daily administration of low-dose cisplatin with those radiotherapy alone for oral cancer

International Nuclear Information System (INIS)

Kurita, Hiroshi; Azegami, Takuya; Kobayashi, Hirokazu; Kurashina, Kenji; Tanaka, Kouichi; Kotani, Akira; Oguchi, Masahiko; Tamura, Minoru.

1997-01-01

The purpose of this study was to compare the effect of preoperative radiotherapy and daily administration of low-dose cisplatin with those of radiotherapy alone for oral cancer. Ten patients underwent preoperative radiotherapy of 30 to 40 Gy with concomitant daily administration of low-dose cisplatin (5 mg/body or 5 mg/m 2 ). Ten patients received external radiotherapy alone. The locoregional response rates (complete response and partial response) did not differ significantly between the two groups (80% for combined therapy and 60% for radiotherapy alone). On histopathologic evaluation of surgical specimens, however, the combined-therapy group (80%) had a higher response rate than did the radiotherapy-alone group (10%; p<0.01). We conclude that daily administration of low-dose cisplatin enhances the efficacy of radiotherapy against primary tumors. We also suggested that combined therapy may be beneficial as an initial treatment for oral cancer before a planned operation. (author)

High-Dose-Rate Brachytherapy and External-Beam Radiotherapy for Hormone-Naïve Low- and Intermediate-Risk Prostate Cancer: A 7-Year Experience

International Nuclear Information System (INIS)

Aluwini, Shafak; Rooij, Peter H. van; Kirkels, Wim J.; Jansen, Peter P.; Praag, John O.; Bangma, Chris H.; Kolkman-Deurloo, Inger-Karine K.

2012-01-01

Purpose: To report clinical outcomes and early and late complications in 264 hormone-naïve patients with low- and intermediate-risk prostate cancer treated with high-dose-rate brachytherapy (HDR-BT) in combination with external-beam radiotherapy (EBRT). Methods and Materials: Between February 2000 and July 2007, 264 patients underwent HDR-BT in combination with EBRT as a treatment for their low- to intermediate-risk prostate cancer. The HDR-BT was performed using ultrasound-based implantation. The total HDR-BT dose was 18 Gy in 3 fractions within 24 h, with a 6-h minimum interval. The EBRT started 2 weeks after HDR-BT and was delivered in 25 fractions of 1.8 Gy to 45 Gy within 5 weeks. Results: After a mean follow-up of 74.5 months, 4 patients (1.5%) showed prostate-specific antigen progression according to the American Society for Radiation Oncology definition and 8 patients (3%) according to the Phoenix definition. A biopsy-proven local recurrence was registered in 1 patient (0.4%), and clinical progression (bone metastases) was documented in 2 patients (0.7%). Seven-year actuarial freedom from biochemical failure was 97%, and 7-year disease-specific survival and overall survival were 100% and 91%, respectively. Toxicities were comparable to other series. Conclusions: Treatment with interstitial HDR-BT plus EBRT shows a low incidence of late complications and a favorable oncologic outcome after 7 years follow-up.

The optimal fraction size in high-dose-rate brachytherapy: dependency on tissue repair kinetics and low-dose rate

International Nuclear Information System (INIS)

Sminia, Peter; Schneider, Christoph J.; Fowler, Jack F.

2002-01-01

Background and Purpose: Indications of the existence of long repair half-times on the order of 2-4 h for late-responding human normal tissues have been obtained from continuous hyperfractionated accelerated radiotherapy (CHART). Recently, these data were used to explain, on the basis of the biologically effective dose (BED), the potential superiority of fractionated high-dose rate (HDR) with large fraction sizes of 5-7 Gy over continuous low-dose rate (LDR) irradiation at 0.5 Gy/h in cervical carcinoma. We investigated the optimal fraction size in HDR brachytherapy and its dependency on treatment choices (overall treatment time, number of HDR fractions, and time interval between fractions) and treatment conditions (reference low-dose rate, tissue repair characteristics). Methods and Materials: Radiobiologic model calculations were performed using the linear-quadratic model for incomplete mono-exponential repair. An irradiation dose of 20 Gy was assumed to be applied either with HDR in 2-12 fractions or continuously with LDR for a range of dose rates. HDR and LDR treatment regimens were compared on the basis of the BED and BED ratio of normal tissue and tumor, assuming repair half-times between 1 h and 4 h. Results: With the assumption that the repair half-time of normal tissue was three times longer than that of the tumor, hypofractionation in HDR relative to LDR could result in relative normal tissue sparing if the optimum fraction size is selected. By dose reduction while keeping the tumor BED constant, absolute normal tissue sparing might therefore be achieved. This optimum HDR fraction size was found to be largely dependent on the LDR dose rate. On the basis of the BED NT/TUM ratio of HDR over LDR, 3 x 6.7 Gy would be the optimal HDR fractionation scheme for replacement of an LDR scheme of 20 Gy in 10-30 h (dose rate 2-0.67 Gy/h), while at a lower dose rate of 0.5 Gy/h, four fractions of 5 Gy would be preferential, still assuming large differences between tumor

Comparison of low and high dose rate brachytherapy in the treatment of uterine cervix cancer. Retrospective analysis of two sequential series

International Nuclear Information System (INIS)

Ferrigno, Robson; Nishimoto, Ines Nobuko; Ribeiro dos Santos Novaes, Paulo Eduardo; Pellizzon, Antonio Cassio Assis; Conte Maia, Maria Aparecida; Fogarolli, Ricardo Cesar; Salvajoli, Joao Victor

2005-01-01

Purpose: This retrospective analysis aims to report on the comparative outcome of cervical cancer patients treated with low dose rate (LDR) and high dose rate (HDR) brachytherapy. Methods and Materials: From 1989 to 1995, 190 patients were treated with low dose rate (LDR) brachytherapy (LDR group) and from 1994 to 2001, 118 patients were treated with high dose rate (HDR) brachytherapy (HDR group). FIGO stage distribution for the LDR group was Stage I: 6.3%; Stage II: 57.4%; and Stage III: 36.3% and for the HDR group Stage I: 9.3%; Stage II: 43.2%; and Stage III: 47.4%. All patients were treated with telecobalt external-beam radiotherapy (EBR). Median doses of LDR brachytherapy at Point A were 40 Gy and 50 Gy for patients treated with 1 and 2 implants, respectively. All patients from the HDR group were treated with 24 Gy in 4 fractions of 6 Gy to Point A. Survival, disease-free survival, local control, and late complications at 5 years, were endpoints compared for both groups. Results: Median follow-up time for LDR and HDR groups was 70 months (range, 8-127 months) and 33 months (range, 4-117 months), respectively. For all stages combined, overall survival, disease-free survival, and local control at 5 years were better in the LDR group (69% vs. 55%, p = 0.007; 73% vs. 56%, p = 0.002; and 74% vs. 65%; p = 0.04, respectively). For clinical Stages I and II, no differences was seen in overall survival, disease-free survival, and local control at 5 years between the two groups. For clinical Stage III, overall survival and disease-free survival at 5 years were better in the LDR group than in the HDR group (46% vs. 36%, p = 0.04 and 49% vs. 37%, p = 0.03, respectively), and local control was marginally higher in the LDR group than in the HDR group (58% vs. 50%, p = 0.19). The 5-year probability of rectal complications was higher in the LDR group than in the HDR group (16% vs. 8%, p = 0.03) and 5-year probability of small bowel and urinary complications was not

Low dose rate brachytherapy (LDR-BT) as monotherapy for early stage prostate cancer in Italy: practice and outcome analysis in a series of 2237 patients from 11 institutions.

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Fellin, Giovanni; Mirri, Maria A; Santoro, Luigi; Jereczek-Fossa, Barbara A; Divan, Claudio; Mussari, Salvatore; Ziglio, Francesco; La Face, Beniamino; Barbera, Fernando; Buglione, Michela; Bandera, Laura; Ghedi, Barbara; Di Muzio, Nadia G; Losa, Andrea; Mangili, Paola; Nava, Luciano; Chiarlone, Renato; Ciscognetti, Nunzia; Gastaldi, Emilio; Cattani, Federica; Spoto, Ruggero; Vavassori, Andrea; Giglioli, Francesca R; Guarneri, Alessia; Cerboneschi, Valentina; Mignogna, Marcello; Paoluzzi, Mauro; Ravaglia, Valentina; Chiumento, Costanza; Clemente, Stefania; Fusco, Vincenzo; Santini, Roberto; Stefanacci, Marco; Mangiacotti, Francesco P; Martini, Marco; Palloni, Tiziana; Schinaia, Giuseppe; Lazzari, Grazia; Silvano, Giovanni; Magrini, Stefano; Ricardi, Umberto; Santoni, Riccardo; Orecchia, Roberto

2016-09-01

Low-dose-rate brachytherapy (LDR-BT) in localized prostate cancer is available since 15 years in Italy. We realized the first national multicentre and multidisciplinary data collection to evaluate LDR-BT practice, given as monotherapy, and outcome in terms of biochemical failure. Between May 1998 and December 2011, 2237 patients with early-stage prostate cancer from 11 Italian community and academic hospitals were treated with iodine-125 ((125)I) or palladium-103 LDR-BT as monotherapy and followed up for at least 2 years. (125)I seeds were implanted in 97.7% of the patients: the mean dose received by 90% of target volume was 145 Gy; the mean target volume receiving 100% of prescribed dose (V100) was 91.1%. Biochemical failure-free survival (BFFS), disease-specific survival (DSS) and overall survival (OS) were estimated using Kaplan-Meier method. Log-rank test and multivariable Cox regression were used to evaluate the relationship of covariates with outcomes. Median follow-up time was 65 months. 5- and 7-year DSS, OS and BFFS were 99 and 98%, 94 and 89%, and 92 and 88%, respectively. At multivariate analysis, the National Comprehensive Cancer Network score (p LDR-BT. This first multicentre Italian report confirms LDR-BT as an excellent curative modality for low-/intermediate-risk prostate cancer. Multidisciplinary teams may help to select adequately patients to be treated with brachytherapy, with a direct impact on the implant quality and, possibly, on outcome.

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

International Nuclear Information System (INIS)

Tanaka, Satoshi; Sasagawa, Sumiko; Ichinohe, Kazuaki; Matsumoto, Tsuneya; Otsu, Hiroshi; Sato, Fumiaki

2002-01-01

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 g-rays irradiation on SPF mice, using life-span and pathological changes as parameters. Continuous irradiation with g-rays for 400 days was performed using 137 Cs γ-rays at dose-rates of 20 mGy/day, 1 mGy/day and 0.05 mGy/day with accumulated doses equivalent to 8,000 mGy, 400 mGy and 20 mGy, respectively. All mice were kept until they died a natural death. As of 2002 March 31, 3,999 of the total 4,000 mice have died. Preliminary analyses of data show that 20 mGy/day suggested a shortened life span in both sexes. Partial results show that the most common lethal neoplasms in the pooled data of non-irradiated 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. Experiment 2 - Effects on the progeny of chronic low dose-rate g-ray irradiated SPF mice: pilot study, was started in 1999 and is currently in progress. (author)

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

International Nuclear Information System (INIS)

Bong, Jin Jong; Kang, Yu Mi; Shin, Suk Chull; Choi, Moo Hyun; Choi, Seung Jin; Kim, Hee Sun; Lee, Kyung Mi

2012-01-01

To determine the biological effects of low-dose-rate radiation ( 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.

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.

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)

Changes of chromosome aberration rate and micronucleus frequency along with accumulated dose in continuously irradiated mice with a low dose rate of γ-rays

International Nuclear Information System (INIS)

Tanaka, Kimio; Izumi, Jun; Yanai, Takanori; Ichinohe, Kazuaki; Matsumoto, Tsuneya

2003-01-01

Chromosome aberrations in chronically exposed workers in nuclear facilities and medical radiologists have been reported. However chronological change of chromosome aberration rates along with accumulated dose has not been well studied. Chromosome aberrations and micronuclei in spleen lymphocytes were observed serially in mice continuously irradiated with a low dose rate of 20 mGy/day up to 400 days. Chromosome aberration rates were rapidly increased to 11.1% at 1 Gy, while micronucleus incidence increased at 5 Gy. After these doses their increase rates were saturated. Micronucleus incidence in bone marrow erythroblasts was higher than in spleen cells. These chronological changes of cytogenetic aberrations seem to be induced through a balance between developments of chromosome aberrations and micronuclei, and life span of spleen lymphocytes. These results will be helpful for risk assessment in low dose rate radiation exposure. (author)

Effect of low dose rate irradiation on doped silica core optical fibers

International Nuclear Information System (INIS)

Friebele, E.J.; Askins, C.G.; Gingerich, M.E.

1984-01-01

The optical attenuation induced in multimode doped silica core optical fiber waveguides by a year's exposure to low dose rate (1 rad/day) ionizing radiation was studied, allowing a characterization of fibers deployed in these environments and a determination of the permanent induced loss in the waveguides. Variations in the induced attenuation at 0.85 μm have been observed with changes in the dose rate between 1 rad/day and 9000 rads/min. These dose rate dependences have been found to derive directly from the recovery that occurs during the exposure; the recovery data predict little or no dose rate dependence of the damage at 1.3 μm. The low dose rate exposure has been found to induce significant permanent attenuation in the 0.7-1.7-μm spectral region in all fibers containing P in the core, whether doped uniformly across the diameter or constrained to a narrow spike on the centerline. Whereas permanent loss was induced at 0.85 μm in a P-free binary Ge-doped silica core fiber by the year's exposure, virtually no damage was observed at 1.3 μm

Late change of normal tissue treated either by high dose rate or low dose rate interstitial brachytherapy. A retrospective comparative study on oral and oropharyngeal mucosa

International Nuclear Information System (INIS)

Nose, Takayuki; Koizumi, Masahiko; Nishiyama, Kinji; Inoue, Toshihiko

2002-01-01

The purpose of this study was to compare late changes of normal tissue treated either by high dose rate (HDR) or low dose rate (LDR) interstitial brachytherapy. For HDR group, 22 oropharynx cancer patients who were treated by HDR Ir-192 interstitial brachytherapy with/without external beam radiotherapy in Osaka (Osaka Medical Center for Cancer and Cardiovascular Diseases and Osaka University Hospital) during June 1994 through April 2000 and came to the follow-up clinics during July 2000 through December 2000 were studied. For LDR group, 26 oropharynx cancer patients who were treated by LDR Ir-192 interstitial brachytherapy with/without external beam radiotherapy in Nancy (Centre Alexis Vautrin) during February 1989 through July 1998 and came to the follow-up clinics during April 1999 through July 1999 were studied. The standard HDR schedules were 54 Gy/9 fr/5-6 days for monotherapy and 18-24 Gy/3-4 fr/2-3 days following 45 Gy external beam radiotherapy. The standard LDR schedules were 65 Gy/5-6 days for monotherapy and 15-25 Gy/2-3 days following 50 Gy external beam radiotherapy. For evaluation of the late changes, we scored the mucosal and muscular changes inside the treated volume using the modified Dische score system and the RTOG/EORTC late radiation morbidity scoring scheme. For 6 items of the modified Dische score system, no significant difference was found between HDR and LDR groups. For the remaining 2 items (pallor, mobility impairment of faucial pillars), LDR group showed higher scores (p=0.010, 0.002). LDR group showed a trend toward higher scores for the RTOG/EORTC scheme (p=0.059). Some predict late effects by HDR interstitial brachytherapy to be severer than by LDR because no dose-rate effects can be expected. Our study, however, showed at least equivalent or even milder late changes by HDR. Appropriate fractionation schedule and extra geometrical sparing effects by optimized dose distribution of HDR group might result in milder late changes. With our

The direct biologic effects of radioactive 125I seeds on pancreatic cancer cells PANC-1, at continuous low-dose rates.

Science.gov (United States)

Wang, Jidong; Wang, Junjie; Liao, Anyan; Zhuang, Hongqing; Zhao, Yong

2009-08-01

The relative biologic effectiveness of model 6711 125I seeds (Ningbo Junan Pharmaceutical Technology Company,Ningbo, China) and their effects on growth, cell cycle, and apoptosis in human pancreatic cancer cell line PANC-1 were examined in the present study. PANC-1 cells were exposed to the absorbed doses of 1, 2, 4, 6, 8, and 10 Gyeither with 125I seeds (initial dose rate, 2.59 cGy=h) or with 60Co g-ray irradiation (dose rate, 221 cGy=min),respectively. Significantly greater numbers of apoptotic PANC-1 cells were detected following the continuouslow-dose-rate (CLDR) irradiation of 125I seeds, compared with cells irradiated with identical doses of 60Co g-ray. The D(0) for 60Co g-ray and 125I seed irradiation were 2.30 and 1.66, respectively. The survival fraction after 125Iseed irradiation was significantly lower than that of 60Co g-ray, with a relative biologic effectiveness of 1.39.PANC-1 cells were dose dependently arrested in the S-phase by 60Co g-rays and in the G2=M phase by 125I seeds,24 hour after irradiation. CLDR irradiation by 125I seeds was more effective in inducing cell apoptosis in PANC-1cells than acute high-dose-rate 60Co g irradiation. Interestingly, CLDR irradiation by 125I seeds can cause PANC-1cell-cycle arrest at the G2=M phase and induce apoptosis, which may be an important mechanism underlying 125Iseed-induced PANC-1 cell inhibition.

Effects of low dose rate irradiation on induction of myeloid leukemia in mice

International Nuclear Information System (INIS)

Furuse, Takeshi

1999-01-01

We investigated the induction of myeloid leukemia and other kinds of neoplasias in C3H male mice irradiated at several dose rate levels. We compared the incidence of neoplasias among these groups, obtained dose and dose rate effectiveness factors (DDREF) for myeloid leukemia. C3H/He male mice were exposed to whole body gamma-ray irradiation at 8 weeks of age. All mice were maintained for their entire life span and teh pathologically examined after their death. Radiation at a high dose-rate of 882 mGy/min (group H), a medium dose-rate of 95.6 mGy/min (group M), and low dose-rates of 0.298 mGy/min (group L-A), 0.067 mGy/min (group L-B) or 0.016 mGy/min (group L-C) were delivered from 137 Cs sources. The mice in group L were irradiated continuously for 22 hours daily up to total doses of 1, 2, 3, 4, 10 Gy over a period of 3 days to 200 days. As for the induction of neoplasias, myeloid leukemia developed significantly more frequently in irradiated groups than in unirradiated groups. The time distribution of mice dying from myeloid leukemia did not show a difference between groups H and L. The incidence of myeloid leukemia showed a greater increase in the high dose-rate groups than in the low and medium dose-rate groups in the dose range over 2 Gy, it also showed significant increases in the groups irradiated with 1 Gy of various dose rate, but the difference between these groups was not clear. These dose effect curves had their highest values on each curve at about 3 Gy. We obtained DDREF values of 2-3 by linear fittings for their dose response curves of dose ranges in which leukemia incidences were increasing. (author)

Low doses of Paclitaxel repress breast cancer invasion through DJ-1/KLF17 signalling pathway.

Science.gov (United States)

Ismail, Ismail Ahmed; El-Sokkary, Gamal H; Saber, Saber H

2018-04-27

Paclitaxel (taxol) is an important agent against many tumours, including breast cancer. Ample data documents that paclitaxel inhibits breast cancer metastasis while others prove that paclitaxel enhances breast cancer metastasis. The mechanisms by which paclitaxel exerts its action are not well established. This study focuses on the effect of paclitaxel, particularly the low doses on breast cancer metastasis and the mechanisms that regulate it. Current results show that, paclitaxel exerts significant cytotoxicity even at low doses in both MCF-7 and MDA-MB-231 cells. Interestingly, paclitaxel significantly inhibits cell invasion and migration, decreases Snail and increases E-cadherin mRNA expression levels at the indicated low doses. Furthermore, paclitaxel-inhibiting breast cancer metastasis is associated with down-regulation of DJ-1 and ID-1 mRNA expression level with a concurrent increase in KLF17 expression. Under the same experimental conditions, paclitaxel induces KLF17 and concurrently represses ID-1 protein levels. Our results show for the first time that paclitaxel inhibits breast cancer metastasis through regulating DJ-1/KLF17/ID-1 signalling pathway; repressed DJ-1 and ID-1 and enhanced KLF17 expression. © 2018 John Wiley & Sons Australia, Ltd.

Analysis of final products from the liquid alkanes radiolysis at low dose, low temperature and high dose rate

International Nuclear Information System (INIS)

Tilquin, B.; Doncker, J. de.

1991-01-01

Yields of final products (dimers) from the radiolysis of n-hexane and 2,3-dimethylbutane are studied by capillary chromatographic techniques for trace analysis. Reaction of intermediates with the products, the alkane molecules or impurities, is reduced by using low dose (1 kGy), low temperature (195 K) and high dose rate (LINAC). Temperature is the most important experiment variable; by reducing the temperature, reactions with significant activation energies do not compete with radical-radical termination reactions. Products from LINAC radiolysis provide information about active species (reactive fragment, allylic radical...) which deserve a more detailed examination by direct methods [fr

Gamma Low-Dose-Rate Ionizing Radiation Stimulates Adaptive Functional and Molecular Response in Human Aortic Endothelial Cells in a Threshold-, Dose-, and Dose Rate-Dependent Manner.

Science.gov (United States)

Vieira Dias, Juliana; Gloaguen, Celine; Kereselidze, Dimitri; Manens, Line; Tack, Karine; Ebrahimian, Teni G

2018-01-01

A central question in radiation protection research is whether low-dose and low-dose-rate (LDR) exposures to ionizing radiation play a role in progression of cardiovascular disease. The response of endothelial cells to different LDR exposures may help estimate risk of cardiovascular disease by providing the biological mechanism involved. We investigated the effect of chronic LDR radiation on functional and molecular responses of human aorta endothelial cells (HAoECs). Human aorta endothelial cells were continuously irradiated at LDR (6 mGy/h) for 15 days and analyzed at time points when the cumulative dose reached 0.05, 0.5, 1.0, and 2.0 Gy. The same doses were administered acutely at high-dose rate (HDR; 1 Gy/min). The threshold for the loss of angiogenic capacity for both LDR and HDR radiations was between 0.5 and 1.0 Gy. At 2.0 Gy, angiogenic capacity returned to normal only for HAoEC exposed to LDR radiation, associated with increased expression of antioxidant and anti-inflammatory genes. Pre-LDR, but not pre-HDR, radiation, followed by a single acute 2.0 Gy challenge dose sustained the expression of antioxidant and anti-inflammatory genes and stimulated angiogenesis. Our results suggest that dose rate is important in cellular response and that a radioadaptive response is involved for a 2.0 Gy dose at LDR.

Repair and dose-response at low doses

International Nuclear Information System (INIS)

Totter, J.R.; Weinberg, A.M.

1977-04-01

The DNA of each individual is subject to formation of some 2-4 x 10 14 ion pairs during the first 30 years of life from background radiation. If a single hit is sufficient to cause cancer, as is implicit in the linear, no-threshold theories, it is unclear why all individuals do not succumb to cancer, unless repair mechanisms operate to remove the damage. We describe a simple model in which the exposed population displays a distribution of repair thresholds. The dose-response at low dose is shown to depend on the shape of the threshold distribution at low thresholds. If the probability of zero threshold is zero, the response at low dose is quadratic. The model is used to resolve a longstanding discrepancy between observed incidence of leukemia at Nagasaki and the predictions of the usual linear hypothesis

High and low dose-rate brachytherapy for cervical carcinoma

International Nuclear Information System (INIS)

Orton, C.G.

1998-01-01

For the brachytherapy component of the r[iation treatment of cervical carcinoma, high dose rate (HDR) is slowly replacing conventional low dose rate (LDR) due primarily to r[iation safety and other physical benefits attributed to the HDR modality. Many r[iation oncologists are reluctant to make this change because of perceived r[iobiological dis[vantages of HDR. However, in clinical practice HDR appears to be as effective as LDR but with a lower risk of late complications, as demonstrated by one randomized clinical trial and two comprehensive literature and practice surveys. The reason for this appears to be that the r[iobiological dis[vantages of HDR are outweighed by the physical [vantages. (orig.)

High-Dose-Rate Brachytherapy as a Monotherapy for Favorable-Risk Prostate Cancer: A Phase II Trial

International Nuclear Information System (INIS)

Barkati, Maroie; Williams, Scott G.; Foroudi, Farshad; Tai, Keen Hun; Chander, Sarat; Dyk, Sylvia van; See, Andrew; Duchesne, Gillian M.

2012-01-01

Purpose: There are multiple treatment options for favorable-risk prostate cancer. High-dose-rate (HDR) brachytherapy as a monotherapy is appealing, but its use is still investigational. A Phase II trial was undertaken to explore the value of such treatment in low-to-intermediate risk prostate cancer. Methods and Materials: This was a single-institution, prospective study. Eligible patients had low-risk prostate cancer features but also Gleason scores of 7 (51% of patients) and stage T2b to T2c cancer. Treatment with HDR brachytherapy with a single implant was administered over 2 days. One of four fractionation schedules was used in a dose escalation study design: 3 fractions of 10, 10.5, 11, or 11.5 Gy. Patients were assessed with the Common Terminology Criteria for Adverse Events version 2.0 for urinary toxicity, the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scoring schema for rectal toxicity, and the Expanded Prostate Cancer Index Composite (EPIC) questionnaire to measure patient-reported health-related quality of life. Biochemical failure was defined as a prostate-specific antigen (PSA) nadir plus 2 ng/ml. Results: Between 2003 and 2008, 79 patients were enrolled. With a median follow-up of 39.5 months, biochemical relapse occurred in 7 patients. Three- and 5-year actuarial biochemical control rates were 88.4% (95% confidence interval [CI], 78.0-96.2%) and 85.1% (95% CI, 72.5-94.5%), respectively. Acute grade 3 urinary toxicity was seen in only 1 patient. There was no instance of acute grade 3 rectal toxicity. Rates of late grade 3 rectal toxicity, dysuria, hematuria, urinary retention, and urinary incontinence were 0%, 10.3%, 1.3%, 9.0%, and 0%, respectively. No grade 4 or greater toxicity was recorded. Among the four (urinary, bowel, sexual, and hormonal) domains assessed with the EPIC questionnaire, only the sexual domain did not recover with time. Conclusions: HDR brachytherapy as a monotherapy for favorable

High-Dose-Rate Brachytherapy as a Monotherapy for Favorable-Risk Prostate Cancer: A Phase II Trial

Energy Technology Data Exchange (ETDEWEB)

Barkati, Maroie [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Williams, Scott G., E-mail: scott.williams@petermac.org [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Department of Pathology, University of Melbourne, Melbourne (Australia); Foroudi, Farshad; Tai, Keen Hun; Chander, Sarat [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Department of Pathology, University of Melbourne, Melbourne (Australia); Dyk, Sylvia van [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); See, Andrew [Ballarat Austin Radiation Oncology Centre, Ballarat (Australia); Duchesne, Gillian M. [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Department of Pathology, University of Melbourne, Melbourne (Australia)

2012-04-01

Purpose: There are multiple treatment options for favorable-risk prostate cancer. High-dose-rate (HDR) brachytherapy as a monotherapy is appealing, but its use is still investigational. A Phase II trial was undertaken to explore the value of such treatment in low-to-intermediate risk prostate cancer. Methods and Materials: This was a single-institution, prospective study. Eligible patients had low-risk prostate cancer features but also Gleason scores of 7 (51% of patients) and stage T2b to T2c cancer. Treatment with HDR brachytherapy with a single implant was administered over 2 days. One of four fractionation schedules was used in a dose escalation study design: 3 fractions of 10, 10.5, 11, or 11.5 Gy. Patients were assessed with the Common Terminology Criteria for Adverse Events version 2.0 for urinary toxicity, the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scoring schema for rectal toxicity, and the Expanded Prostate Cancer Index Composite (EPIC) questionnaire to measure patient-reported health-related quality of life. Biochemical failure was defined as a prostate-specific antigen (PSA) nadir plus 2 ng/ml. Results: Between 2003 and 2008, 79 patients were enrolled. With a median follow-up of 39.5 months, biochemical relapse occurred in 7 patients. Three- and 5-year actuarial biochemical control rates were 88.4% (95% confidence interval [CI], 78.0-96.2%) and 85.1% (95% CI, 72.5-94.5%), respectively. Acute grade 3 urinary toxicity was seen in only 1 patient. There was no instance of acute grade 3 rectal toxicity. Rates of late grade 3 rectal toxicity, dysuria, hematuria, urinary retention, and urinary incontinence were 0%, 10.3%, 1.3%, 9.0%, and 0%, respectively. No grade 4 or greater toxicity was recorded. Among the four (urinary, bowel, sexual, and hormonal) domains assessed with the EPIC questionnaire, only the sexual domain did not recover with time. Conclusions: HDR brachytherapy as a monotherapy for favorable

Consequences of the exposure at low dose rates-contribution of animal experimentation. Consequences de l'exposition aux faibles debits de dose. Apport de l'experimentation animale

Energy Technology Data Exchange (ETDEWEB)

Masse, R. (CEA Centre d' Etudes de Fontenay-aux-Roses, 92 (FR). Direction des Sciences du Vivant)

1990-01-01

The exposure of laboratory animals to the various types of radiations will induce cancers in relation with the tissue absorbed doses. The shape of the dose-effet relationship is most variable. It is important to distinguish which tumours are comparable to human tumours. Those showing more analogies answer but seldom to the classical lineo-quadratic relationship; however, a strong attenuation of induction is demonstrated at low dose rates. Quasi-threshold relationships are seen after the exposure of some tissues to high-LET radiations. These observations question the validity of generalizing the radiobiologists' dual action theory, setting the origin of the dose-effect relationship in the induction of events within the DNA molecule. There is an alternative in the cellular collaboration events; it assumes that the effectiveness per dose unit decreases constantly as an inverse function of the dose rate.

Harderian Gland Tumorigenesis: Low-Dose and LET Response

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Chang, Polly Y. [SRI International, Menlo Park, CA (United States). Biosciences Div.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Cucinotta, Francis A. [Univ. of Nevada, Las Vegas, NV (United States). Dept. of Health Physics and Diagnostic Sciences; Bjornstad, Kathleen A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Bakke, James [SRI International, Menlo Park, CA (United States). Biosciences Div.; Rosen, Chris J. [SRI International, Menlo Park, CA (United States). Biosciences Div.; Du, Nicholas [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Fairchild, David G. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Cacao, Eliedonna [Univ. of Nevada, Las Vegas, NV (United States). Dept. of Health Physics and Diagnostic Sciences; Blakely, Eleanor A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.

2016-04-19

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

Risk of low-doses in radiodiagnosis; Risque des faibles doses en radiodiagnostic. Mythes, reglementation et rationalite

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Cordoliani, Y.S.; Sarrazin, J.L.; Le Frian, G.; Soulie, D.; Leveque, C. [Hopital d`Instruction des Armees du Val-de-Grace, 75 - Paris (France)

1997-12-31

The effect of low doses of X-rays is inferred from the indubitable effects of high doses in human carcinogenesis, Genetic and teratogenic effects are mainly inferred from animal experimentation because clinical surveys of irradiated pregnant women have failed to demonstrate such consequences in the children, except for mental retardation after Japanese atomic bombing. Since no evidence of carcinogenic effect has been produced by epidemiological studies for doses lower than 500 mSv. the estimation of the risk due to low doses has been extrapolated from the linear relation between dose and cancers at high doses. Such an extrapolation gives a maximal risk which is falsely used as a probability of cancer. The actual risk lies between zero and this maximal number, and many epidemiologic surveys in people receiving doses much higher than the mean level of background irradiation failed to demonstrate higher rate of cancer. The explanation of this fact, which is supported by the most recent biological data, is the efficacy of the DNA repair system at low level of exposure to ionizing radiations. We expose the principles of regulation of radioprotection for workers, and give estimations of the doses delivered to the patients and the personnel by diagnostic investigations, by comparing these doses with those of natural irradiation. Practical aspect for conventional and computed radiology are exposed for patients and workers. (authors)

Human health effects of low doses of ionizing radiation: the BEIR III controversy

International Nuclear Information System (INIS)

Radford, E.P.

1980-01-01

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

Neither high-dose nor low-dose brachytherapy increases flap morbidity in salvage treatment of recurrent head and neck cancer

Directory of Open Access Journals (Sweden)

Peter W. Henderson

2016-08-01

Full Text Available Purpose: While brachytherapy is often used concurrently with flap reconstruction following surgical ablation for head and neck cancer, it remains unclear whether it increases morbidity in the particularly high risk subset of patients undergoing salvage treatment for recurrent head and neck cancer (RH&NC. Material and methods : A retrospective chart review was undertaken that evaluated patients with RH&NC who underwent flap coverage after surgical re-resection and concomitant brachytherapy. The primary endpoint was flap viability, and the secondary endpoints were flap and recipient site complications. Results : In the 23 subjects included in series, flap viability and skin graft take was 100%. Overall recipient site complication rate was 34.8%, high-dose radiation (HDR group 50%, and low-dose radiation (LDR group 29.4%. There was no statistically significant difference between these groups. Conclusions : In patients who undergo flap reconstruction and immediate postoperative radiotherapy following salvage procedures for RH&NC, flap coverage of defects in combination with brachytherapy remains a safe and effective means of providing stable soft tissue coverage.

Effects of low doses of ionizing radiation

International Nuclear Information System (INIS)

Masse, R.

2006-01-01

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.)

Choline PET based dose-painting in prostate cancer - Modelling of dose effects

International Nuclear Information System (INIS)

Niyazi, Maximilian; Bartenstein, Peter; Belka, Claus; Ganswindt, Ute

2010-01-01

Several randomized trials have documented the value of radiation dose escalation in patients with prostate cancer, especially in patients with intermediate risk profile. Up to now dose escalation is usually applied to the whole prostate. IMRT and related techniques currently allow for dose escalation in sub-volumes of the organ. However, the sensitivity of the imaging modality and the fact that small islands of cancer are often dispersed within the whole organ may limit these approaches with regard to a clear clinical benefit. In order to assess potential effects of a dose escalation in certain sub-volumes based on choline PET imaging a mathematical dose-response model was developed. Based on different assumptions for α/β, γ50, sensitivity and specificity of choline PET, the influence of the whole prostate and simultaneous integrated boost (SIB) dose on tumor control probability (TCP) was calculated. Based on the given heterogeneity of all potential variables certain representative permutations of the parameters were chosen and, subsequently, the influence on TCP was assessed. Using schedules with 74 Gy within the whole prostate and a SIB dose of 90 Gy the TCP increase ranged from 23.1% (high detection rate of choline PET, low whole prostate dose, high γ50/ASTRO definition for tumor control) to 1.4% TCP gain (low sensitivity of PET, high whole prostate dose, CN + 2 definition for tumor control) or even 0% in selected cases. The corresponding initial TCP values without integrated boost ranged from 67.3% to 100%. According to a large data set of intermediate-risk prostate cancer patients the resulting TCP gains ranged from 22.2% to 10.1% (ASTRO definition) or from 13.2% to 6.0% (CN + 2 definition). Although a simplified mathematical model was employed, the presented model allows for an estimation in how far given schedules are relevant for clinical practice. However, the benefit of a SIB based on choline PET seems less than intuitively expected. Only under the

Radiation Dose-rate Reduction Pattern in Well-differentiated Thyroid Cancer Treated with I-131.

Science.gov (United States)

Khan, Shahbaz Ahmad; Khan, Muhammad Saqib; Arif, Muhammad; Durr-e-Sabih; Rahim, Muhammad Kashif; Ahmad, Israr

2015-07-01

To determine the patterns of dose rate reduction in single and multiple radioiodine (I-131) therapies in cases of well differentiated thyroid cancer patients. Analytical series. Department of Nuclear Medicine and Radiation Physics, Multan Institute of Nuclear Medicine and Radiotherapy (MINAR), Multan, Pakistan, from December 2006 to December 2013. Ninety three patients (167 therapies) with well differentiated thyroid cancer treated with different doses of I-131 as an in-patient were inducted. Fifty four patients were given only single I-131 therapy dose ranging from 70 mCi (2590 MBq) to 150 mCi (5550 MBq). Thirty nine patients were treated with multiple I-131 radioisotope therapy doses ranging from 80 mCi (2960 MBq) to 250 mCi (9250 MBq). T-test was applied on the sample data showed statistically significant difference between the two groups with p-value (p < 0.01) less than 0.05 taken as significant. There were 68 females and 25 males with an age range of 15 to 80 years. Mean age of the patients were 36 years. Among the 93 cases of first time Radio Active Iodine (RAI) therapy, 59 cases (63%) were discharged after 48 hours. Among 39 patients who received RAI therapy second time or more, most were discharged earlier after achieving acceptable discharge dose rate i.e 25 µSv/hour; 2 out of 39 (5%) were discharged after 48 hours. In 58% patients, given single I-131 therapy dose, majority of these were discharged after 48 hours without any major complications. For well differentiated thyroid cancer patients, rapid dose rate reduction is seen in patients receiving second or subsequent radioiodine (RAI) therapy, as compared to first time receiving RAI therapy.

Relationship to carcinogenesis of repetitive low-dose radiation exposure

International Nuclear Information System (INIS)

Ootsuyama, Akira

2016-01-01

We studied the carcinogenic effects caused by repetitive irradiation at a low dose, which has received attention in recent years, and examined the experimental methods used to evaluate radiation-induced carcinogenesis. For this experiment, we selected a mouse with as few autochthonous cancers as possible. Skin cancer was selected as the target for analysis, because it is a rare cancer in mice. Beta-rays were selected as the radiation source. The advantage of using beta-rays is weaker penetration power into tissues, thus protecting organs, such as the digestive and hematogenous organs. The benefit of our experimental method is that only skin cancer requires monitoring, and it is possible to perform long-term experiments. The back skin of mice was exposed repetitively to beta-rays three times a week until the occurrence of cancer or death, and the dose per exposure ranged from 0.5 to 11.8 Gy. With the high-dose range (2.5-11.8 Gy), the latency period and carcinogenic rate were almost the same in each experimental group. When the dose was reduced to 1-1.5 Gy, the latency period increased, but the carcinogenic rate remained. When the dose was further reduced to 0.5 Gy, skin cancer never happened, even though we continued irradiation until death of the last mouse in this group. The lifespan of 0.5 Gy group mice was the same as that of the controls. We showed that the 0.5 Gy dose did not cause cancer, even in mice exposed repetitively throughout their life span, and thus refer to 0.5 Gy as the threshold-like dose. (author)

Risk of Low Dose/Low Dose Rate Ionizing Radiation to Humans Symposium Annual Meeting of the Environmental Mutagen Society: Agenda and Abstracts

Energy Technology Data Exchange (ETDEWEB)

Veigl, Martina L. [Environmental Mutagen Society (EMS), Reston, VA (United States); Case Western Reserve Univ., Cleveland, OH (United States). Case Comprehensive Cancer Center; Morgan, William F. [Univ. of Maryland, College Park, MD (United States); Schwartz, Jeffrey L. [Univ. of Washington, Seattle, WA (United States)

2009-11-11

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. This report shows the agenda and abstracts for this symposium.

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

International Nuclear Information System (INIS)

Isobe, Y.; Sagisaka, M.; Garner, F.; Okita, T.

2007-01-01

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 -9 to 4x10 -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)

Comparison of high-dose-rate and low-dose-rate brachytherapy in the treatment of endometrial carcinoma

International Nuclear Information System (INIS)

Fayed, Alaa; Mutch, David G.; Rader, Janet S.; Gibb, Randall K.; Powell, Matthew A.; Wright, Jason D.; El Naqa, Issam; Zoberi, Imran; Grigsby, Perry W.

2007-01-01

Purpose: To compare the outcomes for endometrial carcinoma patients treated with either high-dose-rate (HDR) or low-dose-rate (LDR) brachytherapy. Methods and Materials: This study included 1,179 patients divided into LDR (1,004) and HDR groups (175). Patients with International Federation of Gynecology and Obstetrics (FIGO) surgical Stages I-III were included. All patients were treated with postoperative irradiation. In the LDR group, the postoperative dose applied to the vaginal cuff was 60-70 Gy surface doses to the vaginal mucosa. The HDR brachytherapy prescription was 6 fractions of 2 Gy each to a depth of 0.5 cm from the surface of the vaginal mucosa. Overall survival, disease-free survival, local control, and complications were endpoints. Results: For all stages combined, the overall survival, disease-free survival, and local control at 5 years in the LDR group were 70%, 69%, and 81%, respectively. For all stages combined, the overall survival, disease-free survival, and local control at 5 years in the HDR group were 68%, 62%, and 78%, respectively. There were no significant differences in early or late Grade III and IV complications in the HDR or LDR groups. Conclusion: Survival outcomes, pelvic tumor control, and Grade III and IV complications were not significantly different in the LDR brachytherapy group compared with the HDR group

Mechanism of suppressive effect of low dose radiation on cancer cell dissemination in mice

International Nuclear Information System (INIS)

Fu Haiqing; Li Xiuyi; Chen Yubing; Zhang Yingchun; Liu Shuzheng

1997-01-01

Influence of low dose radiation on immunity in C57 BL/6 mice injected with cancer cells was studied. In mice given 75 mGy WBI 24 h before injection of Lewis lung carcinoma cells or B 16 melanoma cells, the percentage of S-phase thymocytes and CD 3+ thymocytes, the splenic NK cell activity, IL-2 secretion and γIFN secretion were found to be potentiated 2∼8 day after irradiation in comparison with the sham-irradiation mice. The results suggest that low dose radiation might suppress cancer cell dissemination via the enhancement of immune reactivity

The health effects of low-dose ionizing radiation

International Nuclear Information System (INIS)

Dixit, A.N.; Dixit, Nishant

2012-01-01

It has been established by various researches, that high doses of ionizing radiation are harmful to health. There is substantial controversy regarding the effects of low doses of ionizing radiation despite the large amount of work carried out (both laboratory and epidemiological). Exposure to high levels of radiation can cause radiation injury, and these injuries can be relatively severe with sufficiently high radiation doses. Prolonged exposure to low levels of radiation may lead to cancer, although the nature of our response to very low radiation levels is not well known at this time. Many of our radiation safety regulations and procedures are designed to protect the health of those exposed to radiation occupationally or as members of the public. According to the linear no-threshold (LNT) hypothesis, any amount, however small, of radiation is potentially harmful, even down to zero levels. The threshold hypothesis, on the other hand, emphasizes that below a certain threshold level of radiation exposure, any deleterious effects are absent. At the same time, there are strong arguments, both experimental and epidemiological, which support the radiation hormesis (beneficial effects of low-level ionizing radiation). These effects cannot be anticipated by extrapolating from harmful effects noted at high doses. Evidence indicates an inverse relationship between chronic low-dose radiation levels and cancer incidence and/or mortality rates. Examples are drawn from: 1) state surveys for more than 200 million people in the United States; 2) state cancer hospitals for 200 million people in India; 3) 10,000 residents of Taipei who lived in cobalt-60 contaminated homes; 4) high-radiation areas of Ramsar, Iran; 5) 12 million person-years of exposed and carefully selected control nuclear workers; 6) almost 300,000 radon measurements of homes in the United States; and 7) non-smokers in high-radon areas of early Saxony, Germany. This evidence conforms to the hypothesis that

Evaluation of functioning of high dose rate brachytherapy at the Instituto Nacional do Cancer

International Nuclear Information System (INIS)

Guedes, Laura M.A.; Barreto, Rodrigo V.; Silva, Penha M.; Macedo, Afranio A.; Borges, Solange C.; Martinez, Valeria P.O.

2001-01-01

Quality control tests are very useful tools to assure the quality of patient's treatment. A daily control of the high dose rate micro selectron was performed based on the security parameters of the equipment and on the quickness of performance. The purpose of this report is to evaluate and to discuss the errors found during the first three years with the high dose rate brachytherapy, at the Instituto Nacional de Cancer. (author)

Effects of low dose irradiation on NK activity of normal individuals and patients with cancer

International Nuclear Information System (INIS)

Tian Hailin; Su Liaoyuan

1994-10-01

Effects of low dose irradiation on NK activity of lymphocytes and on K 562 cells were studied. The NK activity was determined by means of 3 H-TdR release assay. While 3 H-TdR incorporation was used to reflect functional changes of K 562 cells after low dose irradiation. 21 patients with cancer and 10 normal individuals were detected. The results indicated that the NK activity of lymphocytes in normal individuals increased significantly after 10 and 50 cGy γ-ray irradiation, while in patients with cancer the NK activity of lymphocytes increased only at the dose of 50 cGy irradiation. The increase of NK activity in normal individuals was higher than that in patients with cancer after same doses of irradiation. When K 562 cells were irradiated by 10 cGy γ-rays, the 3 H-TdR incorporation value increased. After exposed to over 50 cGy the stimulating effect disappeared

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

Energy Technology Data Exchange (ETDEWEB)

Sakai, Kazuo; Iwasaki, Toshiyasu; Hoshi, Yuko; Nomura, Takaharu; Ina, Yasuhiro; Tanooka, Hiroshi [Central Research Institute of Electric Power Industry, Low Dose Radiation Research Center, Komae, Tokyo (Japan)

2003-07-01

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 {sup 137}Cs 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)

In vitro and in vivo effects of low dose HTO contamination modulated by dose rate

International Nuclear Information System (INIS)

Petcu, I.; Savu, D.; Moisoi, N.; Koeteles, G.J.

1997-01-01

The experiment performed in vitro intended to examine whether an adaptive response could be elicited on lymphocytes by low-level contamination of whole blood with tritiated water and if the modification of the dose rate has any influence on it. Lymphocytes pre-exposed to 3 HOH (0.2 - 6.6 MBq/ml) and subsequently irradiated with I Gy γ-rays showed micronuclei frequency significantly lower (40% - 45%) than the expected member (sum of the yields induced by 3 HOH and γ-rays separately). The degree of the radioresistance induced by HTO pre-treatments became higher with decreasing dose-rate for a rather similar total adapting dose. In vivo, the aim of the study was to investigate if different dose rates are inducing modulation of the lipid peroxidation level and of the thymidine uptake in different tissues of animals contaminated by HTO ingestion. The total doses varied between 5 and 20 cGy and were delivered as chronic (100 days) or acute contamination (5 days). It was observed that only doses about 20 cGy caused a dose-rate dependent increase of the lipid peroxidation level in the tissues of small intestine, kidney and spleen. Both chronic and acute contamination did produce reduced incorporation of thymidine in the cells of bone marrow. The most effective decrease of thymidine uptake was induced by the acute contamination in the lower dose domain (approx. 5 cGy). Our hypothesis is that in this dose domain the modification of thymidine uptake could be due to changes at the level of membrane transport. (author)

Modified Exponential (MOE) Models: statistical Models for Risk Estimation of Low dose Rate Radiation

International Nuclear Information System (INIS)

Ogata, H.; Furukawa, C.; Kawakami, Y.; Magae, J.

2004-01-01

Simultaneous inclusion of dose and dose-rate is required to evaluate the risk of long term irradiation at low dose-rates, since biological responses to radiation are complex processes that depend both on irradiation time and total dose. Consequently, it is necessary to consider a model including cumulative dose,dose-rate and irradiation time to estimate quantitative dose-response relationship on the biological response to radiation. In this study, we measured micronucleus formation and (3H) thymidine uptake in U2OS, human osteosarcoma cell line, as indicators of biological response to gamma radiation. Cells were exposed to gamma ray in irradiation room bearing 50,000 Ci 60Co. After irradiation, they were cultured for 24h in the presence of cytochalasin B to block cytokinesis, and cytoplasm and nucleus were stained with DAPI and propidium iodide. The number of binuclear cells bearing a micronucleus was counted under a florescence microscope. For proliferation inhibition, cells were cultured for 48 h after the irradiation and (3h) thymidine was pulsed for 4h before harvesting. We statistically analyzed the data for quantitative evaluation of radiation risk at low dose/dose-rate. (Author)

Low-dose aspirin, non-steroidal anti-inflammatory drugs, selective COX-2 inhibitors and breast cancer recurrence

DEFF Research Database (Denmark)

Cronin-Fenton, Deirdre P; Heide-Jørgensen, Uffe; Ahern, Thomas P

2016-01-01

BACKGROUND: Aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and selective COX-2 inhibitors may improve outcomes in breast cancer patients. We investigated the association of aspirin, NSAIDs, and use of selective COX-2 inhibitors with breast cancer recurrence. METHODS: We identified incident...... stage I-III Danish breast cancer patients in the Danish Breast Cancer Cooperative Group registry, who were diagnosed during 1996-2008. Prescriptions for aspirin (>99% low-dose aspirin), NSAIDs, and selective COX-2 inhibitors were ascertained from the National Prescription Registry. Follow-up began....... RESULTS: We identified 34,188 breast cancer patients with 233,130 person-years of follow-up. Median follow-up was 7.1 years; 5,325 patients developed recurrent disease. Use of aspirin, NSAIDs, or selective COX-2 inhibitors was not associated with the rate of recurrence (HRadjusted aspirin = 1.0, 95% CI...

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.)

Late complications after high-dose-rate interstitial brachytherapy for tongue cancer

International Nuclear Information System (INIS)

Shimizutani, Kimishige; Inoue, Takehiro; Inoue, Toshihiko; Yoshioka, Yasuo; Teshima, Teruki; Kakimoto, Naoya; Murakami, Shumei; Furukawa, Souhei; Fuchihata, Hajime

2005-01-01

The objectives of this study was to analyze the treatment results and late complications of high-dose-rate (HDR) interstitial brachytherapy (ISBT) for early (T1N0, T2N0) mobile tongue cancer using the microSelectron-HDR. From January 1993 through April 2001, a total of 72 patients with early squamous cell carcinomas of the mobile tongue were treated with microSelectron-HDR interstitial brachytherapy at the Department of Radiology, Osaka University Hospital. Of the patients, 18% were treated with a combination of prior external radiation and HDR-ISBT, and 82% were treated with HDR-ISBT alone. For HDR-ISBT alone, all cases were treated with a total dose of 54 Gy/9 fractions every 5 days or 60 Gy/10 fractions every 8 days. In combined therapy with an external dose of 30 to 40 Gy, HDR-ISBT was given at a total dose of 42-50 Gy. The Brinkman and alcohol indexes were used to analyze the incidence of late complications after HDR-ISBT. The 2- and 5-year local control rates were 85% and 82%, respectively. Fifteen of 72 patients (21%) treated with HDR-ISBT had late complications. Ten of 15 patients (67%) with late complications had a Brinkman index exceeding 600. HDR-ISBT is useful and easily applied under local anesthesia to early or superficial lesions of the mobile tongue. However, we found an increase in late complications, such as soft-tissue ulcers and bone exposure, after irradiation of tongue cancer with 60 Gy HDR-ISBT in patients with a Brinkman index greater than 600. (author)

Dose rate effects of low-LET ionizing radiation on fish cells

Energy Technology Data Exchange (ETDEWEB)

Vo, Nguyen T.K. [McMaster University, Radiation Sciences Program, School of Graduate and Postdoctoral Studies, Hamilton, ON (Canada); Seymour, Colin B.; Mothersill, Carmel E. [McMaster University, Radiation Sciences Program, School of Graduate and Postdoctoral Studies, Hamilton, ON (Canada); McMaster University, Department of Biology, Hamilton, ON (Canada)

2017-11-15

Radiobiological responses of a highly clonogenic fish cell line, eelB, to low-LET ionizing radiation and effects of dose rates were studied. In acute exposure to 0.1-12 Gy of gamma rays, eelB's cell survival curve displayed a linear-quadratic (LQ) relationship. In the LQ model, α, β, and α/β ratio were 0.0024, 0.037, and 0.065, respectively; for the first time that these values were reported for fish cells. In the multi-target model, n, D{sub o}, and D{sub q} values were determined to be 4.42, 2.16, and 3.21 Gy, respectively, and were the smallest among fish cell lines being examined to date. The mitochondrial potential response to gamma radiation in eelB cells was at least biphasic: mitochondria hyperpolarized 2 h and then depolarized 5 h post-irradiation. Upon receiving gamma rays with a total dose of 5 Gy, dose rates (ranging between 83 and 1366 mGy/min) had different effects on the clonogenic survival but not the mitochondrial potential. The clonogenic survival was significantly higher at the lowest dose rate of 83 mGy/min than at the other higher dose rates. Upon continuous irradiation with beta particles from tritium at 0.5, 5, 50, and 500 mGy/day for 7 days, mitochondria significantly depolarized at the three higher dose rates. Clearly, dose rates had differential effects on the clonogenic survival of and mitochondrial membrane potential in fish cells. (orig.)

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)

Hazelton, W.D.; Curtis, S.B.; Moolgavkar, S.H.; Hutchinson, F.; Krewski, D.

2003-01-01

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

Life span and tumorigenesis in mice exposed to continuous low dose-rate gamma-rays

International Nuclear Information System (INIS)

Tanaka, Satoshi; Braga-Tanaka III, Ignacia; Takabatake, Takashi; Ichinohe, Kazuaki; Tanaka, Kimio; Matsumoto, Tsuneya; Sato, Fumiaki

2004-01-01

Two experiments were conducted to evaluate late biological effects of chronic low dose-rate radiation. 1: Late effects of chronic low dose-rate gamma-ray irradiation on SPF mice, using life span and pathological changes as parameters. Continuous irradiation for approximately 400 days was performed using 137 Cs 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 their natural death. Statistical analyses show that the life spans of the both sexes irradiated at 20 mGy/day (p<0.0001) and of females irradiated at 1 mGy/day (p<0.05) were significantly shorter than those of the control group. There was no evidence of lengthened life span in mice continuously exposed to very low dose-rates of gama-rays. Pathodological examinations showed that the most frequently observed lethal neoplasms in males were malignant lymphomas, liver, lung, and soft tissue neoplasms, whereas, in females, malignant lymphomas and soft tissue neoplasms were common. No significant difference in the causes of death and mortality rates between groups. Hematopoietic neoplasms (malignant lymphoma and myeloid leukemia), liver, lung and soft tissue neoplasms, showed a tendency to appear at a younger age in both sexes irradiated at 20 mGy/day. Experiment 2: effects on the progeny of chronic low dose-rate gamma-ray irradiated SPF mice: preliminary study. No significant difference was observed between non-irradiated group and irradiated group with regards to litter size, sex ratio and causes of death in F1 and F2 mice. (author)

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

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

International Nuclear Information System (INIS)

Kal, H.B.; Bijman, J.Th.

1981-01-01

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.)

Radiotherapy alone in the treatment of uterine cervix cancer with telecobalt and low-dose-rate brachytherapy: retrospective analysis of results and variables

International Nuclear Information System (INIS)

Ferrigno, Robson; Campos de Oliveira Faria, Sergio Luis; Weltman, Eduardo; Salvajoli, Joao Victor; Segreto, Roberto Araujo; Pastore, Ayrton; Nadalin, Wladimir

2003-01-01

Purpose: This retrospective analysis aims to report results and variables from patients with cervix cancer treated by radiation therapy alone with telecobalt and low-dose-rate brachytherapy (LDRB). Methods and Materials: Between September 1989 and September 1995, 190 patients with histologic diagnosis of cervix carcinoma were treated with telecobalt for external beam radiotherapy (EBR), followed by one or two insertions of LDRB. Stage distribution according to patients was the following: IB, 12; IIA, 4; IIB, 105; and IIIB, 69. Median dose of EBR at whole pelvis was 40 Gy, and median parametrial doses for Stages II and III patients were 50 Gy and 60 Gy, respectively. Median doses of LDRB at point A for patients treated with one and two insertions were 38 Gy and 50 Gy, respectively. Results: Median follow-up time was 70 months (range: 8-127 months). Overall survival, disease-free survival, and 5-year local control of patients at Stages I, II, and III were 83%, 78%, and 46%; 83%, 82%, and 49%; and 92%, 87%, and 58%, respectively. Overall incidence of late complications in the rectum, small bowel, and urinary tract was 15.3% (19/190), 4.2% (8/190), and 6.8% (13/190), respectively. The actuarial 5-year rectal, small bowel, and urinary incidence of late complications was 16.1%, 4.6%, and 7.6%, respectively. Clinical stage was the only significant variable for overall 5-year survival (p = 0.001), for disease-free survival (p=0.001), and for local control (p=0.001). Stage II patients more than 50 years old had better disease-free survival and local control at 5 years (p=0.004). None of the analyzed variables influenced the actuarial 5-year incidence of late complications. Conclusions: Results of this series suggest that the use of telecobalt equipment for EBR with doses up to 50 Gy at whole pelvis, prior to brachytherapy, is an acceptable technique for radiation therapy alone in the treatment of cervix cancer, especially in developing countries, including Brazil, where

Comparison of the result of radiation alone and radiation with daily low dose cisplatin in management of locally advanced cervical cancer

International Nuclear Information System (INIS)

Kim, Hun Jung; Kim, Woo Chul; Lee, Mee Jo; Kim, Chul Su; Song, Eun Seop; Loh, John J. K.

2004-01-01

An analysis was to compare the results of radiation alone with those of radiation with daily low dose cisplatin as a radiation sensitizer in locally advanced cervical cancer. A retrospective analysis of 59 patients diagnosed with locally advanced uterine cervix cancer between December 1996 and March 2001 was performed. Thirty one patients received radiation alone and 28 patients received daily low dose cisplatin, as a radiation sensitizer, and radiation therapy. The median follow-up period was 34 months, ranging from 2.5 to 73 months. The radiation therapy consisted of 4500 cGy external beam irradiation to the whole pelvis (midline block after 3060 cGy), a 900 ∼ 1,000 cGy boost to the involved parametrium and high dose-rate intracavitary brachytherapy (a total dose of 3,000 ∼ 3,500 cGy/500 cGy per fraction to point A, twice per week). In the chemoradiation group, 10 mg of daily intravenous cisplatin was given daily from the 1st day of radiation therapy to the 20th day of radiation therapy. According to the FIGO classification, the patients were subdivided into 51 (86.4%) and 8 (13.6%) stages IIB and stage IIIB, respectively. The overall 5 year survival rate was 65.65% and according to treatment modality were 56.75% and 73.42% in the radiation alone and chemoradiation groups, respectively (ρ = 0.180). The 5 year disease-free survival rates were 49.39% and 63.34% in the radiation alone and chemoradiation groups, respectively (ρ = 0.053). The 5 year locoregional control rates were 52.34% and 73.58% in the radiation alone and chemoradiation groups, respectively (ρ = 0.013). The 5 year distant disease-free survival rates were 59.29% and 81.46% in the radiation alone and chemoradiation groups, respectively (ρ = 0.477). Treatment related hematologic toxicity were prominent in the chemoradiation group. Leukopenia (≥ 3 grade) occurred in 3.2% and 28.5% of the radiation alone and chemoradiation groups, respectively (ρ = 0.02). There were no statistical differences

Comparison of the result of radiation alone and radiation with daily low dose cisplatin in management of locally advanced cervical cancer

Energy Technology Data Exchange (ETDEWEB)

Kim, Hun Jung; Kim, Woo Chul; Lee, Mee Jo; Kim, Chul Su; Song, Eun Seop; Loh, John J. K. [Inha University Medical College, Inchon (Korea, Republic of)

2004-09-15

An analysis was to compare the results of radiation alone with those of radiation with daily low dose cisplatin as a radiation sensitizer in locally advanced cervical cancer. A retrospective analysis of 59 patients diagnosed with locally advanced uterine cervix cancer between December 1996 and March 2001 was performed. Thirty one patients received radiation alone and 28 patients received daily low dose cisplatin, as a radiation sensitizer, and radiation therapy. The median follow-up period was 34 months, ranging from 2.5 to 73 months. The radiation therapy consisted of 4500 cGy external beam irradiation to the whole pelvis (midline block after 3060 cGy), a 900 {approx} 1,000 cGy boost to the involved parametrium and high dose-rate intracavitary brachytherapy (a total dose of 3,000 {approx} 3,500 cGy/500 cGy per fraction to point A, twice per week). In the chemoradiation group, 10 mg of daily intravenous cisplatin was given daily from the 1st day of radiation therapy to the 20th day of radiation therapy. According to the FIGO classification, the patients were subdivided into 51 (86.4%) and 8 (13.6%) stages IIB and stage IIIB, respectively. The overall 5 year survival rate was 65.65% and according to treatment modality were 56.75% and 73.42% in the radiation alone and chemoradiation groups, respectively ({rho} = 0.180). The 5 year disease-free survival rates were 49.39% and 63.34% in the radiation alone and chemoradiation groups, respectively ({rho} = 0.053). The 5 year locoregional control rates were 52.34% and 73.58% in the radiation alone and chemoradiation groups, respectively ({rho} = 0.013). The 5 year distant disease-free survival rates were 59.29% and 81.46% in the radiation alone and chemoradiation groups, respectively ({rho} = 0.477). Treatment related hematologic toxicity were prominent in the chemoradiation group. Leukopenia ({>=} 3 grade) occurred in 3.2% and 28.5% of the radiation alone and chemoradiation groups, respectively ({rho} = 0.02). There were

Low and very low doses, new recommendations?

International Nuclear Information System (INIS)

Foucher, N.

1999-01-01

The topic of the seminar organized by the world council of nuclear workers (WONUC) was the effects of low or very low doses on human health. Discussions centred round the linearity of the relation between dose and effect in the evaluation and management of the health hazard. The recommendations proposed by ICPR (international commission for radiological protection) are based on this linearity as a precaution. On the one hand it is remembered that low dose irradiation might be beneficial. It has been proved that the irradiation of the whole body is efficient in case of Hodgkin lymphoma. On the other hand it is remembered that doses as low as 10 mSv in utero have led to an excess of cancer in children. Studies based on experimentally radio-induced cancers have been carried out in Japan, China, Canada and France.Their results seem to be not consistent with the hypothesis of linearity. During the last decade a lot of work has been made but a conclusion is far to be reached, it is said that the American department of energy (DOE) has invited bids in 1999 to launch research programs in order to clarify the situation. (A.C.)

Comparison of one and two low dose rate brachytherapy insertions in the treatment of stage IIB cervix cancer with radiation therapy alone

International Nuclear Information System (INIS)

Ferrigno, Robson; Faria, S.L.C.O.

1996-01-01

Purpose/Objective: To compare one and two intracavitary brachytherapy with low dose rate in the management of stage IIB cervix cancer through a prospective and randomized trial. Materials and Methods: From September 1989 to December 1992, 81 patients with stage IIB cervix cancer were randomized in two arms according to the number of intracavitary brachytherapy insertion to be realized. Of these, 34 were treated by two intracavitary insertions (group A) and 47 by one insertion (group B). The external beam radiotherapy (EBRT) was realized through a Cobalt unit at whole pelvis with total dose of 40Gy in 20 fractions of 2,0Gy, in box arrangement, followed by parametrial complementation of 10Gy. The brachytherapy was realized right after the end of EBRT. The patients from group A were underwent to two insertions of 25Gy, calculated at point A, defined by the Manchester system. The interval between each insertions was 2 weeks. The patients from group B were underwent to one insertion of 40 Gy at point A. The average dose rate was 60cGy per hour at point A. Results: With the follow up ranging from 36 to 75 months and medium of 55 months, the disease free survival of the patients from group A was not statistically different of those from group B, 70,6% and 72,3% respectively (p=0,711). Local recurrence occurred in four patients from group A (11,7%) and in eight from group B (17%). Distant metastasis occurred in one patient from group A (2,9%) and in two from group B (4,2%). Three patients from group A (8,8%) and three from group B (6,4%) were lost to follow up and considered as dead. The causes of death among patients from group A were progression of local disease in four, distant metastasis in one, complicated diabetes mellitus in one and actinic intestinal complications in other one. The cause of deaths among patients from group B were progression of local disease in eight and distant metastasis in two. The grade I and II rectal complications rate was 5,9% and 6,3% at

Low-Dose Aspirin Reduces Breast Cancer Risk in Women with Diabetes: A Nationwide Retrospective Cohort Study in Taiwan.

Science.gov (United States)

Yang, Yi-Sun; Kornelius, Edy; Chiou, Jeng-Yuan; Lai, Yung-Rung; Lo, Shih-Chang; Peng, Chiung-Huei; Huang, Chien-Ning

2017-12-01

Low-dose aspirin is commonly used for preventing cardiovascular disease in people with diabetes, but its association with cancer remains controversial. This study used a nationwide population-based reimbursement database to investigate the relationship between low-dose aspirin use and breast cancer incidence in women with diabetes. This retrospective cohort study was conducted using data retrieved from the National Health Insurance Research Database in Taiwan from January 1, 1998 to December 31, 2011. Women diagnosed as having diabetes with low-dose aspirin use (75-165 mg daily) were identified as the study population, whereas those without low-dose aspirin use were selected as the comparison group. We analyzed 148,739 patients with diabetes. Their mean age (standard deviation) was 63.3 (12.8) years. A total of 27,378 patients were taking aspirin. Overall, the use of aspirin in patients with diabetes reduced the risk of breast cancer by 18% (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.71-0.94) after adjustment for potential confounders, namely age and comorbidities. Specifically, a cumulative dose of aspirin exceeding 88,900 mg was observed to reduce the risk of breast cancer by 47% (HR, 0.53, 95% CI, 0.43-0.67); however, low (aspirin did not reduce the risk of breast cancer. Our findings suggest that a cumulative aspirin dosage of more than 88,900 mg daily was associated with a reduced risk of breast cancer in women with diabetes. However, additional studies are necessary to confirm these findings.

Pre-operative combined 5-FU, low dose leucovorin, and sequential radiation therapy for unresectable rectal cancer

International Nuclear Information System (INIS)

Minsky, B.D.; Cohen, A.M.; Kemeny, N.; Enker, W.E.; Kelsen, D.P.; Schwartz, G.; Saltz, L.; Dougherty, J.; Frankel, J.; Wiseberg, J.

1993-01-01

The authors performed a Phase 1 trial to determine the maximum tolerated dose of combined pre-operative radiation (5040 cGy) and 2 cycles (bolus daily x 5) of 5-FU and low dose LV (20 mg/m2), followed by surgery and 10 cycles of post-operative LV/5-FU in patients with unresectable primary or recurrent rectal cancer. Twelve patients were entered. The initial dose of 5-FU was 325 mg/m2. 5-FU was to be escalated while the LV remained constant at 20 mg/m2. Chemotherapy began on day 1 and radiation on day 8. The post-operative chemotherapy was not dose escalated; 5-FU: 425 mg/m2 and LV: 20 mg/m2. The median follow-up was 14 months (7--16 months). Following pre-operative therapy, the resectability rate with negative margins was 91% and the pathologic complete response rate was 9%. For the combined modality segment (preoperative) the incidence of any grade 3+ toxicity was diarrhea: 17%, dysuria: 8%, mucositis: 8%, and erythema: 8%. The median nadir counts were WBC: 3.1, HGB: 8.8, and PLT: 153000. The maximum tolerated dose of 5-FU for pre-operative combined LV/5-FU/RT was 325 mg/m2 with no escalation possible. Therefore, the recommended dose was less than 325 mg/m2. Since adequate doses of 5-FU to treat systemic disease could not be delivered until at least 3 months (cycle 3) following the start of therapy, the authors do not recommend that this 5-FU, low dose LV, and sequential radiation therapy regimen be used as presently designed. However, given the 91% resectability rate they remain encouraged with this approach. 31 refs., 1 fig., 2 tabs

Estimation of outdoor and indoor effective dose and excess lifetime cancer risk from Gamma dose rates in Gonabad, Iran

Energy Technology Data Exchange (ETDEWEB)

Jafaria, R.; Zarghania, H.; Mohammadia, A., E-mail: rvzreza@gmail.com [Paramedical faculty, Birjand University of Medical Sciences, Birjand (Iran, Islamic Republic of)

2017-07-01

Background gamma irradiation in the indoor and outdoor environments is a major concern in the world. The study area was Gonabad city. Three stations and buildings for background radiation measurement of outdoor and indoor were randomly selected and the Geiger-Muller detector (X5C plus) was used. All dose rates on display of survey meter were recorded and mean of all data in each station and buildings was computed and taken as measured dose rate of that particular station. The average dose rates of background radiation were 84.2 nSv/h for outdoor and 108.6 nSv/h for indoor, maximum and minimum dose rates were 88.9 nSv/h and 77.7 nSv/h for outdoor measurements and 125.4 nSv/h and 94.1 nSv/h for indoor measurements, respectively. Results show that the annual effective dose is 0.64 mSv, which compare to global level of the annual effective dose 0.48 mSv is high. Estimated excess lifetime cancer risk was 2.24×10{sup -3} , indicated that it is large compared to the world average value of 0.25×10{sup -3}. (author)

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

International Nuclear Information System (INIS)

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 ( 1 / 100 to 1 / 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

Low-level radiation: The cancer controversy

International Nuclear Information System (INIS)

Stewart, A.M.

1990-01-01

According to early studies it would be safe to assume there are no late effects of radiation apart from cancer, no lasting selective effects of the early deaths of A-bomb victims, and no cancer risk at low dose levels (below 20 rad). The nuclear establishment had good reason to believe that a potentially dangerous situation had been completely defused, and optimists were still free to regard daily exposure to background radiation as a benign influence. For several years the only indication to the contrary was the Oxford survey's finding on prenatal X-rays. But today we face the possibility that there are other late effects of radiation besides cancer; and the possibility that the selection effects of the two nuclear explosions are still reflected in death rates among survivors and are the reason why no cancer effects have been found at low dose levels. If these possibilities are confirmed, we may one day realize how fortunate it was that the Oxford survey findings put a brake on the enthusiasms of nuclear power advocates. Otherwise, we might never have pressed for direct studies of the effects of low doses of radiation. 7 refs

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

International Nuclear Information System (INIS)

Suzuki, Keiji; Mitsutake, Norisato; Yamashita, Shunichi

2012-01-01

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)

Dose-Escalated Robotic SBRT for Stage I-II Prostate Cancer

Directory of Open Access Journals (Sweden)

Robert eMeier

2015-04-01

Full Text Available Abstract: Stereotactic body radiotherapy (SBRT is the precise external delivery of very high-dose radiotherapy to targets in the body, with treatment completed in one to five fractions. SBRT should be an ideal approach for organ-confined prostate cancer because (I dose escalation should yield improved rates of cancer control; (II the unique radiobiology of prostate cancer favors hypofractionation and (III the conformal nature of SBRT minimizes high-dose radiation delivery to immediately adjacent organs, potentially reducing complications. This approach is also more convenient for patients, and is cheaper than intensity modulated radiotherapy (IMRT. Several external beam platforms are capable of delivering SBRT for early-stage prostate cancer, although most of the mature reported series have employed a robotic non-coplanar platform (i.e., CyberKnife. Several large studies report 5-year biochemical relapse rates which compare favorably to IMRT. Rates of late GU toxicity are similar to those seen with IMRT, and rates of late rectal toxicity may be less than with IMRT and low dose rate (LDR brachytherapy. Patient-reported quality of life (QOL outcomes appear similar to IMRT in the urinary domain. Bowel QOL may be less adversely affected by SBRT than with other radiation modalities. After five years of follow-up, SBRT delivered on a robotic platform is yielding outcomes at least as favorable as IMRT, and may be considered appropriate therapy for stage I-II prostate cancer.

Bladder/lung cancer mortality in Blackfoot-disease (BFD)-endemic area villages with low (water arsenic levels--an exploration of the dose-response Poisson analysis.

Science.gov (United States)

Lamm, Steven H; Robbins, Shayhan A; Zhou, Chao; Lu, Jun; Chen, Rusan; Feinleib, Manning

2013-02-01

To examine the analytic role of arsenic exposure on cancer mortality among the low-dose (well water arsenic level villages in the Blackfoot-disease (BFD) endemic area of southwest Taiwan and with respect to the southwest regional data. Poisson analyses of the bladder and lung cancer deaths with respect to arsenic exposure (μg/kg/day) for the low-dose (villages with exposure defined by the village median, mean, or maximum and with or without regional data. Use of the village median well water arsenic level as the exposure metric introduced misclassification bias by including villages with levels >500 μg/L, but use of the village mean or the maximum did not. Poisson analyses using mean or maximum arsenic levels showed significant negative cancer slope factors for models of bladder cancers and of bladder and lung cancers combined. Inclusion of the southwest Taiwan regional data did not change the findings when the model contained an explanatory variable for non-arsenic differences. A positive slope could only be generated by including the comparison population as a separate data point with the assumption of zero arsenic exposure from drinking water and eliminating the variable for non-arsenic risk factors. The cancer rates are higher among the low-dose (villages in the BFD area than in the southwest Taiwan region. However, among the low-dose villages in the BFD area, cancer risks suggest a negative association with well water arsenic levels. Positive differences from regional data seem attributable to non-arsenic ecological factors. Copyright © 2012 Elsevier Inc. All rights reserved.

Physical mechanisms contributing to enhanced bipolar gain degradation at low dose rates

International Nuclear Information System (INIS)

Fleetwood, D.M.; Reber, R.A. Jr.; Winokur, P.S.; Kosier, S.L.; Schrimpf, R.D.; Wei, A.; DeLaus, M.; Combs, W.E.; Pease, R.L.

1994-01-01

The authors have performed capacitance-voltage (C-V) and thermally-stimulated-current (TSC) measurements on non-radiation-hard MOS capacitors simulating screen oxides of modern bipolar technologies. For 0-V irradiation of ∼25 C, the net trapped-positive-charge density (N ox ) inferred from midgap C-V shifts is ∼25--40% greater for low-dose-rate ( 2 )/s) than for high-dose-rate (> 100 rad(SiO 2 )/s) exposure. Device modeling shows that such a difference in screen-oxide N ox is enough to account for the enhanced low-rate gain degradation often observed in bipolar devices, due to the ∼ exp(N ox 2 ) dependence of the excess base current. At the higher rates, TSC measurements reveal a ∼10% decrease in trapped-hole density over low rates. Also, at high rates, up to ∼2.5-times as many trapped holes are compensated by electrons in border traps than at low rates for these devices and irradiation conditions. Both the reduction in trapped-hole density and increased charge compensation reduce the high-rate midgap shift. A physical model is developed which suggests that both effects are caused by time-dependent space charge in the bulk of these soft oxides associated with slowly transporting and/or metastably trapped holes (e.g., in Eδ' centers). On the basis of this model, bipolar transistors and screen-oxide capacitors were irradiated at 60 C at 200 rad(SiO 2 )/s in a successful effort to match low-rate damage. these surprising results provide insight into enhanced low-rate bipolar gain degradation and suggest potentially promising new approaches to bipolar and BiCMOS hardness assurance for space applications

Effects of low dose rate irradiation on life span prolongation of human premature-aging syndrome model mice

International Nuclear Information System (INIS)

Nomura, Takaharu

2006-01-01

We previously showed that Type II diabetes model mice prolonged of their life span by life long low dose rate irradiation. We also found that antioxidant function in variety tissues of some strain of mice were enhancement after low dose/low dose rate irradiation. The prolongation of life span might depend on certain damaged level of reactive oxygen species. We thought the effect of the prolongation was due to the enhancement of the antioxidant activities after irradiation. We investigated whether the enhancement of antioxidant activities after low dose rate irradiation had an effect on life span prolongation. Four-week-old female human premature-aging syndrome model mice, kl/kl (klotho) mice, which the life span of this model mouse is about 65 days, were irradiated with gamma rays at 0.35, 0.70 or 1.2 mGy/hr. The 0.70 mGy/hr-irradiated group remarkably effected on the prolongation of their life span. Some mice of the group were extremely survived for about and more 100 days. Antioxidant activities in the irradiated groups were enhancement by low dose rate irradiation, however the dependence of the dose rates were not clearly difference. These results suggest that the antioxidant activities in this model mouse were enhanced by the low dose rate irradiation, and may make it possible to prolong the life span of this mouse. (author)

Exposures at low doses and biological effects of ionizing radiations

International Nuclear Information System (INIS)

Masse, R.

2000-01-01

Everyone is exposed to radiation from natural, man-made and medical sources, and world-wide average annual exposure can be set at about 3.5 mSv. Exposure to natural sources is characterised by very large fluctuations, not excluding a range covering two orders of magnitude. Millions of inhabitants are continuously exposed to external doses as high as 10 mSv per year, delivered at low dose rates, very few workers are exposed above the legal limit of 50 mSv/year, and referring to accidental exposures, only 5% of the 116 000 people evacuated following the Chernobyl disaster encountered doses above 100 mSv. Epidemiological survey of accidentally, occupationally or medically exposed groups have revealed radio-induced cancers, mostly following high dose-rate exposure levels, only above 100 mSv. Risk coefficients were derived from these studies and projected into linear models of risk (linear non-threshold hypothesis: LNT), for the purpose of risk management following exposures at low doses and low dose-rates. The legitimacy of this approach has been questioned, by the Academy of sciences and the Academy of medicine in France, arguing: that LNT was not supported by Hiroshima and Nagasaki studies when neutron dose was revisited; that linear modelling failed to explain why so many site-related cancers were obviously nonlinearly related to the dose, and especially when theory predicted they ought to be; that no evidence could be found of radio-induced cancers related to natural exposures or to low exposures at the work place; and that no evidence of genetic disease could be shown from any of the exposed groups. Arguments were provided from cellular and molecular biology helping to solve this issue, all resulting in dismissing the LNT hypothesis. These arguments included: different mechanisms of DNA repair at high and low dose rate; influence of inducible stress responses modifying mutagenesis and lethality; bystander effects allowing it to be considered that individual

Measurement bias dependence of enhanced bipolar gain degradation at low dose rates

International Nuclear Information System (INIS)

Witczak, S.C.; Lacoe, R.C.; Mayer, D.C.; Fleetwood, D.M.

1998-03-01

Oxide trapped charge, field effects from emitter metallization, and high level injection phenomena moderate enhanced gain degradation of lateral pnp transistors at low dose rates. Hardness assurance tests at elevated irradiation temperatures require larger design margins for low power measurement biases

Effects of low doses of ionizing radiation; Effets des faibles doses de rayonnements ionisants

Energy Technology Data Exchange (ETDEWEB)

Masse, R. [Office de Protection contre les Rayonnements Ionisants, 78 - le Vesinet (France)

2006-07-01

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.)

Bone cancer from radium: canine dose response explains data for mice and humans

International Nuclear Information System (INIS)

Raabe, O.G.; Book, S.A.; Parks, N.J.

1980-01-01

Analysis of lifetime studies of 243 beagles with skeletal burdens of radium-226 shows that the distribution of bone cancers clusters about a linear function of the logarithms of radiation dose rate to the skeleton and time from exposure until death. Similar relations displaced by species-dependent response ratios also provide satisfactory descriptions of the reported data on deaths from primary bone cancers in people and mice exposed to radium-226. The median cumulative doses (or times) leading to death from bone tumors are 2.9 times larger for dogs than for mice and 3.6 times larger for people than for dogs. These response ratios are well correlated with the normal life expectancies. The cumulative radiation dose required to give significant risk of bone cancer is found to be much less at lower dose rates than at higher rates, but the time required for the tumors to be manifested is longer. At low dose rates, this time exceeds the normal life-span and appears as a practical threshold, which for bone cancer is estimated to occur at an average cumulative radiation dose to the skeleton of about 50 to 110 rads for the three species

Radiation-induced attenuation in polarization maintaining fibers: low dose rate response, stress, and materials effects

International Nuclear Information System (INIS)

Gingerich, M.E.; Friebele, E.J.; Hickey, S.J.; Brambani, L.A.; Onstott, J.R.

1989-01-01

The loss induced in polarization-maintaining (PM) fibers by low dose rate <0.01 Gy/h, where 1 Gy = 100 rads(Si) radiation exposure has been found to vary from <0.4 to ∼6 dB/km-10 Gy, depending on the wavelength of measurement and the fiber. Correlations have been established between low dose rate response and the ''permanent'' induced loss determined by fitting the recovery of the induced loss following high dose rate exposure to nth-order kinetics. Using this technique, both 0.85- and 1.3-μm PM fibers have been found which show virtually no permanent incremental loss and would therefore appear to be resistant to low dose rate radiation environments. The asymmetric stress inherent in PM fibers has been shown to reduce the permanent induced loss, while the recovery of the radiation-induced attenuation was found to be enhanced in fibers with Ge-F-doped silica clads

Cytogenetic biodosimetry and dose-rate effect after radioiodine therapy for thyroid cancer

Energy Technology Data Exchange (ETDEWEB)

Khvostunov, Igor K. [Russian Ministry of Health Care, A.F. Tsyb Medical Radiological Research Center, Branch of the National Medical Research Radiological Centre, Obninsk, Kaluga Region (Russian Federation); Nagasaki University, Department of Radiation Molecular Epidemiology, Atomic Bomb Disease Institute, Nagasaki (Japan); Saenko, Vladimir A.; Yamashita, Shunichi [Nagasaki University, Department of Radiation Molecular Epidemiology, Atomic Bomb Disease Institute, Nagasaki (Japan); Krylov, Valeri; Rodichev, Andrei [Russian Ministry of Health Care, A.F. Tsyb Medical Radiological Research Center, Branch of the National Medical Research Radiological Centre, Obninsk, Kaluga Region (Russian Federation)

2017-08-15

This study set out to investigate chromosomal damage in peripheral blood lymphocytes of thyroid cancer patients receiving {sup 131}I for thyroid remnant ablation or treatment of metastatic disease. The observed chromosomal damage was further converted to the estimates of whole-body dose to project the adverse side effects. Chromosomal aberration analysis was performed in 24 patients treated for the first time or after multiple courses. Blood samples were collected before treatment and 3 or 4 days after administration of 2-4 GBq of {sup 131}I. Both conventional cytogenetic and chromosome 2, 4 and 12 painting assays were used. To account for dose-rate effect, a dose-protraction factor was applied to calculate the whole-body dose. The mean dose was 0.62 Gy (95% CI: 0.44-0.77 Gy) in the subgroup of patients treated one time and 0.67 Gy (95% CI: 0.03-1.00 Gy) in re-treated patients. These dose estimates are about 1.7-fold higher than those disregarding the effect of exposure duration. In re-treated patients, the neglected dose-rate effect can result in underestimation of the cumulative whole-body dose by the factor ranging from 2.6 to 6.8. Elevated frequency of chromosomal aberrations observed in re-treated patients before radioiodine therapy allows estimation of a cumulative dose received from all previous treatments. (orig.)

Scintillator performance at low dose rates and low temperatures for the CMS High Granularity Calorimeter for HL-LHC

CERN Document Server

Ricci-Tam, Francesca

2018-01-01

The High Luminosity LHC (HL-LHC) will integrate 10 times more luminosity than the LHC, posing significant challenges for radiation tolerance, especially for forward calorimetry, and highlights the issue for future colliders. As part of its HL-LHC upgrade program, the CMS collaboration is designing a High Granularity Calorimeter to replace the existing endcap calorimeters. The upgrade includes both electromagnetic and hadronic components, with the latter using a mixture of silicon sensors (in the highest radiation regions at high pseudorapidity) and scintillator as its active components. The scintillator will nevertheless receive large doses accumulated at low dose rates, and will have to operate at low temperature - around -30 degrees Celsius. We discuss measurements of scintillator radiation tolerance, from in-situ measurements from the current CMS endcap calorimeters, and from measurements at low temperature and low dose-rate at gamma sources in the laboratory.

Dependence of total dose response of bipolar linear microcircuits on applied dose rate

International Nuclear Information System (INIS)

McClure, S.; Will, W.; Perry, G.; Pease, R.L.

1994-01-01

The effect of dose rate on the total dose radiation hardness of three commercial bipolar linear microcircuits is investigated. Total dose tests of linear bipolar microcircuits show larger degradation at 0.167 rad/s than at 90 rad/s even after the high dose rate test is followed by a room temperature plus a 100 C anneal. No systematic correlation could be found for degradation at low dose rate versus high dose rate and anneal. Comparison of the low dose rate with the high dose rate anneal data indicates that MIL-STD-883, method 1019.4 is not a worst-case test method when applied to bipolar microcircuits for low dose rate space applications

Cellular sensitivity and low dose-rate recovery in Fanconi anaemia fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Burnet, N.G.; Wurm, R.; Tait, D.M.; Peacock, J.H. (Institute of Cancer Research, Sutton (United Kingdom). Surrey Branch Royal Marsden Hospital, Sutton (United Kingdom))

1994-06-01

Fanconi anaemia (FA) is a rare inherited condition characterized by developmental abnormalities and progressive bone marrow failure, which requires bone marrow transplantation for successful treatment. This involves the use of alkylating agents and total body or thoraco-abdominal irradiation. Both chemical clastogens and irradiation cause increased chromosome damage in FA cells compared with controls. In some studies FA fibroblasts have been found to be more radiosensitive than normal. From these data it has been inferred that patients with FA might be more sensitive than normal to radiotherapy. However, increased radiosensitivity of FA fibroblasts has not been a uniform finding. The radiosensitivity of fibroblasts from two FA patients was studied at high and low dose-rate (LDR), and their sensitivity compared with normal strains. Both FA strains fell at the sensitive end of the range, but both demonstrated marked dose-rate sparing, with D[sub 0.01] recovery factors of 1.23 and 1.27, similar to the normal strains. These recovery factors are inconsistent with the suggestion that FA patients are recovery deficient. The data indicate that at least some FA strains are capable of LDR recovery, and imply that these patients would probably have a clinical benefit from fractionated or low dose-rate total body irradiation. (Author).

Cellular sensitivity and low dose-rate recovery in Fanconi anaemia fibroblasts

International Nuclear Information System (INIS)

Burnet, N.G.; Wurm, R.; Tait, D.M.; Peacock, J.H.

1994-01-01

Fanconi anaemia (FA) is a rare inherited condition characterized by developmental abnormalities and progressive bone marrow failure, which requires bone marrow transplantation for successful treatment. This involves the use of alkylating agents and total body or thoraco-abdominal irradiation. Both chemical clastogens and irradiation cause increased chromosome damage in FA cells compared with controls. In some studies FA fibroblasts have been found to be more radiosensitive than normal. From these data it has been inferred that patients with FA might be more sensitive than normal to radiotherapy. However, increased radiosensitivity of FA fibroblasts has not been a uniform finding. The radiosensitivity of fibroblasts from two FA patients was studied at high and low dose-rate (LDR), and their sensitivity compared with normal strains. Both FA strains fell at the sensitive end of the range, but both demonstrated marked dose-rate sparing, with D 0.01 recovery factors of 1.23 and 1.27, similar to the normal strains. These recovery factors are inconsistent with the suggestion that FA patients are recovery deficient. The data indicate that at least some FA strains are capable of LDR recovery, and imply that these patients would probably have a clinical benefit from fractionated or low dose-rate total body irradiation. (Author)

Comparison of traditional low-dose-rate to optimized and nonoptimized high-dose-rate tandem and ovoid dosimetry

International Nuclear Information System (INIS)

Decker, William E.; Erickson, Beth; Albano, Katherine; Gillin, Michael

2001-01-01

Purpose: Few dose specification guidelines exist when attempting to perform high-dose-rate (HDR) dosimetry. The purpose of this study was to model low-dose-rate (LDR) dosimetry, using parameters common in HDR dosimetry, to achieve the 'pear-shape' dose distribution achieved with LDR tandem and ovoid applications. Methods and Materials: Radiographs of Fletcher-Suit LDR applicators and Nucletron 'Fletcher-like' HDR applicators were taken with the applicators in an idealized geometry. Traditional Fletcher loadings of 3M Cs-137 sources and the Theratronics Planning System were used for LDR dosimetry. HDR dosimetry was performed using the Nucletron Microselectron HDR UPS V11.22 with an Ir-192 source. Dose optimization points were initially located along a line 2 cm lateral to the tandem, beginning at the tandem tip at 0.5-cm intervals, ending at the sail, and optimized to 100% of the point A dose. A single dose optimization point was also placed laterally from the center of each ovoid equal to the radius of the ovoid (ovoid surface dose). For purposes of comparison, dose was also calculated for points A and B, and a point located 1 cm superior to the tandem tip in the plane of the tandem, (point F). Four- and 6-cm tandem lengths and 2.0-, 2.5-, and 3.0-cm ovoid diameters were used for this study. Based on initial findings, dose optimization schemes were developed to best approximate LDR dosimetry. Finally, radiographs were obtained of HDR applications in two patients. These radiographs were used to compare the optimization schemes with 'nonoptimized' treatment plans. Results: Calculated doses for points A and B were similar for LDR, optimized HDR, and nonoptimized HDR. The optimization scheme that used tapered dose points at the tandem tip and optimized a single ovoid surface point on each ovoid to 170% of point A resulted in a good approximation of LDR dosimetry. Nonoptimized HDR resulted in higher doses at point F, the bladder, and at points lateral to the tandem tip

Facility for gamma irradiations of cultured cells at low dose rates: design, physical characteristics and functioning

International Nuclear Information System (INIS)

Esposito, Giuseppe; Anello, Pasquale; Pecchia, Ilaria; Tabocchini, Maria Antonella; Campa, Alessandro

2016-01-01

We describe a low dose/dose rate gamma irradiation facility (called LIBIS) for in vitro biological systems, for the exposure, inside a CO_2 cell culture incubator, of cells at a dose rate ranging from few μGy/h to some tens of mGy/h. Three different "1"3"7Cs sources are used, depending on the desired dose rate. The sample is irradiated with a gamma ray beam with a dose rate uniformity of at least 92% and a percentage of primary 662 keV photons greater than 80%. LIBIS complies with high safety standards. - Highlights: • A gamma irradiation facility for chronic exposures of cells was set up at the Istituto Superiore di Sanità. • The dose rate uniformity and the percentage of primary 662 keV photons on the sample are greater than 92% and 80%, respectively. • The GEANT4 code was used to design the facility. • Good agreement between simulation and experimental dose rate measurements has been obtained. • The facility will allow to safely investigate different issues about low dose rate effects on cultured cells.

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

NARCIS (Netherlands)

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

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

International Nuclear Information System (INIS)

Walstam, Rune

1980-01-01

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.)

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.

Lifetime radiation risks from low-dose rate radionuclides in beagles

International Nuclear Information System (INIS)

Goldman, M.; Rosenblatt, L.S.

1985-01-01

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 90 Sr [low linear energy transfer (LET)] in their diets (D-dogs) through adulthood. A second group (R-dogs) was given fractionated doses of 225 Ra (high LET) as young adults. A third group of 44 was given a single injection of 90 Sr 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 90 Sr, 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

Brachytherapy optimization using radiobiological-based planning for high dose rate and permanent implants for prostate cancer treatment

Science.gov (United States)

Seeley, Kaelyn; Cunha, J. Adam; Hong, Tae Min

2017-01-01

We discuss an improvement in brachytherapy--a prostate cancer treatment method that directly places radioactive seeds inside target cancerous regions--by optimizing the current standard for delivering dose. Currently, the seeds' spatiotemporal placement is determined by optimizing the dose based on a set of physical, user-defined constraints. One particular approach is the ``inverse planning'' algorithms that allow for tightly fit isodose lines around the target volumes in order to reduce dose to the patient's organs at risk. However, these dose distributions are typically computed assuming the same biological response to radiation for different types of tissues. In our work, we consider radiobiological parameters to account for the differences in the individual sensitivities and responses to radiation for tissues surrounding the target. Among the benefits are a more accurate toxicity rate and more coverage to target regions for planning high-dose-rate treatments as well as permanent implants.

Dose Rate Effects in Linear Bipolar Transistors

Science.gov (United States)

Johnston, Allan; Swimm, Randall; Harris, R. D.; Thorbourn, Dennis

2011-01-01

Dose rate effects are examined in linear bipolar transistors at high and low dose rates. At high dose rates, approximately 50% of the damage anneals at room temperature, even though these devices exhibit enhanced damage at low dose rate. The unexpected recovery of a significant fraction of the damage after tests at high dose rate requires changes in existing test standards. Tests at low temperature with a one-second radiation pulse width show that damage continues to increase for more than 3000 seconds afterward, consistent with predictions of the CTRW model for oxides with a thickness of 700 nm.

Low dose epidemiology

International Nuclear Information System (INIS)

Tirmarche, M.; Hubert, P.

1992-01-01

Actually, epidemiological studies have to establish if the assessment of cancer risk can be verified at low chronic radiation doses. The population surveillance must be very long, the side effects and cancers of such radiation appearing much later. In France, this epidemiological study on nuclear workers have been decided recently. Before describing the experiment and french projects in epidemiology of nuclear workers, the authors present the main english and american studies

Preoperative 5-FU, low-dose leucovorin, and radiation therapy for locally advanced and unresectable rectal cancer

International Nuclear Information System (INIS)

Minsky, Bruce D.; Cohen, Alfred M.; Enker, Warren E.; Saltz, Leonard; Guillem, Jose G.; Paty, Philip B.; Kelsen, David P.; Kemeny, Nancy; Ilson, David; Bass, Joanne; Conti, John

1997-01-01

Purpose: We report the local control and survival of two Phase I dose escalation trials of combined preoperative 5-fluorouracil (5-FU), low-dose leucovorin (LV), and radiation therapy followed by postoperative LV/5-FU for the treatment of patients with locally advanced and unresectable rectal cancer. Methods and Materials: A total of 36 patients (30 primary and 6 recurrent) received two monthly cycles of LV/5-FU (bolus daily x 5). Radiation therapy (50.40 Gy) began on day 1 in the 25 patients who received concurrent treatment and on day 8 in the 11 patients who received sequential treatment. Postoperatively, patients received a median of four monthly cycles of LV/5-FU. Results: The resectability rate with negative margins was 97%. The complete response rate was 11% pathologic and 14% clinical for a total of 25%. The 4-year actuarial disease-free survival was 67% and the overall survival was 76%. The crude local failure rate was 14% and the 4-year actuarial local failure rate was 30%. Crude local failure was lower in the four patients who had a pathologic complete response (0%) compared with those who either did not have a pathologic complete response (16%) or who had a clinical complete response (20%). Conclusion: Our preliminary data with the low-dose LV regimen reveal encouraging downstaging, local control, and survival rates. Additional follow-up is needed to determine the 5-year results. The benefit of downstaging on local control is greatest in patients who achieve a pathologic complete response

Results of radiation therapy for uterine cervical cancer using high dose rate remote after loading system

International Nuclear Information System (INIS)

Ogawa, Yoshihiro; Nemoto, Kenji

2003-01-01

In Japan, radiotherapy with high dose rate remote after loading system (HDR-RALS) for intracavitary brachytherapy is the standard treatment for more than 30 years. This report showed the usefulness of HDR-RALS for uterine cervical cancer. From 1980 through 1999, 442 patients with uterine cervical cancers (stage I: 66, stage II: 161, stage III: 165, stage IV: 50) were treated. Radiotherapy was performed both external teletherapy and HDR-RALS. Overall survival rate at 5 years was 60.2%. The 5-year actuarial incidence of all complications was 16.4%. The 5-year actuarial incidence of all complications in cases treated with the sum doses of whole pelvic irradiation (without central shield) and RALS up to 49 Gy, 50 to 59 Gy or larger doses were 7.5%, 11.0% and 25.2%, respectively. Radiation therapy using HDR-RALS was very effective. While the dose of whole pelvic irradiation was increased, the actuarial incidence of all complications was increased. (author)

Adjuvant high dose rate vaginal cuff brachytherapy for early stage endometrial cancer

International Nuclear Information System (INIS)

Tannehill, S.P.; Petereit, D.G.; Schink, J.C.; Grosen, E.A.; Hartenbach, E.M.; Thomadsen, B.R.; Buchler, D.A.

1997-01-01

Objective: To determine the efficacy and complications of adjuvant high dose rate (HDR) vaginal cuff brachytherapy (VCB) in patients (pts) with low risk endometrial carcinoma. Materials and Methods: Since 1989, 154 patients were treated with outpatient adjuvant VCB for low risk endometrial cancer (Stage IA-14%, Stage IB-82%). Four percent of patients with stage IC disease were treated with VCB only because of medical contraindications to pelvic radiation. Patients had the following histologic grades: 53% grade 1, 40% grade 2, 5% grade 3 and 3% unknown (99%-adenocarcinoma, <1% papillary serous histology). Seventy-three percent of patients had their surgery (TAH-BSO) performed at an outside institution with minimal surgical assessment of the lymph nodes. At a median of 6 weeks after surgery, patients were treated with 2 HDR VCB insertions delivered 1 week apart. Ovoids were placed at the vaginal apex to deliver 16.2 Gy per fraction to the vaginal surface (LDR equivalent of 60 Gy at 100 cGy/h) under conscious outpatient sedation. All clinical endpoints were calculated using the Kaplan Meier method. Complications were scored using the RTOG 5-tiered system. Results: The median time in the brachytherapy suite was 60 minutes with no acute complications observed. With a median follow-up of 33 months (3-79 months), the 4-year overall and disease-free survival were 93% and 96% respectively. Five patients (3%) recurred: 2 intra-abdominally, 1 with lung metastases, and 2 in the pelvic lymph nodes. There were no vaginal cuff recurrences. The single patient with an isolated pelvic sidewall recurrence was salvaged with pelvic RT. Six patients developed a small area of asymptomatic necrosis at the vaginal cuff, which spontaneously healed at a median time of 4 months. There were no grade 3 or greater late tissue toxicities. No patient experienced significant vaginal stenosis, with 20% of the patients experiencing mild fibrosis of the vaginal apex. Conclusions: Adjuvant HDR VCB in 2

High dose rate brachytherapy for medically inoperable stage I endometrial cancer

Energy Technology Data Exchange (ETDEWEB)

Petereit, Daniel G; Sarkaria, Jann N; Schink, Julian; Springman, Scott R; Kinsella, Timothy J; Buchler, Dolores A

1995-07-01

Purpose/Objective: To determine the efficacy of high dose rate (HDR) brachytherapy in patients with medically inoperable endometrial cancer clinically confined to the corpus. Materials and Methods: Forty-two patients with endometrial cancer and an intact uterus have been treated since 1989 with HDR brachytherapy. Twenty-six patients with medically inoperable Stage I disease were treated with radiation alone and form the basis of this study. Obesity was assessed using the body mass index (BMI kg/m{sup 2}) scale. Patients with a BMI above 28 were considered obese and those above 35 morbidly obese, per standard anesthesia guidelines. Brachytherapy was delivered in 5 HDR insertions, 1 week apart, without any external beam radiation. The following doses were delivered per insertion: 5.7 Gy to point S, 7.0 Gy to point W, 8.2 Gy to the vaginal surface and 9.2 Gy to point M. Point M represents the conventional point A dose, while points S and W are myometrial points. A single tandem with either ovoids or cylinders was placed, unless the uterine cavity would accommodate 2 tandems. All treatments were outpatient using intravenous fentanyl and midazolam for sedation. Pelvic ultrasound was commonly used at the time of brachytherapy to verify tandem placement. Three year clinical endpoints were calculated using the Kaplan Meier method. Results: The median follow-up for the study cohort was 21 months with follow-up greater than 36 months in 11 patients. Seventeen of the 26 patients were inoperable due to morbid obesity (median weight and BMI; 316 lbs and 55 kg/m{sup 2}, respectively); the other patients had poor cardiopulmonary reserve {+-} obesity. The median age, KPS (Karnofsky Performance Status), weight, ASA (American Society of Anesthesiologists' Physical Class System) and BMI were 63 yrs, 80%, 285 lbs, 3 and 49 kg/m{sup 2}, respectively. Two patients with an ASA of 3 and 4 died from acute cardio-pulmonary events within 30 days of the last insertion, emphasizing the need

High dose rate brachytherapy for medically inoperable stage I endometrial cancer

International Nuclear Information System (INIS)

Petereit, Daniel G.; Sarkaria, Jann N.; Schink, Julian; Springman, Scott R.; Kinsella, Timothy J.; Buchler, Dolores A.

1995-01-01

Purpose/Objective: To determine the efficacy of high dose rate (HDR) brachytherapy in patients with medically inoperable endometrial cancer clinically confined to the corpus. Materials and Methods: Forty-two patients with endometrial cancer and an intact uterus have been treated since 1989 with HDR brachytherapy. Twenty-six patients with medically inoperable Stage I disease were treated with radiation alone and form the basis of this study. Obesity was assessed using the body mass index (BMI kg/m 2 ) scale. Patients with a BMI above 28 were considered obese and those above 35 morbidly obese, per standard anesthesia guidelines. Brachytherapy was delivered in 5 HDR insertions, 1 week apart, without any external beam radiation. The following doses were delivered per insertion: 5.7 Gy to point S, 7.0 Gy to point W, 8.2 Gy to the vaginal surface and 9.2 Gy to point M. Point M represents the conventional point A dose, while points S and W are myometrial points. A single tandem with either ovoids or cylinders was placed, unless the uterine cavity would accommodate 2 tandems. All treatments were outpatient using intravenous fentanyl and midazolam for sedation. Pelvic ultrasound was commonly used at the time of brachytherapy to verify tandem placement. Three year clinical endpoints were calculated using the Kaplan Meier method. Results: The median follow-up for the study cohort was 21 months with follow-up greater than 36 months in 11 patients. Seventeen of the 26 patients were inoperable due to morbid obesity (median weight and BMI; 316 lbs and 55 kg/m 2 , respectively); the other patients had poor cardiopulmonary reserve ± obesity. The median age, KPS (Karnofsky Performance Status), weight, ASA (American Society of Anesthesiologists' Physical Class System) and BMI were 63 yrs, 80%, 285 lbs, 3 and 49 kg/m 2 , respectively. Two patients with an ASA of 3 and 4 died from acute cardio-pulmonary events within 30 days of the last insertion, emphasizing the need for accurate pre

Correlations of post-implant regional dosimetric parameters at 24 hours and one month, with clinical results of low-dose-rate brachytherapy for localized prostate cancer

Directory of Open Access Journals (Sweden)

Eiichiro Okazaki

2017-12-01

Full Text Available Purpose : To evaluate the correlations of post-implant regional dosimetrics at 24 hours (24 h and 1 month after implant procedures, with clinical outcomes of low-dose-rate (LDR brachytherapy for localized prostate cancer. Material and methods : Between January 2008 and December 2014, 130 consecutive patients treated for localized prostate cancer, receiving definitive iodine-125 ( 125 I brachytherapy treatment were retrospectively analyzed. All patients underwent post-implant CT imaging for dosimetric analysis at 24 h and 1 month after implantation procedure. Prostate contours were divided into quadrants: anterior-superior (ASQ, posterior-superior (PSQ, anterior-inferior (AIQ, and posterior-inferior (PIQ. Predictive factors and cut-off values of biochemical failure-free survival (BFFS and toxicities of LDR brachytherapy were analyzed. Results : The median follow-up time was 69.5 months. Seven patients (5.4% had biochemical failure. The 3-year and 5-year BFFS rates were 96.7% and 93.1%, respectively. On multivariate analysis, prostate-specific antigen and Gleason score were significant prognostic factors for biochemical failure. D 90 (the minimal dose received by 90% of the volume of PSQ and PIQ at 24 h, and D 90 of PSQ at 1 month were also significant factors. The cut-off values of PSQ D 90 were 145 Gy at 24 h and 160 Gy at 1 month. D 90 of the whole prostate was not significant at 24 h and at 1 month. D 90 of PSQ at 1 month was a significant factor for rectal hemorrhage. Conclusions : Post-implant D 90 of PSQ is significantly associated with BFFS for localized prostate cancer not only at 1 month, but also at 24 hours. D 90 of PSQ at 1 month is also a significant factor for rectal hemorrhage.

Low-level laser therapy for the prevention of low salivary flow rate after radiotherapy and chemotherapy in patients with head and neck cancer

International Nuclear Information System (INIS)

Gonnelli, Fernanda Aurora Stabile; Palma, Luiz Felipe; Giordani, Adelmo Jose; Dias, Rodrigo Souza; Segreto, Roberto Araujo; Segreto, Helena Regina Comodo; Deboni, Aline Lima Silva

2016-01-01

Objective: to determine whether low-level laser therapy can prevent salivary hypofunction after radiotherapy and chemotherapy in head and neck cancer patients. Materials and methods: ee evaluated 23 head and neck cancer patients, of whom 13 received laser therapy and 10 received clinical care only. An InGaAlP laser was used intra-orally (at 660 nm and 40 mW) at a mean dose of 10.0 J/cm 2 and extra-orally (at 780 nm and 15 mW) at a mean dose of 3.7 J/cm 2 , three times per week, on alternate days. Stimulated and unstimulated sialometry tests were performed before the first radiotherapy and chemotherapy sessions (NO) and at 30 days after the end of treatment (N30). Results: At N30, the mean salivary flow rates were significantly higher among the laser therapy patients than among the patients who received clinical care only, in the stimulated and unstimulated sialometry tests (p = 0.0131 and p = 0.0143, respectively). Conclusion: low-level laser therapy, administered concomitantly with radiotherapy and chemotherapy, appears to mitigate treatment induced salivary hypofunction in patients with head and neck cancer. (author)

Low-level laser therapy for the prevention of low salivary flow rate after radiotherapy and chemotherapy in patients with head and neck cancer

Energy Technology Data Exchange (ETDEWEB)

Gonnelli, Fernanda Aurora Stabile [Faculdades Metropolitanas Unidas (FMU), Sao Paulo, SP (Brazil); Palma, Luiz Felipe; Giordani, Adelmo Jose; Dias, Rodrigo Souza; Segreto, Roberto Araujo; Segreto, Helena Regina Comodo [Universidade Federal de Sao Paulo (EPM/UNIFESP), Sao Paulo, SP (Brazil). Escola Paulista de Medicina; Deboni, Aline Lima Silva

2016-03-15

Objective: to determine whether low-level laser therapy can prevent salivary hypofunction after radiotherapy and chemotherapy in head and neck cancer patients. Materials and methods: ee evaluated 23 head and neck cancer patients, of whom 13 received laser therapy and 10 received clinical care only. An InGaAlP laser was used intra-orally (at 660 nm and 40 mW) at a mean dose of 10.0 J/cm{sup 2} and extra-orally (at 780 nm and 15 mW) at a mean dose of 3.7 J/cm{sup 2} , three times per week, on alternate days. Stimulated and unstimulated sialometry tests were performed before the first radiotherapy and chemotherapy sessions (NO) and at 30 days after the end of treatment (N30). Results: At N30, the mean salivary flow rates were significantly higher among the laser therapy patients than among the patients who received clinical care only, in the stimulated and unstimulated sialometry tests (p = 0.0131 and p = 0.0143, respectively). Conclusion: low-level laser therapy, administered concomitantly with radiotherapy and chemotherapy, appears to mitigate treatment induced salivary hypofunction in patients with head and neck cancer. (author)

Low dose intravesical heparin as prophylaxis against recurrent noninvasive (stage Ta) bladder cancer

DEFF Research Database (Denmark)

Bitsch, M; Hermann, G G; Andersen, J P

1990-01-01

A controlled randomized clinical trial was conducted to examine the efficacy of topical low dose heparin (0.125 gm./l., 25,000 units per l.) as prophylaxis against recurrent noninvasive (stage Ta) transitional cell bladder cancer. Transurethral tumor resection was done with irrigation fluid conta...

TU-H-207A-08: Estimating Radiation Dose From Low-Dose Lung Cancer Screening CT Exams Using Tube Current Modulation

International Nuclear Information System (INIS)

Hardy, A; Bostani, M; McMillan, K; Zankl, M; Cagnon, C; McNitt-Gray, M

2016-01-01

Purpose: The purpose of this work is to estimate effective and lung doses from a low-dose lung cancer screening CT protocol using Tube Current Modulation (TCM) across patient models of different sizes. Methods: Monte Carlo simulation methods were used to estimate effective and lung doses from a low-dose lung cancer screening protocol for a 64-slice CT (Sensation 64, Siemens Healthcare) that used TCM. Scanning parameters were from the AAPM protocols. Ten GSF voxelized patient models were used and had all radiosensitive organs identified to facilitate estimating both organ and effective doses. Predicted TCM schemes for each patient model were generated using a validated method wherein tissue attenuation characteristics and scanner limitations were used to determine the TCM output as a function of table position and source angle. The water equivalent diameter (WED) was determined by estimating the attenuation at the center of the scan volume for each patient model. Monte Carlo simulations were performed using the unique TCM scheme for each patient model. Lung doses were tallied and effective doses were estimated using ICRP 103 tissue weighting factors. Effective and lung dose values were normalized by scanspecific 32 cm CTDIvol values based upon the average tube current across the entire simulated scan. Absolute and normalized doses were reported as a function of WED for each patient. Results: For all ten patients modeled, the effective dose using TCM protocols was below 1.5 mSv. Smaller sized patient models experienced lower absolute doses compared to larger sized patients. Normalized effective and lung doses showed some dependence on patient size (R2 = 0.77 and 0.78, respectively). Conclusion: Effective doses for a low-dose lung screening protocol using TCM were below 1.5 mSv for all patient models used in this study. Institutional research agreement, Siemens Healthcare; Past recipient, research grant support, Siemens Healthcare; Consultant, Toshiba America Medical

TU-H-207A-08: Estimating Radiation Dose From Low-Dose Lung Cancer Screening CT Exams Using Tube Current Modulation

Energy Technology Data Exchange (ETDEWEB)

Hardy, A; Bostani, M [University of California, Los Angeles, Los Angeles, CA (United States); McMillan, K [Mayo Clinic, Rochester, MN (United States); Zankl, M [Helmholtz Zentrum Munchen, Neuherberg (Germany); Cagnon, C [UCLA Medical Center, Los Angeles, CA (United States); McNitt-Gray, M [UCLA School of Medicine, Los Angeles, CA (United States)

2016-06-15

Purpose: The purpose of this work is to estimate effective and lung doses from a low-dose lung cancer screening CT protocol using Tube Current Modulation (TCM) across patient models of different sizes. Methods: Monte Carlo simulation methods were used to estimate effective and lung doses from a low-dose lung cancer screening protocol for a 64-slice CT (Sensation 64, Siemens Healthcare) that used TCM. Scanning parameters were from the AAPM protocols. Ten GSF voxelized patient models were used and had all radiosensitive organs identified to facilitate estimating both organ and effective doses. Predicted TCM schemes for each patient model were generated using a validated method wherein tissue attenuation characteristics and scanner limitations were used to determine the TCM output as a function of table position and source angle. The water equivalent diameter (WED) was determined by estimating the attenuation at the center of the scan volume for each patient model. Monte Carlo simulations were performed using the unique TCM scheme for each patient model. Lung doses were tallied and effective doses were estimated using ICRP 103 tissue weighting factors. Effective and lung dose values were normalized by scanspecific 32 cm CTDIvol values based upon the average tube current across the entire simulated scan. Absolute and normalized doses were reported as a function of WED for each patient. Results: For all ten patients modeled, the effective dose using TCM protocols was below 1.5 mSv. Smaller sized patient models experienced lower absolute doses compared to larger sized patients. Normalized effective and lung doses showed some dependence on patient size (R2 = 0.77 and 0.78, respectively). Conclusion: Effective doses for a low-dose lung screening protocol using TCM were below 1.5 mSv for all patient models used in this study. Institutional research agreement, Siemens Healthcare; Past recipient, research grant support, Siemens Healthcare; Consultant, Toshiba America Medical

Radiation proctitis after the high dose rate brachytherapy for prostate cancer

International Nuclear Information System (INIS)

Kitano, Masashi; Katsumata, Tomoe; Satoh, Takefumi

2006-01-01

We reviewed the medical records of 12 patients treated for rectal bleeding after high-dose rate brachytherapy for prostate cancer. All patients developed grade 2 proctitis according to the Common Terminology Criteria for Adverse Events (CTCAC) and no patients needed blood transfusion. The patients were treated with argon plasma coagulation (APC) and/or steroid suppositories. The bleeding stopped or improved in 11 patients. Although re-bleeding was noticed in 7 patients the same treatment was effective in 5 patients. (author)

Clinical and dosimetric results of three-dimensional image-guided and pulsed dose rate curie-therapy in locally advanced cervical cancers

International Nuclear Information System (INIS)

Mazeron, R.; Gilmore, J.; Dumas, I.; Abrous-Anane, S.; Haberer, S.; Verstraet, R.; Champoudry, J.; Martinetti, F.; Morice, P.; Haie-Meller, C.

2011-01-01

The authors report a review of data obtained between 2004 and 2009 on 130 women who had been treated by optimized pulsed-rate curie-therapy for a locally advanced cervical cancer. Results are discussed in terms of cancer stage, treatment (with or without concomitant chemotherapy), planning method (MRI, scanography), delivered doses in the clinical target volumes, surgery, relapse occurrence and localizations, global survival probability, local control, undesirable side effects, occurrence of intestine or urinary toxicity. It appears that the association of a concomitant chemo-radiotherapy and optimized curie-therapy results in a good local-regional control and a low toxicity level. Short communication

A Phase II Study of Fixed-Dose Rate Gemcitabine Plus Low-Dose Cisplatin Followed by Consolidative Chemoradiation for Locally Advanced Pancreatic Cancer

International Nuclear Information System (INIS)

Ko, Andrew H.; Quivey, Jeanne M.; Venook, Alan P.; Bergsland, Emily K.; Dito, Elizabeth R.N.; Schillinger, Brian R.N.; Tempero, Margaret A.

2007-01-01

Purpose: The optimal strategy for treating locally advanced pancreatic cancer remains controversial, including the respective roles and timing of chemotherapy and radiation. We conducted a Phase II nonrandomized trial to evaluate sequential chemotherapy followed by chemoradiation in this patient population. Methods and Materials: Chemotherapy naive patients with locally advanced pancreatic adenocarcinoma were treated with fixed-dose rate gemcitabine (1,000 mg/m 2 at 10 mg/m 2 /min) plus cisplatin 20 mg/m 2 on Days 1 and 15 of a 28-day cycle. Those without evidence of extrapancreatic metastases after six cycles of chemotherapy received radiation (5,040 cGy over 28 fractions) with concurrent capecitabine (800 mg/m 2 orally twice daily on the day of radiation) as a radiosensitizer. Results: A total of 25 patients were enrolled with a median follow-up time of 656 days. Twelve patients (48%) successfully received all six cycles of chemotherapy plus chemoradiation. Eight patients (32%) progressed during chemotherapy, including 7 with extrapancreatic metastases. Grade 3/4 hematologic toxicities were uncommon. Two patients sustained myocardial infarctions during chemotherapy, and 4 were hospitalized for infectious complications, although none in the setting of neutropenia. Median time to progression was 10.5 months and median survival was 13.5 months, with an estimated 1-year survival rate of 62%. Patients receiving all components of therapy had a median survival of 17.0 months. Conclusions: A strategy of initial fixed-dose rate gemcitabine-based chemotherapy, followed by chemoradiation, shows promising efficacy for treatment of locally advanced disease. A substantial proportion of patients will be identified early on as having extrapancreatic disease and spared the potential toxicities associated with radiation

Cancer incidence among a cohort of subjects exposed to low-dose rate chronic radiation exposure in utero and after birth in the techa riverbank villages

International Nuclear Information System (INIS)

Ostroumova, E.V.; Akleyev, A.V.; Akleyev, A.V.; Hall, P.

2003-01-01

As a result of releases of liquid radioactive waste by the Mayak Production Association (PA) into the Techa River since 1949 till 1956 the population of the Riverside villages was exposed to a protracted effect of combined (external and internal) radiation. The 1-st-generation offspring of exposed residents born on 01.01.1950 and later were exposed both in utero and after birth. In all, 46 cancer cases, including 4 cases of leukemia, were registered among the study cohort members numbering 7,890 subjects born in the Techa Riverside villages in the Chelyabinsk province over the period since 1950 till 1998. No significant differences were noted in cancer incidence rates between men and women. Cancer incidence in the offspring's cohort was by 30-35% higher compared with the unexposed population of the USSR and Russia, the differences, however, are statistically insignificant. No influence of the parents total gonadal dose on cancer development in offspring was observed. The positive dose-effect dependence of cancer incidence on both antenatal and postnatal exposure was traced

Dose rate effect from the relationship between ICRU rectal dose and local control rate in intracavitary radiotherapy for carcinoma of the uterine cervix. Six fraction HDR and three-fraction LDR in three weeks

International Nuclear Information System (INIS)

Jingu, Kenichi; Akita, Yuzou; Ohmagari, Jyunichi

2001-01-01

The dose rate effect, low dose rate radiotherapy (LDR)/high dose rate radiotherapy (HDR), was calculated using the isoeffect ICRU rectal dose by intracavitary radiotherapy (ICRT) for uterine cervix cancer. The subjects analyzed consisted of 78 LDR and 74 HDR patients whose ICRU rectal dose could be calculated and whose local control as stage II/III cases could be evaluated. The point A dose in ICRT was 45-55 Gy/3 fractions/3 weeks for LDR and 30 Gy/6 fractions/3 weeks for HDR. The dose effect relationships associated with local control at each whole pelvis external radiation dose were calculated using the double integration method and Probit analysis, and the 50% and 90% local control ICRU rectal doses were calculated from this relationship. Finally, the dose rate effect LDR/HDR was determined from 50% and 90% local control doses. The dose rate effect calculated from the 50% local control dose was 1.24 and that from the 90% local control dose was 1.14. (author)

Intestinal morphological effect of brachytherapy of low rate of dose, administrated in therapeutic form and its clinical manifestations in uterine cervix tumors

International Nuclear Information System (INIS)

Mendoza, Carmen; Contreras, Manuel

2005-01-01

Brachytherapy is effective to eradicate cancer in the cervix, in order to obtain the control of disease we use high dose with vesical and rectum toxicity. The objective is to investigate if brachytherapy by itself is the cause of intestinal damage, to know in addition if the intensity of the clinic manifestations is in direct relation to the given radiation dose and this gets worse when it is received in several applications. Hypothesis: The intensity of the radiation with brachytherapy of low rate of dose is proportional to the degree of clinical manifestations and morphologic damage of the intestine. A prospective analysis was made inpatients with cancer of cervix from september 2000 to june 2004. Each patient who enters to the department of brachytherapy of the hospital must be done laboratory examination that includes plaque and coagulation test before being accepted. We use the clinical card and a table in order to register data concerning teletherapy, implants of brachytherapy of low rate of dose, symptoms of intestinal toxicity and details of colonoscopia. Subsequent to the hospitable discharge the patient is sent to gastroenterology for clinical evaluation and to realize colonoscopia. From september 2000 to june 2004, 540 patients entered, 80 patients (15%) displayed intestinal manifestations, all received teletherapy and brachytherapy, nobody else received brachytherapy in exclusive form and only one patient (0.1%) received the total of the dose in 2 applications. The equipment of teletherapy Primus with energy of 6 and 18 Mv and implants of brachytherapy Manchester were used (70/55 patients). 79 (98%) patients received dose between 85-75 Gy in one single application, 58 (72%) received the total of the dose to the tumor, 21 (26%) in vaginal mucosa. Discussion: Brachytherapy is the cause of the damages in the intestinal mucosa. (The author)

Analysis of complications in a prospective randomized trial comparing two brachytherapy low dose rates in cervical carcinoma

Energy Technology Data Exchange (ETDEWEB)

NONE

1994-07-30

The analysis of complications in a prospective randomized trial comparing two preoperative brachytherapy low-dose rates in early stage cervical cancer is presented. The objective of this trial was to determine the benefits, if any, of the higher-dose rate within the therapeutic aresenal for this patient population, in terms of survival, local control, and complications. Overall survival, 85% at 2 years and local control, 93% at 2 years, were similarly distributed between the two groups. Regardless of their nature and severity, 139 and 175 complications were observed among 63% and 75% of patients, in the 0.4 and 0.8 Gy/h dose rate groups respectively. Gynecologic and urinary complications were the most frequent (38% and 28% of all complications), followed by vascular (15%), digestive (10%), nervous (5%), and cutaneous (5%). A total of 14 and 17 severe complications (Grade 3) were observed in 7% and 13% of patients, respectively in the 0.4 and 0.8 Gy/h dose rate groups (p = 0.12) Nonparametric survival methods used to compare the time to the first complication did not show a significant difference between the two groups: 62% and 72% at 2 years (p = 0.27). When the first complication and its evolution were considered (early complications), the prevalence of complications was not significantly different between the two groups: 28% vs. 34% at 2 years (p = 0.31). In this prospective trial, patients were regularly followed-up and complications of varying nature and severity were observed in succession during follow-up. When successive complications and their evolution were taken into account, the prevalence of complications was significantly greater in the higher-dose rate group: 30% vs 45% at 2 years (p = 0.03). The results of this trial showed that long-term effects of treatment, when represented by prevalence of complications over time, were more frequent in the higher dose rate group. 33 refs., 3 figs., 5 tabs.

Low dose irradiation facilitates hepatocellular carcinoma genesis involving HULC.

Science.gov (United States)

Li, Yuan; Ge, Chang; Feng, Guoxing; Xiao, Huiwen; Dong, Jiali; Zhu, Changchun; Jiang, Mian; Cui, Ming; Fan, Saijun

2018-03-24

Irradiation exposure positive correlates with tumor formation, such as breast cancer and lung cancer. However, whether low dose irradiation induces hepatocarcinogenesis and the underlying mechanism remain poorly defined. In the present study, we reported that low dose irradiation facilitated the proliferation of hepatocyte through up-regulating HULC in vitro and in vivo. Low dose irradiation exposure elevated HULC expression level in hepatocyte. Deletion of heightened HULC erased the cells growth accelerated following low dose irradiation exposure. CDKN1, the neighbor gene of HULC, was down-regulated by overexpression of HULC following low dose irradiation exposure via complementary base pairing, resulting in promoting cell cycle process. Thus, our findings provide new insights into the mechanism of low dose irradiation-induced hepatocarcinogenesis through HULC/CDKN1 signaling, and shed light on the potential risk of low dose irradiation for the development of hepatocellular carcinoma in pre-clinical settings. © 2018 Wiley Periodicals, Inc.

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)

Burlakova, E.B.; Erokhin, V.N.

2001-01-01

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 [ru

Critical reevaluation of the dose-response relationships for carcinogenic effects of low-level ionizing radiation

International Nuclear Information System (INIS)

Upton, Arthur C.

2002-01-01

In recent decades, it has been customary, for radiation protection purposes, to assume that the overall risk of radiation- included cancer increases as a linear-nonthreshold function of the dose. The existing data do not exclude the existence of a threshold, however, and the dose-response relationship is known to vary depending on the type of cancer in question, the dose, dose rate and LET of the radiation, the age, sex and physiological state of the exposed individuals, and other variables, including the potential influence of adaptive responses and bystander effects at low doses. In light of advancing knowledge, therefore, the dose-response relationship for carcinogenic effects of low-level radiation has been reevaluated periodically by the National Council on Radiation Protection and Measurements, the International Commission of Radiological Protection, the United Nations Scientific Committee on the Effects of Atomic Radiation, the U.S. National Academy of Sciences Committee on the Effects of Atomic Radiation, the U.S. National Academy of Sciences, and other organizations. The most recent such reviews have generally found the weight of evidence to suggest that lesions which are precursors to cancer (i.e., mutations and chromosome aberrations), and certain types of cancer as well, may increase in frequency linearly aberrations), and certain types of cancer as well, may increase in frequency linearly with the dose in the low-dose domain. On this basis, it is concluded that no alternative dose-response model for the carcinogenic effects of low-level radiation is ore plausible than the linear-nonthreshold model, although other dose-response relationships cannot be excluded. (author)

Exposure to low-dose radiation and the risk of breast cancer among women with a familial or genetic predisposition: a meta-analysis

International Nuclear Information System (INIS)

Jansen-van der Weide, Marijke C.; Greuter, Marcel J.W.; Pijnappel, Ruud M.; Jansen, Liesbeth; Oosterwijk, Jan C.; Bock, Geertruida H. de

2010-01-01

Women with familial or genetic aggregation of breast cancer are offered screening outside the population screening programme. However, the possible benefit of mammography screening could be reduced due to the risk of radiation-induced tumours. A systematic search was conducted addressing the question of how low-dose radiation exposure affects breast cancer risk among high-risk women. A systematic search was conducted for articles addressing breast cancer, mammography screening, radiation and high-risk women. Effects of low-dose radiation on breast cancer risk were presented in terms of pooled odds ratios (OR). Of 127 articles found, 7 were selected for the meta-analysis. Pooled OR revealed an increased risk of breast cancer among high-risk women due to low-dose radiation exposure (OR = 1.3, 95% CI: 0.9- 1.8). Exposure before age 20 (OR = 2.0, 95% CI: 1.3-3.1) or a mean of ≥5 exposures (OR = 1.8, 95% CI: 1.1-3.0) was significantly associated with a higher radiation-induced breast cancer risk. Low-dose radiation increases breast cancer risk among high-risk women. When using low-dose radiation among high-risk women, a careful approach is needed, by means of reducing repeated exposure, avoidance of exposure at a younger age and using non-ionising screening techniques. (orig.)

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

International Nuclear Information System (INIS)

Pershenkov, V.S.; Cherepko, S.V.; Maslov, V.B.; Belyakov, V.V.; Sogoyan, A.V.; Ulimov, N.; Emelianov, V.V.

1999-01-01

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)

The status of low dose rate and future of high dose rate Cf-252 brachytherapy

International Nuclear Information System (INIS)

Rivard, M.J.; Wierzbicki, J.G.; Van den Heuvel, F.; Chuba, P.J.; Fontanesi, J.

1997-12-01

This work describes the current status of the US low dose rate (LDR) Cf-252 brachytherapy program. The efforts undertaken towards development of a high dose rate (HDR) remotely after loaded Cf-252 source, which can accommodate 1 mg or greater Cf-252, are also described. This HDR effort is a collaboration between Oak Ridge National Laboratory (ORNL), commercial remote after loader manufactures, the Gershenson Radiation Oncology Center (ROC), and Wayne State University. To achieve this goal, several advances in isotope chemistry and source preparation at ORNL must be achieved to yield a specific material source loading of greater than or equal 1 mg Cf-252 per mm3. Development work with both radioactive and non-radioactive stand-ins for Cf-252 have indicated the feasibility of fabricating such sources. As a result, the decreased catheter diameter and computer controlled source placement will permit additional sites (e.g. brain, breast, prostate, lung, parotid, etc.) to be treated effectively with Cf-252 sources. Additional work at the Radiochemical Engineering and Development Center (REDC) remains in source fabrication, after loader modification, and safe design. The current LDR Cf-252 Treatment Suite at the ROC is shielded and licensed to hold up to 1 mg of Cf-252. This was designed to maintain cumulative personnel exposure, both external to the room and in direct isotope handling, at less than 20 microSv/hr. However, cumulative exposure may be greatly decreased if a Cf-252 HDR unit is employed which would eliminate direct isotope handling and decrease treatment times from tilde 3 hours to an expected range of 3 to 15 minutes. Such a Cf-252 HDR source will also demonstrate improved dose distributions over current LDR treatments due to the ability to step the point-like source throughout the target volume and weight the dwell time accordingly

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)

Chen, H.H.; Jia, R.F.; Yu, L.; Zhao, M.J.; Shao, C.L.; Cheng, W.Y.

2008-01-01

Purpose: To investigate bystander effects of low-dose-rate (LDR) 125 I 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 125 I 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 125 I 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 125 I 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

Validity of the linear no-threshold theory of radiation carcinogenesis at low doses

International Nuclear Information System (INIS)

Cohen, B.L.

1999-01-01

A great deal is known about the cancer risk of high radiation doses from studies of Japanese A-bomb survivors, patients exposed for medical therapy, occupational exposures, etc. But the vast majority of important applications deal with much lower doses, usually accumulated at much lower dose rates, referred to as 'low-level radiation' (LLR). Conventionally, the cancer risk from LLR has been estimated by the use of linear no-threshold theory (LNT). For example, it is assumed that the cancer risk from 0 01 Sr (100 mrem) of dose is 0 01 times the risk from 1 Sv (100 rem). In recent years, the former risk estimates have often been reduced by a 'dose and dose rate reduction factor', which is taken to be a factor of 2. But otherwise, the LNT is frequently used for doses as low as one hundred-thousandth of those for which there is direct evidence of cancer induction by radiation. It is the origin of the commonly used expression 'no level of radiation is safe' and the consequent public fear of LLR. The importance of this use of the LNT can not be exaggerated and is used in many applications in the nuclear industry. The LNT paradigm has also been carried over to chemical carcinogens, leading to severe restrictions on use of cleaning fluids, organic chemicals, pesticides, etc. If the LNT were abandoned for radiation, it would probably also be abandoned for chemical carcinogens. In view of these facts, it is important to consider the validity of the LNT. That is the purpose of this paper. (author)

Dose-response characteristics of low- and intermediate-risk prostate cancer treated with external beam radiotherapy

International Nuclear Information System (INIS)

Cheung, Rex; Tucker, Susan L.; Lee, Andrew K.; Crevoisier, Renaud de; Dong Lei; Kamat, Ashish; Pisters, Louis; Kuban, Deborah

2005-01-01

Purpose: In this era of dose escalation, the benefit of higher radiation doses for low-risk prostate cancer remains controversial. For intermediate-risk patients, the data suggest a benefit from higher doses. However, the quantitative characterization of the benefit for these patients is scarce. We investigated the radiation dose-response relation of tumor control probability in low-risk and intermediate-risk prostate cancer patients treated with radiotherapy alone. We also investigated the differences in the dose-response characteristics using the American Society for Therapeutic Radiology and Oncology (ASTRO) definition vs. an alternative biochemical failure definition. Methods and materials: This study included 235 low-risk and 387 intermediate-risk prostate cancer patients treated with external beam radiotherapy without hormonal treatment between 1987 and 1998. The low-risk patients had 1992 American Joint Committee on Cancer Stage T2a or less disease as determined by digital rectal examination, prostate-specific antigen (PSA) levels of ≤10 ng/mL, and biopsy Gleason scores of ≤6. The intermediate-risk patients had one or more of the following: Stage T2b-c, PSA level of ≤20 ng/mL but >10 ng/mL, and/or Gleason score of 7, without any of the following high-risk features: Stage T3 or greater, PSA >20 ng/mL, or Gleason score ≥8. The logistic models were fitted to the data at varying points after treatment, and the dose-response parameters were estimated. We used two biochemical failure definitions. The ASTRO PSA failure was defined as three consecutive PSA rises, with the time to failure backdated to the mid-point between the nadir and the first rise. The second biochemical failure definition used was a PSA rise of ≥2 ng/mL above the current PSA nadir (CN + 2). The failure date was defined as the time at which the event occurred. Local, nodal, and distant relapses and the use of salvage hormonal therapy were also failures. Results: On the basis of the

Incidence of colorectal cancer in new users and non-users of low-dose aspirin without existing cardiovascular disease: A cohort study using The Health Improvement Network.

Science.gov (United States)

Cea Soriano, Lucía; Soriano-Gabarró, Montse; García Rodríguez, Luis A

2017-12-01

Evidence regarding the chemo-protective effects of aspirin has influenced expert opinion in favour of low-dose aspirin use in certain patient populations without cardiovascular disease (CVD). The effects of aspirin in reducing the incidence of colorectal cancer (CRC) may be a large contributor to this favourable risk-benefit profile of low-dose aspirin in primary CVD prevention. Using The Health Improvement Network, we estimated the incidence of CRC in individuals free of CVD and either prescribed or not prescribed prophylactic low-dose aspirin. Two cohorts - new-users of low-dose aspirin (N=109,426) and a comparator cohort of non-users (N=154,056) at start of follow-up - were followed (maximum 13years) to identify incident CRC cases. Individuals with a record of CVD, cancer or low-dose aspirin prescription before start of follow-up were excluded. 2330 incident cases of CRC occurred; 885 in the aspirin cohort and 1445 in the comparator cohort, after mean follow-ups of 5.43years and 5.17years, respectively. Incidence rates of CRC per 10,000 person-years (95% confidence interval) were 14.90 (13.95-15.92) in the aspirin cohort and 18.15 (17.24-19.12) in the comparator cohort; incidence rate ratio 0.82 (0.76-0.89) adjusted for age, sex and primary care practitioner (PCP) visits in the previous year. Lower incidence rates were seen in the aspirin cohort for all strata evaluated (gender, age group and number of PCP visits in the previous year) except those aged ≥80years. Among most individuals without established CVD, initiation of low-dose aspirin is associated with a reduced incidence of CRC. Copyright © 2017 Elsevier B.V. All rights reserved.

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)

Takizawa, Hirotaka

2012-01-01

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)

Treatment of carcinoma of uterine cervix with high-dose-rate intracavitary irradiation using Ralstron

International Nuclear Information System (INIS)

Suh, C.O.; Kim, G.E.; Loh, J.J.K.

1988-01-01

From May 1979 through December 1981, a total of 530 patients with carcinoma of the uterine cervix were treated with radiation therapy with curative intent. Of the 530 patients, 365 were treated with a high-dose-rate remote-controlled afterloading system (RALS) using a cobalt source, and 165 patients received a low dose rate using a radium source. External pelvic irradiation with a total of 40-50 Gy to the whole pelvis followed by intracavitary radiation (ICR) with a total dose of 30-39 Gy in ten to 13 fractions to point A was the treatment protocol. ICR was given three times a week with a dose of 3 Gy per fraction. Five-year actuarial survival rate with high-dose-rate ICR by stage was as follows: stage I:82.7% (N = 19) stage II:69.6% (N = 184), and stage III:52.2% (N = 156). The above results were comparable with those with conventional low-dose-rate ICR treatment, and late complications were far less. The application of high-dose-rate ICR was technically simple and easily performed on an outpatient basis without anesthesia, and the patients tolerated it very well. Radiation exposure to personnel was virtually none as compared with that of low-dose-rate ICR. Within a given period of time, more patients can be treated with high-dose-rate ICR because of the short treatment time. The authors therefore conclude that high-dose-rate ICR is suitable for a cancer center where a large number of patients are to be treated

Critical reevaluation of the dose-response relationships for carcinogenic effects of low-level ionizing radiation

International Nuclear Information System (INIS)

Upton, A.C.

2003-01-01

In recent decades, it has been customary, for radiation protection purposes, to assume that the overall risk of radiation-induced cancer increases as a linear-nonthreshold function of the dose. The existing data do not exclude the existence of a threshold, however, and the dose-response relationship is known to vary, depending on the type of cancer in queation, the dose, dose rate, and LET of the radiation, the age, sex, and physiological state of the exposed individuals, and other variables, including the potential influence of adaptive responses and bystander effects at low doses. In light of advncing knowledge, therefore, the dose-response relationship for carcinogenic effects of low-level radiation has been reevaluated periodically by the National Council on Radiation Protection and Measurements, the International Commission of Radiological Protection, the United Nations Scientific Committee on the Effects of Atomic Radiation, the U.S. National Academy of Sciences, and other organizations. The most recent such reviews have generally found the weight of evidence to suggest that lesions which are precursors to cancer (i.e., mutations and chromosome aberrations), and certain types of cancer as well, may increase in frequency linearly with the dose in the low-dose domain. On this basis, it is concluded that no alternative dose-response model for the carcinogenic effects of low-level radiation is more plausible than the linear-nonthreshold model, although other dose-response relationships cannot be excluded. (authors)

A combination of high dose rate (10X FFF/2400 MU/min/10 MV X-rays) and total low dose (0.5 Gy) induces a higher rate of apoptosis in melanoma cells in vitro and superior preservation of normal melanocytes.

Science.gov (United States)

Sarojini, Sreeja; Pecora, Andrew; Milinovikj, Natasha; Barbiere, Joseph; Gupta, Saakshi; Hussain, Zeenathual M; Tuna, Mehmet; Jiang, Jennifer; Adrianzen, Laura; Jun, Jaewook; Catello, Laurice; Sanchez, Diana; Agarwal, Neha; Jeong, Stephanie; Jin, Youngjin; Remache, Yvonne; Goy, Andre; Ndlovu, Alois; Ingenito, Anthony; Suh, K Stephen

2015-10-01

The aim of this study was to determine the apoptotic effects, toxicity, and radiosensitization of total low dose irradiation delivered at a high dose rate in vitro to melanoma cells, normal human epidermal melanocytes (HEM), or normal human dermal fibroblasts (HDF) and to study the effect of mitochondrial inhibition in combination with radiation to enhance apoptosis in melanoma cells. Cells irradiated using 10X flattening filter-free (FFF) 10 MV X-rays at a dose rate of 400 or 2400 MU/min and a total dose of 0.25-8 Gy were analyzed by cell/colony counting, MitoTracker, MTT, and DNA-damage assays, as well as by quantitative real-time reverse transcriptase PCR in the presence or absence of mitochondrial respiration inhibitors. A dose rate of 2400 MU/min killed on average five-fold more melanoma cells than a dose rate 400 MU/min at a total dose of 0.5 Gy and preserved 80% survival of HEM and 90% survival of HDF. Increased apoptosis at the 2400 MU/min dose rate is mediated by greater DNA damage, reduced cell proliferation, upregulation of apoptotic genes, and downregulation of cell cycle genes. HEM and HDF were relatively unharmed at 2400 MU/min. Radiation induced upregulation of mitochondrial respiration in both normal and cancer cells, and blocking the respiration with inhibitors enhanced apoptosis only in melanoma cells. A high dose rate with a low total dose (2400 MU/min, 0.5 Gy/10X FFF 10 MV X-rays) enhances radiosensitivity of melanoma cells while reducing radiotoxicity toward HEM and HDF. Selective cytotoxicity of melanoma cells is increased by blocking mitochondrial respiration.

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

International Nuclear Information System (INIS)

Wang Jidong; Wang Junjie; Zhuang Hongqing; Liao Anyan; Zhao Yong

2008-01-01

Objective: To investigate the relative biological effectiveness(RBE) of National Model 6711 125 I seeds and the response patterns of PANC-1 exposed to 125 I 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 60 Co 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 125 I seeds relative to 60 Co was determined. Results: The cell death rate for continuous low- dose-rate (LDR) irradiation by 125 I seeds was greater than 60 Co 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 125 I seeds and 60 Co. The survival fractions of 125 I were lower than those of 60 Co, and the RBE of 125 I relative to 60 Co was determined to be 1.45. Conclusion: The cell-killing effects for continuous low-dose-rate (LDR) irradiation by 125 I seeds are greater than acute high-dose-rate of 60 Co. (authors)

Ionizing radiation decreases human cancer mortality rates

International Nuclear Information System (INIS)

Luckey, T.D.

1997-01-01

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)

Regular and low-dose aspirin, other non-steroidal anti-inflammatory medications and prospective risk of HER2-defined breast cancer: the California Teachers Study.

Science.gov (United States)

Clarke, Christina A; Canchola, Alison J; Moy, Lisa M; Neuhausen, Susan L; Chung, Nadia T; Lacey, James V; Bernstein, Leslie

2017-05-01

Regular users of aspirin may have reduced risk of breast cancer. Few studies have addressed whether risk reduction pertains to specific breast cancer subtypes defined jointly by hormone receptor (estrogen and progesterone receptor) and human epidermal growth factor receptor 2 (HER2) expression. This study assessed the prospective risk of breast cancer (overall and by subtype) according to use of aspirin and other non-steroidal anti-inflammatory medications (NSAIDs) in a cohort of female public school professionals in California. In 1995 - 1996, participants in the California Teachers Study completed a baseline questionnaire on family history of cancer and other conditions, use of NSAIDs, menstrual and reproductive history, self-reported weight and height, living environment, diet, alcohol use, and physical activity. In 2005-2006, 57,164 participants provided some updated information, including use of NSAIDs and 1457 of these participants developed invasive breast cancer before January 2013. Multivariable Cox proportional hazards regression models provided hazard rate ratios (HRR) for the association between NSAID use and risk of invasive breast cancer as well as hormone receptor- and HER2-defined subtypes. Developing breast cancer was associated inversely with taking three or more tablets of low-dose aspirin per week (23% of participants). Among women reporting this exposure, the HRR was 0.84 (95% confidence interval (CI) 0.72-0.98) compared to those not taking NSAIDs and this was particularly evident in women with the hormone receptor-positive/HER2-negative subtype (HRR = 0.80, 95% CI 0.66-0.96). Use of three or more tablets of "other" NSAIDs was marginally associated with lower risk of breast cancer (HRR = 0.79, 95% CI 0.62-1.00). Other associations with NSAIDs were generally null. Our observation of reduced risk of breast cancer, among participants who took three or more tablets of low-dose aspirin weekly, is consistent with other reports looking at

The novel nomogram of Gleason sum upgrade: possible application for the eligible criteria of low dose rate brachytherapy.

Science.gov (United States)

Budäus, Lars; Graefen, Markus; Salomon, Georg; Isbarn, Hendrik; Lughezzani, Giovanni; Sun, Maxine; Chun, Felix K H; Schlomm, Thorsten; Steuber, Thomas; Haese, Alexander; Koellermann, Jens; Sauter, Guido; Fisch, Margit; Heinzer, Hans; Huland, Hartwig; Karakiewicz, Pierre I

2010-10-01

To examine the rate of Gleason sum upgrading (GSU) from a sum of 6 to a Gleason sum of ≥7 in patients undergoing radical prostatectomy (RP), who fulfilled the recommendations for low dose rate brachytherapy (Gleason sum 6, prostate-specific antigen ≤10 ng/mL, clinical stage ≤T2a and prostate volume ≤50 mL), and to test the performance of an existing nomogram for prediction of GSU in this specific cohort of patients. The analysis focused on 414 patients, who fulfilled the European Society for Therapeutic Radiation and Oncology and American Brachytherapy Society criteria for low dose rate brachytherapy (LD-BT) and underwent a 10-core prostate biopsy followed by RP. The rate of GSU was tabulated and the ability of available clinical and pathological parameters for predicting GSU was tested. Finally, the performance of an existing GSU nomogram was explored. The overall rate of GSU was 35.5%. When applied to LD-BT candidates, the existing nomogram was 65.8% accurate versus 70.8% for the new nomogram. In decision curve analysis tests, the new nomogram fared substantially better than the assumption that no patient is upgraded and better than the existing nomogram. GSU represents an important issue in LD-BT candidates. The new nomogram might improve patient selection for LD-BT and cancer control outcome by excluding patients with an elevated probability of GSU. © 2010 The Japanese Urological Association.

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.

Development of a high sensitivity pinhole type gamma camera using semiconductors for low dose rate fields

Science.gov (United States)

Ueno, Yuichiro; Takahashi, Isao; Ishitsu, Takafumi; Tadokoro, Takahiro; Okada, Koichi; Nagumo, Yasushi; Fujishima, Yasutake; Yoshida, Akira; Umegaki, Kikuo

2018-06-01

We developed a pinhole type gamma camera, using a compact detector module of a pixelated CdTe semiconductor, which has suitable sensitivity and quantitative accuracy for low dose rate fields. In order to improve the sensitivity of the pinhole type semiconductor gamma camera, we adopted three methods: a signal processing method to set the discriminating level lower, a high sensitivity pinhole collimator and a smoothing image filter that improves the efficiency of the source identification. We tested basic performances of the developed gamma camera and carefully examined effects of the three methods. From the sensitivity test, we found that the effective sensitivity was about 21 times higher than that of the gamma camera for high dose rate fields which we had previously developed. We confirmed that the gamma camera had sufficient sensitivity and high quantitative accuracy; for example, a weak hot spot (0.9 μSv/h) around a tree root could be detected within 45 min in a low dose rate field test, and errors of measured dose rates with point sources were less than 7% in a dose rate accuracy test.

The limiting dose rate and its importance in radiation protection

International Nuclear Information System (INIS)

Bakkiam, D.; Sonwani, Swetha; Arul Ananthakumar, A.; Mohankumar, Mary N.

2012-01-01