Evidence for dose and dose rate effects in human and animal radiation studies

2018 ◽  
Vol 47 (3-4) ◽  
pp. 97-112 ◽  
Author(s):  
M.P. Little
Keyword(s):  
Dose Rate ◽  
Dose Response ◽  
Low Dose ◽  
Atomic Bomb ◽  
Dose Range ◽  
Quadratic Model ◽  
Linear Quadratic ◽  
Dose Rates ◽  
Atomic Bomb Survivors ◽  
Linear Quadratic Model

For stochastic effects such as cancer, linear-quadratic models of dose are often used to extrapolate from the experience of the Japanese atomic bomb survivors to estimate risks from low doses and low dose rates. The low dose extrapolation factor (LDEF), which consists of the ratio of the low dose slope (as derived via fitting a linear-quadratic model) to the slope of the straight line fitted to a specific dose range, is used to derive the degree of overestimation (if LDEF > 1) or underestimation (if LDEF < 1) of low dose risk by linear extrapolation from effects at higher doses. Likewise, a dose rate extrapolation factor (DREF) can be defined, consisting of the ratio of the low dose slopes at high and low dose rates. This paper reviews a variety of human and animal data for cancer and non-cancer endpoints to assess evidence for curvature in the dose response (i.e. LDEF) and modifications of the dose response by dose rate (i.e. DREF). The JANUS mouse data imply that LDEF is approximately 0.2–0.8 and DREF is approximately 1.2–2.3 for many tumours following gamma exposure, with corresponding figures of approximately 0.1–0.9 and 0.0–0.2 following neutron exposure. This paper also cursorily reviews human data which allow direct estimates of low dose and low dose rate risk.

scholarly journals Effects of G2 checkpoint dynamics on the low-dose hyper-radiosensitivity

2017 ◽  
Author(s):  
Oluwole Olobatuyi ◽  
Gerda de Vries ◽  
Thomas Hillen
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Low Dose ◽  
Radiation Treatment ◽  
Dose Range ◽  
Experimental Studies ◽  
Quadratic Model ◽  
Linear Quadratic ◽  
G2 Checkpoint ◽  
Linear Quadratic Model

AbstractWe develop and analyze a system of differential equations to investigate the effects of G2 checkpoint dynamics on the low-dose hyper-radiosensitivity. In experimental studies, it has been found that certain cell lines are more sensitive to low-dose radiation than would be expected from the classical Linear Quadratic model (LQ model). In fact, it is frequently observed that cells incur more damage at a low dose (say 0.3 Gy) than at higher dose (say 1 Gy). This effect has been termed hyper-radiosensitivity (HRS). The HRS is followed by a period of relative radioresistance (per unit dose) of cell kill over the dose range of ~ 0.5 - 1 Gy. This latter phenomenon is termed increased radioresistance (IRR). These effects depend on the type of cells and on their phase in the cell cycle. Here we focus on the HRS phenomenon by fitting a model for the cell cycle that includes G2-checkpoint dynamics and radiation treatment to surviving fraction data for different cell lines including glioma cells, prostate cancer cells, as well as to cell populations that are enriched in certain phases of the cell cycle. The HRS effect is measured in the literature through , the ratio of slope αs, of the surviving fraction curve at zero dose to slope α of the corresponding LQ model. We derive an explicit formula for this ratio and we show that it corresponds very closely to experimental observations. Finally, we can identify the dependence of this ratio on the surviving fraction at 2 Gy. It was speculated in the literature that such a relation exists. Our theoretical analysis will help to more systematically identify the HRS in cell lines and opens doors to analyze its use in cancer treatment.PACS and mathematical subject classification numbers as needed.

scholarly journals Clinical comparison of toxicity pattern of two linear quadratic model-baesd fractionation schemes of high-dose-rate intracavitary brachytherapy for cervical cancer

2016 ◽  
Author(s):  
Ankit Batra
Keyword(s):  
Cervical Cancer ◽  
Dose Rate ◽  
High Dose Rate ◽  
Sub Saharan Africa ◽  
Quadratic Model ◽  
Intracavitary Brachytherapy ◽  
High Dose ◽  
Linear Quadratic ◽  
Carcinoma Cervix ◽  
Linear Quadratic Model

Introduction: Carcinoma cervix is the fourth (GLOBACON 2012) most common cancer among women worldwide, and the main cancer affecting women in Sub-Saharan Africa, Central America and south-central Asia. In India, approx. 1,23,000 (GLOBACON 2012) new cases of carcinoma cervix are diagnosed each year. Brachytherapy is an integral part of treatment of cancer cervix. In the context of a developing country like us where maximum utilization of the resource is of prime importance to provide treatment to the large patient cohort, shortening the treatment duration and number of fractions always increases efficiency. In order to maximize the logistic benefits of HDR-BT while improving patient compliance and resource sparing, various fractionation regimens are used. Fractionation and dose adjustments of the total dose are radiobiologically important factors in lowering the incidence of complications without compromising the treatment results. Aim: To compare patient outcomes and complications using two linear-quadratic model-based fractionation schemes of high-dose-rate intracavitary brachytherapy (HDR-IC) used to treat cervical cancer. Materials and Methods: A prospective randomized study on 318 patients, with histologically proven advanced carcinoma cervix (stages IIB-IIIB) was enrolled in the study. All patients received External Beam Radio Therapy (EBRT) 50 Gy in 25 fractions with concurrent chemotherapy (cisplatin 35 mg/m2) followed by IntraCavitary brachytherapy using high dose rate equipment. Patients were randomised after completion of EBRT into two arms: (1) Arm 1: HDR ICRT 6.5 Gy per fraction for 3 fractions, a week apart. (2) Arm 2: HDR ICRT, 9 Gy per fraction for 2 fractions, 1 week apart. On completion of treatment, patients were assessed monthly for 3 months followed by 3 monthly thereafter. Treatment response was assessed according to WHO criteria after one month of completion of radiotherapy. The RTOG criteria were used for radiation induced toxicities. We analyzed late toxicities in terms of Rectal, Bladder, Small Bowel toxicity and Vaginal Stenosis. Results: Acute reactions in both the groups were comparable. None of the patient developed Grade 4 toxicity in our study and no toxicity related mortality was encountered. A slightly high frequency of late toxicity was observed in 9Gy Arm patients but was not statistically significant. Conclusion: In our setup, HDR brachytherapy at 9 Gy per fraction in two fractions is safe, effective and resource saving method with good local control, survival, and manageable normal tissue toxicity.

scholarly journals Mechanical Properties of 20% Cold-Worked 316 Stainless Steel Irradiated at Low Dose Rate

2002 ◽  
Author(s):  
Todd R. Allen ◽  
Hanchung Tsai ◽  
James I. Cole ◽  
Joji Ohta ◽  
Kenji Dohi ◽  
...  
Keyword(s):  
Stainless Steel ◽  
Dose Rate ◽  
Work Hardening ◽  
Low Dose ◽  
Dose Range ◽  
Total Elongation ◽  
316 Stainless Steel ◽  
Dose Rates ◽  
Low Dose Rate ◽  
Cold Worked

To assess the effects of long-term, low-dose-rate neutron exposure on mechanical strength and ductility, tensile properties were measured on irradiated 20% cold-worked Type 316 stainless steel. Samples were prepared from reactor core components retrieved from the EBR-II reactor following final shutdown. Sample locations were chosen to cover a dose range of 1–47 dpa at temperatures from 371–385°C and dose rates from 0.8–2.8 × 10−7 dpa/s. These dose rates are about one order of magnitude lower than those of typical EBR-II in-core experiments. Irradiation cuased hardening, with the yield strength (YS) following approximately the same trend as the ultimate tensile strength (UTS). At higher dose, the difference between the UTS and YS decreases, suggesting the work-hardening capability of the material is decreasing with increasing dose. Both the uniform elongation and total elongation decrease up to the largest dose. Unlike the strength data, the ductility reduction showed no signs of saturating at 20 dpa. While the material retained respectable ductility at 20 dpa, the uniform and total elongation decreased to &lt;1 and &lt;3%, respectively, at 47 dpa. Fracture in the 30 dpa specimen is mainly ductile but with local regions of mixed-mode failure consisting of dimples and microvoids. The fracture surface of the higher-exposure 47 dpa specimen displays significantly more brittle features. The fracture consists of maily small facets and slip bands that suggest channel fracture. The hardening in these low-dose-rate components differs from that measured in test samples irradiated in EBR-II at higher-dose-rate. The material irradiated at higher dose rate loses work hardening capactiy faster than the lower dose rate material, although this effect could be due to compositional differences.

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