Variable RBE in proton therapy: comparison of different model predictions and their influence on clinical-like scenarios

International Nuclear Information System (INIS)

Giovannini, Giulia; Böhlen, Till; Cabal, Gonzalo; Bauer, Julia; Tessonnier, Thomas; Frey, Kathrin; Debus, Jürgen; Mairani, Andrea; Parodi, Katia

2016-01-01

In proton radiation therapy a constant relative biological effectiveness (RBE) of 1.1 is usually assumed. However, biological experiments have evidenced RBE dependencies on dose level, proton linear energy transfer (LET) and tissue type. This work compares the predictions of three of the main radio-biological models proposed in the literature by Carabe-Fernandez, Wedenberg, Scholz and coworkers. Using the chosen models, a spread-out Bragg peak (SOBP) as well as two exemplary clinical cases (single field and two fields) for cranial proton irradiation, all delivered with state-of-the-art pencil-beam scanning, have been analyzed in terms of absorbed dose, dose-averaged LET (LET D ), RBE-weighted dose (D RBE ) and biological range shift distributions. In the systematic comparison of RBE predictions by the three models we could show different levels of agreement depending on (α/β) x and LET values. The SOBP study emphasizes the variation of LET D and RBE not only as a function of depth but also of lateral distance from the central beam axis. Application to clinical-like scenario shows consistent discrepancies from the values obtained for a constant RBE of 1.1, when using a variable RBE scheme for proton irradiation in tissues with low (α/β) x , regardless of the model. Biological range shifts of 0.6– 2.4 mm (for high (α/β) x ) and 3.0 – 5.4 mm (for low (α/β) x ) were found from the fall-off analysis of individual profiles of RBE-weighted fraction dose along the beam penetration depth. Although more experimental evidence is needed to validate the accuracy of the investigated models and their input parameters, their consistent trend suggests that their main RBE dependencies (dose, LET and (α/β) x ) should be included in treatment planning systems. In particular, our results suggest that simpler models based on the linear-quadratic formalism and LET D might already be sufficient to reproduce important RBE dependencies for re-evaluation of plans optimized with

WE-FG-BRB-02: Spatial Mapping of the RBE of Scanned Particle Beams

Energy Technology Data Exchange (ETDEWEB)

Grosshans, D. [The University of Texas MD Anderson Cancer Center (United States)

2016-06-15

The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences between particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to

submitter Variable RBE in proton therapy: comparison of different model predictions and their influence on clinical-like scenarios

CERN Document Server

Giovannini, Giulia; Cabal, Gonzalo; Bauer, Julia; Tessonnier, Thomas; Frey, Kathrin; Debus, Jürgen; Mairani, Andrea; Parodi, Katia

2016-01-01

Background: In proton radiation therapy a constant relative biological effectiveness (RBE) of 1.1 is usually assumed. However, biological experiments have evidenced RBE dependencies on dose level, proton linear energy transfer (LET) and tissue type. This work compares the predictions of three of the main radio-biological models proposed in the literature by Carabe-Fernandez, Wedenberg, Scholz and coworkers. Methods: Using the chosen models, a spread-out Bragg peak (SOBP) as well as two exemplary clinical cases (single field and two fields) for cranial proton irradiation, all delivered with state-of-the-art pencil-beam scanning, have been analyzed in terms of absorbed dose, dose-averaged LET $(LET_D)$, RBE-weighted dose $(D_{RBE})$ and biological range shift distributions. Results: In the systematic comparison of RBE predictions by the three models we could show different levels of agreement depending on $(α/β) x$ and LET values. The SOBP study emphasizes the variation of LET D and RBE not only as a functi...

Review of RBE values of 15 MeV neutrons for effects on normal tissues

NARCIS (Netherlands)

Broerse, J.J.

1974-01-01

Values of the relative biological effectiveness (RBE) of fast neutrons for effect on normal tissue depend not only on the neutron energy and the dose, but also on the type of tissue irradiated. Values of the RBE of 15 MeV neutrons are reviewed for rapidly proliferating rodent tissue, such as mouse

RBE/absorbed dose relationship of d(50)-Be neutrons determined for early intestinal tolerance in mice

International Nuclear Information System (INIS)

Gueulette, J.; Wambersie, A.

1978-01-01

RBE/absorbed dose relationship of d(50)-Be neutrons (ref.: 60 Co) was determined using intestinal tolerance in mice (LD50) after single and fractionated irradiation. RBE is 1.8 for a single fraction (about 1000 rad 60 Co dose); it increases when decreasing dose and reaches the plateau value of 2.8 for a 60 Co dose of about 200 rad. This RBE value is used for the clinical applications with the cyclotron 'Cyclone' at Louvain-la-Neuve [fr

NIRS methods of specifying carbon ion dose verification of RBE and tumour specific radiosensitivity

International Nuclear Information System (INIS)

Matsufuji, Naruhiro; Kanai, Tatsuaki; Kanematsu, Nobuyuki

2006-01-01

Clinical dose distribution of therapeutic carbon beams, currently used at National Institute of Radiological Sciences (NIRS) Heavy Ion Medical Accelerator in Chiba (HIMAC), is designed based on in-vitro Human Salivary Gland (HSG) cell survival response and clinical experiences of fast neutron radiotherapy. At first, the biological dose distribution is designed so as to cause a flat biological effect on HSG cells in spread-out Bragg peak (SOBP) region. Then, the entire biological dose distribution is evenly raised in order to attain relative biological effectiveness (RBE)=3.0 at a depth where dose-averaged linear energy transfer (LET) is 80 keV/μm. A retrospective analysis was made to examine appropriateness on the estimation of the biological effectiveness of carbon-ion radiotherapy using resultant data of clinical trials at HIMAC. Using this RBE system, over 2,700 patients have been treated by carbon beams. As a part of these patient data, local control rate of non-small lung cancer, were analysed to verify the clinical RBE of the carbon beam. The local control rate was compared with those for published by groups of Gunma University and Massachusetts General Hospital. Using a simplified tumour control probability (TCP) model, clinical RBE values were obtained for different level of the tumour control probability. For the 50% level of the clinical TCP, the RBE values nearly coincide with those of in-vitro human salivary gland cell survival at 10%. For the higher level of the clinical TCP, the RBE values approach closer to those adapted in clinical trials at HIMAC. The approach was also applied for those of chordoma, bone and soft tissue sarcoma and rectal cancer. Difference in radiosensitivity is observed for the tumours. (author)

Theory of RBE. Progress report, January 1, 1977--December 1977

International Nuclear Information System (INIS)

Katz, R.

1977-09-01

Emulsion-processing combinations have been found which match the response of mammalian cells to x-rays. The grain size of these emulsions is in the implied range of sensitive element sizes in biological cells. The fading of the latent image may parallel biological repair. In consequence studies are under way of the variation in emulsion response to low LET radiations of different quality, of ''Elkind repair'', and of dose fractionation. Predictions of OER and RBE of mammalian cells to high LET radiations, from track structure theory, have been verified, once again, in Bevalac experiments. Experiment has now shown that high temperature traps in LiF respond favorably to neutrons, while low temperature traps respond favorably to gamma-rays. This result is consistent with our identification of supralinear high temperature traps as from an unidentified 2-hit trap structure. In collaboration with Oak Ridge colleagues, Monte-Carlo studies of the electron slowing down spectra of source electrons from 1 keV to 1 MeV in liquid water are being integrated into the theory of RBE. The yield of several different ions is nearly independent of the initial energy of source electrons. The results raise questions as to the physical basis for biological observations of RBE differences for x- and gamma-rays

Ensemble of cell survival experiments after ion irradiation for validation of RBE models

Energy Technology Data Exchange (ETDEWEB)

Friedrich, Thomas; Scholz, Uwe; Scholz, Michael [GSI Helmholtzzentrum fuer Schwerionenforschung, Darmstadt (Germany); Durante, Marco [GSI Helmholtzzentrum fuer Schwerionenforschung, Darmstadt (Germany); Institut fuer Festkoerperphysik, TU Darmstadt, Darmstadt (Germany)

2012-07-01

There is persistent interest in understanding the systematics of the relative biological effectiveness (RBE). Models such as the Local Effect Model (LEM) or the Microdosimetric Kinetic Model have the goal to predict the RBE. For the validation of these models a collection of many in-vitro cell survival experiments is most appropriate. The set-up of an ensemble of in-vitro cell survival data comprising about 850 survival experiments after both ion and photon irradiation is reported. The survival curves have been taken out from publications. The experiments encompass survival curves obtained in different labs, using different ion species from protons to uranium, varying irradiation modalities (shaped or monoenergetic beam), various energies and linear energy transfers, and a whole variety of cell types (human or rodent; normal, mutagenic or tumor; radioresistant or -sensitive). Each cell survival curve has been parameterized by the linear-quadratic model. The photon parameters have been added to the data base to allow to calculate the experimental RBE to any survival level. We report on experimental trends found within the data ensemble. The data will serve as a testing ground for RBE models such as the LEM. Finally, a roadmap for further validation and first model results using the data base in combination with the LEM are presented.

Theory of RBE. Progress report, 1 January 1976--31 December 1976

International Nuclear Information System (INIS)

Katz, R.

1976-09-01

Experimental studies of emulsion-processing combinations have demonstrated that a range of hittedness, from 1 to 8-or-more, can be achieved with specially processed nuclear research emulsions of the Ilford K series, encompassing the range of supralinear response displayed by biological cells. In analogy with the response of biological cells to high LET radiations, the processes of ion-kill and gamma-kill have been displayed for these emulsions, in that x-rays blacken emulsion in circumstances that single alpha-particles, or even single fission fragments, leave no visible track. Track structure theory and the theory of RBE have been extended to these multi-hit detectors. Supralinearity in thermoluminescent dosimeters has been tentatively identified as due to a population of 2-or-more hit trapping sites, coexisting with the linear 1-or-more hit sites. Inferences from this identification that the response to high-LET radiations is linear and that 2-hit sites must display an RBE greater than 1 are consistent with some experimental observations. This is a second solid state detector having the capacity to mimic the response of biological systems identified from the theory of RBE

Theory of RBE. Progress report, 1 January 1975--31 December 1975

International Nuclear Information System (INIS)

Katz, R.

1975-09-01

Calculations from the theory of RBE have been so simplified that RBE, D/sub x/, and oxygen enhancement ratio for a mixed radiation environment (say, pions, neutrons, and gamma-rays) can be calculated with an HP-65 pocket programmable calculator, once equivalent track segment bombardments have been found for the components of the mix, from theory or from experiment. With a least-squares seeking computer program, cellular radiosensitivity parameters have been evaluated (with 95 percent confidence limits) for many biological cells for which survival data is available at different LET's. Typically there is good agreement with visually fitted parameters, with confidence limits ranging from a few percent on up, depending on the quantity and quality of the data. The procedure reveals internal inconsistencies in the data, and may be used as the basis for the design of efficient experiments. Studies of many-hit nuclear emulsions have been initiated. These emulsions will exhibit RBE-LET properties similar to those of biological cells and tissues, and will be useful as a model system in studies of low-dose and dose-rate effects in radiobiology. A first quantitative result is that Ilford K-1 emulsion is an 8 +- 1 or-more hit detector. (auth)

Relative biological effectiveness (RBE) of alpha radiation in cultured porcine aortic endothelial cells.

Science.gov (United States)

Thomas, Patricia; Tracy, Bliss; Ping, Tilly; Baweja, Anar; Wickstrom, Mark; Sidhu, Narinder; Hiebert, Linda

2007-03-01

Northern peoples can receive elevated radiation doses (1- 10 mSv/y) from transfer of polonium-210 (210Po) through the lichen-caribou-human food chain. Ingested 210Po is primarily blood-borne and thus many of its short range alpha particles irradiate the endothelial cells lining the blood vessels. The relative biological effectiveness (RBE) of alpha particles vs. x-rays was examined in porcine aortic endothelial cells as a surrogate for understanding what might happen to human endothelial cells in northern populations consuming traditional foods. Cultured porcine aortic endothelial cells were exposed to x-ray and 210Po alpha particle radiation. Alpha irradiation was applied to the cell cultures internally via the culture medium and externally, using thin-bottomed culture dishes. The results given here are based on the external irradiation method, which was found to be more reliable. Dose-response curves were compared for four lethal endpoints (cell viability, live cell fraction, release of lactate dehydrogenase [LDH] and clonogenic survival) to determine the relative biological effectiveness (RBE) of alpha radiation. The alpha RBE for porcine cells varied from 1.6-21, depending on the endpoint: 21.2+/-4.5 for cell viability, 12.9+/-2.7 for decrease in live cell number, 5.3+/-0.4 for LDH release to the medium but only 1.6 +/-0.1 for clonogenic survival. The low RBE of 1.6 was due to x-ray hypersensitivity of endothelial cells at low doses.

Relative biological effectiveness (RBE) of proton beams in radiotherapy

International Nuclear Information System (INIS)

Calugaru, V.

2011-01-01

Treatment planning in proton therapy uses a generic value for the Relative Biological Efficiency (RBE) of 1.1 relative to 60 Co gamma-rays throughout the Spread Out Bragg Peak (SOBP). We have studied the variation of the RBE at three positions in the SOBP of the 76 and 201 MeV proton beams used for cancer treatment at the Institut Curie Proton Therapy in Orsay (ICPO) in two human tumor cell lines using clonogenic cell death and the incidence of DNA double-strand breaks (DSB) as measured by pulse-field gel electrophoresis without and with endonuclease treatment to reveal clustered lesions as endpoints.The RBE for induced cell killing by the 76 MeV beam increased with depth in the SOBP. However for the 201 MeV protons it was close to that for 137 Cs gamma-rays and did not vary significantly. The incidence of DSBs and clustered lesions was higher for protons than for 137 Cs g-rays, but did not depend on the proton energy or the position in the SOBP. In the second part of our work, we have shown using cell clones made deficient for known repair genes by stable or transient shRNA transfection, that the D-NHEJ pathway determine the response to protons. The response of DNA damages created in the distal part of the 76 MeV SOBP suggests that those damages belong to the class of DNA 'complex lesions' (LMDS). It also appears that the particle fluence is a major determinant of the outcome of treatment in the distal part of the SOBP. (author)

Relative Biologic Effectiveness (RBE) of 50 kV X-rays Measured in a Phantom for Intraoperative Tumor-Bed Irradiation

Energy Technology Data Exchange (ETDEWEB)

Liu, Qi; Schneider, Frank; Ma, Lin; Wenz, Frederik [Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim (Germany); Herskind, Carsten, E-mail: carsten.herskind@medma.uni-heidelberg.de [Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim (Germany)

2013-03-15

Purpose: Intraoperative radiation therapy (IORT) with low-energy x-rays is used to treat the tumor bed during breast-conserving surgery. The purpose was to determine the relative biologic effectiveness (RBE) of 50-kV x-rays for inactivation of cells irradiated in a tumor-bed phantom. Methods and Materials: The RBE was determined for clonogenic inactivation of human tumor and normal cells (MCF7, human umbilical vein endothelial cells, normal skin fibroblasts), and hamster V79 cells. The 50-kV x-rays from the Intrabeam machine (Carl Zeiss Surgical) with a spherical 4-cm applicator were used. Cells were irradiated in a water-equivalent phantom at defined distances (8.1-22.9 mm) from the applicator surface. The 50-kV x-rays from a surface therapy machine (Dermopan, Siemens) were included for comparison; 6-MV x-rays were used as reference radiation. Results: At 8.1-mm depth in the phantom (dose rate 15.1 Gy/h), mean RBE values of 50-kV x-rays from Intrabeam were 1.26 to 1.42 for the 4 cell types at doses yielding surviving fractions in the range of 0.01 to 0.5. Confidence intervals were in the range of 1.2 and 1.5. Similar RBE values were found for 50-kV x-rays from Dermopan for V79 (1.30, CI 1.25-1.36, P=.74) and GS4 (1.42, CI 1.30-1.54, P=.67). No significant dependence of RBE on dose was found for Intrabeam, but RBE decreased at a larger distance (12.7 mm; 9.8 Gy/h). Conclusions: An increased clinically relevant RBE was found for cell irradiation with Intrabeam at depths in the tumor bed targeted by IORT. The reduced RBE values at larger distances may be related to increased repair of sublethal damage during protracted irradiation or to hardening of the photon beam energy.

The RB/E2F pathway and regulation of RNA processing

Energy Technology Data Exchange (ETDEWEB)

Ahlander, Joseph [Department of Molecular and Cellular Biology, 1007 East Lowell Street, University of Arizona, Tucson, AZ 85721 (United States); Bosco, Giovanni, E-mail: gbosco@email.arizona.edu [Department of Molecular and Cellular Biology, 1007 East Lowell Street, University of Arizona, Tucson, AZ 85721 (United States)

2009-07-03

The retinoblastoma tumor suppressor protein (RB) is inactivated in a majority of cancers. RB restricts cell proliferation by inhibiting the E2F family of transcription factors. The current model for RB/E2F function describes its role in regulating transcription at gene promoters. Whether the RB or E2F proteins might play a role in gene expression beyond transcription initiation is not well known. This review describes evidence that points to a novel role for the RB/E2F network in the regulation of RNA processing, and we propose a model as a framework for future research. The elucidation of a novel role of RB in RNA processing will have a profound impact on our understanding of the role of this tumor suppressor family in cell and developmental biology.

Aspects of OER and RBE relevant to neutron therapy

International Nuclear Information System (INIS)

Field, S.B.; Hornsey, S.

1979-01-01

This chapter contains information concerning the mechanisms involved in neutron radiotherapy. Early studies on the attempts of using neutrons in radiotherapy are described. The rationale for fast neutron therapy is discussed as well as the relationships between OER and LET. Tissue responses include: repopulation of surviving cells; repair of sublethal damage; and slow repair. These mechanisms are considered separately. The relationships between RBE and dose per fraction for damage to skin, intestine, esophagus, lungs, hemopoietic tissue, and nerve tissue are discussed. Factors governing the effects of fractionation of dose in neutron radiotherapy are presented. Observations on mammalian cells and tissues show a general reduction in RBE with increasing neutron energy. The benefits of using mixed treatments, part with neutrons and the remainder with photons, are discussed. Problems with this approach include uncertainties of how the combination will effect normal tissue, how it effects slow repair, or its potentially lethal damage. Tumor response, as compared with x rays, to single and multiple doses of radiation is described. Clinical results are given

RBE of tritium for induction of myeloid leukemia in CBA/H mice

International Nuclear Information System (INIS)

Myers, D.K.; Jackson, J.S.; Gragtmans, N.J.; Jones, A.R.; Dunford, D.W.; Wyatt, H.M.; Percy, D.H.

1990-05-01

In order to help resolve uncertainties as to the most appropriate quality factor for tritium beta rays, a large experiment was carried out to measure the relative biological effectiveness (RBE) of tritiated water compared to X rays for the induction of myeloid leukemia in male mice of CBA/H strain. The study was designed to estimate the lifetime incidence of myeloid leukemia in seven groups of about 750 mice each; radiation exposures were approximately 0, 1, 2 and 3 grays both for tritiated water and X rays. The lifetime incidence of leukemia in these mice increased from 0.13% in the control group to 6-8% in groups exposed to higher radiation doses. The results were fitted to various equations relating leukemia incidence to radiation dose, using both the raw data and data corrected for cumulative animal-days at risk. The calculated RBE values for tritium beta rays compared to X rays ranged from 1.0 ± 0.5 to 1.3 ± 0.3. A best estimate of the RBE for this experiment was about 1.2 ± 0.3. A Q value of 1 would thus appear to be more appropriate than a Q of 2 for tritium beta rays

RBE of Cf-252 neutrons as determined by its lethal, mutagenic, and cytogenetic effects on human cells

International Nuclear Information System (INIS)

Ban, Sadayuki

1989-01-01

To assess the biological effects of neutrons, a man-made spontaneously fissioning isotope, Cf-252, is useful as an experimental model to obtain basic biological data on mixed radiation of gamma-rays and neutrons. The paper describes the lethal effect of Cf-252 radiation on human skin fibroblasts, its lethal and mutagenic effect on HeLa MR cells, and the micronuclei inducing effect on human peripheral lymphocytes. Dose-survival responses of three fibroblast cell strains exposed to Cf-252 radiation are measured. Individual difference is larger than the experimental fluctuation. D 10 values of each strain are obtained from the linear model and linear-quadratic model. Though the dose rate of X-ray is higher than that of Cf-252 radiations, the mean value of RBE(n+γ) is simply obtained as 1.86+0.31 (RBE:relative biological effectiveness). RBE(n) of Cf-252 neutrons to high-dose-rate X-rays is 2.29. After X-ray irradiation, the survival curve of HeLa MR cells gives an extrapolation number of 3.6. It is 1.3 after Cf-252 irradiation. At 50% survival, RBE(n+γ) and RBE(n) are 2.05 and 2.6, respectively. At 10% survival they are 2.05 and 2.6. The mutation frequencies after X-ray irradiation showed a significant non-linear increase with dose. Those after Cf-252 irradiation increase linearly with dose. (N.K.)

Experiment designed to measure the RBE of tritium for the induction of myeloid leukaemia in animals

Energy Technology Data Exchange (ETDEWEB)

Johnson, J R; Myers, D K; Gragtmans, N J

1986-01-01

The range in RBE vales measured for tritium can be attributed to differences in the biological endpoints measured, the reference radiation to which the effects of tritium were compared, and the tritium dosimetry of the particular study. Since the principal risk of low-level irradiation is the induction of cancers, it would be desirable to utilise this endpoint in tritium RBE experiments if these experiments are to be used to evaluate the quality factor for tritium. Furthermore, it would be desirable to use 200 k Vp X rays as the reference radiation since this radiation was suggested by ICRP as the standard reference to be used in the calculation of dose equivalents. Acute myeloid leukaemia is one of the earliest recognised examples of radiogenic cancer in humans and this endpoint has also been the subject of animal studies. A brief review is given of these animal studies to see if this endpoint is suitable for an experiment to measure the tritium RBE relative to 200 k Vp X rays. It was concluded that the male CBA/H mouse would be a suitable species and an experiment involving 5000 animals in four to five year study would be required to provide a useful estimate of the RBE for tritium.

Theory of RBE. Third triennial report, 1 January 1967--31 December 1975

International Nuclear Information System (INIS)

Katz, R.

1975-09-01

From a single set of themes, the theory of RBE has developed a picture of the response of many biological, physical, and chemical systems to radiations of different quality, that depends on a model of the structure of the tracks of nuclear projectiles in condensed matter. Its characterizations arise from the tracks of heavy ions in nuclear emulsions, as extended to accommodate biological cells. Most recently emulsions have been identified whose radiosensitivity changes with radiation quality parallel those of biological cells. From experimentally determined radiosensitivity parameters, the theory predicts response to a range of radiations, and includes synergistic effects of mixed radiation fields, making it possible to calculate the RBE of a mixed field of neutrons and gamma-rays, and to specify the dosimetric measurements required to make these predictions

RBE of neutrons for induction of cell reproductive death and chromosome aberrations in three cell lines

International Nuclear Information System (INIS)

Zoetelief, J.; Kuijpers, W.C.; Baten-Wittwer, A.; Barendsen, G.W.

1983-01-01

The authors have compared the RBE values for induction of dicentrics and centric rings with those for cell inactivation and with the mean or effective quality factors (Q) recommended for radiation protection. The induction of cell reproductive death and chromosome aberrations has been investigated in plateau phase cultures of established lines of a rat rhabdomyosarcoma, a rat ureter carcinoma and Chinese hamster cells for single doses of 300 kV X-rays and 0.5, 4.2 and 15 MeV neutrons. The different cell lines show considerable variations in sensitivity and the RBE values obtained are presented in tabular form. The mean RBE values for the rat rhabdomyosarcoma cells are lower than those for the other two relatively resistant cell lines. Those for the Chinese hamster cells extrapolated to levels according to low doses of X-rays are in good agreement with the quoted Q values. (Auth./C.F.)

Calculation and experimental verification of the RBE-weighted dose for scanned ion beams in the presence of target motion

International Nuclear Information System (INIS)

Gemmel, A; Rietzel, E; Kraft, G; Durante, M; Bert, C

2011-01-01

We present an algorithm suitable for the calculation of the RBE-weighted dose for moving targets with a scanned particle beam. For verification of the algorithm, we conducted a series of cell survival measurements that were compared to the calculations. Calculation of the relative biological effectiveness (RBE) with respect to tumor motion was included in the treatment planning procedure, in order to fully assess its impact on treatment delivery with a scanned ion beam. We implemented an algorithm into our treatment planning software TRiP4D which allows determination of the RBE including its dependence on target tissue, absorbed dose, energy and particle spectra in the presence of organ motion. The calculations are based on time resolved computed tomography (4D-CT) and the corresponding deformation maps. The principal of the algorithm is illustrated in in silico simulations that provide a detailed view of the different compositions of the energy and particle spectra at different target positions and their consequence on the resulting RBE. The calculations were experimentally verified with several cell survival measurements using a dynamic phantom and a scanned carbon ion beam. The basic functionality of the new dose calculation algorithm has been successfully tested in in silico simulations. The algorithm has been verified by comparing its predictions to cell survival measurements. Four experiments showed in total a mean difference (standard deviation) of −1.7% (6.3%) relative to the target dose of 9 Gy (RBE). The treatment planning software TRiP is now capable to calculate the patient relevant RBE-weighted dose in the presence of target motion and was verified against cell survival measurements.

WE-FG-BRB-00: The Challenges of Predicting RBE Effects in Particle Therapy and Opportunities for Improving Cancer Therapy

Energy Technology Data Exchange (ETDEWEB)

NONE

2016-06-15

The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences between particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to

SU-F-T-132: Variable RBE Models Predict Possible Underestimation of Vaginal Dose for Anal Cancer Patients Treated Using Single-Field Proton Treatments

Energy Technology Data Exchange (ETDEWEB)

McNamara, A; Underwood, T; Wo, J; Paganetti, H [Massachusetts General Hospital & Harvard Medical School, Boston, MA (United States)

2016-06-15

Purpose: Anal cancer patients treated using a posterior proton beam may be at risk of vaginal wall injury due to the increased linear energy transfer (LET) and relative biological effectiveness (RBE) at the beam distal edge. We investigate the vaginal dose received. Methods: Five patients treated for anal cancer with proton pencil beam scanning were considered, all treated to a prescription dose of 54 Gy(RBE) over 28–30 fractions. Dose and LET distributions were calculated using the Monte Carlo simulation toolkit TOPAS. In addition to the standard assumption of a fixed RBE of 1.1, variable RBE was considered via the application of published models. Dose volume histograms (DVHs) were extracted for the planning treatment volume (PTV) and vagina, the latter being used to calculate the vaginal normal tissue complication probability (NTCP). Results: Compared to the assumption of a fixed RBE of 1.1, the variable RBE model predicts a dose increase of approximately 3.3 ± 1.7 Gy at the end of beam range. NTCP parameters for the vagina are incomplete in the current literature, however, inferring value ranges from the existing data we use D{sub 50} = 50 Gy and LKB model parameters a=1–2 and m=0.2–0.4. We estimate the NTCP for the vagina to be 37–48% and 42–47% for the fixed and variable RBE cases, respectively. Additionally, a difference in the dose distribution was observed between the analytical calculation and Monte Carlo methods. We find that the target dose is overestimated on average by approximately 1–2%. Conclusion: For patients treated with posterior beams, the vaginal wall may coincide with the distal end of the proton beam and may receive a substantial increase in dose if variable RBE models are applied compared to using the current clinical standard of RBE equal to 1.1. This could potentially lead to underestimating toxicities when treating with protons.

Rio Blanco gas composition: preproduction testing of the RBE-01 wellhead

International Nuclear Information System (INIS)

Smith, C.F.; Fontanilla, J.E.

1976-01-01

The chemical composition and radionuclide concentration of Rio Blanco gas samples collected prior to the production testing of the RBE-01 well and analyzed at LLL are presented. The analytical procedures and their uncertainties are briefly summarized. Information that associates the analytical data with the field operations is included

Feasibility study of an experiment to measure the RBE of tritium for the induction of myeloid leukemia in animals

International Nuclear Information System (INIS)

Gragtmans, N.J.; Johnson, J.R.; Myers, D.K.

1986-02-01

A variety of RBE values ranging from about 1 to 3 for tritium have been measured by different investigators. The reason for this range in RBE can be attributed to differences in the biological endpoints measured, the reference radiation to which the effects of tritium were compared, and the tritium dosimetry of the particular study. Since the principal risk of low-level irradiation is the induction of cancers, it would be desirable to utilize this endpoint in tritium RBE experiments if these experiments are to be used to evaluate the quality factor for tritium. Furthermore, it would be desirable to use 200 kVp X-rays as the reference radiation since this radiation was suggested by ICRP as the standard reference to be used in the calculation of dose equivalents for purposes of radiation protection. Acute myeloid leukemia is one of the earliest recognized examples of radiogenic cancer in humans and this endpoint has also been the subject of animal studies. This report gives the results of a review of these animal studies to see if this endpoint is suitable for an experiment to measure the tritium RBE relative to 200 kVp X-rays. It was concluded that the male CBA/H mouse, would be a suitable species and an experiment involving 5000 animals in a four to five year study would be required to provide a useful estimate of the RBE for tritium. 72 refs

RBE of cells irradiated by carbon ions

International Nuclear Information System (INIS)

Li Wenjian; Zhou Guangming; Wei Zengquan; Wang Jufang; Dang Bingrong; Li Qiang; Xie Hongmei

2002-01-01

The mouse melanoma cells (B16), human cervical squamous carcinoma cells (HeLa), Chinese hamster pulmonary cells V79, and human hepatoma cells (SMMC-7721) were collected for studying. The cells of 5 x 10 5 /ml were seeded in 35 mm diameter petri dish and allowed to grow one day, and then the medium in petri dishes was removed away, the cells were washed once with phosphate-buffered saline (PBS), petri dishes was covered with 4μm thickness Mylar film. The cells were irradiated by 12 C ion beam with LETs of 125.5, 200, 700 keV/μm in water generated from HIRFL (Heavy Ion Research Facility in Lanzhou). For 60 Co γ-ray experiment, the cells of 5 x 10 4 /ml were grown in 20 ml culture flasks including 1.5 ml cell suspension and directly used for irradiation. Following irradiation, the cells were trypsinized, counted, plated at appropriate densities in growth medium and then seeded in 60 mm diameter culture dishes. Each dish was filled 4 ml standard medium, and incubated for 8-12 days at 37 degree C incubator containing 5% CO 2 . The cultures were then rinsed with PBS buffer at pH 6.8, fixed with Carnoy's fluid, stained for 8 min with Giemsa (1:20, pH 6.8), and colonies containing more than 50 cells were scored. Their relative biological effectivenesses (RBE) were investigated. The results show that RBE depends on cellular types and increases with increasing of cellular survival level when LET is at 125.5 keV/μm, and decreases with increasing LET when LET ≥ 125.5 keV/μm

Monte Carlo simulations of the cellular S-value, lineal energy and RBE for BNCT

International Nuclear Information System (INIS)

Liu Chingsheng; Tung Chuanjong

2006-01-01

Due to the non-uniform uptake of boron-containing pharmaceuticals in cells and the short-ranged alpha and lithium particles, microdosimetry provides useful information on the cellular dose and response of boron neutron capture therapy (BNCT). Radiation dose and quality in BNCT may be expressed in terms of the cellular S-value and the lineal energy spectrum. In the present work, Monte Carlo simulations were performed to calculate these microdosimetric parameters for different source-target configurations and sizes in cells. The effective relative biological effectiveness (RBE) of the Tsing Hua Open-pool Reactor (THOR) epithermal neutron beam was evaluated using biological weighting functions that depended on the lineal energy. RBE changes with source-target configurations and sizes were analyzed. (author)

The relative biological effectiveness (RBE) of high-energy electrons, x-rays and Co-60 gamma-rays

International Nuclear Information System (INIS)

Kiyono, Kunihiro

1974-01-01

Linac (Mitsubishi-Shimizu 15 MeV medical linear accelerator) electron beams with actual generated energies of 8, 10, 12 and 15 MeV were compared with X-ray beams having energies of 8 and 10 MV. The RBE values were calculated from 50 percent hatch-ability (LD 50 ) in silk-worm embryos, 30-days lethality (LDsub(50/30)) in ddY mice, and mean lethal dose (Do) in cultured mouse YL cells or human FL cells. To estimate the RBE in clinical experiments, LRD (leukocyte reduction dose) value was calculated for each patient irradiated on the chest or lumbar vertebrae. It was concluded that there is little difference in practical significance between 8 to 10 MV X-rays and 8 to 15 MeV electrons, and that the biological effects of Linac radiations are about 90 to 100 percent of the effect of 60 Co gamma rays. The RBE values gradually decreased, contrary to the elevation of energy between 8 and 15 MeV for electrons and between 8 and 10 MV for X-rays. These values were compared with those of earlier reviews of work in this field, and were briefly discussed. (Evans, J.)

Impaired degradation followed by enhanced recycling of epidermal growth factor receptor caused by hypo-phosphorylation of tyrosine 1045 in RBE cells

International Nuclear Information System (INIS)

Gui, Anping; Kobayashi, Akira; Motoyama, Hiroaki; Kitazawa, Masato; Takeoka, Michiko; Miyagawa, Shinichi

2012-01-01

Since cholangiocarcinoma has a poor prognosis, several epidermal growth factor receptor (EGFR)-targeted therapies with antibody or small molecule inhibitor treatment have been proposed. However, their effect remains limited. The present study sought to understand the molecular genetic characteristics of cholangiocarcinoma related to EGFR, with emphasis on its degradation and recycling. We evaluated EGFR expression and colocalization by immunoblotting and immunofluorescence, cell surface EGFR expression by fluorescence-activated cell sorting (FACS), and EGFR ubiquitination and protein binding by immunoprecipitation in the human cholangiocarcinoma RBE and immortalized cholangiocyte MMNK-1 cell lines. Monensin treatment and Rab11a depletion by siRNA were adopted for inhibition of EGFR recycling. Upon stimulation with EGF, ligand-induced EGFR degradation was impaired and the expression of phospho-tyrosine 1068 and phospho-p44/42 MAPK was sustained in RBE cells as compared with MMNK-1 cells. In RBE cells, the process of EGFR sorting for lysosomal degradation was blocked at the early endosome stage, and non-degradated EGFR was recycled to the cell surface. A disrupted association between EGFR and the E3 ubiquitin ligase c-Cbl, as well as hypo-phosphorylation of EGFR at tyrosine 1045 (Tyr1045), were also observed in RBE cells. In RBE cells, up-regulation of EGFR Tyr1045 phosphorylation is a potentially useful molecular alteration in EGFR-targeted therapy. The combination of molecular-targeted therapy determined by the characteristics of individual EGFR phosphorylation events and EGFR recycling inhibition show promise in future treatments of cholangiocarcinoma

Controlling Depth of Cellular Quiescence by an Rb-E2F Network Switch

Directory of Open Access Journals (Sweden)

Jungeun Sarah Kwon

2017-09-01

Full Text Available Quiescence is a non-proliferative cellular state that is critical to tissue repair and regeneration. Although often described as the G0 phase, quiescence is not a single homogeneous state. As cells remain quiescent for longer durations, they move progressively deeper and display a reduced sensitivity to growth signals. Deep quiescent cells, unlike senescent cells, can still re-enter the cell cycle under physiological conditions. Mechanisms controlling quiescence depth are poorly understood, representing a currently underappreciated layer of complexity in growth control. Here, we show that the activation threshold of a Retinoblastoma (Rb-E2F network switch controls quiescence depth. Particularly, deeper quiescent cells feature a higher E2F-switching threshold and exhibit a delayed traverse through the restriction point (R-point. We further show that different components of the Rb-E2F network can be experimentally perturbed, following computer model predictions, to coarse- or fine-tune the E2F-switching threshold and drive cells into varying quiescence depths.

Experimental RBE values of high LET radiations at low doses and the implications for quality factor assignment

International Nuclear Information System (INIS)

Sinclair, W.K.

1985-01-01

RBE determinations of special relevance to the quality factor assigned for radiation protection purposes are those relating to the effects of special importance at low doses, namely carcinogenesis and mutagenesis. Measurements of RBE that enable the maximum value of RBE, namely RBEsub(M), to be determined at low doses require data points as low as 0.1 Gy or even 0.01 Gy or high LET radiation. Corresponding data points as low as 0.5 Gy to 0.25 Gy or less of low LET radiation are also needed. Relatively few such measurements have been made, but many more are available now than formerly. A review of recent RBEs for tumour induction, life shortening, transformation, cytogenetics and genetic endpoints, which updated an earlier review, indicates a broad range of results. The principle findings are that X rays are more effective than hard γ rays at low doses by a factor of about 2, and that fission neutrons, alpha particles and heavy ions may be 30-50 times more effective, on the average, (some endpoints give higher, some lower values) than hard γ rays. The data would seem to indicate that in order to provide approximately equal protection against the risks at low doses from all radiations, adjustments upward in the quality factors for high LET radiations need to be considered. (author)

TU-EF-304-10: Efficient Multiscale Simulation of the Proton Relative Biological Effectiveness (RBE) for DNA Double Strand Break (DSB) Induction and Bio-Effective Dose in the FLUKA Monte Carlo Radiation Transport Code

Energy Technology Data Exchange (ETDEWEB)

Moskvin, V; Tsiamas, P; Axente, M; Farr, J [St. Jude Children’s Research Hospital, Memphis, TN (United States); Stewart, R [University of Washington, Seattle, WA. (United States)

2015-06-15

Purpose: One of the more critical initiating events for reproductive cell death is the creation of a DNA double strand break (DSB). In this study, we present a computationally efficient way to determine spatial variations in the relative biological effectiveness (RBE) of proton therapy beams within the FLUKA Monte Carlo (MC) code. Methods: We used the independently tested Monte Carlo Damage Simulation (MCDS) developed by Stewart and colleagues (Radiat. Res. 176, 587–602 2011) to estimate the RBE for DSB induction of monoenergetic protons, tritium, deuterium, hellium-3, hellium-4 ions and delta-electrons. The dose-weighted (RBE) coefficients were incorporated into FLUKA to determine the equivalent {sup 6}°60Co γ-ray dose for representative proton beams incident on cells in an aerobic and anoxic environment. Results: We found that the proton beam RBE for DSB induction at the tip of the Bragg peak, including primary and secondary particles, is close to 1.2. Furthermore, the RBE increases laterally to the beam axis at the area of Bragg peak. At the distal edge, the RBE is in the range from 1.3–1.4 for cells irradiated under aerobic conditions and may be as large as 1.5–1.8 for cells irradiated under anoxic conditions. Across the plateau region, the recorded RBE for DSB induction is 1.02 for aerobic cells and 1.05 for cells irradiated under anoxic conditions. The contribution to total effective dose from secondary heavy ions decreases with depth and is higher at shallow depths (e.g., at the surface of the skin). Conclusion: Multiscale simulation of the RBE for DSB induction provides useful insights into spatial variations in proton RBE within pristine Bragg peaks. This methodology is potentially useful for the biological optimization of proton therapy for the treatment of cancer. The study highlights the need to incorporate spatial variations in proton RBE into proton therapy treatment plans.

Incidence of CNS Injury for a Cohort of 111 Patients Treated With Proton Therapy for Medulloblastoma: LET and RBE Associations for Areas of Injury

Energy Technology Data Exchange (ETDEWEB)

Giantsoudi, Drosoula; Sethi, Roshan V. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Yeap, Beow Y. [Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts (United States); Eaton, Bree R. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Ebb, David H. [Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts (United States); Caruso, Paul A.; Rapalino, Otto [Department of Radiology (O.R.) at the Massachusetts General Hospital, Boston, Massachusetts (United States); Chen, Yen-Lin E.; Adams, Judith A.; Yock, Torunn I.; Tarbell, Nancy J.; Paganetti, Harald [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); MacDonald, Shannon M., E-mail: smacdonald@mgh.harvard.edu [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

2016-05-01

Background: Central nervous system (CNS) injury is a rare complication of radiation therapy for pediatric brain tumors, but its incidence with proton radiation therapy (PRT) is less well defined. Increased linear energy transfer (LET) and relative biological effectiveness (RBE) at the distal end of proton beams may influence this risk. We report the incidence of CNS injury in medulloblastoma patients treated with PRT and investigate correlations with LET and RBE values. Methods and Materials: We reviewed 111 consecutive patients treated with PRT for medulloblastoma between 2002 and 2011 and selected patients with clinical symptoms of CNS injury. Magnetic resonance imaging (MRI) findings for all patients were contoured on original planning scans (treatment change areas [TCA]). Dose and LET distributions were calculated for the treated plans using Monte Carlo system. RBE values were estimated based on LET-based published models. Results: At a median follow-up of 4.2 years, the 5-year cumulative incidence of CNS injury was 3.6% for any grade and 2.7% for grade 3+. Three of 4 symptomatic patients were treated with a whole posterior fossa boost. Eight of 10 defined TCAs had higher LET values than the target but statistically nonsignificant differences in RBE values (P=.12). Conclusions: Central nervous system and brainstem injury incidence for PRT in this series is similar to that reported for photon radiation therapy. The risk of CNS injury was higher for whole posterior fossa boost than for involved field. Although no clear correlation with RBE values was found, numbers were small and additional investigation is warranted to better determine the relationship between injury and LET.

Incidence of CNS Injury for a Cohort of 111 Patients Treated With Proton Therapy for Medulloblastoma: LET and RBE Associations for Areas of Injury

International Nuclear Information System (INIS)

Giantsoudi, Drosoula; Sethi, Roshan V.; Yeap, Beow Y.; Eaton, Bree R.; Ebb, David H.; Caruso, Paul A.; Rapalino, Otto; Chen, Yen-Lin E.; Adams, Judith A.; Yock, Torunn I.; Tarbell, Nancy J.; Paganetti, Harald; MacDonald, Shannon M.

2016-01-01

Background: Central nervous system (CNS) injury is a rare complication of radiation therapy for pediatric brain tumors, but its incidence with proton radiation therapy (PRT) is less well defined. Increased linear energy transfer (LET) and relative biological effectiveness (RBE) at the distal end of proton beams may influence this risk. We report the incidence of CNS injury in medulloblastoma patients treated with PRT and investigate correlations with LET and RBE values. Methods and Materials: We reviewed 111 consecutive patients treated with PRT for medulloblastoma between 2002 and 2011 and selected patients with clinical symptoms of CNS injury. Magnetic resonance imaging (MRI) findings for all patients were contoured on original planning scans (treatment change areas [TCA]). Dose and LET distributions were calculated for the treated plans using Monte Carlo system. RBE values were estimated based on LET-based published models. Results: At a median follow-up of 4.2 years, the 5-year cumulative incidence of CNS injury was 3.6% for any grade and 2.7% for grade 3+. Three of 4 symptomatic patients were treated with a whole posterior fossa boost. Eight of 10 defined TCAs had higher LET values than the target but statistically nonsignificant differences in RBE values (P=.12). Conclusions: Central nervous system and brainstem injury incidence for PRT in this series is similar to that reported for photon radiation therapy. The risk of CNS injury was higher for whole posterior fossa boost than for involved field. Although no clear correlation with RBE values was found, numbers were small and additional investigation is warranted to better determine the relationship between injury and LET.

Incidence of CNS Injury for a Cohort of 111 Patients Treated With Proton Therapy for Medulloblastoma: LET and RBE Associations for Areas of Injury.

Science.gov (United States)

Giantsoudi, Drosoula; Sethi, Roshan V; Yeap, Beow Y; Eaton, Bree R; Ebb, David H; Caruso, Paul A; Rapalino, Otto; Chen, Yen-Lin E; Adams, Judith A; Yock, Torunn I; Tarbell, Nancy J; Paganetti, Harald; MacDonald, Shannon M

2016-05-01

Central nervous system (CNS) injury is a rare complication of radiation therapy for pediatric brain tumors, but its incidence with proton radiation therapy (PRT) is less well defined. Increased linear energy transfer (LET) and relative biological effectiveness (RBE) at the distal end of proton beams may influence this risk. We report the incidence of CNS injury in medulloblastoma patients treated with PRT and investigate correlations with LET and RBE values. We reviewed 111 consecutive patients treated with PRT for medulloblastoma between 2002 and 2011 and selected patients with clinical symptoms of CNS injury. Magnetic resonance imaging (MRI) findings for all patients were contoured on original planning scans (treatment change areas [TCA]). Dose and LET distributions were calculated for the treated plans using Monte Carlo system. RBE values were estimated based on LET-based published models. At a median follow-up of 4.2 years, the 5-year cumulative incidence of CNS injury was 3.6% for any grade and 2.7% for grade 3+. Three of 4 symptomatic patients were treated with a whole posterior fossa boost. Eight of 10 defined TCAs had higher LET values than the target but statistically nonsignificant differences in RBE values (P=.12). Central nervous system and brainstem injury incidence for PRT in this series is similar to that reported for photon radiation therapy. The risk of CNS injury was higher for whole posterior fossa boost than for involved field. Although no clear correlation with RBE values was found, numbers were small and additional investigation is warranted to better determine the relationship between injury and LET. Published by Elsevier Inc.

Dynamical behaviors of Rb-E2F pathway including negative feedback loops involving miR449.

Science.gov (United States)

Yan, Fang; Liu, Haihong; Hao, Junjun; Liu, Zengrong

2012-01-01

MiRNAs, which are a family of small non-coding RNAs, regulate a broad array of physiological and developmental processes. However, their regulatory roles have remained largely mysterious. E2F is a positive regulator of cell cycle progression and also a potent inducer of apoptosis. Positive feedback loops in the regulation of Rb-E2F pathway are predicted and shown experimentally. Recently, it has been discovered that E2F induce a cluster of miRNAs called miR449. In turn, E2F is inhibited by miR449 through regulating different transcripts, thus forming negative feedback loops in the interaction network. Here, based on the integration of experimental evidence and quantitative data, we studied Rb-E2F pathway coupling the positive feedback loops and negative feedback loops mediated by miR449. Therefore, a mathematical model is constructed based in part on the model proposed in Yao-Lee et al. (2008) and nonlinear dynamical behaviors including the stability and bifurcations of the model are discussed. A comparison is given to reveal the implication of the fundamental differences of Rb-E2F pathway between regulation and deregulation of miR449. Coherent with the experiments it predicts that miR449 plays a critical role in regulating the cell cycle progression and provides a twofold safety mechanism to avoid excessive E2F-induced proliferation by cell cycle arrest and apoptosis. Moreover, numerical simulation and bifurcation analysis shows that the mechanisms of the negative regulation of miR449 to three different transcripts are quite distinctive which needs to be verified experimentally. This study may help us to analyze the whole cell cycle process mediated by other miRNAs more easily. A better knowledge of the dynamical behaviors of miRNAs mediated networks is also of interest for bio-engineering and artificial control.

RBE of heavy ions (carbon, neon, helium, proton) for acute cell death of pancreatic islet cells

International Nuclear Information System (INIS)

Tsubouchi, Susumu; Fukutsu, Kumiko; Itsukaichi, Hiromi

2003-01-01

At this fiscal year, only two times irradiation experiments with neon and helium beams were performed to obtain relative biological effectiveness (RBE) of heavy ions (carbon, neon, helium, proton) for acute cell death of pancreatic islet cells in vivo. First of all this project was designed to obtain RBE of 290 MeV carbon and 400 MeV neon beams in the high linear energy transfer (LET) region for acute cell death of pancreatic islets of golden hamster (Mesocricetus auratus) in the condition of in both in vivo and in vitro systems. As mentioned in previous report, in vitro system, however, resulted in ill success. This in vitro experiment was tentatively shelved for the time being. In return in vivo experiments for low LET region of neon beams (32.5 KeV/u), carbon beams (15.0 KeV/u) and helium beams (2 KeV/u) were performed in these two years. Last year these results together with those previously obtained for 200 KeV X-ray, 70 MeV proton, 290 MeV carbon (60 KeV/u), and neon (100 KeV/u) beams were reconsidered. At this year dose response relations (25, 50, 100, 150, and 200 Gy respectively) in acute cell death of pancreatic islets studied histologically after whole body irradiation of 3 weeks young male golden hamster with lower LET helium beams (2 KeV/u) and neon beams (32.5 KeV/u). Results indicated that mean cell lethal dose (Do) of helium beams (2 KeV/u) and neon beams (32.5 KeV/u) were 38 Gy and 49 Gy, respectively. Previously obtained Do data for 200 KeV x-ray, 70 MeV proton, 290 MeV carbon (15 KeV/u), 400 MeV neon (32.5 KeV/u), 290 MeV carbon (60 KeV/u), and 400 MeV neon (100 KeV/u) beams were 37 Gy, 38 Gy, 38 Gy, 49 Gy, 75 Gy, and 200 Gy, respectively. From these data estimated RBE of neon (100 KeV/u and 32.5 KeV/u), carbon (60 KeV/u and 15.0 KeV/u), 70 MeV proton and 150 MeV helium (2 KeV/u) beams were 0.19, 0.76, 0.49, 0.97, 0.97, 0.97, respectively. Therefore the order of RBE (or radiosensitivities) of islets cells with these various heavy ion beams was

Inverse gamma ray dose rate effect in californium-252 RBE experiment with human T-1 cells irradiated in vitro

International Nuclear Information System (INIS)

Todd, P.; Feola, J.M.

1986-01-01

Metabolically deoxygenated suspensions of human T-1 cells were used to determine the RBE in hypoxia of low dose rate (LDR) Cf-252 radiation compared to LDR gamma radiation. Based upon the initial portion of the survival curves the RBE was 5.0 ± 1.0 for all components of the Cf-252 radiation and 7.1 ± 1.7 for the neutrons alone. An inverse dose rate effect was observed for LDR gamma radiation in which greater cell sensitivity was observed at lower dose rates and longer irradiation periods. It was demonstrated that there was little or no sublethal damage repair or cell progression during LDR at 21 deg C, and the observed decrease in cell survival probability with increasing irradiation time at a given dose was attributable to reoxygenation of the cell suspensions during the course of LDR exposures. (Auth.)

Theory of RBE. Annual technical progress report, 1 January--31 December, 1994

International Nuclear Information System (INIS)

Katz, R.

1994-01-01

In researching the theory of RBE, attention is focused on several topics of importance. They include: improving knowledge of the radial distribution of dose about the path of an energetic heavy ion in different media; calculations which have demonstrated that three Escherichia coli mutants behave as 1-hit detectors; lethal mutations in a nematode induced by gamma radiation and heavy ion beams; prevalence in cancer induction in the Harderian gland by HZE particles; subtleties in the analysis of radiobiological data; low-dose irradiation effects; high LET effects; cellular radiosensitivity parameters; and radial dose calculations for mammalian cells

[miR-503-5p inhibits the proliferation of T24 and EJ bladder cancer cells by interfering with the Rb/E2F signaling pathway].

Science.gov (United States)

Li, Xiaohui; Han, Xingtao; Yang, Jinhui; Sun, Jiantao; Wei, Pengtao

2017-10-01

Objective To observe the effect of microRNA-503-5p (miR-503-5p) on the growth of T24 and EJ bladder cancer cells, and explore the possible molecular mechanism. Methods The miR-504-5p mimics or miR-NC was transfected into T24 and EJ cells. The target gene of miR-503-5p was predicted by bioinformatics. The expressions of E2F transcription factor 3 (E2F3) mRNA and Rb/E2F signaling pathway mRNA were detected by the real-time quantitative PCR (qPCR). The expressions of Rb/E2F signal pathway proteins E2F3, cyclin E, CDK2, Rb and p-Rb were detected by Western blotting. The cell cycle of bladder cancer cell lines was determined by flow cytometry. MTT assay and plate cloning assay were performed to observe the proliferation ability of bladder cancer cells. Results After miR-503-5p mimics transfection, the expression of miR-503-5p in bladder cancer cells significantly increased. The increased expression of miR-503-5p significantly reduced the expressions of E2F3 mRNA and Rb/E2F signaling pathway mRNA in bladder cancer cells. What's more, the expressions of Rb/E2F signal pathway proteins were down-regulated. The bladder cancer cells were arrested in G0/G1 phase, and their growth was significantly inhibited by miR-503-5p. Conclusion The miR-503-5p over-expression can inhibit the growth of bladder cancer cell lines T24 and EJ by down-regulating the expression of the Rb/E2F signaling pathway.

RBE of 0,85 MeV neutrons in guinea pigs with intestinal form of radiation sickness

International Nuclear Information System (INIS)

Shaporov, V.N.; Sokolova, T.I.; Nasonova, T.A.; Aleshin, S.N.

1989-01-01

Relative biological effectiveness (RBE) coefficient of 0.85 MeV neutrons was 1.87 in comparison with 0.66 MeV γ-radiation ( 137 Cs) when estimated by the death rate of guinea pigs with intestinal form of radiation sickness. LD 50/5 was 5.9 and 11.06 respectively. Features of the mortality rate dynamics, clinical picture and pathoanatomical changes are discussed

The relationships between RBE and LET for different types of lethal damage in mammalian cells: biophysical and molecular mechanisms

NARCIS (Netherlands)

Barendsen, G. W.

1994-01-01

The relative biological effectiveness (RBE) of radiations as a function of linear energy transfer (LET) is analyzed for different types of damage causing reproductive death of mammalian cells. Survival curves are evaluated assuming a linear-quadratic dose dependence of the induction of reproductive

Theory of RBE. Fifth triennial report, 1 January 1967-31 December 1981

International Nuclear Information System (INIS)

Katz, R.

1981-07-01

A single theme, that the response of a detector to gamma-rays (interpreted probabilistically through an extension of target theory) can be mapped into the region surrounding the path of an energetic heavy ion, through the local dose deposited by its delta-rays, has been the continuing basis of the present research. In order to systematize the understanding of RBE we have introduced new concepts to create a predictive theory of radiation response, of the structure of particle tracks, in a wide range of physical and biological systems. We have built a theory that is more generally applicable, to physical as well as to biological detectors, using the same basic concepts and operationally defined parameters. This procedure enables us to make quantitative experimental tests of the validity of our conceptual structure. We have created a systematic classification of detector properties, and have shown how their response varies with the numerical values of detector parameters within these classifications. Especially for 1-hit detection, our theory is universally accepted and applied. Originally created to explain the RBE of dry enzymes and viruses, it has been extended to scintillation counters, to particle tracks in nuclear emulsions, to thermoluminescent dosimeters, to lyo-luminescence, to single strand breaks in DNA, to the formation of color centers in crystals, and onwards. The extension of this conceptual system to biology required the many-hit detector, with its potential for the accumulation of sub-lethal damage. We have predicted the response of biological cells in high LET environments from this theory. It has served as the stimulus for discovering many hit physical systems (emulsions, photoresists) which respond preferentially to high LET radiations

On the dose calculation at the cellular level and its implications for the RBE of {sup 99m}Tc and {sup 123}I

Energy Technology Data Exchange (ETDEWEB)

Freudenberg, R., E-mail: robert.freudenberg@uniklinikum-dresden.de; Runge, R.; Maucksch, U.; Berger, V.; Kotzerke, J. [University Hospital/Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Department of Nuclear Medicine, Dresden, Saxony 01307 (Germany)

2014-06-15

Purpose: Based on the authors’ previous findings concerning the radiotoxicity of{sup 99m}Tc, the authors compared the cellular survival under the influence of this nuclide with that following exposure to the Auger electron emitter {sup 123}I. To evaluate the relative biological effectiveness (RBE) of both radionuclides, knowledge of the absorbed dose is essential. Thus, the authors present the dose calculations and discuss the results based on different models of the radionuclide distribution. Both different target volumes and the influence of the uptake kinetics were considered. Methods: Rat thyroid PC Cl3 cells in culture were incubated with either{sup 99m}Tc or {sup 123}I or were irradiated using 200 kV x-rays in the presence or absence of perchlorate. The clonogenic cell survival was measured via colony formation. In addition, the intracellular radionuclide uptake was quantified. Single-cell dose calculations were based on Monte Carlo simulations performed using Geant4. Results: Compared with external radiation using x-rays (D{sub 37} = 2.6 Gy), the radionuclides {sup 99m}Tc (D{sub 37} = 3.5 Gy), and {sup 123}I (D{sub 37} = 3.8 Gy) were less toxic in the presence of perchlorate. In the absence of perchlorate, the amount of activity a{sub 37} that was necessary to reduce the surviving fraction (SF) to 0.37 was 22.8 times lower for {sup 99m}Tc and 12.4 times lower for {sup 123}I because of the dose increase caused by intracellular radionuclide accumulation. When the cell nucleus was considered as the target for the dose calculation, the authors found a RBE of 2.18 for {sup 99m}Tc and RBE = 3.43 for {sup 123}I. Meanwhile, regarding the dose to the entire cell, RBE = 0.75 for {sup 99m}Tc and RBE = 1.87 for {sup 123}I. The dose to the entire cell was chosen as the dose criterion because of the intracellular radionuclide accumulation, which was found to occur solely in the cytoplasm. The calculated number of intracellular decays per cell was (975 ± 109) decays

Dynamical behaviors of Rb-E2F pathway including negative feedback loops involving miR449.

Directory of Open Access Journals (Sweden)

Fang Yan

Full Text Available MiRNAs, which are a family of small non-coding RNAs, regulate a broad array of physiological and developmental processes. However, their regulatory roles have remained largely mysterious. E2F is a positive regulator of cell cycle progression and also a potent inducer of apoptosis. Positive feedback loops in the regulation of Rb-E2F pathway are predicted and shown experimentally. Recently, it has been discovered that E2F induce a cluster of miRNAs called miR449. In turn, E2F is inhibited by miR449 through regulating different transcripts, thus forming negative feedback loops in the interaction network. Here, based on the integration of experimental evidence and quantitative data, we studied Rb-E2F pathway coupling the positive feedback loops and negative feedback loops mediated by miR449. Therefore, a mathematical model is constructed based in part on the model proposed in Yao-Lee et al. (2008 and nonlinear dynamical behaviors including the stability and bifurcations of the model are discussed. A comparison is given to reveal the implication of the fundamental differences of Rb-E2F pathway between regulation and deregulation of miR449. Coherent with the experiments it predicts that miR449 plays a critical role in regulating the cell cycle progression and provides a twofold safety mechanism to avoid excessive E2F-induced proliferation by cell cycle arrest and apoptosis. Moreover, numerical simulation and bifurcation analysis shows that the mechanisms of the negative regulation of miR449 to three different transcripts are quite distinctive which needs to be verified experimentally. This study may help us to analyze the whole cell cycle process mediated by other miRNAs more easily. A better knowledge of the dynamical behaviors of miRNAs mediated networks is also of interest for bio-engineering and artificial control.

Relative biological effectiveness (R.B.E.) of Cf-252 vs. acute Co-60 and low dose rate Cs-137 irradiation by spleen weight loss

International Nuclear Information System (INIS)

Maruyama, Y.; Feola, J.M.; Magura, C.; Beach, J.L.

1986-01-01

R.B.E. of Cf-252 on lymphoid tissue was assessed by radiation study of spleen weight loss following acute Co-60, and low dose rate (L.D.R.) Cs-137 and Cf-252 irradiations. Acute Co-60 and L.D.R. Cs-137 dose-response followed two component exponential curves with a 1.3-fold greater effect of L.D.R. Cs-137 vs. acute Co-60 on the first slope and 1.9-fold greater effect for the 2nd slope. L.D.R. Cf-252 response was 1.3 x greater than acute Co-60 but was 1.0 vs. L.D.R. Cs-137 for the first slope indicating a similar effect of Cf-252 mixed neutron/gamma radiation to L.D.R. gamma radiation in producing spleen shrinkage. There was no effect of different sequences and schedules of mixing acute Co-60 with Cf-252 irradiation observed by endogenous CFU-S survival. The R.B.E. of 1.0 - 1.9 indicates that lymphohemopoietic in vivo, presumably well oxygenated, does not respond acutely or as sensitively as hypoxic tumor where R.B.E. is 5 - 7. (author)

RBE of 0.85 MeV neutrons in Guinea pigs with a cerebral form of radiation sickness

International Nuclear Information System (INIS)

Shaporov, V.N.; Sokolova, T.I.; Nasonova, T.A.; Aleshin, S.I.

1989-01-01

The RBE coefficient of neutrons (0.85 MeV) was 1.87 in comparison with that of electron radiation (8 MeV) as determined by the death rate of guinea pigs with the cerebral form of radiation sickness. LD 50/1.5 amounted to 43.2 and 80.7 Gy. The dynamics of clinical symptoms at the height of the disease is discussed

Major compound-dependent variations of 10B(nα)7 Li RBE for the 9L RAT gliosarcoma in vitro and in vivo

International Nuclear Information System (INIS)

Coderre, J.A.; Makar, M.S.; Micca, P.L.; Nawrocky, M.M.; Joel, D.D.; Slatkin, D.N.

1991-01-01

Relative biological effectiveness (RBE) values for the high linear-energy-transfer (LET) radiations produced during born neutron capture therapy (BNCT) were determined using the 9L rat gliosarcorna both in vitro and as an intracerebral tumor. In the absence of 10 B, the combined effect of the recoiling protons from the 14 N(n,p) 14 C and the 1 H(n,n')p reactions, compared to an iso-effect endpoint produced by 250 kVp x-rays, yielded RBEs for these high-LET protons of 4.4 in vitro and 3.8 in an in vivo/in vitro assay. RBEs for the 10 B(n,α) 7 Li reaction were calculated from cell survival data following reactor irradiation in the presence or in the absence of the either of the amino acid, p-boronophenylalanine (BPA) or the sulfhydryl dodecaborane dimer (BSSB). With BPA, RBE values ranged from 3.5 to 11.4, while under the same set of conditions with BSSB, RBE values ranged from 1.1 to 4.3. In vitro, higher RBEs for the 10 B(n,α) 7 Li reaction using BPA than with BSSB suggest a difference in distribution of 10 B relative to the nucleus

Relative biological effectiveness (RBE) of fast neutrons with the Dunning rat prostate tumor R3327-HI

International Nuclear Information System (INIS)

Wenz, F.; Lohr, F.; Peschke, P.; Wolber, G.; Hoever, K.H.; Hahn, E.W.

1993-01-01

Human prostate tumors are known to be good candidates for neutron therapy. The Dunning rat prostate tumor system R3327 was found in many studies to be an excellent model for human prostate tumors. There is still a paucity of studies on the response of the Dunning tumors to fast neutrons. Tumors of the R3327-HI subline are moderately well differentiated and mucin producing. They show one euploid cell population, a bromodeoxyuridine labelling index of 5%, a potential doubling time of 8.9 days, a volume doubling time of about ten days and a cell loss rate of 10%. Tumors were transplanted s.c. in the distal thigh of Copenhagen rats and treated with 60 Co-photons (10, 20, 30, 40 Gy, 45 cGy/min) and 14-MeV-neutrons (8, 10, 12 Gy, 7 to 11 cGy/min). Tumor volumes were measured twice weekly. Growth delay was defined as time in days until the tumors reached twice their treatment volume. Linear regressions on the median growth delays of the different treatment groups were calculated. The ratio of the neutron- and photon-slopes yielded an RBE of 3.1±0.3. Additionally isoeffect-RBE values between 2.3 and 2.6 were graphically estimated. (orig.) [de

Rapid MCNP simulation of DNA double strand break (DSB) relative biological effectiveness (RBE) for photons, neutrons, and light ions.

Science.gov (United States)

Stewart, Robert D; Streitmatter, Seth W; Argento, David C; Kirkby, Charles; Goorley, John T; Moffitt, Greg; Jevremovic, Tatjana; Sandison, George A

2015-11-07

To account for particle interactions in the extracellular (physical) environment, information from the cell-level Monte Carlo damage simulation (MCDS) for DNA double strand break (DSB) induction has been integrated into the general purpose Monte Carlo N-particle (MCNP) radiation transport code system. The effort to integrate these models is motivated by the need for a computationally efficient model to accurately predict particle relative biological effectiveness (RBE) in cell cultures and in vivo. To illustrate the approach and highlight the impact of the larger scale physical environment (e.g. establishing charged particle equilibrium), we examined the RBE for DSB induction (RBEDSB) of x-rays, (137)Cs γ-rays, neutrons and light ions relative to γ-rays from (60)Co in monolayer cell cultures at various depths in water. Under normoxic conditions, we found that (137)Cs γ-rays are about 1.7% more effective at creating DSB than γ-rays from (60)Co (RBEDSB  =  1.017) whereas 60-250 kV x-rays are 1.1 to 1.25 times more efficient at creating DSB than (60)Co. Under anoxic conditions, kV x-rays may have an RBEDSB up to 1.51 times as large as (60)Co γ-rays. Fission neutrons passing through monolayer cell cultures have an RBEDSB that ranges from 2.6 to 3.0 in normoxic cells, but may be as large as 9.93 for anoxic cells. For proton pencil beams, Monte Carlo simulations suggest an RBEDSB of about 1.2 at the tip of the Bragg peak and up to 1.6 a few mm beyond the Bragg peak. Bragg peak RBEDSB increases with decreasing oxygen concentration, which may create opportunities to apply proton dose painting to help address tumor hypoxia. Modeling of the particle RBE for DSB induction across multiple physical and biological scales has the potential to aid in the interpretation of laboratory experiments and provide useful information to advance the safety and effectiveness of hadron therapy in the treatment of cancer.

RBE-LET relationships for different types of lethal radiation damage in mammalian cells: comparison with DNA dsb and an interpretation of differences in radiosensitivity

NARCIS (Netherlands)

Barendsen, G. W.

1994-01-01

Relative biological effectiveness (RBE), as a function of linear energy transfer (LET), is evaluated for different types of damage contributing to mammalian cell reproductive death. Survival curves are analysed assuming a linear-quadratic dose dependence of lethal lesions. The linear term represents

RBE of the NCT beam at Petten (The Netherlands) for intestinal crypt regeneration in mice

International Nuclear Information System (INIS)

Gueulette, J.; Coster, B.M. de; Wambersie, A.; Stecher-Rasmussen, F.; Huiskamp, R.; Moss, R.; Morrissey, J.

2000-01-01

RBE of the BNCT epithermal neutron beam at Petten (The Netherlands) has been determined for intestinal crypt regeneration in mice i.e. an in vivo system. No boron was administered. This experiment is part of an IAEA programme aiming at intercomparing radiobiologically the NCT neutron beams of different facilities world-wide. Six MV photons were used as the reference radiation. For the NCT beam at Petten, irradiation times ranging between 1 and 3 hours were applied. These low dose rate irradiations (∼3 Gy/hour) were found ∼2.4 more effective than acute photon irradiations. This type of experiment - repeated at different BNCT facilities - will improve harmonisation in the radiobiological specification of NCT neutron beams and facilitate exchange of clinical information. (author)

RBE [relative biological effectiveness] of tritium beta radiation to gamma radiation and x-rays analyzed by both molecular and genetic methods

International Nuclear Information System (INIS)

Lee, W.R.

1988-01-01

The relative biological effectiveness (RBE) of tritium beta radiation to 60 Co gamma radiation was determined using sex-linked recessive lethals (SLRL) induced in Drosophila melanogaster spermatozoa as the biological effect. The SLRL test, a measure of mutations induced in germ cells transmitted through successive generations, yields a linear dose-response curve in the range used in these experiments. From these ratios of the slopes of the 3 H beta and the 60 Co gamma radiation linear dose response curves, an RBE of 2.7 is observed. When sources of error are considered, this observation suggests that the tritium beta particle is 2.7 ± 0.3 times more effective per unit of energy absorbed in inducing gene mutations transmitted to successive generation than 60 Co gamma radiation. Ion tracks with a high density of ions (high LET) are more efficient than tracks with a low ion density (low LET) in inducing transmissible mutations, suggesting interaction among products of ionization. Molecular analysis of x-ray induced mutations shows that most mutations are deletions ranging from a few base pairs as determined from sequence data to multi locus deletions as determined from complementation tests and Southern blots. 14 refs., 1 fig

Microdosimetry spectra and RBE of 1H, 4He, 7Li and 12C nuclei in water studied with Geant4

International Nuclear Information System (INIS)

Burigo, Lucas; Pshenichnov, Igor; Mishustin, Igor; Bleicher, Marcus

2014-01-01

A Geant4-based Monte Carlo model for Heavy-Ion Therapy (MCHIT) is used to study radiation fields of 1 H, 4 He, 7 Li and 12 C beams with similar ranges (∼160–180 mm) in water. Microdosimetry spectra are simulated for wall-less and walled Tissue Equivalent Proportional Counters (TEPCs) placed outside or inside a phantom, as in experiments performed, respectively, at NIRS, Japan and GSI, Germany. The impact of fragmentation reactions on microdosimetry spectra is investigated for 4 He, 7 Li and 12 C, and contributions from nuclear fragments of different charge are evaluated for various TEPC positions in the phantom. The microdosimetry spectra measured on the beam axis are well described by MCHIT, in particular, in the vicinity of the Bragg peak. However, the simulated spectra for the walled TEPC far from the beam axis are underestimated. Relative Biological Effectiveness (RBE) of the considered beams is estimated using a modified microdosimetric-kinetic model. Calculations show a similar rise of the RBE up to 2.2–2.9 close to the Bragg peak for helium, lithium and carbon beams compared to the modest values of 1–1.2 at the plateau region. Our results suggest that helium and lithium beams are also promising options for cancer therapy

Algorithms for the optimization of RBE-weighted dose in particle therapy.

Science.gov (United States)

Horcicka, M; Meyer, C; Buschbacher, A; Durante, M; Krämer, M

2013-01-21

We report on various algorithms used for the nonlinear optimization of RBE-weighted dose in particle therapy. Concerning the dose calculation carbon ions are considered and biological effects are calculated by the Local Effect Model. Taking biological effects fully into account requires iterative methods to solve the optimization problem. We implemented several additional algorithms into GSI's treatment planning system TRiP98, like the BFGS-algorithm and the method of conjugated gradients, in order to investigate their computational performance. We modified textbook iteration procedures to improve the convergence speed. The performance of the algorithms is presented by convergence in terms of iterations and computation time. We found that the Fletcher-Reeves variant of the method of conjugated gradients is the algorithm with the best computational performance. With this algorithm we could speed up computation times by a factor of 4 compared to the method of steepest descent, which was used before. With our new methods it is possible to optimize complex treatment plans in a few minutes leading to good dose distributions. At the end we discuss future goals concerning dose optimization issues in particle therapy which might benefit from fast optimization solvers.

Generalized concept of the LET-RBE relationship of radiation-induced chromosome aberration and cell death

International Nuclear Information System (INIS)

Takatsuji, Toshihiro; Yoshikawa, Isao; Sasaki, Masao S.

1999-01-01

The frequency of chromosome aberrations per traversal of a nucleus by a charged particle at the low dose limit increases proportionally to the square of the linear energy transfer (LET), peaks at about 100 keV/μm and then decreases with further increase of LET. This has long been interpreted as an excessive energy deposition over the necessary energy required to produce a biologically effective event. Here, we present an alternative interpretation. Cell traversed by a charged particle has certain probability to receive lethal damage leading to direct death. Such events may increase with an increase of LET and the number of charged particles traversing the cell. Assuming that the lethal damage is distributed according to a Poisson distribution, the probability that a cell has no such damage is expressed by e -cLx , where c is a constant, L is LET, and x is the number of charged particles traversing the cell. From these assumptions, the frequency of chromosome aberration in surviving cells can be described by Y=αSD+βS 2 D 2 with the empirical relation Y=αD+βD 2 in the low LET region, where S=e -cL , α is a value proportional to LET, β is a constant, and D is the absorbed dose. This model readily explains the empirically established relationship between LET and relative biological effectiveness (RBE). The model can also be applied to clonogenic survival. If cells can survive and they have neither unstable chromosome aberrations nor other lethal damage, the LET-RBE relationship for clonogenic survival forms a humped curve. The relationship between LET and inactivation cross-section becomes proportional to the square of LET in the low LET region when the frequency of a directly lethal events is sufficiently smaller than unity, and the inactivation cross-section saturates to the cell nucleus cross-sectional area with an increase in LET in the high LET region. (author)

Enhanced neoplastic transformation by mammography X rays relative to 200 kVp X rays: indication for a strong dependence on photon energy of the RBE(M) for various end points.

Science.gov (United States)

Frankenberg, D; Kelnhofer, K; Bär, K; Frankenberg-Schwager, M

2002-01-01

The fundamental assumption implicit in the use of the atomic bomb survivor data to derive risk estimates is that the gamma rays of Hiroshima and Nagasaki are considered to have biological efficiencies equal to those of other low-LET radiations up to 10 keV/microm, including mammography X rays. Microdosimetric and radiobiological data contradict this assumption. It is therefore of scientific and public interest to evaluate the efficiency of mammography X rays (25-30 kVp) to induce cancer. In this study, the efficiency of mammography X rays relative to 200 kVp X rays to induce neoplastic cell transformation was evaluated using cells of a human hybrid cell line (CGL1). For both radiations, a linear-quadratic dose-effect relationship was observed for neoplastic transformation of CGL1 cells; there was a strong linear component for the 29 kVp X rays. The RBE(M) of mammography X rays relative to 200 kVp X rays was determined to be about 4 for doses energies of transformation of CGL1 cells. Both the data available in the literature and the results of the present study strongly suggest an increase of RBE(M) for carcinogenesis in animals, neoplastic cell transformation, and clastogenic effects with decreasing photon energy or increasing LET to an RBE(M) approximately 8 for mammography X rays relative to 60Co gamma rays.

Quality assurance (QA) program in BNCT. RBE of 7 NCT beams for intestinal crypt regeneration in mice

International Nuclear Information System (INIS)

John, Gueulette; De Coster, Blanche-Marie; Wambersie, Andre; Gregoire, Vincent; Rasmussen, Finn S.; Auterinen, Iiro; Binns, Peter; Blaumann, Herman; Matsumura, Akira; Liu Hongming

2006-01-01

The epithermal neutron beams presently used for Neutron Capture Therapy (NCT) differ substantially in their composition (relative contribution of the different dose components to the total dose), in their dose rate (depending on the power of the reactor) as well as in their general feature (e.g. beam delivery system). Each of these elements might alter significantly the biological effectiveness of the beams. Therefore, the Relative Biological Effectiveness (RBE) of 7 NCT beams was intercompared, for a reference biological system (crypt regeneration in mice) and under well-defined irradiation conditions. This type of experiments - which should facilitate the exchange of radiobiological/clinical information - should take part of the Quality Assurance (QA) procedure of all NCT beams. (author)

Determination of Relative Biological Efficacy (RBE) and Oxygen Enhancement Ratio (OER) for the entire negative and positive pion beam profile using Vicia faba roots and Drosophila embryos as biological model systems

International Nuclear Information System (INIS)

Baarli, J.; Bianchi, M.; Keusch, F.; Mindek, G.; Sullivan, A.H.

As an introduction to preclinical studies, pilot studies of pion beams are planned with relatively simple biological model systems that can be quickly evaluated and that yield indicative data for further action. Inhibition of growth was studied in Vicia faba roots, a biological system excellently suited for RBE and OER studies. For comparison there are already results from a low-intensity pion irradiation. A second system used Drosophila embryos 1 and 4 hours old, which are especially well suited for LET studies. The unambiguous criterion will be failure to slip out of the oolemma. The smallness of the objects (their beam sensitivity) will make it possible to determine empirically the peak region and to determine Gain factors; furthermore, the known dependency of RBE on the development stage promises highly informative results

Repair of potentially lethal radiation damage: comparison of neutron and x-ray RBE and implications for radiation therapy

International Nuclear Information System (INIS)

Hall, E.J.; Kraljevic, U.

1976-01-01

Experiments with Chinese hamster cells have shown that neutron irradiation does not result in repair of potentially lethal damage (PLD), i.e., that which can be influenced by changes in environmental conditions following irradiation. Since PLD is presumed to be repaired in tumors but not in normal tissues, this absence of differential sparing of tumor cells relative to normal tissues--a feature characteristic of irradiation with x rays--represents an advantage of neutrons in addition to their reduced oxygen effect. At a given dose, the difference in relative biological effectiveness (RBE) between tumors and normal tissues corresponds to a 5 percent increase in tumor dose with no concomitant increase in dose to normal tissues, which could be significant in cancer therapy

Relative biological effectiveness (RBE) of fission neutrons and gamma rays at occupational exposure levels: Volume 1, Studies on the genetic effects in mice of 60 equal once-weekly exposures to fission neutrons and gamma rays

International Nuclear Information System (INIS)

Grahn, D.; Carnes, B.A.

1987-10-01

The relative biological effectiveness (RBE) values for low doses of fission neutrons compared to 60 Co gamma rays were determined with four separate assessments of genetic damage induced in young hybrid male mice. Both radiations were delivered at low dose levels over about one-half the adult lifetime as 60 once-weekly exposures. Genetic damage assessed included both transient and residual injury. The latter is more critical, as residual genetic injury can be transmitted to subsequent generations long after the radiation exposures have ceased. Assays were performed periodically during the 60-week exposure period and at 10 or more weeks after the irradiations had terminated. RBE values, with few exceptions, ranged between 5 and 15 for transient injury and between 25 and 50 for different types of residual genetic injury. The most important form of residual genetic damage in this study was the balanced reciprocal chromosome translocation. These translocations continue to be transmitted throughout reproductive life and can lead to reduced fertility and increased prenatal mortality. The best estimate of the RBE value for translocations was 45 +- 10. Implications and recommendations with regard to the neutron quality factor will be presented conjointly with the findings from the data obtained in this same project on life shortening and on the risks of incidence or death from neoplastic disease. 64 refs., 23 tabs

The r.b.e. of different-energy neutrons as determined by human bone-marrow cell-culture techniques

International Nuclear Information System (INIS)

Boeyum, A.; Carsten, A.L.; Chikkappa, G.; Cook, L.; Bullis, J.; Honikel, L.; Cronkite, E.P.

1978-01-01

The effect of X-rays and different-energy neutrons on human bone-marrow cells was studied using two different cell-culture techniques - diffusion chamber (DC) growth and colony formation in vitro (CFU-C). Based on the survival and proliferative granulocytes in DC on day 13, the D 0 value was 80 rad with X-rays, and 117 rad as measured by the CFU-C assay. The D 0 values for neutrons depended on the radiation source and the energy level. The r.b.e. values, which dropped with increasing energy levels of mono-energetic neutrons, were (i) 0.44 MeV; DC 3.7, CFU-C 4.1; (ii) 6 MeV; DC 1.8, CFU-C 2.0; (iii) 15 MeV; DC 1.6, CFU-C 1.6; (iv) fission neutrons; DC 2.6, CFU-C 2.4. (author)

Limiting values for the RBE of fission neutrons at low doses for life shortening in mice

International Nuclear Information System (INIS)

Storer, J.B.; Mitchell, T.J.

1984-01-01

The authors have analyzed recently published data on the effects of low doses of fission neutrons on the mean survival times of mice. The analysis for single-dose exposures was confined to doses of 20 rad or less, while for fractionated exposures only total doses of 80 rad or less were considered. They fitted the data to the frequently used power function model: life shortening = βD/sup γ/, where D is the radiation dose. They show that, at low doses per fraction, either the effects are not additive or the dose-effect curve for single exposures cannot show a greater negative curvature than about the 0.9 power of dose. Analysis of the data for γ rays showed that an exponent of 1.0 gave an acceptable fit. They conclude that at neutron doses of 20 rad or less the RBE for life shortening is constant and ranges from 13 to 22 depending on mouse strain and sex

MO-FG-CAMPUS-TeP3-02: Benchmarks of a Proton Relative Biological Effectiveness (RBE) Model for DNA Double Strand Break (DSB) Induction in the FLUKA, MCNP, TOPAS, and RayStation™ Treatment Planning System

Energy Technology Data Exchange (ETDEWEB)

Stewart, R [University of Washington, Seattle, WA (United States); Streitmatter, S [University of Utah Hospitals, Salt Lake City, UT (United States); Traneus, E [RAYSEARCH LABORATORIES AB, Stockholm (Sweden); Moskvin, V [St. Jude Children’s Hospital, Memphis, TN (United States); Schuemann, J [Massachusetts General Hospital, Boston, MA (United States)

2016-06-15

Purpose: Validate implementation of a published RBE model for DSB induction (RBEDSB) in several general purpose Monte Carlo (MC) code systems and the RayStation™ treatment planning system (TPS). For protons and other light ions, DSB induction is a critical initiating molecular event that correlates well with the RBE for cell survival. Methods: An efficient algorithm to incorporate information on proton and light ion RBEDSB from the independently tested Monte Carlo Damage Simulation (MCDS) has now been integrated into MCNP (Stewart et al. PMB 60, 8249–8274, 2015), FLUKA, TOPAS and a research build of the RayStation™ TPS. To cross-validate the RBEDSB model implementation LET distributions, depth-dose and lateral (dose and RBEDSB) profiles for monodirectional monoenergetic (100 to 200 MeV) protons incident on a water phantom are compared. The effects of recoil and secondary ion production ({sub 2}H{sub +}, {sub 3}H{sub +}, {sub 3}He{sub 2+}, {sub 4}He{sub 2+}), spot size (3 and 10 mm), and transport physics on beam profiles and RBEDSB are examined. Results: Depth-dose and RBEDSB profiles among all of the MC models are in excellent agreement using a 1 mm distance criterion (width of a voxel). For a 100 MeV proton beam (10 mm spot), RBEDSB = 1.2 ± 0.03 (− 2–3%) at the tip of the Bragg peak and increases to 1.59 ± 0.3 two mm distal to the Bragg peak. RBEDSB tends to decrease as the kinetic energy of the incident proton increases. Conclusion: The model for proton RBEDSB has been accurately implemented into FLUKA, MCNP, TOPAS and the RayStation™TPS. The transport of secondary light ions (Z > 1) has a significant impact on RBEDSB, especially distal to the Bragg peak, although light ions have a small effect on (dosexRBEDSB) profiles. The ability to incorporate spatial variations in proton RBE within a TPS creates new opportunities to individualize treatment plans and increase the therapeutic ratio. Dr. Erik Traneus is employed full-time as a Research Scientist

Impact of respiratory motion on variable relative biological effectiveness in 4D-dose distributions of proton therapy.

Science.gov (United States)

Ulrich, Silke; Wieser, Hans-Peter; Cao, Wenhua; Mohan, Radhe; Bangert, Mark

2017-11-01

Organ motion during radiation therapy with scanned protons leads to deviations between the planned and the delivered physical dose. Using a constant relative biological effectiveness (RBE) of 1.1 linearly maps these deviations into RBE-weighted dose. However, a constant value cannot account for potential nonlinear variations in RBE suggested by variable RBE models. Here, we study the impact of motion on recalculations of RBE-weighted dose distributions using a phenomenological variable RBE model. 4D-dose calculation including variable RBE was implemented in the open source treatment planning toolkit matRad. Four scenarios were compared for one field and two field proton treatments for a liver cancer patient assuming (α∕β) x  = 2 Gy and (α∕β) x  = 10 Gy: (A) the optimized static dose distribution with constant RBE, (B) a static recalculation with variable RBE, (C) a 4D-dose recalculation with constant RBE and (D) a 4D-dose recalculation with variable RBE. For (B) and (D), the variable RBE was calculated by the model proposed by McNamara. For (C), the physical dose was accumulated with direct dose mapping; for (D), dose-weighted radio-sensitivity parameters of the linear quadratic model were accumulated to model synergistic irradiation effects on RBE. Dose recalculation with variable RBE led to an elevated biological dose at the end of the proton field, while 4D-dose recalculation exhibited random deviations everywhere in the radiation field depending on the interplay of beam delivery and organ motion. For a single beam treatment assuming (α∕β) x  = 2 Gy, D 95 % was 1.98 Gy (RBE) (A), 2.15 Gy (RBE) (B), 1.81 Gy (RBE) (C) and 1.98 Gy (RBE) (D). The homogeneity index was 1.04 (A), 1.08 (B), 1.23 (C) and 1.25 (D). For the studied liver case, intrafractional motion did not reduce the modulation of the RBE-weighted dose postulated by variable RBE models for proton treatments.

SU-E-T-547: Modeling Biological Response to Proton Irradiation and Evaluating Its Potential Clinical Consequences

Energy Technology Data Exchange (ETDEWEB)

Taleei, R; Peeler, C; Guan, F; Patel, D; Titt, U; Mirkovic, D; Grosshans, D; Mohan, R [Departments of Radiation Physics and Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX (United States)

2015-06-15

Purpose: In addition to physical uncertainties, proton therapy may also be associated with biologic uncertainties. Currently a generic RBE value of 1.1 is used for treatment planning. In this work the effects of variable RBE, in comparison to a fixed RBE, were evaluated by calculating the effective dose for proton treatments. Methods: The repair misrepair fixation (RMF) model was used to calculate variable proton RBEs. The RBE weighted spread-out Bragg peak (SOBP) dose in water phantom was calculated using Monte Carlo simulation and compared to 1.1 weighted SOBP dose. A head and neck proton treatment was used to evaluate the potential effects, by comparing the head and neck treatment plan computed with a commercial treatment planning system that incorporates fixed RBE of 1.1 and a Monte Carlo treatment planning system that incorporates variable RBE. Results: RBE calculations along the depth of SOBP showed that the RBE at the entrance is approximately 1 and reaches 1.1 near the center of the SOBP. However, in distal regions the RBE rises to higher values (up to 3.5 depending on the cell type). Comparison of commercial treatment plans using a fixed RBE of 1.1 and Monte Carlo using variable RBE showed noticeable differences in the effective dose distributions. Conclusion: The comparison of the treatment planning with fixed and variable RBE shows that using commercial treatment planning systems that incorporate fixed RBE (1.1) could Result in overestimation of the effective dose to part of head and neck target volumes, while underestimating the effective dose to the normal tissue beyond the tumor. The accurate variable RBE as a function of proton beam energy in patient should be incorporated in treatment planning to improve the accuracy of effective dose calculation.

Sulforaphane induces cell cycle arrest by protecting RB-E2F-1 complex in epithelial ovarian cancer cells

Directory of Open Access Journals (Sweden)

Morris Robert

2010-03-01

Full Text Available Abstract Background Sulforaphane (SFN, an isothiocyanate phytochemical present predominantly in cruciferous vegetables such as brussels sprout and broccoli, is considered a promising chemo-preventive agent against cancer. In-vitro exposure to SFN appears to result in the induction of apoptosis and cell-cycle arrest in a variety of tumor types. However, the molecular mechanisms leading to the inhibition of cell cycle progression by SFN are poorly understood in epithelial ovarian cancer cells (EOC. The aim of this study is to understand the signaling mechanisms through which SFN influences the cell growth and proliferation in EOC. Results SFN at concentrations of 5 - 20 μM induced a dose-dependent suppression of growth in cell lines MDAH 2774 and SkOV-3 with an IC50 of ~8 μM after a 3 day exposure. Combination treatment with chemotherapeutic agent, paclitaxel, resulted in additive growth suppression. SFN at ~8 μM decreased growth by 40% and 20% on day 1 in MDAH 2774 and SkOV-3, respectively. Cells treated with cytotoxic concentrations of SFN have reduced cell migration and increased apoptotic cell death via an increase in Bak/Bcl-2 ratio and cleavage of procaspase-9 and poly (ADP-ribose-polymerase (PARP. Gene expression profile analysis of cell cycle regulated proteins demonstrated increased levels of tumor suppressor retinoblastoma protein (RB and decreased levels of E2F-1 transcription factor. SFN treatment resulted in G1 cell cycle arrest through down modulation of RB phosphorylation and by protecting the RB-E2F-1 complex. Conclusions SFN induces growth arrest and apoptosis in EOC cells. Inhibition of retinoblastoma (RB phosphorylation and reduction in levels of free E2F-1 appear to play an important role in EOC growth arrest.

Relative Biological Effectiveness Variation Along Monoenergetic and Modulated Bragg Peaks of a 62-MeV Therapeutic Proton Beam: A Preclinical Assessment

International Nuclear Information System (INIS)

Chaudhary, Pankaj; Marshall, Thomas I.; Perozziello, Francesca M.; Manti, Lorenzo; Currell, Frederick J.; Hanton, Fiona; McMahon, Stephen J.; Kavanagh, Joy N.; Cirrone, Giuseppe Antonio Pablo; Romano, Francesco; Prise, Kevin M.; Schettino, Giuseppe

2014-01-01

Purpose: The biological optimization of proton therapy can be achieved only through a detailed evaluation of relative biological effectiveness (RBE) variations along the full range of the Bragg curve. The clinically used RBE value of 1.1 represents a broad average, which disregards the steep rise of linear energy transfer (LET) at the distal end of the spread-out Bragg peak (SOBP). With particular attention to the key endpoint of cell survival, our work presents a comparative investigation of cell killing RBE variations along monoenergetic (pristine) and modulated (SOBP) beams using human normal and radioresistant cells with the aim to investigate the RBE dependence on LET and intrinsic radiosensitvity. Methods and Materials: Human fibroblasts (AG01522) and glioma (U87) cells were irradiated at 6 depth positions along pristine and modulated 62-MeV proton beams at the INFN-LNS (Catania, Italy). Cell killing RBE variations were measured using standard clonogenic assays and were further validated using Monte Carlo simulations and the local effect model (LEM). Results: We observed significant cell killing RBE variations along the proton beam path, particularly in the distal region showing strong dose dependence. Experimental RBE values were in excellent agreement with the LEM predicted values, indicating dose-averaged LET as a suitable predictor of proton biological effectiveness. Data were also used to validate a parameterized RBE model. Conclusions: The predicted biological dose delivered to a tumor region, based on the variable RBE inferred from the data, varies significantly with respect to the clinically used constant RBE of 1.1. The significant RBE increase at the distal end suggests also a potential to enhance optimization of treatment modalities such as LET painting of hypoxic tumors. The study highlights the limitation of adoption of a constant RBE for proton therapy and suggests approaches for fast implementation of RBE models in treatment planning

Relative biological effectiveness of tritiated water on cultured mammalian cells at molecular and cellular level

International Nuclear Information System (INIS)

Okada, S.; Sakai, K.; Nakamura, N.

1986-01-01

Factors that affect RBE values have been investigated in cultured cells. It was shown that: (1) Different RBE values were obtained with the same tritiated water treated cells depending upon the biological end-point; this may be related to target size. (2) The RBE value for one end-point (e.g. cell killing) in different cell types was often different. In some cells, the RBE value increased with reducing dose; in other cells, the value remained constant. (3) The RBE value for tritiated water seemed to fit a general RBE-LET relationship. These results suggest that although the RBE value might vary from 1 to 2 when cells are exposed to HTO, there are situations where the value becomes higher than 2; these are associated with low dose and low dose rate exposures in some cell types. (author)

Identification and functional analysis of a second RBF-2 binding site within the HIV-1 promoter

International Nuclear Information System (INIS)

Dahabieh, Matthew S.; Ooms, Marcel; Malcolm, Tom; Simon, Viviana; Sadowski, Ivan

2011-01-01

Transcription from the HIV-1 long terminal repeat (LTR) is mediated by numerous host transcription factors. In this study we characterized an E-box motif (RBE1) within the core promoter that was previously implicated in both transcriptional activation and repression. We show that RBE1 is a binding site for the RBF-2 transcription factor complex (USF1, USF2, and TFII-I), previously shown to bind an upstream viral element, RBE3. The RBE1 and RBE3 elements formed complexes of identical mobility and protein constituents in gel shift assays, both with Jurkat T-cell nuclear extracts and recombinant USF/TFII-I. Furthermore, both elements are regulators of HIV-1 expression; mutations in LTR-luciferase reporters and in HIV-1 molecular clones resulted in decreased transcription, virion production, and proviral expression in infected cells. Collectively, our data indicate that RBE1 is a bona fide RBF-2 binding site and that the RBE1 and RBE3 elements are necessary for mediating proper transcription from the HIV-1 LTR.

SU-F-T-196: Hypo-Fractionation with Intensity Modulated Proton Therapy for Unilateral Metallic Prosthesis Prostate Cancer Patients

Energy Technology Data Exchange (ETDEWEB)

Rana, S; Park, S [McLaren Proton Therapy Center, Karmanos Cancer Institute at McLaren-Flint, Flint, MI (United States); Zheng, Y [Procure Proton Therapy Center, Oklahoma City, OK (United States); Zhang, Y [University of Cincinnati Medical Center, Liberty Township, OH (United States); Pokharel [21st Century Oncology, Estero, FL (United States); Cheng, C [Vantage Oncology, West Hills, CA (United States)

2016-06-15

Purpose: The purpose of this study is to investigate the dosimetric feasibility of hypo-fractionated intensity modulated proton therapy (IMPT) for unilateral metallic prosthesis prostate cancer patients based on proton collaborative group (PCG)-GU002-10 (NCT01230866) protocol criteria. Methods: A total of five unilateral metallic prosthesis prostate cancer cases were included in this retrospective study. For each case, IMPT plans were generated for treatment to be delivered with 7.6 Gy[RBE] per fraction in 5 fractions per week for a total dose of 38 Gy(RBE). Each plan was generated using two anterior-oblique beams and one lateral beam. Treatment plans were optimized with an objective meeting PCG-GU002-10 (NCT01230866) protocol criteria: (i) planning target volume (PTV): D99.5% > 36.1 Gy[RBE], (ii) rectum: V24 < 35%, V33.6 < 10%, (iii) bladder: V39 < 8 cc, and (iv) femoral head: V23 < 1cc. Results: All five cases satisfied PTV D99.5% (average=36.82 Gy[RBE]; range, 36.36–37.13 Gy[RBE]). PTV D95% ranged from 36.66 Gy[RBE] to 38.65 Gy[RBE] and PTV V100 ranged from 95.47% to 97.95%. For the rectum, V24 was less than 35% (average=14.07 Gy[RBE]; range, 6.22–18.42%, whereas V33.6 Gy[RBE] was less than 10% (average=6.83; range, 3.06 – 9.15%). Rectal mean dose ranged from 4.22 Gy[RBE] to 9.97 Gy[RBE]. For the bladder, V39 was found to be less than 8 cc (average=3.69 cc; range, 0.19–7.68 cc). Bladder mean dose ranged from 4.22 Gy[RBE] to 18.83 Gy[RBE]. For the femoral head, V23 was 0 in all five cases. Conclusion: All five unilateral metallic prosthesis prostate cancer IMPT plans generated with one lateral and two anterior-oblique beams satisfied the dosimetric criteria of PCG-GU002-10 (NCT01230866) protocol.

Low LET protons focused to submicrometer shows enhanced radiobiological effectiveness

International Nuclear Information System (INIS)

Schmid, T E; Zlobinskaya, O; Michalski, D; Molls, M; Multhoff, G; Greubel, C; Hable, V; Girst, S; Siebenwirth, C; Dollinger, G; Schmid, E

2012-01-01

This study shows that enhanced radiobiological effectiveness (RBE) values can be generated focusing low linear energy transfer (LET) radiation and thus changing the microdose distribution. 20 MeV protons (LET = 2.65 keV µm −1 ) are focused to submicrometer diameter at the ion microprobe superconducting nanoprobe for applied nuclear (Kern) physics experiments of the Munich tandem accelerator. The RBE values, as determined by measuring micronuclei (RBE MN = 1.48 ± 0.07) and dicentrics (RBE D = 1.92 ± 0.15), in human–hamster hybrid (A L ) cells are significantly higher when 117 protons were focused to a submicrometer irradiation field within a 5.4 × 5.4 µm 2 matrix compared to quasi homogeneous in a 1 × 1 µm 2 matrix applied protons (RBE MN = 1.28 ± 0.07; RBE D = 1.41 ± 0.14) at the same average dose of 1.7 Gy. The RBE values are normalized to standard 70 kV (dicentrics) or 200 kV (micronuclei) x-ray irradiation. The 117 protons applied per point deposit the same amount of energy like a 12 C ion with 55 MeV total energy (4.48 MeV u −1 ). The enhancements are about half of that obtained for 12 C ions (RBE MN = 2.20 ± 0.06 and RBE D = 3.21 ± 0.10) and they are attributed to intertrack interactions of the induced damages. The measured RBE values show differences from predictions of the local effect model (LEM III) that is used to calculate RBE values for irradiation plans to treat tumors with high LET particles. (paper)

Investigating the robustness of ion beam therapy treatment plans to uncertainties in biological treatment parameters

CERN Document Server

Boehlen, T T; Dosanjh, M; Ferrari, A; Fossati, P; Haberer, T; Mairani, A; Patera, V

2012-01-01

Uncertainties in determining clinically used relative biological effectiveness (RBE) values for ion beam therapy carry the risk of absolute and relative misestimations of RBE-weighted doses for clinical scenarios. This study assesses the consequences of hypothetical misestimations of input parameters to the RBE modelling for carbon ion treatment plans by a variational approach. The impact of the variations on resulting cell survival and RBE values is evaluated as a function of the remaining ion range. In addition, the sensitivity to misestimations in RBE modelling is compared for single fields and two opposed fields using differing optimization criteria. It is demonstrated for single treatment fields that moderate variations (up to +/-50\\%) of representative nominal input parameters for four tumours result mainly in a misestimation of the RBE-weighted dose in the planning target volume (PTV) by a constant factor and only smaller RBE-weighted dose gradients. Ensuring a more uniform radiation quality in the PTV...

Integration of TP53, DREAM, MMB-FOXM1 and RB-E2F target gene analyses identifies cell cycle gene regulatory networks.

Science.gov (United States)

Fischer, Martin; Grossmann, Patrick; Padi, Megha; DeCaprio, James A

2016-07-27

Cell cycle (CC) and TP53 regulatory networks are frequently deregulated in cancer. While numerous genome-wide studies of TP53 and CC-regulated genes have been performed, significant variation between studies has made it difficult to assess regulation of any given gene of interest. To overcome the limitation of individual studies, we developed a meta-analysis approach to identify high confidence target genes that reflect their frequency of identification in independent datasets. Gene regulatory networks were generated by comparing differential expression of TP53 and CC-regulated genes with chromatin immunoprecipitation studies for TP53, RB1, E2F, DREAM, B-MYB, FOXM1 and MuvB. RNA-seq data from p21-null cells revealed that gene downregulation by TP53 generally requires p21 (CDKN1A). Genes downregulated by TP53 were also identified as CC genes bound by the DREAM complex. The transcription factors RB, E2F1 and E2F7 bind to a subset of DREAM target genes that function in G1/S of the CC while B-MYB, FOXM1 and MuvB control G2/M gene expression. Our approach yields high confidence ranked target gene maps for TP53, DREAM, MMB-FOXM1 and RB-E2F and enables prediction and distinction of CC regulation. A web-based atlas at www.targetgenereg.org enables assessing the regulation of any human gene of interest. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

7th Workshop on heavy charged particles in biology and medicine. Book of abstracts

International Nuclear Information System (INIS)

Kraft, G.; Langbein, K.

2000-09-01

The topics of the workshop were as follows: RBE experiments, reference data for treatment planning, RBE models, integration of RBE into treatment planning, clinical results. All papers are available as separate moduls in this database. (MG)

Can We Advance Proton Therapy for Prostate? Considering Alternative Beam Angles and Relative Biological Effectiveness Variations When Comparing Against Intensity Modulated Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Underwood, Tracy, E-mail: tunderwood@mgh.harvard.edu [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Department of Medical Physics and Bioengineering, University College London, London (United Kingdom); Giantsoudi, Drosoula; Moteabbed, Maryam; Zietman, Anthony; Efstathiou, Jason; Paganetti, Harald; Lu, Hsiao-Ming [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States)

2016-05-01

Purpose: For prostate treatments, robust evidence regarding the superiority of either intensity modulated radiation therapy (IMRT) or proton therapy is currently lacking. In this study we investigated the circumstances under which proton therapy should be expected to outperform IMRT, particularly the proton beam orientations and relative biological effectiveness (RBE) assumptions. Methods and Materials: For 8 patients, 4 treatment planning strategies were considered: (A) IMRT; (B) passively scattered standard bilateral (SB) proton beams; (C) passively scattered anterior oblique (AO) proton beams, and (D) AO intensity modulated proton therapy (IMPT). For modalities (B)-(D) the dose and linear energy transfer (LET) distributions were simulated using the TOPAS Monte Carlo platform and RBE was calculated according to 3 different models. Results: Assuming a fixed RBE of 1.1, our implementation of IMRT outperformed SB proton therapy across most normal tissue metrics. For the scattered AO proton plans, application of the variable RBE models resulted in substantial hotspots in rectal RBE weighted dose. For AO IMPT, it was typically not possible to find a plan that simultaneously met the tumor and rectal constraints for both fixed and variable RBE models. Conclusion: If either a fixed RBE of 1.1 or a variable RBE model could be validated in vivo, then it would always be possible to use AO IMPT to dose-boost the prostate and improve normal tissue sparing relative to IMRT. For a cohort without rectum spacer gels, this study (1) underlines the importance of resolving the question of proton RBE within the framework of an IMRT versus proton debate for the prostate and (2) highlights that without further LET/RBE model validation, great care must be taken if AO proton fields are to be considered for prostate treatments.

Examination of GyE system for HIMAC carbon therapy

International Nuclear Information System (INIS)

Kanai, Tatsuaki; Matsufuji, Naruhiro; Miyamoto, Tadaaki; Mizoe, Junetsu; Kamada, Tadashi; Tsuji, Hiroshi; Kato, Hirotoshi; Baba, Masayuki; Tsujii, Hirohiko

2006-01-01

Purpose: A retrospective analysis was made to examine appropriateness in the estimation of the biologic effectiveness of carbon-ion radiotherapy using resultant data from clinical trials at the heavy-ion medical accelerator complex (HIMAC) at the National Institute of Radiological Sciences in Chiba, Japan. Methods and Materials: At HIMAC, relative biologic effectiveness (RBE) values of therapeutic carbon beams were determined based on experimental results of cell responses, on values expected with the linear-quadratic model, and based on experiences with neutron therapy. We use fixed RBE values independent of dose levels, although this apparently contradicts radiobiologic observations. Our RBE system depends only on LET of the heavy-ion radiation fields. With this RBE system, over 2,000 patients have been treated by carbon beams. With data from these patients, the local control rate of non-small-cell lung cancer was analyzed to verify the clinical RBE of the carbon beam. The local control rate was compared with rates published by groups from Gunma University and Massachusetts General Hospital. Using a simplified tumor control probability (TCP) model, clinical RBE values were obtained for different levels of TCP. Results: For the 50% level of the clinical TCP, the RBE values nearly coincide with those for in vitro human salivary gland cell survival at 10%. For the higher levels of clinical TCP, the RBE values approach closer to those adapted in clinical trials at HIMAC

SU-F-T-128: Dose-Volume Constraints for Particle Therapy Treatment Planning

Energy Technology Data Exchange (ETDEWEB)

Stewart, R; Smith, W; Hendrickson, K; Meyer, J; Cao, N; Lee, E; Gopan, O; Sandison, G; Parvathaneni, U; Laramore, G [University of Washington, Seattle, WA (United States)

2016-06-15

Purpose: Determine equivalent Organ at Risk (OAR) tolerance dose (TD) constraints for MV x-rays and particle therapy. Methods: Equivalent TD estimates for MV x-rays are determined from an isoeffect, regression-analysis of published and in-house constraints for various fractionation schedules (n fractions). The analysis yields an estimate of (α/β) for an OAR. To determine equivalent particle therapy constraints, the MV x-ray TD(n) values are divided by the RBE for DSB induction (RBE{sub DSB}) or cell survival (RBE{sub S}). Estimates of (RBE{sub DSB}) are computed using the Monte Carlo Damage Simulation, and estimates of RBES are computed using the Repair-Misrepair-Fixation (RMF) model. A research build of the RayStation™ treatment planning system implementing the above model is used to estimate (RBE{sub DSB}) for OARs of interest in 16 proton therapy patient plans (head and neck, thorax, prostate and brain). Results: The analysis gives an (α/β) estimate of about 20 Gy for the trachea and heart and 2–4 Gy for the esophagus, spine, and brachial plexus. Extrapolation of MV x-ray constraints (n = 1) to fast neutrons using RBE{sub DSB} = 2.7 are in excellent agreement with clinical experience (n = 10 to 20). When conventional (n > 30) x-ray treatments are used as the reference radiation, fast neutron RBE increased to a maximum of 6. For comparison to a constant RBE of 1.1, the RayStation™ analysis gave estimates of proton RBE{sub DSB} from 1.03 to 1.33 for OARs of interest. Conclusion: The presented system of models is a convenient formalism to synthesize from multiple sources of information a set of self-consistent plan constraints for MV x-ray and hadron therapy treatments. Estimates of RBE{sub DSB} from the RayStation™ analysis differ substantially from 1.1 and vary among patients and treatment sites. A treatment planning system that incorporates patient and anatomy-specific corrections in proton RBE would create opportunities to increase the therapeutic

Cellular- and micro-dosimetry of heterogeneously distributed tritium.

Science.gov (United States)

Chao, Tsi-Chian; Wang, Chun-Ching; Li, Junli; Li, Chunyan; Tung, Chuan-Jong

2012-01-01

The assessment of radiotoxicity for heterogeneously distributed tritium should be based on the subcellular dose and relative biological effectiveness (RBE) for cell nucleus. In the present work, geometry-dependent absorbed dose and RBE were calculated using Monte Carlo codes for tritium in the cell, cell surface, cytoplasm, or cell nucleus. Penelope (PENetration and Energy LOss of Positrins and Electrons) code was used to calculate the geometry-dependent absorbed dose, lineal energy, and electron fluence spectrum. RBE for the intestinal crypt regeneration was calculated using a lineal energy-dependent biological weighting function. RBE for the induction of DNA double strand breaks was estimated using a nucleotide-level map for clustered DNA lesions of the Monte Carlo damage simulation (MCDS) code. For a typical cell of 10 μm radius and 5 μm nuclear radius, tritium in the cell nucleus resulted in much higher RBE-weighted absorbed dose than tritium distributed uniformly. Conversely, tritium distributed on the cell surface led to trivial RBE-weighted absorbed dose due to irradiation geometry and great attenuation of beta particles in the cytoplasm. For tritium uniformly distributed in the cell, the RBE-weighted absorbed dose was larger compared to tritium uniformly distributed in the tissue. Cellular- and micro-dosimetry models were developed for the assessment of heterogeneously distributed tritium.

TU-AB-BRC-02: Accuracy Evaluation of GPU-Based OpenCL Carbon Monte Carlo Package (goCMC) in Biological Dose and Microdosimetry in Comparison to FLUKA Simulations

Energy Technology Data Exchange (ETDEWEB)

Taleei, R; Peeler, C; Qin, N; Jiang, S; Jia, X [UT Southwestern Medical Center, Dallas, TX (United States)

2016-06-15

Purpose: One of the most accurate methods for radiation transport is Monte Carlo (MC) simulation. Long computation time prevents its wide applications in clinic. We have recently developed a fast MC code for carbon ion therapy called GPU-based OpenCL Carbon Monte Carlo (goCMC) and its accuracy in physical dose has been established. Since radiobiology is an indispensible aspect of carbon ion therapy, this study evaluates accuracy of goCMC in biological dose and microdosimetry by benchmarking it with FLUKA. Methods: We performed simulations of a carbon pencil beam with 150, 300 and 450 MeV/u in a homogeneous water phantom using goCMC and FLUKA. Dose and energy spectra for primary and secondary ions on the central beam axis were recorded. Repair-misrepair-fixation model was employed to calculate Relative Biological Effectiveness (RBE). Monte Carlo Damage Simulation (MCDS) tool was used to calculate microdosimetry parameters. Results: Physical dose differences on the central axis were <1.6% of the maximum value. Before the Bragg peak, differences in RBE and RBE-weighted dose were <2% and <1%. At the Bragg peak, the differences were 12.5% caused by small range discrepancy and sensitivity of RBE to beam spectra. Consequently, RBE-weighted dose difference was 11%. Beyond the peak, RBE differences were <20% and primarily caused by differences in the Helium-4 spectrum. However, the RBE-weighted dose agreed within 1% due to the low physical dose. Differences in microdosimetric quantities were small except at the Bragg peak. The simulation time per source particle with FLUKA was 0.08 sec, while goCMC was approximately 1000 times faster. Conclusion: Physical doses computed by FLUKA and goCMC were in good agreement. Although relatively large RBE differences were observed at and beyond the Bragg peak, the RBE-weighted dose differences were considered to be acceptable.

The relative biological effectiveness of out-of-field dose

International Nuclear Information System (INIS)

Balderson, Michael; Koger, Brandon; Kirkby, Charles

2016-01-01

Purpose: using simulations and models derived from existing literature, this work investigates relative biological effectiveness (RBE) for out-of-field radiation and attempts to quantify the relative magnitudes of different contributing phenomena (spectral, bystander, and low dose hypersensitivity effects). Specific attention is paid to external beam radiotherapy treatments for prostate cancer. Materials and methods: using different biological models that account for spectral, bystander, and low dose hypersensitivity effects, the RBE was calculated for different points moving radially out from isocentre for a typical single arc VMAT prostate case. The RBE was found by taking the ratio of the equivalent dose with the physical dose. Equivalent doses were calculated by determining what physical dose would be necessary to produce the same overall biological effect as that predicted using the different biological models. Results: spectral effects changed the RBE out-of-field less than 2%, whereas response models incorporating low dose hypersensitivity and bystander effects resulted in a much more profound change of the RBE for out-of-field doses. The bystander effect had the largest RBE for points located just outside the edge of the primary radiation beam in the cranial caudal (z-direction) compared to low dose hypersensitivity and spectral effects. In the coplanar direction, bystander effect played the largest role in enhancing the RBE for points up to 8.75 cm from isocentre. Conclusions: spectral, bystander, and low dose hypersensitivity effects can all increase the RBE for out-of-field radiation doses. In most cases, bystander effects seem to play the largest role followed by low dose hypersensitivity. Spectral effects were unlikely to be of any clinical significance. Bystander, low dose hypersensitivity, and spectral effect increased the RBE much more in the cranial caudal direction (z-direction) compared with the coplanar directions. (paper)

METHODS OF ASSESSMENT OF THE RELATIVE BIOLOGICAL EFFECTIVENESS OF NEUTRONS IN NEUTRON THERAPY

Directory of Open Access Journals (Sweden)

V. A. Lisin

2017-01-01

Full Text Available The relative biological effectiveness (RBE of fast neutrons is an important factor influencing the quality of neutron therapy therefore, the assessment of RBE is of great importance. Experimental and clinical studies as well as different mathematical and radiobiological models are used for assessing RBE. Research is conducted for neutron sources differing in the method of producing particles, energy and energy spectrum. Purpose: to find and analyze the dose-dependence of fast neutron RBE in neutron therapy using the U-120 cyclotron and NG-12I generator. Material and methods: The optimal method for assessing the relative biological effectiveness of neutrons for neutron therapy was described. To analyze the dependence of the RBE on neutron dose, the multi-target model of cell survival was applied. Results: The dependence of the RBE of neutrons produced from the U-120 cyclotron and NG-120 generator on the dose level was found for a single irradiation of biological objects. It was shown that the function of neutron dose was consistent with similar dependencies found by other authors in the experimental and clinical studies.

Direct Comparison of Biologically Optimized Spread-out Bragg Peaks for Protons and Carbon Ions

International Nuclear Information System (INIS)

Wilkens, Jan J.; Oelfke, Uwe

2008-01-01

Purpose: In radiotherapy with hadrons, it is anticipated that carbon ions are superior to protons, mainly because of their biological properties: the relative biological effectiveness (RBE) for carbon ions is supposedly higher in the target than in the surrounding normal tissue, leading to a therapeutic advantage over protons. The purpose of this report is to investigate this effect by using biological model calculations. Methods and Materials: We compared spread-out Bragg peaks for protons and carbon ions by using physical and biological optimization. The RBE for protons and carbon ions was calculated according to published biological models. These models predict increased RBE values in regions of high linear energy transfer (LET) and an inverse dependency of the RBE on dose. Results: For pure physical optimization, protons yield a better dose distribution along the central axis. In biologically optimized plans, RBE variations for protons were relatively small. For carbon ions, high RBE values were found in the high-LET target region, as well as in the low-dose region outside the target. This means that the LET dependency and dose dependency of the RBE can cancel each other. We show this for radioresistant tissues treated with two opposing beams, for which the predicted carbon RBE within the target volume was lower than outside. Conclusions: For tissue parameters used in this study, the model used does not predict a biologic advantage of carbon ions. More reliable model parameters and clinical trials are necessary to explore the true potential of radiotherapy with carbon ions

Gene conversion in yeast as a function of linear energy transfer (LET) for low-LET radiation

International Nuclear Information System (INIS)

Unrau, P.; Morrison, D.P.; Johnson, J.R.

1992-05-01

The relative biological effectiveness (RBE) for low-LET radiation is known to depend on such factors as LET and dose rate. Microdosimetric calculations indicate that the biological target size could also be an important parameter, and calculations predict that the RBE for effects produced by hits in target sizes below about 100 nm should be unity for all low LET radiation. We have measured that RBE for gene conversion in yeast (a small target) for five different low LET photon sources, and the results were consistent with an RBE of unity, which agrees with microdosimetric predictions. 4 refs

Cell inactivation and chromosomal aberrations induced by X-rays and fast neutrons in cells of the Chinese hamster. 1

International Nuclear Information System (INIS)

Tolkendorf, E.

1979-01-01

Asynchronously grown cultures of Chinese hamster cells V79-4 were irradiated in suspension with 180 kV X-rays and fast neutrons (average energy of 6.2 MeV). The damage was assessed by measuring cell survival and frequencies of chromosome aberrations in the first post-irradiation metaphases. The experimental data for survival and chromosome aberrations were fitted by computer programmes. From the fitted curves the relative biological effectiveness (RBE) of fast neutrons was calculated. The RBE shows a similar dose dependence for killed and aberrant cells. The RBE decreases with increasing dose and amounts to approximately 5 for both effects for small neutron doses. The highest RBE is found for asymmetrical chromosomal exchanges and is dependent on the neutron dose, too. However, for isochromatid deletions the RBE is dose independent with a value of 3.6. (author)

Neutron and photon clonogenic survival curves of two chemotherapy resistant human intermediate-grade non-Hodgkin lymphoma cell lines

International Nuclear Information System (INIS)

Aref, Amr; Yudelev, Mark; Mohammad, Ramzi; Choudhuri, Rajani; Orton, Colin; Al-Katib, Ayad

1999-01-01

Background: The potential role of neutron therapy in the management of intermediate-grade non-Hodgkin lymphoma (IGNHL) has not been examined because of the belief that the anticipated radiobiological effectiveness (RBE) would be uniformly very low. Purpose: To determine the fast neutron RBE for two chemotherapy-resistant IGNHL cell lines. Methods and Materials: Conventional soft agar clonogenic survival curves following irradiation by 60 Co and fast neutron were established for two IGNHL cell lines. These cell lines, WSU-DLCL2 and SK-DHL2B, were found in previous studies to be able to repair sublethal damage, and were also resistant to L-Pam and doxorubicin chemotherapy. Results: When the surviving fraction after 2 Gy photon was chosen as the biological endpoint, the RBE for WSU-DLCL2 and SK-DHL2B measured 3.34 and 3.06. Similarly, when 10% survival was considered, the RBE for these two cell lines measured 2.54 and 2.59. The RBE, as measured by the ratios α neutron/α photon, for WSU-DLCL2, SK-DHL2B cell lines are 6.67 and 5.65, respectively. These results indicate that the RBE for these IGNHL cell lines is higher than the average RBE for cell lines of other histological types. Conclusion: Fast neutron irradiation may be of potential value in treating selected cases of IGNHL

Lateral variations of radiobiological properties of therapeutic fields of 1H, 4He, 12C and 16O ions studied with Geant4 and microdosimetric kinetic model

Science.gov (United States)

Dewey, Sophie; Burigo, Lucas; Pshenichnov, Igor; Mishustin, Igor; Bleicher, Marcus

2017-07-01

As known, in cancer therapy with ion beams the relative biological effectiveness (RBE) of ions changes in the course of their propagation in tissues. Such changes are caused not only by increasing the linear energy transfer (LET) of beam particles with the penetration depth towards the Bragg peak, but also by nuclear reactions induced by beam nuclei leading to the production of various secondary particles. Although the changes of RBE along the beam axis have been studied quite well, much less attention has been paid to the evolution of RBE in the transverse direction, perpendicular to the beam axis. In order to fill this gap, we simulated radiation fields of 1H, 4He, 12C and 16O nuclei of 20 mm in diameter by means of a Geant4-based Monte Carlo model for heavy-ion therapy connected with the modified microdosimetric kinetic model to describe the response of normal ((α/β)_x-rays=3.8 Gy) and early-responding ((α/β)_x-rays=10 Gy) tissues. Depth and radial distributions of saturation-corrected dose-mean lineal energy, RBE and RBE-weighted dose are investigated for passive beam shaping and active beam scanning. The field of 4He has a small lateral spread as compared with 1H field, and it is characterised by a modest lateral variation of RBE suggesting the use of fixed RBE values across the field transverse cross section at each depth. Reduced uncertainties of RBE on the boundary of a 4He treatment field can be advantageous in a specific case of an organ at risk located in lateral proximity to the target volume. It is found that the lateral distributions of RBE calculated for 12C and 16O fields demonstrate fast variations in the radial direction due to changes of dose and composition of secondary fragments in the field penumbra. Nevertheless, the radiation fields of all four projectiles at radii larger than 20 mm can be characterized by a common RBE value defined by tissue radiosensitivity. These findings can help, in particular, in accessing the transverse

Targeted alpha therapy of mCRPC. Dosimetry estimate of {sup 213}bismuth-PSMA-617

Energy Technology Data Exchange (ETDEWEB)

Kratochwil, Clemens; Afshar-Oromieh, Ali; Rathke, Hendrik; Giesel, Frederik L. [University Hospital Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany); Schmidt, Karl [ABX-CRO, Dresden (Germany); Bruchertseifer, Frank; Morgenstern, Alfred [European Commission - Joint Research Centre, Directorate for Nuclear Safety and Security, Karlsruhe (Germany); Haberkorn, Uwe [University Hospital Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany); German Cancer Research Center (DKFZ), Cooperation Unit Nuclear Medicine, Heidelberg (Germany)

2018-01-15

PSMA-617 is a small molecule targeting the prostate-specific membrane antigen (PSMA). In this work, we estimate the radiation dosimetry for this ligand labeled with the alpha-emitter {sup 213}Bi. Three patients with metastatic prostate cancer underwent PET scans 0.1 h, 1 h, 2 h, 3 h, 4 h and 5 h after injection of {sup 68}Ga-PSMA-617. Source organs were kidneys, liver, spleen, salivary glands, bladder, red marrow and representative tumor lesions. The imaging nuclide {sup 68}Ga was extrapolated to the half-life of {sup 213}Bi. The residence times of {sup 213}Bi were forwarded to the instable daughter nuclides. OLINDA was used for dosimetry calculation. Results are discussed in comparison to literature data for {sup 225}Ac-PSMA-617. Assuming a relative biological effectiveness of 5 for alpha radiation, the dosimetry estimate revealed equivalent doses of mean 8.1 Sv{sub RBE5}/GBq for salivary glands, 8.1 Sv{sub RBE5}/GBq for kidneys and 0.52 Sv{sub RBE5}/GBq for red marrow. Liver (1.2 Sv{sub RBE5}/GBq), spleen (1.4 Sv{sub RBE5}/GBq), bladder (0.28 Sv{sub RBE5}/GBq) and other organs (0.26 Sv{sub RBE5}/GBq) were not dose-limiting. The effective dose is 0.56 Sv{sub RBE5}/GBq. Tumor lesions were in the range 3.2-9.0 Sv{sub RBE5}/GBq (median 7.6 Sv{sub RBE5}/GBq). Kidneys would limit the cumulative treatment activity to 3.7 GBq; red marrow might limit the maximum single fraction to 2 GBq. Despite promising results, the therapeutic index was inferior compared to {sup 225}Ac-PSMA-617. Dosimetry of {sup 213}Bi-PSMA-617 is in a range traditionally considered reasonable for clinical application. Nevertheless, compared to {sup 225}Ac-PSMA-617, it suffers from higher perfusion-dependent off-target radiation and a longer biological half-life of PSMA-617 in dose-limiting organs than the physical half-life of {sup 213}Bi, rendering this nuclide as a second choice radiolabel for targeted alpha therapy of prostate cancer. (orig.)

To the radiotoxicity of {sup 99m}Tc radiopharmaceuticals

Energy Technology Data Exchange (ETDEWEB)

Ftacnikova, S [Inst. of Preventive and Clinical Medicine, 83301 Bratislava (Slovakia)

1996-12-31

In this paper the radiotoxicity and RBE values of Auger electrons for {sup 99m}Tc radiopharmaceuticals were discussed. Expression for the expected RBE for {sup 99m}Tc compounds is given. For the Auger electrons emitted in the decay of {sup 99m}Tc the RBE(Auger) = 10 and a value of 20 for the radiation weighing factor were recommended. (J.K.) 4 refs.

Fast Biological Modeling for Voxel-based Heavy Ion Treatment Planning Using the Mechanistic Repair-Misrepair-Fixation Model and Nuclear Fragment Spectra

Energy Technology Data Exchange (ETDEWEB)

Kamp, Florian [Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut (United States); Department of Radiation Oncology, Technische Universität München, Klinikum Rechts der Isar, München (Germany); Physik-Department, Technische Universität München, Garching (Germany); Cabal, Gonzalo [Experimental Physics–Medical Physics, Ludwig Maximilians University Munich, Garching (Germany); Mairani, Andrea [Medical Physics Unit, Centro Nazionale Adroterapia Oncologica (CNAO), Pavia (Italy); Heidelberg Ion-Beam Therapy Center, Heidelberg (Germany); Parodi, Katia [Experimental Physics–Medical Physics, Ludwig Maximilians University Munich, Garching (Germany); Wilkens, Jan J. [Department of Radiation Oncology, Technische Universität München, Klinikum Rechts der Isar, München (Germany); Physik-Department, Technische Universität München, Garching (Germany); Carlson, David J., E-mail: david.j.carlson@yale.edu [Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut (United States)

2015-11-01

Purpose: The physical and biological differences between heavy ions and photons have not been fully exploited and could improve treatment outcomes. In carbon ion therapy, treatment planning must account for physical properties, such as the absorbed dose and nuclear fragmentation, and for differences in the relative biological effectiveness (RBE) of ions compared with photons. We combined the mechanistic repair-misrepair-fixation (RMF) model with Monte Carlo-generated fragmentation spectra for biological optimization of carbon ion treatment plans. Methods and Materials: Relative changes in double-strand break yields and radiosensitivity parameters with particle type and energy were determined using the independently benchmarked Monte Carlo damage simulation and the RMF model to estimate the RBE values for primary carbon ions and secondary fragments. Depth-dependent energy spectra were generated with the Monte Carlo code FLUKA for clinically relevant initial carbon ion energies. The predicted trends in RBE were compared with the published experimental data. Biological optimization for carbon ions was implemented in a 3-dimensional research treatment planning tool. Results: We compared the RBE and RBE-weighted dose (RWD) distributions of different carbon ion treatment scenarios with and without nuclear fragments. The inclusion of fragments in the simulations led to smaller RBE predictions. A validation of RMF against measured cell survival data reported in published studies showed reasonable agreement. We calculated and optimized the RWD distributions on patient data and compared the RMF predictions with those from other biological models. The RBE values in an astrocytoma tumor ranged from 2.2 to 4.9 (mean 2.8) for a RWD of 3 Gy(RBE) assuming (α/β){sub X} = 2 Gy. Conclusions: These studies provide new information to quantify and assess uncertainties in the clinically relevant RBE values for carbon ion therapy based on biophysical mechanisms. We present results from

SU-F-T-682: In-Vivo Simulation of the Relative Biological Effectiveness in Proton Therapy Using a Monte Carlo Method

International Nuclear Information System (INIS)

Oesten, H; Loeck, S; Wohlfahrt, P; Helmbrecht, S; Tillner, F; Schuemann, J; Luehr, A

2016-01-01

Purpose: In proton therapy, the relative biological effectiveness (RBE) – compared with conventional photon therapy – is routinely set to 1.1. However, experimental in vitro studies indicate evidence for the variability of the RBE. To clarify the impact on patient treatment, investigation of the RBE in a preclinical case study should be performed. Methods: The Monte Carlo software TOPAS was used to simulate the radiation field of an irradiation setup at the experimental beamline of the proton therapy facility (OncoRay) in Dresden, Germany. Simulations were performed on cone beam CT-data (CBCT) of a xenogeneous mouse with an orthotopic lung carcinoma obtained by an in-house developed small animal image-guided radiotherapy device. A homogeneous physical fraction dose of 1.8Gy was prescribed for the contoured tumor volume. Simulated dose and linear energy transfer distributions were used to estimate RBE values in the mouse based on an RBE model by Wedenberg et al. To characterize radiation sensitivity of normal and tumor tissue, α/β-ratios were taken from the literature for NB1RGB (10.1Gy) and human squamous lung cancer (6.2Gy) cell lines, respectively. Results: Good dose coverage of the target volume was achieved with a spread-out Bragg peak (SOBP). The contra-lateral lung was completely spared from receiving radiation. An increase in RBE towards the distal end of the SOBP from 1.07 to 1.35 and from 1.05 to 1.3 was observed when considering normal tissue and tumor, respectively, with the highest RBE values located distal to the target volume. Conclusion: Modeled RBE values simulated on CBCT for experimental preclinical proton therapy varied with tissue type and depth in a mouse and differed therefore from a constant value of 1.1. Further translational work will include, first, conducting preclinical experiments and, second, analogous RBE studies in patients using experimentally verified simulation settings for our clinically used patient-specific beam

SU-F-T-682: In-Vivo Simulation of the Relative Biological Effectiveness in Proton Therapy Using a Monte Carlo Method

Energy Technology Data Exchange (ETDEWEB)

Oesten, H [OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universitaet Dresden (Germany); Massachusetts General Hospital, Boston, MA (Germany); Loeck, S; Wohlfahrt, P [OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universitaet Dresden (Germany); Helmbrecht, S [OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universitaet Dresden (Germany); Institute of Radiation Physics, Helmholtz-Zentrum Dresden-Rossendorf (Germany); Tillner, F [OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universitaet Dresden (Germany); Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universitaet Dresden (Germany); Schuemann, J [Massachusetts General Hospital, Boston, MA (United States); Luehr, A [OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universitaet Dresden (Germany); German Cancer Consortium (DKTK), Dresden (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany)

2016-06-15

Purpose: In proton therapy, the relative biological effectiveness (RBE) – compared with conventional photon therapy – is routinely set to 1.1. However, experimental in vitro studies indicate evidence for the variability of the RBE. To clarify the impact on patient treatment, investigation of the RBE in a preclinical case study should be performed. Methods: The Monte Carlo software TOPAS was used to simulate the radiation field of an irradiation setup at the experimental beamline of the proton therapy facility (OncoRay) in Dresden, Germany. Simulations were performed on cone beam CT-data (CBCT) of a xenogeneous mouse with an orthotopic lung carcinoma obtained by an in-house developed small animal image-guided radiotherapy device. A homogeneous physical fraction dose of 1.8Gy was prescribed for the contoured tumor volume. Simulated dose and linear energy transfer distributions were used to estimate RBE values in the mouse based on an RBE model by Wedenberg et al. To characterize radiation sensitivity of normal and tumor tissue, α/β-ratios were taken from the literature for NB1RGB (10.1Gy) and human squamous lung cancer (6.2Gy) cell lines, respectively. Results: Good dose coverage of the target volume was achieved with a spread-out Bragg peak (SOBP). The contra-lateral lung was completely spared from receiving radiation. An increase in RBE towards the distal end of the SOBP from 1.07 to 1.35 and from 1.05 to 1.3 was observed when considering normal tissue and tumor, respectively, with the highest RBE values located distal to the target volume. Conclusion: Modeled RBE values simulated on CBCT for experimental preclinical proton therapy varied with tissue type and depth in a mouse and differed therefore from a constant value of 1.1. Further translational work will include, first, conducting preclinical experiments and, second, analogous RBE studies in patients using experimentally verified simulation settings for our clinically used patient-specific beam

Impact of tissue specific parameters on the predition of the biological effectiveness for treatment planning in ion beam therapy

International Nuclear Information System (INIS)

Gruen, Rebecca Antonia

2014-01-01

Treatment planning in ion beam therapy requires a reliable estimation of the relative biological effectiveness (RBE) of the irradiated tissue. For the pilot project at GSI Helmholtzzentrum fuer Schwerionenforschung GmbH and at other European ion beam therapy centers RBE prediction is based on a biophysical model, the Local Effect Model (LEM). The model version in use, LEM I, is optimized to give a reliable estimation of RBE in the target volume for carbon ion irradiation. However, systematic deviations are observed for the entrance channel of carbon ions and in general for lighter ions. Thus, the LEM has been continuously developed to improve accuracy. The recent version LEM IV has proven to better describe in-vitro cell experiments. Thus, for the clinical application of LEM IV it is of interest to analyze potential differences compared to LEM I under treatment-like conditions. The systematic analysis presented in this work is aiming at the comparison of RBE-weighted doses resulting from different approaches and model versions for protons and carbon ions. This will facilitate the assessment of consequences for clinical application and the interpretation of clinical results from different institutions. In the course of this thesis it has been shown that the RBE-weighted doses predicted on the basis of LEM IV for typical situations representing chordoma treatments differ on average by less than 10 % to those based on LEM I and thus also allow a consistent interpretation of the clinical results. At Japanese ion beam therapy centers the RBE is estimated using their clinical experience from neutron therapy in combination with in-vitro measurements for carbon ions (HIMAC approach). The methods presented in this work allow direct comparison of the HIMAC approach and the LEM and thus of the clinical results obtained at Japanese and European ion beam therapy centers. Furthermore, the sensitivity of the RBE on the model parameters was evaluated. Among all parameters the

Temporal Lobe Reactions After Carbon Ion Radiation Therapy: Comparison of Relative Biological Effectiveness–Weighted Tolerance Doses Predicted by Local Effect Models I and IV

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Gillmann, Clarissa, E-mail: clarissa.gillmann@med.uni-heidelberg.de [Department of Radiation Oncology and Radiation Therapy, Heidelberg University Hospital, Heidelberg (Germany); Jäkel, Oliver [Department of Radiation Oncology and Radiation Therapy, Heidelberg University Hospital, Heidelberg (Germany); Heidelberg Ion Beam Therapy Center (HIT), Heidelberg (Germany); Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg (Germany); Schlampp, Ingmar [Department of Radiation Oncology and Radiation Therapy, Heidelberg University Hospital, Heidelberg (Germany); Karger, Christian P. [Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg (Germany)

2014-04-01

Purpose: To compare the relative biological effectiveness (RBE)–weighted tolerance doses for temporal lobe reactions after carbon ion radiation therapy using 2 different versions of the local effect model (LEM I vs LEM IV) for the same patient collective under identical conditions. Methods and Materials: In a previous study, 59 patients were investigated, of whom 10 experienced temporal lobe reactions (TLR) after carbon ion radiation therapy for low-grade skull-base chordoma and chondrosarcoma at Helmholtzzentrum für Schwerionenforschung (GSI) in Darmstadt, Germany in 2002 and 2003. TLR were detected as visible contrast enhancements on T1-weighted MRI images within a median follow-up time of 2.5 years. Although the derived RBE-weighted temporal lobe doses were based on the clinically applied LEM I, we have now recalculated the RBE-weighted dose distributions using LEM IV and derived dose-response curves with Dmax,V-1 cm³ (the RBE-weighted maximum dose in the remaining temporal lobe volume, excluding the volume of 1 cm³ with the highest dose) as an independent dosimetric variable. The resulting RBE-weighted tolerance doses were compared with those of the previous study to assess the clinical impact of LEM IV relative to LEM I. Results: The dose-response curve of LEM IV is shifted toward higher values compared to that of LEM I. The RBE-weighted tolerance dose for a 5% complication probability (TD{sub 5}) increases from 68.8 ± 3.3 to 78.3 ± 4.3 Gy (RBE) for LEM IV as compared to LEM I. Conclusions: LEM IV predicts a clinically significant increase of the RBE-weighted tolerance doses for the temporal lobe as compared to the currently applied LEM I. The limited available photon data do not allow a final conclusion as to whether RBE predictions of LEM I or LEM IV better fit better clinical experience in photon therapy. The decision about a future clinical application of LEM IV therefore requires additional analysis of temporal lobe reactions in a

Modeling the biophysical effects in a carbon beam delivery line by using Monte Carlo simulations

Science.gov (United States)

Cho, Ilsung; Yoo, SeungHoon; Cho, Sungho; Kim, Eun Ho; Song, Yongkeun; Shin, Jae-ik; Jung, Won-Gyun

2016-09-01

The Relative biological effectiveness (RBE) plays an important role in designing a uniform dose response for ion-beam therapy. In this study, the biological effectiveness of a carbon-ion beam delivery system was investigated using Monte Carlo simulations. A carbon-ion beam delivery line was designed for the Korea Heavy Ion Medical Accelerator (KHIMA) project. The GEANT4 simulation tool kit was used to simulate carbon-ion beam transport into media. An incident energy carbon-ion beam with energy in the range between 220 MeV/u and 290 MeV/u was chosen to generate secondary particles. The microdosimetric-kinetic (MK) model was applied to describe the RBE of 10% survival in human salivary-gland (HSG) cells. The RBE weighted dose was estimated as a function of the penetration depth in the water phantom along the incident beam's direction. A biologically photon-equivalent Spread Out Bragg Peak (SOBP) was designed using the RBE-weighted absorbed dose. Finally, the RBE of mixed beams was predicted as a function of the depth in the water phantom.

Characterization of relative biological effectiveness for conventional radiation therapy: a comparison of clinical 6 MV X-rays and 137Cs.

Science.gov (United States)

Howard, Michelle; Beltran, Chris; Sarkaria, Jann; Herman, Michael G

2017-09-01

Various types of radiation are utilized in the treatment of cancer. Equal physical doses of different radiation types do not always result in the same amount of biological damage. In order to account for these differences, a scaling factor known as the relative biological effectiveness (RBE) can be used. 137Cesium (137Cs) has been used as a source of radiation in a significant body of radiation therapy research. However, high-energy X-rays, such as 6 MV X-rays, are currently used clinically to treat patients. To date, there is a gap in the literature regarding the RBE comparison of these two types of radiation. Therefore, the purpose of this study was to investigate the RBE of 137Cs relative to that of 6 MV X-rays. To determine the RBE, five cell lines were irradiated [Chinese hamster ovary (CHO); human lung adenocarcinoma (A549); human glioma (U251); human glioma (T98); and human osteosarcoma (U2OS)] by both types of radiation and assessed for cell survival using a clonogenic assay. Three of the five cell lines resulted in RBE values of ~1.00 to within 11% for all survival fractions, showing the physical and biological dose for these two types of radiation were equivalent. The other two cell lines gave RBE values differing from 1.00 by up to 36%. In conclusion, the results show the range in biological effect seen between cell lines, and therefore cell type must be considered when characterizing RBE. © The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Early Toxicity in Patients Treated With Postoperative Proton Therapy for Locally Advanced Breast Cancer

Energy Technology Data Exchange (ETDEWEB)

Cuaron, John J. [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Chon, Brian; Tsai, Henry; Goenka, Anuj; DeBlois, David [Procure Proton Therapy Center, Somerset, New Jersey (United States); Ho, Alice; Powell, Simon [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Hug, Eugen [Procure Proton Therapy Center, Somerset, New Jersey (United States); Cahlon, Oren, E-mail: cahlono@mskcc.org [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Procure Proton Therapy Center, Somerset, New Jersey (United States)

2015-06-01

Purpose: To report dosimetry and early toxicity data in breast cancer patients treated with postoperative proton radiation therapy. Methods and Materials: From March 2013 to April 2014, 30 patients with nonmetastatic breast cancer and no history of prior radiation were treated with proton therapy at a single proton center. Patient characteristics and dosimetry were obtained through chart review. Patients were seen weekly while on treatment, at 1 month after radiation therapy completion, and at 3- to 6-month intervals thereafter. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. Frequencies of toxicities were tabulated. Results: Median dose delivered was 50.4 Gy (relative biological equivalent [RBE]) in 5 weeks. Target volumes included the breast/chest wall and regional lymph nodes including the internal mammary lymph nodes (in 93%). No patients required a treatment break. Among patients with >3 months of follow-up (n=28), grade 2 dermatitis occurred in 20 patients (71.4%), with 8 (28.6%) experiencing moist desquamation. Grade 2 esophagitis occurred in 8 patients (28.6%). Grade 3 reconstructive complications occurred in 1 patient. The median planning target volume V95 was 96.43% (range, 79.39%-99.60%). The median mean heart dose was 0.88 Gy (RBE) [range, 0.01-3.20 Gy (RBE)] for all patients, and 1.00 Gy (RBE) among patients with left-sided tumors. The median V20 of the ipsilateral lung was 16.50% (range, 6.1%-30.3%). The median contralateral lung V5 was 0.34% (range, 0%-5.30%). The median maximal point dose to the esophagus was 45.65 Gy (RBE) [range, 0-65.4 Gy (RBE)]. The median contralateral breast mean dose was 0.29 Gy (RBE) [range, 0.03-3.50 Gy (RBE)]. Conclusions: Postoperative proton therapy is well tolerated, with acceptable rates of skin toxicity. Proton therapy favorably spares normal tissue without compromising target coverage. Further follow-up is necessary to assess for clinical outcomes and cardiopulmonary

The response of mouse skin to re-irradiation with x-rays or fast neutrons

International Nuclear Information System (INIS)

Tsukiyama, Iwao; Egawa, Sunao; Kumazawa, Akiyoshi; Iino, Yuu.

1986-01-01

Effects of neutrons and x-rays on mouse skin which had been previously irradiated with x-rays were investigated. Two tattoo marks were placed in the hairless legs of mice at intervals of 15 mm. The legs were exposed to various doses of x-ray and neutrons to determine the relative biological effectiveness (RBE) using the contraction of the skin as an index. The RBE was 0.93 - 1.73. The legs of the mice were preexposed to 25 Gy of x-ray, and exposed 4 months later. The contraction of the skin began earlier than after the first irradiation. RBE was 2.18 - 2.47. This RBE was higher than that in untreated mice. These results suggest that previously irradiated normal tissues are much more sensitive to neutrons than to x-rays. (author)

Assessment of potential advantages of relevant ions for particle therapy: A model based study

Energy Technology Data Exchange (ETDEWEB)

Grün, Rebecca, E-mail: r.gruen@gsi.de [Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt 64291 (Germany); Institute of Medical Physics and Radiation Protection, University of Applied Sciences Gießen, Gießen 35390 (Germany); Medical Faculty of Philipps-University Marburg, Marburg 35032 (Germany); Friedrich, Thomas; Krämer, Michael; Scholz, Michael [Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt 64291 (Germany); Zink, Klemens [Institute of Medical Physics and Radiation Protection, University of Applied Sciences Gießen, Gießen 35390, Germany and Department of Radiotherapy and Radiation Oncology, University Medical Center Giessen and Marburg, Marburg 35043 (Germany); Durante, Marco [Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt 64291, Germany and Department of Condensed Matter Physics, Darmstadt University of Technology, Darmstadt 64289 (Germany); Engenhart-Cabillic, Rita [Medical Faculty of Philipps-University Marburg, Marburg 35032, Germany and Department of Radiotherapy and Radiation Oncology, University Medical Center Giessen and Marburg, Marburg 35043 (Germany)

2015-02-15

Purpose: Different ion types offer different physical and biological advantages for therapeutic applications. The purpose of this work is to assess the advantages of the most commonly used ions in particle therapy, i.e., carbon ({sup 12}C), helium ({sup 4}He), and protons ({sup 1}H) for different treatment scenarios. Methods: A treatment planning analysis based on idealized target geometries was performed using the treatment planning software TRiP98. For the prediction of the relative biological effectiveness (RBE) that is required for biological optimization in treatment planning the local effect model (LEM IV) was used. To compare the three ion types, the peak-to-entrance ratio (PER) was determined for the physical dose (PER{sub PHY} {sub S}), the RBE (PER{sub RBE}), and the RBE-weighted dose (PER{sub BIO}) resulting for different dose-levels, field configurations, and tissue types. Further, the dose contribution to artificial organs at risk (OAR) was assessed and a comparison of the dose distribution for the different ion types was performed for a patient with chordoma of the skull base. Results: The study showed that the advantages of the ions depend on the physical and biological properties and the interplay of both. In the case of protons, the consideration of a variable RBE instead of the clinically applied generic RBE of 1.1 indicates an advantage in terms of an increased PER{sub RBE} for the analyzed configurations. Due to the fact that protons show a somewhat better PER{sub PHY} {sub S} compared to helium and carbon ions whereas helium shows a higher PER{sub RBE} compared to protons, both protons and helium ions show a similar RBE-weighted dose distribution. Carbon ions show the largest variation of the PER{sub RBE} with tissue type and a benefit for radioresistant tumor types due to their higher LET. Furthermore, in the case of a two-field irradiation, an additional gain in terms of PER{sub BIO} is observed when using an orthogonal field configuration

A comparison of the potential therapeutic gain of p(66)/Be neutrons and d(14)/Be neutrons

International Nuclear Information System (INIS)

Slabbert, Jacobus P.; Theron, Therina; Zoelzer, Friedo; Streffer, Christian; Boehm, Lothar

2000-01-01

Purpose: To determine the relationship between photon sensitivity and neutron sensitivity and between neutron RBE and photon resistance for two neutron modalities (with mean energies of 6 and 29 MeV) using human tumor cell lines spanning a wide range of radiosensitivities, the principal objective being whether or not a neutron advantage can be demonstrated. Methods and Materials: Eleven human tumor cell lines with mean photon inactivation doses of 1.65-4.35 Gy were irradiated with 0-5.0 Gy of p(66)/Be neutrons (mean energy of 29 MeV) at Faure, S.A. and the same plating was irradiated on the same day with 0-10.0 Gy of Cobalt-γ-rays . Twelve human tumor cell lines, many of which were identical with the above selection, and spanning mean photon inactivation doses of 1.75-4.08 Gy, were irradiated with 0-4 Gy of d(14)/Be neutrons (mean energy of 6 MeV) and with 0-10 Gy of 240 kVp X-rays at the Essen Klinikum. Cell survival was determined by the clonogenic assay, and data were fitted to the linear quadratic equation. Results: 1. Using the mean inactivation dose, a significant correlation was found to exist between neutron sensitivity and photon sensitivity. However, this correlation was more pronounced in the Faure beam (r 2 = 0.89 , p ≤ 0.0001) than in the Essen beam (r 2 = 0.65, p = 0.0027). 2. No significant relationship could be established between neutron RBE and photon resistance for both modalities (p = 0.69 and p = 0.07, respectively). 3. Using α-coefficients as a criterion, the neutron sensitivity for the Faure beam correlated with photon sensitivity (p = 0.001), but this did not apply to the Essen beam (p = 0.27). 4. The neutron RBE for the Essen beam derived from α-coefficients showed a steep increase with photon resistance (p = 0.003). In the Faure beam there was no increase of RBE with photon resistance (p = 0.494). Conclusion: Radiobiological differences between high-energy and low-energy neutrons are particularly apparent in the dependence of the

Effect of edema, relative biological effectiveness, and dose heterogeneity on prostate brachytherapy

International Nuclear Information System (INIS)

Wang, Jian Z.; Mayr, Nina A.; Nag, Subir; Montebello, Joseph; Gupta, Nilendu; Samsami, Nina; Kanellitsas, Christos

2006-01-01

Many factors influence response in low-dose-rate (LDR) brachytherapy of prostate cancer. Among them, edema, relative biological effectiveness (RBE), and dose heterogeneity have not been fully modeled previously. In this work, the generalized linear-quadratic (LQ) model, extended to account for the effects of edema, RBE, and dose heterogeneity, was used to assess these factors and their combination effect. Published clinical data have shown that prostate edema after seed implant has a magnitude (ratio of post- to preimplant volume) of 1.3-2.0 and resolves exponentially with a half-life of 4-25 days over the duration of the implant dose delivery. Based on these parameters and a representative dose-volume histogram (DVH), we investigated the influence of edema on the implant dose distribution. The LQ parameters (α=0.15 Gy -1 and α/β=3.1 Gy) determined in earlier studies were used to calculate the equivalent uniform dose in 2 Gy fractions (EUD 2 ) with respect to three effects: edema, RBE, and dose heterogeneity for 125 I and 103 Pd implants. The EUD 2 analysis shows a negative effect of edema and dose heterogeneity on tumor cell killing because the prostate edema degrades the dose coverage to tumor target. For the representative DVH, the V 100 (volume covered by 100% of prescription dose) decreases from 93% to 91% and 86%, and the D 90 (dose covering 90% of target volume) decrease from 107% to 102% and 94% of prescription dose for 125 I and 103 Pd implants, respectively. Conversely, the RBE effect of LDR brachytherapy [versus external-beam radiotherapy (EBRT) and high-dose-rate (HDR) brachytherapy] enhances dose effect on tumor cell kill. In order to balance the negative effects of edema and dose heterogeneity, the RBE of prostate brachytherapy was determined to be approximately 1.2-1.4 for 125 I and 1.3-1.6 for 103 Pd implants. These RBE values are consistent with the RBE data published in the literature. These results may explain why in earlier modeling studies

Physical and biological factors determining the effective proton range

International Nuclear Information System (INIS)

Grün, Rebecca; Friedrich, Thomas; Krämer, Michael; Scholz, Michael; Zink, Klemens; Durante, Marco; Engenhart-Cabillic, Rita

2013-01-01

Purpose: Proton radiotherapy is rapidly becoming a standard treatment option for cancer. However, even though experimental data show an increase of the relative biological effectiveness (RBE) with depth, particularly at the distal end of the treatment field, a generic RBE of 1.1 is currently used in proton radiotherapy. This discrepancy might affect the effective penetration depth of the proton beam and thus the dose to the surrounding tissue and organs at risk. The purpose of this study was thus to analyze the impact of a tissue and dose dependent RBE of protons on the effective range of the proton beam in comparison to the range based on a generic RBE of 1.1.Methods: Factors influencing the biologically effective proton range were systematically analyzed by means of treatment planning studies using the Local Effect Model (LEM IV) and the treatment planning software TRiP98. Special emphasis was put on the comparison of passive and active range modulation techniques.Results: Beam energy, tissue type, and dose level significantly affected the biological extension of the treatment field at the distal edge. Up to 4 mm increased penetration depth as compared to the depth based on a constant RBE of 1.1. The extension of the biologically effective range strongly depends on the initial proton energy used for the most distal layer of the field and correlates with the width of the distal penumbra. Thus, the range extension, in general, was more pronounced for passive as compared to active range modulation systems, whereas the maximum RBE was higher for active systems.Conclusions: The analysis showed that the physical characteristics of the proton beam in terms of the width of the distal penumbra have a great impact on the RBE gradient and thus also the biologically effective penetration depth of the beam

Natural Disaster Induced Losses at Household Level: A Study on the Disaster Affected Migrants

Science.gov (United States)

Ishtiaque, A.; Nazem, N. I.; Jerin, T.

2015-12-01

Given its geographical location Bangladesh frequently confronts natural disasters. Disaster induced losses often obligate socio-economic dislocation from rural areas to large urban centers. After incurring what type/amount of losses people migrate is still unknown. In this paper we focus on migrants who migrated due to natural disasters. Thus, the objectives of this paper are, first, ascertaining the proportion of disaster migrants in Dhaka city; second, determining types of natural disasters which compel rural out-migration; third, assessing the resource and economic losses stem from these disasters at household level. Using the slum database (N = 4966), we select eight slums randomly with a purpose to include migrants from maximum districts available. In order to identify the proportion of disaster affected migrants a census is conducted in 407 households of those 8 slums and the result demonstrates that 18.43% of the migrants are disaster affected, which was only 5% in 1993. Out of all hydro-meteorological disasters, river bank erosion (RBE), followed by flood, drives most people out of their abode. However, unlike RBE migrants, migrants affected by flood usually return to their origin after certain period. In-depth interviews on the disaster migrants reveal that RBE claims total loss of homestead land & agricultural land while flood causes 20% and 23% loss respectively. Agricultural income decreases 96% because of RBE whereas flood victims encounter 98% decrease. People also incur 79% & 69% loss in livestock owing to RBE and flood severally. These disasters cause more than eighty percent reduction in total monthly income. Albeit RBE appears more vigorous but total economic loss is greater in flood- on average each household experiences a loss of BDT 350,555 due to flood and BDT 300,000 on account of RBE. Receiving no substantial support from community or government the affected people are compelled to migrate.

Relative Biological Effectiveness of HZE Particles for Chromosomal Exchanges and Other Surrogate Cancer Risk Endpoints.

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Eliedonna Cacao

Full Text Available The biological effects of high charge and energy (HZE particle exposures are of interest in space radiation protection of astronauts and cosmonauts, and estimating secondary cancer risks for patients undergoing Hadron therapy for primary cancers. The large number of particles types and energies that makeup primary or secondary radiation in HZE particle exposures precludes tumor induction studies in animal models for all but a few particle types and energies, thus leading to the use of surrogate endpoints to investigate the details of the radiation quality dependence of relative biological effectiveness (RBE factors. In this report we make detailed RBE predictions of the charge number and energy dependence of RBE's using a parametric track structure model to represent experimental results for the low dose response for chromosomal exchanges in normal human lymphocyte and fibroblast cells with comparison to published data for neoplastic transformation and gene mutation. RBE's are evaluated against acute doses of γ-rays for doses near 1 Gy. Models that assume linear or non-targeted effects at low dose are considered. Modest values of RBE (10 are predicted at low doses <0.1 Gy. The radiation quality dependence of RBE's against the effects of acute doses γ-rays found for neoplastic transformation and gene mutation studies are similar to those found for simple exchanges if a linear response is assumed at low HZE particle doses. Comparisons of the resulting model parameters to those used in the NASA radiation quality factor function are discussed.

The induction of somatic mutations by high-LET radiations using the drosophila assay system

International Nuclear Information System (INIS)

Yoshikawa, Isao; Takatsuji, Toshihiro

2004-01-01

Two types of somatic mutation in Drosophila melanogaster were examined to evaluate the relative biological effectiveness (RBE) of 252 Cf neutrons and heavy ions (carbon ions and neon ions) accelerated with a synchrotron for inducing mutations as a function of linear energy transfer (LET). One is the loss of heterozygosity for wing-hair mutations and the other the reversion of the mutant white-ivory. The measurements were made using a combined mutation assay system; so that induced mutant wing-hair clones as well as revertant eye-color clones could be detected simultaneously in the same fly. Larvae were irradiated at the age of 3 days post-oviposition. The efficiency of 252 Cf neutrons for inducing wing-hair mosaic spots is very high, RBE=8.5, but that for eye-color mosaic spot is almost equal (RBE=1.2) to that of 137 Cs γ-rays. RBE-LET relationships were obtained for the induction of wing-hair and eye-color mosaic spots. The RBE of carbon and neon ions for producing wing-hair mosaic spots increased with increasing LET values. The RBE for the induction of eye-color mutants did not change with LET. These relationships suggest that more complex types of DNA damage such as non-rejoinable strand breaks or clustered double strand breaks that increase with LET may be responsible for inducing the wing-hair mutation, while simpler forms of molecular damage may induce reversion in the white-ivory allele. (author)

Selection of carbon beam therapy: biophysical models of carbon beam therapy.

Science.gov (United States)

Matsufuji, Naruhiro

2018-03-01

Variation in the relative biological effectiveness (RBE) within the irradiation field of a carbon beam makes carbon-ion radiotherapy unique and advantageous in delivering the therapeutic dose to a deep-seated tumor, while sparing surrounding normal tissues. However, it is crucial to consider the RBE, not only in designing the dose distribution during treatment planning, but also in analyzing the clinical response retrospectively. At the National Institute of Radiological Sciences, the RBE model was established based on the response of human salivary gland cells. The response was originally handled with a linear-quadratic model, and later with a microdosimetric kinetic model. Retrospective analysis with a tumor-control probability model of non-small cell cancer treatment revealed a steep dose response in the tumor, and that the RBE of the tumor was adequately estimated using the model. A commonly used normal tissue complication probability model has not yet fully been accountable for the variable RBE of carbon ions; however, analysis of rectum injury after prostate cancer treatment suggested a highly serial-organ structure for the rectum, and a steep dose response similar to that observed for tumors.

The relative biological effectiveness of I-125 and Pd-103

International Nuclear Information System (INIS)

Ling, C. Clifton; Li, William X.; Anderson, Lowell L.

1995-01-01

Purpose: To determine the relative biological effectiveness (RBE) of I-125 and Pd-103 relative to Co-60. Methods and Materials: A cell line REC:ras, derived from rat embryo cells, was used. Cells in exponential or plateau phase were irradiated at dose rates of about 0.07 Gy/h and 0.14 Gy/h. To circumvent the interface effect, cells were grown and irradiated on membranes made of cellulose acetate, which has an effective Z of 7.5. I-125 and Pd-103 seeds were placed in a custom designed template that yielded a homogeneous dose distribution in the plane of the cell culture. The dose rates of irradiation were measured by calibrated thermoluminescence dosimetry (TLD) chips. Results and Conclusions: Our measurements yielded an RBE of about 1.4 for I-125 at dose rates of about 0.07 Gy/h, and an RBE of about 1.9 for Pd-103 at dose rates of about 0.07 Gy/h and 0.14 Gy/h. The RBE of I-125 is similar to those measured by other investigators, the RBE for Pd-103 is being reported for the first time

The quantitative description of radiation-unduced cell inactivation. 9. Some remarks on the relative biological effect of ionizing radiation upon reproductive death of diploid and polyploid cells

International Nuclear Information System (INIS)

Barsukov, V.S.; Malinovskij, O.V.

1978-01-01

A model of repproductive death of cells is suggested and tested on the basis of data on relative biological efficiency (RBE) with provision for microdosimetry approaches. The model considers irradiation of cells with charged particles under conditions of linear energy transfers (LET) to the cell nucleus by a particle. This energy is subject to great fluctuations, and irradiation of a cell should be characterized not by the absorbed dose but rather by its stochastic analogue - specific energy. It appears then that RBE should be determined from the specific energy-response relationshjp rather than from dose-response relationship. The followjng main results were obtained: experimental relationship between the yield of sublesions, one-track and two-track lethals and LET correspond to that expected from the literature data; under the conditions considered, RBE can be determined from absorbed dose-pesponse dependency; RBE for sublesions, one- and two-track lethals taken separatly does not depend on the radiation dose and the relationshjp between the resulting RBE and the response is governed by redistribution of contributions of one- and two-track lethals at different doses. The plausibility of the model suggested is thus confirmed

Interpretation of proton relative biological effectiveness using lesion induction, lesion repair, and cellular dose distribution

International Nuclear Information System (INIS)

Paganetti, H.

2005-01-01

Phenomenological biophysical models have been successfully used to estimate the relative biological effectiveness (RBE) of ions. The predictive power of these models is limited because they require measured dose-response data that are not necessarily available for all clinically relevant end points. Furthermore, input parameters often lack mechanistic interpretation. In order to link RBE to more fundamental biological parameters we combine the concepts of two well-established biophysical models, i.e., the phenomenological 'track structure' model and the more mechanistic 'lethal lesion/potentially lethal lesion' (LPL) model. We parametrize a relation between RBE, dose homogeneity in the cell nucleus and induction rates for different lesion types. The macroscopic dose-response relationship is described in the LPL model and the microscopic, subcellular, relationship is determined by the local dose deposition pattern. The formalism provides a framework for a mechanistic interpretation of RBE values

Fifteen symposia on microdosimetry: implications for modern particle-beam cancer radiotherapy

CERN Document Server

Wambersie, A; Gueulette, J; Pihet, P

2015-01-01

The objective of microdosimetry was, and still is, to identify physical descriptions of the initial physical processes of ionising radiation interacting with biological matter which correlate with observed radiobiological effects with a view to improve the understanding of radiobiological mechanisms and effects. The introduction of therapy with particles starting with fast neutrons followed by negative pions, protons and light ions necessitated the application of biological weighting factors for absorbed dose in order to account for differences of the relative biological effectiveness (RBE). Dedicated radiobiological experiments in therapy beams with mammalian cells and with laboratory animals provided sets of RBE values which are used to evaluate empirical ‘clinical RBE values’. The combination of such experiments with microdosimetric measurements in identical conditions offered the possibility to establish semi-empirical relationships between microdosimetric parameters and results of RBE studies.

Synergistic interaction between the neutron and gamma radiation on LACA mice hemopoietic stem cells

Energy Technology Data Exchange (ETDEWEB)

Xu, H

1982-02-01

Based on the radiation action dual theory of DNA single and double strand breaks, a hypothetical RBE mathematical model for the effect of the mixed radiation of neutron and gamma rays on LACA mice hemopoietic stem cells was formulated. In comparison of the RBE values of different ratio of neutron and gamma-ray mixed radiation with their theoretical additive RBE values, the preliminary impression is that the mixed radiation is more effective than that of the theoretical additive effect. It seems that the existence of synergist in the mixed radiation might be valid.

Ecodosimetry weighting factor (eR) for non-human biota

International Nuclear Information System (INIS)

Trivedi, A.; Gentner, N.E.

2000-01-01

The ICRP's radiological protection guidance for humans recognizes that equal absorbed doses of different types of radiation can have different biological effects in humans. ICRP publication 60 thus prescribes radiation weighting factors, w R values, to modify the absorbed dose (Gy) to effective dose (Sv) to enable the risk from different types of radiation to be compared on an equivalent basis. The w R values are selected on the basis of various considerations, including the linear energy transfer of the radiation and relative biological effectiveness (RBE) values (which are the ratios of the absorbed dose of reference to test radiation that produce an equivalent level of effect, for a given endpoint, system and dose level). There is no similar factor for non-human biota. It would be useful to have one: assessment of possible impacts on non-human biota (particularly from alpha-emitters and tritium beta-rays) is important for Canadian nuclear facilities. We propose a radiation equivalency factor 'e R ' for biota to fulfill a role equivalent to that occupied by w R in human radiation protection. RBE values for deterministic effects such as reproduction, fecundity and survival in biota are the critical bases for selection of e R values. These deterministic effects in populations are far more relevant to the assessment endpoints in ecological risk assessment than are stochastic effects, to which RBE values in human radiation protection relate. For tritium β-rays, most determinations support RBE values of 2-3 for deterministic effects when referenced to gamma radiation but little more than unity when x-rays are the reference radiation. This is because x-rays themselves have RBE -2 if referenced to gamma rays. Despite this, the ICRP assigns a w R of 1 to all electrons and all photons, including tritium beta-rays. Therefore, if e R is constrained to an integer, 1 is more appropriate than a value of 2 for tritium beta-rays. An RBE factor of 200-300 for alpha particles in

Small bowel toxicity after high dose spot scanning-based proton beam therapy for paraspinal/retroperitoneal neoplasms

Energy Technology Data Exchange (ETDEWEB)

Schneider, R.A.; Albertini, F.; Koch, T.; Ares, C.; Lomax, A.; Goitein, G. [Paul Scherrer Institute PSI, Villigen (Switzerland). Center for Proton Therapy; Vitolo, V. [Fondazione CNAO, Pavia (Italy); Hug, E.B. [Paul Scherrer Institute PSI, Villigen (Switzerland). Center for Proton Therapy; ProCure Proton Therapy Centers, New York, NY (United States)

2013-12-15

Purpose: Mesenchymal tumours require high-dose radiation therapy (RT). Small bowel (SB) dose constraints have historically limited dose delivery to paraspinal and retroperitoneal targets. This retrospective study correlated SB dose-volume histograms with side-effects after proton radiation therapy (PT). Patients and methods: Between 1997 and 2008, 31 patients (mean age 52.1 years) underwent spot scanning-based PT for paraspinal/retroperitoneal chordomas (81 %), sarcomas (16 %) and meningiom (3 %). Mean total prescribed dose was 72.3 Gy (relative biologic effectiveness, RBE) delivered in 1.8-2 Gy (RBE) fractions. Mean follow-up was 3.8 years. Based on the pretreatment planning CT, SB dose distributions were reanalysed. Results: Planning target volume (PTV) was defined as gross tumour volume (GTV) plus 5-7 mm margins. Mean PTV was 560.22 cm{sup 3}. A mean of 93.2 % of the PTV was covered by at least 90 % of the prescribed dose. SB volumes (cm{sup 3}) receiving doses of 5, 20, 30, 40, 50, 60, 70, 75 and 80 Gy (RBE) were calculated to give V5, V20, V30, V40, V50, V60, V70, V75 and V80 respectively. In 7/31 patients, PT was accomplished without any significant SB irradiation (V5 = 0). In 24/31 patients, mean maximum dose (Dmax) to SB was 64.1 Gy (RBE). Despite target doses of > 70 Gy (RBE), SB received > 50 and > 60 Gy (RBE) in only 61 and 54 % of patients, respectively. Mean SB volumes (cm{sup 3}) covered by different dose levels (Gy, RBE) were: V20 (n = 24): 45.1, V50 (n = 19): 17.7, V60 (n = 17): 7.6 and V70 (n = 12): 2.4. No acute toxicity {>=} grade 2 or late SB sequelae were observed. Conclusion: Small noncircumferential volumes of SB tolerated doses in excess of 60 Gy (RBE) without any clinically-significant late adverse effects. This small retrospective study has limited statistical power but encourages further efforts with higher patient numbers to define and establish high-dose threshold models for SB toxicity in modern radiation oncology. (orig.)

Analysis of Relative Biological Effectiveness of Proton Beams and Isoeffective Dose Profiles Using Geant4

Directory of Open Access Journals (Sweden)

Hosseini M. A.

2017-06-01

Full Text Available Background: The assessment of RBE quantity in the treatment of cancer tumors with proton beams in treatment planning systems (TPS is of high significance. Given the significance of the issue and the studies conducted in the literature, this quantity is fixed and is taken as equal to 1.1. Objective: The main objective of this study was to assess RBE quantity of proton beams and their variations in different depths of the tumor. This dependency makes RBE values used in TPS no longer be fixed as they depend on the depth of the tumor and therefore this dependency causes some changes in the physical dose profile. Materials and Methods: The energy spectrum of protons was measured at various depths of the tumor using proton beam simulations and well as the complete simulation of a cell to a pair of DNA bases through Monte Carlo GEANT4. The resulting energy spectrum was used to estimate the number of double-strand breaks generated in cells. Finally, RBE values were calculated in terms of the penetration depth in the tumor. Results and Conclusion: The simulation results show that the RBE value not fixed terms of the depth of the tumor and it differs from the clinical value of 1.1 at the end of the dose profile and this will lead to a non-uniform absorbed dose profile. Therefore, to create a uniform impact dose area, deep-finishing systems need to be designed by taking into account deep RBE values.

Estimate of the therapeutic ratio for charged particle beams

International Nuclear Information System (INIS)

Phillips, T.S.; Goldstein, L.S.

1980-01-01

To establish the RBE in normal and tumor tissue of heavy ion beams, the dose response for normal tissues, tumors and hypoxic and euoxic cells in vitro to single fraction irradiation and their ability to recover has been studied. The data demonstrate that the therapeutic ratio (RBE in tumor/RBE in normal tissue) of the murine systems increases with increasing LET up to the LET of the peak of the modulated neon beam. Although the argon beam has some features which make it attractive for therapy, its application may be limited because of its unfavorable biological depth-dose distribution

Neutron-induced mutation experiments. Progress report, March 1, 1976--February 28, 1977

International Nuclear Information System (INIS)

Abrahamson, S.

1976-11-01

Results are from studies of experiments in Drosophila on the relative mutagenic effectiveness of neutrons of different energies employing X-linked recessive lethal and specific locus mutation tests. The energies and doses employed to data are .43 MeV (500, 1000, and 1500 R, in progress), .68 MeV (250, 500, 1000, and 1500 R), 2 and 6 MeV (250 and 500 R), and 15 MeV (250, 500, 1000, 1500 and 3000 R). .68 MeV neutrons appear to have an RBE between 3.3 to 4.5, 15 MeV neutrons an RBE between 1.9 to 2.2, and 2 and 6 MeV neutrons RBE's of intermediate values. The data for both .68 and 15 MeV neutrons do not yet differentiate between a linear and quadratic dose/frequency response curve for the doses studied. The specific locus mutation data also indicate the highest RBE for .68 MeV, followed by 2 and 6 MeV respectively

The FLUKA Monte Carlo code coupled with the local effect model for biological calculations in carbon ion therapy

CERN Document Server

Mairani, A; Kraemer, M; Sommerer, F; Parodi, K; Scholz, M; Cerutti, F; Ferrari, A; Fasso, A

2010-01-01

Clinical Monte Carlo (MC) calculations for carbon ion therapy have to provide absorbed and RBE-weighted dose. The latter is defined as the product of the dose and the relative biological effectiveness (RBE). At the GSI Helmholtzzentrum fur Schwerionenforschung as well as at the Heidelberg Ion Therapy Center (HIT), the RBE values are calculated according to the local effect model (LEM). In this paper, we describe the approach followed for coupling the FLUKA MC code with the LEM and its application to dose and RBE-weighted dose calculations for a superimposition of two opposed C-12 ion fields as applied in therapeutic irradiations. The obtained results are compared with the available experimental data of CHO (Chinese hamster ovary) cell survival and the outcomes of the GSI analytical treatment planning code TRiP98. Some discrepancies have been observed between the analytical and MC calculations of absorbed physical dose profiles, which can be explained by the differences between the laterally integrated depth-d...

Lung Cancer Cell Line Screen Links Fanconi Anemia/BRCA Pathway Defects to Increased Relative Biological Effectiveness of Proton Radiation

International Nuclear Information System (INIS)

Liu, Qi; Ghosh, Priyanjali; Magpayo, Nicole; Testa, Mauro; Tang, Shikui; Gheorghiu, Liliana; Biggs, Peter; Paganetti, Harald; Efstathiou, Jason A.; Lu, Hsiao-Ming; Held, Kathryn D.; Willers, Henning

2015-01-01

Purpose: Growing knowledge of genomic heterogeneity in cancer, especially when it results in altered DNA damage responses, requires re-examination of the generic relative biological effectiveness (RBE) of 1.1 of protons. Methods and Materials: For determination of cellular radiosensitivity, we irradiated 17 lung cancer cell lines at the mid-spread-out Bragg peak of a clinical proton beam (linear energy transfer, 2.5 keV/μm). For comparison, 250-kVp X rays and 137 Cs γ-rays were used. To estimate the RBE of protons relative to 60 Co (Co60eq), we assigned an RBE(Co60Eq) of 1.1 to X rays to correct the physical dose measured. Standard DNA repair foci assays were used to monitor damage responses. FANCD2 was depleted using RNA interference. Results: Five lung cancer cell lines (29.4%) exhibited reduced clonogenic survival after proton irradiation compared with X-irradiation with the same physical doses. This was confirmed in a 3-dimensional sphere assay. Corresponding proton RBE(Co60Eq) estimates were statistically significantly different from 1.1 (P≤.05): 1.31 to 1.77 (for a survival fraction of 0.5). In 3 of these lines, increased RBE was correlated with alterations in the Fanconi anemia (FA)/BRCA pathway of DNA repair. In Calu-6 cells, the data pointed toward an FA pathway defect, leading to a previously unreported persistence of proton-induced RAD51 foci. The FA/BRCA-defective cells displayed a 25% increase in the size of subnuclear 53BP1 foci 18 hours after proton irradiation. Conclusions: Our cell line screen has revealed variations in proton RBE that are partly due to FA/BRCA pathway defects, suggesting that the use of a generic RBE for cancers should be revisited. We propose that functional biomarkers, such as size of residual 53BP1 foci, may be used to identify cancers with increased sensitivity to proton radiation

WE-H-BRA-07: Mechanistic Modelling of the Relative Biological Effectiveness of Heavy Charged Particles

Energy Technology Data Exchange (ETDEWEB)

McMahon, S [Massachusetts General Hospital, Boston, MA (United States); Queen’s University, Belfast, Belfast (United Kingdom); McNamara, A; Schuemann, J; Paganetti, H [Massachusetts General Hospital, Boston, MA (United States); Prise, K [Queen’s University, Belfast, Belfast (United Kingdom)

2016-06-15

Purpose Uncertainty in the Relative Biological Effectiveness (RBE) of heavy charged particles compared to photons remains one of the major uncertainties in particle therapy. As RBEs depend strongly on clinical variables such as tissue type, dose, and radiation quality, more accurate individualised models are needed to fully optimise treatments. MethodsWe have developed a model of DNA damage and repair following X-ray irradiation in a number of settings, incorporating mechanistic descriptions of DNA repair pathways, geometric effects on DNA repair, cell cycle effects and cell death. Our model has previously been shown to accurately predict a range of biological endpoints including chromosome aberrations, mutations, and cell death. This model was combined with nanodosimetric models of individual ion tracks to calculate the additional probability of lethal damage forming within a single track. These lethal damage probabilities can be used to predict survival and RBE for cells irradiated with ions of different Linear Energy Transfer (LET). ResultsBy combining the X-ray response model with nanodosimetry information, predictions of RBE can be made without cell-line specific fitting. The model’s RBE predictions were found to agree well with empirical proton RBE models (Mean absolute difference between models of 1.9% and 1.8% for cells with α/β ratios of 9 and 1.4, respectively, for LETs between 0 and 15 keV/µm). The model also accurately recovers the impact of high-LET carbon ion exposures, showing both the reduced efficacy of ions at extremely high LET, as well as the impact of defects in non-homologous end joining on RBE values in Chinese Hamster Ovary cells.ConclusionOur model is predicts RBE without the inclusion of empirical LET fitting parameters for a range of experimental conditions. This approach has the potential to deliver improved personalisation of particle therapy, with future developments allowing for the calculation of individualised RBEs. SJM is

Lung Cancer Cell Line Screen Links Fanconi Anemia/BRCA Pathway Defects to Increased Relative Biological Effectiveness of Proton Radiation

Energy Technology Data Exchange (ETDEWEB)

Liu, Qi; Ghosh, Priyanjali; Magpayo, Nicole [Laboratory of Cellular and Molecular Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Testa, Mauro; Tang, Shikui [Division of Radiation Physics, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Gheorghiu, Liliana [Laboratory of Cellular and Molecular Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Biggs, Peter; Paganetti, Harald [Division of Radiation Physics, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Efstathiou, Jason A. [Laboratory of Cellular and Molecular Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Lu, Hsiao-Ming [Division of Radiation Physics, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Held, Kathryn D. [Laboratory of Cellular and Molecular Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Willers, Henning, E-mail: hwillers@mgh.harvard.edu [Laboratory of Cellular and Molecular Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

2015-04-01

Purpose: Growing knowledge of genomic heterogeneity in cancer, especially when it results in altered DNA damage responses, requires re-examination of the generic relative biological effectiveness (RBE) of 1.1 of protons. Methods and Materials: For determination of cellular radiosensitivity, we irradiated 17 lung cancer cell lines at the mid-spread-out Bragg peak of a clinical proton beam (linear energy transfer, 2.5 keV/μm). For comparison, 250-kVp X rays and {sup 137}Cs γ-rays were used. To estimate the RBE of protons relative to {sup 60}Co (Co60eq), we assigned an RBE(Co60Eq) of 1.1 to X rays to correct the physical dose measured. Standard DNA repair foci assays were used to monitor damage responses. FANCD2 was depleted using RNA interference. Results: Five lung cancer cell lines (29.4%) exhibited reduced clonogenic survival after proton irradiation compared with X-irradiation with the same physical doses. This was confirmed in a 3-dimensional sphere assay. Corresponding proton RBE(Co60Eq) estimates were statistically significantly different from 1.1 (P≤.05): 1.31 to 1.77 (for a survival fraction of 0.5). In 3 of these lines, increased RBE was correlated with alterations in the Fanconi anemia (FA)/BRCA pathway of DNA repair. In Calu-6 cells, the data pointed toward an FA pathway defect, leading to a previously unreported persistence of proton-induced RAD51 foci. The FA/BRCA-defective cells displayed a 25% increase in the size of subnuclear 53BP1 foci 18 hours after proton irradiation. Conclusions: Our cell line screen has revealed variations in proton RBE that are partly due to FA/BRCA pathway defects, suggesting that the use of a generic RBE for cancers should be revisited. We propose that functional biomarkers, such as size of residual 53BP1 foci, may be used to identify cancers with increased sensitivity to proton radiation.

The RBE of tritium-beta exposure for the induction of the adaptive response and apoptosis; cellular defense mechanisms against the biological effects of ionizing radiation

International Nuclear Information System (INIS)

Boreham, D.R.; Bahen, M.E.; Dolling, J-A.

1997-01-01

Adaption to radiation is one of a few biological responses that has been demonstrated to occur in mammalian cells exposed to doses of ionizing radiation in the occupational exposure range. The adaptive response has been well characterized in the yeast Saccharomyces cerevisiae, although the doses required to induce the response are higher than in mammalian cells. When yeast cells are primed with sublethal doses of gamma-radiation, they subsequently undergo an adaptive response and develop resistance to radiation, heat the chemical mutagens in a time and dose dependent manner. We have used this model system to assess the relative ability of tritium-beta radiation to induce the adaptive response the examined tritium-induced radiation resistance, thermal tolerance and suppression of mutation. The results show that sublethal priming doses of tritium caused yeast cells to develop resistance to radiation, heat, and a chemical mutagen MNNG. The magnitude and kinetics of the response, per unit dose, were the same for tritium and gamma-radiation. Therefore, the relative biological effectiveness (RBE) of tritium induction of the adaptive response was about 1.0. Apoptosis is a genetically programmed cell death or cell suicide. Cells damaged by radiation can be selectively removed from the population by apoptosis and therefore eliminated as a potential cancer risk to the organism. Since we have previously shown that apoptosis is a sensitive indicator of radiation damage in human lymphocytes exposed to low doses, we have used this endpoint to investigate the potency of tritium-beta radiation. Initially, tritium was compared to X-rays for relative effectiveness at inducing apoptosis. The results showed the lymphocytes irradiated in vitro with X-rays or tritium had similar levels of apoptosis per unit dose. Therefore the relative biology effectiveness of tritium for induction of apoptosis in human lymphocytes was also about 1. In the work presented here, we have demonstrated that

RBE from a microdosimetric approach

Energy Technology Data Exchange (ETDEWEB)

Prestwich, W V; Nunes, J; Kwok, C S [McMaster Univ., Hamilton, ON (Canada); [Hamilton Regional Cancer Centre, ON (Canada)

1995-09-01

This report reviews the current status of microdosimetry and knowledge regarding the response of biological systems to radiation fields of differing linear energy transfer (LET). The primary objective is to investigate the potential application to radon daughter lung dosimetry. The concept of track structure and its statistical behaviour is discussed and applied to estimate the yield of double strand breaks (DSBs). The general microdosimetric approach to modelling radiation response is presented in terms of the hit-size effectiveness function and the behaviour for specific proposed functions is examined. Radiobiological investigations of the DSB, chromosome aberration and oncogenic transformation end points are reviewed with emphasis on recent developments. A simplified model system is developed illustrating the potential for analysis of the risk from radon daughter inhalation and published research directed towards this goal is discussed. (author). 66 refs., 3 tabs., 17 figs.

RBE from a microdosimetric approach

International Nuclear Information System (INIS)

Prestwich, W.V.; Nunes, J.; Kwok, C.S.

1995-09-01

This report reviews the current status of microdosimetry and knowledge regarding the response of biological systems to radiation fields of differing linear energy transfer (LET). The primary objective is to investigate the potential application to radon daughter lung dosimetry. The concept of track structure and its statistical behaviour is discussed and applied to estimate the yield of double strand breaks (DSBs). The general microdosimetric approach to modelling radiation response is presented in terms of the hit-size effectiveness function and the behaviour for specific proposed functions is examined. Radiobiological investigations of the DSB, chromosome aberration and oncogenic transformation end points are reviewed with emphasis on recent developments. A simplified model system is developed illustrating the potential for analysis of the risk from radon daughter inhalation and published research directed towards this goal is discussed. (author). 66 refs., 3 tabs., 17 figs

Relative biological effectiveness if alpha radiation for human lung exposure

International Nuclear Information System (INIS)

Yarmoshenko, I.; Kirdin, I.; Zhukovsky, M.

2006-01-01

Full text of publication follows: The concept of RBE, which introduced by ICRP and ICRU about 50 years ago to compare biological effects of ionizing radiation of different types, still continues to be the essential element of current and projected radiation protection systems in terms of deriving quantities (quality factor and radiation weighting factor). For example, RBE for the stochastic effects induction has to be considered for appropriate radiation weighting of the absorbed dose while estimating equivalent dose. Simulation of lung cancer radiation risk for the cases of inhalation of radon progeny and incorporation of plutonium in lung in comparison with external reference radiation allows assessment of RBE for alpha-radiation. Specific radiation risk models were developed by results of the direct epidemiological studies and used for such simulation. Simulation included published risk models for nuclear workers of the Mayak facilities in the former Soviet Union exposed to incorporated plutonium (Kreisheimer et al., 2003; Gilbert et al., 2004) and underground miners exposed to radon progenies (BEIR VI, 1999). Additionally lung cancer risk model was developed for a case of population indoor radon exposure. Lung cancer risk related to external exposure is estimated using the risk model develop ed using data of Life Span Study of Japanese atomic bomb survivors. By results of lifetime lung cancer risk simulation using Monte Carlo approach estimated median value of RBE in case of indoor radon exposure is 1.5 (with 90% range 0.4 to 7). In case of the two models developed by BEIR VI for lung cancer risk due to radon exposure in underground miners the median values of RBE are 2.1 and 4.4 (with 90% ranges 0.3 to 17 and 0.7 to 45) respectively.Two different models for lung cancer risk related to plutonium exposure resulted in close estimates of RBE: median value of 12 and 13 (with 90% range 4 to 104 and 4 to 136) respectively. Considerable discrepancy between RBE

Implementation of spot scanning dose optimization and dose calculation for helium ions in Hyperion

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Fuchs, Hermann, E-mail: hermann.fuchs@meduniwien.ac.at [Department of Radiation Oncology, Division of Medical Radiation Physics, Medical University of Vienna/AKH Vienna, Vienna 1090, Austria and Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Vienna 1090 (Austria); Alber, Markus [Department for Oncology, Aarhus University Hospital, Aarhus 8000 (Denmark); Schreiner, Thomas [PEG MedAustron, Wiener Neustadt 2700 (Austria); Georg, Dietmar [Department of Radiation Oncology, Division of Medical Radiation Physics, Medical University of Vienna/AKH Vienna, Vienna 1090 (Austria); Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Vienna 1090 (Austria); Comprehensive Cancer Center, Medical University of Vienna/AKH Vienna, Vienna 1090 (Austria)

2015-09-15

Purpose: Helium ions ({sup 4}He) may supplement current particle beam therapy strategies as they possess advantages in physical dose distribution over protons. To assess potential clinical advantages, a dose calculation module accounting for relative biological effectiveness (RBE) was developed and integrated into the treatment planning system Hyperion. Methods: Current knowledge on RBE of {sup 4}He together with linear energy transfer considerations motivated an empirical depth-dependent “zonal” RBE model. In the plateau region, a RBE of 1.0 was assumed, followed by an increasing RBE up to 2.8 at the Bragg-peak region, which was then kept constant over the fragmentation tail. To account for a variable proton RBE, the same model concept was also applied to protons with a maximum RBE of 1.6. Both RBE models were added to a previously developed pencil beam algorithm for physical dose calculation and included into the treatment planning system Hyperion. The implementation was validated against Monte Carlo simulations within a water phantom using γ-index evaluation. The potential benefits of {sup 4}He based treatment plans were explored in a preliminary treatment planning comparison (against protons) for four treatment sites, i.e., a prostate, a base-of-skull, a pediatric, and a head-and-neck tumor case. Separate treatment plans taking into account physical dose calculation only or using biological modeling were created for protons and {sup 4}He. Results: Comparison of Monte Carlo and Hyperion calculated doses resulted in a γ{sub mean} of 0.3, with 3.4% of the values above 1 and γ{sub 1%} of 1.5 and better. Treatment plan evaluation showed comparable planning target volume coverage for both particles, with slightly increased coverage for {sup 4}He. Organ at risk (OAR) doses were generally reduced using {sup 4}He, some by more than to 30%. Improvements of {sup 4}He over protons were more pronounced for treatment plans taking biological effects into account. All

Protective effect of Radix Bupleuri extract against liver cirrhosis in rats

African Journals Online (AJOL)

Some DENinduced rats were also treated with RBE, which was obtained by extracting dried Radix Bupleuri in water, for 8 weeks. Afterwards, biochemical indices and oxidative stress markers were assessed. Results: RBE significantly decreased serum concentrations of both alanine transaminase (137.3 ± 4.4 U/L, p < 0.01) ...

Carbon-Ion Radiation Therapy for Pelvic Recurrence of Rectal Cancer

Energy Technology Data Exchange (ETDEWEB)

Yamada, Shigeru, E-mail: s_yamada@nirs.go.jp [Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Kamada, Tadashi [Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Ebner, Daniel K. [Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Brown University Alpert Medical School, Providence, Rhode Island (United States); Shinoto, Makoto [Ion Beam Therapy Center, SAGA HIMAT Foundation, Saga (Japan); Terashima, Kotaro [Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Isozaki, Yuka; Yasuda, Shigeo; Makishima, Hirokazu; Tsuji, Hiroshi; Tsujii, Hirohiko [Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Isozaki, Tetsuro; Endo, Satoshi [Graduate School of Medicine, Chiba University, Chiba (Japan); Takahashi, Keiichi [Tokyo Metropolitan Cancer and Infectious Disease Center, Komagome, Tokyo (Japan); Sekimoto, Mitsugu [National Hospital Organization Osaka National Hospital, Osaka (Japan); Saito, Norio [National Cancer Center Hospital East, Kashiwa, Chiba (Japan); Matsubara, Hisahiro [Graduate School of Medicine, Chiba University, Chiba (Japan)

2016-09-01

Purpose: Investigation of the treatment potential of carbon-ion radiation therapy in pelvic recurrence of rectal cancer. Methods and Materials: A phase 1/2 dose escalation study was performed. One hundred eighty patients (186 lesions) with locally recurrent rectal cancer were treated with carbon-ion radiation therapy (CIRT) (phase 1/2: 37 and 143 patients, respectively). The relapse locations were 71 in the presacral region, 82 in the pelvic sidewalls, 28 in the perineum, and 5 near the colorectal anastomosis. A 16-fraction in 4 weeks dose regimen was used, with total dose ranging from 67.2 to 73.6 Gy(RBE); RBE-weighted absorbed dose: 4.2 to 4.6 Gy(RBE)/fraction. Results: During phase 1, the highest total dose, 73.6 Gy(RBE), resulted in no grade >3 acute reactions in the 13 patients treated at that dose. Dose escalation was halted at this level, and this dose was used for phase 2, with no other grade >3 acute reactions observed. At 5 years, the local control and survival rates at 73.6 Gy(RBE) were 88% (95% confidence interval [CI], 80%-93%) and 59% (95% CI, 50%-68%), respectively. Conclusion: Carbon-ion radiation therapy may be a safe and effective treatment option for locally recurrent rectal cancer and may serve as an alternative to surgery.

Beneficial Effects of Ethanolic and Hexanic Rice Bran Extract on Mitochondrial Function in PC12 Cells and the Search for Bioactive Components

Directory of Open Access Journals (Sweden)

Stephanie Hagl

2015-09-01

Full Text Available Mitochondria are involved in the aging processes that ultimately lead to neurodegeneration and the development of Alzheimer’s disease (AD. A healthy lifestyle, including a diet rich in antioxidants and polyphenols, represents one strategy to protect the brain and to prevent neurodegeneration. We recently reported that a stabilized hexanic rice bran extract (RBE rich in vitamin E and polyphenols (but unsuitable for human consumption has beneficial effects on mitochondrial function in vitro and in vivo (doi:10.1016/j.phrs.2013.06.008, 10.3233/JAD-132084. To enable the use of RBE as food additive, a stabilized ethanolic extract has been produced. Here, we compare the vitamin E profiles of both extracts and their effects on mitochondrial function (ATP concentrations, mitochondrial membrane potential, mitochondrial respiration and mitochondrial biogenesis in PC12 cells. We found that vitamin E contents and the effects of both RBE on mitochondrial function were similar. Furthermore, we aimed to identify components responsible for the mitochondria-protective effects of RBE, but could not achieve a conclusive result. α-Tocotrienol and possibly also γ-tocotrienol, α-tocopherol and δ-tocopherol might be involved, but hitherto unknown components of RBE or a synergistic effect of various components might also play a role in mediating RBE’s beneficial effects on mitochondrial function.

Development, Beam characterization and chromosomal effectiveness of X-rays of RBC characteristic X-ray generator

International Nuclear Information System (INIS)

Endo, Satoru; Hoshi, Masaharu; Takada, Jun; Takatsuji, Toshihiro; Ejima, Yosuke; Saigusa, Shin; Tachibana, Akira; Sasaki, Masao S.

2006-01-01

A characteristic hot-filament type X-ray generator was constructed for irradiation of cultured cells. The source provides copper K, iron K, chromium K, molybdenum L, aluminium K and carbon K shell characteristic X-rays. When cultured mouse m5S cells were irradiated and frequencies of dicentrics were fitted to a linear-quadratic model, Y=αD+βD 2 , the chromosomal effectiveness was not a simple function of photon energy. The α-terms increased with the decrease of the photon energy and then decreased with further decrease of the energy with an inflection point at around 10 keV. The β-terms stayed constant for the photon energy down to 10 keV and then increased with further decrease of energy. Below 10 keV, the relative biological effectiveness (RBE) at low doses was proportional to the photon energy, which contrasted to that for high energy X- or γ-rays where the RBE was inversely related with the photon energy. The reversion of the energy dependency occurred at around 1-2 Gy, where the RBE of soft X-rays was insensitive to X-ray energy. The reversion of energy-RBE relation at a moderate dose may shed light on the controversy on energy dependency of RBE of ultrasoft X-rays in cell survival experiments. (author)

WE-FG-BRB-04: RBEs for Human Lung Cancer Cells Exposed to Protons and Heavier Ions: Implications for Clinical Use of Charged Particles in Cancer Therapy

Energy Technology Data Exchange (ETDEWEB)

Held, K. [Massachusetts General Hospital (United States)

2016-06-15

The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences between particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to

WE-FG-BRB-03: Challenges and Opportunities for Implementing Biological Optimization in Particle Therapy

Energy Technology Data Exchange (ETDEWEB)

Carlson, D. [Yale University School of Medicine (United States)

2016-06-15

The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences between particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to

Site suitability for riverbed filtration system in Tanah Merah, Kelantan-A physical model study for turbidity removal

Science.gov (United States)

Ghani, Mastura; Adlan, Mohd Nordin; Kamal, Nurul Hana Mokhtar; Aziz, Hamidi Abdul

2017-10-01

A laboratory physical model study on riverbed filtration (RBeF) was conducted to investigate site suitability of soil from Tanah Merah, Kelantan for RBeF. Soil samples were collected and transported to the Geotechnical Engineering Laboratory, Universiti Sains Malaysia for sieve analysis and hydraulic conductivity tests. A physical model was fabricated with gravel packs laid at the bottom of it to cover the screen and then soil sample were placed above gravel pack for 30 cm depth. River water samples from Lubok Buntar, Kedah were used to simulate the effectiveness of RBeF for turbidity removal. Turbidity readings were tested at the inlet and outlet of the filter with specified flow rate. Results from soil characterization show that the soil samples were classified as poorly graded sand with hydraulic conductivity ranged from 7.95 x 10-3 to 6.61 x 10-2 cm/s. Turbidity removal ranged from 44.91% - 92.75% based on the turbidity of water samples before filtration in the range of 33.1-161 NTU. The turbidity of water samples after RBeF could be enhanced up to 2.53 NTU. River water samples with higher turbidity of more than 160 NTU could only reach 50% or less removal by the physical model. Flow rates of the RBeF were in the range of 0.11-1.61 L/min while flow rates at the inlet were set up between 2-4 L/min. Based on the result of soil classification, Tanah Merah site is suitable for RBeF whereas result from physical model study suggested that 30 cm depth of filter media is not sufficient to be used if river water turbidity is higher.

Outcomes and Acute Toxicities of Proton Therapy for Pediatric Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System

International Nuclear Information System (INIS)

McGovern, Susan L.; Okcu, M. Fatih; Munsell, Mark F.; Kumbalasseriyil, Nancy; Grosshans, David R.; McAleer, Mary F.; Chintagumpala, Murali; Khatua, Soumen; Mahajan, Anita

2014-01-01

Purpose: Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system is a rare cancer primarily affecting children younger than 5 years old. Because patients are young and receive intensive chemotherapy, there is concern regarding late radiation toxicity, particularly as survival rates improve. Therefore, there is interest in using proton therapy to treat these tumors. This study was undertaken to investigate outcomes and acute toxicities associated with proton therapy for AT/RT. Methods and Materials: The records of 31 patients with AT/RT treated with proton radiation from October 2008 to August 2013 were reviewed. Demographics, treatment characteristics, and outcomes were recorded and analyzed. Results: Median age at diagnosis was 19 months (range, 4-55 months), with a median age at radiation start of 24 months (range, 6-62 months). Seventeen patients received local radiation with a median dose of 50.4 GyRBE (range, 9-54 GyRBE). Fourteen patients received craniospinal radiation; half received 24 GyRBE or less, and half received 30.6 GyRBE or more. For patients receiving craniospinal radiation, the median tumor dose was 54 GyRBE (range, 43.2-55.8 GyRBE). Twenty-seven patients (87%) completed the planned radiation. With median follow-up of 24 months for all patients (range, 3-53 months), median progression-free survival was 20.8 months and median overall survival was 34.3 months. Five patients (16%) developed clinical findings and imaging changes in the brainstem 1 to 4 months after radiation, consistent with radiation reaction; all cases resolved with steroids or bevacizumab. Conclusions: This is the largest report of children with AT/RT treated with proton therapy. Preliminary survival outcomes in this young pediatric population are encouraging compared to historic results, but further study is warranted

Outcomes and Acute Toxicities of Proton Therapy for Pediatric Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System

Energy Technology Data Exchange (ETDEWEB)

McGovern, Susan L., E-mail: slmcgove@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Okcu, M. Fatih [Texas Children' s Hematology and Oncology Centers, Department of Pediatrics, Baylor College of Medicine, Houston, Texas (United States); Munsell, Mark F. [Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Kumbalasseriyil, Nancy; Grosshans, David R.; McAleer, Mary F. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chintagumpala, Murali [Texas Children' s Hematology and Oncology Centers, Department of Pediatrics, Baylor College of Medicine, Houston, Texas (United States); Khatua, Soumen [Department of Pediatrics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mahajan, Anita [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2014-12-01

Purpose: Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system is a rare cancer primarily affecting children younger than 5 years old. Because patients are young and receive intensive chemotherapy, there is concern regarding late radiation toxicity, particularly as survival rates improve. Therefore, there is interest in using proton therapy to treat these tumors. This study was undertaken to investigate outcomes and acute toxicities associated with proton therapy for AT/RT. Methods and Materials: The records of 31 patients with AT/RT treated with proton radiation from October 2008 to August 2013 were reviewed. Demographics, treatment characteristics, and outcomes were recorded and analyzed. Results: Median age at diagnosis was 19 months (range, 4-55 months), with a median age at radiation start of 24 months (range, 6-62 months). Seventeen patients received local radiation with a median dose of 50.4 GyRBE (range, 9-54 GyRBE). Fourteen patients received craniospinal radiation; half received 24 GyRBE or less, and half received 30.6 GyRBE or more. For patients receiving craniospinal radiation, the median tumor dose was 54 GyRBE (range, 43.2-55.8 GyRBE). Twenty-seven patients (87%) completed the planned radiation. With median follow-up of 24 months for all patients (range, 3-53 months), median progression-free survival was 20.8 months and median overall survival was 34.3 months. Five patients (16%) developed clinical findings and imaging changes in the brainstem 1 to 4 months after radiation, consistent with radiation reaction; all cases resolved with steroids or bevacizumab. Conclusions: This is the largest report of children with AT/RT treated with proton therapy. Preliminary survival outcomes in this young pediatric population are encouraging compared to historic results, but further study is warranted.

Comparative analysis of chromosome aberrations induced in human lymphocytes in vitro by various types of ionizing radiations

International Nuclear Information System (INIS)

Todorov, S.L.

1979-01-01

Certain problems of comparative analyses of radiation-induced dicentrics in human lymphocytes following various types of ionizing radiations are considered as follows: 1. Equations best fitting for dose-response kinetics; 2. Use of dicentrics for analysing the RBE of various types of radiations; 3. The relationship between RBE and LET as seen by the analysis of dicentrics. (author)

Radiotoxicity of gadolinium-148 and radium-223 in mouse testes: Relative biological effectiveness of alpha-particle emitters in vivo

International Nuclear Information System (INIS)

Howell, R.W.; Goddu, S.M.; Narra, V.R.

1997-01-01

The biological effects of radionuclides that emit α particles are of considerable interest in view of their potential for therapy and their presence in the environment. The present work is a continuation of our ongoing effort to study the radiotoxicity of α-particle emitters in vivo using the survival of murine testicular sperm heads as the biological end point. Specifically, the relative biological effectiveness (RBE) of very low-energy α particles (3.2 MeV) emitted by 148 Gd is investigated and determined to be 7.4 ± 2.4 when compared to the effects of acute external 120 kVp X rays. This datum, in conjunction with our earlier results for 210 Po and 212 Pb in equilibrium with its daughters, is used to revise and extend the range of validity of our previous RBE-energy relationship for α particles emitted by tissue-incorporated radionuclides. The new empirical relationship is given by RBE α = 9.14 - 0.510 E α , where 3 α 223 Ra (in equilibrium with its daughters) experimentally in the same biological model and comparing the value obtained experimentally with the predicted value. The resulting RBE values are 5.4 ± 0.9 and 5.6, respectively. This close agreement strongly supports the adequacy of the empirical RBE-E α relationship to predict the biological effects of α-particle emitters in vivo. 42 refs., 5 figs., 1 tab

Relative biological effectiveness of alpha-particle emitters in vivo at low doses

International Nuclear Information System (INIS)

Howell, R.W.; Azure, M.T.; Narra, V.R.; Rao, D.V.

1994-01-01

The therapeutic potential of radionuclides that emit α particles, as well as their associated health hazards, have attracted considerable attention. The 224 Ra daughters 212 Pb and 212 Bi, by virtue of their radiation properties which involve emission of α and β particles in their decay to stable 208 Pb, have been proposed as candidates for radioimmunotherapy. Using mouse testes as the experimental model and testicular spermhead survival as the biological end point, the present work examines the radiotoxicity of 212 Pb and its daughters. When 212 Pb, in equilibrium with its daughters 212 Bi, 212 Po and 208 Tl, was administered directly into the testis, the dose required to achieve 37% survival (D 37 ) was 0.143 ± 0.014 Gy and the corresponding RBE of the mixed radiation field was 4.7 when compared to the D 37 for acute external 120 kVp X rays. This datum, in conjunction with our earlier results for 210 Po, was used to obtain an RBE-LET relationship for α particles emitted by tissue-incorporated radionuclides: RBE α = 4.8 - 6.1 x 10 -2 LET + 1.0 x 10 -3 LET 2 . Similarly, the dependence of RBE on α-particle energy E α was given by RBE α = 22 E α -0.73 . These relationships, based on in vivo experimental data, may be valuable in predicting biological effects of α-particle emitters. 46 refs., 6 figs

A parameter study to determine the optimal source neutron energy in boron neutron capture therapy of brain tumours

Energy Technology Data Exchange (ETDEWEB)

Nievaart, V A [Reactor Physics Department, Delft University of Technology, Mekelweg 15, 2629JB Delft (Netherlands); Moss, R L [Joint Research Centre of the European Commission, Postbus 2, 1755ZG Petten (Netherlands); Kloosterman, J L [Reactor Physics Department, Delft University of Technology, Mekelweg 15, 2629JB Delft (Netherlands); Hagen, T H J J van der [Reactor Physics Department, Delft University of Technology, Mekelweg 15, 2629JB Delft (Netherlands); Dam, H van [Reactor Physics Department, Delft University of Technology, Mekelweg 15, 2629JB Delft (Netherlands)

2004-09-21

The values of the parameters used in boron neutron capture therapy (BNCT) to calculate a given dose to human tissue vary with patients due to different physical, biological and/or medical circumstances. Parameters include the tissue dimensions, the {sup 10}B concentration and the relative biological effectiveness (RBE) factors for the different dose components associated with BNCT. Because there is still no worldwide agreement on RBE values, more often than not, average values for these parameters are used. It turns out that the RBE-problem can be circumvented by taking into account all imaginable parameter values. Approaching this quest from another angle: the outcome will also provide the parameters (and values) which influence the optimal source neutron energy. For brain tumours it turns out that the {sup 10}B concentration, the RBE factors for {sup 10}B as well as fast neutrons, together with the dose limit set for healthy tissue, affect the optimal BNCT source neutron energy. By using source neutrons of a few keV together with neutrons of a few eV, it ensures that, under all imaginable circumstances, a maximum of alpha (and lithium) particles can be delivered in the tumour.

Quantification of Radiation-induced DNA Damage following intracellular Auger-Cascades

DEFF Research Database (Denmark)

Fredericia, Nina Pil Møntegaard

2017-01-01

Purpose: The aim my PhD study and the topic of this thesis is to investigate the radiotoxicity and the Relative Biological effectiveness (RBE) of intracellular Auger cascades. A special focus is kept on obtaining reliable absorbed dose calculations and using matched dose rate profiles for the Auger......-values (SC-values). The work can be divided into three steps; Examination of the bio-kinetics of the Auger emitter 131Cs used in the study, calculations of the SC-values and finally the measurement of the RBE of intracellular 131Cs decays, through ƴH2AX and clonogenic cell survival assay. Methods: A series....../(Bq*Sec)/pL for HeLa nuclei and from 7.45*10-4 to 7.63 *10-4 Gy/(Bq*Sec)/pL for V79 nuclei. The SC-values were shown to be were very robust and almost independent of cellular and nuclear size. A RBE value of 1 was obtained for HeLa cells using ƴH2AX assays. RBE values of 4.5 ± 0.5 and 3.8 ± 0.8 were obtained for He...

Low LET protons focused to submicrometer shows enhanced radiobiological effectiveness

Science.gov (United States)

Schmid, T. E.; Greubel, C.; Hable, V.; Zlobinskaya, O.; Michalski, D.; Girst, S.; Siebenwirth, C.; Schmid, E.; Molls, M.; Multhoff, G.; Dollinger, G.

2012-10-01

This study shows that enhanced radiobiological effectiveness (RBE) values can be generated focusing low linear energy transfer (LET) radiation and thus changing the microdose distribution. 20 MeV protons (LET = 2.65 keV µm-1) are focused to submicrometer diameter at the ion microprobe superconducting nanoprobe for applied nuclear (Kern) physics experiments of the Munich tandem accelerator. The RBE values, as determined by measuring micronuclei (RBEMN = 1.48 ± 0.07) and dicentrics (RBED = 1.92 ± 0.15), in human-hamster hybrid (AL) cells are significantly higher when 117 protons were focused to a submicrometer irradiation field within a 5.4 × 5.4 µm2 matrix compared to quasi homogeneous in a 1 × 1 µm2 matrix applied protons (RBEMN = 1.28 ± 0.07; RBED = 1.41 ± 0.14) at the same average dose of 1.7 Gy. The RBE values are normalized to standard 70 kV (dicentrics) or 200 kV (micronuclei) x-ray irradiation. The 117 protons applied per point deposit the same amount of energy like a 12C ion with 55 MeV total energy (4.48 MeV u-1). The enhancements are about half of that obtained for 12C ions (RBEMN = 2.20 ± 0.06 and RBED = 3.21 ± 0.10) and they are attributed to intertrack interactions of the induced damages. The measured RBE values show differences from predictions of the local effect model (LEM III) that is used to calculate RBE values for irradiation plans to treat tumors with high LET particles.

Distinct difference in relative biological effectiveness of 252Cf neutrons for the induction of mitotic crossing over and intragenic reversion of the white-ivory allele in Drosophila melanogaster

International Nuclear Information System (INIS)

Yoshikawa, Isao; Hoshi, Masaharu; Ikenaga, Mituo

1996-01-01

The relative biological effectiveness (RBE) of 252 Cf neutrons was determined for two different types of somatic mutations, i.e., loss of heterozygosity for wing-hair mutations and reversion of the mutant white-ivory eye-color, in Drosophila melanogaster. Loss of heterozygosity for wing-hair mutations results predominantly from mitotic crossing over induced in wing anlage cells of larvae, while the reverse mutation of eye-color is due to an intragenic structural change in the white locus on the X-chromosome. For a quantitative comparison of RBE values for these events, we have constructed a combined mutation assay system so that induced mutant wing-hair clones as well as revertant eye-color clones can be detected simultaneously in the same individuals. Larvae were irradiated at the age of 80±4 h post-oviposition with 252 Cf neutrons or 137 Cs γ-rays, and male adult flies were examined under the microscope for the presence of the two types of clonal mosaic spots appearing. The induction of wing-hair spots per dose unit was much greater for 252 Cf neutrons than for 137 Cs γ -rays, whereas the frequencies of eye-color reversion were similar for neutrons and γ-rays. The estimated RBE values of neutrons were 8.5 and 1.2 for the induction of mutant wing-hair spots and revertant eye-color spots, respectively. These results indicate that the RBE of neutrons is much greater for mitotic crossing over in comparison to the intragenic white-ivory reversion events. Possible causes for the difference in RBE are discussed

In Vivo Radiobiological Characterization of Proton Beam at the National Cancer Center in Korea: Effect of the Chk2 Mutation

International Nuclear Information System (INIS)

Kim, Sang Soo; Choo, Dong Wan; Shin, Dongho; Baek, Hye Jung; Kim, Tae Hyun; Motoyama, Noboru; De Coster, Blanche M.; Gueulette, John; Furusawa, Yoshiya; Ando, Koichi; Cho, Kwan Ho

2011-01-01

Purpose: The relative biological effectiveness (RBE) in the presence or absence of CHK2 was estimated at the Korean National Cancer Center Proton Therapy Center (NCCPTC). Methods and Materials: The proton beam was fixed at 210 MeV with 6-cm spread-out Bragg peaks (SOBPs) because this is expected to be the most frequently used clinical setting. X-rays were obtained using a 6-MV conventional linear accelerator. The RBE was estimated from the survival of jejunal crypt in C3H/He and Chk2 -/- mice. Results: The estimated RBEs of the NCCPTC at the middle of the SOBP were 1.10 and 1.05 in the presence and absence of CHK2, respectively. The doses that reduced the number of regenerated crypt per jejunal circumference to 20 (D 20 ) in C3H/He mice were 14.8 Gy (95% confidence interval [CI], 13.7-15.9) for X-rays and 13.5 Gy (95% CI, 14.5-15.5) for protons. By contrast, the doses of D 20 in Chk2 -/- mice were 15.7 Gy (95% CI, 15.0-16.4) and 14.9 Gy (95% CI, 14.0-15.8) for X-rays and protons, respectively. Conclusions: The RBE of the NCCPTC is clearly within the range of RBEs determined at other facilities and is consistent with the generic RBE value of 1.10 for 150- to 250-MeV beams. The mutation of Chk2 gave rise to radioresistance but exhibited similar RBE.

Phase 1 Study of Dose Escalation in Hypofractionated Proton Beam Therapy for Non-Small Cell Lung Cancer

Energy Technology Data Exchange (ETDEWEB)

Gomez, Daniel R., E-mail: dgomez@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gillin, Michael [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liao, Zhongxing [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wei, Caimiao [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lin, Steven H.; Swanick, Cameron; Alvarado, Tina; Komaki, Ritsuko; Cox, James D.; Chang, Joe Y. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2013-07-15

Background: Many patients with locally advanced non-small cell lung cancer (NSCLC) cannot undergo concurrent chemotherapy because of comorbidities or poor performance status. Hypofractionated radiation regimens, if tolerable, may provide an option to these patients for effective local control. Methods and Materials: Twenty-five patients were enrolled in a phase 1 dose-escalation trial of proton beam therapy (PBT) from September 2010 through July 2012. Eligible patients had histologically documented lung cancer, thymic tumors, carcinoid tumors, or metastatic thyroid tumors. Concurrent chemotherapy was not allowed, but concurrent treatment with biologic agents was. The dose-escalation schema comprised 15 fractions of 3 Gy(relative biological effectiveness [RBE])/fraction, 3.5 Gy(RBE)/fraction, or 4 Gy(RBE)/fraction. Dose constraints were derived from biologically equivalent doses of standard fractionated treatment. Results: The median follow-up time for patients alive at the time of analysis was 13 months (range, 8-28 months). Fifteen patients received treatment to hilar or mediastinal lymph nodes. Two patients experienced dose-limiting toxicity possibly related to treatment; 1 received 3.5-Gy(RBE) fractions and experienced an in-field tracheoesophageal fistula 9 months after PBT and 1 month after bevacizumab. The other patient received 4-Gy(RBE) fractions and was hospitalized for bacterial pneumonia/radiation pneumonitis 4 months after PBT. Conclusion: Hypofractionated PBT to the thorax delivered over 3 weeks was well tolerated even with significant doses to the lungs and mediastinal structures. Phase 2/3 trials are needed to compare the efficacy of this technique with standard treatment for locally advanced NSCLC.

Survival of parenchymal hepatocytes exposed to 14.3-MeV neutrons

International Nuclear Information System (INIS)

Jirtle, R.L.; Gould, M.N.; DeLuca, P.M. Jr.; Pearson, D.W.

1982-01-01

This report presents the results of the measurement of a dose survival curve and RBE values for rat hepatic cells irradiated in vivo with 14.3 MeV neutrons. The purpose was to determine the RBE for neutrons as a function of dose, and whether hepatocytes exposed to neutrons are as efficient at repairing potentially lethal damage as they are after exposure to low LET radiation

A Multidisciplinary Orbit-Sparing Treatment Approach That Includes Proton Therapy for Epithelial Tumors of the Orbit and Ocular Adnexa

Energy Technology Data Exchange (ETDEWEB)

Holliday, Emma B. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Esmaeli, Bita [Orbital Oncology and Ophthalmic Plastic Surgery Program, Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Pinckard, Jamie [School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, Texas (United States); Garden, Adam S.; Rosenthal, David I.; Morrison, William H. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Kies, Merrill S. [Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gunn, G. Brandon; Fuller, C. David; Phan, Jack; Beadle, Beth M. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Zhu, Xiarong Ronald; Zhang, Xiaodong [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Frank, Steven J., E-mail: sjfrank@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2016-05-01

Purpose: Postoperative radiation is often indicated in the treatment of malignant epithelial tumors of the orbit and ocular adnexa. We present details of radiation technique and toxicity data after orbit-sparing surgery followed by adjuvant proton radiation therapy. Methods and Materials: Twenty patients underwent orbit-sparing surgery followed by proton therapy for newly diagnosed malignant epithelial tumors of the lacrimal gland (n=7), lacrimal sac/nasolacrimal duct (n=10), or eyelid (n=3). Tumor characteristics, treatment details, and visual outcomes were obtained from medical records. Acute and chronic toxicity were prospectively scored using Common Terminology Criteria for Adverse Events version 4.0. Results: The median radiation dose was 60 Gy(RBE) (relative biological effectiveness; [range 50-70 Gy]); 11 patients received concurrent chemotherapy. Dose to ipsilateral anterior optic structures was reduced in 13 patients by having them gaze away from the target during treatment. At a median follow-up time of 27.1 months (range 2.6-77.2 months), no patient had experienced local recurrence; 1 had regional and 1 had distant recurrence. Three patients developed chronic grade 3 epiphora, and 3 developed grade 3 exposure keratopathy. Four patients experienced a decrease in visual acuity from baseline but maintained vision sufficient to perform all activities of daily living without difficulty. Patients with grade ≥3 chronic ocular toxicity had higher maximum dose to the ipsilateral cornea (median 46.3 Gy[RBE], range 36.6-52.7 Gy[RBE] vs median 37.4 Gy[RBE], range 9.0-47.3 Gy(RBE); P=.017). Conclusions: Orbit-sparing surgery for epithelial tumors of the orbit and ocular adnexa followed by proton therapy successfully achieved disease control and was well tolerated. No patient required orbital exenteration or enucleation. Chronic grade 3 toxicity was associated with high maximum dose to the cornea. An eye-deviation technique can be used to limit the maximum

A phenomenological biological dose model for proton therapy based on linear energy transfer spectra.

Science.gov (United States)

Rørvik, Eivind; Thörnqvist, Sara; Stokkevåg, Camilla H; Dahle, Tordis J; Fjaera, Lars Fredrik; Ytre-Hauge, Kristian S

2017-06-01

The relative biological effectiveness (RBE) of protons varies with the radiation quality, quantified by the linear energy transfer (LET). Most phenomenological models employ a linear dependency of the dose-averaged LET (LET d ) to calculate the biological dose. However, several experiments have indicated a possible non-linear trend. Our aim was to investigate if biological dose models including non-linear LET dependencies should be considered, by introducing a LET spectrum based dose model. The RBE-LET relationship was investigated by fitting of polynomials from 1st to 5th degree to a database of 85 data points from aerobic in vitro experiments. We included both unweighted and weighted regression, the latter taking into account experimental uncertainties. Statistical testing was performed to decide whether higher degree polynomials provided better fits to the data as compared to lower degrees. The newly developed models were compared to three published LET d based models for a simulated spread out Bragg peak (SOBP) scenario. The statistical analysis of the weighted regression analysis favored a non-linear RBE-LET relationship, with the quartic polynomial found to best represent the experimental data (P = 0.010). The results of the unweighted regression analysis were on the borderline of statistical significance for non-linear functions (P = 0.053), and with the current database a linear dependency could not be rejected. For the SOBP scenario, the weighted non-linear model estimated a similar mean RBE value (1.14) compared to the three established models (1.13-1.17). The unweighted model calculated a considerably higher RBE value (1.22). The analysis indicated that non-linear models could give a better representation of the RBE-LET relationship. However, this is not decisive, as inclusion of the experimental uncertainties in the regression analysis had a significant impact on the determination and ranking of the models. As differences between the models were

SU-F-T-208: An Efficient Planning Approach to Posterior Fossa Tumor Bed Boosts Using Proton Pencil Beam Scanning in Fixed-Beam Room

International Nuclear Information System (INIS)

Ju, N; Chen, C; Gans, S; Hug, E; Cahlon, O; Chon, B; Tsai, H; Sine, K; Mah, D; Wolden, S; Yeh, B

2016-01-01

Purpose: A fixed-beam room could be underutilized in a multi-room proton center. We investigated the use of proton pencil beam scanning (PBS) on a fixed-beam as an alternative for posterior fossa tumor bed (PF-TB) boost treatments which were usually treating on a gantry with uniform scanning. Methods: Five patients were treated with craniospinal irradiation (CSI, 23.4 or 36.0 Gy(RBE)) followed by a PF-TB boost to 54 Gy(RBE) with proton beams. Three PF-TB boost plans were generated for each patient: (1) a uniform scanning (US) gantry plan with 4–7 posterior fields shaped with apertures and compensators (2) a PBS plan using bi-lateral and vertex fields with a 3-mm planning organ-at-risk volume (PRV) expansion around the brainstem and (3) PBS fields using same beam arrangement but replacing the PRV with robust optimization considering a 3-mm setup uncertainty. Results: A concave 54-Gy(RBE) isodose line surrounding the brainstem could be achieved using all three techniques. The mean V95% of the PTV was 99.7% (range: 97.6% to 100%) while the V100% of the PTV ranged from 56.3% to 93.1% depending on the involvement of the brainstem with the PTV. The mean doses received by 0.05 cm"3 of the brainstem were effectively identical: 54.0 Gy(RBE), 53.4 Gy(RBE) and 53.3 Gy(RBE) for US, PBS optimized with PRV, and PBS optimized with robustness plans respectively. The cochlea mean dose increased by 23% of the prescribed boost dose in average from the bi-lateral fields used in the PBS plan. Planning time for the PBS plan with PRV was 5–10 times less than the US plan and the robustly optimized PBS plan. Conclusion: We have demonstrated that a fixed-beam with PBS can deliver a dose distribution comparable to a gantry plan using uniform scanning. Planning time can be reduced substantially using a PRV around the brainstem instead of robust optimization.

Exponential Increase in Relative Biological Effectiveness Along Distal Edge of a Proton Bragg Peak as Measured by Deoxyribonucleic Acid Double-Strand Breaks

Energy Technology Data Exchange (ETDEWEB)

Cuaron, John J., E-mail: cuaronj@mskcc.org [Memorial Sloan Kettering Cancer Center, New York, New York (United States); Chang, Chang [Texas Center for Proton Therapy, Irving, Texas (United States); Lovelock, Michael; Higginson, Daniel S. [Memorial Sloan Kettering Cancer Center, New York, New York (United States); Mah, Dennis [Procure Proton Therapy Center, Somerset, New Jersey (United States); Cahlon, Oren; Powell, Simon [Memorial Sloan Kettering Cancer Center, New York, New York (United States)

2016-05-01

Purpose: To quantify the relative biological effectiveness (RBE) of the distal edge of the proton Bragg peak, using an in vitro assay of DNA double-strand breaks (DSBs). Methods and Materials: U2OS cells were irradiated within the plateau of a spread-out Bragg peak and at each millimeter position along the distal edge using a custom slide holder, allowing for simultaneous measurement of physical dose. A reference radiation signal was generated using photons. The DNA DSBs at 3 hours (to assess for early damage) and at 24 hours (to assess for residual damage and repair) after irradiation were measured using the γH2AX assay and quantified via flow cytometry. Results were confirmed with clonogenic survival assays. A detailed map of the RBE as a function of depth along the Bragg peak was generated using γH2AX measurements as a biological endpoint. Results: At 3 hours after irradiation, DNA DSBs were higher with protons at every point along the distal edge compared with samples irradiated with photons to similar doses. This effect was even more pronounced after 24 hours, indicating that the impact of DNA repair is less after proton irradiation relative to photons. The RBE demonstrated an exponential increase as a function of depth and was measured to be as high as 4.0 after 3 hours and as high as 6.0 after 24 hours. When the RBE-corrected dose was plotted as a function of depth, the peak effective dose was extended 2-3 mm beyond what would be expected with physical measurement. Conclusions: We generated a highly comprehensive map of the RBE of the distal edge of the Bragg peak, using a direct assay of DNA DSBs in vitro. Our data show that the RBE of the distal edge increases with depth and is significantly higher than previously reported estimates.

Response of rat spinal cord to single and fractionated doses of accelerated heavy ions

International Nuclear Information System (INIS)

Leith, J.T.; McDonald, M.; Powers-Risius, P.; Bliven, S.F.; Howard, J.

1982-01-01

The thoraco-lumbar (T12-L1) region of the spinal cord of rats was exposed to either single or fractionated (four daily exposures) doses of X rays (230 kVp) or heavy ions. The heavy ions used were carbon and neon, and the relative biological effectiveness (RBE) of both the plateau ionization region and the midpeak region of 4-cm spread-out Bragg peaks of each heavy ion were investigated. For single doses of carbon and neon ions in the plateau ionization region, RBE values of 1.45 +/- 0.25 (propagated 95% confidence limits) and 1.46 +/- 0.33, respectively, were obtained. In the spread peak regions for carbon and neon ions, the RBE values were 1.48 +/- 0.18 and 1.86 +/- 0.42, respectively. These values were obtained using the dose needed to produce 50% paralysis in a group of irradiated rats as the isoeffect comparison dose (ED 50 dose). Similarly, in groups of rats receiving four daily exposures, the RBE values for carbon and neon ions in the plateau ionization region were 1.31 +/- 0.27 and 1.80 +/- 0.24, respectively. In the spread peak regions of ionization for carbon and neon ions, the RBE values were 1.95 +/- 0.19 and 2.18 +/- 0.23, respectively. Similar values for RBE were obtained using changes in the activity of enzymes in spinal cord tissue (cyclic nucleotide phosphohydrolase and γ-glutamyl transpeptidase). Also, it was estimated that, for X irradiation, the fractional amount of dose repaired (at the ED 50 dose) was 0.64 +/- 0.10 (95% confidence limits). For carbon and neon ions in the plateau ionization region, the values for the fractional amount of dose repaired were 0.70 +/- 0.27 and 0.48 +/- 0.20, and for carbon and neon ions in the spread peak region of ionization, the fractional repair values were 0.40 +/- 0.10 and 0.52 +/- 0.17. Spinal cord tissue therefore shows a high capacity for subeffective damage repair

Risk assessment for cancer induction after low- and high-LET therapeutic irradiation

International Nuclear Information System (INIS)

Engels, H.; Menzel, H.G.; Pihet, P.; Wambersie, A.

1999-01-01

The risk of induction of a second primary cancer after a therapeutic irradiation with conventional photon beams is well recognized and documented. However, in general, it is totally overwhelmed by the benefit of the treatment. The same is true to a large extent for the combinations of radiation and drug therapy. After fast neutron therapy, the risk of induction of a second cancer is greater than after photon therapy. Neutron RBE increases with decreasing dose and there is a wide evidence that neutron RBE is greater for cancer induction (and for other late effects relevant in radiation protection) than for cell killing. Animal data on RBE for tumor induction are reviewed, as well as other biological effects such as life shortening, malignant cell transformation in vitro, chromosome aberrations, genetic effects. These effects can be related, directly or indirectly, to cancer induction to the extent that they express a 'genomic' lesions. Almost no reliable human epidemiological data are available so far. For fission neutrons a RBE for cancer induction of about 20 relative to photons seems to be a reasonable assumption. For fast neutrons, due to the difference in energy spectrum, a RBE of 10 can be assumed. After proton beam therapy (low-LET radiation), the risk of secondary cancer induction, relative to photons, can be divided by a factor of 3, due to the reduction of integral dose (as an average). The RBE of heavy-ions for cancer induction can be assumed to be similar to fission neutrons, i.e. about 20 relative to photons. However, after heavy-ion beam therapy, the risk should be divided by 3, as after proton therapy, due to the excellent physical selectivity of the irradiation. Therefore, a risk 5 to 10 times higher than photons could be assumed. This range is probably a pessimistic estimate for carbon ions since most of the normal tissues, at the level of the initial plateau, are irradiated with low-LET radiation. (orig.)

SU-F-T-208: An Efficient Planning Approach to Posterior Fossa Tumor Bed Boosts Using Proton Pencil Beam Scanning in Fixed-Beam Room

Energy Technology Data Exchange (ETDEWEB)

Ju, N; Chen, C; Gans, S; Hug, E; Cahlon, O; Chon, B; Tsai, H; Sine, K; Mah, D [Procure Treatment Center, Somerset, New Jersey (United States); Wolden, S [Memorial Sloan Kettering Cancer Center, New York, NY (United States); Yeh, B [Mount Sinai Hospital, New York, NY (United States)

2016-06-15

Purpose: A fixed-beam room could be underutilized in a multi-room proton center. We investigated the use of proton pencil beam scanning (PBS) on a fixed-beam as an alternative for posterior fossa tumor bed (PF-TB) boost treatments which were usually treating on a gantry with uniform scanning. Methods: Five patients were treated with craniospinal irradiation (CSI, 23.4 or 36.0 Gy(RBE)) followed by a PF-TB boost to 54 Gy(RBE) with proton beams. Three PF-TB boost plans were generated for each patient: (1) a uniform scanning (US) gantry plan with 4–7 posterior fields shaped with apertures and compensators (2) a PBS plan using bi-lateral and vertex fields with a 3-mm planning organ-at-risk volume (PRV) expansion around the brainstem and (3) PBS fields using same beam arrangement but replacing the PRV with robust optimization considering a 3-mm setup uncertainty. Results: A concave 54-Gy(RBE) isodose line surrounding the brainstem could be achieved using all three techniques. The mean V95% of the PTV was 99.7% (range: 97.6% to 100%) while the V100% of the PTV ranged from 56.3% to 93.1% depending on the involvement of the brainstem with the PTV. The mean doses received by 0.05 cm{sup 3} of the brainstem were effectively identical: 54.0 Gy(RBE), 53.4 Gy(RBE) and 53.3 Gy(RBE) for US, PBS optimized with PRV, and PBS optimized with robustness plans respectively. The cochlea mean dose increased by 23% of the prescribed boost dose in average from the bi-lateral fields used in the PBS plan. Planning time for the PBS plan with PRV was 5–10 times less than the US plan and the robustly optimized PBS plan. Conclusion: We have demonstrated that a fixed-beam with PBS can deliver a dose distribution comparable to a gantry plan using uniform scanning. Planning time can be reduced substantially using a PRV around the brainstem instead of robust optimization.

Response of the skin of hamsters to fractionated irradiation with X rays or accelerated carbon ions

International Nuclear Information System (INIS)

Leith, J.T.; Powers-Risius, P.; Woodruff, K.H.; McDonald, M.; Howard, J.

1981-01-01

The ventral thoracic skin of hamsters was irradiated with either single, split (two fractions given in 24 hr), or multiple (five fractions given daily) exposures of X rays or accelerated carbon ions using a 4-cm spread Bragg peak. Animals were positioned in the heavy-ion beam so that the ventral thoracic skin surface was 1 cm distal to the proximal peak of the modified beam. Early skin reactions from 6 to 30 days postirradiation were assessed. Using the average skin reactions produced in this period, it was found that the relative biological effect (RBE) for single doses of carbon ions was about 1.6 (5-17 Gy per fraction), for two fractions about 1.8 (5-17 Gy perfraction), and for five fractions about 1.9 (2.4-7.2 Gy per fraction). The fractional amount of sublethal damage repaired after carbon ion irradiation was about 0.3 (at dose levels of 2.4-8.0 Gy per fraction) compared to a value of about 0.45 (at dose levels of 60-13.0 Gy per fraction) found for the fractionated X irradiations, indicting about a 33% decrease in the relative amount of sublethal damage repaired after carbon ion irradiation in this position in the spread Bragg curve. Also, data were interpreted using plots of the reciprocal total dose needed to produce a given level of skin damage versus the dose per fraction used in the multifraction experiments, and of the RBE versus dose per fraction obtained from a nonparametric analysis of the responses. These approaches allow estimation of RBE at dose levels relevant to the clinical situation. Also, estimation may be made of the maximum permissible RBE by using the zero dose intercept value from the linear reciprocal dose plot. With this approach, the RBE at a dose level of 2 Gy is about 2.5 and the maximum RBE value is about 2.7

Evaluating Intensity Modulated Proton Therapy Relative to Passive Scattering Proton Therapy for Increased Vertebral Column Sparing in Craniospinal Irradiation in Growing Pediatric Patients

International Nuclear Information System (INIS)

Giantsoudi, Drosoula; Seco, Joao; Eaton, Bree R.; Simeone, F. Joseph; Kooy, Hanne; Yock, Torunn I.; Tarbell, Nancy J.; DeLaney, Thomas F.; Adams, Judith; Paganetti, Harald; MacDonald, Shannon M.

2017-01-01

Purpose: At present, proton craniospinal irradiation (CSI) for growing children is delivered to the whole vertebral body (WVB) to avoid asymmetric growth. We aimed to demonstrate the feasibility and potential clinical benefit of delivering vertebral body sparing (VBS) versus WVB CSI with passively scattered (PS) and intensity modulated proton therapy (IMPT) in growing children treated for medulloblastoma. Methods and Materials: Five plans were generated for medulloblastoma patients, who had been previously treated with CSI PS proton radiation therapy: (1) single posteroanterior (PA) PS field covering the WVB (PS-PA-WVB); (2) single PA PS field that included only the thecal sac in the target volume (PS-PA-VBS); (3) single PA IMPT field covering the WVB (IMPT-PA-WVB); (4) single PA IMPT field, target volume including thecal sac only (IMPT-PA-VBS); and (5) 2 posterior-oblique (−35°, +35°) IMPT fields, with the target volume including the thecal sac only (IMPT2F-VBS). For all cases, 23.4 Gy (relative biologic effectiveness [RBE]) was prescribed to 95% of the spinal canal. The dose, linear energy transfer, and variable-RBE-weighted dose distributions were calculated for all plans using the tool for particle simulation, version 2, Monte Carlo system. Results: IMPT VBS techniques efficiently spared the anterior vertebral bodies (AVBs), even when accounting for potential higher variable RBE predicted by linear energy transfer distributions. Assuming an RBE of 1.1, the V10 Gy(RBE) decreased from 100% for the WVB techniques to 59.5% to 76.8% for the cervical, 29.9% to 34.6% for the thoracic, and 20.6% to 25.1% for the lumbar AVBs, and the V20 Gy(RBE) decreased from 99.0% to 17.8% to 20.0% for the cervical, 7.2% to 7.6% for the thoracic, and 4.0% to 4.6% for the lumbar AVBs when IMPT VBS techniques were applied. The corresponding percentages for the PS VBS technique were higher. Conclusions: Advanced proton techniques can sufficiently reduce the dose to the vertebral

Evaluating Intensity Modulated Proton Therapy Relative to Passive Scattering Proton Therapy for Increased Vertebral Column Sparing in Craniospinal Irradiation in Growing Pediatric Patients

Energy Technology Data Exchange (ETDEWEB)

Giantsoudi, Drosoula, E-mail: dgiantsoudi@mgh.harvard.edu; Seco, Joao; Eaton, Bree R.; Simeone, F. Joseph; Kooy, Hanne; Yock, Torunn I.; Tarbell, Nancy J.; DeLaney, Thomas F.; Adams, Judith; Paganetti, Harald; MacDonald, Shannon M.

2017-05-01

Purpose: At present, proton craniospinal irradiation (CSI) for growing children is delivered to the whole vertebral body (WVB) to avoid asymmetric growth. We aimed to demonstrate the feasibility and potential clinical benefit of delivering vertebral body sparing (VBS) versus WVB CSI with passively scattered (PS) and intensity modulated proton therapy (IMPT) in growing children treated for medulloblastoma. Methods and Materials: Five plans were generated for medulloblastoma patients, who had been previously treated with CSI PS proton radiation therapy: (1) single posteroanterior (PA) PS field covering the WVB (PS-PA-WVB); (2) single PA PS field that included only the thecal sac in the target volume (PS-PA-VBS); (3) single PA IMPT field covering the WVB (IMPT-PA-WVB); (4) single PA IMPT field, target volume including thecal sac only (IMPT-PA-VBS); and (5) 2 posterior-oblique (−35°, +35°) IMPT fields, with the target volume including the thecal sac only (IMPT2F-VBS). For all cases, 23.4 Gy (relative biologic effectiveness [RBE]) was prescribed to 95% of the spinal canal. The dose, linear energy transfer, and variable-RBE-weighted dose distributions were calculated for all plans using the tool for particle simulation, version 2, Monte Carlo system. Results: IMPT VBS techniques efficiently spared the anterior vertebral bodies (AVBs), even when accounting for potential higher variable RBE predicted by linear energy transfer distributions. Assuming an RBE of 1.1, the V10 Gy(RBE) decreased from 100% for the WVB techniques to 59.5% to 76.8% for the cervical, 29.9% to 34.6% for the thoracic, and 20.6% to 25.1% for the lumbar AVBs, and the V20 Gy(RBE) decreased from 99.0% to 17.8% to 20.0% for the cervical, 7.2% to 7.6% for the thoracic, and 4.0% to 4.6% for the lumbar AVBs when IMPT VBS techniques were applied. The corresponding percentages for the PS VBS technique were higher. Conclusions: Advanced proton techniques can sufficiently reduce the dose to the vertebral

Exploration of 'over kill effect' of high-LET Ar- and Fe-ions by evaluating the fraction of non-hit cell and interphase death

International Nuclear Information System (INIS)

Mehnati, P.; Sasaki, Hiroshi; Morimoto, Shigeko; Yatagai, Fumio; Hanaoka, Fumio; Furusawa, Yoshiya; Kanai, Tatsuaki; Kobayashi, Yasuhiko; Wada, Seiichi

2005-01-01

The reason why relative biological effectiveness (RBE) for cell killing fell to less than unity (1.0) with very high-linear energy transfer (LET) heavy-ions ( 40 Ar: 1,640 keV/μm; 56 Fe: 780, 1,200, 2,000 keV/μm) was explored by evaluating the fraction of non-hit cell (time-lapse observation) and cells undergoing interphase death (calculation based on our previous data). Chinese hamster ovary (CHO) cells were exposed to 4 Gy (30% survival dose) of Ar (1,640 keV/μm) or Fe-ions (2,000 keV/μm). About 20% of all cells were judged to be non-hit, and about 10% cells survived radiation damage. About 70% cells died after dividing at least once (reproductive death) or without dividing (interphase death). RBE for reproductive (RBE[R]) and interphase (RBE[I]) death showed a similar LET dependence with maximum around 200 keV/μm. In this LET region, at 30% survival level, about 10% non-survivors underwent interphase death. The corresponding value for very high-LET Fe-ions (2,000 keV/μm) was not particularly high (-15%), whereas that for X-rays was less than 3%. However, reproductive death (67%) predominated over interphase death (33%) even in regard to rather severely damaged cells (1% survival level) after exposure to Fe-ions (2,000 keV/μm). These indicate that interphase death is a type of cell death characteristic for the cells exposed to high-LET radiation and is not caused by 'cellular over kill effect'. Both NHF37 (non-hit fraction at 37% survival) and inactivation cross-section for reproductive death (σ[R]) began to increase when LET exceeded 100 keV/μm. The exclusion of non-hit fraction in the calculation of surviving fraction partially prevented the fall of RBE[R] when LET exceeded 200 keV/μm. On the other hand, the mean number of lethal damage per unit dose (NLD/Gy) showed the same LET-dependent pattern as RBE[R]. These suggest that the increase in non-hit fraction and σ[R] with an increasing LET is caused by enhanced clustering of ionization and DNA damage

Response of mouse skin and bone marrow to heavy charged particles

International Nuclear Information System (INIS)

Ainsworth, E.J.

1980-01-01

Because of the desirability to determine RBE at therapeutically relevant dose levels, our approach was to use a challenge-dose technique. This challenge-dose technique assesses injury accumulation and repair or recovery following administration of comparatively low doses by challenging animals. No previous studies have been conducted using CFU-S irradiated in vivo as a model system to assess the RBE of heavy charged particles for either cell killing or for late effects. The goal of the CFU-S studies reported here was to determine the RBE for cell killing, and to use these data to design experiments to explore the effects of HZE particle dose fractionation on femur CFU-S repopulation and on late effects indicated by a reduction in the size of the CFU-S compartment

R.b.e. of 50 kVp X-rays and 660 keV γ-rays (137Cs) with respect to the production of DNA damage, repair and cell-killing in Escherichia coli K-12

International Nuclear Information System (INIS)

Bonura, T.; Youngs, D.A.; Smith, K.C.

1975-01-01

A comparison has been made of the efficiency of cell-killing, DNA single-strand breakage and double-strand breakage in an Escherichia coli K-12 wild-type strain after irradiation with soft X-rays (50 kVp) and hard γ-rays (660 keV) under aerobic conditions. Irradiation with 50 kVp X-rays resulted in 1.47 times more cell-killing than was observed with 137 Cs γ-rays based on a comparison of D 0 values evaluated from the survival curves. DNA sedimentation studies showed that, although 50 kVp X-rays were 1.93 times more effective than 137 Cs γ-rays in producing DNA double-strand breaks, there was no significant difference between the two qualities of radiation with respect to the initial number of single-strand breaks produced. When the cells were irradiated and allowed to repair maximally in minimal medium, 1.57 times more unrepaired DNA single-strand breaks remained per krad after irradiation with 50 kVp X-rays than with 137 Cs γ-rays. The increased yield of DNA double-strand breaks resulting from 50 kVp X-irradiation may account for most of these additional unrepaired single-strand breaks, since single- and double-strand breaks are indistinguishable on alkaline sucrose gradients. These results suggest that the greater r.b.e. of 50 kVp X-rays may be related to an increased effectiveness for producing DNA double-strand breaks compared with the higher energy 137 Cs γ-rays. (author)

The FLUKA Monte Carlo code coupled with the local effect model for biological calculations in carbon ion therapy

Energy Technology Data Exchange (ETDEWEB)

Mairani, A [University of Pavia, Department of Nuclear and Theoretical Physics, and INFN, via Bassi 6, 27100 Pavia (Italy); Brons, S; Parodi, K [Heidelberg Ion Beam Therapy Center and Department of Radiation Oncology, Im Neuenheimer Feld 450, 69120 Heidelberg (Germany); Cerutti, F; Ferrari, A; Sommerer, F [CERN, 1211 Geneva 23 (Switzerland); Fasso, A [SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025 (United States); Kraemer, M; Scholz, M, E-mail: Andrea.Mairani@mi.infn.i [GSI Biophysik, Planck-Str. 1, D-64291 Darmstadt (Germany)

2010-08-07

Clinical Monte Carlo (MC) calculations for carbon ion therapy have to provide absorbed and RBE-weighted dose. The latter is defined as the product of the dose and the relative biological effectiveness (RBE). At the GSI Helmholtzzentrum fuer Schwerionenforschung as well as at the Heidelberg Ion Therapy Center (HIT), the RBE values are calculated according to the local effect model (LEM). In this paper, we describe the approach followed for coupling the FLUKA MC code with the LEM and its application to dose and RBE-weighted dose calculations for a superimposition of two opposed {sup 12}C ion fields as applied in therapeutic irradiations. The obtained results are compared with the available experimental data of CHO (Chinese hamster ovary) cell survival and the outcomes of the GSI analytical treatment planning code TRiP98. Some discrepancies have been observed between the analytical and MC calculations of absorbed physical dose profiles, which can be explained by the differences between the laterally integrated depth-dose distributions in water used as input basic data in TRiP98 and the FLUKA recalculated ones. On the other hand, taking into account the differences in the physical beam modeling, the FLUKA-based biological calculations of the CHO cell survival profiles are found in good agreement with the experimental data as well with the TRiP98 predictions. The developed approach that combines the MC transport/interaction capability with the same biological model as in the treatment planning system (TPS) will be used at HIT to support validation/improvement of both dose and RBE-weighted dose calculations performed by the analytical TPS.

Gibbs Sampler-Based λ-Dynamics and Rao-Blackwell Estimator for Alchemical Free Energy Calculation.

Science.gov (United States)

Ding, Xinqiang; Vilseck, Jonah Z; Hayes, Ryan L; Brooks, Charles L

2017-06-13

λ-dynamics is a generalized ensemble method for alchemical free energy calculations. In traditional λ-dynamics, the alchemical switch variable λ is treated as a continuous variable ranging from 0 to 1 and an empirical estimator is utilized to approximate the free energy. In the present article, we describe an alternative formulation of λ-dynamics that utilizes the Gibbs sampler framework, which we call Gibbs sampler-based λ-dynamics (GSLD). GSLD, like traditional λ-dynamics, can be readily extended to calculate free energy differences between multiple ligands in one simulation. We also introduce a new free energy estimator, the Rao-Blackwell estimator (RBE), for use in conjunction with GSLD. Compared with the current empirical estimator, the advantage of RBE is that RBE is an unbiased estimator and its variance is usually smaller than the current empirical estimator. We also show that the multistate Bennett acceptance ratio equation or the unbinned weighted histogram analysis method equation can be derived using the RBE. We illustrate the use and performance of this new free energy computational framework by application to a simple harmonic system as well as relevant calculations of small molecule relative free energies of solvation and binding to a protein receptor. Our findings demonstrate consistent and improved performance compared with conventional alchemical free energy methods.

The relative biological effectiveness of antiprotons

DEFF Research Database (Denmark)

Holzscheiter, Michael H.; Alsner, Jan; Bassler, Niels

2016-01-01

Background and purpose: Aside from the enhancement of physical dose deposited by antiprotons annihilating in tissue-like material compared to protons of the same range a further increase of biological effective dose has been demonstrated. This enhancement can be expressed in an increase of the re......Background and purpose: Aside from the enhancement of physical dose deposited by antiprotons annihilating in tissue-like material compared to protons of the same range a further increase of biological effective dose has been demonstrated. This enhancement can be expressed in an increase...... of the relative biological effectiveness (RBE) of antiprotons near the end of range. We have performed the first-ever direct measurement of the RBE of antiprotons both at rest and in flight. Materials and methods: Experimental data were generated on the RBE of an antiproton beam entering a tissue-like target...

Biophysical calculations of cell killing probability by the amorphous track structure model for heavy-ion beams

International Nuclear Information System (INIS)

Kase, Yuki; Matsufuji, Naruhiro; Furusawa, Yoshiya; Kanai, Tatsuaki

2007-01-01

In a treatment planning of heavy-ion radiotherapy, it is necessary to estimate the biological effect of the heavy-ion beams. Physical dose should be associated with the relative biological effectiveness (RBE) at each point. Presently, carbon ion radiotherapy has been carried out at the National Institute Radiological Sciences (NIRS) in Japan and the Gesellschaft fuer Schwerionenforschung mbH (GSI) in Germany. Both facilities take individual approach for the calculation of the RBE value. At NIRS, the classical LQ model has been used while the local effect model (LEM) has been incorporated into the treatment planning system at GSI. The first aim of this study is to explain the RBE model of NIRS by the microdosimetric kinetic model (MKM). In addition, the clarification of similarities and differences between the MKM and the LEM was also investigated. (author)

Endogenous Fluctuations and the Role of Monetary Policy

OpenAIRE

Motolese, Maurizio; Kurz, Mordecai; Jin, Hehui

2002-01-01

This paper studies the dynamic volatility properties of a monetary economy in which agents hold Rational Beliefs (see Kurz (1994), (1997)) rather than Rational Expectations. Except for this feature the examined Rational Belief Equilibrium (in short, RBE) is entirely standard: markets are competitive, prices are flexible and all information is symmetric. The paper demonstrates a) The RBE paradigm offers an integrated theory of real and financial volatility with a high volume of trade. Most vol...

SU-F-T-197: Investigating Optimal Oblique-Beam Arrangement for Bilateral Metallic Prosthesis Prostate Cancer in Pencil Beam Scanning Proton Therapy

Energy Technology Data Exchange (ETDEWEB)

Rana, S; Tesfamicael, B; Park, S [McLaren Proton Therapy Center, Karmanos Cancer Institute at McLaren-Flint, Flint, MI (United States); Zheng, Y; Singh, H; Twyford, T [Procure Proton Therapy Center, Oklahoma City, OK (United States); Cheng, C [Vantage Oncology, West Hills, CA (United States)

2016-06-15

Purpose: The main purpose of this study is to investigate the optimum oblique-beam arrangement for bilateral metallic prosthesis prostate cancer treatment in pencil beam scanning (PBS) proton therapy. Methods: A computed tomography dataset of bilateral metallic prosthesis prostate cancer case was selected for this retrospective study. A total of four beams (rightanterior- oblique [RAO], left-anterior-oblique [LAO], left-posterior-oblique [LPO], and right-posterior-oblique [RPO]) were selected for treatment planning. PBS plans were generated using multi-field-optimization technique for a total dose of 79.2 Gy[RBE] to be delivered in 44 fractions. Specifically, five different PBS plans were generated based on 2.5% ± 2 mm range uncertainty using five different beam arrangements (i)LAO+RAO+LPO+RPO, (ii)LAO+RAO, (iii)LPO+RPO, (iv)RAO+LPO, and (v)LAO+RPO. Each PBS plan was optimized by applying identical dose-volume constraints to the PTV, rectum, and bladder. Treatment plans were then compared based on the dose-volume histograms results. Results: The PTV coverage was found to be greater than 99% in all five plans. The homogeneity index (HI) was found to be almost identical (range, 0.03–0.04). The PTV mean dose was found to be comparable (range, 81.0–81.1 Gy[RBE]). For the rectum, the lowest mean dose (8.0 Gy[RBE]) and highest mean dose (31.1 Gy[RBE]) were found in RAO+LAO plan and LPO+RPO plan, respectively. LAO+RAO plan produced the most favorable dosimetric results of the rectum in the medium-dose region (V50) and high-dose region (V70). For the bladder, the lowest (5.0 Gy[RBE]) and highest mean dose (10.3 Gy[RBE]) were found in LPO+RPO plan and RAO+LAO plan, respectively. Other dosimetric results (V50 and V70) of the bladder were slightly better in LPO+RPO plan than in other plans. Conclusion: Dosimetric findings from this study suggest that two anterior-oblique proton beams arrangement (LAO+RAO) is a more favorable option with the possibility of reducing rectal

Teratogenic and embryolethal effects in mice of fission-spectrum neutrons and γ-rays

International Nuclear Information System (INIS)

Cairnie, A.B.; Grahn, D.; Rayburn, H.B.; Williamson, F.S.; Brown, R.J.

1974-01-01

Fission-spectrum neutrons from the Janus reactor at Argonne National Laboratory were compared with γ-rays in terms of their relative biological effectiveness (RBE) for embryolethal and teratogenic effects in mice. No evidence was found of any processes that were abnormally sensitive to neutrons. The RBE for killing embryos and producing abnormal embryos or specific abnormalities was between 2 and 3. This is close to the values found in other systems for processes involving cell killing. (U.S.)

Human factors reliability Benchmark exercise

International Nuclear Information System (INIS)

Poucet, A.

1989-06-01

The Joint Research Centre of the European Commission has organized a Human Factors Reliability Benchmark Exercise (HF-RBE) with the aim of assessing the state of the art in human reliability modelling and assessment. Fifteen teams from eleven countries, representing industry, utilities, licensing organisations and research institutes, participated in the HF-RBE. The HF-RBE was organized around two study cases: (1) analysis of routine functional Test and Maintenance (T and M) procedures: with the aim of assessing the probability of test induced failures, the probability of failures to remain unrevealed and the potential to initiate transients because of errors performed in the test; (2) analysis of human actions during an operational transient: with the aim of assessing the probability that the operators will correctly diagnose the malfunctions and take proper corrective action. This report contains the final summary reports produced by the participants in the exercise

Workshop on radiobiological effectiveness of neutrons

International Nuclear Information System (INIS)

Stapleton, G.E.; Thomas, R.G.; Thiessen, J.W.

1985-09-01

The radiobiological effectiveness (RBE) of neutrons has become the subject of some heated discussions in both scientific and radiation-protection oriented communities. This has become especially so since the realization that neutron exposures of A-bomb survivors in Hiroshima were considerably lower than previously assumed, thus ''devaluating'' the importance of what we thought was a solid human data base. At the same time, more recent data from radiobiological research appeared to indicate that, at least for some biological endpoints, the RBE of neutrons at low doses and low dose rates was increased dramatically compared to the RBE at higher dose and dose rates. As a consequence, the protection of health against neutrons became a subject of some urgency. The objective of this workshop was to evaluate the existing data base in order to determine the need for additional research in this field. 22 refs., 3 figs., 6 tabs

Biological effects of neutrons

Energy Technology Data Exchange (ETDEWEB)

Ogiu, Toshiaki; Ohmachi, Yasushi; Ishida, Yuka [National Inst. of Radiological Sciences, Chiba (JP)] [and others

2003-03-01

Although the occasion to be exposed to neutrons is rare in our life, except for nuclear accidents like in the critical accident at Tokai-mura in 1999, countermeasures against accident should be always prepared. In the Tokai-mura accident, residents received less than 21 mSv of neutrons and gamma rays. The cancer risks and fetal effects of low doses of neutrons were matters of concern among residents. The purpose of this program is to investigate the relative biological effectiveness (RBE) for leukemias, and thereby to assess risks of neutrons. Animal experiments are planed to obtain the following RBEs: (1) RBE for the induction of leukemias in mice and (2) RBE for effects on fetuses. Cyclotron fast neutrons (10 MeV) and electrostatic accelerator-derived neutrons (2 MeV) are used for exposure in this program. Furthermore, cytological and cytogenetic analyses will be performed. (author)

Biological effectiveness of pulsed and continuous neutron radiation for cells of yeast Saccharomyces

International Nuclear Information System (INIS)

Tsyb, T.S.; Komarova, E.V.; Potetnya, V.I.; Obaturov, G.M.

2001-01-01

Data are presented on biological effectiveness of fast neutrons generated by BR-10 reactor (dose rate up to 3.8 Gy/s) in comparison with neutrons of pulsed BARS-6 reactor (dose rate ∼6x10 6 Gy/s) for yeast Saccharomyces vini cells of a wild type Menri 139-B and radiosensitive Saccharomyces cerevisiae (rad52/rad52; rad54/rad54) mutants which are defective over different systems of DNA reparation. Value of relative biological efficiency (RBE) of continuous radiation for wild stam is from 3.5 up to 2.5 when survival level being 75-10 %, and RBE of pulsed neutron radiation is in the limits of 2.0-1.7 at the same levels. For mutant stam the value of RBE (1.4-1.6) of neutrons is constant at all survival levels and does not depend on dose rate [ru

Relative Biological Effectiveness of Energetic Heavy Ions for Intestinal Tumorigenesis Shows Male Preponderance and Radiation Type and Energy Dependence in APC{sup 1638N/+} Mice

Energy Technology Data Exchange (ETDEWEB)

Suman, Shubhankar; Kumar, Santosh; Moon, Bo-Hyun; Strawn, Steve J.; Thakor, Hemang; Fan, Ziling [Department of Biochemistry and Molecular & Cellular Biology and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia (United States); Shay, Jerry W. [Department of Cell Biology, UT Southwestern Medical Center, Dallas, Texas (United States); Fornace, Albert J. [Department of Biochemistry and Molecular & Cellular Biology and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia (United States); Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah (Saudi Arabia); Datta, Kamal, E-mail: kd257@georgetown.edu [Department of Biochemistry and Molecular & Cellular Biology and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia (United States)

2016-05-01

Purpose: There are uncertainties associated with the prediction of colorectal cancer (CRC) risk from highly energetic heavy ion (HZE) radiation. We undertook a comprehensive assessment of intestinal and colonic tumorigenesis induced after exposure to high linear energy transfer (high-LET) HZE radiation spanning a range of doses and LET in a CRC mouse model and compared the results with the effects of low-LET γ radiation. Methods and Materials: Male and female APC{sup 1638N/+} mice (n=20 mice per group) were whole-body exposed to sham-radiation, γ rays, {sup 12}C, {sup 28}Si, or {sup 56}Fe radiation. For the >1 Gy HZE dose, we used γ-ray equitoxic doses calculated using relative biological effectiveness (RBE) determined previously. The mice were euthanized 150 days after irradiation, and intestinal and colon tumor frequency was scored. Results: The highest number of tumors was observed after {sup 28}Si, followed by {sup 56}Fe and {sup 12}C radiation, and tumorigenesis showed a male preponderance, especially after {sup 28}Si. Analysis showed greater tumorigenesis per unit of radiation (per cGy) at lower doses, suggesting either radiation-induced elimination of target cells or tumorigenesis reaching a saturation point at higher doses. Calculation of RBE for intestinal and colon tumorigenesis showed the highest value with {sup 28}Si, and lower doses showed greater RBE relative to higher doses. Conclusions: We have demonstrated that the RBE of heavy ion radiation-induced intestinal and colon tumorigenesis is related to ion energy, LET, gender, and peak RBE is observed at an LET of 69 keV/μm. Our study has implications for understanding risk to astronauts undertaking long duration space missions.

Radiobiological evaluation of the suitability of negative pions in tumor therapy

International Nuclear Information System (INIS)

Fritz-Niggli, H.

1979-01-01

With the biomedical pion channel of the 590 MeV proton-accelerator of the Swiss Institute for Nuclear Research (SIN) for to test some theoretical conceptions in comparison to several preliminary experiments performed with pions of low dose rate. The dosimetric measurements showed an excellent depth curve with, e.g., a peak/plateau ratio of 2.5, for the momentum of 180 MeV/c and a ratio e - /π - of 0.1. The following systems have been used: Inactivation of single mammalian cells, induction of chromatid aberrations in Chinese hamster cells; small intestine of mouse (early and late effects); early and late effects in the mouse foot; induction of anomalies in mouse embryos; induction of cerebral microvascular damage in neonate rats; proliferation of Ehrlich-ascites carcinoma cells; induction of different types of mutation in different stages of male germ cells and somatic cells (Drosophila). The RBE-values in the peak region vary between 0,7-3.3, and are different even within the same system with the same end point but at different cell stages and conditions. For the plateau region the RBE-values lie mostly under 1 (compared with 140 kV-photons) and can be identical with 29 MeV-photons. The clinically important peak/plateau relation lies over 1 in every experiment and reaches even the value of 4.2. The unexpected RBE-values in peak under 1 lead to a new conception of RBE, the two system theory. In intrinsically radiosensitive euoxic systems (healthy tissue) the RBE of peak (star) pions can be under 1, in intrinsically radioresistant hypoxic systems (tumor cells) over 1. The two systems can also have different vulnerabilities of these repair systems. (orig./MG) 891 MG/orig.- 892 CKA [de

The influence of fractionation on cell survival and premature differentiation after carbon ion irradiation

International Nuclear Information System (INIS)

Wang Jufang; Li Renming; Guo Chuanling; Fournier, C.; K-Weyrather, W.

2008-01-01

To investigate the influence of fractionation on cell survival and radiation induced premature differentiation as markers for early and late effects after X-rays and carbon irradiation. Normal human fibroblasts NHDF, AG1522B and WI-38 were irradiated with 250 kV X-rays, or 266 MeV/u, 195 MeV/u and 11 MeV/u carbon ions. Cytotoxicity was measured by a clonogenic survival assay or by determination of the differentiation pattern. Experiments with high-energy carbon ions show that fractionation induced repair effects are similar to photon irradiation. The relative biological effective (RBE) 10 values for clonogenic survival are 1.3 and 1.6 for irradiation in one or two fractions for NHDF cells and around 1.2 for AG1522B cells regardless of the fractionation scheme. The RBE for a doubling of post mitotic fibroblasts (PMF) in the population is 1 for both single and two fractionated irradiation of NHDF cells. Using 11 MeV/u carbon ions, no repair effect can be seen in WI-38 cells. The RBE 10 for clonogenic survival is 3.2 for single irradiation and 4.9 for two fractionated irradiations. The RBE for a doubling of PMF is 3.1 and 5.0 for single and two fractionated irradiations, respectively. For both cell lines the effects of high-energy carbon ions representing the irradiation of the skin and the normal tissue in the entrance channel are similar to the effects of X-rays. The fractionation effects are maintained. For the lower energy, which is representative for the irradiation of the tumor region, RBE is enhanced for clonogenic survival as well as for premature terminal differentiation. Fractionation effects are not detectable. Consequently, the therapeutic ratio is significantly enhanced by fractionated irradiation with carbon ions. (author)

TH-A-19A-05: Modeling Physics Properties and Biologic Effects Induced by Proton and Helium Ions

Energy Technology Data Exchange (ETDEWEB)

Taleei, R; Titt, U; Peeler, C; Guan, F; Mirkovic, D; Grosshans, D; Mohan, R [UT MD Anderson Cancer Center, Houston, TX (United States)

2014-06-15

Purpose: Currently, proton and carbon ions are used for cancer treatment. More recently, other light ions including helium ions have shown interesting physical and biological properties. The purpose of this work is to study the biological and physical properties of helium ions (He-3) in comparison to protons. Methods: Monte Carlo simulations with FLUKA, GEANT4 and MCNPX were used to calculate proton and He-3 dose distributions in water phantoms. The energy spectra of proton and He-3 beams were calculated with high resolution for use in biological models. The repair-misrepairfixation (RMF) model was subsequently used to calculate the RBE. Results: The proton Bragg curve calculations show good agreement between the three general purpose Monte Carlo codes. In contrast, the He-3 Bragg curve calculations show disagreement (for the magnitude of the Bragg peak) between FLUKA and the other two Monte Carlo codes. The differences in the magnitude of the Bragg peak are mainly due to the discrepancy in the secondary fragmentation cross sections used by the codes. The RBE for V79 cell lines is about 0.96 and 0.98 at the entrance of proton and He-3 ions depth dose respectively. The RBE increases to 1.06 and 1.59 at the Bragg peak of proton and He-3 ions. The results demonstrated that LET, microdosimetric parameters (such as dose-mean lineal energy) and RBE are nearly constant along the plateau region of Bragg curve, while all parameters increase within the Bragg peak and at the distal edge for both proton and He-3 ions. Conclusion: The Monte Carlo codes should revise the fragmentation cross sections to more accurately simulate the physical properties of He-3 ions. The increase in RBE for He-3 ions is higher than for proton beams at the Bragg peak.

Microdosimetric measurements in the thermal neutron irradiation facility of LENA reactor

International Nuclear Information System (INIS)

Colautti, P.; Moro, D.; Chiriotti, S.; Conte, V.; Evangelista, L.; Altieri, S.; Bortolussi, S.; Protti, N.; Postuma, I.

2014-01-01

A twin TEPC with electric-field guard tubes has been constructed to be used to characterize the BNCT field of the irradiation facility of LENA reactor. One of the two mini TEPC was doped with 50 ppm of 10 B in order to simulate the BNC events occurring in BNCT. By properly processing the two microdosimetric spectra, the gamma, neutron and BNC spectral components can be derived with good precision (∼6%). However, direct measurements of 10 B in some doped plastic samples, which were used for constructing the cathode walls, point out the scarce accuracy of the nominal 10 B concentration value. The influence of the Boral ® door, which closes the irradiation channel, has been measured. The gamma dose increases significantly (+51%) when the Boral ® door is closed. The crypt-cell-regeneration weighting function has been used to measure the quality, namely the RBE µ value, of the radiation field in different conditions. The measured RBE µ values are only partially consistent with the RBE values of other BNCT facilities. - Highlights: • A counter with two mini TEPCs, both equipped with electrical-field guard tubes, has been constructed. • The microdosimetric spectrum of the LENA-reactor irradiation vane has been studied. • The radiation-field quality (RBE) assessment confirms that the D n /D tot ratio is not an accurate parameter to characterize the BNCT radiation field

ANALYSIS OF THE EFFICIENCY OF A THERAPEUTIC PROGRAM USING 10.2-MEV FAST NEUTRONS. OPTIMIZATION AND PROSPECTS OF THE DEVELOPMENT OF A PROCEDURE FOR COMBINED PHOTON-NEUTRON THERAPY. THE EXPERIENCE OF THE URAL CENTER FOR NEUTRON THERAPY

Directory of Open Access Journals (Sweden)

E. Yu. Kandakova

2013-01-01

Full Text Available The Ural Center for Neutron Therapy performs combined photon-neutron therapy for cancer patients, by applying an ELLIT-80 gamma unit and a NG-12I neutron generator. After modernization of the NG-12I generator, there was a need for redetermination of the relative biological efficiency (RBE to optimize radiotherapy for the patients. An exotest was used to experimentally estimate RBE according to the survival criteria for stem hematopoietic cells in CBA mice after modernization of the equipment generated by the NG-12I unit with respect to the gamma radiation generated by the ELLIT-80 unit. The investigation established that the RBE factor of NG-12I unit-induced radiation determined as the ratio of equally effective doses (our study used D0 was 1.53 for an acute radiation regimen. During fractional radiation, the RBE factor of neutron radiation was 3.05. That is to say, the total neutron radiation dose replacing 20 % gamma radiation (13 Gy in the used photon-neutron therapy regimen is 4.26 Gy. The experimental findings have led us to conclude that the previously described neuron therapy regimen may be optimized, by increasing the contribution of neutrons to the total course of radiotherapy in a definite category of patients with radioresistant tumors of the head and neck.

The induction of somatic mutations by high-LET radiation observed using the Drosophila assay system

International Nuclear Information System (INIS)

Yoshikawa, Isao; Takatsuji, Toshihiro; Nagano, Masaaki; Hoshi, Masaharu; Takada, Jun; Endo, Satoru

1999-01-01

To evaluate the mutagenic potential of high-LET radiation, an analysis was made on the production of somatic mutations by 252 Cf fission neutron s and heavy particle ions accelerated by a synchrotron. A Drosophila strain that allows simultaneous detection of two types of mutations in an identical fly was constructed. One was a wing-hair mutation and the other was an eye-color mosaic spot mutation. Measurements were made using a combined assay system of both mutation assays. Larvae were exposed to radiation at the age of post-ovipositional day-3. The efficiency of 252 Cf neutrons for inducing wing-hair mosaic spots was very high, the relative biological effectiveness (RBE) = 8.5, but the efficiency for eye-color mosaic spot was nearly equal (RBE = 1.2) to that of 137 Cs γ-rays. The RBE of carbon ions for inducing wing-hair mosaic spots increased as an increase in LET values. The RBE for the induction of eye-color mutants did not change with LET. These relationships suggest that more complex types of DNA damages such as non-rejoinable strand break or clustered double strand break, which increase with LET may be responsible for the induction of wing-hair mutation, while simpler forms of molecular damage may induce a reversion in the white-ivory allele. (M.N.)

Relative biological effectiveness of the therapeutic proton beams at NIRS and Tsukuba University

International Nuclear Information System (INIS)

Ando, Koichi; Koike, Sachiko; Kawachi, Kiyomitsu

1985-01-01

Relative biological effectiveness (RBE) of proton beams dedicated to radiotherapy was examined using a method of simultaneous irradiation. Mice received i.v. transplantation of syngeneic fibrosarcoma (NFSa) cells. These mice were divided into 3 groups on the following day, and thorax was simultaneously irradiated with one of the following beams: 70MeV proton beam at National Institute of Radiological Sciences (NIRS), 250 MeV Proton beam at Tsukuba University (PARMS) and 60 Co γ ray. Ten to 13 days thereafter, lungs were removed for colony counts to give dose-cell survival relationships. RBE of NIRS proton was ranging from 1.01 to 1.12 with an average of 1.06 while that of PARMS proton was ranging from 1.03 to 1.09 with an average of 1.06 at surviving fraction of 0.01. The simultaneous irradiation for RBE study was found to be reliable at large dose-low survival regions. (author)

Protective Effects of Black Rice Extracts on Oxidative Stress Induced by tert-Butyl Hydroperoxide in HepG2 Cells

Science.gov (United States)

Lee, Seon-Mi; Choi, Youngmin; Sung, Jeehye; Kim, Younghwa; Jeong, Heon-Sang; Lee, Junsoo

2014-01-01

Black rice contains many biologically active compounds. The aim of this study was to investigate the protective effects of black rice extracts (whole grain extract, WGE and rice bran extract, RBE) on tert-butyl hydroperoxide (TBHP)-induced oxidative injury in HepG2 cells. Cellular reactive oxygen species (ROS), antioxidant enzyme activities, malondialdehyde (MDA) and glutathione (GSH) concentrations were evaluated as biomarkers of cellular oxidative status. Cells pretreated with 50 and 100 μg/mL of WGE or RBE were more resistant to oxidative stress in a dose-dependent manner. The highest WGE and BRE concentrations enhanced GSH concentrations and modulated antioxidant enzyme activities (glutathione reductase, glutathione-S-transferase, catalase, and superoxide dismutase) compared to TBHP-treated cells. Cells treated with RBE showed higher protective effect compared to cells treated with WGE against oxidative insult. Black rice extracts attenuated oxidative insult by inhibiting cellular ROS and MDA increase and by modulating antioxidant enzyme activities in HepG2 cells. PMID:25580401

Response of rat spinal cord to single and fractionated doses of accelerated heavy ions

International Nuclear Information System (INIS)

Leith, J.L.; McDonald, M.; Powers-Risius, P.; Bliven, S.F.; Walton, R.E.; Woodruff, K.H.; Howard, J.

1980-01-01

The response of rat spinal cord to irradiation with accelerated heavy ions, in particular carbon and neon ions has been studied. Two different ionization regions in the modified Bragg curve for each ion have been studied for both single and fractionated exposures. We have defined the paralytic response as a function of dose and dose per fraction, and we have determined RBE and repair values. The response of rat spinal cord is both dose and LET dependent, which allows the derivation of RBE and repair values

Applications of tissue heterogeneity corrections and biologically effective dose volume histograms in assessing the doses for accelerated partial breast irradiation using an electronic brachytherapy source

Science.gov (United States)

Shi, Chengyu; Guo, Bingqi; Cheng, Chih-Yao; Eng, Tony; Papanikolaou, Nikos

2010-09-01

A low-energy electronic brachytherapy source (EBS), the model S700 Axxent™ x-ray device developed by Xoft Inc., has been used in high dose rate (HDR) intracavitary accelerated partial breast irradiation (APBI) as an alternative to an Ir-192 source. The prescription dose and delivery schema of the electronic brachytherapy APBI plan are the same as the Ir-192 plan. However, due to its lower mean energy than the Ir-192 source, an EBS plan has dosimetric and biological features different from an Ir-192 source plan. Current brachytherapy treatment planning methods may have large errors in treatment outcome prediction for an EBS plan. Two main factors contribute to the errors: the dosimetric influence of tissue heterogeneities and the enhancement of relative biological effectiveness (RBE) of electronic brachytherapy. This study quantified the effects of these two factors and revisited the plan quality of electronic brachytherapy APBI. The influence of tissue heterogeneities is studied by a Monte Carlo method and heterogeneous 'virtual patient' phantoms created from CT images and structure contours; the effect of RBE enhancement in the treatment outcome was estimated by biologically effective dose (BED) distribution. Ten electronic brachytherapy APBI cases were studied. The results showed that, for electronic brachytherapy cases, tissue heterogeneities and patient boundary effect decreased dose to the target and skin but increased dose to the bones. On average, the target dose coverage PTV V100 reduced from 95.0% in water phantoms (planned) to only 66.7% in virtual patient phantoms (actual). The actual maximum dose to the ribs is 3.3 times higher than the planned dose; the actual mean dose to the ipsilateral breast and maximum dose to the skin were reduced by 22% and 17%, respectively. Combining the effect of tissue heterogeneities and RBE enhancement, BED coverage of the target was 89.9% in virtual patient phantoms with RBE enhancement (actual BED) as compared to 95

Applications of tissue heterogeneity corrections and biologically effective dose volume histograms in assessing the doses for accelerated partial breast irradiation using an electronic brachytherapy source

Energy Technology Data Exchange (ETDEWEB)

Shi Chengyu; Guo Bingqi; Eng, Tony; Papanikolaou, Nikos [Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, TX 78229 (United States); Cheng, Chih-Yao, E-mail: shic@uthscsa.ed [Radiation Oncology Department, Oklahoma University Health Science Center, Oklahoma, OK 73104 (United States)

2010-09-21

A low-energy electronic brachytherapy source (EBS), the model S700 Axxent(TM) x-ray device developed by Xoft Inc., has been used in high dose rate (HDR) intracavitary accelerated partial breast irradiation (APBI) as an alternative to an Ir-192 source. The prescription dose and delivery schema of the electronic brachytherapy APBI plan are the same as the Ir-192 plan. However, due to its lower mean energy than the Ir-192 source, an EBS plan has dosimetric and biological features different from an Ir-192 source plan. Current brachytherapy treatment planning methods may have large errors in treatment outcome prediction for an EBS plan. Two main factors contribute to the errors: the dosimetric influence of tissue heterogeneities and the enhancement of relative biological effectiveness (RBE) of electronic brachytherapy. This study quantified the effects of these two factors and revisited the plan quality of electronic brachytherapy APBI. The influence of tissue heterogeneities is studied by a Monte Carlo method and heterogeneous 'virtual patient' phantoms created from CT images and structure contours; the effect of RBE enhancement in the treatment outcome was estimated by biologically effective dose (BED) distribution. Ten electronic brachytherapy APBI cases were studied. The results showed that, for electronic brachytherapy cases, tissue heterogeneities and patient boundary effect decreased dose to the target and skin but increased dose to the bones. On average, the target dose coverage PTV V{sub 100} reduced from 95.0% in water phantoms (planned) to only 66.7% in virtual patient phantoms (actual). The actual maximum dose to the ribs is 3.3 times higher than the planned dose; the actual mean dose to the ipsilateral breast and maximum dose to the skin were reduced by 22% and 17%, respectively. Combining the effect of tissue heterogeneities and RBE enhancement, BED coverage of the target was 89.9% in virtual patient phantoms with RBE enhancement (actual BED) as

Applications of tissue heterogeneity corrections and biologically effective dose volume histograms in assessing the doses for accelerated partial breast irradiation using an electronic brachytherapy source

International Nuclear Information System (INIS)

Shi Chengyu; Guo Bingqi; Eng, Tony; Papanikolaou, Nikos; Cheng, Chih-Yao

2010-01-01

A low-energy electronic brachytherapy source (EBS), the model S700 Axxent(TM) x-ray device developed by Xoft Inc., has been used in high dose rate (HDR) intracavitary accelerated partial breast irradiation (APBI) as an alternative to an Ir-192 source. The prescription dose and delivery schema of the electronic brachytherapy APBI plan are the same as the Ir-192 plan. However, due to its lower mean energy than the Ir-192 source, an EBS plan has dosimetric and biological features different from an Ir-192 source plan. Current brachytherapy treatment planning methods may have large errors in treatment outcome prediction for an EBS plan. Two main factors contribute to the errors: the dosimetric influence of tissue heterogeneities and the enhancement of relative biological effectiveness (RBE) of electronic brachytherapy. This study quantified the effects of these two factors and revisited the plan quality of electronic brachytherapy APBI. The influence of tissue heterogeneities is studied by a Monte Carlo method and heterogeneous 'virtual patient' phantoms created from CT images and structure contours; the effect of RBE enhancement in the treatment outcome was estimated by biologically effective dose (BED) distribution. Ten electronic brachytherapy APBI cases were studied. The results showed that, for electronic brachytherapy cases, tissue heterogeneities and patient boundary effect decreased dose to the target and skin but increased dose to the bones. On average, the target dose coverage PTV V 100 reduced from 95.0% in water phantoms (planned) to only 66.7% in virtual patient phantoms (actual). The actual maximum dose to the ribs is 3.3 times higher than the planned dose; the actual mean dose to the ipsilateral breast and maximum dose to the skin were reduced by 22% and 17%, respectively. Combining the effect of tissue heterogeneities and RBE enhancement, BED coverage of the target was 89.9% in virtual patient phantoms with RBE enhancement (actual BED) as compared to 95

SU-F-T-193: Evaluation of a GPU-Based Fast Monte Carlo Code for Proton Therapy Biological Optimization

Energy Technology Data Exchange (ETDEWEB)

Taleei, R; Qin, N; Jiang, S [UT Southwestern Medical Center, Dallas, TX (United States); Peeler, C [UT MD Anderson Cancer Center, Houston, TX (United States); Jia, X [The University of Texas Southwestern Medical Ctr, Dallas, TX (United States)

2016-06-15

Purpose: Biological treatment plan optimization is of great interest for proton therapy. It requires extensive Monte Carlo (MC) simulations to compute physical dose and biological quantities. Recently, a gPMC package was developed for rapid MC dose calculations on a GPU platform. This work investigated its suitability for proton therapy biological optimization in terms of accuracy and efficiency. Methods: We performed simulations of a proton pencil beam with energies of 75, 150 and 225 MeV in a homogeneous water phantom using gPMC and FLUKA. Physical dose and energy spectra for each ion type on the central beam axis were scored. Relative Biological Effectiveness (RBE) was calculated using repair-misrepair-fixation model. Microdosimetry calculations were performed using Monte Carlo Damage Simulation (MCDS). Results: Ranges computed by the two codes agreed within 1 mm. Physical dose difference was less than 2.5 % at the Bragg peak. RBE-weighted dose agreed within 5 % at the Bragg peak. Differences in microdosimetric quantities such as dose average lineal energy transfer and specific energy were < 10%. The simulation time per source particle with FLUKA was 0.0018 sec, while gPMC was ∼ 600 times faster. Conclusion: Physical dose computed by FLUKA and gPMC were in a good agreement. The RBE differences along the central axis were small, and RBE-weighted dose difference was found to be acceptable. The combined accuracy and efficiency makes gPMC suitable for proton therapy biological optimization.

Genetic control of radiosensitivity modification of some yeast strons

International Nuclear Information System (INIS)

Petin, V.G.; Zhurakovskaya, I.P.

1982-01-01

The genetic determination of the relative biological effectiveness (RBE) of densely ionizing particles and cysteamine's radioprotective effect on irradiated cells, demonstrated earlier on yeast cells of different genotype, has been proved on diploid wild-type cells of Saccharomyces cerevisial yeasts, solitary mutants, homozygous with respect to rad 2 and rad 54, and double mutant containing both locuses in homozygous state. It is shown that RBE of α-particles and radioprotector's efficiency depend on repair system's activity. A possible mechanism of the participation of postirradiation recovery processes in the modification of cell radiosensitivity is discussed [ru

Site Specific Microbeam Irradiation: Defining a Bystander Effect. Final Technical Report

International Nuclear Information System (INIS)

Brenner, David J.

2003-01-01

There is evidence that low-energy x-rays as used in mammography have an increased biological effectiveness relative to higher-energy photons. However, the RBE values are not large, probably less than 2. Thus it is unlikely that the radiation risk alone could prove to be a ''show stopper'' regarding screening mammography because, for older women, the benefit is likely to considerably outweigh the radiation risk. Nevertheless, the RBE for low-energy x-rays might reasonably be taken into account when assessing the recommended age to commence such annual screening

RBE determination of tumors by serum aldolase

Energy Technology Data Exchange (ETDEWEB)

Dalluege, K H [Akademie der Wissenschaften der DDR, Berlin. Zentralinstitut fuer Krebsforschung

1981-06-01

In patients with histologically ascertained bronchial carcinoma the tumor volume and the plasma volume was determined before therapy. Following the first irradiation of the tumor with a /sup 60/Co pendulum technique over the diseased side with 5 Gy for the 80% isodose determination of aldolase and creatin kinase was performed frequently during 24 h. A peak of serum aldolase was found 16 - 18 h after irradiation. The aldolase values of this peak were higher for undifferentiated carcinomas than for squamous cell carcinomas and proportional to the size of the tumor. The hypothesis is made that by means of this method using different radiation qualities their 'relative biological effectiveness' can be determined.

Dose to the Developing Dentition During Therapeutic Irradiation: Organ at Risk Determination and Clinical Implications

International Nuclear Information System (INIS)

Thompson, Reid F.; Schneider, Ralf A.; Albertini, Francesca; Lomax, Antony J.; Ares, Carmen; Goitein, Gudrun; Hug, Eugen B.

2013-01-01

Purpose: Irradiation of pediatric facial structures can cause severe impairment of permanent teeth later in life. We therefore focused on primary and permanent teeth as organs at risk, investigating the ability to identify individual teeth in children and infants and to correlate dose distributions with subsequent dental toxicity. Methods and Materials: We retrospectively reviewed 14 pediatric patients who received a maximum dose >20 Gy(relative biological effectiveness, RBE) to 1 or more primary or permanent teeth between 2003 and 2009. The patients (aged 1-16 years) received spot-scanning proton therapy with 46 to 66 Gy(RBE) in 23 to 33 daily fractions for a variety of tumors, including rhabdomyosarcoma (n=10), sarcoma (n=2), teratoma (n=1), and carcinoma (n=1). Individual teeth were contoured on axial slices from planning computed tomography (CT) scans. Dose-volume histogram data were retrospectively obtained from total calculated delivered treatments. Dental follow-up information was obtained from external care providers. Results: All primary teeth and permanent incisors, canines, premolars, and first and second molars were identifiable on CT scans in all patients as early as 1 year of age. Dose-volume histogram analysis showed wide dose variability, with a median 37 Gy(RBE) per tooth dose range across all individuals, and a median 50 Gy(RBE) intraindividual dose range across all teeth. Dental follow-up revealed absence of significant toxicity in 7 of 10 patients but severe localized toxicity in teeth receiving >20 Gy(RBE) among 3 patients who were all treated at <4 years of age. Conclusions: CT-based assessment of dose distribution to individual teeth is feasible, although delayed calcification may complicate tooth identification in the youngest patients. Patterns of dental dose exposure vary markedly within and among patients, corresponding to rapid dose falloff with protons. Severe localized dental toxicity was observed in a few patients receiving the

SU-E-T-494: Influence of Proton Track-Cell Nucleus Incidence Angle On Relative Biological Effectiveness

Energy Technology Data Exchange (ETDEWEB)

Pater, P; Backstrom, G; Enger, S; Seuntjens, J; El Naqa, I [McGill University, Montreal, Quebec (Canada); Villegas, F; Ahnesjo, A [Uppsala University, Uppsala (Sweden)

2015-06-15

Purpose: To explain a Monte Carlo (MC) simulation artifact whereby differences in relative biological effectiveness (RBE) in the induction of initial double strand breaks are observed as a function of the proton track incidence angles in a geometric cell nucleus model. Secondly, to offer an alternative isotropic irradiation procedure to mitigate this effect. Methods: MC tracks of 1 MeV protons were generated in an event-by-event mode. They were overlaid on a cylindrical model of a cell nucleus containing 6×109 nucleotide base pairs. The tracks incidence angle θ with respect to the cell nucleus’s axis was varied in 10 degrees intervals, each time generating one hundred fractions of ∼2 Gy. Strand breaks were scored in the modeled DNA sugar-phosphate groups and further sub-classified into single or double strand breaks (ssbs or dsbs). For each angle, an RBE for the induction of initial dsbs with reference to Co-60 was calculated. Results: Our results show significant angular dependencies of RBE, with maximum values for incidence angles parallel to the nucleus central axis. Further examination shows that the higher cross-sections for the creation of dsbs is due to the preferential alignment of tracks with geometrical sub-parts of the cell nucleus model, especially the nucleosomes containing the sugar-phosphate groups. To alleviate the impact of this simulation artifact, an average RBE was calculated with a procedure based on a weighted sampling of the angular data. Conclusion: This work demonstrates a possible numerical artifact in estimated RBE if the influence of the particle incidence angle is not correctly taken into account. A correction procedure is presented to better conform the simulations to real-life experimental conditions. We would like to acknowledge support from the Fonds de recherche du Quebec Sante (FRQS), from the CREATE Medical Physics Research Training Network grant (number 432290) of NSERC, support from NSERC under grants RGPIN 397711-11 and

Relative Biological Effectiveness of HZE Fe Ions for Induction ofMicro-Nuclei at Low Doses

Energy Technology Data Exchange (ETDEWEB)

Groesser, Torsten; Chun, Eugene; Rydberg, Bjorn

2007-01-16

Dose-response curves for induction of micro-nuclei (MN) was measured in Chinese hamster V79 and xrs6 (Ku80-) cells and in human mammary epithelial MCF10A cells in the dose range of 0.05-1 Gy. The Chinese Hamster cells were exposed to 1 GeV/u Fe ions, 600 MeV/u Fe ions, and 300 MeV/u Fe ions (LETs of 151, 176 and 235 keV/{micro}m respectively) as well as with 320 kVp X-rays as reference. Second-order polynomials were fitted to the induction curves and the initial slopes (the alpha values) were used to calculate RBE. For the repair proficient V79 cells the RBE at these low doses increased with LET. The values obtained were 3.1 (LET=151 keV/{micro}m), 4.3 (LET = 176 keV/{micro}m) and 5.7 (LET = 235 keV/{micro}m), while the RBE was close to 1 for the repair deficient xrs6 cells regardless of LET. For the MCF10A cells the RBE was determined for 1 GeV/u Fe ions and found to be 5.4, slightly higher than for V79 cells. To test the effect of shielding, the 1 GeV/u Fe ion beam was intercepted by various thickness of high-density polyethylene plastic absorbers, which resulted in energy loss and fragmentation. It was found that the MN yield for V79 cells placed behind the absorbers decreased in proportion to the decrease in dose both before and after the Fe ion Bragg peak (excluding the area around the Fe-ion Bragg peak itself), indicating that RBE did not change significantly due to shielding. At the Bragg peak the effectiveness for MN formation per unit dose was decreased, indicating an 'overkill' effect by low-energy very high-LET Fe ions.

SU-F-T-124: Radiation Biological Equivalent Presentations OfLEM-1 and MKM Approaches in the Carbon-Ion Radiotherapy

International Nuclear Information System (INIS)

Hsi, W; Jiang, G; Sheng, Y

2016-01-01

Purpose: To study the correlations of the radiation biological equivalent doses (BED) along depth and lateral distance between LEM-1 and MKM approaches. Methods: In NIRS-MKM (Microdosimetric Kinetic Model) approach, the prescribed BED, referred as C-Eq, doses aims to present the relative biological effectiveness (RBE) for different energies of carbon-ions on a fixed 10% survival value of HCG cell with respect to convention X-ray. Instead of a fixed 10% survival, the BED doses of LEM-1 (Local Effect Model) approach, referred as X-Eq, aims to present the RBE over the whole survival curve of chordoma-like cell with alpha/beta ratio of 2.0. The relationship of physical doses as a function of C-Eq and X-Eq doses were investigated along depth and lateral distance for various sizes of cubic targets in water irradiated by carbon-ions. Results: At the center of each cubic target, the trends between physical and C-Eq or X-Eq doses can be described by a linear and 2nd order polynomial functions, respectively. Using fit functions can then calculate a scaling factor between C-Eq and X-Eq doses to have similar physical doses. With equalized C-Eq and X-Eq doses at the depth of target center, over- and under-estimated X-Eq to C-Eq are seen for depths before and after the target center, respectively. Near the distal edge along depth, sharp rising of RBE value is observed for X-Eq, but sharp dropping of RBE value is observed for C-Eq. For lateral locations near and just outside 50% dose level, sharp raising of RBE value is also seen for X-Eq, while only minor increasing with fast dropping for C-Eq. Conclusion: An analytical function to model the differences between the CEq and X-Eq doses along depth and lateral distance need to further investigated to explain varied clinic outcome of specific cancers using two different approaches to calculated BED doses.

The relative biological effectiveness for carbon and oxygen ion beams using the raster-scanning technique in hepatocellular carcinoma cell lines.

Directory of Open Access Journals (Sweden)

Daniel Habermehl

Full Text Available BACKGROUND: Aim of this study was to evaluate the relative biological effectiveness (RBE of carbon (12C and oxygen ion (16O-irradiation applied in the raster-scanning technique at the Heidelberg Ion beam Therapy center (HIT based on clonogenic survival in hepatocellular carcinoma cell lines compared to photon irradiation. METHODS: Four human HCC lines Hep3B, PLC, HepG2 and HUH7 were irradiated with photons, 12C and 16O using a customized experimental setting at HIT for in-vitro trials. Cells were irradiated with increasing physical photon single doses of 0, 2, 4 and 6 Gy and heavy ion-single doses of 0, 0.125, 0.5, 1, 2, 3 Gy (12C and 16O. SOBP-penetration depth and extension was 35 mm +/-4 mm and 36 mm +/-5 mm for carbon ions and oxygen ions respectively. Mean energy level and mean linear energy transfer (LET were 130 MeV/u and 112 keV/um for 12C, and 154 MeV/u and 146 keV/um for 16O. Clonogenic survival was computated and relative biological effectiveness (RBE values were defined. RESULTS: For all cell lines and both particle modalities α- and β-values were determined. As expected, α-values were significantly higher for 12C and 16O than for photons, reflecting a steeper decline of the initial slope of the survival curves for high-LET beams. RBE-values were in the range of 2.1-3.3 and 1.9-3.1 for 12C and 16O, respectively. CONCLUSION: Both irradiation with 12C and 16O using the raster-scanning technique leads to an enhanced RBE in HCC cell lines. No relevant differences between achieved RBE-values for 12C and 16O were found. Results of this work will further influence biological-adapted treatment planning for HCC patients that will undergo particle therapy with 12C or 16O.

Spot Scanning and Passive Scattering Proton Therapy: Relative Biological Effectiveness and Oxygen Enhancement Ratio in Cultured Cells.

Science.gov (United States)

Iwata, Hiromitsu; Ogino, Hiroyuki; Hashimoto, Shingo; Yamada, Maho; Shibata, Hiroki; Yasui, Keisuke; Toshito, Toshiyuki; Omachi, Chihiro; Tatekawa, Kotoha; Manabe, Yoshihiko; Mizoe, Jun-etsu; Shibamoto, Yuta

2016-05-01

To determine the relative biological effectiveness (RBE), oxygen enhancement ratio (OER), and contribution of the indirect effect of spot scanning proton beams, passive scattering proton beams, or both in cultured cells in comparison with clinically used photons. The RBE of passive scattering proton beams at the center of the spread-out Bragg peak (SOBP) was determined from dose-survival curves in 4 cell lines using 6-MV X rays as controls. Survival of 2 cell lines after spot scanning and passive scattering proton irradiation was then compared. Biological effects at the distal end region of the SOBP were also investigated. The OER of passive scattering proton beams and 6 MX X rays were investigated in 2 cell lines. The RBE and OER values were estimated at a 10% cell survival level. The maximum degree of protection of radiation effects by dimethyl sulfoxide was determined to estimate the contribution of the indirect effect against DNA damage. All experiments comparing protons and X rays were made under the same biological conditions. The RBE values of passive scattering proton beams in the 4 cell lines examined were 1.01 to 1.22 (average, 1.14) and were almost identical to those of spot scanning beams. Biological effects increased at the distal end of the SOBP. In the 2 cell lines examined, the OER was 2.74 (95% confidence interval, 2.56-2.80) and 3.08 (2.84-3.11), respectively, for X rays, and 2.39 (2.38-2.43) and 2.72 (2.69-2.75), respectively, for protons (Pcells between X rays and protons). The maximum degree of protection was significantly higher for X rays than for proton beams (P<.05). The RBE values of spot scanning and passive scattering proton beams were almost identical. The OER was lower for protons than for X rays. The lower contribution of the indirect effect may partly account for the lower OER of protons. Copyright © 2016 Elsevier Inc. All rights reserved.

Health-service Use in Women with Binge Eating Disorders

Science.gov (United States)

Dickerson, John; DeBar, Lynn; Perrin, Nancy A.; Lynch, Frances; Wilson, G. Terence; Rosselli, Francine; Kraemer, Helena C.; Striegel-Moore, Ruth H.

2014-01-01

Objective To compare health-care utilization between participants who met DSM-IV criteria for Binge Eating Disorder (BED) and those engaged in Recurrent Binge Eating (RBE) and to evaluate whether objective binge eating (OBE) days, a key measurement for diagnosing BED, predicted health-care costs. Method We obtained utilization and cost data from electronic medical records to augment patient reported data for 100 adult female members of a large health maintenance organization (HMO) who were enrolled in a randomized clinical trial to treat binge eating. Results Total costs did not differ between the BED and RBE groups (β=−0.117, z=−0.48, p=0.629), nor did the number of OBE days predictor total costs (β= −0.017, z=−1.01, p=0.313). Conclusions Findings suggest that the medical impairment, as assessed through health care costs, caused by BED may not be greater than impairment caused by RBE. The current threshold number of two OBE days/week as a criterion for BED may need to be reconsidered PMID:21823138

Study of radiation-induced chromosomal aberrations

International Nuclear Information System (INIS)

Wolfring, E.

2004-06-01

A method for determining chromosomal aberrations was established for the purpose of examining the relative biological effectiveness (RBE) of photon radiation with respect to mammary epithelium cells. Cells were exposed to 25 kV X-radiation and to 200 kV X-radiation for comparison and the resulting concentrations of chromosomal aberrations were compared. The RBE M value for radiation-induced fragmentation was found to be 4.2 ± 2.4, while the RBE M value for radiation-induced generation of dicentric chromosomes was found to be 0.5 ± 0.5. In addition to the evaluation of chromosomal aberrations the number of cell cycles undergone by the cells was monitored by means of BrDU staining. As expected, the proportion of cells which underwent more than one cell cycle following exposure to 5 Gy was very low in both cases, amounting to 1.9% (25 kV) and 3.2 (200 kV). Non-radiated cells yielded control values of 26.0% and 12.6%, suggesting variations in external conditions from day to day

Study of radiation-induced chromosomal aberrations; Untersuchung strahleninduzierter Chromosomenaberrationen. Bestrahlung der Brustdruesenepithelzelllinie MCF-12A mit Roentgenstrahlung aus konventionellen Roentgenroehren und Bestimmung der Dosis-Effekt-Kurve. Studienarbeit

Energy Technology Data Exchange (ETDEWEB)

Wolfring, E. [Technische Univ. Bergakademie Freiberg (Germany). Interdisziplinaeres Oekologisches Zentrum

2004-06-01

A method for determining chromosomal aberrations was established for the purpose of examining the relative biological effectiveness (RBE) of photon radiation with respect to mammary epithelium cells. Cells were exposed to 25 kV X-radiation and to 200 kV X-radiation for comparison and the resulting concentrations of chromosomal aberrations were compared. The RBE{sub M} value for radiation-induced fragmentation was found to be 4.2 {+-} 2.4, while the RBE{sub M} value for radiation-induced generation of dicentric chromosomes was found to be 0.5 {+-} 0.5. In addition to the evaluation of chromosomal aberrations the number of cell cycles undergone by the cells was monitored by means of BrDU staining. As expected, the proportion of cells which underwent more than one cell cycle following exposure to 5 Gy was very low in both cases, amounting to 1.9% (25 kV) and 3.2 (200 kV). Non-radiated cells yielded control values of 26.0% and 12.6%, suggesting variations in external conditions from day to day.

Survey of methods used to asses human reliability in the human factors reliability benchmark exercise

International Nuclear Information System (INIS)

Poucet, A.

1988-01-01

The Joint Research Centre of the European Commission has organised a Human Factors Reliability Benchmark Exercise (HF-RBE) with the aim to assess the state-of-the-art in human reliability modelling and assessment. Fifteen teams from eleven countries, representing industry, utilities, licensing organisations and research institutes, participate in the HF-RBE, which is organised around two study cases: (1) analysis of routine functional test and maintenance procedures, with the aim to assess the probability of test-induced failures, the probability of failures to remain unrevealed, and the potential to initiate transients because of errors performed in the test; and (2) analysis of human actions during an operational transient, with the aim to assess the probability that the operators will correctly diagnose the malfunctions and take proper corrective action. The paper briefly reports how the HF-RBE was structured and gives an overview of the methods that have been used for predicting human reliability in both study cases. The experience in applying these methods is discussed and the results obtained are compared. (author)

Carbon-ion scanning lung treatment planning with respiratory-gated phase-controlled rescanning: simulation study using 4-dimensional CT data.

Science.gov (United States)

Takahashi, Wataru; Mori, Shinichiro; Nakajima, Mio; Yamamoto, Naoyoshi; Inaniwa, Taku; Furukawa, Takuji; Shirai, Toshiyuki; Noda, Koji; Nakagawa, Keiichi; Kamada, Tadashi

2014-11-11

To moving lung tumors, we applied a respiratory-gated strategy to carbon-ion pencil beam scanning with multiple phase-controlled rescanning (PCR). In this simulation study, we quantitatively evaluated dose distributions based on 4-dimensional CT (4DCT) treatment planning. Volumetric 4DCTs were acquired for 14 patients with lung tumors. Gross tumor volume, clinical target volume (CTV) and organs at risk (OARs) were delineated. Field-specific target volumes (FTVs) were calculated, and 48Gy(RBE) in a single fraction was prescribed to the FTVs delivered from four beam angles. The dose assessment metrics were quantified by changing the number of PCR and the results for the ungated and gated scenarios were then compared. For the ungated strategy, the mean dose delivered to 95% of the volume of the CTV (CTV-D95) was in average 45.3 ± 0.9 Gy(RBE) even with a single rescanning (1 × PCR). Using 4 × PCR or more achieved adequate target coverage (CTV-D95 = 46.6 ± 0.3 Gy(RBE) for ungated 4 × PCR) and excellent dose homogeneity (homogeneity index =1.0 ± 0.2% for ungated 4 × PCR). Applying respiratory gating, percentage of lung receiving at least 20 Gy(RBE) (lung-V20) and heart maximal dose, averaged over all patients, significantly decreased by 12% (p lung tumors without gating. The use of a respiratory-gated strategy in combination with PCR reduced excessive doses to OARs.

The therapeutic ratio in BNCT: Assessment using the Rat 9L gliosarcoma brain tumor and spinal cord models

International Nuclear Information System (INIS)

Coderre, J.A.; Micca, P.L.; Nawrocky, M.M.; Fisher, C.D.; Bywaters, A.; Morris, G.M.; Hopewell, J.W.

1996-01-01

During any radiation therapy, the therapeutic tumor dose is limited by the tolerance of the surrounding normal tissue within the treatment volume. The short ranges of the products of the 10 B(n,α) 7 Li reaction produced during boron neutron capture therapy (BNCT) present an opportunity to increase the therapeutic ratio (tumor dose/normal tissue dose) to levels unprecedented in photon radiotherapy. The mixed radiation field produced during BNCT comprises radiations with different linear energy transfer (LET) and different relative biological effectiveness (RBE). The short ranges of the two high-LET products of the 'B(n,a)'Li reaction make the microdistribution of the boron relative to target cell nuclei of particular importance. Due to the tissue specific distribution of different boron compounds, the term RBE is inappropriate in defining the biological effectiveness of the 10 B(n,α) 7 Li reaction. To distinguish these differences from true RBEs we have used the term open-quotes compound biological effectivenessclose quotes (CBE) factor. The latter can be defined as the product of the true, geometry-independent, RBE for these particles times a open-quotes boron localization factorclose quotes, which will most likely be different for each particular boron compound. To express the total BNCT dose in a common unit, and to compare BNCT doses with the effects of conventional photon irradiation, multiplicative factors (RBEs and CBEs) are applied to the physical absorbed radiation doses from each high-LET component. The total effective BNCT dose is then expressed as the sum of RBE-corrected physical absorbed doses with the unit Gray-equivalent (Gy-Eq)

Dosimetric comparative analysis between 10 MV Megavoltage unidirectional beam and boron neutron capture therapy for brain tumors treatment

International Nuclear Information System (INIS)

Brandao, Samia F.; Campos, Tarcisio P.R.

2011-01-01

This paper present a comparative dosimetric analysis between boron neutron capture therapy and 10 MV megavoltage employed in brain tumor treatments, limited to a unidirectional beam. A computational phantom of a human head was developed to be used in computational simulations of the two protocols, conducted in MCNP5 code. This phantom represents several head's structures, mainly, the central nervous system and a tumor that represents a Glioblastoma Multiform - one of the most malignant and aggressive brain tumors. Absorbed and biological weighted dose rates and neutron fluency in the computational phantom were evaluated from the MCNP5 code. The biologically weighted dose rate to 10 MV megavoltage beam presented no specificity in deposited dose in tumor. The average total biologically weighted dose rate in tumor was 9.93E-04 RBE.Gy.h"-"1/Mp.s"-"1 while in healthy tissue it was 8.67E-04 RBE.Gy.h"-"1/Mp.s"-1. On the BNCT simulations the boron concentration was particularly relevant since the largest dose deposition happened in borate tissues. The average total biologically weighted dose rate in tumor was 3.66E-02 RBE.Gy.h"-"1/Mp.s"-"1 while in healthy tissue it was 1.39E-03 RBE.Gy.h"-"1/Mp.s"-"1. In comparison to the 10 MV megavoltage beam, BNCT showed clearly a largest dose deposition in the tumor, on average, 37 times larger than in the megavoltage beam, while in healthy tissue that average was only 1,6 time larger in BNCT. (author)

Velocity-specific strength recovery after a second bout of eccentric exercise.

Science.gov (United States)

Barss, Trevor S; Magnus, Charlene R A; Clarke, Nick; Lanovaz, Joel L; Chilibeck, Philip D; Kontulainen, Saija A; Arnold, Bart E; Farthing, Jonathan P

2014-02-01

A bout of eccentric exercise (ECC) has the protective effect of reducing muscle damage during a subsequent bout of ECC known as the "repeated bout effect" (RBE). The purpose of this study was to determine if the RBE is greater when both bouts of ECC are performed using the same vs. different velocity of contraction. Thirty-one right-handed participants were randomly assigned to perform an initial bout of either fast (3.14 rad·s [180°·s]) or slow (0.52 rad·s [30°·s]) maximal isokinetic ECCs of the elbow flexors. Three weeks later, the participants completed another bout of ECC at the same velocity (n = 16), or at a different velocity (n = 15). Indirect muscle damage markers were measured before, immediately after, and at 24, 48, and 72 hours postexercise. Measures included maximal voluntary isometric contraction (MVC) strength (dynamometer), muscle thickness (MT; ultrasound), delayed onset muscle soreness (DOMS; visual analog scale), biceps and triceps muscle activation amplitude (electromyography), voluntary activation (interpolated twitch), and twitch torque. After the repeated bout, MVC strength recovered faster compared with the same time points after the initial bout for only the same velocity group (p = 0.017), with no differences for all the other variables. Irrespective of velocity, MT and DOMS were reduced after the repeated bout compared with that of the initial bout at 24, 48, and 72 hours with a corresponding increase in TT at 72 hours (p effects contribute to the RBE. The current findings support the idea of multiple mechanisms contributing to the RBE.

RBEs and cytogenetic hereditary effects induced by neutron beams in mice

International Nuclear Information System (INIS)

Du Zeji; Li Yanyi; Liu Degui

1994-01-01

The RBEs and cytogenetic hereditary effects of different dose of neutron beams on chromosome aberrations and micronuclei of bone marrow cells in mice were observed. The results indicated that micronuclei frequency of occurrence and chromosome aberration frequency caused by neutrons increased with doses. The relationship was feasible to Y aD n . The lower energy of neutrons had the smaller value of RBE. RBE determined by CSACR were larger than that by MNCF. RBEs decreased with increasing of neutron doses, especially within the low range of doses. There was a linear relationship between CSACR and MNCF caused by neutron beams and γ-ray

A treatment planning comparison of BPA- or BSH-based BNCT of malignant gliomas

International Nuclear Information System (INIS)

Capala, J.; Coderre, J.A.; Chanana, A.D.

1996-01-01

Accurate delivery of the prescribed dose during clinical BNCT requires knowledge (or reasonably valid assumptions) about the boron concentrations in tumor and normal tissues. For conversion of physical dose (Gy) into photon-equivalent dose (Gy-Eq), relative biological effectiveness (RBE) and/or compound-adjusted biological effectiveness (CBE) factors are required for each tissue. The BNCT treatment planning software requires input of the following values: the boron concentration in blood and tumor, RBEs in brain, tumor and skin for the high-LET beam components, the CBE factors for brain, tumor, and skin, and the RBE for the gamma component

Radiobiological effects of tritiated water short-term exposure on V79 clonogenic cell survival

DEFF Research Database (Denmark)

Siragusa, Mattia; Fredericia, Nina Pil Møntegaard; Jensen, Mikael

2018-01-01

We set out to improve the accuracy of absorbed dose calculations for in-vitro measurements of the Relative Biological Effectiveness (RBE) of tritiated water (HTO) for the clonogenic cell survival assay, also considering the influence of the end-of-track Linear Energy Transfer (LET) of low-energy...... in suspension are usually comparable to those for adherent cells. RBEs calculated at the 10% survival fraction through the use of the average energy are almost similar to those obtained with the beta-spectrum. For adherent cells, an RBE of 1.6 was found when HTO cell survival curves were compared to acute γ...

Planning comparison between intensity modulated radiation therapy and intensity modulated proton therapy in a case of head and neck cancer

Science.gov (United States)

Nguyen, T. T. C.; Nguyen, B. T.; Mai, N. V.

2018-03-01

In this work, we made the comparison between IMRT plan and IMPT plan for a head and neck case. We used Prowess Panther to perform IMRT plan and LAP- CERR for IMPT plan. The result showed that IMPT plan had better coverage than IMRT plan. In the IMRT plan, normal structures received higher dose with higher volume. Especially, the maximum dose of spinal cord is 31.5 Gy (RBE) using IMRT technique compared to 13.5 Gy (RBE) using IMPT technique. These results showed that IMPT is beneficial for head and neck cancer compared to IMRT technique.

Magnetic structures: neutron diffraction studies

International Nuclear Information System (INIS)

Bouree-Vigneron, F.

1990-01-01

Neutron diffraction is often an unequivocal method for determining magnetic structures. Here we present some typical examples, stressing the sequence through experiments, data analysis, interpretation and modelisation. Two series of compounds are chosen: Tb Ni 2 Ge 2 and RBe 13 (R = Gd, Tb, Dy, Ho, Er). Depending on the nature of the elements, the magnetic structures produced can be commensurate, incommensurate or even show a transition between two such phases as a function of temperature. A model, taking magnetic exchange and anisotropy into account, will be presented in the case of commensurate-incommensurate magnetic transitions in RBe 13

Negative pion irradiation of mammalian cells

International Nuclear Information System (INIS)

Dertinger, H.; Luecke-Huhle, C.; Schlag, H.; Weibezahn, K.F.

1976-01-01

Monolayers and spheroids of Chinese hamster cells (V79) were subjected to negative pion irradiation under aerobic conditions. R.b.e. values in the pion peak of 1.8 and 1.5 were obtained for monolayers and spheroids, respectively, whereas the r.b.e. for the plateau was found to be slightly higher than 1. In addition, it was observed that the higher resistance of the V79 spheroid cells than the monolayers to γ-irradiation is not diminished in the pion peak, suggesting that the underlying phenomenon of intercellular communication influences cell survival even after high-LET irradiation. (author)

Evaluation of neutron irradiation fields for BNCT by using absorbed dose in a phantom

International Nuclear Information System (INIS)

Aizawa, O.

1993-01-01

In a previous paper, the author defined the open-quotes irradiation timeclose quotes as the time of irradiation in which the maximum open-quotes total background doseclose quotes becomes 2,500 RBE-cGy. In this paper, he has modified the definition a little as the time of irradiation in which the maximum open-quotes lμg/g B-10 doseclose quotes becomes 3,000 RBE-cGy, because he assumed that normal tissue contained 1μg/g B-10. Moreover, he has modified the dose criteria for BNCT as follows: The open-quotes eye doseclose quotes, open-quotes total body doseclose quotes and open-quotes except-head doseclose quotes should be less that 200, 100 and 50 RBE-cGy, respectively. He has added one more criterion for BNCT that the thermal neutron fluence at the tumor position should be over 2.5x10 12 n/cm 2 at the open-quotes irradiation timeclose quotes. The distance from the core side to the irradiation port in the open-quotes old configurationclose quotes of the Musashi reactor (TRIGA-II, 100kW) was 160 cm. He is now planning to design an eccentric core and to move the reactor core nearer to the irradiation port, distance between the core side and the irradiation port to be 140, 130 and 120cm. The other assumptions used in this paper are as follows: (1) The B-10 concentrations in tumor are 30 and/or 10μg/g. (2) The depth of the tumor is 5.0 cm to 5.5 cm from the surface. (3) The RBE values used are 1.0 for all gamma rays and 2.3 for B 10 (n,α) reaction products. (4) The RBE values for neutrons are the following three cases: the first case is using 1.6 for all neutrons; the second one is using 3.2 for non-thermal neutrons and 1.6 for thermal neutrons; the third case is using 4.8 for fast neutrons, 3.2 for faster epithermal and epithermal neutrons, and 1.6 for thermal neutrons

The relative biological effectiveness of a high energy neutron beam for micronuclei induction in T-lymphocytes of different individuals

Energy Technology Data Exchange (ETDEWEB)

Slabbert, J.P., E-mail: jps@tlabs.ac.z [NRF iThemba LABS (Laboratory for Accelerated Based Sciences), Somerset West (South Africa); Dept. of Medical Imaging and Clinical Oncology, University of Stellenbosch (South Africa); August, L. [NRF iThemba LABS (Laboratory for Accelerated Based Sciences), Somerset West (South Africa); Vral, A. [Dept. of Basic Medical Sciences, Ghent University (Belgium); Symons, J. [NRF iThemba LABS (Laboratory for Accelerated Based Sciences), Somerset West (South Africa)

2010-12-15

In assessing the radiation risk of personnel exposed to cosmic radiation fields as it pertains to radiological damage during travel in civilian aircrafts, it is particularly important to know the relative biological effectiveness (RBE) for high energy neutrons. It has been the subject of numerous investigations in recent years using different neutron energies and cytogenetic examinations. Variations in the radiosensitivity of white blood cells for different individuals are likely to influence the estimate of the relative biological effectiveness for high energy neutrons. This as such observations have been noted in the response of different cancer cell lines with varying inherent sensitivities. In this work the radiosensitivities of T-lymphocytes of different individuals to the p(66)/Be neutron beam at iThemba LABS were measured using micronuclei formations and compared to that noted following exposure to {sup 60}Co {gamma}-rays. The principle objective of this investigation was to establish if a relationship between neutron RBE and variation in biological response to {sup 60}Co {gamma}-rays for lymphocytes from different individuals could be determined. Peripheral blood samples were collected from four healthy donors and isolated lymphocytes were exposed to different doses of {sup 60}Co {gamma}-rays (1-5 Gy) and p(66)/Be neutrons (0.5-2.5 Gy). One sample per donor was not exposed to radiation and served as a control. Lymphocytes were stimulated using PHA and cultured to induce micronuclei in cytokinesis-blocked cells. Micronuclei yields were numerated using fluorescent microscopy. Radiosensitivities and RBE values were calculated from the fitted parameters describing the micronuclei frequency dose response data. Dissimilar dose response curves for different donors were observed reflecting varying inherent sensitivities to both neutron and gamma radiation. A clear reduction in the dose limiting RBE{sub M} is noted for donors with lymphocytes more sensitive to

In vitro evaluation of 213Bi-rituximab versus external gamma irradiation for the treatment of B-CLL patients: relative biological efficacy with respect to apoptosis induction and chromosomal damage

International Nuclear Information System (INIS)

Vandenbulcke, Katia; Lahorte, Christophe; Slegers, Guido; De Vos, Filip; Dierckx, Rudi A.; Offner, Fritz; Philippe, Jan; Apostolidis, Christos; Molinet, Roger; Nikula, Tuomo K.; Bacher, Klaus; De Gelder, Virginie; Vral, Anne; Thierens, Hubert

2003-01-01

External source radiotherapy and beta radioimmunotherapy (RIT) are effective treatments for lymphoid malignancies. The development of RIT with alpha emitters is attractive because of the high linear energy transfer (LET) and short path length, allowing higher tumour cell kill and lower toxicity to healthy tissues. We assessed the relative biological efficacy (RBE) of alpha RIT (in vitro) compared to external gamma irradiation with respect to induction of apoptosis in B chronic lymphocytic leukaemia (B-CLL) and induction of chromosomal damage in healthy donor B and T lymphocytes. The latter was measured by a micronucleus assay. 213 Bi was eluted from a 225 Ac generator and conjugated to CD20 antibody (rituximab) with CHX-A''-DTPA as a chelator. B-CLL cells from five patients were cultured for 24 h in RPMI/10% FCS while exposed to 213 Bi conjugated to CD20 antibody or after external 60 Co gamma irradiation. Binding assays were performed in samples of all patients to calculate the total absorbed dose. Apoptosis was scored by flow cytometric analyses of the cells stained with annexin V-FITC and 7-AAD. Apoptosis was expressed as % excess over spontaneous apoptosis in control. Full dose range experiments demonstrated 213 Bi-conjugated CD20 antibody to be more effective than equivalent doses of external gamma irradiation, but showed that similar plateau values were reached at 10 Gy. The RBE for induction of apoptosis in B-CLL was 2 between 1.5 and 7 Gy. The micronucleus yield in lymphocytes of healthy volunteers was measured to assess the late toxicity caused by induction of chromosomal instability. While gamma radiation induced a steady increase in micronucleus yields in B and T cells, the damage induced by 213 Bi was more dramatic, with RBE ranging from 5 to 2 between 0.1 Gy and 2 Gy respectively. In contrast to gamma irradiation, 213 Bi inhibited mitogen-stimulated mitosis almost completely at 2 Gy. In conclusion, high-LET targeted alpha particle exposure killed B

Disruption of SLX4-MUS81 Function Increases the Relative Biological Effectiveness of Proton Radiation

Energy Technology Data Exchange (ETDEWEB)

Liu, Qi [Laboratory of Cellular and Molecular Radiation Oncology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Underwood, Tracy S.A.; Kung, Jong [Division of Radiation Physics, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Wang, Meng [Laboratory of Cellular and Molecular Radiation Oncology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Lu, Hsiao-Ming; Paganetti, Harald [Division of Radiation Physics, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Held, Kathryn D.; Hong, Theodore S.; Efstathiou, Jason A. [Laboratory of Cellular and Molecular Radiation Oncology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Willers, Henning, E-mail: hwillers@mgh.harvard.edu [Laboratory of Cellular and Molecular Radiation Oncology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

2016-05-01

Purpose: Clinical proton beam therapy has been based on the use of a generic relative biological effectiveness (RBE) of ∼1.1. However, emerging data have suggested that Fanconi anemia (FA) and homologous recombination pathway defects can lead to a variable RBE, at least in vitro. We investigated the role of SLX4 (FANCP), which acts as a docking platform for the assembly of multiple structure-specific endonucleases, in the response to proton irradiation. Methods and Materials: Isogenic cell pairs for the study of SLX4, XPF/ERCC1, MUS81, and SLX1 were irradiated at the mid-spread-out Bragg peak of a clinical proton beam (linear energy transfer 2.5 keV/μm) or with 250 kVp x-rays, and the clonogenic survival fractions were determined. To estimate the RBE of the protons relative to cobalt-60 photons (Co60Eq), we assigned a RBE(Co60Eq) of 1.1 to x-rays to correct the physical dose measured. Standard DNA repair foci assays were used to monitor the damage responses, and the cell cycle distributions were assessed by flow cytometry. The poly(ADP-ribose) polymerase inhibitor olaparib was used for comparison. Results: Loss of SLX4 function resulted in an enhanced proton RBE(Co60Eq) of 1.42 compared with 1.11 for wild-type cells (at a survival fraction of 0.1; P<.05), which correlated with increased persistent DNA double-strand breaks in cells in the S/G{sub 2} phase. Genetic analysis identified the SLX4-binding partner MUS81 as a mediator of resistance to proton radiation. Both proton irradiation and olaparib treatment resulted in a similar prolonged accumulation of RAD51 foci in SLX4/MUS81-deficient cells, suggesting a common defect in the repair of DNA replication fork-associated damage. Conclusions: A defect in the FA pathway at the level of SLX4 results in hypersensitivity to proton radiation, which is, at least in part, due to impaired MUS81-mediated processing of replication forks that stall at clustered DNA damage. In vivo and clinical studies are needed to

Relative biological effectiveness in canine osteosarcoma cells irradiated with accelerated charged particles

Science.gov (United States)

Maeda, Junko; Cartwright, Ian M.; Haskins, Jeremy S.; Fujii, Yoshihiro; Fujisawa, Hiroshi; Hirakawa, Hirokazu; Uesaka, Mitsuru; Kitamura, Hisashi; Fujimori, Akira; Thamm, Douglas H.; Kato, Takamitsu A.

2016-01-01

Heavy ions, characterized by high linear energy transfer (LET) radiation, have advantages compared with low LET protons and photons in their biological effects. The application of heavy ions within veterinary clinics requires additional background information to determine heavy ion efficacy. In the present study, comparison of the cell-killing effects of photons, protons and heavy ions was investigated in canine osteosarcoma (OSA) cells in vitro. A total of four canine OSA cell lines with various radiosensitivities were irradiated with 137Cs gamma-rays, monoenergetic proton beams, 50 keV/µm carbon ion spread out Bragg peak beams and 200 keV/µm iron ion monoenergetic beams. Clonogenic survival was examined using colony-forming as says, and relative biological effectiveness (RBE) values were calculated relative to gamma-rays using the D10 value, which is determined as the dose (Gy) resulting in 10% survival. For proton irradiation, the RBE values for all four cell lines were 1.0–1.1. For all four cell lines, exposure to carbon ions yielded a decreased cell survival compared with gamma-rays, with the RBE values ranging from 1.56–2.10. Iron ions yielded the lowest cell survival among tested radiation types, with RBE values ranging from 3.51–3.69 observed in the three radioresistant cell lines. The radiosensitive cell line investigated demonstrated similar cell survival for carbon and iron ion irradiation. The results of the present study suggest that heavy ions are more effective for killing radioresistant canine OSA cells when compared with gamma-rays and protons. This markedly increased efficiency of cell killing is an attractive reason for utilizing heavy ions for radioresistant canine OSA. PMID:27446477

DNA double-strand breaks induced by high-energy neon and iron ions in human fibroblasts. I. Pulsed-field gel electrophoresis method

International Nuclear Information System (INIS)

Rydberg, B.; Loebrich, M.; Cooper, P.K.

1994-01-01

The relative effectiveness of high-energy neon and iron ions for the production of DNA double-strand breaks was measured in one transformed and one nontransformed human fibroblast cell line using pulsed-field gel electrophoresis. The DNA released from the gel plug (fraction of activity released: FAR) as well as the size distribution of the DNA entering the gel were used to compare the effects of the heavy-ion exposure with X-ray exposure. Both methods gave similar results, indicating similar distributions of breaks over megabase-pair distances for the heavy ions and the X rays. The relative biological effectiveness (RBE) compared to 225 kVp X rays of initially induced DNA double-strand breaks was found to be 0.85 for 425 MeV/u neon ions (LET 32 keV/μm) and 0.42-0.55 for 250-600 MeV/u iron ions (LET 190-350 keV/μm). Postirradiation incubation showed less efficient repair of breaks induced by the neon ions and the 600 MeV/u iron ions compared to X rays. Survival experiments demonstrated RBE values larger than one for cell killing by the heavy ions in parallel experiments (neon: RBE = 1.2, iron: RBE = 2.3-3.0, based on D 10 values). It is concluded that either the initial yield of DNA double-strand breaks induced by the high-energy particles is lower than the yield for X rays, or the breaks induced by heavy ions are present in clusters that cannot be resolved with the technique used. These results are confirmed in the accompanying paper. 48 refs., 5 figs., 2 tabs

Overview of research and therapy facilities for radiobiological experimental work in particle therapy. Report from the European Particle Therapy Network radiobiology group.

Science.gov (United States)

Dosanjh, Manjit; Jones, Bleddyn; Pawelke, Jörg; Pruschy, Martin; Sørensen, Brita Singers

2018-04-24

Particle therapy (PT) as cancer treatment, using protons or heavier ions, can provide a more favorable dose distribution compared to X-rays. While the physical characteristics of particle radiation have been the aim of intense research, less focus has been placed on the actual biological responses arising from particle irradiation. One of the biggest challenges for proton radiobiology is the RBE, with an increasing concern that the clinically-applied generic RBE-value of 1.1 is an approximation, as RBE is a complex quantity, depending on both biological and physical parameters, such as dose, LET, cellular and tissue radiobiological characteristics, as well as the endpoints being studied. Most of the available RBE data derive from in vitro experiments, with very limited in vivo data available, especially in late-reacting tissues, which provide the main constraints and influence the quality of life endpoints in radiotherapy. There is a need for systematic, large-scale studies to thoroughly establish the biology of particle radiation in a number of different experimental models in order to refine biophysical mathematical models that can potentially be used to guide PT. The overall objective of the European Particle Therapy Network (EPTN) WP6 is to form a network of research and therapy facilities in order to coordinate and standardize the radiobiological experiments, to obtain more accurate predictive parameters than in the past. Coordinated research is required in order to obtain the most appropriate experimental data. The aim in this paper is to describe the available radiobiology infrastructure of the centers involved in EPTN WP6. Copyright © 2018 Elsevier B.V. All rights reserved.

What kind of radiobiology should be done at a hadron therapy center

International Nuclear Information System (INIS)

Kraft, G.; Kraft-Weyrather, W.; Taucher-Scholz, G.; Scholz, M.

1997-01-01

Although therapy with heavy particles like neutrons, protons or heavier ions has now a rather long history of several decades, but there are more open questions than settled problems. This fact is really amazing because the use of the high LET particles, neutrons and heavy ions was strongly motivated by radiobiological arguments. Presently, the use of protons with a better physical dose distribution is more widely accepted than neutrons or heavy ions where the expected high LET benefit could not be verified clinically. This demonstrates that predictions made on the basis of radiobiological experiments cannot be transferred directly from in vitro experiments to the therapy situation. In particular, it is not possible to transfer an average RBE value measured in vitro in an extended exposure field to the treatment situation. Therefore, in the following section the dependence of RBE on LET, dose and radiosensitivity will be summarized and compared to models. Basic experiments illustrating the RBE problem in a particle field will be described. The fundamentals of a recently developed track structure model will be given and calculations will be compared to experiments. Finally, a short outline of possible future developments for radiobiology will be presented. (orig.)

Microscopical investigation of cellular effects of 135 MeV/amu carbon along the path of the beam

International Nuclear Information System (INIS)

Furuse, Masako; Soga, Fuminori; Matsumoto, Shinji

1993-01-01

The difference in biological effects are normally described by the concept of RBE. However, the RBE values depend on the LET along a trajectory and also on complicated parameters such as the distribution of the energy deposition due to the difference in the spread of secondary electrons perpendicular to a beam axis. The authors are interested in the use of a biological dosimeter of microorganisms which can directly compare biological effects such as survival level. The survival rate of yeast cells was tested for this purpose with a carbon beam at 135 MeV/amu from the RIKEN ring cyclotron. The haploid cells of a wild type and a radiation sensitive mutant were used. Yeast is a simple eukaryote, and it has been used as the test organism especially for the studies on the relation between DNA double-strand breaks and cell killing. The materials used, the experimental method and the results are reported. The survival data of the wild type and the radiation sensitive mutant at stationary and log phases were obtained, and the values were used for the RBE estimation. The resistance seemed due to the action of enzymatic repair mechanism. (K.I.)

Induction of spinal cord paralysis by negative pi-mesons

International Nuclear Information System (INIS)

Amols, H.I.; Yuhas, J.M.

1981-01-01

As part of an investigation on late non-neoplastic injury induced by negative pi-mesons (pions), a series of studies have been performed using pion beams for the induction of spinal cord paralysis in the Fisher 344 rat. Groups of rats were exposed to 1, 5 or 15 daily doses of peak pions or X rays. Paralysis appeared earlier after treatment with pions than after X-rays even in a comparison of groups with similar final incidences. A single dose RBE for spinal cord paralysis of 1.3 was found. The RBE rises to a value of 3.2 if the total dose is given as a series of 15 daily exposures. These RBEs are far larger than those observed using other late injury end-points, such as tubular degeneration in the kidney or fibrosis and sclerosis in the support structures of the colon for which the single dose RBE is less than 1.2. The biological and/or physical basis for the high sensitivity of the spinal cord to peak pions has not yet been resolved, but these data have suggested caution in exposing the spinal cord to peak pions in clinical trials. (author)

20neon ion- and x-ray-induced mammary carcinogenesis in female rats

International Nuclear Information System (INIS)

Shellabarger, C.J.; Baum, J.W.; Holtzman, S.; Stone, J.P.

1983-01-01

One of the proposed uses of heavy ion irradiation is to image lesions of the human female breast. The rat model system was chosen to assess the carcinogenic potential of heavy ion irradiation in the belief that data obtained from rat studies would have a qualitatively predictive value for the human female. Accordingly, female rats were exposed to 20 Ne ions at the BEVALAC and studied for the development of mammary neoplasia for 312 +- 2 days at Brookhaven along with rats exposed concurrently to x-irradiation or to no irradiation. As the dose of either type of radiation was increased the percent of rats with mammary adenocarcinomas, and the percent of rats with mammary fibroadenomas, tended to increase. At a prevalence of 20%, the RBE for 20 Neon ions for mammary adenocarcinomas was estimated to be larger than 5 and for mammary fibroadenomas the RBE was estimated to be less than 2. No conclusion was reached concerning whether or not the RBE might vary with dose. We suggest that 20 Ne ions do have a carcinogenic potential for rat mammary tissue and that this carcinogenic potential is likely to be greater than for x-irradiation. (DT)

DNA damage produced by exposure of supercoiled plasmid DNA to high- and low-LET ionizing radiation: Effects of hydroxyl radical quenchers. DNA breakage, neutrons, OH radicals

International Nuclear Information System (INIS)

Peak, J.G.; Ito, T.; Peak, M.J.; Robb, F.T.

1994-01-01

A supercoiled plasmid of 7300 base pairs was isolated and exposed in an aqueous environment to 60 Co γ rays and JANUS 0.85 MeV fission-spectrum neutrons. Dose responses for the production of single-strand breaks (SSBs), double-strand breaks (DSBs) and alkali-labile sites (ALSs) were compared with computations made from the conversion of the supercoil to its relaxed and linear forms. The relative biological effectiveness (RBE) for production of SSBs and DSBs was similar to that previously measured in the cellular environment. The RBE for destruction of genetic transforming activity of M13 viral DNA followed that for DNA damage. This is in contrast to the situation for biological effects such as lethality, mutagenesis, and cellular transformation measured in mammalian cells, where the RBE values are reversed. The role of hydroxyl (OH) radical in DNA damage induction by neutrons was investigated by exposure of plasmid in the presence of known quenchers of this species. Of four quenchers tested, all were able to reduce the yields of both SSBs and DSBs. These findings are consistent with a model for SSB and DSB induction by high linear energy transfer that involves OH radical mediation

Quantitative radiation dose-response relationships for normal tissues in man - I. Gustatory tissues response during photon and neutron radiotherapy

International Nuclear Information System (INIS)

Mossman, K.L.

1982-01-01

Quantitative radiation dose-response curves for normal gustatory tissue in man were studied. Taste function, expressed as taste loss, was evaluated in 84 patients who were given either photon or neutron radiotherapy for tumors in the head and neck region. Patients were treated to average tumor doses of 6600 cGy (photon) or 2200 cGy intervals for photon patients and 320-cGy intervals for neutron patients during radiotherapy. The dose-response curves for photons and neutrons were analyzed by fitting a four-parameter logistic equation to the data. Photon and neutron curves differed principally in their relative position along the dose axis. Comparison of the dose-response curves were made by determination of RBE. At 320 cGy, the lowest neutron dose at which taste measurements were made, RBE = 5.7. If this RBE is correct, then the therapeutic gain factor may be equal to or less than 1, indicating no biological advantage in using neutrons over photons for this normal tissue. These studies suggest measurements of taste function and evaluation of dose-response relationships may also be useful in quantitatively evaluating the efficacy of chemical modifiers of radiation response such as hypoxic cell radiosensitizers and radioprotectors

Radiobiological aspects of application of BR-10 reactor neutrons for radiotherapy of malignant tumours

International Nuclear Information System (INIS)

Ul'yanenko, S.E.; Kuznetsova, M.N.; Obaturov, G.M.

1992-01-01

Possibilities to increase the factor of therapeutical gain (FTG) by optimizing irradiation conditions and using hyperglycemia were studied. It is shown that relative biological effectiveness (RBE) of neutrons in fission spectrum of the BR-10 reactor in the dose range from 10 Gy used one time is 4.2-4.5 for tumours and 4.0-4.2 for normal skin; in case of fractionated irradiation by neutrons (1-8 fractions in the range of 6-10 Gy) RBE increases practically 1.5 fold; employment of neutron beam filters and hyperglycemia in conditions of combined gamma-neutron procedures of irradiation permits a considerable increase in FTG. 3 refs

Mutagenic action of radiation with different LET on Bacillus subtilis cells

International Nuclear Information System (INIS)

edinennyj Inst. Yadernykh Issledovanij, Dubna (Russian Federation))" data-affiliation=" (Obedinennyj Inst. Yadernykh Issledovanij, Dubna (Russian Federation))" >Borejko, A.V.; edinennyj Inst. Yadernykh Issledovanij, Dubna (Russian Federation))" data-affiliation=" (Obedinennyj Inst. Yadernykh Issledovanij, Dubna (Russian Federation))" >Krasavin, E.A.

1997-01-01

The induction of the his - -> his + mutants in vegetative and spores of Bacillus subtilis wild type cells irradiated with γ-rays and helium ions (LET = 20-80 keV/μm) has been investigated. It was shown that the dose dependence of the mutation induction in vegetative cells is described by a linear-quadratic function of dose in case of both γ-rays and helium ions. RBE (LET) dependencies on the lethal and mutagenic effect of radiation have a local maximum. The maximum of RBE (LET) dependence on the mutagenic assay is shifted at the low region of LET in comparison with the lethal effect of irradiation. (author)

Relative biological effectiveness of 160 MeV protons. II. Biological data and their interpretation in terms of microdosimetry

International Nuclear Information System (INIS)

Hall, E.J.; Kellerer, A.M.; Rossi, H.H.; Lam, Y.M.P.

1978-01-01

The radiobiological effectiveness of 160 MeV protons was measured relative to 60 Co γ rays using Chinese hamster cells cultured in vitro. Separate experiments were performed with cells irradiated in suspension, or attached to plastic tissue culture flasks. Proton irradiations were performed in the incident plateau of the depth dose profile and with the Bragg peak spread out to cover 10 cm. In all cases the relative biological effectiveness (RBE) for protons relative to gamma rays was 1.2 for doses in excess of about 200 rad. The attached cell experiments indicate an increasing RBE at low doses, which is consistent with the microdosimetric measurements

Evaluation of RBE of thermal neutron capture reaction

International Nuclear Information System (INIS)

Fukuda, Hiroshi; Matsuzawa, Taiju; Kobayashi, Toru; Kanda, Keiji.

1985-01-01

B16 melanoma cells were grown in a flask (Falcon 3031). When the cells reached the latter stage of logarithmic phase, B-boric acid (92 % concentrated 10 B) was added to the flask until 5 μg/ml medium was attained (Medium I). The other medium did not contain 10 B (Medium II). After both media were exposed to thermal neutrons, survival curves were obtained from the colony method and the absorbed dose of the cells were obtained from the mathematical models. Survival curves from the colony method had no shoulders, showing that Do was 0.95 x 10 12 n/cm 2 in Medium I and 3.2 x 10 12 n/cm 2 in Medium II. Do calculated by mathematical models was 0.507 Gy in Medium I and 0.604 Gy in Medium II. REB of thermal neutrons was 3.04 in Medium I and 2.55 in Medium II. REB of 10 B (n, α) 7 Li reaction was 3.30. (Namekawa, K.)

Direct evaluation of radiobiological parameters from clinical data in the case of ion beam therapy: an alternative approach to the relative biological effectiveness

International Nuclear Information System (INIS)

Cometto, A; Russo, G; Giordanengo, S; Marchetto, F; Cirio, R; Attili, A; Bourhaleb, F; Milian, F M

2014-01-01

The relative biological effectiveness (RBE) concept is commonly used in treatment planning for ion beam therapy. Whether models based on in vitro/in vivo RBE data can be used to predict human response to treatments is an open issue. In this work an alternative method, based on an effective radiobiological parameterization directly derived from clinical data, is presented. The method has been applied to the analysis of prostate cancer trials with protons and carbon ions. Prostate cancer trials with proton and carbon ion beams reporting 5 year-local control (LC5) and grade 2 (G2) or higher genitourinary toxicity rates (TOX) were selected from literature to test the method. Treatment simulations were performed on a representative subset of patients to produce dose and linear energy transfer distribution, which were used as explicative physical variables for the radiobiological modelling. Two models were taken into consideration: the microdosimetric kinetic model (MKM) and a linear model (LM). The radiobiological parameters of the LM and MKM were obtained by coupling them with the tumor control probability and normal tissue complication probability models to fit the LC5 and TOX data through likelihood maximization. The model ranking was based on the Akaike information criterion. Results showed large confidence intervals due to the limited variety of available treatment schedules. RBE values, such as RBE = 1.1 for protons in the treated volume, were derived as a by-product of the method, showing a consistency with current approaches. Carbon ion RBE values were also derived, showing lower values than those assumed for the original treatment planning in the target region, whereas higher values were found in the bladder. Most importantly, this work shows the possibility to infer the radiobiological parametrization for proton and carbon ion treatment directly from clinical data. (paper)

Biological intercomparison using gut crypt survivals for proton and carbon-ion beams

International Nuclear Information System (INIS)

Uzawa, Akiko; Ando, Koichi; Furusawa, Yoshiya

2007-01-01

Charged particle therapy depends on biological information for the dose prescription. Relative biological effectiveness or RBE for this requirement could basically be provided by experimental data. As RBE values of protons and carbon ions depend on several factors such as cell/tissue type, biological endpoint, dose and fractionation schedule, a single RBE value could not deal with all different radiosensitivities. However, any biological model with accurate reproducibility is useful for comparing biological effectiveness between different facilities. We used mouse gut crypt survivals as endpoint, and compared the cell killing efficiency of proton beams at three Japanese facilities. Three Linac X-ray machines with 4 and 6 MeV were used as reference beams, and there was only a small variation (coefficient of variance<2%) in biological effectiveness among them. The RBE values of protons relative to Linac X-rays ranged from 1.0 to 1.11 at the middle of a 6-cm SOBP (spread-out Bragg peak) and from 0.96 to 1.01 at the entrance plateau. The coefficient of variance for protons ranged between 4.0 and 5.1%. The biological comparison of carbon ions showed fairly good agreement in that the difference in biological effectiveness between National Institute of Radiological Sciences (NIRS)/ Heavy Ion Medical Accelerator in Chiba (HIMAC) and Gesellschaft fur Schwerionenforschung (GSI)/Heavy Ion Synchrotron (SIS) was 1% for three positions within the 6-cm SOBP. The coefficient of variance was <1.7, <0.6 and <1.6% for proximal, middle and distal SOBP, respectively. We conclude that the inter-institutional variation of biological effectiveness is smaller for carbon ions than protons, and that beam-spreading methods of carbon ions do not critically influence gut crypt survival. (author)

Microdosimetric evaluation of relative biological effectiveness for 103PD, 125I, 241AM, and 192IR brachytherapy sources

International Nuclear Information System (INIS)

Wuu, C.S.; Kliauga, P.; Zaider, M.; Amols, H.I.

1996-01-01

Purpose: To determine the microdosimetric-derived relative biological effectiveness (RBE) of 103 Pd, 125 I, 241 Am, and 192 Ir brachytherapy sources at low doses and/or low dose rates. Methods and Materials: The Theory of Dual Radiation Action can be used to predict expected RBE values based on the spatial distribution of energy deposition at microscopic levels from these sources. Single-event lineal energy spectra for these isotopes have been obtained both experimentally and theoretically. A grid-defined wall-less proportional counter was used to measure the lineal energy distributions. Unlike conventional Rossi proportional counters, the counter used in these measurements has a conducting nylon fiber as the central collecting anode and has no metal parts. Thus, the Z-dependence of the photoelectric effect is eliminated as a source of measurement error. Single-event spectra for these brachytherapy sources have been also calculated by: (a) the Monte Carlo code MCNP to generate the electron slowing down spectrum, (b) transport of monoenergetic electron tracks, event by event, with our Monte Carlo code DELTA, (c) using the concept of associated volume to obtain the lineal energy distribution f(y) for each monoenergetic electron, and (d) obtaining the composite lineal energy spectrum for a given brachytherapy source based on the electron spectrum calculated at step (a). Results: Relative to 60 Co, the RBE values obtained from this study are: 2.3 for 103 Pd, 2.1 for 125 I, 2.1 for 241 Am, and 1.3 for 192 Ir. Conclusions: These values are consistent with available data from in vitro cell survival experiments. We suggest that, at least for these brachytherapy sources, microdosimetry may be used as a credible alternative to time-consuming (and often uncertain) radiobiological experiments to obtain information on radition quality and make reliable predictions of RBE in low dose rate brachytherapy

Biological intercomparison using gut crypt survivals for proton and carbon ions

International Nuclear Information System (INIS)

Uzawa, Akiko; Ando, Koichi; Furusawa, Yoshiya

2006-01-01

Charged particle therapy depends on biological information for the dose prescription. Relative biological effectiveness or relative biological effectiveness (RBE) for this requirement could basically be provided by experimental data. As RBE values of protons and carbon ions depend on several factors such as cell/tissue type, endpoint, dose and fractionation schedule, a single RBE value could not function as a master key to open all rooms filled with guests of different radiosensitivities. However, any biological model with accurate reproducibility is useful for comparing biological effectiveness between different facilities. We used mouse gut crypt survivals as endpoint, and compared the cell killing efficiency of proton beams at three Japanese facilities. Three Linac X-ray machines with 4 and 6 MeV were used as reference beams, and there was only a small variation (coefficient of variance <2%) in biological effectiveness among them. The RBE values of protons relative to Linac X-rays ranged from 1.0 to 1.11 at the middle of a 6-cm SOBP (spread-out Bragg peak) and from 0.96 to 1.01 at the entrance plateau. The coefficient of variance for protons ranged between 4.0 and 5.1%. The biological comparison of carbon ions showed fairly good agreement in that the difference in biological effectiveness between National Institute of Radiological Sciences (NIRS)/Heavy Ion Medical Accelerator in Chiba (HIMAC) and Gesellschaft fur Schwerionenforschung (GSI)/Heavy Ion Synchrotron (SIS) was 1% for three positions within the 6-cm SOBP. The coefficient of variance was <1.7, <0.6 and <1.6% for proximal, middle and distal SOBP, respectively. We conclude that the inter-institutional variation of biological effectiveness is smaller for carbon ions than protons, and that beam-spreading methods of carbon ions do not critically influence gut crypt survival. (author)

Monte Carlo based dosimetry and treatment planning for neutron capture therapy of brain tumors

International Nuclear Information System (INIS)

Zamenhof, R.G.; Clement, S.D.; Harling, O.K.; Brenner, J.F.; Wazer, D.E.; Madoc-Jones, H.; Yanch, J.C.

1990-01-01

Monte Carlo based dosimetry and computer-aided treatment planning for neutron capture therapy have been developed to provide the necessary link between physical dosimetric measurements performed on the MITR-II epithermal-neutron beams and the need of the radiation oncologist to synthesize large amounts of dosimetric data into a clinically meaningful treatment plan for each individual patient. Monte Carlo simulation has been employed to characterize the spatial dose distributions within a skull/brain model irradiated by an epithermal-neutron beam designed for neutron capture therapy applications. The geometry and elemental composition employed for the mathematical skull/brain model and the neutron and photon fluence-to-dose conversion formalism are presented. A treatment planning program, NCTPLAN, developed specifically for neutron capture therapy, is described. Examples are presented illustrating both one and two-dimensional dose distributions obtainable within the brain with an experimental epithermal-neutron beam, together with beam quality and treatment plan efficacy criteria which have been formulated for neutron capture therapy. The incorporation of three-dimensional computed tomographic image data into the treatment planning procedure is illustrated. The experimental epithermal-neutron beam has a maximum usable circular diameter of 20 cm, and with 30 ppm of B-10 in tumor and 3 ppm of B-10 in blood, it produces a beam-axis advantage depth of 7.4 cm, a beam-axis advantage ratio of 1.83, a global advantage ratio of 1.70, and an advantage depth RBE-dose rate to tumor of 20.6 RBE-cGy/min (cJ/kg-min). These characteristics make this beam well suited for clinical applications, enabling an RBE-dose of 2,000 RBE-cGy/min (cJ/kg-min) to be delivered to tumor at brain midline in six fractions with a treatment time of approximately 16 minutes per fraction

Modeling the yield of double-strand breaks due to formation of multiply damaged sites in irradiated plasmid DNA

International Nuclear Information System (INIS)

Xapsos, M.A.; Pogozelski, W.K.

1996-01-01

Although double-strand breaks have long been recognized as an important type of DNa lesion, it is well established that this broad class of damage does not correlate well with indicators of the effectiveness of radiation as the cellular level. Assays of double-strand breaks do not distinguish the degree of complexity or clustering of singly damaged sites produced in a single energy deposition event, which is currently hypothesized to be key to understanding cellular end points. As a step toward this understanding, double-strand breaks that are formed proportionally to dose in plasmid DNA are analyzed from the mechanistic aspect to evaluate the yield that arises from multiply damaged sites as hypothesized by Ward (Prog. Nucleic Acid Res. Mol. Biol. 35, 95-125, 1988) and Goodhead (Int. J. Radiat. Biol. 65, 7-17, 1994) as opposed to the yield that arises form single hydroxyl radicals as hypothesized by Siddiqi and Bothe (Radiat. Res. 112, 449-463, 1987). For low-LET radiation such as γ rays, the importance of multiply damaged sites is shown to increase with the solution's hydroxyl radical scavenging capacity. For moderately high-LET radiation such as 100 keV/μm helium ions, a much different behavior is observed. In this case, a large fraction of double-strand breaks are formed as a result of multiply damaged sties over a broad range of scavenging conditions. Results also indicate that the RBE for common cellular end points correlates more closely with the RBE for common cellular end points correlates more closely with the RBE for multiply damaged sites than with the RBE for total double-strand breaks over a range of LET up to at least 100 keV/μm. 22 refs., 3 figs., 2 tabs

The relative biological effectiveness of fractionated doses of fast neutrons (42 MeVd→Be) for normal tissues. Pt. 3

International Nuclear Information System (INIS)

Rezvani, M.; Hopewell, J.W.; Robbins, M.E.C.; Hamlet, R.; Barnes, D.W.H.; Sansom, J.M.; Adams, P.J.V.

1990-01-01

The effect of single and fractionated doses of fast neutrons (42 MeV d→Bc ) on the early and late radiation responses of the pig lung have been assessed by the measurement of changes in lung function using a 133 Xe washout technique. The results obtained for irradiation schedules with fast neutrons have been compared with those after photon irradiation. There was no statistically significant difference between the values for the relative biological effectiveness (RBE) for the early and late radiation response of the lung. The RBE of the neutron beam increased with decreasing size of dose/fraction with an upper limit value of 4.39 ± 0.94 for infinitely small X-ray doses per fraction. (author)

Induction of micronuclei by irradiation with neutrons produced from 600 MeV protons

CERN Document Server

Diehl-Marshall, I

1980-01-01

Chromosome damage can be detected by the observation of micronuclei . Because its sensitivity, the micronuclei induciton in meristems of Vicia faba bean roots has been selected to determine the radiation damage produced by doses ranging from 1 to 82 cGy of neutrons. The average number of miconuclei found between 24 and 48 hours after irradiation was plotted as a funciton of dose. The RBE values, using as reference radiation 60 Co y-rays, ranged from 3.5 for a neutron dose of 82 cGy to 18 for a neutron of 1 cGy. Even higher RBE values were deduced at low doses from the evaluation of cells containing multiple micronuclei.

Dosimetry implications of BSH biodistribution study at OSU

International Nuclear Information System (INIS)

Gupta, N.; Albertson, B.J.; Gahbauer, R.A.; Barth, R.F.; Goodman, J.H.

2000-01-01

A BSH biodistribution study was performed at Ohio State University, where tumor, normal brain, and blood boron concentrations of patients undergoing tumor debulking surgery were acquired. The results of this biodistribution study are subjects of other presentations in this meeting. In this paper, we present an overview of the dosimetry implications of this biodistribution data. The analysis for this paper assumed that the tumor boron RBE was factor of two higher than the normal brain boron RBE. Our conclusions from this analysis were that with the tumor/blood ratios observed in our patients for times of up to 14 hours post commencement of boron infusion, one could not successfully treat patients with BNCT using BSH. (author)

Human factors reliability benchmark exercise

International Nuclear Information System (INIS)

Poucet, A.

1989-08-01

The Joint Research Centre of the European Commission has organised a Human Factors Reliability Benchmark Exercise (HF-RBE) with the aim of assessing the state of the art in human reliability modelling and assessment. Fifteen teams from eleven countries, representing industry, utilities, licensing organisations and research institutes, participated in the HF-RBE. The HF-RBE was organised around two study cases: (1) analysis of routine functional Test and Maintenance (TPM) procedures: with the aim of assessing the probability of test induced failures, the probability of failures to remain unrevealed and the potential to initiate transients because of errors performed in the test; (2) analysis of human actions during an operational transient: with the aim of assessing the probability that the operators will correctly diagnose the malfunctions and take proper corrective action. This report summarises the contributions received from the participants and analyses these contributions on a comparative basis. The aim of this analysis was to compare the procedures, modelling techniques and quantification methods used, to obtain insight in the causes and magnitude of the variability observed in the results, to try to identify preferred human reliability assessment approaches and to get an understanding of the current state of the art in the field identifying the limitations that are still inherent to the different approaches

Relative biological effectiveness of tritium for induction of myeloid leukemia in CBA/H mice

International Nuclear Information System (INIS)

Johnson, J.R.; Myers, D.K.; Jackson, J.S.; Dunford, D.W.; Gragtmans, N.J.; Wyatt, H.M.; Jones, A.R.; Percy, D.H.

1995-01-01

To help resolve uncertainties as to the most appropriate weighting factor for tritium β rays, a large experiment was carried out to measure the relative biological effectiveness (RBE) of tritiated water compared to X rays for the induction of myeloid leukemia in male mice of the CBA/H strain. The study was designed to estimate the lifetime incidence of myeloid leukemia in seven groups of about 750 mice each; radiation exposures were approximately 0, 1, 2 and 3 Gy both for tritiated water and for X rays. The lifetime incidence of leukemia in these mice increased from 0.13% in the control group to 6-8% in groups exposed to higher radiation doses. The results were fitted to various equations relating leukemia incidence to radiation dose, using both the raw data and data corrected for cumulative mouse-days at risk. The calculated RBE values for tritium 13 rays compared to X rays ranged from 1.0 ± 0.5 to 1.3 ± 0.3. A best estimate of the RBE for this experiment was about 1.2 ± 0.3. A w R value of 1 would thus appear to be more appropriate than a W R of 2 for tritium β rays. (author)

Relative biological effectiveness of tritium for induction of myeloid leukemia in CBA/H mice

Energy Technology Data Exchange (ETDEWEB)

Johnson, J.R. [Battelle Pacific Northwest Labs., Health Protection Branch, Health Div., Richland, WA (United States); Myers, D.K.; Jackson, J.S.; Dunford, D.W.; Gragtmans, N.J.; Wyatt, H.M.; Jones, A.R. [Atomic Energy of Canada Limited, Chalk River, Ontairo (Canada); Percy, D.H. [Univ. of Guelph, Ontario Veterinary College, Guelph, Ontario (Canada)

1995-07-01

To help resolve uncertainties as to the most appropriate weighting factor for tritium {beta} rays, a large experiment was carried out to measure the relative biological effectiveness (RBE) of tritiated water compared to X rays for the induction of myeloid leukemia in male mice of the CBA/H strain. The study was designed to estimate the lifetime incidence of myeloid leukemia in seven groups of about 750 mice each; radiation exposures were approximately 0, 1, 2 and 3 Gy both for tritiated water and for X rays. The lifetime incidence of leukemia in these mice increased from 0.13% in the control group to 6-8% in groups exposed to higher radiation doses. The results were fitted to various equations relating leukemia incidence to radiation dose, using both the raw data and data corrected for cumulative mouse-days at risk. The calculated RBE values for tritium 13 rays compared to X rays ranged from 1.0 {+-} 0.5 to 1.3 {+-} 0.3. A best estimate of the RBE for this experiment was about 1.2 {+-} 0.3. A w{sub R} value of 1 would thus appear to be more appropriate than a W{sub R} of 2 for tritium {beta} rays. (author)

Relative biological effectiveness of tritium for induction of myeloid leukemia in CBA/H mice.

Science.gov (United States)

Johnson, J R; Myers, D K; Jackson, J S; Dunford, D W; Gragtmans, N J; Wyatt, H M; Jones, A R; Percy, D H

1995-10-01

To help resolve uncertainties as to the most appropriate weighting factor for tritium beta rays, a large experiment was carried out to measure the relative biological effectiveness (RBE) of tritiated water compared to X rays for the induction of myeloid leukemia in male mice of the CBA/H strain. The study was designed to estimate the lifetime incidence of myeloid leukemia in seven groups of about 750 mice each; radiation exposures were approximately 0, 1, 2 and 3 Gy both for tritiated water and for X rays. The lifetime incidence of leukemia in these mice increased from 0.13% in the control group to 6-8% in groups exposed to higher radiation doses. The results were fitted to various equations relating leukemia incidence to radiation dose, using both the raw data and data corrected for cumulative mouse-days at risk. The calculated RBE values for tritium beta rays compared to X rays ranged from 1.0 +/- 0.5 to 1.3 +/- 0.3. A best estimate of the RBE for this experiment was about 1.2 +/- 0.3. A wR value of 1 would thus appear to be more appropriate than a wR of 2 for tritium beta rays.

Effect of x rays and neutrons on repair and regeneration in the rat spinal cord

International Nuclear Information System (INIS)

van der Kogel, A.J.; Sissingh, H.A.; Zoetelief, J.

1982-01-01

Clinical and experimental results of neutron irradiation have shown higher RBE values for the central nervous system (CNS) than for most other normal tissues. This is because of a considerable impairment of a large capacity of the CNS to repair subeffective damage induced by low LET radiation. Decreasing the dose per fraction of X rays increases the CNS tolerance significantly; this has no effect for neutrons. In the cervical spinal cord and the brain, two types of delayed damage can be described, so-called early and late. Different target cells are assumed to be involved, oligodendroglial cells in the early, and vascular endothelim in the late type. In the lumbar cord, the main lesion is nerve root necrosis, with the Schwann cell as the most probable target. These target cells show differences in response to X rays and neutrons, resulting in different RBE values. The highest RBE is obtained for cervical white matter necrosis. In addition to cellular repair of subeffective damage, long-term tissue regeneration is observed in the spinal cord, beginning at different times for the various types of damage. With neutrons, the rate of long-term regeneration is at least similar, or even more pronounced than for X rays

Effect of x rays and neutrons on repair and regeneration in the rat spinal cord

International Nuclear Information System (INIS)

Van der Kogel, A.J.; Sissingh, H.A.; Zoetelief, J.

1982-01-01

Clinical and experimental results of neutron irradiation have shown higher RBE values for the central nervous system (CNS) than for most other normal tissues. This is because of a considerable impairment of the large capacity of the CNS to repair subeffective damage induced by low LET radiation. Decreasing the dose per fraction of X rays increases the CNS tolerance significantly; this has no effect for neutrons. In the cervical spinal cord and the brain, two types of delayed damage can be described, so-called early and late. Different target cells are assumed to be involved, oligodendroglial cells in the early, and vascular endothelium in the late type. In the lumbar cord, the main lesion is nerve root necrosis, with the Schwann cell as the most probable target. These target cells show differences in response to X rays and neutrons, resulting in different RBE values. The highest RBE is obtained for cervical white matter necrosis. In addition to cellular repair of subeffective damage, long-term tissue regeneration is observed in the spinal cord, beginning at different times for the various types of damage. With neutrons, the rate of long-term regeneration is at least similar, or even more pronounced than for X rays

WE-FG-202-03: Quantitative CT-Based Analysis to Assess Lung Injury Following Proton Radiotherapy

International Nuclear Information System (INIS)

Underwood, T; Grassberger, C; Willers, H; MacDonald, S; Jimenez, R; Paganetti, H

2016-01-01

Purpose: Relative to photon alternatives, the increased dose-conformity associated with proton therapy is expected to reduce the extent of radiation-induced lung toxicity. However, analysis of follow-up data is yet to be published in this area. In this study we retrospectively analyzed late-phase HU changes for proton therapy cohorts of chest wall and lung patients. Methods: From our institution’s register of patients treated using double-scattered protons, all chest wall and stereotactic lung cases (treated 2011–2012 and 2008–2014 respectively) were initially considered. Follow-up CT data were accessible for 10 chest wall cases (prescribed 50.4 GyRBE in 28 fractions) and 16 lung cases (prescribed 42–50 GyRBE in 3–4 fractions). CT time-points ranged from 0.5–3.5 years post-treatment. Planning doses were recalculated using TOPAS Monte Carlo simulations and mapped onto the follow-up images using deformable registration. Excluding internal target volumes, changes in HU between each patient’s planning and follow-up CT(s) were evaluated for dose bins of 2–30 GyRBE (2 GyRBE increments). Results: Linear increases in HU per unit dose, with correlations statistically significant at the 1% level (one-sided Spearman’s rank test), were evident for all 10 chest wall cases and 14/16 lung cases. The mean changes in HU/Gy were: 1.76 (SD=0.73) for the chest wall cohort, and 1.40 (SD=0.87) for the lung cohort. The median scan times post treatment were 21 and 12 months respectively. All 26 patients developed solid consolidation (scar-like radiographic opacities) within the exposed lung(s). Conclusion: Analysis of follow-up CTs revealed statistically significant correlations in HU-change/dose for two proton cohorts (lung and chest wall). Quantitatively, the late-phase changes we report broadly match published photon data. Further analysis of such radiographic changes, particularly via matched cohort studies drawing upon consistent imaging protocols, could play an

In vitro evaluation of {sup 213}Bi-rituximab versus external gamma irradiation for the treatment of B-CLL patients: relative biological efficacy with respect to apoptosis induction and chromosomal damage

Energy Technology Data Exchange (ETDEWEB)

Vandenbulcke, Katia; Lahorte, Christophe; Slegers, Guido [Department of Radiopharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, 9000, Gent (Belgium); De Vos, Filip; Dierckx, Rudi A. [Division of Nuclear Medicine, Ghent University Hospital (Belgium); Offner, Fritz [Department of Hematology, Ghent University Hospital (Belgium); Philippe, Jan [Department of Clinical Chemistry, Ghent University Hospital (Belgium); Apostolidis, Christos; Molinet, Roger; Nikula, Tuomo K. [European Commission, Joint Research Centre, Institute for Transuranium Elements, Karlsruhe (Germany); Bacher, Klaus; De Gelder, Virginie; Vral, Anne; Thierens, Hubert [Department of Anatomy, Embryology, Histology and Medical Physics, Ghent University (Belgium)

2003-10-01

External source radiotherapy and beta radioimmunotherapy (RIT) are effective treatments for lymphoid malignancies. The development of RIT with alpha emitters is attractive because of the high linear energy transfer (LET) and short path length, allowing higher tumour cell kill and lower toxicity to healthy tissues. We assessed the relative biological efficacy (RBE) of alpha RIT (in vitro) compared to external gamma irradiation with respect to induction of apoptosis in B chronic lymphocytic leukaemia (B-CLL) and induction of chromosomal damage in healthy donor B and T lymphocytes. The latter was measured by a micronucleus assay. {sup 213}Bi was eluted from a {sup 225}Ac generator and conjugated to CD20 antibody (rituximab) with CHX-A''-DTPA as a chelator. B-CLL cells from five patients were cultured for 24 h in RPMI/10% FCS while exposed to {sup 213}Bi conjugated to CD20 antibody or after external {sup 60}Co gamma irradiation. Binding assays were performed in samples of all patients to calculate the total absorbed dose. Apoptosis was scored by flow cytometric analyses of the cells stained with annexin V-FITC and 7-AAD. Apoptosis was expressed as % excess over spontaneous apoptosis in control. Full dose range experiments demonstrated {sup 213}Bi-conjugated CD20 antibody to be more effective than equivalent doses of external gamma irradiation, but showed that similar plateau values were reached at 10 Gy. The RBE for induction of apoptosis in B-CLL was 2 between 1.5 and 7 Gy. The micronucleus yield in lymphocytes of healthy volunteers was measured to assess the late toxicity caused by induction of chromosomal instability. While gamma radiation induced a steady increase in micronucleus yields in B and T cells, the damage induced by {sup 213}Bi was more dramatic, with RBE ranging from 5 to 2 between 0.1 Gy and 2 Gy respectively. In contrast to gamma irradiation, {sup 213}Bi inhibited mitogen-stimulated mitosis almost completely at 2 Gy. In conclusion, high

Influence of Residual Tumor Volume and Radiation Dose Coverage in Outcomes for Clival Chordoma

Energy Technology Data Exchange (ETDEWEB)

McDonald, Mark W., E-mail: markmcdonaldmd@gmail.com [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana (United States); Indiana University Health Proton Therapy Center, Bloomington, Indiana (United States); Linton, Okechukwu R. [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana (United States); Moore, Michael G.; Ting, Jonathan Y. [Department of Otolaryngology, Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, Indiana (United States); Cohen-Gadol, Aaron A.; Shah, Mitesh V. [Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, Indiana (United States); Goodman Campbell Brain and Spine, Indianapolis, Indiana (United States)

2016-05-01

Purpose: The purpose of this study was to evaluate factors associated with tumor control in clival chordomas. Methods and Materials: A retrospective review of 39 patients treated with surgery and proton therapy for clival chordomas between 2004 and 2014 was performed. The median prescribed dose was 77.4 Gy (relative biological effectiveness [RBE]); range was 70.2-79.2 Gy (RBE). Minimum and median doses to gross tumor volume (GTV), radiation dose received by 1 cm{sup 3} of GTV (D1cm{sup 3}), and the equivalent uniform dose were calculated. Receiver operating characteristics curves evaluated the predictive sensitivity and specificity for local failure of potential cutpoint values for GTV and D1cm{sup 3}. Results: After a median follow-up of 51 months, the 5-year estimate of local control (LC) was 69.6% (95% confidence interval [CI] 50.0%-89.2%), and overall survival (OS) was 81.4% (95% CI: 65.3%-97.5%). Tumor histology, GTV at the time of radiation, and prescribed radiation dose were significantly associated with local control on multivariate analysis, whereas D1cm{sup 3} was associated with overall survival. Compared to those patients whose conditions remained controlled, patients experiencing tumor failure had statistically significant larger GTVs and lower D1cm{sup 3}, and prescribed and median doses to GTV. A subset of 21 patients with GTV of ≤20 cm{sup 3} and D1cm{sup 3} of >67 Gy (RBE) had a median follow-up of 47 months. The 5-year estimate of local control in this subset was 81.1% (95% CI: 61.7%-100%; P=.004, overall comparison by GTV ≤20 cm{sup 3} stratified by D1cm{sup 3}). A D1cm{sup 3} of 74.5 Gy (RBE) had 80% sensitivity for local control and 60% specificity, whereas a GTV of 9.3 cm{sup 3} had 80% sensitivity for local control and 66.7% specificity. Conclusions: Local control of clival chordomas was associated with both smaller size of residual tumor and more complete high-dose coverage of residual tumor. Multidisciplinary care should seek

WE-FG-202-03: Quantitative CT-Based Analysis to Assess Lung Injury Following Proton Radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Underwood, T [Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); University College London, London (United Kingdom); Grassberger, C; Willers, H; MacDonald, S; Jimenez, R; Paganetti, H [Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States)

2016-06-15

Purpose: Relative to photon alternatives, the increased dose-conformity associated with proton therapy is expected to reduce the extent of radiation-induced lung toxicity. However, analysis of follow-up data is yet to be published in this area. In this study we retrospectively analyzed late-phase HU changes for proton therapy cohorts of chest wall and lung patients. Methods: From our institution’s register of patients treated using double-scattered protons, all chest wall and stereotactic lung cases (treated 2011–2012 and 2008–2014 respectively) were initially considered. Follow-up CT data were accessible for 10 chest wall cases (prescribed 50.4 GyRBE in 28 fractions) and 16 lung cases (prescribed 42–50 GyRBE in 3–4 fractions). CT time-points ranged from 0.5–3.5 years post-treatment. Planning doses were recalculated using TOPAS Monte Carlo simulations and mapped onto the follow-up images using deformable registration. Excluding internal target volumes, changes in HU between each patient’s planning and follow-up CT(s) were evaluated for dose bins of 2–30 GyRBE (2 GyRBE increments). Results: Linear increases in HU per unit dose, with correlations statistically significant at the 1% level (one-sided Spearman’s rank test), were evident for all 10 chest wall cases and 14/16 lung cases. The mean changes in HU/Gy were: 1.76 (SD=0.73) for the chest wall cohort, and 1.40 (SD=0.87) for the lung cohort. The median scan times post treatment were 21 and 12 months respectively. All 26 patients developed solid consolidation (scar-like radiographic opacities) within the exposed lung(s). Conclusion: Analysis of follow-up CTs revealed statistically significant correlations in HU-change/dose for two proton cohorts (lung and chest wall). Quantitatively, the late-phase changes we report broadly match published photon data. Further analysis of such radiographic changes, particularly via matched cohort studies drawing upon consistent imaging protocols, could play an

The relative biological effectiveness of radiations of different quality

International Nuclear Information System (INIS)

Anon.

1990-01-01

This paper is a review of the literature relevant to the selection of relative biological effectiveness (RBE) values for use in arriving at values of the quality factor (Q). Emphasis is placed on response to small ( M . In a wide variety of systems, the RBE M for fast (fission) neutrons, with low doses and dose rates, appears to be of the order of 20 or more compared to moderately filtered 250 kVp x rays and 40 or more compared to higher energy gamma rays. These values, which are much larger than those observed with large doses delivered at high dose rates, are due mainly, but not entirely, to a decrease in the slope of the curve for the ow-LET reference radiation at low dose

Late biological effects in the lung of C3H inbred mice following exposure to fast neutrons and 60Co-γ-rays

International Nuclear Information System (INIS)

Magdon, E.

1980-01-01

Histological changes in the lung tissue following local irradiation of the thorax of C 3 H inbred mice were analyzed. The investigation was continued up to 500 d following irradiation with 2 - 8 Gy neutrons and 4 - 30 Gy 60 Co γ-rays, respectively. The study revealed a clear dose dependence and higher effectivity of fast neutrons as to the late effects of the lungs. An increase of the portion of affected connective tissue in the lung was demonstrable already after a dose of 2.5 Gy neutrons and 5 Gy 60 Co γ-rays, respectively. The RBE of fast neutrons for late biological effects on the lung is discussed in connection with previous findings for the RBE of acute effects on tumor and normal tissue. (author)

The relative biological effectiveness of fractionated doses of fast neutrons (42 MeV sub d yields Be ) for normal tissues. Pt. 3; Effects on lung function

Energy Technology Data Exchange (ETDEWEB)

Rezvani, M.; Hopewell, J.W.; Robbins, M.E.C.; Hamlet, R. (Churchill Hospital, Oxford (UK)); Barnes, D.W.H.; Sansom, J.M.; Adams, P.J.V. (Medical Research Council, Harwell (UK). Radiobiological Research Unit)

1990-11-01

The effect of single and fractionated doses of fast neutrons (42 MeV{sub d{yields}Bc}) on the early and late radiation responses of the pig lung have been assessed by the measurement of changes in lung function using a {sup 133}Xe washout technique. The results obtained for irradiation schedules with fast neutrons have been compared with those after photon irradiation. There was no statistically significant difference between the values for the relative biological effectiveness (RBE) for the early and late radiation response of the lung. The RBE of the neutron beam increased with decreasing size of dose/fraction with an upper limit value of 4.39 {plus minus} 0.94 for infinitely small X-ray doses per fraction. (author).

Relative biological effectiveness of protons and heavy particles

International Nuclear Information System (INIS)

Vyglenov, A.; Fedorenko, B.; Kabachenko, A.

1986-01-01

The genetic effectiveness was studied of protons (9 GeB/nuclon, 0,72 Gy/min), α-particles (4 GeB/nuclon, 0,9 Gy/min) and carbon ions (4 GeB/nuclon 0,36 Gy/min). The translocation yield in mouse spermatogonia was used as indicator of radiation-induced genetic injury. Reciprocal translocation were registered six months after the irradiation on spermatocytes in diakinesmetaphase I. Comparison was made with gamma-irradiated animals from 60 Co source with dose rate 1,44 Gy/min. The relative biological effectiveness (RBE) was determined by comparing the regression coefficients from the linear dose translocation yield dependency. The values of the RBE coefficients were 0.8, 0.9 and 1.2, accordingly for protons, α-particles and carbon ions

The ICRP opinion of the calculation of doses and risks associated with exposures to tritium

International Nuclear Information System (INIS)

Paquetla, F.; Harrison, J.

2009-01-01

As the management of exposures to tritium, just like for other radionuclides, relies on the effective dose calculation, it also requires the application of coefficients to take the variety of radiations and the sensitivity of the different irradiated tissues into account. The authors discuss the determination and the use of the weighting factor (Wr) which reflects the relative biological effectiveness (RBE) of different types of radiation. They outline that some researchers asked for a review of this factor, and that the RBE is related to several parameters. All this and other issues entail uncertainties. The authors then give the opinion of the ICRP on this issue and notably for the assessment of the individual risk of cancer after exposure to tritium

The effect of energy spectrum change on DNA damage in and out of field in 10-MV clinical photon beams.

Science.gov (United States)

Ezzati, A O; Xiao, Y; Sohrabpour, M; Studenski, M T

2015-01-01

The aim of this study was to quantify the DNA damage induced in a clinical megavoltage photon beam at various depths in and out of the field. MCNPX was used to simulate 10 × 10 and 20 × 20 cm(2) 10-MV photon beams from a clinical linear accelerator. Photon and electron spectra were collected in a water phantom at depths of 2.5, 12.5 and 22.5 cm on the central axis and at off-axis points out to 10 cm. These spectra were used as an input to a validated microdosimetric Monte Carlo code, MCDS, to calculate the RBE of induced DSB in DNA at points in and out of the primary radiation field at three depths. There was an observable difference in the energy spectra for photons and electrons for points in the primary radiation field and those points out of field. In the out-of-field region, the mean energy for the photon and electron spectra decreased by a factor of about six and three from the in-field mean energy, respectively. Despite the differences in spectra and mean energy, the change in RBE was photon and electron spectra, these changes do not correlate with a change in RBE in a clinical MV photon beam as the electron spectra are dominated by electrons with energies >20 keV.

Extension of TOPAS for the simulation of proton radiation effects considering molecular and cellular endpoints

International Nuclear Information System (INIS)

Polster, Lisa; Schuemann, Jan; Rinaldi, Ilaria; McNamara, Aimee L; Paganetti, Harald; Burigo, Lucas; Stewart, Robert D; Attili, Andrea; Carlson, David J; Sato, Tatsuhiko; Ramos Méndez, José; Faddegon, Bruce; Perl, Joseph

2015-01-01

The aim of this work is to extend a widely used proton Monte Carlo tool, TOPAS, towards the modeling of relative biological effect (RBE) distributions in experimental arrangements as well as patients.TOPAS provides a software core which users configure by writing parameter files to, for instance, define application specific geometries and scoring conditions. Expert users may further extend TOPAS scoring capabilities by plugging in their own additional C++ code. This structure was utilized for the implementation of eight biophysical models suited to calculate proton RBE. As far as physics parameters are concerned, four of these models are based on the proton linear energy transfer, while the others are based on DNA double strand break induction and the frequency-mean specific energy, lineal energy, or delta electron generated track structure. The biological input parameters for all models are typically inferred from fits of the models to radiobiological experiments.The model structures have been implemented in a coherent way within the TOPAS architecture. Their performance was validated against measured experimental data on proton RBE in a spread-out Bragg peak using V79 Chinese Hamster cells.This work is an important step in bringing biologically optimized treatment planning for proton therapy closer to the clinical practice as it will allow researchers to refine and compare pre-defined as well as user-defined models. (paper)

Long-term outcomes after proton therapy, with concurrent chemotherapy, for stage II–III inoperable non-small cell lung cancer

International Nuclear Information System (INIS)

Nguyen, Quynh-Nhu; Ly, Ngoc Bui; Komaki, Ritsuko; Levy, Lawrence B.; Gomez, Daniel R.; Chang, Joe Y.; Allen, Pamela K.; Mehran, Reza J.; Lu, Charles; Gillin, Michael; Liao, Zhongxing; Cox, James D.

2015-01-01

Purpose: We report long-term disease control, survival, and toxicity for patients with locally advanced non-small cell lung cancer prospectively treated with concurrent proton therapy and chemotherapy on a nonrandomized case-only observational study. Methods: All patients received passive-scatter proton therapy, planned with 4D-CT–based simulation; all received proton therapy concurrent with weekly chemotherapy. Endpoints were local and distant control, disease-free survival (DFS), and overall survival (OS). Results: The 134 patients (21 stage II, 113 stage III; median age 69 years) had a median gross tumor volume (GTV) of 70 cm 3 (range, 5–753 cm 3 ); 77 patients (57%) received 74 Gy(RBE), and 57 (42%) received 60–72 Gy(RBE) (range, 60–74.1 Gy(RBE)). At a median follow-up time of 4.7 years, median OS times were 40.4 months (stage II) and 30.4 months (stage III). Five-year DFS rates were 17.3% (stage II) and 18.0% (stage III). OS, DFS, and local and distant control rates at 5 years did not differ by disease stage. Age and GTV were related to OS and DFS. Toxicity was tolerable, with 1 grade 4 esophagitis and 16 grade 3 events (2 pneumonitis, 6 esophagitis, 8 dermatitis). Conclusion: This report of outcomes after proton therapy for 134 patients indicated that this regimen produced excellent OS with tolerable toxicity

Spot-Scanning Proton Radiation Therapy for Pediatric Chordoma and Chondrosarcoma: Clinical Outcome of 26 Patients Treated at Paul Scherrer Institute

Energy Technology Data Exchange (ETDEWEB)

Rombi, Barbara [Center for Proton Therapy, Paul Scherrer Institute, Villigen (Switzerland); ATreP (Provincial Agency for Proton Therapy), Trento (Italy); Ares, Carmen, E-mail: carmen.ares@psi.ch [Center for Proton Therapy, Paul Scherrer Institute, Villigen (Switzerland); Hug, Eugen B. [Center for Proton Therapy, Paul Scherrer Institute, Villigen (Switzerland); ProCure Proton Therapy Center, Somerset, New Jersey (United States); Schneider, Ralf; Goitein, Gudrun; Staab, Adrian; Albertini, Francesca; Bolsi, Alessandra; Lomax, Antony J. [Center for Proton Therapy, Paul Scherrer Institute, Villigen (Switzerland); Timmermann, Beate [Center for Proton Therapy, Paul Scherrer Institute, Villigen (Switzerland); WestGerman Proton Therapy Center Essen (Germany)

2013-07-01

Purpose: To evaluate the clinical results of fractionated spot-scanning proton radiation therapy (PT) in 26 pediatric patients treated at Paul Scherrer Institute for chordoma (CH) or chondrosarcoma (CS) of the skull base or axial skeleton. Methods and Materials: Between June 2000 and June 2010, 19 CH and 7 CS patients with tumors originating from the skull base (17) and the axial skeleton (9) were treated with PT. Mean age at the time of PT was 13.2 years. The mean prescribed dose was 74 Gy (relative biological effectiveness [RBE]) for CH and 66 Gy (RBE) for CS, at a dose of 1.8-2.0 Gy (RBE) per fraction. Results: Mean follow-up was 46 months. Actuarial 5-year local control (LC) rates were 81% for CH and 80% for CS. Actuarial 5-year overall survival (OS) was 89% for CH and 75% for CS. Two CH patients had local failures: one is alive with evidence of disease, while the other patient succumbed to local recurrence in the surgical pathway. One CS patient died of local progression of the disease. No high-grade late toxicities were observed. Conclusions: Spot-scanning PT for pediatric CH and CS patients resulted in excellent clinical outcomes with acceptable rates of late toxicity. Longer follow-up time and larger cohort are needed to fully assess tumor control and late effects of treatment.

Analysis of the radiation related morbidity observed in a randomized trial of neutron therapy for bladder cancer

International Nuclear Information System (INIS)

Duncan, W.; Williams, J.R.; Kerr, G.R.; Arnott, S.J.; Quilty, P.M.; Rodger, A.; MacDougall, R.H.; Jack, W.J.

1986-01-01

This report is an analysis of the morbidity in the bladder and bowel observed in a randomized trial of d(15)+Be neutrons versus megavoltage photons in the treatment of bladder cancer. Acute reactions in the bladder and bowel were significantly worse after photon therapy. Of the patients treated with photons 45.7% had severe reactions in the bladder compared with 10.6% after neutron therapy (p less than 0.001). Severe acute bowel reactions were observed in 8.5% of the patients after photon therapy compared with 3.8% after neutron therapy (p less than 0.05). Late reactions were significantly worse after neutrons. Severe late reactions in the bladder were seen in 58.5% of patients after neutron therapy and in 40.5% after photon therapy (p less than 0.05). In the bowel they were observed in 53.3% of patients after neutron therapy compared with 8% after photon therapy (p less than 0.0001). The disparity in the degree of early and late complications makes assessment of RBE values difficult. It is estimated that for bladder morbidity the RBE value, for photon dose fractions of 2.75 Gy, is less than 3.3 for early reactions and equal to 3.4 for late effects. The respective RBE values for early and late effects in the bowel are less than 3.4 and 3.8

Feasibility of Proton Beam Therapy for Ocular Melanoma Using a Novel 3D Treatment Planning Technique

Energy Technology Data Exchange (ETDEWEB)

Hartsell, William F., E-mail: whartsell@chicagocancer.org [Northwestern Medicine Chicago Proton Center, Proton Collaborative Group, Warrenville, Illinois (United States); Kapur, Rashmi [Retina Consultants, Des Plaines, Illinois (United States); Hartsell, Siobhan O' Connor; Sweeney, Patrick [Northwestern Medicine Chicago Proton Center, Warrenville, Illinois (United States); Lopes, Caitlin [Rush Medical College, Chicago, Illinois (United States); Duggal, Amanda [Northwestern Medicine Chicago Proton Center, Warrenville, Illinois (United States); Cohen, Jack [Department of Ophthalmology, Rush University, Chicago, Illinois (United States); Chang, John [Northwestern Medicine Chicago Proton Center, Proton Collaborative Group, Warrenville, Illinois (United States); Polasani, Rajeev S. [Northwestern Medicine Central DuPage Hospital, Winfield, Illinois (United States); Dunn, Megan [Northwestern Medicine Chicago Proton Center, Proton Collaborative Group, Warrenville, Illinois (United States); Pankuch, Mark [Northwestern Medicine Chicago Proton Center, Proton Collaborative Group, Warrenville, Illinois (United States)

2016-05-01

Purpose: We evaluated sparing of normal structures using 3-dimensional (3D) treatment planning for proton therapy of ocular melanomas. Methods and Materials: We evaluated 26 consecutive patients with choroidal melanomas on a prospective registry. Ophthalmologic work-up included fundoscopic photographs, fluorescein angiography, ultrasonographic evaluation of tumor dimensions, and magnetic resonance imaging of orbits. Three tantalum clips were placed as fiducial markers to confirm eye position for treatment. Macula, fovea, optic disc, optic nerve, ciliary body, lacrimal gland, lens, and gross tumor volume were contoured on treatment planning compute tomography scans. 3D treatment planning was performed using noncoplanar field arrangements. Patients were typically treated with 3 fields, with at least 95% of planning target volume receiving 50 GyRBE in 5 fractions. Results: Tumor stage was T1a in 10 patients, T2a in 10 patients, T2b in 1 patient, T3a in 2 patients, T3b in 1 patient, and T4a in 2 patients. Acute toxicity was mild. All patients completed treatment as planned. Mean optic nerve dose was 10.1 Gy relative biological effectiveness (RBE). Ciliary body doses were higher for nasal (mean: 11.4 GyRBE) than temporal tumors (5.8 GyRBE). Median follow-up was 31 months (range: 18-40 months). Six patients developed changes which required intraocular bevacizumab or corticosteroid therapy, but only 1 patient developed neovascular glaucoma. Five patients have since died: 1 from metastatic disease and 4 from other causes. Two patients have since required enucleation: 1 due to tumor and 1 due to neovascular glaucoma. Conclusions: 3D treatment planning can be used to obtain appropriate coverage of choroidal melanomas. This technique is feasible with relatively low doses to anterior structures, and appears to have acceptable rates of local control with low risk of enucleation. Further evaluation and follow-up is needed to determine optimal dose-volume relationships for

SU-F-T-189: Dosimetric Comparison of Spot-Scanning Proton Therapy Techniques for Liver Tumors Close to the Skin Surface

International Nuclear Information System (INIS)

Takao, S; Matsuzaki, Y; Matsuura, T; Umegaki, K; Fujii, Y; Fujii, T; Katoh, N; Shimizu, S; Shirato, H

2016-01-01

Purpose: Spot-scanning technique has been utilized to achieve conformal dose distribution to large and complicated tumors. This technique generally does not require patient-specific devices such as aperture and compensator. The commercially available spot-scanning proton therapy (SSPT) systems, however, cannot deliver proton beams to the region shallower than 4 g/cm2. Therefore some range compensation device is required to treat superficial tumors with SSPT. This study shows dosimetric comparison of the following treatment techniques: (i) with a tabletop bolus, (ii) with a nozzle-mounted applicator, and (iii) without any devices and using intensity-modulated proton therapy (IMPT) technique. Methods: The applicator composed of a combination of a mini-ridge filter and a range shifter has been manufactured by Hitachi, Ltd., and the tabletop bolus was made by .decimal, Inc. Both devices have been clinically implemented in our facility. Three patients with liver tumors close to the skin surface were examined in this study. Each treatment plan was optimized so that the prescription dose of 76 Gy(RBE) or 66 Gy(RBE) would be delivered to 99% of the clinical target volume in 20 fractions. Three beams were used for tabletop bolus plan and IMPT plan, whereas two beams were used in the applicator plan because the gantry angle available was limited due to potential collision to patient and couch. The normal liver, colon, and skin were considered as organs at risk (OARs). Results: The target heterogeneity index (HI = D_5/D_9_5) was 1.03 on average in each planning technique. The mean dose to the normal liver was considerably less than 20 Gy(RBE) in all cases. The dose to the skin could be reduced by 20 Gy(RBE) on average in the IMPT plan compared to the applicator plan. Conclusion: It has been confirmed that all treatment techniques met the dosimetric criteria for the OARs and could be implemented clinically.

SU-F-T-189: Dosimetric Comparison of Spot-Scanning Proton Therapy Techniques for Liver Tumors Close to the Skin Surface

Energy Technology Data Exchange (ETDEWEB)

Takao, S; Matsuzaki, Y [Proton Beam Therapy Center, Hokkaido University Hospital, Sapporo, Hokkaido (Japan); Matsuura, T; Umegaki, K [Faculty of Engineering, Hokkaido University, Sapporo, Hokkaido (Japan); Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Hokkaido (Japan); Fujii, Y; Fujii, T [Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido (Japan); Katoh, N [Department of Radiation Oncology, Hokkaido University Hospital, Sapporo, Hokkaido (Japan); Shimizu, S; Shirato, H [Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Hokkaido (Japan); Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido (Japan)

2016-06-15

Purpose: Spot-scanning technique has been utilized to achieve conformal dose distribution to large and complicated tumors. This technique generally does not require patient-specific devices such as aperture and compensator. The commercially available spot-scanning proton therapy (SSPT) systems, however, cannot deliver proton beams to the region shallower than 4 g/cm2. Therefore some range compensation device is required to treat superficial tumors with SSPT. This study shows dosimetric comparison of the following treatment techniques: (i) with a tabletop bolus, (ii) with a nozzle-mounted applicator, and (iii) without any devices and using intensity-modulated proton therapy (IMPT) technique. Methods: The applicator composed of a combination of a mini-ridge filter and a range shifter has been manufactured by Hitachi, Ltd., and the tabletop bolus was made by .decimal, Inc. Both devices have been clinically implemented in our facility. Three patients with liver tumors close to the skin surface were examined in this study. Each treatment plan was optimized so that the prescription dose of 76 Gy(RBE) or 66 Gy(RBE) would be delivered to 99% of the clinical target volume in 20 fractions. Three beams were used for tabletop bolus plan and IMPT plan, whereas two beams were used in the applicator plan because the gantry angle available was limited due to potential collision to patient and couch. The normal liver, colon, and skin were considered as organs at risk (OARs). Results: The target heterogeneity index (HI = D{sub 5}/D{sub 95}) was 1.03 on average in each planning technique. The mean dose to the normal liver was considerably less than 20 Gy(RBE) in all cases. The dose to the skin could be reduced by 20 Gy(RBE) on average in the IMPT plan compared to the applicator plan. Conclusion: It has been confirmed that all treatment techniques met the dosimetric criteria for the OARs and could be implemented clinically.

Feasibility of Proton Beam Therapy for Ocular Melanoma Using a Novel 3D Treatment Planning Technique

International Nuclear Information System (INIS)

Hartsell, William F.; Kapur, Rashmi; Hartsell, Siobhan O'Connor; Sweeney, Patrick; Lopes, Caitlin; Duggal, Amanda; Cohen, Jack; Chang, John; Polasani, Rajeev S.; Dunn, Megan; Pankuch, Mark

2016-01-01

Purpose: We evaluated sparing of normal structures using 3-dimensional (3D) treatment planning for proton therapy of ocular melanomas. Methods and Materials: We evaluated 26 consecutive patients with choroidal melanomas on a prospective registry. Ophthalmologic work-up included fundoscopic photographs, fluorescein angiography, ultrasonographic evaluation of tumor dimensions, and magnetic resonance imaging of orbits. Three tantalum clips were placed as fiducial markers to confirm eye position for treatment. Macula, fovea, optic disc, optic nerve, ciliary body, lacrimal gland, lens, and gross tumor volume were contoured on treatment planning compute tomography scans. 3D treatment planning was performed using noncoplanar field arrangements. Patients were typically treated with 3 fields, with at least 95% of planning target volume receiving 50 GyRBE in 5 fractions. Results: Tumor stage was T1a in 10 patients, T2a in 10 patients, T2b in 1 patient, T3a in 2 patients, T3b in 1 patient, and T4a in 2 patients. Acute toxicity was mild. All patients completed treatment as planned. Mean optic nerve dose was 10.1 Gy relative biological effectiveness (RBE). Ciliary body doses were higher for nasal (mean: 11.4 GyRBE) than temporal tumors (5.8 GyRBE). Median follow-up was 31 months (range: 18-40 months). Six patients developed changes which required intraocular bevacizumab or corticosteroid therapy, but only 1 patient developed neovascular glaucoma. Five patients have since died: 1 from metastatic disease and 4 from other causes. Two patients have since required enucleation: 1 due to tumor and 1 due to neovascular glaucoma. Conclusions: 3D treatment planning can be used to obtain appropriate coverage of choroidal melanomas. This technique is feasible with relatively low doses to anterior structures, and appears to have acceptable rates of local control with low risk of enucleation. Further evaluation and follow-up is needed to determine optimal dose-volume relationships for

Logic Estimation of the Optimum Source Neutron Energy for BNCT of Brain Tumors

International Nuclear Information System (INIS)

Dorrah, M.A.; Gaber, F.A.; Abd Elwahab, M.A.; Kotb, M.A.; Mohammed, M.M.

2012-01-01

BNCT is very complicated technique; primarily due to the complexity of element composition of the brain. Moreover; numerous components contributes to the over all radiation dose both to normal brain and to tumor. Simple algebraic summation cannot be applied to these dose components, since each component should at first be weighed by its relative biological effectiveness (RBE) value. Unfortunately, there is no worldwide agreement on these RBE values. For that reason, the parameters required for accurate planning of BNCT of brain tumors located at different depths in brain remained obscure. The most important of these parameters is; the source neutron energy. Thermal neutrons were formerly employed for BNCT, but they failed to prove therapeutic efficacy. Later on; epithermal neutrons were suggested proposing that they would be enough thermalized while transporting in the brain tissues. However; debate aroused regarding the source neutrons energy appropriate for treating brain tumors located at different depths in brain. Again, the insufficient knowledge regarding the RBE values of the different dose components was a major obstacle. A new concept was adopted for estimating the optimum source neutrons energy appropriate for different circumstances of BNCT. Four postulations on the optimum source neutrons energy were worked out, almost entirely independent of the RBE values of the different dose components. Four corresponding condition on the optimum source neutrons energy were deduced. An energy escalation study was carried out investigating 65 different source neutron energies, between 0.01 eV and 13.2 MeV. MCNP4B Monte C arlo neutron transport code was utilized to study the behavior of neutrons in the brain. The deduced four conditions were applied to the results of the 65 steps of the neutron energy escalation study. A source neutron energy range of few electron volts (eV) to about 30 keV was estimated to be the most appropriate for BNCT of brain tumors located at

Linear Energy Transfer-Guided Optimization in Intensity Modulated Proton Therapy: Feasibility Study and Clinical Potential

Energy Technology Data Exchange (ETDEWEB)

Giantsoudi, Drosoula, E-mail: dgiantsoudi@partners.org [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Grassberger, Clemens; Craft, David; Niemierko, Andrzej; Trofimov, Alexei; Paganetti, Harald [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States)

2013-09-01

Purpose: To investigate the feasibility and potential clinical benefit of linear energy transfer (LET) guided plan optimization in intensity modulated proton therapy (IMPT). Methods and Materials: A multicriteria optimization (MCO) module was used to generate a series of Pareto-optimal IMPT base plans (BPs), corresponding to defined objectives, for 5 patients with head-and-neck cancer and 2 with pancreatic cancer. A Monte Carlo platform was used to calculate dose and LET distributions for each BP. A custom-designed MCO navigation module allowed the user to interpolate between BPs to produce deliverable Pareto-optimal solutions. Differences among the BPs were evaluated for each patient, based on dose–volume and LET–volume histograms and 3-dimensional distributions. An LET-based relative biological effectiveness (RBE) model was used to evaluate the potential clinical benefit when navigating the space of Pareto-optimal BPs. Results: The mean LET values for the target varied up to 30% among the BPs for the head-and-neck patients and up to 14% for the pancreatic cancer patients. Variations were more prominent in organs at risk (OARs), where mean LET values differed by a factor of up to 2 among the BPs for the same patient. An inverse relation between dose and LET distributions for the OARs was typically observed. Accounting for LET-dependent variable RBE values, a potential improvement on RBE-weighted dose of up to 40%, averaged over several structures under study, was noticed during MCO navigation. Conclusions: We present a novel strategy for optimizing proton therapy to maximize dose-averaged LET in tumor targets while simultaneously minimizing dose-averaged LET in normal tissue structures. MCO BPs show substantial LET variations, leading to potentially significant differences in RBE-weighted doses. Pareto-surface navigation, using both dose and LET distributions for guidance, provides the means for evaluating a large variety of deliverable plans and aids in

Linear Energy Transfer-Guided Optimization in Intensity Modulated Proton Therapy: Feasibility Study and Clinical Potential

International Nuclear Information System (INIS)

Giantsoudi, Drosoula; Grassberger, Clemens; Craft, David; Niemierko, Andrzej; Trofimov, Alexei; Paganetti, Harald

2013-01-01

Purpose: To investigate the feasibility and potential clinical benefit of linear energy transfer (LET) guided plan optimization in intensity modulated proton therapy (IMPT). Methods and Materials: A multicriteria optimization (MCO) module was used to generate a series of Pareto-optimal IMPT base plans (BPs), corresponding to defined objectives, for 5 patients with head-and-neck cancer and 2 with pancreatic cancer. A Monte Carlo platform was used to calculate dose and LET distributions for each BP. A custom-designed MCO navigation module allowed the user to interpolate between BPs to produce deliverable Pareto-optimal solutions. Differences among the BPs were evaluated for each patient, based on dose–volume and LET–volume histograms and 3-dimensional distributions. An LET-based relative biological effectiveness (RBE) model was used to evaluate the potential clinical benefit when navigating the space of Pareto-optimal BPs. Results: The mean LET values for the target varied up to 30% among the BPs for the head-and-neck patients and up to 14% for the pancreatic cancer patients. Variations were more prominent in organs at risk (OARs), where mean LET values differed by a factor of up to 2 among the BPs for the same patient. An inverse relation between dose and LET distributions for the OARs was typically observed. Accounting for LET-dependent variable RBE values, a potential improvement on RBE-weighted dose of up to 40%, averaged over several structures under study, was noticed during MCO navigation. Conclusions: We present a novel strategy for optimizing proton therapy to maximize dose-averaged LET in tumor targets while simultaneously minimizing dose-averaged LET in normal tissue structures. MCO BPs show substantial LET variations, leading to potentially significant differences in RBE-weighted doses. Pareto-surface navigation, using both dose and LET distributions for guidance, provides the means for evaluating a large variety of deliverable plans and aids in

Anatomical robust optimization to account for nasal cavity filling variation during intensity-modulated proton therapy: a comparison with conventional and adaptive planning strategies

Science.gov (United States)

van de Water, Steven; Albertini, Francesca; Weber, Damien C.; Heijmen, Ben J. M.; Hoogeman, Mischa S.; Lomax, Antony J.

2018-01-01

The aim of this study is to develop an anatomical robust optimization method for intensity-modulated proton therapy (IMPT) that accounts for interfraction variations in nasal cavity filling, and to compare it with conventional single-field uniform dose (SFUD) optimization and online plan adaptation. We included CT data of five patients with tumors in the sinonasal region. Using the planning CT, we generated for each patient 25 ‘synthetic’ CTs with varying nasal cavity filling. The robust optimization method available in our treatment planning system ‘Erasmus-iCycle’ was extended to also account for anatomical uncertainties by including (synthetic) CTs with varying patient anatomy as error scenarios in the inverse optimization. For each patient, we generated treatment plans using anatomical robust optimization and, for benchmarking, using SFUD optimization and online plan adaptation. Clinical target volume (CTV) and organ-at-risk (OAR) doses were assessed by recalculating the treatment plans on the synthetic CTs, evaluating dose distributions individually and accumulated over an entire fractionated 50 GyRBE treatment, assuming each synthetic CT to correspond to a 2 GyRBE fraction. Treatment plans were also evaluated using actual repeat CTs. Anatomical robust optimization resulted in adequate CTV doses (V95%  ⩾  98% and V107%  ⩽  2%) if at least three synthetic CTs were included in addition to the planning CT. These CTV requirements were also fulfilled for online plan adaptation, but not for the SFUD approach, even when applying a margin of 5 mm. Compared with anatomical robust optimization, OAR dose parameters for the accumulated dose distributions were on average 5.9 GyRBE (20%) higher when using SFUD optimization and on average 3.6 GyRBE (18%) lower for online plan adaptation. In conclusion, anatomical robust optimization effectively accounted for changes in nasal cavity filling during IMPT, providing substantially improved CTV and

TH-CD-209-06: LET-Based Adjustment of IMPT Plans Using Prioritized Optimization

Energy Technology Data Exchange (ETDEWEB)

Unkelbach, J; Giantsoudi, D; Paganetti, H [Massachusetts General Hospital, Boston, MA (United States); Botas, P [Massachusetts General Hospital, Boston, MA (United States); Heidelberg University, Heidelberg, DE (Germany); Qin, N; Jia, X [The University of Texas Southwestern Medical Ctr, Dallas, TX (United States)

2016-06-15

Purpose: In-vitro experiments suggest an increase in proton relative biological effectiveness (RBE) towards the end of range. However, proton treatment planning and dose reporting for clinical outcome assessment has been based on physical dose and constant RBE. Therefore, treatment planning for intensity-modulated proton therapy (IMPT) is unlikely to transition radically to pure RBE-based planning. We suggest a hybrid approach where treatment plans are initially created based on physical dose constraints and prescriptions, and are subsequently altered to avoid high linear energy transfer (LET) in critical structures while limiting the degradation of the physical dose distribution. Methods: To allow fast optimization based on dose and LET we extended a GPU-based Monte-Carlo code towards providing dose-averaged LET in addition to dose for all pencil beams. After optimizing an initial IMPT plan based on physical dose, a prioritized optimization scheme is used to modify the LET distribution while constraining the physical dose objectives to values close to the initial plan. The LET optimization step is performed based on objective functions evaluated for the product of physical dose and LET (LETxD). To first approximation, LETxD represents a measure of the additional biological dose that is caused by high LET. Regarding optimization techniques, LETxD has the advantage of being a linear function of the pencil beam intensities. Results: The method is applicable to treatments where serial critical structures with maximum dose constraint are located in or near the target. We studied intra-cranial tumors (high-grade meningiomas, base-of-skull chordomas) where the target (CTV) overlaps with the brainstem and optic structures. Often, high LETxD in critical structures can be avoided while minimally compromising physical dose planning objectives. Conclusion: LET-based re-optimization of IMPT plans represents a pragmatic approach to bridge the gap between purely physical dose

Stochastic basis for curve shape, RBE and temporal dependence

International Nuclear Information System (INIS)

Bond, V.P.

1982-01-01

This paper uses biophysical-microdosimetric quantities, measured in a physical surrogate or phantom cell, to explain the shape of absorbed dose-quantal cell response curves, the role of radiation quality and the influence of dose rate. Responses expected are explored first in simple autonomous cell systems, followed by increasingly-complex systems. Complications seen with increasingly-complex systems appear to be confined largely to the higher dose and dose rate ranges

Cancer risks and neutron RBE's from Hiroshima and Nagasaki

International Nuclear Information System (INIS)

Dobson, R.L.; Straume, T.

1982-01-01

The new radiation dose estimates for Hiroshima and Nagasaki are here combined with epidemiologic data from the A-bomb survivors and examined radiobiologically for compatability with other human and experimental data. The new doses show certain improvements over the original T65 doses. However, they suggest for chronic granulocytic leukemia, total malignancies, and chromosome aberrations, at neutron doses of 1 rad, RBEs in excess of 100, higher than expected from other findings. This and other indications suggest that either there are unrecognized systematic problems with the various radiobiological data, or the new doses are deficient in neutrons for Hiroshima, by a factor of about five. If in fact there were actually some 5-fold more dose from neutrons at Hiroshima than estimated by the new calculations, the RBEs would agree well with laboratory results, and other inconsistencies would largely disappear. Cancer risks are estimated for neutrons from the new doses and are compared with those estimated from radiobiologically reconciled doses (the new doses adjusted by adding approximately 5-fold more neutrons). The latter estimates appear more reasonable. For low-LET radiation, cancer risk estimates are altered very little by the new dose estimates for Nagasaki

Cancer risks and neutron RBE's from Hiroshima and Nagasaki

International Nuclear Information System (INIS)

Dobson, R.L.; Straume, T.

1982-01-01

The new radiation dose estimates for Hiroshima and Nagasaki are radiobiologically examined for compatability with other human and experimental data. The new doses show certain improvements over the original T65 doses. However, they suggest for chronic granulocytic leukemia, total malignancies, and chromosome aberrations, at neutron doses of 1 rad, RBEs in excess of 100, higher than expected from other findings. This and other indications suggest that either there are unrecognized systematic problems with the various radiobiological data, or the new doses are deficient in neutrons for Hiroshima, by a factor of about five. If in fact there were actually some 5-fold more dose from neutrons at Hiroshima than estimated by the new calculations, the RBEs would agree well with laboratory results, and other inconsistencies would largely disappear. Cancer risks are estimated for neutrons from the new doses and are compared with those estimated from radiobiologically reconciled doses (the new doses adjusted by adding approximately 5-fold more neutrons). The latter appear more reasonable. For low-LET radiation, cancer risk estimates are changed very little by the new dose estimates for Nagasaki

Unilateral irradiation of pigs in a mixed neutrons+gamma field. Early results

International Nuclear Information System (INIS)

Lemaitre, Guy; Maas, Jean.

1982-08-01

Pigs (16-20kg) were irradiated with 60 Co gamma or in a mixed field (neutron + gamma from the pulsed reactor SILENE). Pigs were unilaterally exposed by the left side. Each experimental group was composed of twelve animals and one control. Within the dose range explored (reference dose is mid-line tissue dose): 4-9.8 Gy of gamma rays only; 4.6 - 5.7 Gy of neutrons and gamma rays, pigs presented the haematopioetic form of the acute radiation sickness. At 5 Gy mixed field was more harmful than gamma rays only. Therefore the numerical value of neutron RBE (lethality 50 p cent within 30 days) is more than one. Experiments will be carried out in order to determine RBE values more accurately. Bone marrow dose will also be determined [fr

Some long-term effects of negative pions in mice exposed to partial body irradiation

International Nuclear Information System (INIS)

Coggle, J.E.

1977-01-01

The long-term effects of partial body exposure of one-day-old mice given either 60 Co γ rays or negative pions have been studied. Both radiations produced considerable life-shortening; for pions 6.8 +- 1.5% of life was lost per 100 rad and for γ rays the value was 5.7 +- 0.5% per 100 rad. The RBE of pions for ten weeks of life-shortening was about 1.3 compared with 60 Co γ rays, although at lower doses the RBE may be higher reaching about two for six weeks of life-shortening. The incidence rate of tumours at any particular age was greater in mice irradiated with pions at the peak and in those given higher doses of γ rays than in the controls. (author)

Efficacy and satisfaction rate comparing endometrial ablation by rollerball electrocoagulation to uterine balloon thermal ablation in a randomised controlled trial.

NARCIS (Netherlands)

Zon-Rabelink, I.A.A. van; Vleugels, M.P.; Merkus, J.M.W.M.; Graaf, R.M. de

2004-01-01

OBJECTIVE: To compare two methods of endometrial ablation, hysteroscopic rollerball electrocoagulation (RBE) and non-hysteroscopic uterine balloon thermal ablation (Thermachoice trade mark ), regarding efficacy for reducing dysfunctional uterine bleeding and patients satisfaction rate. METHODS: A

Endometrial ablation by rollerball electrocoagulation compared to uterine balloon thermal ablation. Technical and safety aspects.

NARCIS (Netherlands)

Zon-Rabelink, I.A.A. van; Vleugels, M.P.; Merkus, J.M.W.M.; Graaf, R.M. de

2003-01-01

OBJECTIVE: To compare two methods of endometrial ablation, hysteroscopic rollerball electrocoagulation (RBE) and non-hysteroscopic uterine balloon thermal (UBT) ablation (Thermachoice), regarding intra- and post-operative technical complications and safety aspects. STUDY DESIGN: A randomised

RBE of Monoenergetic Fast Neutrons: Cytogenetic Effects in Maize; EBR des Neutrons Rapides Monoenergeniques: Effets Cytogenetiques sur le Mais; Obeh monoehnergeticheskikh bystrykh nejtronov: tsitogeneticheskie izmeneniya u kukuruzy; EBR de los Neutrones Rapidos Monoenergeticos: Efectos Citogeneticos en el Maiz

Energy Technology Data Exchange (ETDEWEB)

Smith, H. H.; Bateman, J. L.; Quastler, H.; Rossi, H. H. [Biology and Medical Departments, Brookhaven National Laboratory, Upton, NY (United States)

1964-05-15

The maize used in these experiments has the advantage for RBE studies of yielding a basically first-order dose-response curve with low as well as with high LET radiations. An exposure apparatus was used which produced essentially equal dose rates in five rings of seeds placed so as to intercept neutrons of 0.43, 0.65, 1.00, 1.50 and 1.80 MeV. The mutant sectors produced in leaves are believed to be due mostly to simple chromosome breakage and deletion. Experiments were performed at dosages that gave responses which were linear, below saturation levels, and overlapping in range for the monoenergetic fast neutrons and 250 kVp X-rays. RBE values, calculated from relative slopes of linear-regression lines for neutrons and X-rays ranged from 42 to 135 with an overall average of about 70. Fast neutrons of 0.43 MeV energy were the most efficient, of those used, in producing g{sub 2} mutant sectors. (author) [French] Pour les etudes sur l'EBR, le maft utilise au cours des experiences offre l'avantage de donner une courbe dose-reponse qui est essentiellement de premier ordre, que le TLE du rayonnement soit faible ou eleve. Les auteurs ont utilise un appareil d'irradiation assurant des debits de dose pratiquement egaux dans cinq couronnes de semences disposees de maniere a intercepter les neutrons de 0,43, 0,65, 1,00, 1,50 et 1,80 MeV. On pense que les secteurs mutants produits dans les feuilles sont dus essentiellement a une rupture et une disparition de chromosomes simples. Les auteurs ont fait des experiences a des doses qui ont donne des reponses lineaires, inferieures au niveau de saturation et se chevauchant dans le cas des neutrons rapides et des rayons X de 250 kV-crete. Les valeurs de l'EBR calculees d'apres la comparaison des pentes des courbes de regression lineaire pour les neutrons et les rayons X varient de 42 a 135, avec une valeur moyenne d'environ 70. Parmi les neutrons utilises, les neutrons rapides de 0,43 MeV ont ete les plus efficaces pour produire des

Biological effectiveness of neutron irradiation on animals and man

Energy Technology Data Exchange (ETDEWEB)

Straume, T.

1982-11-01

Neutron experiments on a highly radiosensitive in vivo system - oocytes in mice - provide new insight into the nature of the radiosensitive targets of these important cells. With the radiobiological literature as background, neutron data from animals and humans are integrated, and the controversial question of radiation protection standards for neutrons is addressed. Oocyte killing in juvenile mice by 0.43-MeV, /sup 252/Cf-fission, and 15 MeV neutrons, compared with that by /sup 60/Co gamma rays, yields unusually low neutron RBEs (relative biological effectiveness). At 0.1 rad of 0.43-MeV neutrons the RBE is only 1.8, contrasting greatly with values of 100 or more reported at low-doses for other endpoints. In mice just prior to birth, however, when oocytes are less radiosensitive, the neutron RBE is much higher, similar to values for most other mammalian endpoints. This dramatic change in neutron RBE with mouse age (occurring within 2 to 3 days) can be explained as the result of a shift from a less radiosensitive target (presumably nuclear DNA) to a much more radiosensitive one (probably the oocyte plasma membrane). Using various approaches, a value for the neutron Quality Factor (Q, a radiation protection standard) is estimated as 17 (+-100%), much lower than 100 which has been suggested. With the large uncertainty, 17 is not markedly different from the value of 10 presently in general use.

Assessment of improved organ at risk sparing for meningioma: Light ion beam therapy as boost versus sole treatment option

International Nuclear Information System (INIS)

Mock, Ulrike; Georg, Dietmar; Sölkner, Lukas; Suppan, Christian; Vatnitsky, Stanislav M.; Flechl, Birgit; Mayer, Ramona; Dieckmann, Karin; Knäusl, Barbara

2014-01-01

Purpose: To compare photons, protons and carbon ions and their combinations for treatment of atypical and anaplastical skull base meningioma. Material and methods: Two planning target volumes (PTV initial /PTV boost ) were delineated for 10 patients (prescribed doses 50 Gy(RBE) and 10 Gy(RBE)). Plans for intensity modulated photon (IMXT), proton (IMPT) and carbon ion therapy ( 12 C) were generated assuming a non-gantry scenario for particles. The following combinations were compared: IMXT + IMXT/IMPT/ 12 C; IMPT + IMPT/ 12 C; and 12 C + 12 C. Plan quality was evaluated by target conformity and homogeneity (CI, HI), V 95% , D 2% and D 50% and dose-volume-histogram (DVH) parameters for organs-at-risk (OAR). If dose escalation was possible, it was performed until OAR tolerance levels were reached. Results: CI was worst for IMXT. HI < 0.05 ± 0.01 for 12 C was significantly better than for IMXT. For all treatment options dose escalation above 60 Gy(RBE) was possible for four patients, but impossible for six patients. Compared to IMXT + IMXT, ion beam therapy showed an improved sparing for most OARs, e.g. using protons and carbon ions D 50% was reduced by more than 50% for the ipsilateral eye and the brainstem. Conclusion: Highly conformal IMPT and 12 C plans could be generated with a non-gantry scenario. Improved OAR sparing favors both sole 12 C and/or IMPT plans

Stochastic E2F activation and reconciliation of phenomenological cell-cycle models.

Science.gov (United States)

Lee, Tae J; Yao, Guang; Bennett, Dorothy C; Nevins, Joseph R; You, Lingchong

2010-09-21

The transition of the mammalian cell from quiescence to proliferation is a highly variable process. Over the last four decades, two lines of apparently contradictory, phenomenological models have been proposed to account for such temporal variability. These include various forms of the transition probability (TP) model and the growth control (GC) model, which lack mechanistic details. The GC model was further proposed as an alternative explanation for the concept of the restriction point, which we recently demonstrated as being controlled by a bistable Rb-E2F switch. Here, through a combination of modeling and experiments, we show that these different lines of models in essence reflect different aspects of stochastic dynamics in cell cycle entry. In particular, we show that the variable activation of E2F can be described by stochastic activation of the bistable Rb-E2F switch, which in turn may account for the temporal variability in cell cycle entry. Moreover, we show that temporal dynamics of E2F activation can be recast into the frameworks of both the TP model and the GC model via parameter mapping. This mapping suggests that the two lines of phenomenological models can be reconciled through the stochastic dynamics of the Rb-E2F switch. It also suggests a potential utility of the TP or GC models in defining concise, quantitative phenotypes of cell physiology. This may have implications in classifying cell types or states.

Biological effectiveness of neutron irradiation on animals and man

International Nuclear Information System (INIS)

Straume, T.

1982-11-01

Neutron experiments on a highly radiosensitive in vivo system - oocytes in mice - provide new insight into the nature of the radiosensitive targets of these important cells. With the radiobiological literature as background, neutron data from animals and humans are integrated, and the controversial question of radiation protection standards for neutrons is addressed. Oocyte killing in juvenile mice by 0.43-MeV, 252 Cf-fission, and 15 MeV neutrons, compared with that by 60 Co gamma rays, yields unusually low neutron RBEs (relative biological effectiveness). At 0.1 rad of 0.43-MeV neutrons the RBE is only 1.8, contrasting greatly with values of 100 or more reported at low-doses for other endpoints. In mice just prior to birth, however, when oocytes are less radiosensitive, the neutron RBE is much higher, similar to values for most other mammalian endpoints. This dramatic change in neutron RBE with mouse age (occurring within 2 to 3 days) can be explained as the result of a shift from a less radiosensitive target (presumably nuclear DNA) to a much more radiosensitive one (probably the oocyte plasma membrane). Using various approaches, a value for the neutron Quality Factor (Q, a radiation protection standard) is estimated as 17 (+-100%), much lower than 100 which has been suggested. With the large uncertainty, 17 is not markedly different from the value of 10 presently in general use

Absorbed dose estimates to structures of the brain and head using a high-resolution voxel-based head phantom

International Nuclear Information System (INIS)

Evans, Jeffrey F.; Blue, Thomas E.; Gupta, Nilendu

2001-01-01

The purpose of this article is to demonstrate the viability of using a high-resolution 3-D head phantom in Monte Carlo N-Particle (MCNP) for boron neutron capture therapy (BNCT) structure dosimetry. This work describes a high-resolution voxel-based model of a human head and its use for calculating absorbed doses to the structures of the brain. The Zubal head phantom is a 3-D model of a human head that can be displayed and manipulated on a computer. Several changes were made to the original head phantom which now contains over 29 critical structures of the brain and head. The modified phantom is a 85x109x120 lattice of voxels, where each voxel is 2.2x2.2x1.4 mm 3 . This model was translated into MCNP lattice format. As a proof of principle study, two MCNP absorbed dose calculations were made (left and right lateral irradiations) using a uniformly distributed neutron disk source with an 1/E energy spectrum. Additionally, the results of these two calculations were combined to estimate the absorbed doses from a bilateral irradiation. Radiobiologically equivalent (RBE) doses were calculated for all structures and were normalized to 12.8 Gy-Eq. For a left lateral irradiation, the left motor cortex receives the limiting RBE dose. For a bilateral irradiation, the insula cortices receive the limiting dose. Among the nonencephalic structures, the parotid glands receive RBE doses that were within 15% of the limiting dose

EFFECTS OF A 4-WEEK ECCENTRIC TRAINING PROGRAM ON THE REPEATED BOUT EFFECT IN YOUNG ACTIVE WOMEN

Directory of Open Access Journals (Sweden)

Rodrigo Fernandez-Gonzalo

2011-12-01

Full Text Available The aim of this study was to analyze the responses of women to the repeated bout effect (RBE and to a short eccentric training program. Twenty-four young females were randomly assigned to a training group (TG, n = 14 or a control group (CG, n = 10. They performed two identical acute eccentric bouts (120 repetitions at 70% of 1RM in a leg-press device in an 8 weeks interval. TG followed a 4-week-eccentric-training program between the bouts. Maximal isometric contraction, range of motion, peak power and quadriceps muscle soreness were compared between and within groups before and after the two acute eccentric bouts. TG and CG presented significant losses of isometric strength and peak power, and an increment in soreness after the first bout. Isometric strength and peak power were recovered faster in CG after the second bout (p < 0.05 compared with TG, which showed a similar recovery of these parameters after the second bout compared with the first one. A decrease in soreness and a faster recovery of range of motion were found in TG (p < 0.05 following the second bout compared with the first one, but not in CG. Data indicate that a 4-week eccentric training program may prevent the RBE over those adaptations related with muscle damage (e.g. strength loss, but it may increase RBE impact on inflammatory processes (e.g. soreness.

Dependence of Early and Late Chromosomal Aberrations on Radiation Quality and Cell Types

Science.gov (United States)

Lu, Tao; Zhang, Ye; Krieger, Stephanie; Yeshitla, Samrawit; Goss, Rosalin; Bowler, Deborah; Kadhim, Munira; Wilson, Bobby; Rohde, Larry; Wu, Honglu

2017-01-01

Exposure to radiation induces different types of DNA damage, increases mutation and chromosome aberration rates, and increases cellular transformation in vitro and in vivo. The susceptibility of cells to radiation depends on genetic background and growth condition of cells, as well as types of radiation. Mammalian cells of different tissue types and with different genetic background are known to have different survival rate and different mutation rate after cytogenetic insults. Genomic instability, induced by various genetic, metabolic, and environmental factors including radiation, is the driving force of tumorigenesis. Accurate measurements of the relative biological effectiveness (RBE) is important for estimating radiation-related risks. To further understand genomic instability induced by charged particles and their RBE, we exposed human lymphocytes ex vivo, human fibroblast AG1522, human mammary epithelial cells (CH184B5F5/M10), and bone marrow cells isolated from CBA/CaH(CBA) and C57BL/6 (C57) mice to high energy protons and Fe ions. Normal human fibroblasts AG1522 have apparently normal DNA damage response and repair mechanisms, while mammary epithelial cells (M10) are deficient in the repair of DNA DSBs. Mouse strain CBA is radio-sensitive while C57 is radio-resistant. Metaphase chromosomes at different cell divisions after radiation exposure were collected and chromosome aberrations were analyzed as RBE for different cell lines exposed to different radiations at various time points up to one month post irradiation.

‘Survival’: a simulation toolkit introducing a modular approach for radiobiological evaluations in ion beam therapy

Science.gov (United States)

Manganaro, L.; Russo, G.; Bourhaleb, F.; Fausti, F.; Giordanengo, S.; Monaco, V.; Sacchi, R.; Vignati, A.; Cirio, R.; Attili, A.

2018-04-01

One major rationale for the application of heavy ion beams in tumour therapy is their increased relative biological effectiveness (RBE). The complex dependencies of the RBE on dose, biological endpoint, position in the field etc require the use of biophysical models in treatment planning and clinical analysis. This study aims to introduce a new software, named ‘Survival’, to facilitate the radiobiological computations needed in ion therapy. The simulation toolkit was written in C++ and it was developed with a modular architecture in order to easily incorporate different radiobiological models. The following models were successfully implemented: the local effect model (LEM, version I, II and III) and variants of the microdosimetric-kinetic model (MKM). Different numerical evaluation approaches were also implemented: Monte Carlo (MC) numerical methods and a set of faster analytical approximations. Among the possible applications, the toolkit was used to reproduce the RBE versus LET for different ions (proton, He, C, O, Ne) and different cell lines (CHO, HSG). Intercomparison between different models (LEM and MKM) and computational approaches (MC and fast approximations) were performed. The developed software could represent an important tool for the evaluation of the biological effectiveness of charged particles in ion beam therapy, in particular when coupled with treatment simulations. Its modular architecture facilitates benchmarking and inter-comparison between different models and evaluation approaches. The code is open source (GPL2 license) and available at https://github.com/batuff/Survival.

Radiosensitivity and repair capacity of two xenografted human soft tissue sarcomas to photons and fast neutrons

International Nuclear Information System (INIS)

Budach, V.; Stuschke, M.; Budach, W.; Krause, U.; Streffer, C.; Sack, H.

1989-01-01

The radiation response, the relative biological effectiveness (RBE) and sublethal damage repair of two xenografted human soft tissue sarcomas after single doses and fractionated irradiation with 60 Co and 5.8 MeV fast neutrons are presented. (author)

Present status and program of radiobiological tritium research in Japan

International Nuclear Information System (INIS)

Tazima, Y.

1981-01-01

Recent projects of the study on the biological effects of tritium in Japan, were reviewed. The investigations were about the behavior of tritium in food chain, i.e., intake to organ or tissue, retention, and distribution, and in genetic stage. As an example RBE studies on the induction of mutations in the silkworm and on transforming were described. Tritiated water was injected into wild type female pupae and radiation dose-rate was calculated from the radioactivity transmitted to the deposited eggs. γ-ray irradiation was carried out, in parallel, at approximately similar dose rates. RBE of THO for mutation fell between 1 and 2. The experiments with transforming principle of B. subtilis showed that the treatment of the bacterial spore with 3 H-glycelin or 3 H-water derived more inactive transformation with the decrease of the concentrations. (Nakanishi, T.)

Neutron-induced mutation experiments. Progress report, March 1, 1975--February 29, 1976

International Nuclear Information System (INIS)

Abrahamson, S.

1975-11-01

The relative mutagenic effectiveness of neutrons of different energies were compared with x radiation in mice and Drosophila oogonia employing X-linked recessive lethal and specific locus mutation tests. The energies and doses used were 0.68 MeV, 2 MeV, and 6 MeV (250 and 500 0 R), and 15 MeV (250, 500, and 1000 0 R). The data thus far collected from the recessive lethal test indicate that 0.68 MeV neutrons have the highest RBE among the energies tested, followed by 6 and 2 MeV. The specific locus mutation data also indicate the highest RBE for 0.68 MeV, followed respectively by 2 and 6 MeV. The 15 MeV data is as of now incompletely analyzed, as are some dose points of 2 and 6 MeV

Clonorchis sinensis granulin: identification, immunolocalization, and function in promoting the metastasis of cholangiocarcinoma and hepatocellular carcinoma.

Science.gov (United States)

Wang, Caiqin; Lei, Huali; Tian, Yanli; Shang, Mei; Wu, Yinjuan; Li, Ye; Zhao, Lu; Shi, Mengchen; Tang, Xin; Chen, Tingjin; Lv, Zhiyue; Huang, Yan; Tang, Xiaoping; Yu, Xinbing; Li, Xuerong

2017-05-25

Long-term infections by Clonorchis sinensis are associated with cholangitis, cholecystitis, liver fibrosis, cirrhosis, and even liver cancer. Molecules from the worm play vital roles in disease progress. In the present study, we identified and explored molecular characterization of C. sinensis granulin (CsGRN), a growth factor-like protein from C. sinensis excretory/secretory products (CsESPs). The encoding sequence and conserved domains of CsGRN were identified and analysed by bioinformatics tools. Recombinant CsGRN (rCsGRN) protein was expressed in Escherichia coli BL21 (DE3). The localisation of CsGRN in adult worms and Balb/c mice infected with C. sinensis was investigated by immunofluorescence and immunohistochemistry, respectively. Stable CsGRN-overexpressed cell lines of hepatoma cells (PLC-GRN cells) and cholangiocarcinoma cells (RBE-GRN cells) were constructed by transfection of eukaryotic expression plasmid of pEGFP-C1-CsGRN. The effects on cell migration and invasion of CsGRN were assessed through the wound-healing assay and transwell assay. The levels of matrix metalloproteinase 2 and 9 (MMP2 and MMP9) in PLC-GRN or RBE-GRN cells were detected by real-time PCR (qRT-PCR). The levels of E-cadherin, vimentin, N-cadherin, zona occludens proteins (ZO-1), β-catenin, phosphorylated ERK (p-ERK) and phosphorylated AKT (p-AKT) were analysed by Western blotting. CsGRN, including the conserved GRN domains, was confirmed to be a member of the granulin family. CsGRN was identified as an ingredient of CsESPs. CsGRN was localised in the tegument and testes of the adult worm. Furthermore, it appeared in the cytoplasm of hepatocytes and biliary epithelium cells from infected Balb/c mouse. The enhancement of cell migration and invasion of PLC-GRN and RBE-GRN cells were observed. In addition, CsGRN upregulated the levels of vimentin, N-cadherin, β-catenin, MMP2 and MMP9, while it downregulated the level of ZO-1 in PLC-GRN/RBE-GRN cells. In total proteins of liver tissue

Biological dose estimation for charged-particle therapy using an improved PHITS code coupled with a microdosimetric kinetic model

International Nuclear Information System (INIS)

Sato, Tatsuhiko; Watanabe, Ritsuko; Kase, Yuki; Niita, Koji; Sihver, Lembit

2009-01-01

High-energy heavy ions (HZE particles) have become widely used for radiotherapy of tumors owing to their high biological effectiveness. In the treatment planning of such charged-particle therapy, it is necessary to estimate not only physical but also biological dose, which is the product of physical dose and relative biological effectiveness (RBE). In the Heavy-ion Medical Accelerator in Chiba (HIMAC), the biological dose is estimated by a method proposed by Kanai et al., which is based on the linear-quadratic (LQ) model with its parameters α and β determined by the dose distribution in terms of the unrestricted linear energy transfer (LET). Thus, RBE is simply expressed as a function of LET in their model. However, RBE of HZE particles cannot be uniquely determined from their LET because of their large cross sections for high-energy δ-ray production. Hence, development of a biological dose estimation model that can explicitly consider the track structure of δ-rays around the trajectory of HZE particles is urgently needed. Microdosimetric quantities such as lineal energy y are better indexes for representing RBE of HZE particles in comparison to LET, since they can express the decrease of ionization densities around their trajectories due to the production of δ-rays. The difference of the concept between LET and y is illustrated in Figure 1. However, the use of microdosimetric quantities in computational dosimetry was severely limited because of the difficulty in calculating their probability densities (PDs) in macroscopic matter. We therefore improved the 3-dimensional particle transport simulation code PHITS, providing it with the capability of estimating the microdosimetric PDs in a macroscopic framework by incorporating a mathematical function that can instantaneously calculate the PDs around the trajectory of HZE particles with precision equivalent to a microscopic track-structure simulation. A new method for estimating biological dose from charged

Comparative study of G2 delay and survival after /sup 241/Americium-. cap alpha. and /sup 60/Cobalt-. gamma. irradiation

Energy Technology Data Exchange (ETDEWEB)

Luecke-Huhle, C.; Comper, W.; Hieber, L.; Pech, M.

1982-06-01

Survival and G2 delay following exposure to either /sup 60/Cobalt-..gamma..-rays or /sup 241/Americium-..cap alpha..-particles were studied in eight mammalian cell lines of human and animal origin including human fibroblasts from normal individuals and from patients with Ataxia telangiectasia or Fanconi's anemia. For both endpoints the effectiveness of alpha particle was greater as compared to ..gamma..-rays. RBE values for G2 delay (4.6-9.2) were in general comparable to RBE values derived from initial slopes of survival curves but higher compared to the ratio of mean inactivation doses. Ataxia cells were particularly sensitive to cell killing by ..gamma..-irradiation, however, showed average sensitivity to ..cap alpha..-particles of high LET. With the exception of Ataxia cells, cell killing and G2 delay seem to be related processes if individual cell cycle parameters are taken into account.

Development and performance evaluation of a dynamic phantom for biological dosimetry of moving targets

Science.gov (United States)

Gemmel, A.; Bert, C.; Saito, N.; von Neubeck, C.; Iancu, G.; K-Weyrather, W.; Durante, M.; Rietzel, E.

2010-06-01

A dynamic phantom has been developed to allow for measurement of 3D cell survival distributions and the corresponding distributions of the RBE-weighted dose (RBED) in the presence of motion. The phantom consists of two 96-microwell plates holding Chinese hamster ovary cells inside a container filled with culture medium and is placed on a movable stage. Basic biological properties of the phantom were investigated without irradiation and after irradiation with a carbon ion beam, using both a stationary (reference) exposure and exposure during motion of the phantom perpendicular to the beam with beam tracking. There was no statistically significant difference between plating efficiency measured in the microwells with and without motion (0.75) and values reported in the literature. Mean differences between measured and calculated cell survival for these two irradiation modes were within ±5% of the target dose of 6 Gy (RBE).

Differential gene expression in primary fibroblasts induced by proton and cobalt-60 beam irradiation

DEFF Research Database (Denmark)

Nielsen, Steffen; Bassler, Niels; Grzanka, Leszek

2017-01-01

profile: entrance, mid-SOBP and at the SOBP distal edge. Dose was delivered in three fractions × 3.5 Gy(RBE) (RBE 1.1). Cobalt-60 (Co-60) irradiation was used as reference. Real-time qPCR was performed to determine gene expression levels for 17 genes associated with inflammation response, fibrosis...... and angiogenesis. RESULTS: Differences in median gene expression levels were observed for multiple genes such as IL6, IL8 and CXCL12. Median IL6 expression was 30%, 24% and 47% lower in entrance, mid-SOBP and SOBP distal edge groups than in Co-60 irradiated cells. No genes were found to be oppositely regulated...... fibroblast cultures. Inflammatory factors were generally less extensively upregulated by proton irradiation compared with Co-60 photon irradiation. These effects may possibly influence the development of normal tissue damage in patients treated with proton beam therapy....

Cellular track model of biological damage to mammalian cell cultures from galactic cosmic rays

International Nuclear Information System (INIS)

Cucinotta, F.A.; Katz, R.; Wilson, J.W.; Townsend, L.W.; Nealy, J.E.; Shinn, J.L.

1991-02-01

The assessment of biological damage from the galactic cosmic rays (GCR) is a current interest for exploratory class space missions where the highly ionizing, high-energy, high-charge ions (HZE) particles are the major concern. The relative biological effectiveness (RBE) values determined by ground-based experiments with HZE particles are well described by a parametric track theory of cell inactivation. Using the track model and a deterministic GCR transport code, the biological damage to mammalian cell cultures is considered for 1 year in free space at solar minimum for typical spacecraft shielding. Included are the effects of projectile and target fragmentation. The RBE values for the GCR spectrum which are fluence-dependent in the track model are found to be more severe than the quality factors identified by the International Commission on Radiological Protection publication 26 and seem to obey a simple scaling law with the duration period in free space

Cytotoxicity of 125I decay in the DNA double strand break repair deficient mutant cell line, xrs-5

International Nuclear Information System (INIS)

Yasui, L.S.

1992-01-01

Survival of parental Chinese hamster ovary (CHO) K1 cells and the DNA double strand break (DSB) repair deficient mutant, xrs-5 was determined after accumulation of 125 I decays. Both CHO and xrs-5 cells were extremely sensitive to accumulated 125 I decays. D o values for CHO and xrs-5 cells were 40 and approximately 7 decays per cell, respectively. Difference in cell survival between CHO and xrs-5 cells was not due to differences in overall 125 IUdR incorporation, differences in labelling index (LI) or differences in plating efficiency (PE). Relative biological effectiveness (RBE) values calculated relative to 137 Cs gamma radiation survival values (D o and D 10 ) were higher in xrs-5 cells compared with CHO cells, although both CHO and xrs-5 cells have high RBE values that correspond to a high sensitivity of CHO and xrs-5 cells to 125 I decay. (Author)

Biokinetics of radioiodine (125I) during pre and post-natal development and the interference with the induction of developmental effects in the mouse brain

International Nuclear Information System (INIS)

Konermann, G.

1992-01-01

On day 13 post-conception, pregnant mice were injected with equal activities of either 125 I-sodium iodide or 5-( 125 I)-iodo-2-deoxyuridine in order to study the biokinetic behaviour in relation to the induction of developmental long-term damage to the brain. Brain weight, cortex diameters and alignment of cortical neurons were more affected by 125 I-IUdR (37-231 kBq.g -1 ) than by 125 I-NaI, consistent with decay sites within the DNA or mainly extranuclear sites, respectively. Dose calculations according to the MIRD scheme gave underestimates of the radiotoxicity, especially for the DNA bound 125 I. This is consistent with pronounced RBE effects derived from in vitro studies. The transfer of these RBE effects to the developing brain is, however, limited by the complex interference between the manifestation and compensation of damage within the prolonged response chains. (author)

Cellular track model of biological damage to mammalian cell cultures from galactic cosmic rays

Science.gov (United States)

Cucinotta, Francis A.; Katz, Robert; Wilson, John W.; Townsend, Lawrence W.; Nealy, John E.; Shinn, Judy L.

1991-01-01

The assessment of biological damage from the galactic cosmic rays (GCR) is a current interest for exploratory class space missions where the highly ionizing, high-energy, high-charge ions (HZE) particles are the major concern. The relative biological effectiveness (RBE) values determined by ground-based experiments with HZE particles are well described by a parametric track theory of cell inactivation. Using the track model and a deterministic GCR transport code, the biological damage to mammalian cell cultures is considered for 1 year in free space at solar minimum for typical spacecraft shielding. Included are the effects of projectile and target fragmentation. The RBE values for the GCR spectrum which are fluence-dependent in the track model are found to be more severe than the quality factors identified by the International Commission on Radiological Protection publication 26 and seem to obey a simple scaling law with the duration period in free space.

A Monte Carlo-based treatment-planning tool for ion beam therapy

CERN Document Server

Böhlen, T T; Dosanjh, M; Ferrari, A; Haberer, T; Parodi, K; Patera, V; Mairan, A

2013-01-01

Ion beam therapy, as an emerging radiation therapy modality, requires continuous efforts to develop and improve tools for patient treatment planning (TP) and research applications. Dose and fluence computation algorithms using the Monte Carlo (MC) technique have served for decades as reference tools for accurate dose computations for radiotherapy. In this work, a novel MC-based treatment-planning (MCTP) tool for ion beam therapy using the pencil beam scanning technique is presented. It allows single-field and simultaneous multiple-fields optimization for realistic patient treatment conditions and for dosimetric quality assurance for irradiation conditions at state-of-the-art ion beam therapy facilities. It employs iterative procedures that allow for the optimization of absorbed dose and relative biological effectiveness (RBE)-weighted dose using radiobiological input tables generated by external RBE models. Using a re-implementation of the local effect model (LEM), theMCTP tool is able to perform TP studies u...

Development and performance evaluation of a dynamic phantom for biological dosimetry of moving targets

Energy Technology Data Exchange (ETDEWEB)

Gemmel, A; Bert, C; Saito, N; Von Neubeck, C; Iancu, G; K-Weyrather, W; Durante, M; Rietzel, E, E-mail: alexander.ag.gemmel@siemens.co [GSI Helmholtzzentrum fuer Schwerionenforschung, Planckstr 1, 64291 Darmstadt (Germany)

2010-06-07

A dynamic phantom has been developed to allow for measurement of 3D cell survival distributions and the corresponding distributions of the RBE-weighted dose (RBED) in the presence of motion. The phantom consists of two 96-microwell plates holding Chinese hamster ovary cells inside a container filled with culture medium and is placed on a movable stage. Basic biological properties of the phantom were investigated without irradiation and after irradiation with a carbon ion beam, using both a stationary (reference) exposure and exposure during motion of the phantom perpendicular to the beam with beam tracking. There was no statistically significant difference between plating efficiency measured in the microwells with and without motion (0.75) and values reported in the literature. Mean differences between measured and calculated cell survival for these two irradiation modes were within {+-}5% of the target dose of 6 Gy (RBE).

Alpha-particles induce preneoplastic transformation of rat tracheal epithelial cells in culture

International Nuclear Information System (INIS)

Thomassen, D.G.; Seiler, F.A.; Shyr, L.-J.; Griffith, W.C.

1990-01-01

To characterize the potential role of high-l.e.t. radiation in respiratory carcinogenesis, the cytotoxic and transforming potency of 5.5 MeV α-particles from electroplated sources of 238 Pu were determined using primary cultures of rat tracheal epithelial cells. RBE for cell killing by α-particles versus X-rays varied with dose, and ranged between 4 and 1.5 for α doses in the range 0.2-4 Gy. At equally toxic doses (relative survival 0.18-0.2), all three agents induced similar frequencies of preneoplastic transformation. For preneoplastic transformation induced by doses of α- and X-radiations giving 80 per cent toxicity, an α RBE of 2.4 was derived. The similar RBEs for cell killing and for preneoplastic transformation suggest an association between the type or degree of radiation-induced damage responsible for both cell killing and cell transformation. (author)

Exercise Based- Pain Relief Program

DEFF Research Database (Denmark)

Zadeh, Mahdi Hossein

in the current study was to use exercise induced- muscle damage followed by ECC as an acute pain model and observe its effects on the sensitivity of the nociceptive system and blood supply in healthy subjects. Then, the effect of a repeated bout of the same exercise as a healthy pain relief strategy......Exercise-based pain management programs are suggested for relieving from musculoskeletal pain; however the pain experienced after unaccustomed, especially eccentric exercise (ECC) alters people´s ability to participate in therapeutic exercises. Subsequent muscle pain after ECC has been shown...... to cause localized pressure pain and hyperalgesia. A prior bout of ECC has been repeatedly reported to produce a protective adaptation known as repeated bout effect (RBE). One of the main scopes of the current project was to investigate the adaptations by which the RBE can be resulted from. The approach...

Clinical application of fast neutrons

International Nuclear Information System (INIS)

Battermann, J.J.

1981-01-01

The results of treatments and clinical experiments with neutrons (from a medical d+T neutron generator with an output of 10 12 neutrons per second) are reported and discussed. Data on RBE values are presented after single doses and multiple fractions of neutrons and 60 Co-gamma rays on pulmonary metastases. The results of pilot studies on head and neck tumours, brain tumours and pelvic tumours are discussed. The accuracy of the calculated dose is tested with some in-vivo experiments during neutron irradiation of the pelvis. Estimations of RBE values for tumour control, skin damage and intestinal damage after fractionated neutron therapy are dealt with and the results obtained in treatment of sarcomas are discussed. The preliminary results are given of some clinical trials in Amsterdam. Also some data from other centres are reviewed. From these data some remarks about the future of neutron therapy are made. (Auth.)

Effect of neutrons with an energy of 0.35 and 0.85 MeV and gamma radiation of 60Co on the organ cultures of the human bone marrow

International Nuclear Information System (INIS)

Zherbin, E.A.; Kolesnikova, A.I.; Konoplyannikov, A.G.; Khoptynskaya, S.K.; Obaturov, G.M.; Kapchigashev, S.P.

1979-01-01

A comparative study of the radiation injury of human hemopoietic cells under the effect of γ radiation of 60 Co in doses from 100 to 1500 rad, 0.85 MeV neutrons in doses from 50 to 600 rad and 0.35 MeV neutrons in doses from 30 to 600 rad was carried out using the method of organic cultivation of bone marrow. Under the effect of the above radiation types, the fissionable granulocytes (promyelocytes and myelocytes) and lymphocytes are most radiosensitive among the 4-day organic cultures. The dose dependence of the decrease in relative and absolute content of these cell forms in the cultures as well as the dose dependence of the decrease in total cell structure in the cultures were revealed. It has been found that the dose dependence for the above tests consists of two components: radiosensitive and radioresistant ones. The radiation doses causing death in 50% of cells in relation to control (D 50 ) were determined. On the bases of D 50 values, the coefficients of relative biological efficiency (RBE) were calculated for 0.85 and 0.35 MeV neutrons. The RBE coefficients are confined in the 1.4-3.4 and 2.4-6.7 intervals respectively. It has been confirmed that 0.35 MeV neutrons are 1.5-2 times more effective than 0.85 MeV neutrons. The coefficients of RBE neutrons calculated for radioresistant cell components are higher than the corresponding values estimated according to D 50 value; in some cases they reach values ranging from 6 to 10

Dose estimation of heavy ion beam by microdosimetry. Examination of the method to estimate biological effect from physical measurement of radiation quality

International Nuclear Information System (INIS)

Kase, Yuki; Sakama, Makoto; Tsuzuki, Daigo; Abe, Kyoko; Saotome, Naoya; Matsufuji, Naruhiro; Kanai, Tatsuaki; Matsumoto, Kouki; Furusawa, Yoshiya

2007-01-01

The absorbed dose (AD) of heavy ion (HI) beam (here, carbon beam) in HI therapy (unit, EGy) (D st ) to exert the actual clinical effect is for the irradiation of tumors deep in the body and is thus estimated by AD corrected with the relative biological effectiveness (RBE) of clinical endpoint: i.e., the relation is expressed by the equation RBE=D st /D rad | same-effect (D rad is AD of the reference X-ray to yield the same effect as the HI used for the intended clinical endpoint). This paper describes the process of the estimation in the title with consideration of depth dependences of AD of HI in accordance to Bragg curve, and of biological AD as determined by colony assay of human salivary gland tumor cells: in NIRS, the desired AD in HI therapy is calculated by multiplying 1.5 to physically measured AD of HI at RBE 10% (10% survival of the cells). This factor has been obtained by microdosimetry of Heavy Ion Medical Accelerator in Chiba (HIMAC) ions in NIRS with a small spherical proportional counter (LET-1/2, Far West Technology) of the diameter 1.27 cm having the tissue equivalent plastic wall and chamber filled with 4.4 kPa of propane-based gas to make the tissue-equivalence size 1.0 μm diameter. The measuring principle is based on the microdosimetric kinetic model reported previously. The calculated dose is found to agree with AD in HI therapeutic planning within 10% fluctuation. (R.T.)

Specification of carbon ion dose at the National Institute of Radiological Sciences (NIRS)

International Nuclear Information System (INIS)

Matsufuji, Naruhiro; Nakai, Tatsuaki; Kanematsu, Nobuyuki

2007-01-01

The clinical dose distributions of therapeutic carbon beams, currently used at National Institute of Radiological Sciences (NIRS) Heavy Ion Medical Accelerator in Chiba (HIMAC), are based on in-vitro Human Salivary Gland (HSG) cell survival response and clinical experience from fast neutron radiotherapy. Moderate radiosensitivity of HSG cells is expected to be a typical response of tumours to carbon beams. At first, the biological dose distribution is designed so as to cause a flat biological effect on HSG cells in the spread-out Bragg peak (SOBP) region. Then, the entire biological dose distribution is evenly raised in order to attain a RBE (relative biological effectiveness)=3.0 at a depth where dose-averaged LET (linear energy transfer) is 80 keV/μm. At that point, biological experiments have shown that carbon ions can be expected to have a biological effect identical to fast neutrons, which showed a clinical RBE of 3.0 for fast neutron radiotherapy at NIRS. The resulting clinical dose distribution in this approximation is not dependent on dose level, tumour type or fractionation scheme and thus reduces the unknown parameters in the analysis of the clinical results. The width SOBP and the clinical/physical dose at the center of SOBP specify the dose distribution. The clinical results analyzed in terms of tumor control probability (TCP) were found to show good agreement with the expected RBE value at higher TCP levels. The TCP analysis method was applied for the prospective dose estimation of hypofractionation. (author)

Neutrons and carcinogenesis: a cautionary tale

International Nuclear Information System (INIS)

Hall, E.J.

1996-01-01

The best estimates for radiation induced cancer and leukemia are based on the Japanese survivors of Hiroshima and Nagasaki. With the earlier dosimetry systems of the 1960's, it was possible to derive an RBE (relative biological effectiveness) for neutrons from the Japanese data, because it was thought that there was a significant neutron dose at Hiroshima compared with Nagasaki. The estimated RBE of about 20 was consistent with laboratory estimates for oncogenic transformation in vitro and tumors in animals. The revised dosimetry of the 1980's [DS 86] essentially eliminated the neutron component at Hiroshima, and consequently removed the only neutron RBE estimate based on human data. However, recent neutron activation measurements indicate that these may indeed have been thermal neutrons at Hiroshima, and measurements of the ratio of inter- to intra-chromosomal aberrations in peripheral lymphocytes of survivors also tend to indicate that the biologically effective dose was dominated by neutrons. Another area in which the large biological effectiveness of neutrons assumes importance is the production of photoneutrons in high energy medical linear accelerators (Linacs). An increasing number of accelerators operating in the 18 to 20 MV range are coming into routine clinical use and at this energy, photoneutrons generated largely in the collimators result in a total body dose to the patient. The increased risk of second malignancies must be balanced against the slight improvement in percentage depth doses compared with more conventional machines operating at to 10 MV, below the threshold for photoneutron production. (author)

The magnitude of muscle strain does not influence serial sarcomere number adaptations following eccentric exercise.

Science.gov (United States)

Butterfield, Timothy A; Herzog, Walter

2006-02-01

It is generally accepted that eccentric exercise, when performed by a muscle that is unaccustomed to that type of contraction, results in a delayed onset of muscle soreness (DOMS). A prolonged exposure to eccentric exercise leads to the disappearance of the signs and symptoms associated with DOMS, which has been referred to as the repeated bout effect (RBE). Although the mechanisms underlying the RBE remain unclear, several mechanisms have been proposed, including the serial sarcomere number addition following exercise induced muscle damage. In the traditional DOMS and RBE protocols, muscle injury has been treated as a global parameter, with muscle force and strain assumed to be uniform throughout the muscle. To assess the effects of muscle-tendon unit strain, fiber strain, torque and injury on serial sarcomere number adaptations, three groups of New Zealand White (NZW) rabbits were subjected to chronic repetitive eccentric exercise bouts of the ankle dorsiflexors for 6 weeks. These eccentric exercise protocols consisted of identical muscle tendon unit (MTU) strain, but other mechanical factors were systematically altered. Following chronic eccentric exercise, serial sarcomere number adaptations were not identical between the three eccentric exercise protocols, and serial sarcomere number adaptations were not uniform across all regions of the muscle. Peak torque and relaxation fiber strain were the best predictors of serial sarcomere number across all three protocols. Therefore, MTU strain does not appear to be the primary cause for sarcomerogenesis, and differential adaptations within the muscle may be explained by the nonuniform architecture of the muscle, resulting in differential local fiber strains.

Somatostatin-receptor-targeted α-emitting 213Bi is therapeutically more effective than β--emitting 177Lu in human pancreatic adenocarcinoma cells

International Nuclear Information System (INIS)

Nayak, Tapan K.; Norenberg, Jeffrey P.; Anderson, Tamara L.; Prossnitz, Eric R.; Stabin, Michael G.; Atcher, Robert W.

2007-01-01

Introduction: Advance clinical cancer therapy studies of patients treated with somatostatin receptor (sstr)-targeted [DOTA 0 -Tyr 3 ]octreotide (DOTATOC) labeled with low-linear-energy-transfer (LET) β - -emitters have shown overall response rates in the range of 15-33%. In order to improve outcomes, we sought to compare the therapeutic effectiveness of sstr-targeted high-LET α-emitting 213 Bi to that of low-LET β - -emitting 177 Lu by determining relative biological effectiveness (RBE) using the external γ-beam of 137 Cs as reference radiation. Methods: Sstr-expressing human pancreatic adenocarcinoma Capan-2 cells and A549 control cells were used for this study. The effects of different radiation doses of 213 Bi and 177 Lu labeled to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid and sstr-targeted DOTATOC were investigated with a clonogenic cell survival assay. Apoptosis was measured using the Cell Death Detection ELISA PLUS 10x kit. Results: Using equimolar DOTATOC treatment with concurrent irradiation with a 137 Cs source as reference radiation, the calculated RBE of [ 213 Bi]DOTATOC was 3.4, as compared to 1.0 for [ 177 Lu]DOTATOC. As measured in terms of absorbance units, [ 213 Bi]DOTATOC caused a 2.3-fold-greater release of apoptosis-specific mononucleosomes and oligonucleosomes than [ 177 Lu]DOTATOC at the final treatment time of 96 h (P 213 Bi]DOTATOC is therapeutically more effective in decreasing survival than is [ 177 Lu]DOTATOC in human pancreatic adenocarcinoma cells due to its comparatively higher RBE

Radiation biophysical studies with mammalian cells and a modulated carbon ion beam

International Nuclear Information System (INIS)

Chapman, J.D.; Blakely, E.A.; Smith, K.C.; Urtasun, R.C.; Lyman, J.T.; Tobias, C.A.

1978-01-01

Chinese hamster (V-79) and human kidney (T-1) cells were irradiated in stirred suspensions placed at various positions in the plateau and extended Bragg peak of a 400-MeV/amu carbon ion beam. The range of the ions was modulated by a lead (translational) ridge filter and a brass (spiral) ridge filter designed to produce extended peaks of approximately 4 and 10 cm, respectively. Stationary-phase and G 1 -phase populations of Chinese hamster cells were found to have different absolute radiosensitivities which, in turn, were different from that of asynchronous human kidney cells. The increase in relative biological effectiveness (RBE) observed as carbon ions were slowed down and stopped in water was similar for the three cell populations at doses greater than 400 rad. At lower doses the RBE was greater for the hamster cell populations than for the human kidney cells. The gain in RBE (at the 50% survival level) between the plateaus and the middle region of the extended peaks was approximately 2.0 and 1.7 for the 4- and 10-cm extended peaks, respectively. Oxygen enhancement ratios (OER) were determined at the 10% survival levels with stationary-phase populations of hamster cells. Values of 2.8, 2.65, and 1.65 were obtained for the OER of 220-kV x rays, plateau carbon, and the middle region of the 4-cm carbon peak, respectively. Across the 10-cm carbon peak the OER was found to vary between values of 2.4 to 1.55 from the proximal to distal positions

Calculated LET-Spectrum of Antiprotons

DEFF Research Database (Denmark)

Bassler, Niels

-LET components resulting from the annihilation. Though, the calculations of dose-averaged LET in the entry region may suggest that the RBE of antiprotons in the plateau region could significantly differ from unity. Materials and Methods Monte Carlo simulations using FLUKA were performed for calculating...

Neutron RBEs at Hiroshima

International Nuclear Information System (INIS)

Brenner, D.J.

1988-01-01

The recent reassessment (DS86) of radiation doses at Hiroshima and Nagasaki will have a profound influence on radiation protection standards. One important aspect is the almost order of magnitude reduction in estimated neutron doses at Hiroshima: in the previous dosimetry, the generally increased (per dose) hazard at Hiroshima compared to Nagasaki was interpreted as being due to neutrons having a greater per dose effectiveness, and, on this basis, RBEs were estimated. For example, the RBE for all cancers except leukemia could be estimated to be between about 15 and 50 (80% confidence level). However, the corresponding estimate with the new dosimetry is between 0 and 90 (50% confidence level). Thus it appears, prima facie, that no useful RBE data can be derived from the epidemiological data at Hiroshima. An attempt is made in this study to generate RBEs at Hiroshima based on radiobiological considerations, but making as few assumptions as possible

Study of biological effects of accelerated heavy ions irradiation on rices: Pt. 1

International Nuclear Information System (INIS)

Liu Zhensheng; Qiu Quanfa; Huang Wenzhong; Mei Mantong; Yang, T.C.H.

1991-01-01

The dried rice seeds were irradiated with accelerated 56 Fe and 40 Ar ion beams or 60 Co γ-rays at various doses. The irradiation effects on seeding growth as well as micronuclei and chronosome aberration induction were observed. The results indicated that the seeding height raduction, frequency of micronucleated cells and frequency of chromosome aberrations all appeared to dose dependent for these three types of rediation. The RBE value for seeding height reduction, determined at fifity percent of hight inhibition level, was found to be about 6.3, 1.9 and 1 for 56 Fe, 40 Ar and 60 Co γ-ray respectively. However, the RBE values for the frequency of micronucleated cells were about 11, 4 and 1 for 56 Fe and 40 Ar particles and 60 Co γ-ray. It appeared that the effectiveness of high LET radiation in inducing biological effects at the first generation was higler than that of low LET radiation, especially in inducing the micronuclei formation

Screening for Binge Eating Disorders Using the Patient Health Questionnaire in a Community Sample

Science.gov (United States)

Striegel-Moore, Ruth H.; Perrin, Nancy; DeBar, Lynn; Wilson, G. Terence; Rosselli, Francine; Kraemer, Helena C.

2009-01-01

Objective To examine the operating characteristics of the Patient Health Questionnaire eating disorder module (PHQ-ED) for identifying bulimia nervosa/binge eating disorder (BN/BED) or recurrent binge eating (RBE) in a community sample, and to compare true positive (TP) versus false positive (FP) cases on clinical validators. Method 259 screen positive individuals and a random sample of 89 screen negative cases completed a diagnostic interview. Sensitivity, specificity, and Positive Predictive Value (PPV) were calculated. TP and FP cases were compared using t-tests and Chi-Square tests. Results The PHQ-ED had high sensitivity (100%) and specificity (92%) for detecting BN/BED or RBE, but PPV was low (15% or 19%). TP and FP cases did not differ significantly on frequency of subjective bulimic episodes, objective overeating, restraint, on BMI, and on self-rated health. Conclusions The PHQ-ED is recommended for use in large populations only in conjunction with follow-up questions to rule out cases without objective bulimic episodes. PMID:19424976

Repeated Bout Effect Was More Expressed in Young Adult Males Than in Elderly Males and Boys

Directory of Open Access Journals (Sweden)

Giedrius Gorianovas

2013-01-01

Full Text Available This study investigated possible differences using the same stretch-shortening exercise (SSE protocol on generally accepted monitoring markers (dependent variables: changes in creatine kinase, muscle soreness, and voluntary and electrically evoked torque in males across three lifespan stages (childhood versus adulthood versus old age. The protocol consisted of 100 intermittent (30 s interval between jumps drop jumps to determine the repeated bout effect (RBE (first and second bouts performed at a 2-week interval. The results showed that indirect symptoms of exercise-induced muscle damage after SSE were more expressed in adult males than in boys and elderly males, suggesting that the muscles of boys and elderly males are more resistant to exercise-induced damage than those of adult males. RBE was more pronounced in adult males than in boys and elderly males, suggesting that the muscles of boys and elderly males are less adaptive to exercise-induced muscle damage than those of adult males.

Evolving role of hadron irradiation: Potential and risks of hadrons heavier than protons

International Nuclear Information System (INIS)

Levy, Richard P.

2007-01-01

Proton irradiation has been developed to achieve the clinical benefit of improved 3D-dose distribution, with biological properties similar to X-rays. Neutron irradiation, though much less 3D-conformal than proton treatment, has been developed to take advantage of increased relative biologic effectiveness (RBE). Irradiation with hadrons heavier than protons (e.g. carbon and neon ions) exhibits the unique combination of improved 3D-dose distribution and increased RBE. The synchrotron technology is rapidly developing to improve the efficiency of delivering these heavier hadrons clinically, but important issues remain regarding optimization of dose and fractionation parameters in the treatment of various histopathologies located in different portions of the anatomy. Many laboratory animal and in vitro cellular studies, and some clinical studies, have been performed to enable better understanding of how to adjust dose-fractionation selection to improve the therapeutic ratio of tumor-cell kill to normal-tissue injury. This paper highlights the enhanced therapeutic potential and associated risks of treatment with these heavier hadrons

Biokinetics of radioiodine ( sup 125 I) during pre and post-natal development and the interference with the induction of developmental effects in the mouse brain

Energy Technology Data Exchange (ETDEWEB)

Konermann, G. (Freiburg Univ. (Germany). Inst. fuer Biophysik und Strahlenbiologie)

1992-01-01

On day 13 post-conception, pregnant mice were injected with equal activities of either {sup 125}I-sodium iodide or 5-({sup 125}I)-iodo-2-deoxyuridine in order to study the biokinetic behaviour in relation to the induction of developmental long-term damage to the brain. Brain weight, cortex diameters and alignment of cortical neurons were more affected by {sup 125}I-IUdR (37-231 kBq.g{sup -1}) than by {sup 125}I-NaI, consistent with decay sites within the DNA or mainly extranuclear sites, respectively. Dose calculations according to the MIRD scheme gave underestimates of the radiotoxicity, especially for the DNA bound {sup 125}I. This is consistent with pronounced RBE effects derived from in vitro studies. The transfer of these RBE effects to the developing brain is, however, limited by the complex interference between the manifestation and compensation of damage within the prolonged response chains. (author).

Investigation of pion-treated human skin nodules for therapeutic gain

International Nuclear Information System (INIS)

Kligerman, M.M.; Sala, J.M.; Wilson, S.; Yuhas, J.M.

1978-01-01

A patient with multiple metastatic tumor nodules in the skin, from a primary breast carcinoma, was treated with graded doses of pions and x rays to establish skin tolerance. She was followed up for 346 days, permitting observation of time to regrowth of the tumor nodules. All 16 of these had disappeared after treatment, without significant correlation with type of radiation or dose, or with nodule size. However, time to regrowth depended both on the type and the dose of radiation. Earlier, relative biological effectiveness (RBE), was established at 1.42 for acute skin injury. Using this RBE to normalize doses of pions and x rays causing equivalent acute skin injury, and plotting those doses vs time to regrowth of tumor nodules, yielded a therapeutic gain (37.5%) in favor of pions. No late skin or subcutaneous tissue changes were seen, and no qualitative difference between pions and x rays in late skin effects was observed

Study of the Clinical Proton Beam Relative Biological Effectiveness at the JINR Phasotron, Dubna

CERN Document Server

Vitanova, A; Gaevskii, V N; Molokonov, A G; Spurny, F; Fadeeva, T A; Shmakova, N L

2002-01-01

Proton clinical beams contain particles with high linear energy transfer (LET). Secondary heavy charged particles produced from nuclear interactions and degraded protons at the Bragg peak region are particles with high LET. These particles could enhance the Relative Biological Effectiveness (RBE) of the proton beam. We have carried out two radiobiological experiments to investigate the RBE of 150 MeV clinical proton beam. The irradiation of the Chinese Hamster V79 cells were performed at two points of the depth-dose distribution - at the beam entrance and at the Bragg peak. The contribution of the high LET particles to dosimetric and microdosimetric characteristics in the various depth of proton beam was also experimentally studied using the CR-39 track etched detectors. The LET spectra between 10 and 700 keV/{\\mu}m were measured by means of track detectors and the automatic optical image analyzer LUCIA-II. The relative contribution of the high LET particles to ab! sorbed dose increases from several per cent ...

Towards clinical evidence in particle therapy: ENLIGHT, PARTNER, ULICE and beyond

CERN Document Server

Combs, Stephanie E; Pötter, Richad; Orrechia, Roberto; Haberer, Thomas; Durante, Marco; Fossati, Piero; Parodi, Katia; Balosso, Jacques; Amaldi, Ugo; Baumann, Michael; Debus, Jürgen

2013-01-01

Since the middle of the 20th century, particle therapy has been in focus for patient treatments. In 1946, Robert Wilson proposed the use of charged particles for tumor therapy, and since then, the clinical use of protons and heavier ions, mainly carbon ions, has become more widespread. The first clinical evidence was obtained in Berkeley, treating radiation-resistant targets with various ion species. The main advantage of particle beams derive from their physical properties: through an inverted dose profile, regions within the entry channel of the beam can be spared of dose, while a steep dose deposition can be directed in an energydependent manner into the defined treatment volume (Bragg Peak). The following dose fall-off spares tissue behind the target volume, thus reducing integral dose significantly compared to when using photons. Heavier charged particles, such as carbon ions or oxygen, are additionally associated with an increased relative biological effectiveness (RBE), while the RBE of protons is comm...

Cell survival in carbon beams - comparison of amorphous track model predictions

DEFF Research Database (Denmark)

Grzanka, L.; Greilich, S.; Korcyl, M.

Introduction: Predictions of the radiobiological effectiveness (RBE) play an essential role in treatment planning with heavy charged particles. Amorphous track models ( [1] , [2] , also referred to as track structure models) provide currently the most suitable description of cell survival under i....... Amorphous track modelling of luminescence detector efficiency in proton and carbon beams. 4.Tsuruoka C, Suzuki M, Kanai T, et al. LET and ion species dependence for cell killing in normal human skin fibroblasts. Radiat Res. 2005;163:494-500.......Introduction: Predictions of the radiobiological effectiveness (RBE) play an essential role in treatment planning with heavy charged particles. Amorphous track models ( [1] , [2] , also referred to as track structure models) provide currently the most suitable description of cell survival under ion....... [2] . In addition, a new approach based on microdosimetric distributions is presented and investigated [3] . Material and methods: A suitable software library embrasing the mentioned amorphous track models including numerous submodels with respect to delta-electron range models, radial dose...

Mutation induction and neoplastic transformation in human and human-hamster hybrid cells: dependence on photon energy and modulation in the low-dose range

Energy Technology Data Exchange (ETDEWEB)

Frankenberg, D.; Frankenberg-Schwager, M.; Garg, I.; Pralle, E. [Abt. Klin. Strahlenbiologie und Klin. Strahlenphysik, Universitaet Goettingen, Goettingen (Germany); Uthe, D.; Greve, B.; Severin, E.; Goehde, W. [Institut fuer Strahlenbiologie, Universitaet Muenster, Munster (Germany)

2002-09-01

Mutation induction in the HPRT gene of human fibroblasts after irradiation with mammography-like 29 kVp or 200 kVp x-rays shows radiohypersensitivity for doses smaller than {approx}0.5 Gy. Similarly, mutation induction in the CD 59 gene on human chromosome 11 in A{sub L} cells shows radiohypersensitivity for doses smaller than {approx}0.5 Gy after exposure to 200 kVp x-rays, but not after irradiation with low-filtered 30 kVp x-rays. The RBE values of 29 and 30 kVp x-rays relative to 200 kVp x-rays are strongly dose dependent. For neoplastic transformation of human hybrid (CGL1) cells after irradiation with 29 or 200 kVp x-rays or {sup 60}Co gamma rays a linear-quadratic dose relationship was observed with RBE values of approximately four and eight for mammography relative to 200 kVp x-rays and {sup 60}Co gamma rays, respectively. (author)

Dosimetry of bone metastases in targeted radionuclide therapy with alpha-emitting {sup 223}Ra-dichloride

Energy Technology Data Exchange (ETDEWEB)

Pacilio, Massimiliano [Azienda Ospealiera San Camillo Forlianini, Rome (Italy). Dept. of Medical Physics; Ventroni, Guido; Mango, Lucio [Azienda Ospealiera San Camillo Forlianini, Rome (Italy). Dept. of Nuclear Medicin; De Vincentis, Giuseppe; Di Castro, Elisabetta; Frantellizzi, Viviana; Follacchio, Giulia Anna; Garkavaya, Tatiana [Rome Univ. (Italy). Dept. of Radiological, Oncological and Anatomo Pathological Sciences; Cassano, Bartolomeo; Lorenzon, Leda [Rome Univ. (Italy). Postgraduate School of Medical Physics; Pellegrini, Rosanna; Pani, Roberto [Rome Univ. (Italy). Dept. of Molecular Medicine; Ialongo, Pasquale [Azienda Ospealiera San Camillo Forlianini, Rome (Italy). Dept. of Radiology

2016-01-15

Ra-dichloride is an alpha-emitting radiopharmaceutical used in the treatment of bone metastases from castration-resistant prostate cancer. Image-based dosimetric studies remain challenging because the emitted photons are few. The aim of this study was to implement a methodology for in-vivo quantitative planar imaging, and to assess the absorbed dose to lesions using the MIRD approach. The study included nine Caucasian patients with 24 lesions (6 humeral head lesions, 4 iliac wing lesions, 2 scapular lesions, 5 trochanter lesions, 3 vertebral lesions, 3 glenoid lesions, 1 coxofemoral lesion). The treatment consisted of six injections (one every 4 weeks) of 50 kBq per kg body weight. Gamma-camera calibrations for {sup 223}Ra included measurements of sensitivity and transmission curves. Patients were statically imaged for 30 min, using an MEGP collimator, double-peak acquisition, and filtering to improve the image quality. Lesions were delineated on {sup 99m}Tc-MDP whole-body images, and the ROIs superimposed on the {sup 223}Ra images after image coregistration. The activity was quantified with background, attenuation, and scatter correction. Absorbed doses were assessed deriving the S values from the S factors for soft-tissue spheres of OLINDA/EXM, evaluating the lesion volumes by delineation on the CT images. In 12 lesions with a wash-in phase the biokinetics were assumed to be biexponential, and to be monoexponential in the remainder. The optimal timing for serial acquisitions was between 1 and 5 h, between 18 and 24 h, between 48 and 60 h, and between 7 and 15 days. The error in cumulated activity neglecting the wash-in phase was between 2 % and 12 %. The mean effective half-life (T{sub 1/2eff}) of {sup 223}Ra was 8.2 days (range 5.5-11.4 days). The absorbed dose (D) after the first injection was 0.7 Gy (range 0.2-1.9 Gy). Considering the relative biological effectiveness (RBE) of alpha particles (RBE = 5), D{sub RBE} = 899 mGy/MBq (range 340-2,450 mGy/MBq). The

Biophysical fundamentals and considerations on variation of radiation quality in radiotherapy

International Nuclear Information System (INIS)

Abel, H.

1975-01-01

Considering the primarily critical structures of the cell, the dependence of DNA damage on LET is shown. For clarification of the repair of DNA damages phylogenetic tree analyses and biochemical investigations of repair mechanisms are considered useful. The relationship between oxygen effect and RBE in tumors is demonstrated

Kliimasoojenemise hüsteeria läheb kalliks maksma / Kalev Kallemets

Index Scriptorium Estoniae

Kallemets, Kalev, 1979-

2009-01-01

Autori väitel tähendab praegune EL-i süsinikdioksiidi-kaubanduse kokkulepe Eesti elektrihinna 2-3-kordistumist 2015. või 2020. aastaks, 20% suurune emissioonikärbe ning süsinikdioksiidi kvoodi hinnatõus tähendab lööki Eesti ja Euroopa majandusele

Teratogenic effects of 60Co gamma rays irradiation on rat embryos

International Nuclear Information System (INIS)

Lee, Juing-Yi; Okuda, Hiroe; Tutimoto, Sigeo; Satow, Yukio

1987-01-01

The teratogenicity of 60 Co gamma rays was evaluated in Donryu rats. The results were compared with those of triterated water (HTO) for determining relative biological effectiveness (RBE) for incidence of malformations and LD 50 in rats. Pregnant rats were irradiated with a 60 Co source at a dose-rate of 0.5 Gy/min or 0.01 Gy/min on day 7, 8, 9, 10 or 11 of gestation with 0.8, 1.0, 1.2, 1.5, 2.0, 2.3, 2.5, 2.8 or 3.0 Gy. HTO was administered intraperitoneal injection to pregnant rats at various doses on day 7, 8, 9, 10 and 11 of gestation. The rats were sacrificed on day 18 and the offspring were examined for external and visceral malformations. Mortality, teratogenicity and effects on fetal growth were day-and dosage-dependent in both radiation groups. Congenital malformations were found most frequently in the 9-day irradiated group and followed by the 8, 11, 10 and 7-day irradiated groups. The incidence of cardiovascular anomalies was highest, especially in the day 9 of gestation group, followed by malformations in the central nervous system, craniofacial system, respiratory system, hind limbs and tail. Beta rays from HTO were found to be more effective than γ rays in inducing congenital malformations. The RBE for incidence of malformations and LD 50 was between 1.3 and 1.5. These studies suggest that simulator of tritium irradiation is urgently needed to investigate the biological effects on rats to estimate the human risks, with respect to RBE of tritium beta rays. (author)

Molecular and functional characterization of riboflavin specific transport system in rat brain capillary endothelial cells

Science.gov (United States)

Patel, Mitesh; Vadlapatla, Ramya Krishna; Pal, Dhananjay; Mitra, Ashim K.

2012-01-01

Riboflavin is an important water soluble vitamin (B2) required for metabolic reactions, normal cellular growth, differentiation and function. Mammalian brain cells cannot synthesize riboflavin and must import from systemic circulation. However, the uptake mechanism, cellular translocation and intracellular trafficking of riboflavin in brain capillary endothelial cells are poorly understood. The primary objective of this study is to investigate the existence of riboflavin-specific transport system and delineate the uptake and intracellular regulation of riboflavin in immortalized rat brain capillary endothelial cells (RBE4). The uptake of [3H]-Riboflavin is sodium, temperature and energy dependent but pH independent. [3H]-Riboflavin uptake is saturable with Km and Vmax values of 19 ± 3 µM and 0.235 ± 0.012 picomoles/min/mg protein, respectively. The uptake process is inhibited by unlabelled structural analogs (lumiflavin, lumichrome) but not by structurally unrelated vitamins. Ca++/calmodulin and protein kinase A (PKA) pathways are found to play an important role in the intracellular regulation of [3H]-Riboflavin. Apical and baso-lateral uptake of [3H]-Riboflavin clearly indicate that riboflavin specific transport system is predominantly localized on the apical side of RBE4 cells. A 628 bp band corresponding to riboflavin transporter is revealed in RT-PCR analysis. These findings, for the first time report the existence of a specialized and high affinity transport system for riboflavin in RBE4 cells. Blood-brain barrier (BBB) is a major obstacle limiting drug transport inside the brain as it regulates drug permeation from systemic circulation. This transporter can be utilized for targeted delivery in enhancing brain permeation of highly potent drugs on systemic administration. PMID:22683359

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)

Effectiveness and Safety of Spot Scanning Proton Radiation Therapy for Chordomas and Chondrosarcomas of the Skull Base: First Long-Term Report

International Nuclear Information System (INIS)

Ares, Carmen; Hug, Eugen B.; Lomax, Antony J.; Bolsi, Alessandra; Timmermann, Beate; Rutz, Hans Peter; Schuller, Jan C.; Pedroni, Eros; Goitein, Gudrun

2009-01-01

Purpose: To evaluate effectiveness and safety of spot-scanning-based proton radiotherapy (PT) in skull-base chordomas and chondrosarcomas. Methods and Materials: Between October 1998 and November 2005, 64 patients with skull-base chordomas (n = 42) and chondrosarcomas (n = 22) were treated at Paul Scherrer Institute with PT using spot-scanning technique. Median total dose for chordomas was 73.5 Gy(RBE) and 68.4 Gy(RBE) for chondrosarcomas at 1.8-2.0 Gy(RBE) dose per fraction. Local control (LC), disease specific survival (DSS), and overall survival (OS) rates were calculated. Toxicity was assessed according to CTCAE, v. 3.0. Results: Mean follow-up period was 38 months (range, 14-92 months). Five patients with chordoma and one patient with chondrosarcoma experienced local recurrence. Actuarial 5-year LC rates were 81% for chordomas and 94% for chondrosarcomas. Brainstem compression at the time of PT (p = 0.007) and gross tumor volume >25 mL (p = 0.03) were associated with lower LC rates. Five years rates of DSS and OS were 81% and 62% for chordomas and 100% and 91% for chondrosarcomas, respectively. High-grade late toxicity consisted of one patient with Grade 3 and one patient with Grade 4 unilateral optic neuropathy, and two patients with Grade 3 central nervous system necrosis. No patient experienced brainstem toxicity. Actuarial 5-year freedom from high-grade toxicity was 94%. Conclusions: Our data indicate safety and efficacy of spot-scanning based PT for skull-base chordomas and chondrosarcomas. With target definition, dose prescription and normal organ tolerance levels similar to passive-scattering based PT series, complication-free, tumor control and survival rates are at present comparable.

Cell transformation in vitro by fast neutrons of different energies: implications for mechanisms

International Nuclear Information System (INIS)

Barendsen, G.W.; Gaiser, J.F.

1985-01-01

Studies have been performed to analyse the dependence of the induction of cell transformation and cell reproductive death in cultures of C3H/10T1/2 cells, NBCH-3 cells and WAGR-2 cells on the energy of mono-energetic fast neutrons. The dose-effect relations for 300 kV, 4.2 MeV X rays, 15 MeV and 0.5 MeV neutrons have been analysed on the basis of the representations F(D) = t 1 D+t 2 D 2 and S(D)/S(0) = exp [-a 1 D+a 2 D 2 )] for transformation and survival respectively. The results show that a 1 values for all radiations are a factor of approximately 10 3 larger than corresponding t 1 values. The RBE values for cell reproductive death derived as ratios of a 1 for the various neutrons and 300 kV x rays are similar to the corresponding RBE values for cell transformation derived as ratios of t 1 values of neutrons and X rays. These similarities in the RBE values and differences in absolute values of a 1 and t 1 can be compared with results from published dose-effect relations for reproductive death and chromosome aberrations obtained for other cell lines. The insights obtained can be applied to derive a hypothesis about the induction of these effects, assuming similarities in energy requirements and physico-chemical primary mechanisms of the induction of damage in chromosomes and differences in the specificities of the sites and total size of the targets on chromosomes associated with the various endpoints observed. (author)

SU-E-T-549: Modeling Relative Biological Effectiveness of Protons for Radiation Induced Brain Necrosis

International Nuclear Information System (INIS)

Mirkovic, D; Peeler, C; Grosshans, D; Titt, U; Taleei, R; Mohan, R

2015-01-01

Purpose: To develop a model of the relative biological effectiveness (RBE) of protons as a function of dose and linear energy transfer (LET) for induction of brain necrosis using clinical data. Methods: In this study, treatment planning information was exported from a clinical treatment planning system (TPS) and used to construct a detailed Monte Carlo model of the patient and the beam delivery system. The physical proton dose and LET were computed in each voxel of the patient volume using Monte Carlo particle transport. A follow-up magnetic resonance imaging (MRI) study registered to the treatment planning CT was used to determine the region of the necrosis in the brain volume. Both, the whole brain and the necrosis volumes were segmented from the computed tomography (CT) dataset using the contours drawn by a physician and the corresponding voxels were binned with respect to dose and LET. The brain necrosis probability was computed as a function of dose and LET by dividing the total volume of all necrosis voxels with a given dose and LET with the corresponding total brain volume resulting in a set of NTCP-like curves (probability as a function of dose parameterized by LET). Results: The resulting model shows dependence on both dose and LET indicating the weakness of the constant RBE model for describing the brain toxicity. To the best of our knowledge the constant RBE model is currently used in all clinical applications which may Result in increased rate of brain toxicities in patients treated with protons. Conclusion: Further studies are needed to develop more accurate brain toxicity models for patients treated with protons and other heavy ions

An analysis of particle track effects on solid mammalian tissues

International Nuclear Information System (INIS)

Todd, P.

1992-01-01

The relative biological effectiveness (RBE) and quality factor (Q) at extreme values of linear energy transfer (LET) have been determined on the basis of experiments with single-cell systems and specific tissue responses. In typical single-cell systems, each heavy particle (Ar or Fe) passes through a single cell or no cell. In experiments on animal tissues, however, each heavy particle passes through several cells, and the LET can exceed 200 keV μm -1 in every cell. In most laboratory animal tissue systems, however, only a small portion of the hit cells are capable of expressing the end-point being measured, such as cell killing, mutation or carcinogenesis. The following question was therefore addressed: do RBEs and Q factors derived from single-cell experiments properly account for the damage at high LET when multiple cells are hit by HZE tracks? A review is offered in which measured radiation effects and known tissue properties are combined to estimate on the one hand, the number of cells at risk, p 3 n, per track, where n is the number of cells per track based on tissue and organ geometry, and p 3 is the probability that a cell in the track is capable of expressing the experimental end-point. On the other hand, the tissue and single-cell responses are compared by determining the ratio RBE in tissue/RBE in corresponding single cells. Experimental data from the literature indicate that tissue RBEs at very high LET (Fe and Ar ions) are higher than corresponding single-cell RBEs, especially in tissues in which p 3 n is high. (author)

Human cytogenetic dosimetry: a dose-response relationship for alpha particle radiation from 241Am

International Nuclear Information System (INIS)

DuFrain, R.J.; Littlefield, L.G.; Joiner, E.E.; Frome, E.L.

1979-01-01

Cytogenetic dosimetry estimates to guide treatment of persons internally contaminated with transuranic elements have not previously been possible because appropriate in vitro dose-response curves specifically for alpha particle irradiation of human lymphocytes do not exist. Using well-controlled cytogenetic methods for human lymphocyte culture, an experimentally derived dose-response curve for 241 Am alpha particle (5.49 and 5.44 MeV) radiation of G 0 lymphocytes was generated. Cells were exposed to 43.8, 87.7, 175.3 or 350.6 nCi/ml 241 Am for 1.7 hr giving doses of 0.85, 1.71, 3.42 or 6.84 rad. Based on dicentric chromosome yield, the linear dose-response equation is Y = 4.90(+-0.42) x 10 -2 X, with Y given as dicentrics per cell and X as dose in rads. The study also shows that the two-break asymmetrical exchanges in cells damaged by alpha particle radiation are overdispersed when compared to a Poisson distribution. An example is presented to show how the derived dose-response equation can be used to estimate the radiation dose for a person internally contaminated with an actinide. An experimentally derived RBE value of 118 at 0.85 rad is calculated for the efficiency of 241 Am alpha particle induction of dicentric chromosomes in human G 0 lymphocytes as compared with the efficiency of 60 Co gamma radiation. The maximum theoretical value for the RBE for cytogenetic damage from alpha irradiation was determined to be 278 at 0.1 rad or less which is in marked contrast to previously reported RBE values of approx. 20. (author)

Photon iso-effective dose for cancer treatment with mixed field radiation based on dose-response assessment from human and an animal model: clinical application to boron neutron capture therapy for head and neck cancer

Science.gov (United States)

González, S. J.; Pozzi, E. C. C.; Monti Hughes, A.; Provenzano, L.; Koivunoro, H.; Carando, D. G.; Thorp, S. I.; Casal, M. R.; Bortolussi, S.; Trivillin, V. A.; Garabalino, M. A.; Curotto, P.; Heber, E. M.; Santa Cruz, G. A.; Kankaanranta, L.; Joensuu, H.; Schwint, A. E.

2017-10-01

Boron neutron capture therapy (BNCT) is a treatment modality that combines different radiation qualities. Since the severity of biological damage following irradiation depends on the radiation type, a quantity different from absorbed dose is required to explain the effects observed in the clinical BNCT in terms of outcome compared with conventional photon radiation therapy. A new approach for calculating photon iso-effective doses in BNCT was introduced previously. The present work extends this model to include information from dose-response assessments in animal models and humans. Parameters of the model were determined for tumour and precancerous tissue using dose-response curves obtained from BNCT and photon studies performed in the hamster cheek pouch in vivo models of oral cancer and/or pre-cancer, and from head and neck cancer radiotherapy data with photons. To this end, suitable expressions of the dose-limiting Normal Tissue Complication and Tumour Control Probabilities for the reference radiation and for the mixed field BNCT radiation were developed. Pearson’s correlation coefficients and p-values showed that TCP and NTCP models agreed with experimental data (with r  >  0.87 and p-values  >0.57). The photon iso-effective dose model was applied retrospectively to evaluate the dosimetry in tumours and mucosa for head and neck cancer patients treated with BNCT in Finland. Photon iso-effective doses in tumour were lower than those obtained with the standard RBE-weighted model (between 10% to 45%). The results also suggested that the probabilities of tumour control derived from photon iso-effective doses are more adequate to explain the clinical responses than those obtained with the RBE-weighted values. The dosimetry in the mucosa revealed that the photon iso-effective doses were about 30% to 50% higher than the corresponding RBE-weighted values. While the RBE-weighted doses are unable to predict mucosa toxicity, predictions based on the proposed

Recent Developments of the Local Effect Model (LEM) - Implications of clustered damage on cell transformation

Science.gov (United States)

Elsässer, Thilo

Exposure to radiation of high-energy and highly charged ions (HZE) causes a major risk to human beings, since in long term space explorations about 10 protons per month and about one HZE particle per month hit each cell nucleus (1). Despite the larger number of light ions, the high ionisation power of HZE particles and its corresponding more complex damage represents a major hazard for astronauts. Therefore, in order to get a reasonable risk estimate, it is necessary to take into account the entire mixed radiation field. Frequently, neoplastic cell transformation serves as an indicator for the oncogenic potential of radiation exposure. It can be measured for a small number of ion and energy combinations. However, due to the complexity of the radiation field it is necessary to know the contribution to the radiation damage of each ion species for the entire range of energies. Therefore, a model is required which transfers the few experimental data to other particles with different LETs. We use the Local Effect Model (LEM) (2) with its cluster extension (3) to calculate the relative biological effectiveness (RBE) of neoplastic transformation. It was originally developed in the framework of hadrontherapy and is applicable for a large range of ions and energies. The input parameters for the model include the linear-quadratic parameters for the induction of lethal events as well as for the induction of transformation events per surviving cell. Both processes of cell inactivation and neoplastic transformation per viable cell are combined to eventually yield the RBE for cell transformation. We show that the Local Effect Model is capable of predicting the RBE of neoplastic cell transformation for a broad range of ions and energies. The comparison of experimental data (4) with model calculations shows a reasonable agreement. We find that the cluster extension results in a better representation of the measured RBE values. With this model it should be possible to better

Photon iso-effective dose for cancer treatment with mixed field radiation based on dose-response assessment from human and an animal model: clinical application to boron neutron capture therapy for head and neck cancer.

Science.gov (United States)

González, S J; Pozzi, E C C; Monti Hughes, A; Provenzano, L; Koivunoro, H; Carando, D G; Thorp, S I; Casal, M R; Bortolussi, S; Trivillin, V A; Garabalino, M A; Curotto, P; Heber, E M; Santa Cruz, G A; Kankaanranta, L; Joensuu, H; Schwint, A E

2017-10-03

Boron neutron capture therapy (BNCT) is a treatment modality that combines different radiation qualities. Since the severity of biological damage following irradiation depends on the radiation type, a quantity different from absorbed dose is required to explain the effects observed in the clinical BNCT in terms of outcome compared with conventional photon radiation therapy. A new approach for calculating photon iso-effective doses in BNCT was introduced previously. The present work extends this model to include information from dose-response assessments in animal models and humans. Parameters of the model were determined for tumour and precancerous tissue using dose-response curves obtained from BNCT and photon studies performed in the hamster cheek pouch in vivo models of oral cancer and/or pre-cancer, and from head and neck cancer radiotherapy data with photons. To this end, suitable expressions of the dose-limiting Normal Tissue Complication and Tumour Control Probabilities for the reference radiation and for the mixed field BNCT radiation were developed. Pearson's correlation coefficients and p-values showed that TCP and NTCP models agreed with experimental data (with r  >  0.87 and p-values  >0.57). The photon iso-effective dose model was applied retrospectively to evaluate the dosimetry in tumours and mucosa for head and neck cancer patients treated with BNCT in Finland. Photon iso-effective doses in tumour were lower than those obtained with the standard RBE-weighted model (between 10% to 45%). The results also suggested that the probabilities of tumour control derived from photon iso-effective doses are more adequate to explain the clinical responses than those obtained with the RBE-weighted values. The dosimetry in the mucosa revealed that the photon iso-effective doses were about 30% to 50% higher than the corresponding RBE-weighted values. While the RBE-weighted doses are unable to predict mucosa toxicity, predictions based on the proposed

Comparison of a Rat Primary Cell-Based Blood-Brain Barrier Model With Epithelial and Brain Endothelial Cell Lines: Gene Expression and Drug Transport

Directory of Open Access Journals (Sweden)

Szilvia Veszelka

2018-05-01

Full Text Available Cell culture-based blood-brain barrier (BBB models are useful tools for screening of CNS drug candidates. Cell sources for BBB models include primary brain endothelial cells or immortalized brain endothelial cell lines. Despite their well-known differences, epithelial cell lines are also used as surrogate models for testing neuropharmaceuticals. The aim of the present study was to compare the expression of selected BBB related genes including tight junction proteins, solute carriers (SLC, ABC transporters, metabolic enzymes and to describe the paracellular properties of nine different culture models. To establish a primary BBB model rat brain capillary endothelial cells were co-cultured with rat pericytes and astrocytes (EPA. As other BBB and surrogate models four brain endothelial cells lines, rat GP8 and RBE4 cells, and human hCMEC/D3 cells with or without lithium treatment (D3 and D3L, and four epithelial cell lines, native human intestinal Caco-2 and high P-glycoprotein expressing vinblastine-selected VB-Caco-2 cells, native MDCK and MDR1 transfected MDCK canine kidney cells were used. To test transporter functionality, the permeability of 12 molecules, glucopyranose, valproate, baclofen, gabapentin, probenecid, salicylate, rosuvastatin, pravastatin, atorvastatin, tacrine, donepezil, was also measured in the EPA and epithelial models. Among the junctional protein genes, the expression level of occludin was high in all models except the GP8 and RBE4 cells, and each model expressed a unique claudin pattern. Major BBB efflux (P-glycoprotein or ABCB1 and influx transporters (GLUT-1, LAT-1 were present in all models at mRNA levels. The transcript of BCRP (ABCG2 was not expressed in MDCK, GP8 and RBE4 cells. The absence of gene expression of important BBB efflux and influx transporters BCRP, MRP6, -9, MCT6, -8, PHT2, OATPs in one or both types of epithelial models suggests that Caco-2 or MDCK models are not suitable to test drug candidates which

Sterilization of fruit flies (Diptera: Tephritidae) with X-rays for sterile insect technique programs; Esterilizacao de moscas-das-frutas (Diptera: Tephritidae) com raios-X para programas de tecnica do inseto esteril

Energy Technology Data Exchange (ETDEWEB)

Mastrangelo, Thiago de Araujo

2009-07-01

Recent fear of acts of terrorism provoked an increase of delays and denials in the shipment of radioisotopes. This truly represented a menace to sterile insect production projects around the world. In order to validate the use of a new kind of low-energy Xray irradiator, a series of radiobiological studies on Ceratitis capitata (tsl-VIENNA 8 strain) (Wied., 1824) (Diptera: Tephritidae) and an Argentinean strain of Anastrepha fraterculus (Wied., 1830) (Diptera: Tephritidae) were carried out, also comparing biological effectiveness between X-rays and traditional {gamma} radiation from {sup 60}Co. Pupae 48- 24 h before adult emergence of C. capitata males and both sexes of A. fraterculus were irradiated with doses ranging from 15 to 120 Gy and 10 to 70 Gy respectively. Doses that induce 50, 90 and 99% of sterility were estimated and the hypothesis of Parallelism for the Probit equations was tested. Doses of 82.7 Gy of X-rays and 128.2 Gy of {gamma} rays (thus, a RBE{approx}1.5) induced 99% sterility on medfly males. The fertility of A. fraterculus fertile females crossed with 41 Gy of X-rays and 62.7 Gy of {gamma} rays decreased in 99% comparing with the control group (RBE{approx}1.5). 99% sterility of A. fraterculus irradiated females was achieved with 60-80 Gy (RBE{approx}0.7). The standard quality control parameters of fecundity, adult emergence, fliers and survival were not significantly affected by the two types of radiation (RBE{approx}1) either for medfly or A. fraterculus (p>0.01), being averages in conformity with the values required by FAO/IAEA/USDA. Only fecundity of irradiated A. fraterculus females was severely reduced with increasing doses and no egg was laid at 70 Gy of both radiations. There were no significant differences between X-rays and {gamma} rays regarding mating indices (RSI for medfly, RII, ISI, MRPI and FRPI for A. fraterculus) (p>0.05), what indicated more random matings for fertile and sterile insects. The results demonstrated that no

Proton Arc Reduces Range Uncertainty Effects and Improves Conformality Compared With Photon Volumetric Modulated Arc Therapy in Stereotactic Body Radiation Therapy for Non-Small Cell Lung Cancer

Energy Technology Data Exchange (ETDEWEB)

Seco, Joao, E-mail: jseco@partners.org [Francis H. Burr Proton Therapy Center, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Gu, Guan; Marcelos, Tiago; Kooy, Hanne; Willers, Henning [Francis H. Burr Proton Therapy Center, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

2013-09-01

Purpose: To describe, in a setting of non-small cell lung cancer (NSCLC), the theoretical dosimetric advantages of proton arc stereotactic body radiation therapy (SBRT) in which the beam penumbra of a rotating beam is used to reduce the impact of range uncertainties. Methods and Materials: Thirteen patients with early-stage NSCLC treated with proton SBRT underwent repeat planning with photon volumetric modulated arc therapy (Photon-VMAT) and an in-house-developed arc planning approach for both proton passive scattering (Passive-Arc) and intensity modulated proton therapy (IMPT-Arc). An arc was mimicked with a series of beams placed at 10° increments. Tumor and organ at risk doses were compared in the context of high- and low-dose regions, represented by volumes receiving >50% and <50% of the prescription dose, respectively. Results: In the high-dose region, conformality index values are 2.56, 1.91, 1.31, and 1.74, and homogeneity index values are 1.29, 1.22, 1.52, and 1.18, respectively, for 3 proton passive scattered beams, Passive-Arc, IMPT-Arc, and Photon-VMAT. Therefore, proton arc leads to a 30% reduction in the 95% isodose line volume to 3-beam proton plan, sparing surrounding organs, such as lung and chest wall. For chest wall, V30 is reduced from 21 cm{sup 3} (3 proton beams) to 11.5 cm{sup 3}, 12.9 cm{sup 3}, and 8.63 cm{sup 3} (P=.005) for Passive-Arc, IMPT-Arc, and Photon-VMAT, respectively. In the low-dose region, the mean lung dose and V20 of the ipsilateral lung are 5.01 Gy(relative biological effectiveness [RBE]), 4.38 Gy(RBE), 4.91 Gy(RBE), and 5.99 Gy(RBE) and 9.5%, 7.5%, 9.0%, and 10.0%, respectively, for 3-beam, Passive-Arc, IMPT-Arc, and Photon-VMAT, respectively. Conclusions: Stereotactic body radiation therapy with proton arc and Photon-VMAT generate significantly more conformal high-dose volumes than standard proton SBRT, without loss of coverage of the tumor and with significant sparing of nearby organs, such as chest wall. In addition

Mutagenic effect of tritium on DNA of Drosophila melanogaster. Comprehensive performance report, December 15, 1985-June 1, 1988

International Nuclear Information System (INIS)

Lee, W.R.

1988-01-01

The results of the RBE determination of tritium to cobalt-69 gamma radiation along with a description of methods of treatment and dose determination are given. Using the described procedures for exposing Drosophila to tritiated water, the authors induced mutations by tritium beta radiation and recovered them at the Adh locus

Mutiple simultaneous event model for radiation carcinogenesis

International Nuclear Information System (INIS)

Baum, J.W.

1979-01-01

Theoretical Radiobiology and Risk Estimates includes reports on: Multiple Simultaneous Event Model for Radiation Carcinogenesis; Cancer Risk Estimates and Neutron RBE Based on Human Exposures; A Rationale for Nonlinear Dose Response Functions of Power Greater or Less Than One; and Rationale for One Double Event in Model for Radiation Carcinogenesis

Biological Effectiveness and Application of Heavy Ions in Radiation Therapy Described by a Physical and Biological Model

DEFF Research Database (Denmark)

Olsen, Kjeld J.; Hansen, Johnny W.

is inadequately described by an RBE-factor, whereas the complete formulation of the probability of survival must be used, as survival depends on both radiation quality and dose. The theoretical model of track structure can be used in dose-effect calculations for neutron-, high-LET, and low-LET radiation applied...... simultaneously in therapy....

Verification of the differential biological effectiveness of photons in the energy range of 10 keV - 6 MeV based on oncogenic transformation rates in mouse embryofibroblasts and in the human CGL 1-hybrid cell line

International Nuclear Information System (INIS)

Schmid, E.

2005-01-01

Working on observations of neoplastic transformation in human hybrid CGL1 cells, Frankenberg et al. (Radiat.Res. 157, 99-105, 2002) recently reported a relative biological effectiveness (RBE M ) of 4.3 for mammography X-rays (29 kV) relative to 200 kV X-rays. With reference to data in the literature, they inferred a factor of about 8 relative to 60 Co y-rays and concluded that this result is relevant to risk estimation. However, these conclusions do not appear to be valid. The data from the transformation study exhibit uncertainties in the statistical analysis that preclude any generalisation of the inferred RBE M . The data selected or inferred from the literature are likewise insufficient to support the stated RBEs. We therefore designed a study to repeat, under well-defined irradiation and culture conditions, this earlier investigation and to assess the validity of the high RBE values of 29 kV X-rays that had ben reported. Neoplastic transformation of human CGL1 cell hybrids was examined after exposure to 29 kV X-rays (mammography X-rays) and conventional 220 kV X-rays. The experiments with the two types of X-rays were performed simultaneously and shared the same controls.The transformation yields with both radiation qualities were fitted to the linear-quadratic dependence on absorbed dose, and a corresponding analysis was performed for the data earlier obtained by Frankenberg et al. The transformation yields in the present study exceed those in the earlier investigations substantially and it appears that the difference reflects inadequate feeding conditions of the cell cultures in the early experiments. The standard error bands are derived and are seen to be considerably more narrow than in the present results

Radiosensitivity of Patient-Derived Glioma Stem Cell 3-Dimensional Cultures to Photon, Proton, and Carbon Irradiation

Energy Technology Data Exchange (ETDEWEB)

Chiblak, Sara; Tang, Zili [German Cancer Consortium, Heidelberg (Germany); Molecular and Translational Radiation Oncology, Heidelberg Ion Therapy Center, Heidelberg Institute of Radiation Oncology, University of Heidelberg Medical School and National Center for Tumor Diseases, German Cancer Research Center, Heidelberg (Germany); Campos, Benito; Gal, Zoltan; Unterberg, Andreas [Division of Neurological Research, Department of Neurosurgery, University of Heidelberg Medical School, Heidelberg (Germany); Debus, Jürgen [German Cancer Consortium, Heidelberg (Germany); Molecular and Translational Radiation Oncology, Heidelberg Ion Therapy Center, Heidelberg Institute of Radiation Oncology, University of Heidelberg Medical School and National Center for Tumor Diseases, German Cancer Research Center, Heidelberg (Germany); Herold-Mende, Christel [Division of Neurological Research, Department of Neurosurgery, University of Heidelberg Medical School, Heidelberg (Germany); Abdollahi, Amir, E-mail: a.amir@dkfz.de [German Cancer Consortium, Heidelberg (Germany); Molecular and Translational Radiation Oncology, Heidelberg Ion Therapy Center, Heidelberg Institute of Radiation Oncology, University of Heidelberg Medical School and National Center for Tumor Diseases, German Cancer Research Center, Heidelberg (Germany)

2016-05-01

Purpose: To investigate the radiosensitivity of primary glioma stem cell (GSC) cultures with different CD133 status in a 3-dimensional (3D) model after photon versus proton versus carbon irradiation. Methods and Materials: Human primary GSC spheroid cultures were established from tumor specimens of six consented glioblastoma patients. Human U87MG was used as a classical glioblastoma radioresistant cell line. Cell suspensions were generated by mechanical dissociation of GSC spheroids and embedded in a semi-solid 3D matrix before irradiation. Spheroid-like colonies were manually counted by microscopy. Cells were also recovered and quantified by fluorescence. CD133 expression and DNA damage were evaluated by flow cytometry. Results: The fraction of CD133{sup +} cells varied between 0.014% and 96% in the six GSC cultures and showed a nonsignificant correlation with plating efficiency and survival fractions. The 4 most photon-radioresistant GSC cultures were NCH644, NCH421k, NCH441, and NCH636. Clonogenic survival for proton irradiation revealed relative biologic effectiveness (RBE) in the range of 0.7-1.20. However, carbon irradiation rendered the photon-resistant GSC cultures sensitive, with average RBE of 1.87-3.44. This effect was partly attributed to impaired capability of GSC to repair carbon ion–induced DNA double-strand breaks as determined by residual DNA repair foci. Interestingly, radiosensitivity of U87 cells was comparable to GSC cultures using clonogenic survival as the standard readout. Conclusions: Carbon irradiation is effective in GSC eradication with similar RBE ranges approximately 2-3 as compared with non-stem GSC cultures (U87). Our data strongly suggest further exploration of GSC using classic radiobiology endpoints such as the here-used 3D clonogenic survival assay and integration of additional GSC-specific markers.

Radiosensitivity of Patient-Derived Glioma Stem Cell 3-Dimensional Cultures to Photon, Proton, and Carbon Irradiation

International Nuclear Information System (INIS)

Chiblak, Sara; Tang, Zili; Campos, Benito; Gal, Zoltan; Unterberg, Andreas; Debus, Jürgen; Herold-Mende, Christel; Abdollahi, Amir

2016-01-01

Purpose: To investigate the radiosensitivity of primary glioma stem cell (GSC) cultures with different CD133 status in a 3-dimensional (3D) model after photon versus proton versus carbon irradiation. Methods and Materials: Human primary GSC spheroid cultures were established from tumor specimens of six consented glioblastoma patients. Human U87MG was used as a classical glioblastoma radioresistant cell line. Cell suspensions were generated by mechanical dissociation of GSC spheroids and embedded in a semi-solid 3D matrix before irradiation. Spheroid-like colonies were manually counted by microscopy. Cells were also recovered and quantified by fluorescence. CD133 expression and DNA damage were evaluated by flow cytometry. Results: The fraction of CD133"+ cells varied between 0.014% and 96% in the six GSC cultures and showed a nonsignificant correlation with plating efficiency and survival fractions. The 4 most photon-radioresistant GSC cultures were NCH644, NCH421k, NCH441, and NCH636. Clonogenic survival for proton irradiation revealed relative biologic effectiveness (RBE) in the range of 0.7-1.20. However, carbon irradiation rendered the photon-resistant GSC cultures sensitive, with average RBE of 1.87-3.44. This effect was partly attributed to impaired capability of GSC to repair carbon ion–induced DNA double-strand breaks as determined by residual DNA repair foci. Interestingly, radiosensitivity of U87 cells was comparable to GSC cultures using clonogenic survival as the standard readout. Conclusions: Carbon irradiation is effective in GSC eradication with similar RBE ranges approximately 2-3 as compared with non-stem GSC cultures (U87). Our data strongly suggest further exploration of GSC using classic radiobiology endpoints such as the here-used 3D clonogenic survival assay and integration of additional GSC-specific markers.

SU-E-T-380: Particle Microdosimetry Study Based On 3D-Cylindrical Silicon Radiaton Detectors

Energy Technology Data Exchange (ETDEWEB)

Guardiola, C; Carabe-Fernandez, A [Hospital of the University of Pennsylvania, Philadelphia, PA (United States); Gomez, F [Universidad de Santiago de Compostela USC, Santiago De Compostela (Spain); Pellegrini, G; Fleta, C; Quirion, D; Lozano, M [Instituto de Microelectronica de Barcelona IMB-CNM, CSIC (Spain)

2014-06-01

Purpose: A new design of a solid-state-microdetector based on silicon 3D microfabrication and its performance to characterise Lineal energy, Specific Energy, dose, LET and other microdosimetric variables required for modelling particle relative biological effectiveness (RBE) is presented. Methods: A microdosimeter formed by a matrix of independent sensors with well-defined micrometric cylindrical shape and with a volume similar to those of cellular dimensions is used to measure microdosimetric variables. Each sensor measures the radiation deposited energy which, divided by the mean cord length of the sensors, provides us with the Linear Energy (y) of the radiation as well as its energy distribution, and frequencymean. Starting from the these distributions in different points of a proton beam, we generate biophysical data (e.g. Linear Energy Transfer (LET), Specific Energy (z), etc…) needed for relative biological effectiveness (RBE) calculations radiation effect models used in particle radiotherapy treatment planning. In addition, a Tissue Equivalent Proportional Counter (TEPC) will be used as baseline to calibrate the “y” magnitude of the microdosimeter unit-cells. Results: The experimental measurements will soon be carried out at the Perelman Center for Advanced Medicine (University of Pennsylvania), which provides proton beam for clinical research proposals. The results of distributions measured of the microdosimetric variables from the first tests developed in the proton facility will be presented and compared with Monte Carlo simulations using the Geant4 code. Conclusion: The use of 3D microdosimeters such as the one presented here will enhance the accuracy of RBE calculations normally affected by the inherent uncertainty of monte carlo simulations due to the approximation of material composition and energy dependent physical laws involved in such calculations. The effect of such approximations will be quatified by comparison with absolute measurement of

Radiogenic cell transformation and carcinogenesis

Science.gov (United States)

Yang, T. C.; Georgy, K. A.; Mei, M.; Durante, M.; Craise, L. M.

1995-01-01

Radiation carcinogenesis is one of the major biological effects considered important in the risk assessment for space travel. Various biological model systems, including both cultured cells and animals, have been found useful for studying the carcinogenic effects of space radiations, which consist of energetic electrons, protons and heavy ions. The development of techniques for studying neoplastic cell transformation in culture has made it possible to examine the cellular and molecular mechanisms of radiation carcinogenesis. Cultured cell systems are thus complementary to animal models. Many investigators have determined the oncogenic effects of ionizing and nonionizing radiation in cultured mammalian cells. One of the cell systems used most often for radiation transformation studies is mouse embryonic cells (C3H10T1/2), which are easy to culture and give good quantitative dose-response curves. Relative biological effectiveness (RBE) for heavy ions with various energies and linear energy transfer (LET) have been obtained with this cell system. Similar RBE and LET relationship was observed by investigators for other cell systems. In addition to RBE measurements, fundamental questions on repair of sub- and potential oncogenic lesions, direct and indirect effect, primary target and lesion, the importance of cell-cell interaction and the role of oncogenes and tumor suppressor genes in radiogenic carcinogenesis have been studied, and interesting results have been found. Recently several human epithelial cell systems have been developed, and ionizing radiation have been shown to transform these cells. Oncogenic transformation of these cells, however, requires a long expression time and/or multiple radiation exposures. Limited experimental data indicate high-LET heavy ions can be more effective than low-LET radiation in inducing cell transformation. Cytogenetic and molecular analyses can be performed with cloned transformants to provide insights into basic genetic

Nanoscale dose deposition in cell structures under X-ray irradiation treatment assisted with nanoparticles of a set of elements: an analytical approach to cell survival

Energy Technology Data Exchange (ETDEWEB)

Melo B, W.; Barboza F, M. [Universidad de Sonora, Departamento de Investigacion en Fisica, 83000 Hermosillo, Sonora (Mexico); Chernov, G., E-mail: g.chernovch@gmail.com [Universidad de Sonora, Departamento de Fisica, 83000 Hermosillo, Sonora (Mexico)

2016-10-15

The goal of combining nanoparticles (Nps) with radiation therapy is to increase the differential effect between healthy and tumor tissues. Only some elements have been investigated to be used as radiosensitizers and no systematic experimental or theoretical comparisons between different materials have been developed. MacMahon, et al. (Nano scale, 2016, 8, 581) presents the first systematic computational study of the impact of elemental composition on nanoparticle radiation interaction for kilo voltage and megavoltage X-ray exposure, for a range of elements (Z = 14 - 80). In this study we present and analytical model to assess the cell survival modification responses of cell cultures under irradiation treatments with keV X-rays assisted with Nps of different materials as platinum, hafnium, gadolinium, gold, germanium, iodine and iron. This model starts from the data of radial dose deposition around a single 20 nm diameter Np irradiated with photons of an energy 20 keV higher than the element K-shell binding energy to the nano scale probability of dose distribution inside cell structures with embedded Nps (the assessment of the average dose and the average squared dose in cell structure). Also based on the Local Effect Model we estimate potential biological effects, as is the case of the Relative Biological Effectiveness (RBE). Nano scale dose deposition exhibits a complex dependence on atomic number, as a consequence of the variations in secondary Auger electron spectra, this is manifested in significant variations in RBE. Upon in vitro experiments RBE varies from 1 to 1.6. Values representative of a high radiosensitization were observed for lower energies, ones that are well reproduced by our analytical analysis for cell cultures with a homogeneous distribution of different material Nps. (Author)

Nanoscale dose deposition in cell structures under X-ray irradiation treatment assisted with nanoparticles of a set of elements: an analytical approach to cell survival

International Nuclear Information System (INIS)

Melo B, W.; Barboza F, M.; Chernov, G.

2016-10-01

The goal of combining nanoparticles (Nps) with radiation therapy is to increase the differential effect between healthy and tumor tissues. Only some elements have been investigated to be used as radiosensitizers and no systematic experimental or theoretical comparisons between different materials have been developed. MacMahon, et al. (Nano scale, 2016, 8, 581) presents the first systematic computational study of the impact of elemental composition on nanoparticle radiation interaction for kilo voltage and megavoltage X-ray exposure, for a range of elements (Z = 14 - 80). In this study we present and analytical model to assess the cell survival modification responses of cell cultures under irradiation treatments with keV X-rays assisted with Nps of different materials as platinum, hafnium, gadolinium, gold, germanium, iodine and iron. This model starts from the data of radial dose deposition around a single 20 nm diameter Np irradiated with photons of an energy 20 keV higher than the element K-shell binding energy to the nano scale probability of dose distribution inside cell structures with embedded Nps (the assessment of the average dose and the average squared dose in cell structure). Also based on the Local Effect Model we estimate potential biological effects, as is the case of the Relative Biological Effectiveness (RBE). Nano scale dose deposition exhibits a complex dependence on atomic number, as a consequence of the variations in secondary Auger electron spectra, this is manifested in significant variations in RBE. Upon in vitro experiments RBE varies from 1 to 1.6. Values representative of a high radiosensitization were observed for lower energies, ones that are well reproduced by our analytical analysis for cell cultures with a homogeneous distribution of different material Nps. (Author)

Proton Radiotherapy for Parameningeal Rhabdomyosarcoma: Clinical Outcomes and Late Effects

Energy Technology Data Exchange (ETDEWEB)

Childs, Stephanie K. [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (United States); Kozak, Kevin R. [Department of Radiation Oncology, University of Wisconsin Cancer Center Johnson Creek, Madison, WI (United States); Friedmann, Alison M. [Department of Pediatric Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (United States); Yeap, Beow Y. [Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA (United States); Adams, Judith; MacDonald, Shannon M.; Liebsch, Norbert J.; Tarbell, Nancy J. [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (United States); Yock, Torunn I., E-mail: tyock@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (United States)

2012-02-01

Purpose: To report the clinical outcome and late side effect profile of proton radiotherapy in the treatment of children with parameningeal rhabdomyosarcoma (PM-RMS). Methods and Materials: Seventeen consecutive children with PM-RMS were treated with proton radiotherapy at Massachusetts General Hospital between 1996 and 2005. We reviewed the medical records of all patients and asked referring physicians to report specific side effects of interest. Results: Median patient age at diagnosis was 3.4 years (range, 0.4-17.6). Embryonal (n = 11), alveolar (n = 4), and undifferentiated (n = 2) histologies were represented. Ten patients (59%) had intracranial extension. Median prescribed dose was 50.4 cobalt gray equivalents (GyRBE) (range, 50.4-56.0 GyRBE) delivered in 1.8-2.0-GyRBE daily fractions. Median follow-up was 5.0 years for survivors. The 5-year failure-free survival estimate was 59% (95% confidence interval, 33-79%), and overall survival estimate was 64% (95% confidence interval, 37-82%). Among the 7 patients who failed, sites of first recurrence were local only (n = 2), regional only (n = 2), distant only (n = 2), and local and distant (n = 1). Late effects related to proton radiotherapy in the 10 recurrence-free patients (median follow-up, 5 years) include failure to maintain height velocity (n = 3), endocrinopathies (n = 2), mild facial hypoplasia (n = 7), failure of permanent tooth eruption (n = 3), dental caries (n = 5), and chronic nasal/sinus congestion (n = 2). Conclusions: Proton radiotherapy for patients with PM-RMS yields tumor control and survival comparable to that in historical controls with similar poor prognostic factors. Furthermore, rates of late effects from proton radiotherapy compare favorably to published reports of photon-treated cohorts.

Theory of RBE. Final report, January 1, 1967 - October 31, 1998

International Nuclear Information System (INIS)

Katz, R.

1998-01-01

The report begins with a historical survey of research activity. Next summaries of research accomplishments in the following areas are given: (1) Radiation Dose Distribution; (2) The 1-Hit Detector: Action Cross Sections; (3) Many Hit Detectors; (4) Biological Cells; (5) Implications for Radiation Protection; and (6) Implications for Radiation Oncology with Heavy Ion Beams

Theory of RBE. Final report, January 1, 1967--October 31, 1998

Energy Technology Data Exchange (ETDEWEB)

Katz, R.

1998-10-31

The report begins with a historical survey of research activity. Next summaries of research accomplishments in the following areas are given: (1) Radiation Dose Distribution; (2) The 1-Hit Detector: Action Cross Sections; (3) Many Hit Detectors; (4) Biological Cells; (5) Implications for Radiation Protection; and (6) Implications for Radiation Oncology with Heavy Ion Beams.

Lubatakse püksirihma pingutada / Kadri Bank

Index Scriptorium Estoniae

Bank, Kadri

2008-01-01

Uuringufirma Norstat korraldatud küsitluse tulemustest selgub, et suur osa eestlastest plaanivad 2008. aasta teisel poolaastal enim kärpida oma kulutusi toidule ja kütusele, samas kui vaid veerand elanikest kavatsevad oma tarbimisharjumused samaks jätta. Kommenteerib Pille Liivaauk. Diagramm: Kärbe tabab igat majandussektorit. Tabel: Keskealised tunnevad end turvalisemalt

Genetic effect of neutrons

International Nuclear Information System (INIS)

Luchnik, N.V.; Sevan'kaev, A.V.; Fesenko, Eh.V.

1984-01-01

Gene mutations resulting from neutron effect are considered, but attention is focused on chromosome mutations. Dose curves for different energy of neutrons obtained at different objects are obtained which makes it possible to consider RBE of neutrons depending on their energy and radiation dose and to get some information on the neutron effect on heredity

Inactive and mutagenic effects induced by carbon beams of different LET values in a red yeast strain

International Nuclear Information System (INIS)

Wang Jufang; Lu Dong; Wu Xin; Sun Haining; Ma Shuang; Li Renmin; Li Wenjian

2010-01-01

To evaluate biological action of microorganism exposed to charged particles during the long distance space exploration, induction of inactivation and mutation in a red yeast strain Rhodotorula glutinis AY 91015 by carbon beams of different LET values (14.9-120.0 keV μm -1 ) was investigated. It was found that survival curves were exponential, and mutation curves were linear for all LET values. The dependence of inactivation cross section on LET approached saturation near 120.0 keV μm -1 . The mutation cross section saturated when LET was higher than 58.2 keV μm -1 . Meanwhile, the highest RBE i for inactivation located at 120.0 keV μm -1 and the highest RBE m for mutation was at 58.2 keV μm -1 . The experiments imply that the most efficient mutagenic part of the depth dose profile of carbon ion is at the plateau region with intermediate LET value in which energy deposited is high enough to induce mutagenic lesions but too low to induce over kill effect in the yeast cells.

Relative biological efficiency of 592 MeV protons. Analysis of the biological effect of secondary radiation

International Nuclear Information System (INIS)

Legeay, G.; Baarli, J.

1968-01-01

The relative biological efficiency (RBE) of high energy protons is of importance because of their effects in the field of radioprotection around large accelerators and during space-flights. The nature of the interactions between 592 MeV protons and biological tissues makes it necessary to take into consideration the contribution of secondary radiation to the biological effect. Since it is not possible to obtain from a synchrotron a beam having a sufficiently large cross-section to irradiate large animals, one has to resort to certain devices concerning the mode of exposure when small laboratory animals are used. By irradiating rats individually and in groups, and by using the lethal test as a function of time, the authors show that the value of the RBE is different for animals of the same species having the same biological parameters. Thus there appears an increase in the biological effect due to secondary radiation produced in nuclear cascades which develop in a large volume, for example that of a human being. (author) [fr

Biological effectiveness of high-energy protons - Target fragmentation

International Nuclear Information System (INIS)

Cucinotta, F.A.; Katz, R.; Wilson, J.W.; Townsend, L.W.; Shinn, J.; Hajnal, F.

1991-01-01

High-energy protons traversing tissue produce local sources of high-linear-energy-transfer ions through nuclear fragmentation. The contribution of these target fragments to the biological effectiveness of high-energy protons using the cellular track model is examined. The effects of secondary ions are treated in terms of the production collision density using energy-dependent parameters from a high-energy fragmentation model. Calculations for mammalian cell cultures show that at high dose, at which intertrack effects become important, protons deliver damage similar to that produced by gamma rays, and with fragmentation the relative biological effectiveness (RBE) of protons increases moderately from unity. At low dose, where sublethal damage is unimportant, the contribution from target fragments dominates, causing the proton effectiveness to be very different from that of gamma rays with a strongly fluence-dependent RBE. At high energies, the nuclear fragmentation cross sections become independent of energy. This leads to a plateau in the proton single-particle-action cross section, below 1 keV/micron, since the target fragments dominate. 29 refs

Effects of organically bound tritium (OBT) on cultured midbrain cells from embryonic mice

International Nuclear Information System (INIS)

Wang Bing; Akihiro Shima; Takeshi Yamada; Keiko Watganabe

1997-01-01

Objective: Four kinds of organically bound tritium compounds (OBT s ) including 3 H-thymidine, 3 H-uridine, 3 H-arginine and 3 H-glutamic acid, were investigated on proliferation and differentiation of cultured mouse embryonic midbrain cells (MBCs). Methods: MBCs were isolated from day 11 embryos, cultured at a high concentration with the medium containing OBT. Results: Differentiation of MBC was more sensitive to radiation than proliferation. Dose-dependent decrease of DNA and protein contents were also observed. The RBE values, ranging from 4.6 to 8.7, of β rays from OBTs were obtained when compared with X-irradiation at their ID50s (inhibitory dose that reduced assessment value by 50% of the control) on inhibition of cell proliferation and differentiation, and on reduction of DNA and protein contents of the cultures. The mixed exposure to X-rays and one kind of OBTs or to any two kinds of OBTs resulted in more efficiently inhibitory effect on differentiation. Conclusions: MBC culture system was more sensitive to beta radiation from OBTs than to X-rays, which resulted in very high RBE values

Energy deposition and the formation of biologically significant lesions by accelerated ions

International Nuclear Information System (INIS)

Kiefer, J.

1985-01-01

The assumption that the number of biologically significant lesions depends only on the amount of of energy absorbed in a critical cellular site is not able to explain the increase of RBE with LET and leads to large discrepancies between predicted and measured inactivation cross sections in the LET range between 20 and 200 keV.μm -1 . It has, therefore, to be concluded that not only the amount of energy absorbed but also the spatial pattern of this deposition plays a decisive role. In the model presented it is postulated that two or more energy deposition events in nanometre sites are required for the formation of biologically significant lesions. This cooperative action has to take place in very short times so that only interactions within a single particle track contribute. The mathematical treatment will be outlined and qualitatively shown that the model is able to predict RBE-LET relationships. The calculations use a track structure model based on classical collision mechanics. It is compared with existing experimental results showing good agreement at least for higher particle energies. (author)

Inactive and mutagenic effects induced by carbon beams of different LET values in a red yeast strain

Science.gov (United States)

Wang, Jufang; Lu, Dong; Wu, Xin; Sun, Haining; Ma, Shuang; Li, Renmin; Li, Wenjian

2010-09-01

To evaluate biological action of microorganism exposed to charged particles during the long distance space exploration, induction of inactivation and mutation in a red yeast strain Rhodotorula glutinis AY 91015 by carbon beams of different LET values (14.9-120.0 keV μm -1) was investigated. It was found that survival curves were exponential, and mutation curves were linear for all LET values. The dependence of inactivation cross section on LET approached saturation near 120.0 keV μm -1. The mutation cross section saturated when LET was higher than 58.2 keV μm -1. Meanwhile, the highest RBE i for inactivation located at 120.0 keV μm -1 and the highest RBE m for mutation was at 58.2 keV μm -1. The experiments imply that the most efficient mutagenic part of the depth dose profile of carbon ion is at the plateau region with intermediate LET value in which energy deposited is high enough to induce mutagenic lesions but too low to induce over kill effect in the yeast cells.

Survival of tumor bearing mice by sequencing of low dose rate (LDR) neutron and photon radiation

International Nuclear Information System (INIS)

Onomura, C.I.; Feola, J.M.; Maruyama, Y.

1984-01-01

Cf-252 neutron radiation (NT) has been shown to be effective therapy for bulky, hypoxic human tumor and to produce consistent rapid clearance and 5 year cures. NT has been found to be more or less effective depending upon the schedule in which it is used and upon mixing with photon radiation. In an effort to study this scheduling and photon effect, LSA tumor was irradiated in vivo in a hypoxic, advanced state, in different schedules in combination of NT with Co-60 photons. The LSA lymphoma of C57BL/ym mice represents an accurate system to assess dose-response of tumor cells in vivo. Mean survival time was used as endpoint. A high RBE for LDR Cf-252 NT was observed with a RBE(n) of -- 5.0. The effect was not greatly sensitive to sequence in which photons were used. Comparison studies were also tested relative to LDR Cs-137 photon radiation. The results support the high efficacy of LDR NT for destruction of hypoxic tumor in vivo

The effect of radiation on bioluminescent bacteria: possible use of luminescent bacteria as a biological dosemeter

International Nuclear Information System (INIS)

Mantel, J.; Freidin, M.; Perry, H.

1983-01-01

The purpose of the study was to investigate the response of the bioluminescent Photobacterium phosphoreum to radiation, and the possible use of the bacteria as a biological radiation dosemeter, i.e. a water-equivalent biological system that will compare beams not merely on the basis of absorbed dose, but also have intrinsic RBE values for different radiation beams. Samples were irradiated by a 12 MeV electron beam at a dose rate of 3.0 Gy min -1 , by 60 Co gamma rays at 2.85 Gy min -1 , and by 100 kVsub(p) x-rays at a dose rate of 2.13 Gy min -1 . To study dose-rate dependence, the survival fraction was obtained for a 12 MeV electron beam at 0.50 and 12 Gy min -1 for 20.0 Gy. The survival fraction proved to be independent of dose rate in this range. The results presented in this work indicate that by using bioluminescent bacteria, RBE measurements can be markedly simplified and the results interpreted unequivocally. (U.K.)

The dependence of radiation response on the dose per fraction

International Nuclear Information System (INIS)

Joiner, M.C.

1989-01-01

The linear-quadratic (LQ) model explains the dependence of total dose in a fractionated course on the dose per fraction, in a very wide range of tumour and normal tissue studies, providing the dose per fraction remains above 2 Gy. In the range 2-1 Gy per fraction, some experimental studies show less increase in total dose than predicted by LQ; a probable explanation is incomplete repair between fractions given 2 seen between 1 and 0.1 Gy per fraction. This cannot be explained by incomplete repair; a modified LQ model where α decreases sharply with increasing dose per fraction in the range 0-1 Gy fits these data. The basic LQ model describes data from neutron fractionation studies, so the relationship between relative biological effectiveness (RBE) and X-ray dose per fraction can be expressed in terms of LQ parameters and fitted directly to RBE data. Results from different experiments, different assays and both top-up and full-course fractionation techniques, can all be included in one analysis. (author)

Somatic aberration induction in Tradescantia occidentalis by neutrons, X- and γ-radiations

International Nuclear Information System (INIS)

Dennis, J.A.

1976-01-01

Biological results, including statistical features, are described for the irradiation of Tradescantia occidentalis 250 kVp X-rays, cobalt-60 γ-radiation and monoenergetic neutrons with energies between 0.08 and 15 MeV. The effect studied was that of the induction of pink sectors in the otherwide blue staminal hairs of the flowers at low doses of radiation. Statistical aspects of the results suggest that a fraction of the asynchronous cell population in the hairs is very sensitive to neutron radiation, but not necessarily to lower LET radiations. All the results were fitted by a least-squares method by polynominals of different degrees. Best fits to X- and γ-ray data were provided by second-degree polynominals, and to the neutron data by either second- or third-degree polynominals. Limiting r.b.e. and o.e.r. values at low doses are derived. Some computed microdosimetric parameters are presented in comparison with the r.b.e. values. It is concluded that the effect studied is complex and may not provide a critical test of bio-physical theories of radiation effects. (author)

Dose-response relationship for the induction of structural chromosome aberrations in human spermatozoa after in vitro exposure ti tritium. beta. -rays

Energy Technology Data Exchange (ETDEWEB)

Kamiguchi, Yujiroh; Tateno, Hiroyuki; Mikamo, Kazuya (Asahikawa Medical College (Japan). Department of Biological Sciences)

1990-02-01

THe effects of tritium (HTO) {beta}-rays on human sperm chromosomes were studied using our interspecific in vitro fertilization system between human spermatozoa and zona-free hamster oocytes. Semen samples were treated with media containing 1.53-24.3 mCi/ml HTO for about 80 min. 1290 spermatozoa from the controls and 1842 spermatozoa from the irradiated groups were karyotyped. The incidence of spermatozoa with structural chromosome aberrations increased linearly with increasing dosage. Breakage-type aberrations occurred far more frequently than exchange-type. Chromosome-type aberrations appeared far more frequently than chromatid-ype. All of these types of aberrations showed linear dose-dependent increases. The RBE valus of HTO {beta}-rays relative to X-rays were calculated for the above-mentioned 5 indices, respectively. Their RBE values franged from 1.89 to 3.00 when the absorbed dose was estimated to be the minimum, whereas the values ranged between 1.04 and 1.65 when the absorbed dose was estimated to be the maximum. (author). 15 refs.; 3 figs.; 4 tabs.

Acute skin reactions observed in fractionated proton irradiation

International Nuclear Information System (INIS)

Arimoto, Takuro; Maruhashi, Noboru; Takada, Yoshihisa; Hayakawa, Yoshinori; Inada, Tetsuo; Kitagawa, Toshio

1989-01-01

Between May 1985 and July 1987, 49 skin reactions of 43 patients treated by proton irradiation were observed at the Particle Radiation Medical Science Center (PARMS), the University of Tsukuba. Taking the peak skin score as an endpoint, the radiobiological effects [relative biological effectiveness (RBE) and time-dose relationship] of the proton beam in multi-fractionated treatments were estimated. Factors influencing the skin dose, such as the prescribed tumor dose, tumor site, and number of applied fields, were also analyzed. The following conclusions regarding acute skin reactions to the clinical use of proton irradiation were obtained: 1) the physical skin-sparing effect of proton irradiation in single-field irradiation, especially in superficial regions, is not large compared with that of high-energy photon irradiation; 2) multidirectional proton irradiation significantly reduced the skin dose and severity of acute reasons; 3) the radiobiological effects of the proton beam, RBE and the time factor, estimated in human skin in multi-fractional treatment were slightly smaller than those of X-rays, i.e., 0.92 and -0.25±0.09, respectively. (author)

The protons of space and brain tumors: I. Clinical and dosimetric considerations

International Nuclear Information System (INIS)

Dalrymple, G.V.; Nagle, W.A.; Moss, A.J.; Cavin, L.A.; Broadwater, J.R.; McGuire, E.L.; Eason, C.S.

1989-01-01

Almost 25 years ago a large group of Rhesus monkeys were irradiated with protons (32--2300 MeV). The experiments were designed: (1) To estimate the RBE of protons, per se, and (2) To provide some estimate of the hazards of the radiation environment of space. The initial results showed the RBE to be about 1.0 for acute radiation effects (mortality, hematologic changes, etc). The colony has been maintained at Brooks AFB, TX since irradiation. The survivors of 55 MeV proton irradiation have developed a very high incidence of Glioblastoma multiforme, a highly malignant primary brain tumor. These tumors appeared 1--20 yrs after surface doses of 400--800 rads. Reconstruction of the dosimetry suggests that some areas within the brain may have received doses of 1500--2500 rads. More than 30 radiation induced Glioblastomas have been reported in human patients who had received therapeutic head irradiation. The radiation doses required to induce Glioblastoma were of the same order of magnitude as required to induce Glioblastoma in the Rhesus monkey

Radiobiological effects of heavy ions and protons. [on cells of mammals, bacteria and viruses

Science.gov (United States)

Ryzhov, N. I.; Vorozhtsova, S. V.; Krasavin, Y. A.; Mashinskaya, T. Y.; Savchenko, N. Y.; Fedorov, B. S.; Khlaponina, V. F.; Shelegedin, V. N.; Gut, L.; Sabo, L.

1974-01-01

Radiobiological effects of heavy ions and protons are studied on cells of mammals, bacteria, viruses and DNA of bacteria. Results show that the dose effect dependence bears an exponential character; the reduction of RBE as LET of particle increases reflects the different character of microdistribution of absorbed energy in biological objects with different levels of biological organization.

A Monte Carlo Code (PHOEL) for generating initial energies of photoelectrons and compton electrons produced by photons in water

International Nuclear Information System (INIS)

Turner, J.E.; Modolo, J.T.; Sordi, G.M.A.A.; Hamm, R.N.; Wright, H.A.

1979-01-01

PHOEL provides a source term for a Monte Carlo code which calculates the electron transport and energy degradation in liquid water. This code is used to study the relative biological effectiveness (RBE) of low-LET radiation at low doses. The basic numerical data used and their mathematical treatment are described as well as the operation of the code [pt

Radiation effects on the human organs, app. A

International Nuclear Information System (INIS)

Anon.

1976-01-01

The appendix is subdivided into eleven chapters dealing with radiation effcts on organisms and comprising the following subjects: biological effects of ionizing radiations (dose, LET, RBE, formation of radicals, age and sex, cell types, biological repair), recommendations and protective measures for somatic risks, genetic risks, experimental models and dose-effect relationships, and internal radiation. The groups conclusions are given

Optimization of Monte Carlo particle transport parameters and validation of a novel high throughput experimental setup to measure the biological effects of particle beams.

Science.gov (United States)

Patel, Darshana; Bronk, Lawrence; Guan, Fada; Peeler, Christopher R; Brons, Stephan; Dokic, Ivana; Abdollahi, Amir; Rittmüller, Claudia; Jäkel, Oliver; Grosshans, David; Mohan, Radhe; Titt, Uwe

2017-11-01

Accurate modeling of the relative biological effectiveness (RBE) of particle beams requires increased systematic in vitro studies with human cell lines with care towards minimizing uncertainties in biologic assays as well as physical parameters. In this study, we describe a novel high-throughput experimental setup and an optimized parameterization of the Monte Carlo (MC) simulation technique that is universally applicable for accurate determination of RBE of clinical ion beams. Clonogenic cell-survival measurements on a human lung cancer cell line (H460) are presented using proton irradiation. Experiments were performed at the Heidelberg Ion Therapy Center (HIT) with support from the Deutsches Krebsforschungszentrum (DKFZ) in Heidelberg, Germany using a mono-energetic horizontal proton beam. A custom-made variable range selector was designed for the horizontal beam line using the Geant4 MC toolkit. This unique setup enabled a high-throughput clonogenic assay investigation of multiple, well defined dose and linear energy transfer (LETs) per irradiation for human lung cancer cells (H460) cultured in a 96-well plate. Sensitivity studies based on application of different physics lists in conjunction with different electromagnetic constructors and production threshold values to the MC simulations were undertaken for accurate assessment of the calculated dose and the dose-averaged LET (LET d ). These studies were extended to helium and carbon ion beams. Sensitivity analysis of the MC parameterization revealed substantial dependence of the dose and LET d values on both the choice of physics list and the production threshold values. While the dose and LET d calculations using FTFP_BERT_LIV, FTFP_BERT_EMZ, FTFP_BERT_PEN and QGSP_BIC_EMY physics lists agree well with each other for all three ions, they show large differences when compared to the FTFP_BERT physics list with the default electromagnetic constructor. For carbon ions, the dose corresponding to the largest LET d

Sublethal effects of tritium on aquatic systems

International Nuclear Information System (INIS)

Strand, J.A.; Poston, T.M.

1982-01-01

It is the purpose of this continuing study to determine the relative biological effectiveness (RBE) of 3 H-beta irradiation when compared to 60 Co-gamma irradiation applying the relatively radiosensitive immune process of the rainbow trout, Salmo gairdneri. This study is also designed to investigate the nature of latent expression of immune incompetence in trout exposed to 3 H-irradiation during embryogenesis

Project Rio Blanco definition plan. Additional formation evaluation and production testing

International Nuclear Information System (INIS)

1975-09-01

Since the multiple Rio Blanco detonation three reentry wells have been drilled for test purposes: RB-E-01 (Emplacement Well); RB-AR-2 (Alternate Reentry Well); and RB-U-4 (Formation Evaluation Well). Additional testing in all these wells is now required to resolve some remaining technical questions. A plan describing the procedures, methods, responsibilities, and scheduling of the field operations is presented

Comparison of the cytological effects produced by ionizing radiations of different LET. Progress report, March 1974--April 1975

International Nuclear Information System (INIS)

Riley, E.F. Jr.

1975-01-01

Progress is reported on the following research projects: RBE of neutrons and x radiation for effects on rat lens epithelium; effects of x radiation on tumor cell transplants in mice; effects of fast neutrons on ascites tumors; the sparing effect of dose fractionation in the wounded rat lens; and DNA synthesis in wounded rat lens at various times after irradiation. (U.S.)

Evaluation of normal tissue responses to high-LET radiations

International Nuclear Information System (INIS)

Halnan, K.E.

1979-01-01

Clinical results presented have been analysed to evaluate normal tissue responses to high-LET radiations. Damage to brain, spinal cord, gut, skin, connective tissue and bone has occurred. A high RBE is probable for brain and possible for spinal cord and gut but other reasons for damage are also discussed. A net gain seems likely. Random controlled trials are advocated. (author)

Low energy (soft) x rays

International Nuclear Information System (INIS)

Hoshi, Masaharu; Antoku, Shigetoshi; Russell, W.J.; Miller, R.C.; Nakamura, Nori; Mizuno, Masayoshi; Nishio, Shoji.

1987-05-01

Dosimetry of low-energy (soft) X rays produced by the SOFTEX Model CMBW-2 was performed using Nuclear Associates Type 30 - 330 PTW, Exradin Type A2, and Shonka-Wyckoff ionization chambers with a Keithley Model 602 electrometer. Thermoluminescent (BeO chip) dosimeters were used with a Harshaw Detector 2000-A and Picoammeter-B readout system. Beam quality measurements were made using aluminum absorbers; exposure rates were assessed by the current of the X-ray tube and by exposure times. Dose distributions were established, and the average factors for non-uniformity were calculated. The means of obtaining accurate absorbed and exposed doses using these methods are discussed. Survival of V79 cells was assessed by irradiating them with soft X rays, 200 kVp X rays, and 60 Co gamma rays. The relative biological effectiveness (RBE) values for soft X rays with 0, 0.2, 0.7 mm added thicknesses of aluminum were 1.6, which were compared to 60 Co. The RBE of 200 kVp X rays relative to 60 Co was 1.3. Results of this study are available for reference in future RERF studies of cell survival. (author)

In vitro and in vivo studies of the TRIUMF pion therapy beam

International Nuclear Information System (INIS)

Skarsgard, L.D.; Douglas, B.G.; Denekamp, J.; Chaplin, D.J.; Lam, G.K.; Harrison, R.W.; Kornelsen, R.O.; Palcic, B.

1985-01-01

Patient treatments at TRIUMF (Tri-University Meson Facility, Vancouver, B. C.) use a moving spot raster scan technique where the pion range is modulated in depth for each position of the moving spot. The spot scans in a stepwise fashion and can produce any desired field shape. This approach provides very good dose uniformity across the treatment field and allows maximum flexibility in shaping the treatment volume. Survival of cultured cells has been used as a biological dosimeter to test the isoeffectiveness of the pion dose distributions, which must be shaped in depth to compensate for the depth-dependent LET distribution. Isoeffectiveness across the treatment field has also been verified using this system, which involves irradiating cells supported in a gelatin matrix. The response of pig skin to pion irradiation at TRIUMF has provided a check on the in vivo RBE for acute effects derived from our earlier studies with mouse foot. In addition, the pig skin reactions have been followed for several months to assess the later dermal response. The RBE of our pion beam relative to 270 kVp X rays is approximately 1.5 for both the acute epidermal and the later dermal responses

Observations on late effects in mice exposed to 400 MeV neutrons

CERN Document Server

Covelli, V; Bassani, B; Baarli, Johan; Bianchi, M; Metalli, P; Covelli, V; Di Paola, M; Bassani, B; Baarli, J no 2; Bianchi, M no 2; Metalli, P

1976-01-01

Life-long observations on mortality and pathology at death were carried out on groups of mice irradiated with 250 kV X-rays or exposed to a 400 MeV neutron beam, both directly and after attenuation corresponding to the maximum dose build-up region, at comparable dose-rates. Doses up to 84 rad of 400 MeV neutrons and up to 200 rad of X-rays showed no effect on the longevity of the animals, which suggests an upper limit to the r.b.e. for life-shortening of approximately 2·5. Similar conclusions were drawn from the data on all types of leukemias. For all other neoplasms, the age-specific death-rate showed a similar shortening of the latency times for groups of mice irradiated with 0–84 rad of 400 MeV direct neutrons and 0–400 rad of X-rays, also suggesting an upper limit to the r.b.e. slightly higher than that previously indicated for life-shortening. No definite effect was observed after exposure to the attenuated neutron beam at the doses used in these experiments.

Effect of neon ions on synchronized Chinese hamster cells

International Nuclear Information System (INIS)

Raju, M.R.; Carpenter, S.G.; Tokita, N.; Howard, J.

1985-01-01

The variation in radiosensitivity across the cell cycle after exposure to neon ions and 60 Co γ-rays is reported for cultured hamster cells. The cells were first synchronized by mitotic selection, then resynchronized in the region of the G 1 /S boundary by treatment with 10 -3 M hydroxyurea. Although the use of hydroxyurea improves the synchrony, it does sensitize cells at the G 1 /S boundary to some degree. The cells were exposed at the plateau and the distal peak position of a neon ion beam modified by a 10 cm wide ridge filter. The results indicate that the variation (ratio of maximum to minimum survival after fixed doses of radiation that are approximately matched to produce similar cell killing) was approximately 80 to 100-fold for 60 Co γ-rays and neon ions at the plateau, and 25-fold for distal peak neon ions. While the r.b.e. of distal peak neon ions decreased rapidly with increasing dose for cells in late S-phase, the r.b.e. is independent of dose for cells at the G 1 /S boundary. (author)

Effect of neon ions on synchronized Chinese hamster cells

Energy Technology Data Exchange (ETDEWEB)

Raju, M.R.; Carpenter, S.G.; Tokita, N. (Los Alamos National Lab., NM (USA)); Howard, J. (Lawrence Berkeley Lab., CA (USA))

1985-08-01

The variation in radiosensitivity across the cell cycle after exposure to neon ions and /sup 60/Co ..gamma..-rays is reported for cultured hamster cells. The cells were first synchronized by mitotic selection, then resynchronized in the region of the G/sub 1//S boundary by treatment with 10/sup -3/ M hydroxyurea. Although the use of hydroxyurea improves the synchrony, it does sensitize cells at the G/sub 1//S boundary to some degree. The cells were exposed at the plateau and the distal peak position of a neon ion beam modified by a 10 cm wide ridge filter. The results indicate that the variation (ratio of maximum to minimum survival after fixed doses of radiation that are approximately matched to produce similar cell killing) was approximately 80 to 100-fold for /sup 60/Co ..gamma..-rays and neon ions at the plateau, and 25-fold for distal peak neon ions. While the r.b.e. of distal peak neon ions decreased rapidly with increasing dose for cells in late S-phase, the r.b.e. is independent of dose for cells at the G/sub 1//S boundary.

Prenatal death and malformations after irradiation of mouse zygotes with neutrons or X-rays

International Nuclear Information System (INIS)

Pampfer, S.; Streffer, C.

1988-01-01

Female mice (strain: Heiligenberger Stamm) were irradiated with neutrons (7 MeV) or X-rays when embryos were at the early zygote stage; uterine contents were examined on gestation day 19 for prenatal mortality and malformed fetuses. For both radiation qualities, the dose-dependent survival curve fitted well to a simple exponential equation; the neutron relative biological efficiency (RBE) value was 2.3. The major fraction of deaths induced by exposure to neutrons or X-rays occurred before implantation. Aside from dead embryos, malformed fetuses were observed 19 days p.c. (postconception). The number of malformed fetuses increased with a linear-quadratic function of neutron or X-ray dose. Malformations were mainly gastroschisis, although omphaloceles and anencephalies were also observed. The neutron RBE value for the induction of malformations varied from 2.0 to 2.8 in the dose range tested. Except after 75-cGy neutrons, no significant increase in the proportion of stunted or skeletally malformed fetuses was noted. Our results indicated that the reaction of preimplantation embryos to irradiation could be more complex than the simple all-or-none response considered so far

Inactive and mutagenic effects induced by carbon beams of different LET values in a red yeast strain

Energy Technology Data Exchange (ETDEWEB)

Wang Jufang, E-mail: jufangwang@impcas.ac.c [Institute of Modern Physics, Chinese Academy of Sciences, Nanchang Road No. 509, Lanzhou 730000 (China); Lu Dong; Wu Xin; Sun Haining; Ma Shuang; Li Renmin; Li Wenjian [Institute of Modern Physics, Chinese Academy of Sciences, Nanchang Road No. 509, Lanzhou 730000 (China)

2010-09-15

To evaluate biological action of microorganism exposed to charged particles during the long distance space exploration, induction of inactivation and mutation in a red yeast strain Rhodotorula glutinis AY 91015 by carbon beams of different LET values (14.9-120.0 keV {mu}m{sup -1}) was investigated. It was found that survival curves were exponential, and mutation curves were linear for all LET values. The dependence of inactivation cross section on LET approached saturation near 120.0 keV {mu}m{sup -1}. The mutation cross section saturated when LET was higher than 58.2 keV {mu}m{sup -1}. Meanwhile, the highest RBE{sub i} for inactivation located at 120.0 keV {mu}m{sup -1} and the highest RBE{sub m} for mutation was at 58.2 keV {mu}m{sup -1}. The experiments imply that the most efficient mutagenic part of the depth dose profile of carbon ion is at the plateau region with intermediate LET value in which energy deposited is high enough to induce mutagenic lesions but too low to induce over kill effect in the yeast cells.

Radiation induced genetic damage in Aspergillus nidulans

International Nuclear Information System (INIS)

Georgiou, J.T.

1984-01-01

The mechanism by which ionizing radiation induces genetic damage in haploid and diploid conidia of Aspergillus nidulans was investigated. Although the linear dose-response curves obtained following low LET irradiation implied a 'single-hit' action of radiation, high LET radiations were much more efficient than low LET radiations, which suggests the involvement of a multiple target system. It was found that the RBE values for non-disjunction and mitotic crossing-over were very different. Unlike mitotic crossing-over, the RBE values for non-disjunction were much greater than for cell killing. This suggests that non-disjunction is a particularly sensitive genetical endpoint that is brought about by damage to a small, probably non-DNA target. Radiosensitisers were used to study whether radiation acts at the level of the DNA or some other cellular component. The sensitisation to electrons and/or X-rays by oxygen, and two nitroimidazoles (metronidazole and misonidazole) was examined for radiation induced non-disjunction, mitotic crossing-over, gene conversion, point mutation and cell killing. It was found that these compounds sensitised the cells considerably more to genetic damage than to cell killing. (author)

Relative biological effectiveness of tritium for induction of myeloid leukemia in CBA/H mice

International Nuclear Information System (INIS)

Johnson, J.R.; Myers, D.K.; Jones, A.R.

1995-01-01

To help resolve uncertainties as to the most appropriate weighting factor for tritium β rays, a large experiment was carried out to measure the relative biological effectiveness (RBE) of tritiated water compared to X-rays for the induction of myeloid leukemia in male mice of the CBA/H strain. The study was designed to estimate the lifetime incidence of myeloid leukemia in seven groups of about 750 mice each; radiation exposures were approximately 0, 1, 2 and 3 Gy both for tritiated water and for X rays. The lifetime incidence of leukemia in these mice increased from 0.13% in the control group to 6-8% in groups exposed to higher radiation doses. The results were fitted to various equations relating leukemia incidence to radiation dose, using both the raw data and data corrected for cumulative mouse-days at risk. The calculated RBE values for tritium β rays compared to X rays ranged from 1.0 ± to 1.3 ± 0.3. A w R value or 1 would thus appear to be more appropriate than a w R of 2 tritium β rays. 31 refs., 1 fig., 6 tabs

Dose-to-risk conversion factors for low-level tritium exposures

International Nuclear Information System (INIS)

Straume, T.

1992-01-01

During the past decade, a large number of radiobiological studies have become available for tritium-many of them focusing on the relative biological effectiveness (RBE) of tritium beta rays. These and previous studies indicate that tritium in body water produces the same spectrum of radiogenic effects, e.g., cancer, genetic effects, developmental abnormalities, and reproductive effects, observed following whole-body exposure to penetrating radiations such as gamma rays and x rays. The only significant difference in biological response between tritium beta-rays and the other common low linear-energy transfer (LET) radiations, such as gamma rays and x rays, appears to be the greater biological effectiveness of tritium beta rays. For example, tritium in the oxide form (HTO) is about 2 to 3 times more effective at low doses or low dose rates than gamma rays from 137 Cs or 60 CO (Straume, 1991). When tritium is bound to organic molecules, RBE values may be somewhat larger than those for HTO. It is now clear from the wealth of tritium data available that RBEs for tritium beta rays are higher than the quality factor of unity generally used in radiation protection

Studies on carcinogenic effect of tritiated water

International Nuclear Information System (INIS)

Zou Shuai; Wang Hui; Li Maohe; Lin Suqin

1994-09-01

Studies on carcinogenic effect of tritiated water is introduced in two parts. The first part is an in vitro study in which CHL-1 cells were exposed to tritiated water (9.25 x 10 5 ∼ 3.5 x 10 6 Bq/ml) for 24 ∼ 96 h and the accumulated dose was from 0.055 to 0.88 Gy. In order to estimate RBE of tritium for malignant transformation in CHL-1 cells, the induction of malignant transformation in CHL-1 cells by exposure to gamma rays of 137 Cs was tested. Based on the transformation rates, the RBE of tritium for malignant transformation in CHL-1 cells was estimated to be 1.6. The second part is an in vivo study. In the study, rats were fed with tritiated water (2.22 x 10 5 and 1.11 x 10 5 Bq/ml) for 1.5 a. Rats in control group were fed with tap water. Results showed that in the statistics, the differences in the total tumor incidence and malignant tumor incidence between high and low dose rate groups and control groups were remarkably significant

Need for improved standards in neutron personnel dosimetry

International Nuclear Information System (INIS)

Auxier, J.A.

1976-01-01

There is a continuing need for standards in neutron monitoring. A discussion of special problem areas and the benefits of intercomparisons is given. The RBE for leukemia induction in the survivors of the nuclear bombings of Hiroshima and Nagasaki is greater than ten for absorbed doses in the bone marrow of less than 100 rads; this may have an important impact on neutron standards preparation

General implications of research relevant to quality factors

International Nuclear Information System (INIS)

Dennis, J.A.

1987-01-01

Experiments on animals and mammalian cells in vitro support RBE values for fission neutrons relative low dose rate gamma radiation of about 20-30; and a dose rate reduction factor for low dose rate gamma radiation relative to high dose rates of between 2 to 10. Taken together these suggest that the risks from neutron and gamma radiation are not grossly underestimated in radiological protection. (author)

Density overwrites of internal tumor volumes in intensity modulated proton therapy plans for mobile lung tumors

Science.gov (United States)

Botas, Pablo; Grassberger, Clemens; Sharp, Gregory; Paganetti, Harald

2018-02-01

The purpose of this study was to investigate internal tumor volume density overwrite strategies to minimize intensity modulated proton therapy (IMPT) plan degradation of mobile lung tumors. Four planning paradigms were compared for nine lung cancer patients. Internal gross tumor volume (IGTV) and internal clinical target volume (ICTV) structures were defined encompassing their respective volumes in every 4DCT phase. The paradigms use different planning CT (pCT) created from the average intensity projection (AIP) of the 4DCT, overwriting the density within the IGTV to account for movement. The density overwrites were: (a) constant filling with 100 HU (C100) or (b) 50 HU (C50), (c) maximum intensity projection (MIP) across phases, and (d) water equivalent path length (WEPL) consideration from beam’s-eye-view. Plans were created optimizing dose-influence matrices calculated with fast GPU Monte Carlo (MC) simulations in each pCT. Plans were evaluated with MC on the 4DCTs using a model of the beam delivery time structure. Dose accumulation was performed using deformable image registration. Interplay effect was addressed applying 10 times rescanning. Significantly less DVH metrics degradation occurred when using MIP and WEPL approaches. Target coverage (D99≥slant 70 Gy(RBE)) was fulfilled in most cases with MIP and WEPL (D{{99}WEPL}=69.2+/- 4.0 Gy (RBE)), keeping dose heterogeneity low (D5-D{{95}WEPL}=3.9+/- 2.0 Gy(RBE)). The mean lung dose was kept lowest by the WEPL strategy, as well as the maximum dose to organs at risk (OARs). The impact on dose levels in the heart, spinal cord and esophagus were patient specific. Overall, the WEPL strategy gives the best performance and should be preferred when using a 3D static geometry for lung cancer IMPT treatment planning. Newly available fast MC methods make it possible to handle long simulations based on 4D data sets to perform studies with high accuracy and efficiency, even prior to individual treatment planning.

Spot Scanning Proton Therapy for Malignancies of the Base of Skull: Treatment Planning, Acute Toxicities, and Preliminary Clinical Outcomes

Energy Technology Data Exchange (ETDEWEB)

Grosshans, David R., E-mail: dgrossha@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Zhu, X. Ronald; Melancon, Adam [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Allen, Pamela K. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Poenisch, Falk; Palmer, Matthew [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); McAleer, Mary Frances; McGovern, Susan L. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gillin, Michael [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); DeMonte, Franco [Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chang, Eric L. [Department of Radiation Oncology, University of Southern California Keck School of Medicine, Los Angeles, California (United States); Brown, Paul D.; Mahajan, Anita [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2014-11-01

Purpose: To describe treatment planning techniques and early clinical outcomes in patients treated with spot scanning proton therapy for chordoma or chondrosarcoma of the skull base. Methods and Materials: From June 2010 through August 2011, 15 patients were treated with spot scanning proton therapy for chordoma (n=10) or chondrosarcoma (n=5) at a single institution. Toxicity was prospectively evaluated and scored weekly and at all follow-up visits according to Common Terminology Criteria for Adverse Events, version 3.0. Treatment planning techniques and dosimetric data were recorded and compared with those of passive scattering plans created with clinically applicable dose constraints. Results: Ten patients were treated with single-field-optimized scanning beam plans and 5 with multifield-optimized intensity modulated proton therapy. All but 2 patients received a simultaneous integrated boost as well. The mean prescribed radiation doses were 69.8 Gy (relative biological effectiveness [RBE]; range, 68-70 Gy [RBE]) for chordoma and 68.4 Gy (RBE) (range, 66-70) for chondrosarcoma. In comparison with passive scattering plans, spot scanning plans demonstrated improved high-dose conformality and sparing of temporal lobes and brainstem. Clinically, the most common acute toxicities included fatigue (grade 2 for 2 patients, grade 1 for 8 patients) and nausea (grade 2 for 2 patients, grade 1 for 6 patients). No toxicities of grades 3 to 5 were recorded. At a median follow-up time of 27 months (range, 13-42 months), 1 patient had experienced local recurrence and a second developed distant metastatic disease. Two patients had magnetic resonance imaging-documented temporal lobe changes, and a third patient developed facial numbness. No other subacute or late effects were recorded. Conclusions: In comparison to passive scattering, treatment plans for spot scanning proton therapy displayed improved high-dose conformality. Clinically, the treatment was well tolerated, and

Dose effect comparisons between HFR and BMRR irradiated dogs with respect to healthy tissue tolerance

International Nuclear Information System (INIS)

Huiskamp, R.; Philipp, K.H.I.; Gavin, P.R.; Wheeler, F.J.; Siefert, A.

1993-01-01

Epithermal neutron beams are being developed for the application of boron neutron capture therapy (BNCT) of deep seated tumors, like glioblastoma and astrocytomas, through the intact skin. Epithermal neutrons will be moderated by the tissue mass between skin and tumour to produce the thermal neutrons necessary for the 10 B(n,α) 7 Li reaction in the target tissue. Although the neutron capture cross-sections of elements in normal tissue are several orders of magnitude lower that for boron, the high abundance of hydrogen and nitrogen will cause a significant contribution to the total absorbed radiation dose through the 1 H(n,γ) 2 H and the 14 N(n,p) 14 C reaction, respectively. Due to inevitable incomplete filtration, an epithermal beam will also contain a fast neutron component, i.e. neutrons with energies ≥ 10 keV, and a γ-photon component originating from the reactor and produced in structural and filter materials. Therefore, the resultant radiation consists of a complex of low and high LET radiation of which the constitutents vary rapidly with depth in tissue. Based on the ongoing canine healthy tissue tolerance study at the Brookhaven Medical Research Reactor (BMRR) using the epithermal beam without BSH, the relative biological effectiveness (RBE) of the fast neutron beam component has been determined for skin reactions. In addition, a open-quotes compound factorclose quotes, i.e geometry x RBE, for the 10 B(n,α) 7 Li reaction was derived for dogs irradiated at the BMRR with the epithermal beam and BSH (Gavin et al.). Currently, a healthy tissue tolerance study with BSH is being carried out at the HB11 epithermal beam of the High Flux Reactor at Petten. The present paper describes preliminary dose effect comparisons between High Flux Reactor (HFR) and BMRR irradiated dogs with respect to healthy tissue tolerance in order to refine the BSH compound factors and the fast neutron RBE for skin and brain

Clinical Outcomes and Late Endocrine, Neurocognitive, and Visual Profiles of Proton Radiation for Pediatric Low-Grade Gliomas

International Nuclear Information System (INIS)

Greenberger, Benjamin A.; Pulsifer, Margaret B.; Ebb, David H.; MacDonald, Shannon M.; Jones, Robin M.; Butler, William E.; Huang, Mary S.; Marcus, Karen J.; Oberg, Jennifer A.; Tarbell, Nancy J.; Yock, Torunn I.

2014-01-01

Purpose/Objective(s): Primary low-grade gliomas are common brain tumors of childhood, many of which require radiation therapy (RT) as definitive treatment. Increased conformality of RT could decrease the incidence and severity of late effects. We report our experience with 32 pediatric patients treated with proton RT. Methods and Materials: Thirty-two pediatric patients with low-grade gliomas of the brain or spinal cord were treated with proton RT from 1995 to 2007. Sixteen patients received at least 1 regimen of chemotherapy before definitive RT. The median radiation dose was 52.2 Gy RBE (48.6-54 Gy RBE ). Results: The median age at treatment was 11.0 years (range, 2.7-21.5 years), with a median follow-up time of 7.6 years (range, 3.2-18.2 years). The 6-year and 8-year rates of progression-free survival were 89.7% and 82.8%, respectively, with an 8-year overall survival of 100%. For the subset of patients who received serial neurocognitive testing, there were no significant declines in Full-Scale Intelligence Quotient (P=.80), with a median neurocognitive testing interval of 4.5 years (range, 1.2-8.1 years) from baseline to follow-up, but subgroup analysis indicated some significant decline in neurocognitive outcomes for young children (<7 years) and those with significant dose to the left temporal lobe/hippocampus. The incidence of endocrinopathy correlated with a mean dose of ≥40 Gy RBE to the hypothalamus, pituitary, or optic chiasm. Stabilization or improvement of visual acuity was achieved in 83.3% of patients at risk for radiation-induced injury to the optic pathways. Conclusions: This report of late effects in children with low-grade gliomas after proton RT is encouraging. Proton RT appears to be associated with good clinical outcome, especially when the tumor location allows for increased sparing of the left temporal lobe, hippocampus, and hypothalamic-pituitary axis

Analysis of the DS86 atomic bomb radiation dosimetry methods using data on severe epilation

International Nuclear Information System (INIS)

Stram, D.O.; Mizuno, S.

1989-01-01

This report presents a reanalysis of the Hiroshima and Nagasaki data on severe epilation as an acute radiation effect using both the new DS86 and the old T65D dosimetries. The focus of the report is on several aspects of the data which have previously been examined by Jablon et al. The report examines the uniformity of epilation response across shielding category, across sex and age, and in terms of interactions between city, sex, age, and shielding category; it also investigates the apparent relative biological effectiveness (RBE) of neutrons in the DS86 dose compared with the T65D dose, using both within- and between-city information. In addition the report discusses evidence for nonlinearity in epilation response. The epilation response function exhibits nonlinearity in terms of both a marked increase in slope at about 0.75 Gy, and then, beginning at about 2.5 Gy, a leveling off and eventual decrease in response. The principal conclusions of the report are as follows. The use of the DS86 dosimetry rather than T65D increases the apparent RBE of neutrons compared with gamma dose from approximately 5 to 10. At these values of RBE the slope of the dose response, in a middle range from 0.75-2.5 Gy, is about 165% greater using DS86 than T65D. With respect to the interactions of sex, city, and shielding method, the size and significance of virtually all nonuniformities in epilation response seem using T65D are also evident with DS86. Additionally it seems difficult to find any evidence that DS86 is an improved predictor of epilation response over T65D. Finally, the fact that the nonlinearity in dose response and apparent actual downturn in epilation occurrence rate at the high end of dose is more striking with DS86 than with T65D is found to be due primarily to the common practice of truncating all T65D doses to 600 rad

Dosimetry and radiobiology of negative pions and heavy ions

International Nuclear Information System (INIS)

Raju, M.R.

1978-01-01

The depth dose distribution of pion beams has not been found superior to protons. Pion radiation quality at the plateau region is comparable to conventional low-LET radiations, and radiobiology results also indicate RBE values close to unity. In the pion stopping region, the radiation quality increases considerably. Radiobiology data for negative pions at the Bragg peak position clearly indicate the increase in RBE and the reduction in OER. Even at the Bragg peak position, compared to fast neutrons, the average LET of negative pions is lower. Pion radiobiology data have indicated lower RBE values and higher OER values compared to fast neutrons. The radiation quality of fast neutrons is in between that of carbon and neon ions at the peak region and that of neon ions at the plateau is lower than for fast neutrons. The mean LET value for helium ions, even at the distal end of the peak, is lower than for fast neutrons. Dose localization of heavy ions has been found to decrease slowly with increasing charge of the heavy ion. The intercellular contact that protects cells after exposure to low-LET radiations is not detected after exposure to heavy ions. Single and fractionated doses of heavy ions produce dose-response curves for heavy ions having reduced shoulders but similar slopes when compared to gamma rays. Fractionated treatments of heavy ions produce an enhanced effect in the peak region compared to the plateau region and could lead to a substantial gain in therapeutic ratio. The OER for protons was similar to that for x rays. The OER values for negative pions, helium ions, and carbon ions were larger, for neon ions similar, and for argon ions smaller when compared to fast neutrons.Negative pions, helium ions, and carbon ions may be very effective clinically because the radiation quality of these beams is similar to that of the mixed scheme of neutrons and x rays

Clinical outcomes and toxicity of proton beam therapy for advanced cholangiocarcinoma

International Nuclear Information System (INIS)

Makita, Chiyoko; Kikuchi, Yasuhiro; Hareyama, Masato; Murakami, Masao; Fuwa, Nobukazu; Hata, Masaharu; Inoue, Tomio; Nakamura, Tatsuya; Takada, Akinori; Takayama, Kanako; Suzuki, Motohisa; Ishikawa, Yojiro; Azami, Yusuke; Kato, Takahiro; Tsukiyama, Iwao

2014-01-01

We examined the efficacy and toxicity of proton beam therapy (PBT) for treating advanced cholangiocarcinoma. The clinical data and outcomes of 28 cholangiocarcinoma patients treated with PBT between January 2009 and August 2011 were retrospectively examined. The Kaplan–Meier method was used to estimate overall survival (OS), progression-free survival (PFS), and local control (LC) rates, and the log-rank test to analyze the effects of different clinical and treatment variables on survival. Acute and late toxicities were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. The median age of the 17 male and 11 female patients was 71 years (range, 41 to 84 years; intrahepatic/peripheral cholangiocarcinoma, n = 6; hilar cholangiocarcinoma/Klatskin tumor, n = 6; distal extrahepatic cholangiocarcinoma, n = 3; gallbladder cancer, n = 3; local or lymph node recurrence, n = 10; size, 20–175 mm; median 52 mm). The median radiation dose was 68.2 Gy (relative biological effectiveness [RBE]) (range, 50.6 to 80 Gy (RBE)), with delivery of fractions of 2.0 to 3.2 Gy (RBE) daily. The median follow-up duration was 12 months (range, 3 to 29 months). Fifteen patients underwent chemotherapy and 8 patients, palliative biliary stent placement prior to PBT. OS, PFS, and LC rates at 1 year were 49.0%, 29.5%, and 67.7%, respectively. LC was achieved in 6 patients, and was better in patients administered a biologically equivalent dose of 10 (BED10) > 70 Gy compared to those administered < 70 Gy (83.1% vs. 22.2%, respectively, at 1 year). The variables of tumor size and performance status were associated with survival. Late gastrointestinal toxicities grade 2 or greater were observed in 7 patients <12 months after PBT. Cholangitis was observed in 11 patients and 3 patients required stent replacement. Relatively high LC rates after PBT for advanced cholangiocarcinoma can be achieved by delivery of a BED10 > 70 Gy. Gastrointestinal

Calculation of complication probability of pion treatment at PSI using dose-volume histograms

International Nuclear Information System (INIS)

Nakagawa, Keiichi; Akanuma, Atsuo; Aoki, Yukimasa

1991-01-01

In the conformation technique a target volume is irradiated uniformly as in conventional radiations, whereas surrounding tissue and organs are nonuniformly irradiated. Clinical data on radiation injuries that accumulate with conventional radiation are not applicable without appropriate compensation. Recently a putative solution of this problem was proposed by Lyman using dose-volume histograms. This histogram reduction method reduces a given dose-volume histogram of an organ to a single step which corresponds to the equivalent complication probability by interpolation. As a result it converts nonuniform radiation into a unique dose to the whole organ which has the equivalent likelihood of radiation injury. This method is based on low LET radiation with conventional fractionation schedules. When it is applied to high LET radiation such as negative pion treatment, a high LET dose should be converted to an equivalent photon dose using an appropriate value of RBE. In the present study the histogram reduction method was applied to actual patients treated by the negative pion conformation technique at the Paul Scherrer Institute. Out of evaluable 90 cases of pelvic tumors, 16 developed grade III-IV bladder injury, and 7 developed grade III-IV rectal injury. The 90 cases were divided into roughly equal groups according to the equivalent doses to the entire bladder and rectum. Complication rates and equivalent doses to the full organs in these groups could be represented by a sigmoid dose-effect relation. When RBE from a pion dose to a photon dose is assumed to be 2.1 for bladder injury, the rates of bladder complications fit best to the theoretical complication curve. When the RBE value was 2.3, the rates of rectal injury fit the theoretical curve best. These values are close to the conversion factor of 2.0 that is used in clinical practice at PSI. This agreement suggests the clinical feasibility of the histogram reduction method in conformation radiotherapy. (author)

Clinical Outcomes and Late Endocrine, Neurocognitive, and Visual Profiles of Proton Radiation for Pediatric Low-Grade Gliomas

Energy Technology Data Exchange (ETDEWEB)

Greenberger, Benjamin A. [Harvard Medical School, Boston, Massachusetts (United States); Pulsifer, Margaret B. [Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts (United States); Ebb, David H. [Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts (United States); MacDonald, Shannon M. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Jones, Robin M. [Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts (United States); Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts (United States); Butler, William E. [Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts (United States); Huang, Mary S. [Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts (United States); Marcus, Karen J. [Department of Radiation Oncology, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Oberg, Jennifer A. [Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, New York (United States); Tarbell, Nancy J. [Harvard Medical School, Boston, Massachusetts (United States); Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Yock, Torunn I., E-mail: tyock@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

2014-08-01

Purpose/Objective(s): Primary low-grade gliomas are common brain tumors of childhood, many of which require radiation therapy (RT) as definitive treatment. Increased conformality of RT could decrease the incidence and severity of late effects. We report our experience with 32 pediatric patients treated with proton RT. Methods and Materials: Thirty-two pediatric patients with low-grade gliomas of the brain or spinal cord were treated with proton RT from 1995 to 2007. Sixteen patients received at least 1 regimen of chemotherapy before definitive RT. The median radiation dose was 52.2 Gy{sub RBE} (48.6-54 Gy{sub RBE}). Results: The median age at treatment was 11.0 years (range, 2.7-21.5 years), with a median follow-up time of 7.6 years (range, 3.2-18.2 years). The 6-year and 8-year rates of progression-free survival were 89.7% and 82.8%, respectively, with an 8-year overall survival of 100%. For the subset of patients who received serial neurocognitive testing, there were no significant declines in Full-Scale Intelligence Quotient (P=.80), with a median neurocognitive testing interval of 4.5 years (range, 1.2-8.1 years) from baseline to follow-up, but subgroup analysis indicated some significant decline in neurocognitive outcomes for young children (<7 years) and those with significant dose to the left temporal lobe/hippocampus. The incidence of endocrinopathy correlated with a mean dose of ≥40 Gy{sub RBE} to the hypothalamus, pituitary, or optic chiasm. Stabilization or improvement of visual acuity was achieved in 83.3% of patients at risk for radiation-induced injury to the optic pathways. Conclusions: This report of late effects in children with low-grade gliomas after proton RT is encouraging. Proton RT appears to be associated with good clinical outcome, especially when the tumor location allows for increased sparing of the left temporal lobe, hippocampus, and hypothalamic-pituitary axis.

A Prospective Comparison of the Effects of Interfractional Variations on Proton Therapy and Intensity Modulated Radiation Therapy for Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Moteabbed, Maryam, E-mail: mmoteabbed@partners.org; Trofimov, Alexei; Sharp, Gregory C.; Wang, Yi; Zietman, Anthony L.; Efstathiou, Jason A.; Lu, Hsiao-Ming

2016-05-01

Purpose: To quantify and compare the impact of interfractional setup and anatomic variations on proton therapy (PT) and intensity modulated radiation therapy (IMRT) for prostate cancer. Methods and Materials: Twenty patients with low-risk or intermediate-risk prostate cancer randomized to receive passive-scattering PT (n=10) and IMRT (n=10) were selected. For both modalities, clinical treatment plans included 50.4 Gy(RBE) to prostate and proximal seminal vesicles, and prostate-only boost to 79.2 Gy(RBE) in 1.8 Gy(RBE) per fraction. Implanted fiducials were used for prostate localization and endorectal balloons were used for immobilization. Patients in PT and IMRT arms received weekly computed tomography (CT) and cone beam CT (CBCT) scans, respectively. The planned dose was recalculated on each weekly image, scaled, and mapped onto the planning CT using deformable registration. The resulting accumulated dose distribution over the entire treatment course was compared with the planned dose using dose-volume histogram (DVH) and γ analysis. Results: The target conformity index remained acceptable after accumulation. The largest decrease in the average prostate D{sub 98} was 2.2 and 0.7 Gy for PT and IMRT, respectively. On average, the mean dose to bladder increased by 3.26 ± 7.51 Gy and 1.97 ± 6.84 Gy for PT and IMRT, respectively. These values were 0.74 ± 2.37 and 0.56 ± 1.90 for rectum. Differences between changes in DVH indices were not statistically significant between modalities. All volume indices remained within the protocol tolerances after accumulation. The average pass rate for the γ analysis, assuming tolerances of 3 mm and 3%, for clinical target volume, bladder, rectum, and whole patient for PT/IMRT were 100/100, 92.6/99, 99.2/100, and 97.2/99.4, respectively. Conclusion: The differences in target coverage and organs at risk dose deviations for PT and IMRT were not statistically significant under the guidelines of this protocol.

WE-H-BRA-09: Application of a Modified Microdosimetric-Kinetic Model to Analyze Relative Biological Effectiveness of Ions Relevant to Light Ion Therapy Using the Particle Heavy Ion Transport System

Energy Technology Data Exchange (ETDEWEB)

Butkus, M [Yale-New Haven Hospital, New Haven, CT (United States); Palmer, T [Oregon State University, Corvallis, OR (United States)

2016-06-15

Purpose: To evaluate the dose and biological effectiveness of various ions that could potentially be used for actively scanned particle therapy. Methods: The PHITS Monte Carlo code paired with a microscopic analytical function was used to determine probability distribution functions of the lineal energy in 0.3µm diameter spheres throughout a water phantom. Twenty million primary particles for 1H beams and ten million particles for 4He, 7Li, 10B, 12C, 14N, 16O, and 20Ne were simulated for 0.6cm diameter pencil beams. Beam energies corresponding to Bragg peak depths of 50, 100, 150, 200, 250, and 300mm were used and evaluated transversely every millimeter and radially in annuli with outer radius of 1.0, 2.0, 3.0, 3.2, 3.4, 3.6, 4.0, 5.0, 10.0, 15.0, 20.0 and 25.0mm. The acquired probability distributions were reduced to dose-mean lineal energies and applied to the modified microdosimetric kinetic model for five different cell types to calculate relative biological effectiveness (RBE) compared to 60Co beams at the 10% survival threshold. The product of the calculated RBEs and the simulated physical dose was taken to create biological dose and comparisons were then made between the various ions. Results: Transversely, the 10B beam was seen to minimize relative biological dose in both the constant and accelerated dose change regions, proximal to the Bragg Peak, for all beams traveling greater than 50mm. For the 50mm beam, 7Li was seen to provide the most optimal biological dose profile. Radially small fluctuations (<4.2%) were seen in RBE while physical dose was greater than 1% for all beams. Conclusion: Even with the growing usage of 12C, it may not be the most optimal ion in all clinical situations. Boron was calculated to have slightly enhanced RBE characteristics, leading to lower relative biological doses.

Application of TSH bioindicator for studying the biological efficiency of radiation

International Nuclear Information System (INIS)

Cebulska-Wasilewska, A.; Rekas, K.; Kim, J.K.

1999-01-01

The effectiveness of neutrons from a californium-252 source in the induction of various abnormalities in the Tradescantia clone 4430 stamen hair cells (TSH assay) was studied. Special attention was paid to check whether any enhancement in effects caused by the process of boron neutron capture is visible in the cells enriched with boron ions. Two chemicals (borax and BSH) were applied to introduce boron-10 ions into cells. Inflorescences, normal or prepared with chemicals containing boron, were irradiated in the air with neutrons from the 252 Cf source at KOREI, Taejon, Korea. To estimate the relative biological effectiveness (RBE) of the boron under the study, Tradescantia inflorescences without chemical pretreatment were irradiated with various doses of X-rays. The ranges of radiation doses for neutrons were 0-0.1Gy and for X-rays 0-0.5 Gy. After time needed to complete the postirradiation repair tradescantia cuttings were transported to Cracow were screening of gene and lethal mutations in somatic cells of stamen hairs have been done and dose response relationships were plotted. In two independent experimental studies an alternation of dose-response curves was observed, probably due to slight changes in the postexposure plant treatment. However, it has not results in the change of the maximal RBE values, which for the induction of gene mutations were estimated as 5.6 in the pilot studies and 5.8 one year later. Inflorescences pretreated with borax and BSH responded to neutrons differently. The values of RBE have changed from 5.6 to 7.9 in the case of plants pretreated with 240 ppm of B-10 from borax, and 5.8 to 7.2 in the case of 400 ppm of B-10 from BSH. The results showed an increase, although statistically insignificant, in biological efficiency of radiation from the 252 Cf source in the samples pretreated with boron containing chemicals. (author)

Characterization of glial cell K-Cl cotransport.

Science.gov (United States)

Gagnon, Kenneth B E; Adragna, Norma C; Fyffe, Robert E W; Lauf, Peter K

2007-01-01

The molecular mechanism of K-Cl cotransport (KCC) consists of at least 4 isoforms, KCC 1, 2, 3, and 4 which, in multiple combinations, exist in most cells, including erythrocytes and neuronal cells. We utilized reverse-transcriptase-polymerase chain reaction (RT-PCR) and ion flux studies to characterize KCC activity in an immortalized in vitro cell model for fibrous astrocytes, the rat C6 glioblastoma cell. Isoform-specific sets of oligonucleotide primers were synthesized for NKCC1, KCC1, KCC2, KCC3, KCC4, and also for NKCC1 and actin. K-Cl cotransport activity was determined by measuring either the furosemide-sensitive, or the Cl(-)-dependent bumetanide-insensitive Rb(+) (a K(+) congener) influx in the presence of the Na/K pump inhibitor ouabain. Rb(+) influx was measured at a fixed external Cl concentrations, [Cl(-)](e), as a function of varying external Rb concentrations, [Rb(+)](e), and at a fixed [Rb(+)](e) as a function of varying [Cl(-)](e), and with equimolar Cl replacement by anions of the chaotropic series. RT-PCR of C6 glioblastoma (C6) cells identified mRNA for three KCC isoforms (1, 3, and 4). NKCC1 mRNA was also detected. The apparent K(m) for KCC-mediated Rb(+) influx was 15 mM [Rb(+)](e), and V(max) 12.5 nmol Rb(+) * mg protein(-1) * minute(-1). The calculated apparent K(m) for external Cl(-) was 13 mM and V(max) 14.4 nmol Rb(+) * mg protein(-1) * minute(-1). The anion selectivity sequence of the furosemide-sensitive Rb(+) influx was Cl(-)>Br-=NO(3)(-)>I(-)=SCN(-)>Sfm(-) (sulfamate). Established activators of K-Cl cotransport, hyposmotic shock and N-ethylmaleimide (NEM) pretreatment, stimulated furosemide-sensitive Rb(+) influx. A ñ50% NEM-induced loss of intracellular K(+) was prevented by furosemide. We have identified by RT-PCR the presence of three distinct KCC isoforms (1, 3, and 4) in rat C6 glioblastoma cells, and functionally characterized the anion selectivity and kinetics of their collective sodium-independent cation-chloride cotransport

MO-A-201-01: A Cliff’s Notes Version of Proton Therapy

International Nuclear Information System (INIS)

Kruse, J.

2016-01-01

Proton therapy is a rapidly growing modality in the fight against cancer. From a high-level perspective the process of proton therapy is identical to x-ray based external beam radiotherapy. However, this course is meant to illustrate for x-ray physicists the many differences between x-ray and proton based practices. Unlike in x-ray therapy, proton dose calculations use CT Hounsfield Units (HU) to determine proton stopping power and calculate the range of a beam in a patient. Errors in stopping power dominate the dosimetric uncertainty in the beam direction, while variations in patient position determine uncertainties orthogonal to the beam path. Mismatches between geometric and range errors lead to asymmetric uncertainties, and so while geometric uncertainties in x-ray therapy are mitigated through the use of a Planning Target Volume (PTV), this approach is not suitable for proton therapy. Robust treatment planning and evaluation are critical in proton therapy, and will be discussed in this course. Predicting the biological effect of a proton dose distribution within a patient is also a complex undertaking. The proton therapy community has generally regarded the Radiobiological Effectiveness (RBE) of a proton beam to be 1.1 everywhere in the patient, but there are increasing data to suggest that the RBE probably climbs higher than 1.1 near the end of a proton beam when the energy deposition density increases. This lecture will discuss the evidence for variable RBE in proton therapy and describe how this is incorporated into current proton treatment planning strategies. Finally, there are unique challenges presented by the delivery process of proton therapy. Many modern systems use a spot scanning technique which has several advantages over earlier scattered beam designs. However, the time dependence of the dose deposition leads to greater concern with organ motion than with scattered protons or x-rays. Image guidance techniques in proton therapy may also differ

MO-A-201-00: A Cliff’s Notes Version of Proton Therapy

International Nuclear Information System (INIS)

2016-01-01

Proton therapy is a rapidly growing modality in the fight against cancer. From a high-level perspective the process of proton therapy is identical to x-ray based external beam radiotherapy. However, this course is meant to illustrate for x-ray physicists the many differences between x-ray and proton based practices. Unlike in x-ray therapy, proton dose calculations use CT Hounsfield Units (HU) to determine proton stopping power and calculate the range of a beam in a patient. Errors in stopping power dominate the dosimetric uncertainty in the beam direction, while variations in patient position determine uncertainties orthogonal to the beam path. Mismatches between geometric and range errors lead to asymmetric uncertainties, and so while geometric uncertainties in x-ray therapy are mitigated through the use of a Planning Target Volume (PTV), this approach is not suitable for proton therapy. Robust treatment planning and evaluation are critical in proton therapy, and will be discussed in this course. Predicting the biological effect of a proton dose distribution within a patient is also a complex undertaking. The proton therapy community has generally regarded the Radiobiological Effectiveness (RBE) of a proton beam to be 1.1 everywhere in the patient, but there are increasing data to suggest that the RBE probably climbs higher than 1.1 near the end of a proton beam when the energy deposition density increases. This lecture will discuss the evidence for variable RBE in proton therapy and describe how this is incorporated into current proton treatment planning strategies. Finally, there are unique challenges presented by the delivery process of proton therapy. Many modern systems use a spot scanning technique which has several advantages over earlier scattered beam designs. However, the time dependence of the dose deposition leads to greater concern with organ motion than with scattered protons or x-rays. Image guidance techniques in proton therapy may also differ

MO-A-201-00: A Cliff’s Notes Version of Proton Therapy

Energy Technology Data Exchange (ETDEWEB)

NONE

2016-06-15

Proton therapy is a rapidly growing modality in the fight against cancer. From a high-level perspective the process of proton therapy is identical to x-ray based external beam radiotherapy. However, this course is meant to illustrate for x-ray physicists the many differences between x-ray and proton based practices. Unlike in x-ray therapy, proton dose calculations use CT Hounsfield Units (HU) to determine proton stopping power and calculate the range of a beam in a patient. Errors in stopping power dominate the dosimetric uncertainty in the beam direction, while variations in patient position determine uncertainties orthogonal to the beam path. Mismatches between geometric and range errors lead to asymmetric uncertainties, and so while geometric uncertainties in x-ray therapy are mitigated through the use of a Planning Target Volume (PTV), this approach is not suitable for proton therapy. Robust treatment planning and evaluation are critical in proton therapy, and will be discussed in this course. Predicting the biological effect of a proton dose distribution within a patient is also a complex undertaking. The proton therapy community has generally regarded the Radiobiological Effectiveness (RBE) of a proton beam to be 1.1 everywhere in the patient, but there are increasing data to suggest that the RBE probably climbs higher than 1.1 near the end of a proton beam when the energy deposition density increases. This lecture will discuss the evidence for variable RBE in proton therapy and describe how this is incorporated into current proton treatment planning strategies. Finally, there are unique challenges presented by the delivery process of proton therapy. Many modern systems use a spot scanning technique which has several advantages over earlier scattered beam designs. However, the time dependence of the dose deposition leads to greater concern with organ motion than with scattered protons or x-rays. Image guidance techniques in proton therapy may also differ

MO-A-201-01: A Cliff’s Notes Version of Proton Therapy

Energy Technology Data Exchange (ETDEWEB)

Kruse, J. [Mayo Clinic (United States)

2016-06-15

Proton therapy is a rapidly growing modality in the fight against cancer. From a high-level perspective the process of proton therapy is identical to x-ray based external beam radiotherapy. However, this course is meant to illustrate for x-ray physicists the many differences between x-ray and proton based practices. Unlike in x-ray therapy, proton dose calculations use CT Hounsfield Units (HU) to determine proton stopping power and calculate the range of a beam in a patient. Errors in stopping power dominate the dosimetric uncertainty in the beam direction, while variations in patient position determine uncertainties orthogonal to the beam path. Mismatches between geometric and range errors lead to asymmetric uncertainties, and so while geometric uncertainties in x-ray therapy are mitigated through the use of a Planning Target Volume (PTV), this approach is not suitable for proton therapy. Robust treatment planning and evaluation are critical in proton therapy, and will be discussed in this course. Predicting the biological effect of a proton dose distribution within a patient is also a complex undertaking. The proton therapy community has generally regarded the Radiobiological Effectiveness (RBE) of a proton beam to be 1.1 everywhere in the patient, but there are increasing data to suggest that the RBE probably climbs higher than 1.1 near the end of a proton beam when the energy deposition density increases. This lecture will discuss the evidence for variable RBE in proton therapy and describe how this is incorporated into current proton treatment planning strategies. Finally, there are unique challenges presented by the delivery process of proton therapy. Many modern systems use a spot scanning technique which has several advantages over earlier scattered beam designs. However, the time dependence of the dose deposition leads to greater concern with organ motion than with scattered protons or x-rays. Image guidance techniques in proton therapy may also differ

Radiation carcinogenesis, laboratory studies

International Nuclear Information System (INIS)

Shellabarger, C.J.

1974-01-01

Laboratory studies on radioinduced carcinogenesis are reviewed. Some topics discussed are: radioinduced neoplasia in relation to life shortening; dose-response relationships; induction of skin tumors in rats by alpha particles and electrons; effects of hormones on tumor response; effects of low LET radiations delivered at low dose-rates; effects of fractionated neutron radiation; interaction of RBE and dose rate effects; and estimates of risks for humans from animal data. (U.S.)

In-Plant Reuse of Pollution Abated Waters.

Science.gov (United States)

1984-08-01

diameter distributions obtained by dif- For example, the adsorption of hydroxymethyl ferentiating cumulative surface area-pore diameter furfural (HMF) in...Activated Carbons G. Basic Concepts of Adsorption on Activated Carbon G-1 Basic Concepts of Adsorption on Activated Carbon Calgon Corporation G-2...been r-un on granular activated carbon to select the proper Cj.rbe--fer -;-the carbon columns and to determine the carbon loading (See Adsorption

Amount of sister chromatid exchanges and survival of Chinese hamster V79-4 cells after irradiation with 0,7 MeV neutrons

International Nuclear Information System (INIS)

Lapidus, I.L.; Nasonova, E.A.

1987-01-01

The dependence of the survival and induction of sister chromatid exchanges (SCEs) in Chinese hamster V79-4 cells on the dose of γ-rays and neutrons with average energy 0.7 MeV has been analysed. The value of RBE for neutrons was 5.5. It has been shown that the number of SCE increased with the dose of γ-irradiation and no induction could be detected after neutron irradiation

Research needs for setting environmental standards

International Nuclear Information System (INIS)

Ellett, W.C.

1978-01-01

The following topics are discussed: risks to humans from ingestion or inhalation of actinides; transport of ingested actinides across the intestinal wall; tissue distribution of transuranics; dose to gonads from transuranics; genetic risks from alpha emitters; RBE for neutrons in gonadal tissues; use of cancer as endpoint for risk analysis; limits for gross alpha activity in drinking water; and high thorium levels in the vicinity of phosphate plants

Proton beam radiotherapy as part of comprehensive regional nodal irradiation for locally advanced breast cancer.

Science.gov (United States)

Verma, Vivek; Iftekaruddin, Zaid; Badar, Nida; Hartsell, William; Han-Chih Chang, John; Gondi, Vinai; Pankuch, Mark; Gao, Ming; Schmidt, Stacey; Kaplan, Darren; McGee, Lisa

2017-05-01

This study evaluates acute toxicity outcomes in breast cancer patients treated with adjuvant proton beam therapy (PBT). From 2011 to 2016, 91 patients (93 cancers) were treated with adjuvant PBT targeting the intact breast/chest wall and comprehensive regional nodes including the axilla, supraclavicular fossa, and internal mammary lymph nodes. Toxicity was recorded weekly during treatment, one month following treatment, and then every 6months according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Charts were retrospectively reviewed to verify toxicities, patient parameters, disease and treatment characteristics, and disease-related outcomes. Median follow-up was 15.5months. Median PBT dose was 50.4 Gray relative biological effectiveness (GyRBE), with subsequent boost as clinically indicated (N=61, median 10 GyRBE). Chemotherapy, when administered, was given adjuvantly (N=42) or neoadjuvantly (N=46). Grades 1, 2, and 3 dermatitis occurred in 23%, 72%, and 5%, respectively. Eight percent required treatment breaks owing to dermatitis. Median time to resolution of dermatitis was 32days. Grades 1, 2, and 3 esophagitis developed in 31%, 33%, and 0%, respectively. PBT displays acceptable toxicity in the setting of comprehensive regional nodal irradiation. Copyright © 2017. Published by Elsevier B.V.

Repair in mouse lung of multifraction X rays and neutrons: extension to 40 fractions

International Nuclear Information System (INIS)

Parkins, C.S.; Fowler, J.F.

1985-01-01

Repair parameters were calculated from measurements of breathing rate and lethality at monthly intervals up to 17 months after irradiation with 1, 10, 20 or 40 equal fractions, down to 1.1 Gy of x-rays and 0.18 Gy of 3 MeV neutrons per fraction. Sparing of neutron damage was negligible when the neutron dose was divided into multiple fractions; progressively greater repair of lung damage was seen after increasing x-ray fractions. Significant increase in the iso-effect dose for 40 x-ray fractions was found compared with 20, even at two fractions per day at six hour intervals, as was the case in the 40 fraction experiment. Data were well fitted by the linear quadratic formula for response vs. dose per fraction and the ratio γ/β yielded values of approx. 3 Gy after x-rays and 30 to 40 Gy after neutron irradiation, not different from γ/β ratios found for up to 20 fractions. Single dose RBE was less than 2, increasing to about six at the lowest dose per fraction measured, agreeing with previous results. The ratio of the γ component for neutrons to that for x-rays was approx. 8, which is therefore the limiting RBE predicted for infinitely small fractional doses. (U.K.)

Induction of malignant transformation in CHL-1 cells by exposure to tritiated water

International Nuclear Information System (INIS)

Zou Shu'ai; Wang Hui

1992-01-01

The induction of neoplastic transformation in CHL-1 cells by low-dose-rate exposure to tritiated water was reported. CHL-1 cells were exposed to tritiated water (9.25 x 10 5 - 3.7 x 10 6 Bq/mL) for 24-96 hours and the accumulated doses were estimated to be 0.055-0.88 Gy, respectively. Neoplastic transformation was found in all exposed cell groups. The morphological study and transplantation test was carried out for demonstration malignancy of the transformed cells and the results show that they are with the morphology and behaviour for malignant tumour cells. For CHL-1 cells exposed to various doses of tritiated water, transformation rates were found to be from 3.28% to 13.0% at dose of 0.055-0.88 Gy. In order to estimate RBE of tritium for malignant transformation in CHL-1 cells, the induction of malignant transformation in CHL-1 cells by exposure to 137 Cs gamma-rays was carried out at dose rates of 0.359 Gy/24 hr and transformation rates for irradiated CHL-1 cells were found to be from 2.59% to 13.4%. Based on these data, RBE of tritium for malignant transformation in CHL-1 cells was estimated to be 1.6

Biological effects of tritiated water in low concentration of human lymphocyte chromosome

International Nuclear Information System (INIS)

Tanaka, K.; Kamada, N.; Sawaeda, S.

1992-01-01

This study was undertaken to investigate the dose-response relationship of tritiated water (HTO) for chromosome aberration in the human lymphocytes, at low dose in vitro exposure ranging from 0.1-1 Gy. The Relative Biological Effectiveness values of HTO with respect to 60 Co gamma ray at a dose rate of 2 cGy/min(15 mCi/ml), at low dose range for the induction of dicentric and centric ring chromosomes were 2.7 in lymphocytes. Also lymphocytes were chronically exposed to HTO for 67 to 80 hrs at different lower dose rates (0.5 and 0.02 cGy/min). There was a 77% decrease in the yields of dicentrics and centric rings, at the dose rate of 0.02cGy/min of HTO, presenting a clear dose rate effect of HTO. The RBE value of HTO relative to 137 Cs gamma ray was 2.0 at the dose rate of 0.02cGy/min(0.15mCi/ml). This suggests that a higher dose rate of HTO exposure has a higher risk and a decrease of RBE value at low dose rate. These results provide useful information for the assessment of health risks in humans specially exposed to low concentration of HTO. (author). 6 refs., 2 figs

Compound biological effectiveness (CBE) factors in human undifferentiated thyroid cancer (UTC)

International Nuclear Information System (INIS)

Dagrosa, M.A.; Pisarev, M.; Chung, Y.; Coderre, J.; Riley, K.; Binns, P.; Kahl, S.

2006-01-01

We determined the CBE values for BPA an BOPP both individually and combined in a human UTC cell line as preliminary data for future treatments with BNCT. In these studies the exponentially growing cell line (ARO) were distributed into the following groups: 1) BPA (10 ppm 10 B) +neutrons; 2) BOPP (10 ppm 10 B) + neutrons; 3) BPA (5 ppm 10 B) + BOPP (5 ppm 10 B) + neutrons; 4) neutrons alone; 5) X-rays. The cells were irradiated in the thermal neutron beam of the MIT Research Reactor (flux=8.5 10 9 n/cm 2 sec). Surviving fraction (SF) was studied as the endpoint from colony forming assays. The RBE of the beam as well as the CBEs for BPA and BOPP both individually and in combination were determined for two different endpoints. At SF of 0.02 and 0.07 respectively the results were beam RBE: 1.2 and 1.2; CBE for BPA: 3.0 and 3.9; CBE for BOPP: 1.6 and 1.7; and the CBE for BPA and BOPP in combination: 2.4 and 2.6. The CBE values for BPA in combination with BOPP appear additive. These are the first measured data for CBEs for UTC that should prove useful for future clinical studies. (author)

Chromosomal aberrations induced by 12C6+ ions and 6Co γ-rays in mouse immature oocytes

International Nuclear Information System (INIS)

Zhang Hong; Duan Xin; Yuan Zhigang; Li Wenjian; Zhou Guangming; Zhou Qingming; Bing Liu; Min Fengling; Li Xiaoda; Xie Yi

2006-01-01

The ovaries of Kun-Ming strain mice (3 weeks) were irradiated with different doses of 12 C 6+ ion or 6 Co γ-ray. Chromosomal aberrations were analyzed in metaphase II oocytes at 7 weeks after irradiation. The relative biological effectiveness (RBE) of 12 C 6+ ion was calculated with respect to 6 Co γ-ray for the induction of chromosomal aberrations. The 12 C 6+ ion and 6 Co γ-ray dose-response relationships for chromosomal aberrations were plotted by linear quadratic models. The data showed that there was a dose-related increase in frequency of chromosomal aberrations in all the treated groups compared to controls. The RBE values for 12 C 6+ ions relative to 6 Co γ-rays were 2.49, 2.29, 1.57, 1.42 or 1.32 for the doses of 0.5, 1.0, 2.0, 4.0 or 6.0 Gy, respectively. Moreover, a different distribution of the various types of aberrations has been found for 12 C 6+ ion and 6 Co γ-ray irradiations. The dose-response relationships for 12 C 6+ ion and 6 Co γ-ray exhibited positive correlations. The results from the present study may be helpful for assessing genetic damage following exposure of immature oocytes to ionizing radiation

New challenges in high-energy particle radiobiology

Science.gov (United States)

2014-01-01

Densely ionizing radiation has always been a main topic in radiobiology. In fact, α-particles and neutrons are sources of radiation exposure for the general population and workers in nuclear power plants. More recently, high-energy protons and heavy ions attracted a large interest for two applications: hadrontherapy in oncology and space radiation protection in manned space missions. For many years, studies concentrated on measurements of the relative biological effectiveness (RBE) of the energetic particles for different end points, especially cell killing (for radiotherapy) and carcinogenesis (for late effects). Although more recently, it has been shown that densely ionizing radiation elicits signalling pathways quite distinct from those involved in the cell and tissue response to photons. The response of the microenvironment to charged particles is therefore under scrutiny, and both the damage in the target and non-target tissues are relevant. The role of individual susceptibility in therapy and risk is obviously a major topic in radiation research in general, and for ion radiobiology as well. Particle radiobiology is therefore now entering into a new phase, where beyond RBE, the tissue response is considered. These results may open new applications for both cancer therapy and protection in deep space. PMID:24198199

Cell survival in spheroids irradiated with heavy-ion beams

International Nuclear Information System (INIS)

Rodriguez, A.; Alpen, E.L.

1981-01-01

Biological investigations with accelerated heavy ions have been carried out regularly at the Lawrence Berkeley Laboratory Bevalac for the past four years. Most of the cellular investigations have been conducted on cell monolayer and suspension culture systems. The studies to date suggest that heavy charged particle beams may offer some radiotherapeutic advantages over conventional radiotherapy sources. The advantages are thought to lie primarily in an increased relative biological effectiveness (RBE), a decrease in the oxygen enhancement ratio (OER), and better tissue distribution dose. Experiments reported here were conducted with 400 MeV/amu carbon ions and 425 MeV/amu neon ions, using a rat brain gliosarcoma cell line grown as multicellular spheroids. Studies have been carried out with x-rays and high-energy carbon and neon ion beams. These studies evaluate high-LET (linear energy transfer) cell survival in terms of RBE and the possible contributions of intercellular communication. Comparisons were made of the post-irradiation survival characteristics for cells irradiated as multicellular spheroids (approximately 100 μm and 300 μm diameters) and for cells irradiated in suspension. These comparisons were made between 225-kVp x-rays, 400 MeV/amu carbon ions, and 425 MeV/amu neon ions

Development of a Novel Lipophilic, Magnetic Nanoparticle for in Vivo Drug Delivery

Directory of Open Access Journals (Sweden)

Torben Moos

2013-04-01

Full Text Available The aim of the present study was to evaluate the transfection potential of chitosan-coated, green-fluorescent magnetic nanoparticles (MNPs (chi-MNPs after encapsulation inside polyethylglycol (PEGylated liposomes that produced lipid-encapsulated chitosan-coated MNPs (lip-MNPs, and also to evaluate how these particles would distribute in vivo after systemic injection. The transfection potential of both chi-MNPs and lip-MNPs was evaluated in vitro in rat brain endothelial 4 (RBE4 cells with and without applying a magnetic field. Subsequently, the MNPs were evaluated in vivo in young rats. The in vitro investigations revealed that the application of a magnetic field resulted in an increased cellular uptake of the particles. The lip-MNPs were able to transfect the RBE4 cells with an incidence of approximately 20% of a commercial transfection agent. The in vivo distribution studies revealed that lip-MNPs had superior pharmacokinetic properties due to evasion of the RES, including hepatic Kuppfer cells and macrophages in the spleen. In conclusion, we were able to design a novel lipid-encapsulated MNP with the ability to carry genetic material, with favorable pharmacokinetic properties, and under the influence of a magnetic field with the capability to mediate transfection in vitro.

Development of a Novel Lipophilic, Magnetic Nanoparticle for in Vivo Drug Delivery

Science.gov (United States)

Linemann, Thomas; Thomsen, Louiza B.; Du Jardin, Kristian G.; Laursen, Jens C.; Jensen, Jesper B.; Lichota, Jacek; Moos, Torben

2013-01-01

The aim of the present study was to evaluate the transfection potential of chitosan-coated, green-fluorescent magnetic nanoparticles (MNPs) (chi-MNPs) after encapsulation inside polyethylglycol (PEG)ylated liposomes that produced lipid-encapsulated chitosan-coated MNPs (lip-MNPs), and also to evaluate how these particles would distribute in vivo after systemic injection. The transfection potential of both chi-MNPs and lip-MNPs was evaluated in vitro in rat brain endothelial 4 (RBE4) cells with and without applying a magnetic field. Subsequently, the MNPs were evaluated in vivo in young rats. The in vitro investigations revealed that the application of a magnetic field resulted in an increased cellular uptake of the particles. The lip-MNPs were able to transfect the RBE4 cells with an incidence of approximately 20% of a commercial transfection agent. The in vivo distribution studies revealed that lip-MNPs had superior pharmacokinetic properties due to evasion of the RES, including hepatic Kuppfer cells and macrophages in the spleen. In conclusion, we were able to design a novel lipid-encapsulated MNP with the ability to carry genetic material, with favorable pharmacokinetic properties, and under the influence of a magnetic field with the capability to mediate transfection in vitro. PMID:24300449

Survival of tumor cells after proton irradiation with ultra-high dose rates

International Nuclear Information System (INIS)

Auer, Susanne; Hable, Volker; Greubel, Christoph; Drexler, Guido A; Schmid, Thomas E; Belka, Claus; Dollinger, Günther; Friedl, Anna A

2011-01-01

Laser acceleration of protons and heavy ions may in the future be used in radiation therapy. Laser-driven particle beams are pulsed and ultra high dose rates of >10 9 Gy s -1 may be achieved. Here we compare the radiobiological effects of pulsed and continuous proton beams. The ion microbeam SNAKE at the Munich tandem accelerator was used to directly compare a pulsed and a continuous 20 MeV proton beam, which delivered a dose of 3 Gy to a HeLa cell monolayer within < 1 ns or 100 ms, respectively. Investigated endpoints were G2 phase cell cycle arrest, apoptosis, and colony formation. At 10 h after pulsed irradiation, the fraction of G2 cells was significantly lower than after irradiation with the continuous beam, while all other endpoints including colony formation were not significantly different. We determined the relative biological effectiveness (RBE) for pulsed and continuous proton beams relative to x-irradiation as 0.91 ± 0.26 and 0.86 ± 0.33 (mean and SD), respectively. At the dose rates investigated here, which are expected to correspond to those in radiation therapy using laser-driven particles, the RBE of the pulsed and the (conventional) continuous irradiation mode do not differ significantly

Accounting for biological effectiveness in radiological protection

International Nuclear Information System (INIS)

Dennis, J.A.

1989-01-01

Relative biological effectiveness (RBE) presents a practical problem to radiological protection when attempts are made to ensure that the assessed risks from different types of radiation and different modes of exposure to radiation are commensurate with one another. Unfortunately, the theoretical understanding of RBE is still in the stage of competing explanations and hypotheses. Furthermore, the division of the concept of dose equivalent into a set of concepts for risk assessment and another set for measurement and control has introduced conflicting requirements of a practical nature that are difficult to resolve. Many of those working in radiobiology and radiation protection have perceived the need to increase the quality factors for photon and neutron radiations. It may be more reasonable to change the quality factors for neutrons than for other radiations. The advantages and disadvantages of different methods for accommodating such changes within the dose-equivalent concepts are to be examined. The method of accommodating such a change that has the least practical disadvantages is to increase the quality factors for all secondary particles produced in tissue by neutron radiations by a constant factor. The only disadvantage would be the perception that the quality factors for these secondary particles were not treated in a consistent fashion for all types of ionising radiation. (author)

Microdosimetry of 0.5 to 2.0 MeV electron beams

International Nuclear Information System (INIS)

Braby, L.A.; Roesch, W.C.

1980-08-01

The energy imparted in microscopic volumes by electron beams with initial energies from 0.5 to 2.0 MeV has been measured at various depths in plastic. The problems associated with measuring energy deposition spectra of low LET radiations are serious, but the potential importance of these measurements in radiation biophysics justifies the effort required to obtain them. Recent results obtained by Goodhead et al. indicate an RBE greater than 2 for 0.3 keV x-rays compared to 250 kV x-rays, and our results with Chlamydomonas reinhardi indicate an RBE of 1.6 for a 1.5 MeV electron beam at a depth of 400 gm/cm 2 in lucite compared to the same beam at the surface. Development of a theory which appears to explain these results in terms of the microscopic distribution of energy deposition has motivated a detailed study of energy deposition spectra for an electron beam attenuated by various thicknesses of lucite. Simulated sites from 0.5 to 1.9 μm in diameter were studied. The values of anti y determined in these single event measurements compare favorably with those calculated from direct measurements of z reported previously. As expected, the means of the distributions increase significantly with increasing depth in an absorber

Neutron-induced mutation experiments. Progress report, March 1, 1977--February 28, 1978

International Nuclear Information System (INIS)

Abrahamson, S.

1977-11-01

Experiments have been carried out to study the relative mutagenic effectiveness for Drosophila female germ cells of neutrons of different energies employing X-linked recessive lethal and specific locus mutation tests. The energies and doses employed to date to study X-linked lethals are 0.43 MeV (500, 1000, 1500, 1900 R (in progress)), 0.68 MeV (250, 500, 1000, 1500 R), 2 MeV (250, 500, 1000, 1500, 2000 R), 6 MeV (250, 500, 1500, 3000 R) and 15 MeV (250, 500, 1000, 1500, 3000 R). 0.43-MeV neutrons appear to have an RBE in the range 1.9 to 4.7, 0.68 MeV 2.8 to 4.3, 2 MeV (incomplete data), 6 MeV 1.7 to 3.2, and 15 MeV 1.7 to 2.2. The data for 0.43-MeV and 0.68-MeV neutrons do not yet differentiate between a linear and a quadratic dose/frequency response curve for the doses studied, but suggest a quadratic relationship. The data for 2, 6 and 15 MeV are inconclusive. The specific locus mutation data indicate the highest RBE for 0.68-MeV neutrons, followed by 2 and 6 MeV, respectively

A comparison of mutagenic effects of common wheat by electron beam, fast neutron and 60Co gamma ray irradiation

International Nuclear Information System (INIS)

An Daochang; Wang Linqing

1988-02-01

After winter wheat was irradiated by electron beam, fast neutron and γ-rays, respectively, the RBE value of electron beam to both fast neutrons and γ-rays was less than one, the RBE value of fast neutron to γ-rays was largely more than one. This results indicated that biological effect of M 1 generation induced by electron beam was less than that of fast neutrons very much, and similar to γ-ray irradiation. With electron beam irradiation, the half-lethal doses of M 1 generation were from 185 to 370 Gy, closer to 370 Gy, the lethal doses from 740 to 925 Gy. M 2 mutation efficiency with electron beam treatment was larger as compared with that with both fast neutrons and γ-rays. A wider mutation spectrum and higher mutation efficiency compared with other physical mutagens can be obtained with electron beam irradiation, about 30% higher than that with γ-ray irradiation. The best doses of irradiation with electron beam were 370 to 555 Gy. Fast neutrons, a better dose of which was 25 Gy, could induce more mutants than that with γ-rays in M 2 generation. The dose in which biological injury reached to 50% was the best dose for M 2 mutants by electron beam irradiation

The Biological Effectiveness of Four Energies of Neon Ions for the Induction of Chromosome Damage in Human Lymphocytes

Science.gov (United States)

George, Kerry; Hada, Megumi; Cucinotta, F. A.

2011-01-01

Chromosomal aberrations were measured in human peripheral blood lymphocytes after in vitro exposure to neon ions at energies of 64, 89, 142, or 267. The corresponding LET values for these energies of neon ranged from 38-103 keV/micrometers and doses delivered were in the 10 to 80 cGy range. Chromosome exchanges were assessed in metaphase and G2 phase cells at first division after exposure using fluorescence in situ hybridization (FISH) with whole chromosome probes and dose response curves were generated for different types of chromosomal exchanges. The yields of total chromosome exchanges were similar for the 64, 89, and 142 MeV exposures, whereas the 267 MeV/u neon with LET of 38 keV/micrometers produced about half as many exchanges per unit dose. The induction of complex type chromosome exchanges (exchanges involving three or more breaks and two or more chromosomes) showed a clear LET dependence for all energies. The ratio of simple to complex type exchanges increased with LET from 18 to 51%. The relative biological effectiveness (RBE) was estimated from the initial slope of the dose response curve for chromosome damage with respect to gamma-rays. The RBE(sub max) values for total chromosome exchanges for the 64 MeV/u was around 30.

Quantitative and Qualitative Differences in Neurocognitive Impairment Induced by 1 GeV 56Fe Ions and X-Rays

Science.gov (United States)

Britten, R.; Mitchell, S.; Parris, B.; Johnson, A.; Singletary-Britten, S.; Lonart, G.; Drake, R.

2008-10-01

During the planned mission to Mars, Astronauts will be exposed to heavy charged particles (Hze). Our group has been determining the relative biological effectiveness (RBE) of Hze (1 GeV 56Fe, LET = 150 kev/um) with respect to neurocognitive impairment, specifically spatial memory, short-term working memory and attentional set shifting. Our current data suggest that Hze have RBE values of about 7 for hippocampal-dependent spatial memory tasks (Barnes Maze) and possibly even higher for certain attentional processes. We have also used MALDI-TOF serum profiling analysis to identify several proteins that are biomarkers of both the level and LET of the radiation exposure, and biomarkers of cognitive performance. Our data suggest that Hze particles have a distinctly different impact upon neurocognitive function in rats than do X-rays. From a mission perspective, attentional set shifting is the neurocognitive function most likely to be impacted by the predicted Hze exposure; unfortunately Set shifting underlies our ability to execute complex plans. The proteins identified could be used to monitor the Astronauts for radiation exposure and any associated loss of neurocognitive function, and some may actually give an insight into the complex processes that lead to radiation-induced cognitive impairment.

Evaluation of permanent alopecia in pediatric medulloblastoma patients treated with proton radiation

International Nuclear Information System (INIS)

Min, Chul Hee; Paganetti, Harald; Winey, Brian A; Adams, Judith; MacDonald, Shannon M; Tarbell, Nancy J; Yock, Torunn I

2014-01-01

To precisely calculate skin dose and thus to evaluate the relationship between the skin dose and permanent alopecia for pediatric medulloblastoma patients treated with proton beams. The dosimetry and alopecia outcomes of 12 children with medulloblastoma (ages 4-15 years) comprise the study cohort. Permanent alopecia was assessed and graded after completion of the entire therapy. Skin threshold doses of permanent alopecia were calculated based on the skin dose from the craniospinal irradiation (CSI) plan using the concept of generalized equivalent uniform dose (gEUD) and accounting for chemotherapy intensity. Monte Carlo simulations were employed to accurately assess uncertainties due to beam range prediction and secondary particles. Increasing the dose of the CSI field or the dose given by the boost field to the posterior fossa increased total skin dose delivered in that region. It was found that permanent alopecia could be correlated with CSI dose with a threshold of about 21 Gy (relative biological effectiveness, RBE) with high dose chemotherapy and 30 Gy (RBE) with conventional chemotherapy. Our results based on 12 patients provide a relationship between the skin dose and permanent alopecia for pediatric medulloblastoma patients treated with protons. The alopecia risk as assessed with gEUD could be predicted based on the treatment plan information

Therapeutic Strategies against Cyclin E1-Amplified Ovarian Cancers

Science.gov (United States)

2017-10-01

provide? During the 2nd year of the project Dr Konstantinopoulos was promoted to Associate Professor of Medicine at Harvard Medical School and was...Biol 19:962-973. PMID: 28737768. PMC5541905. 16 Books or other non-periodical, one-time publications. “Nothing to Report.” Other publications...7. SPECIAL REPORTING REQUIREMENTS: None 8. APPENDICES: None Cited References : 1. Harbour, J.W. and D.C. Dean, The Rb/E2F pathway

Special photographic emulsions for high LET dosimetry

International Nuclear Information System (INIS)

Katz, R.

1978-12-01

The purpose of these investigations into photographic emulsion dosimetry is to attempt to use the photographic emulsion to mimic the response of human tissues to high LET radiations. The program therefore requires that a systematic understanding of the response of mammalian cells to ionizing radiations be achieved. We have been concerned with differences in RBE and in radiation response to both high and LET radiations, and in the interrelationship between observations with these different radiations

European Society for Radiaton Biology - 19th annual meeting

International Nuclear Information System (INIS)

1986-01-01

The proceedings contain 313 abstracts of papers. The topics covered include: biological radiation effects on lipids, hormones, fibroblasts, on bone healing, DNA repair, DNA synthesis, tumor cells, giant cell formation, on the lymphatic system, central nervous system and the hematopoietic system; determination of RBE; radioprotective agents; radiotherapy; dosimetry; radiation induced mutations; oxygen effects; radiosensitivity of tumor cells; hyperthermia and hypoxia effects on radiosensitivity; biological radiation effects on the growth of plants. (J.P.)

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

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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

Impact of breast cancer family history on tumor detection and tumor size in women newly-diagnosed with invasive breast cancer.

Science.gov (United States)

Schwab, Fabienne Dominique; Bürki, Nicole; Huang, Dorothy Jane; Heinzelmann-Schwarz, Viola; Schmid, Seraina Margaretha; Vetter, Marcus; Schötzau, Andreas; Güth, Uwe

2014-03-01

This study evaluated the impact of family history (FH) on tumor detection, the patient's age and tumor size at diagnosis in breast cancer (BC). Furthermore, we investigated whether the impact of FH on these features was dependent on degree of relationship, number of relatives with a BC history, or the age of the affected relative at the time that her BC was diagnosed. Out of the entire cohort (n = 1,037), 244 patients (23.5%) had a positive FH; 159 (15.3%) had first-degree relatives affected with BC and 85 patients (8.2%) had second-degree affected relatives. Compared to women who had no BC-affected relatives, the tumors of women who had positive FH were more often found by radiological breast examination (RBE: 31.7%/27.2%, p = 0.008), and they were smaller (general tumor size: 21.8 mm/26.4 mm, p = 0.003; size of tumors found by breast self-examination (BSE): 26.1 mm/30.6 mm, p = 0.041). However, this positive effect of increased use of BC screening and smaller tumor sizes was only observed in patients whose first-degree relatives were affected (comparison with second-degree affected relatives: RBE: 43.8%/24.7%; odds ratio 2.38, p = 0.007; general tumor size: 19.3 mm/26.3 mm; mean difference (MD) -6.9, p = 0.025; tumor size found by BSE: 22.5 mm/31.0 mm; MD -8.5, p = 0.044). When more second-degree relatives or older relatives were diagnosed with BC, the tumors of these patients were similarly often detected by RBE (relationship: 24.7%/27.2%, p = 0.641; age: 33.7 %/27.2 %, p = 0.177) and had similar tumor sizes (general size: 26.3 mm/26.4 mm, p = 0.960; BSE: 31.0 mm/30.6 mm, p = 0.902) as those of women without a FH. Women with a positive FH generally use mammography screening more often and perceive changes in the breast earlier than women without such history. The increased awareness of BC risk decreases if the relationship is more distant.

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

First evaluation of the biologic effectiveness factors of boron neutron capture therapy (BNCT) in a human colon carcinoma cell line.

Science.gov (United States)

Dagrosa, Maria Alejandra; Crivello, Martín; Perona, Marina; Thorp, Silvia; Santa Cruz, Gustavo Alberto; Pozzi, Emiliano; Casal, Mariana; Thomasz, Lisa; Cabrini, Romulo; Kahl, Steven; Juvenal, Guillermo Juan; Pisarev, Mario Alberto

2011-01-01

DNA lesions produced by boron neutron capture therapy (BNCT) and those produced by gamma radiation in a colon carcinoma cell line were analyzed. We have also derived the relative biologic effectiveness factor (RBE) of the neutron beam of the RA-3- Argentine nuclear reactor, and the compound biologic effectiveness (CBE) values for p-boronophenylalanine ((10)BPA) and for 2,4-bis (α,β-dihydroxyethyl)-deutero-porphyrin IX ((10)BOPP). Exponentially growing human colon carcinoma cells (ARO81-1) were distributed into the following groups: (1) BPA (10 ppm (10)B) + neutrons, (2) BOPP (10 ppm (10)B) + neutrons, (3) neutrons alone, and (4) gamma rays ((60)Co source at 1 Gy/min dose-rate). Different irradiation times were used to obtain total absorbed doses between 0.3 and 5 Gy (±10%) (thermal neutrons flux = 7.5 10(9) n/cm(2) sec). The frequency of micronucleated binucleated cells and the number of micronuclei per micronucleated binucleated cells showed a dose-dependent increase until approximately 2 Gy. The response to gamma rays was significantly lower than the response to the other treatments (p irradiations with neutrons alone and neutrons + BOPP showed curves that did not differ significantly from, and showed less DNA damage than, irradiation with neutrons + BPA. A decrease in the surviving fraction measured by 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolium bromide (MTT) assay as a function of the absorbed dose was observed for all the treatments. The RBE and CBE factors calculated from cytokinesis block micronucleus (CBMN) and MTT assays were, respectively, the following: beam RBE: 4.4 ± 1.1 and 2.4 ± 0.6; CBE for BOPP: 8.0 ± 2.2 and 2.0 ± 1; CBE for BPA: 19.6 ± 3.7 and 3.5 ± 1.3. BNCT and gamma irradiations showed different genotoxic patterns. To our knowledge, these values represent the first experimental ones obtained for the RA-3 in a biologic model and could be useful for future experimental studies for the application of BNCT to colon carcinoma

Dose–Volume Relationships Associated With Temporal Lobe Radiation Necrosis After Skull Base Proton Beam Therapy

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McDonald, Mark W., E-mail: markmcdonaldmd@gmail.com [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana (United States); Indiana University Health Proton Therapy Center, Bloomington, Indiana (United States); Linton, Okechukwu R. [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana (United States); Calley, Cynthia S.J. [Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana (United States)

2015-02-01

Purpose: We evaluated patient and treatment parameters correlated with development of temporal lobe radiation necrosis. Methods and Materials: This was a retrospective analysis of a cohort of 66 patients treated for skull base chordoma, chondrosarcoma, adenoid cystic carcinoma, or sinonasal malignancies between 2005 and 2012, who had at least 6 months of clinical and radiographic follow-up. The median radiation dose was 75.6 Gy (relative biological effectiveness [RBE]). Analyzed factors included gender, age, hypertension, diabetes, smoking status, use of chemotherapy, and the absolute dose:volume data for both the right and left temporal lobes, considered separately. A generalized estimating equation (GEE) regression analysis evaluated potential predictors of radiation necrosis, and the median effective concentration (EC50) model estimated dose–volume parameters associated with radiation necrosis. Results: Median follow-up time was 31 months (range 6-96 months) and was 34 months in patients who were alive. The Kaplan-Meier estimate of overall survival at 3 years was 84.9%. The 3-year estimate of any grade temporal lobe radiation necrosis was 12.4%, and for grade 2 or higher radiation necrosis was 5.7%. On multivariate GEE, only dose–volume relationships were associated with the risk of radiation necrosis. In the EC50 model, all dose levels from 10 to 70 Gy (RBE) were highly correlated with radiation necrosis, with a 15% 3-year risk of any-grade temporal lobe radiation necrosis when the absolute volume of a temporal lobe receiving 60 Gy (RBE) (aV60) exceeded 5.5 cm{sup 3}, or aV70 > 1.7 cm{sup 3}. Conclusions: Dose–volume parameters are highly correlated with the risk of developing temporal lobe radiation necrosis. In this study the risk of radiation necrosis increased sharply when the temporal lobe aV60 exceeded 5.5 cm{sup 3} or aV70 > 1.7 cm{sup 3}. Treatment planning goals should include constraints on the volume of temporal lobes receiving

WE-E-BRE-07: High-Throughput Mapping of Proton Biologic Effect

Energy Technology Data Exchange (ETDEWEB)

Bronk, L; Guan, F; Kerr, M; Dinh, J; Titt, U; Mirkovic, D; Lin, S; Mohan, R; Grosshans, D [UT MD Anderson Cancer Center, Houston, TX (United States)

2014-06-15

Purpose: To systematically relate the relative biological effectives (RBE) of proton therapy to beam linear energy transfer (LET) and dose. Methods: Using a custom irradiation apparatus previously characterized by our group, H460 NSCLCs were irradiated using a clinical 80MeV spot scanning proton beam. Utilizing this system allowed for high-throughput clonogenic assays performed in 96-well tissue culture plates as opposed to the traditional 6-well technique. Each column in the 96-well plate received a set LET-dose combination. By altering the total number of dose repaintings, numerous dose-LET configurations were examined to effectively generate surviving fraction (SF) data over the entire Bragg peak. The clonogenic assay was performed post-irradiation using an INCell Analyzer for colony quantification. SF data were fit to the linear-quadratic model for analysis. Results: Irradiation with increasing LETs resulted in decreased cell survival largely independent of dose. A significant correlation between LET and SF was identified by two-way ANOVA and the extra sum-of-squares F test. This trend was obscured at the lower LET values in the plateau region of the Bragg peak; however, it was clear for LET values at and beyond the Bragg peak. Data fits revealed the SF at a dose of 2Gy (SF2) to be 0.48 for the lowest tested LET (1.55keV/um), 0.47 at the end of the plateau region (4.74keV/um) and 0.33 for protons at the Bragg peak (10.35keV/um). Beyond the Bragg peak we measured SF2s of 0.16 for 15.01keV/um, 0.02 for 16.79keV/um, and 0.004 for 18.06keV/um. Conclusion: We have shown that our methodology enables high-content automated screening for proton irradiations over a range of LETs. The observed decrease in cellular SF in high LET regions confirms an increased RBE of the radiation and suggests further evaluation of proton RBE values is necessary to optimize clinical outcomes. Rosalie B. Hite Graduate Fellowship in Cancer Research, NIH Program Project Grant P01CA021239.

Outcomes of Sinonasal Cancer Treated With Proton Therapy

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Dagan, Roi, E-mail: rdagan@floridaproton.org [Department of Radiation Oncology, University of Florida, Gainesville, Florida (United States); Department of Radiation Oncology, University of Florida, Jacksonville, Florida (United States); Bryant, Curtis; Li, Zuofeng; Yeung, Daniel [Department of Radiation Oncology, University of Florida, Gainesville, Florida (United States); Department of Radiation Oncology, University of Florida, Jacksonville, Florida (United States); Justice, Jeb; Dzieglewiski, Peter; Werning, John [Department of Otolaryngology, University of Florida, Gainesville, Florida (United States); Fernandes, Rui; Pirgousis, Phil [Department of Oral and Maxillofacial Surgery, University of Florida, Jacksonville, Florida (United States); Lanza, Donald C. [Sinus & Nasal Institute of Florida, St. Petersburg, Florida (United States); Morris, Christopher G.; Mendenhall, William M. [Department of Radiation Oncology, University of Florida, Gainesville, Florida (United States); Department of Radiation Oncology, University of Florida, Jacksonville, Florida (United States)

2016-05-01

Purpose: To report disease outcomes after proton therapy (PT) for sinonasal cancer. Methods and Materials: Eighty-four adult patients without metastases received primary (13%) or adjuvant (87%) PT for sinonasal cancers (excluding melanoma, sarcoma, and lymphoma). Common histologies were olfactory neuroblastoma (23%), squamous cell carcinoma (22%), and adenoid cystic carcinoma (17%). Advanced stage (T3 in 25% and T4 in 69%) and high-grade histology (51%) were common. Surgical procedures included endoscopic resection alone (45%), endoscopic resection with craniotomy (12%), or open resection (30%). Gross residual disease was present in 26% of patients. Most patients received hyperfractionated PT (1.2 Gy [relative biological effectiveness (RBE)] twice daily, 99%) and chemotherapy (75%). The median PT dose was 73.8 Gy (RBE), with 85% of patients receiving more than 70 Gy (RBE). Prognostic factors were analyzed using Kaplan-Meier analysis and proportional hazards regression for multiple regression. Dosimetric parameters were evaluated using logistic regression. Serious, late grade 3 or higher toxicity was reported using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4. The median follow-up was 2.4 years for all patients and 2.7 years among living patients. Results: The local control (LC), neck control, freedom from distant metastasis, disease-free survival, cause-specific survival, and overall survival rates were 83%, 94%, 73%, 63%, 70%, and 68%, respectively, at 3 years. Gross total resection and PT resulted in a 90% 3-year LC rate. The 3-year LC rate was 61% for primary radiation therapy and 59% for patients with gross disease. Gross disease was the only significant factor for LC on multivariate analysis, whereas grade and continuous LC were prognostic for overall survival. Six of 12 local recurrences were marginal. Dural dissemination represented 26% of distant recurrences. Late toxicity occurred in 24% of patients (with

Polyploidization of rat hepatocytes due to cell fusion under the effect of radiation of different let

International Nuclear Information System (INIS)

Gil'yano, N.Ya.; Malinovskij, O.V.; Khair, M.B.; Baldychev, A.S.; Smolin, V.A.

1988-01-01

The method of flow cytometry was used to study polyploidization of hepatocytes following X-, γ-, and neutron-irradiation. Ionizing radiation was shown to induce cell polyploidization by two different ways: (1) cells and nuclei fusion, and (2) restriction of mitosis after DNA replication. RBE of 14 MeV neutrons with respect to fusion was about 5x10 3 . With neutron irradiation, the densitivity of cells by fusion was not lower than that by chromosome mutations

Influence of gamma radiation and fast neutrons on the growth of Haplopappus gracilis (Nutt) A. Gray callus

International Nuclear Information System (INIS)

Cebulska-Wasilewska, A.; Wajda, L.; Korzonek, M.; Polska Akademia Nauk, Krakow. Inst. Fizjologii Roslin)

1979-01-01

The sensitivity of the callus of Haplopappus gracilis to gamma radiation and fast neutrons was studied. High doses of radiation cause inhibition of callus growth. At small doses the effect is less pronounced. Stimulation of callus growth was seen. Apart from morphological changes, ionizing radiations lowered the fresh weight ratio of the callus. The RBE value for 5.5 MeV neutrons depended on the dose rate of radiation and the combination of growth medium. (author)

Teratogenic effect of Californium-252 irradiation in rats

International Nuclear Information System (INIS)

Satow, Yukio; Lee, Juing-Yi; Hori, Hiroshi; Okuda, Hiroe; Tsuchimoto, Shigeo; Sawada, Shozo; Yokoro, Kenjiro

1989-01-01

The teratogenicity of Californium-252 (Cf-252) irradiation which generates approximately 70% 2.3 MeV fast neutron and 30% gamma rays was evaluated. A single whole body exposure of Cf-252 at various doses was given to pregnant rats on day 8 or 9 of pregnancy, followed by microscopic autopsy of the fetuses at the terminal stage of pregnancy to search for external and internal malformations. For comparison, pregnant rats were irradiated with various doses of Cobalt-60 (Co-60) standard gamma rays at the same dose rate (1 rad/min.). The doses were 20-120 rad of Cf-252 and 80-220 rad of Co-60. Using frequency of radiation induced malformations observed on day 8 of pregnancy as an index, relative biological effectiveness (RBE) of 2.3-2.7 was obtained from the straight line obtained by modifying by the least squares method the frequency curves of malformed fetuses in total implants and in surviving fetuses. The types of malformations induced by Cf-252 and Co-60 irradiation were alike. Using fetal LD 50 as an index, 2.4 was obtained as RBE when irradiated on day 8 of pregnancy and 3.1 as that when irradiated on day 9. The results showed that Cf-252 had stronger a teratogenic effect than Co-60 gamma rays. (author)

Long-term effects of an intracavitary treatment with californium-252 on normal tissue. [Swine, /sup 226/Ra

Energy Technology Data Exchange (ETDEWEB)

Sullivan, M.F.; Beamer, J.L.; Mahony, T.D.; Cross, F.T.; Lund, J.E.; Endres, G.W.R.

1976-01-01

About one hundred fifty swine were exposed to either radium-226 or californium-252 sources in the uterine cervix to determine an RBE for both acute and long-term effects. That value for early changes in the tissues at risk in the treatment of cervical cancer was between 6.2 and 6.8. The incidence of complications increased with time after exposure, especially among animals treated with /sup 252/Cf. Analysis of rectal injury showed that ulceration occurred frequently within a year postexposure at doses between 1600 and 2400 rad calculated at 2 cm lateral to the source midline. Fat necrosis and smooth muscle atrophy, resulting in a local rectal stricture, were delayed changes observed in some animals. The lower ureter was the site for a greater frequency of complications than the GI tract. Ureteral stricture often occurred at doses of 1200 rad from /sup 252/Cf and 7000 rad from /sup 226/Ra. Observation of delayed effects in the uterine-cervix in animals held up to 4 years postexposure indicate that the RBE for /sup 252/Cf may be increased to a value as high as 18, while repair may have even decreased it to about 5.6 in the rectum. Fifty swine are still being observed for long-term effects after doses above 800 rad from /sup 252/Cf and 5000 rad from /sup 226/Ra.

Effects of charged particles on DNA

International Nuclear Information System (INIS)

Eguchi-Kasai, Kiyomi; Itsukaichi, Hiromi; Murakami, Masahiro

1995-01-01

It can be noted that it is not simple double strand breaks (dsb) but the non-reparable breaks that are associated with high biological effectiveness in the cell killing effect for high LET radiation. Here, we have examined the effectiveness of fast neutrons and low (initial energy = 12 MeV/u) or high (135 MeV/u) energy charged particles on cell death in 19 mammalian cell lines including radiosensitive mutants. Some of the radiosensitive lines were deficient in DNA dsb repair such as LX830, M10, V3, and L5178Y-S cells and showed lower values of relative biological effectiveness (RBE) for fast neutrons if compared with their parent cell lines. The other lines of human ataxia-telangiectasia fibroblasts, irs 1, irs 2, irs 3 and irs 1SF cells, which were also radiosensitive but known as proficient in dsb repair, showed moderate RBEs. Dsb repair deficient mutants showed low RBE values for heavy ions. These experimental findings suggest that the DNA repair system does not play a major role against the attack of high linear energy transfer (LET) radiations. Therefore, we hypothesize that a main cause of cell death induced by high LET radiations is due to non-reparable dsb, which are produced at a higher rate compared to low LET radiations. (author)

Heavy ion induced genetic effects in mammalian cells. Final report

International Nuclear Information System (INIS)

Kiefer, J.; Brend'amour, M.; Casares, A.; Egenolf, R.; Gutermuth, F.; Ikpeme, S.E.; Koch, S.; Kost, M.; Loebrich, M.; Pross, H.D.; Russmann, C.; Schmidt, P.; Schneider, E.; Stoll, U.; Weber, K.J.

2001-01-01

DNA double-strand breaks (DSBs) are generally assumed to be the most relevant initial event producing radiation-induced cellular lethality, as well as mutations and transformations. The dependence of their formation on radiation quality has been recently reviewed. Contrary to earlier observations there seems to be now agreement that the RBE does not increase above unity with increasing LET in mammalian cells when conventional techniques are applied which are not able to resolve smaller fragments. If they are, however, included in the analysis maximum RBE values around 2 are obtained. The situation is different with yeast: An increased effectiveness for DSB induction has been reported with alpha particles, as well as for heavy ions. This may be due to differences in methods or to chromosomal structure, as discussed in more detail in this paper. DSB induction was measured for a LET range of 100 to 11500 keV/? m in yeast cells using pulsed field gel electrophoresis. Under the conditions applied the chromosomes of the yeast cells could be separated according to size allowing the direct quantification of the DSB yield by measuring the intensity of the largest chromosomes. The results demonstrate clearly that DSB induction in yeast depends on radiation quality. The derived cross-sections for DSB induction were also compared to those for cell inactivation determined in parallel experiments under identical irradiation conditions. (orig.)

Linear Energy Transfer Painting With Proton Therapy: A Means of Reducing Radiation Doses With Equivalent Clinical Effectiveness

International Nuclear Information System (INIS)

Fager, Marcus; Toma-Dasu, Iuliana; Kirk, Maura; Dolney, Derek; Diffenderfer, Eric S.; Vapiwala, Neha; Carabe, Alejandro

2015-01-01

Purpose: The purpose of this study was to propose a proton treatment planning method that trades physical dose (D) for dose-averaged linear energy transfer (LET d ) while keeping the radiobiologically weighted dose (D RBE ) to the target the same. Methods and Materials: The target is painted with LET d by using 2, 4, and 7 fields aimed at the proximal segment of the target (split target planning [STP]). As the LET d within the target increases with increasing number of fields, D decreases to maintain the D RBE the same as the conventional treatment planning method by using beams treating the full target (full target planning [FTP]). Results: The LET d increased 61% for 2-field STP (2STP) compared to FTP, 72% for 4STP, and 82% for 7STP inside the target. This increase in LET d led to a decrease of D with 5.3 ± 0.6 Gy for 2STP, 4.4 ± 0.7 Gy for 4STP, and 5.3 ± 1.1 Gy for 7STP, keeping the DRBE at 90% of the volume (DRBE, 90) constant to FTP. Conclusions: LET d painting offers a method to reduce prescribed dose at no cost to the biological effectiveness of the treatment

Linear Energy Transfer Painting With Proton Therapy: A Means of Reducing Radiation Doses With Equivalent Clinical Effectiveness

Energy Technology Data Exchange (ETDEWEB)

Fager, Marcus, E-mail: Marcus.Fager@UPHS.UPenn.edu [Department of Radiation Oncology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Medical Radiation Physics, Stockholm University, Stockholm (Sweden); Toma-Dasu, Iuliana [Medical Radiation Physics, Stockholm University and Karolinska Institutet, Stockholm (Sweden); Kirk, Maura; Dolney, Derek; Diffenderfer, Eric S.; Vapiwala, Neha [Department of Radiation Oncology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Carabe, Alejandro, E-mail: Alejandro.Carabe-Fernandez@UPHS.UPenn.edu [Department of Radiation Oncology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

2015-04-01

Purpose: The purpose of this study was to propose a proton treatment planning method that trades physical dose (D) for dose-averaged linear energy transfer (LET{sub d}) while keeping the radiobiologically weighted dose (D{sub RBE}) to the target the same. Methods and Materials: The target is painted with LET{sub d} by using 2, 4, and 7 fields aimed at the proximal segment of the target (split target planning [STP]). As the LET{sub d} within the target increases with increasing number of fields, D decreases to maintain the D{sub RBE} the same as the conventional treatment planning method by using beams treating the full target (full target planning [FTP]). Results: The LET{sub d} increased 61% for 2-field STP (2STP) compared to FTP, 72% for 4STP, and 82% for 7STP inside the target. This increase in LET{sub d} led to a decrease of D with 5.3 ± 0.6 Gy for 2STP, 4.4 ± 0.7 Gy for 4STP, and 5.3 ± 1.1 Gy for 7STP, keeping the DRBE at 90% of the volume (DRBE, 90) constant to FTP. Conclusions: LET{sub d} painting offers a method to reduce prescribed dose at no cost to the biological effectiveness of the treatment.

Long-term effects of an intracavitary treatment with californium-252 on normal tissue

International Nuclear Information System (INIS)

Sullivan, M.F.; Beamer, J.L.; Mahony, T.D.; Cross, F.T.; Lund, J.E.; Endres, G.W.R.

1976-01-01

About one hundred fifty swine were exposed to either radium-226 or californium-252 sources in the uterine cervix to determine an RBE for both acute and long-term effects. That value for early changes in the tissues at risk in the treatment of cervical cancer was between 6.2 and 6.8. The incidence of complications increased with time after exposure, especially among animals treated with 252 Cf. Analysis of rectal injury showed that ulceration occurred frequently within a year postexposure at doses between 1600 and 2400 rad calculated at 2 cm lateral to the source midline. Fat necrosis and smooth muscle atrophy, resulting in a local rectal stricture, were delayed changes observed in some animals. The lower ureter was the site for a greater frequency of complications than the GI tract. Ureteral stricture often occurred at doses of 1200 rad from 252 Cf and 7000 rad from 226 Ra. Observation of delayed effects in the uterine-cervix in animals held up to 4 years postexposure indicate that the RBE for 252 Cf may be increased to a value as high as 18, while repair may have even decreased it to about 5.6 in the rectum. Fifty swine are still being observed for long-term effects after doses above 800 rad from 252 Cf and 5000 rad from 226 Ra

Induction of specific-locus mutations in the mouse by tritiated water

International Nuclear Information System (INIS)

Russell, W.L.; Cumming, R.B.; Kelly, E.M.; Phipps, E.L.

1978-01-01

The results reported are the first obtained on transmtted gene mutations induced by tritium in any form in any mammal. They are, therefore, of obvious practical importance in the estimaton of the possible biological hazards of man-made tritium in the environment. Male mice were injected intraperitoneally with either 0.75 or 0.50 mCi per gram of body weight of tritiated water. They were then used in our standard specific-locus mutation test in which the treated wild-type stock of mice is mated to a stock homozygous for seven recessive marker genes. Mutations at any of the seven loci are scored in the offspring. The earlier matings provided information on the mutation frequency in germ cells irradiated in postspermatogonial stages, and the later matings gave the mutation frequency in treated spermatogonia. The spermatogonia are the important cells so far as human risks are concerned, and the mouse results for this germ-cell stage yielded a relative biological effectiveness (RBE) of approximately 2 for tritiated water compared with low-dose-rate gamma irradiation. There are various uncertainties involved in arriving at this figure, and the difference between it and l is probably not statistically significant. However, for risk estimation, it seems prudent to use the RBE value of 2, which is, after all, the best point estimate computed from the present data

Estimation of Biological Effects of Tritium.

Science.gov (United States)

Umata, Toshiyuki

2017-01-01

Nuclear fusion technology is expected to create new energy in the future. However, nuclear fusion requires a large amount of tritium as a fuel, leading to concern about the exposure of radiation workers to tritium beta radiation. Furthermore, countermeasures for tritium-polluted water produced in decommissioning of the reactor at Fukushima Daiichi Nuclear Power Station may potentially cause health problems in radiation workers. Although, internal exposure to tritium at a low dose/low dose rate can be assumed, biological effect of tritium exposure is not negligible, because tritiated water (HTO) intake to the body via the mouth/inhalation/skin would lead to homogeneous distribution throughout the whole body. Furthermore, organically-bound tritium (OBT) stays in the body as parts of the molecules that comprise living organisms resulting in long-term exposure, and the chemical form of tritium should be considered. To evaluate the biological effect of tritium, the effect should be compared with that of other radiation types. Many studies have examined the relative biological effectiveness (RBE) of tritium. Hence, we report the RBE, which was obtained with radiation carcinogenesis classified as a stochastic effect, and serves as a reference for cancer risk. We also introduce the outline of the tritium experiment and the principle of a recently developed animal experimental system using transgenic mouse to detect the biological influence of radiation exposure at a low dose/low dose rate.

Alkali-treated titanium selectively regulating biological behaviors of bacteria, cancer cells and mesenchymal stem cells.

Science.gov (United States)

Li, Jinhua; Wang, Guifang; Wang, Donghui; Wu, Qianju; Jiang, Xinquan; Liu, Xuanyong

2014-12-15

Many attentions have been paid to the beneficial effect of alkali-treated titanium to bioactivity and osteogenic activity, but few to the other biological effect. In this work, hierarchical micro/nanopore films were prepared on titanium surface by acid etching and alkali treatment and their biological effects on bacteria, cancer cells and mesenchymal stem cells were investigated. Gram-positive Staphylococcus aureus, Gram-negative Escherichia coli, and human cholangiocarcinoma cell line RBE were used to investigate whether alkali-treated titanium can influence behaviors of bacteria and cancer cells. Responses of bone marrow mesenchymal stem cells (BMMSCs) to alkali-treated titanium were also subsequently investigated. The alkali-treated titanium can potently reduce bacterial adhesion, inhibit RBE and BMMSCs proliferation, while can better promote BMMSCs osteogenesis and angiogenesis than acid-etched titanium. The bacteriostatic ability of the alkali-treated titanium is proposed to result from the joint effect of micro/nanotopography and local pH increase at bacterium/material interface due to the hydrolysis of alkali (earth) metal titanate salts. The inhibitory action of cell proliferation is thought to be the effect of local pH increase at cell/material interface which causes the alkalosis of cells. This alkalosis model reported in this work will help to understand the biologic behaviors of various cells on alkali-treated titanium surface and design the intended biomedical applications. Copyright © 2014 Elsevier Inc. All rights reserved.

Boron neutron capture therapy induces apoptosis of glioma cells through Bcl-2/Bax

OpenAIRE

Wang, Peng; Zhen, Haining; Jiang, Xinbiao; Zhang, Wei; Cheng, Xin; Guo, Geng; Mao, Xinggang; Zhang, Xiang

2010-01-01

Abstract Background Boron neutron capture therapy (BNCT) is an alternative treatment modality for patients with glioma. The aim of this study was to determine whether induction of apoptosis contributes to the main therapeutic efficacy of BNCT and to compare the relative biological effect (RBE) of BNCT, γ-ray and reactor neutron irradiation. Methods The neutron beam was obtained from the Xi'an Pulsed Reactor (XAPR) and γ-rays were obtained from [60Co] γ source of the Fourth Military Medical Un...

Experiments on the Biological Action of Neutrons Performed in the Former Soviet Union: A Historical Review

Science.gov (United States)

2006-10-01

Exposed to x-rays and Fission Neutrons at Different Stages of Postnatal Development. Radio- biologia , 1982, vol. 22, no. 1, pp. 76-81. 10. Bogatyrev A.V...Cyclotron U-120. Radio- biologia , vol. 24, no. 4, pp. 567-569, 1986. 17. Dokshina G.A., Naumenko L.A., Effect of Mixed Gamma-Neutron Radia- tion on...in Drosophila Spermatogenesis on Dose from Fast Neutrons. Radio- biologia , v. 2, no. 3, pp. 420-421, 1963. 4. Alexandrov I.D., Different RBE for Gene

Radiation-induced diploid spermatids in mice

International Nuclear Information System (INIS)

Hacker-Klom, U.; Heiden, Th.; Otto, F.J.; Goehde, W.; Mauro, F.

1989-01-01

Diploid elongated spermatids of mice were enriched by flow cytometry and cell sorting using a new type of sorter (Partec). The sorted abnormal spermatids were identified morphologically and by nuclear area integration. The radiation-induced increase in the frequency of diploid elongated spermatids was monitored with time following acute X-ray exposure of mice. Dose-response curves for acute 60 Co-gamma and 14 MeV neutron irradiations yielded an RBE value of 4.3 for the doubling of the control level. (author)

Biology Division progress report, October 1, 1983-September 30, 1984

International Nuclear Information System (INIS)

Griesmer, R.A.

1985-01-01

The report provides summaries of the aims, scope and progress from October 1983 through September 1984. Major interest was focused on the health effects of neutron- and heavy-ion radiations on animals with particular attention to the carcinogenic responses to low dose levels and to the RBE of various forms of radiation. Among chemical agents, activities concentrated on evaluating and understanding the toxicological interations when mammals are exposed to complex mixtures, either concurrently or successively. Separate abstracts have been prepared for individual sections

Polyploidization of rat hepatocytes due to cell fusion under the effect of radiation of different LET

International Nuclear Information System (INIS)

Khair, M.; Gil'yano, N.Ya.; Malinovskij, O.V.; Smolin, V.A.

1991-01-01

The method of flow cytometry was used to study polyploidization of hepatocytes following X-, γ-, and neutron-irradiation. Ionizing radiation was shown to induce cell polyploidization by two different ways: (1) cells and nuclei fusion, and (2) restriction of mitosis after DNA replication. RBE of 14 MeV neutrons with respect to fusion was about 5x10 3 . With neutron irradiation, the sensitivity of cells by fusion was not lower than that by chromosome mutations. (author). 6 refs., 6 figs

Mammalian genetics and biostatistics

International Nuclear Information System (INIS)

Grahn, D.; Carnes, B.A.; Farrington, B.H.; Lee, C.H.

1985-01-01

This program seeks to assess genetic hazards of single, weekly, and continuous doses of 60 Co gamma rays and single and weekly doses of fission neutrons to provide a basis for estimating relative biological effectiveness (RBE) of fission neutrons, to develop detailed dose-response data at low doses as a basis for studying relationships between linear energy transfer (LET) and the sensitivity of various cell stages, and to develop improved statistical approaches to analytical issues in chemical and radiation toxicology. 3 refs

Analysis of the influence of radiation quality on the effectiveness of small doses for induction of reproductive death and chromosome aberrations in mammalian cells

International Nuclear Information System (INIS)

Barendsen, G.W.

1978-01-01

A comparison of RBE - LET relations are made for reproductive death and chromosome aberrations in mammalian cells, as a means of providing insight into the type of mechanisms involved. An analysis of the survival curves for X-rays and gamma rays is discussed and a schematic representation is presented of differences in the dependence of the effectiveness per unit dose on LET, for which data were derived from experiments with X-rays, gamma rays, fast neutrons and heavy ions. (Auth./C.F.)

Simulation of a Rapid Dropout Event for Highly Relativistic Electrons with the RBE Model

Science.gov (United States)

Kang, S-B.; Fok, M.-C.; Glocer, A.; Min, K.-W.; Choi, C.-R.; Choi, E.; Hwang, J.

2016-01-01

A flux dropout is a sudden and sizable decrease in the energetic electron population of the outer radiation belt on the time scale of a few hours. We simulated a flux dropout of highly relativistic 2.5 MeV electrons using the Radiation Belt Environment model, incorporating the pitch angle diffusion coefficients caused by electromagnetic ion cyclotron (EMIC) waves for the geomagnetic storm events of 23-26 October 2002. This simulation showed a remarkable decrease in the 2.5 MeV electron flux during main phase of the storm, compared to those without EMIC waves. This decrease was independent of magnetopause shadowing or drift loss to the magnetopause. We suggest that the flux decrease was likely to be primarily due to pitch angle scattering to the loss cone by EMIC waves. Furthermore, the 2.5 MeV electron flux calculated with EMIC waves correspond very well with that observed from Solar Anomalous and Magnetospheric Particle EXplorer spacecraft. EMIC wave scattering is therefore likely one of the key mechanisms to understand flux dropouts. We modeled EMIC wave intensities by the Kp index. However, the calculated dropout is a several hours earlier than the observed one. We propose that Kp is not the best parameter to predict EMIC waves.

Biology Division progress report, October 1, 1983-September 30, 1984

Energy Technology Data Exchange (ETDEWEB)

Griesmer, R.A.

1985-01-01

The report provides summaries of the aims, scope and progress from October 1983 through September 1984. Major interest was focused on the health effects of neutron- and heavy-ion radiations on animals with particular attention to the carcinogenic responses to low dose levels and to the RBE of various forms of radiation. Among chemical agents, activities concentrated on evaluating and understanding the toxicological interations when mammals are exposed to complex mixtures, either concurrently or successively. Separate abstracts have been prepared for individual sections. (ACR)

Effect of ionizing radiation on DNA-mediated gene transfer efficiency

International Nuclear Information System (INIS)

Rubin, J.S.; Hall, E.J.; Hei, T.K.

1986-01-01

Ionizing radiation causes a number of molecular changes in cells including DNA damage and gene amplification. In this study the authors examined whether radiation can effect the efficiency of integration and expression of exogenous DNA sequences. They examined both 137 Cs γ rays and various monoenergetic neutron beams. This enabled them to test whether the LET or RBE of the radiation had any effect. Rat2 cells were transfected with various amounts of the bacterial plasmid pSV2-GPT along with carrier DNA for 24 hours

Apoptosis induced by high- and low-LET radiations

International Nuclear Information System (INIS)

Hendry, J.H.; Potten, C.S.; Merritt, A.

1995-01-01

Cell death after irradiation occurs by apoptosis in certain cell populations in tissues. The phenomenon also occurs after high linear energy transfer (LET) irradiation, and the relative biological effectiveness (RBE) is 3 to 4 (with respect to low-LET radiation and apoptosis in intestinal crypts) for neutrons with energies of 14 MeV and up to 600 MeV. It is thought that p53 plays a role in the phenomenon, as radiation-induced apoptosis is not observed in p53-null animals. (orig.)

Cellular and molecular radiobiology of heavy-ion beams

International Nuclear Information System (INIS)

Tobias, C.A.; Blakely, E.A.; Ngo, F.Q.H.; Roots, R.J.; Yang, T.C.H.; Chang, P.Y.; Lommel, L.; Craise, L.M.; Yezzi, M.J.

1982-01-01

Accelerated heavy particles are candidates for use in cancer radiotherapy, and the major goal of our program has been to characterize the biological potential of Bevalac beams for this purpose. Relative biological effectiveness (RBE) values and oxygen enhancement ratio (OER) properties of monoenergetic carbon, neon, and argon beams with initial energies of several hundred MeV/u have been measured as a function of residual range. Bevalac beams with Bragg peaks modified to encompass tumors of various sizes have also been studied using cultured cells in vitro

Mutagenic action of radiation with different LET on Bacillus subtilis cells

International Nuclear Information System (INIS)

Borejko, A.V.; Krasavin, E.A.

1996-01-01

The induction of the his - →his + mutants in vegetative and spores of Bacillus subtilis wild type cells irradiated with γ-rays and helium ions (LET=20-80 keV/μm has been investigated. It was shown that the dose dependence of the mutation induction in vegetative cells is described by a linear-quadratic function of dose in case of both γ-rays and helium ions. RBE (LET) dependence on the mutagenic assay is shifted at the low region of LET. (author). 11 refs., 4 figs

Radiation-induced diploid spermatids in mice

Energy Technology Data Exchange (ETDEWEB)

Hacker-Klom, U; Heiden, Th; Otto, F J; Goehde, W; Mauro, F

1989-05-01

Diploid elongated spermatids of mice were enriched by flow cytometry and cell sorting using a new type of sorter (Partec). The sorted abnormal spermatids were identified morphologically and by nuclear area integration. The radiation-induced increase in the frequency of diploid elongated spermatids was monitored with time following acute X-ray exposure of mice. Dose-response curves for acute /sup 60/Co-gamma and 14 MeV neutron irradiations yielded an RBE value of 4.3 for the doubling of the control level. (author).

Implementation of spot scanning dose optimization and dose calculation for helium ions in Hyperion

DEFF Research Database (Denmark)

Fuchs, Hermann; Alber, Markus; Schreiner, Thomas

2015-01-01

PURPOSE: Helium ions ((4)He) may supplement current particle beam therapy strategies as they possess advantages in physical dose distribution over protons. To assess potential clinical advantages, a dose calculation module accounting for relative biological effectiveness (RBE) was developed...... published so far. The advantage of (4)He seems to lie in the reduction of dose to surrounding tissue and to OARs. Nevertheless, additional biological experiments and treatment planning studies with larger patient numbers and more tumor indications are necessary to study the possible benefits of helium ion...

Patterns of Failure After Proton Therapy in Medulloblastoma; Linear Energy Transfer Distributions and Relative Biological Effectiveness Associations for Relapses

International Nuclear Information System (INIS)

Sethi, Roshan V.; Giantsoudi, Drosoula; Raiford, Michael; Malhi, Imran; Niemierko, Andrzej; Rapalino, Otto; Caruso, Paul; Yock, Torunn I.; Tarbell, Nancy J.; Paganetti, Harald; MacDonald, Shannon M.

2014-01-01

Purpose: The pattern of failure in medulloblastoma patients treated with proton radiation therapy is unknown. For this increasingly used modality, it is important to ensure that outcomes are comparable to those in modern photon series. It has been suggested this pattern may differ from photons because of variations in linear energy transfer (LET) and relative biological effectiveness (RBE). In addition, the use of matching fields for delivery of craniospinal irradiation (CSI) may influence patterns of relapse. Here we report the patterns of failure after the use of protons, compare it to that in the available photon literature, and determine the LET and RBE values in areas of recurrence. Methods and Materials: Retrospective review of patients with medulloblastoma treated with proton radiation therapy at Massachusetts General Hospital (MGH) between 2002 and 2011. We documented the locations of first relapse. Discrete failures were contoured on the original planning computed tomography scan. Monte Carlo calculation methods were used to estimate the proton LET distribution. Models were used to estimate RBE values based on the LET distributions. Results: A total of 109 patients were followed for a median of 38.8 months (range, 1.4-119.2 months). Of the patients, 16 experienced relapse. Relapse involved the supratentorial compartment (n=8), spinal compartment (n=11), and posterior fossa (n=5). Eleven failures were isolated to a single compartment; 6 failures in the spine, 4 failures in the supratentorium, and 1 failure in the posterior fossa. The remaining patients had multiple sites of disease. One isolated spinal failure occurred at the spinal junction of 2 fields. None of the 70 patients treated with an involved-field-only boost failed in the posterior fossa outside of the tumor bed. We found no correlation between Monte Carlo-calculated LET distribution and regions of recurrence. Conclusions: The most common site of failure in patients treated with protons for

Reformulation of a clinical-dose system for carbon-ion radiotherapy treatment planning at the National Institute of Radiological Sciences, Japan

Science.gov (United States)

Inaniwa, Taku; Kanematsu, Nobuyuki; Matsufuji, Naruhiro; Kanai, Tatsuaki; Shirai, Toshiyuki; Noda, Koji; Tsuji, Hiroshi; Kamada, Tadashi; Tsujii, Hirohiko

2015-04-01

At the National Institute of Radiological Sciences (NIRS), more than 8,000 patients have been treated for various tumors with carbon-ion (C-ion) radiotherapy in the past 20 years based on a radiobiologically defined clinical-dose system. Through clinical experience, including extensive dose escalation studies, optimum dose-fractionation protocols have been established for respective tumors, which may be considered as the standards in C-ion radiotherapy. Although the therapeutic appropriateness of the clinical-dose system has been widely demonstrated by clinical results, the system incorporates several oversimplifications such as dose-independent relative biological effectiveness (RBE), empirical nuclear fragmentation model, and use of dose-averaged linear energy transfer to represent the spectrum of particles. We took the opportunity to update the clinical-dose system at the time we started clinical treatment with pencil beam scanning, a new beam delivery method, in 2011. The requirements for the updated system were to correct the oversimplifications made in the original system, while harmonizing with the original system to maintain the established dose-fractionation protocols. In the updated system, the radiation quality of the therapeutic C-ion beam was derived with Monte Carlo simulations, and its biological effectiveness was predicted with a theoretical model. We selected the most used C-ion beam with αr = 0.764 Gy-1 and β = 0.0615 Gy-2 as reference radiation for RBE. The C-equivalent biological dose distribution is designed to allow the prescribed survival of tumor cells of the human salivary gland (HSG) in entire spread-out Bragg peak (SOBP) region, with consideration to the dose dependence of the RBE. This C-equivalent biological dose distribution is scaled to a clinical dose distribution to harmonize with our clinical experiences with C-ion radiotherapy. Treatment plans were made with the original and the updated clinical-dose systems, and both

Application of translocation, γ-H2AX, and Sam68 as a biological indicators for the assessment of radiation exposure in nuclear power plant workers

Energy Technology Data Exchange (ETDEWEB)

Yang, Kwang Hee; Park, Hyung Sun; Nam, Seon Young [Korea Hydro Nuclear Power Co., Seoul (Korea, Republic of)

2014-05-15

This study showed that confirmation of the initial dose estimated by dicentric analysis is provided by the subsequent FISH analysis for translocation frequency and provides further evidence for the valid use of FISH as a retrospective biological dosimeter. The IAEA manual on cytogenetic dosimetry recommends a halftime value of 3 y to correct for the decrease of dicentrics in case of delayed sampling based on the patient data of Buckton. Support for this comes from the cytogenetic follow up of an individual exposed to tritium, which also indicated a decline in dicentrics with a half-time of ∼3 y. Naturally, the RBE of tritium, as well as other kinds of ionizing radiation, depends on the dose, exposure conditions, and studied parameters. The information about the RBE of tritium that is most important from an applied standpoint is that associated with the range of low doses. In our study, the dose dependence of tritium RBE was not identified because of very low dose Tritium (< 1mSv). However, The strong smooth relationship between translocation yield and age is shown in Table 2. The translocation yields reported here are only slightly lower than already published. The implication is that the increase of yield with age could be due to environmental factors, to a natural aging process or both. In addition, we confirmed that γ-H2AX and Sam68 associated with DNA damage and apoptosis, can be new biological indicators for radiation exposure. Radiation workers are exposed to ionizing radiation from various sources. Ionizing radiation produces several types of DNA lesion, including DNA base alterations, DNA. DNA cross-links, and single- and double-strand breaks. As a protocol for biological dosimetry recommended by IAEA (2001), the analysis of solid stained dicentric chromosomes has been used since the mid 1960s. The intervening years have seen great improvements bringing the technique to a point where dicentric analysis has become a routine component of the radiological

In vitro study of the influence of alpha particles irradiation on the pre-neoplastic transformation of rat trachea epithelial cells

International Nuclear Information System (INIS)

Kugel, C.

2001-12-01

Intern contamination by actinide oxide inhalation is potentially one health hazard during the nuclear fuel fabrication process. The aerosol particles can induce pulmonary lesions, such as epithelial cancers in particular. Their toxicity is mainly due to radiotoxicity of α irradiation. The aim of this work was to contribute, by an in vitro model, to the study of the apparition of pre-neoplastic states on epithelial cells after high LET irradiation. Primary cultures of rat tracheal epithelial cells were used. Two rat strain cells, SD TR for Sprague Dawley rats and WF TR for Wistar Furth I Fischer F344 rats, were compared after exposure to a dose range from 0 to 5 Gy. Reproductive cell death, i.e. senescent death, seems to be the main lethal way induced by α and γ irradiations. The nuclear volume of WF TR cells is higher than that of SD TR ones, explaining the higher α radiation-induced lethality of these cells. These WF TR cells are also much sensitive to dose rate and α particles energy. In the same manner, pre-neoplastic transformation rate of the cells seems to depend on the physical parameters of irradiation. But, it mainly varies as a function of cell radiosensitivity, that means cell death. In fact, the transformation rate of sensitive WF TR cells is lower than that of SD TR ones. In term of transformation for SD TR cells, dose-effect relationship fits to a linear and infra linear function after α irradiation, whereas the curve fits to linear and quadratic function after γ irradiation. The Relative Biological Efficiency (RBE) of α particles for lethality and pre-neoplastic transformation were determined for several levels of dose. A constant value of about 3 was found for RBE of lethality whatever the α dose. By contrast, the RBE of transformation has a value of about 10 up to 0.5 Gy and gradually decreases at higher doses to reach a value of 1 at 5 Gy. Similar shapes of dose-effect relationship can be observed for malignant lung tumour induction after

Accelerator Based Neutron Beams for Neutron Capture Therapy

International Nuclear Information System (INIS)

Yanch, Jacquelyn C.

2003-01-01

The DOE-funded accelerator BNCT program at the Massachusetts Institute of Technology has resulted in the only operating accelerator-based epithermal neutron beam facility capable of generating significant dose rates in the world. With five separate beamlines and two different epithermal neutron beam assemblies installed, we are currently capable of treating patients with rheumatoid arthritis in less than 15 minutes (knee joints) or 4 minutes (finger joints) or irradiating patients with shallow brain tumors to a healthy tissue dose of 12.6 Gy in 3.6 hours. The accelerator, designed by Newton scientific Incorporated, is located in dedicated laboratory space that MIT renovated specifically for this project. The Laboratory for Accelerator Beam Applications consists of an accelerator room, a control room, a shielded radiation vault, and additional laboratory space nearby. In addition to the design, construction and characterization of the tandem electrostatic accelerator, this program also resulted in other significant accomplishments. Assemblies for generating epithermal neutron beams were designed, constructed and experimentally evaluated using mixed-field dosimetry techniques. Strategies for target construction and target cooling were implemented and tested. We demonstrated that the method of submerged jet impingement using water as the coolant is capable of handling power densities of up to 6 x 10(sup 7) W/m(sup 2) with heat transfer coefficients of 10(sup 6)W/m(sup 2)-K. Experiments with the liquid metal gallium demonstrated its superiority compared with water with little effect on the neutronic properties of the epithermal beam. Monoenergetic proton beams generated using the accelerator were used to evaluate proton RBE as a function of LET and demonstrated a maximum RBE at approximately 30-40 keV/um, a finding consistent with results published by other researchers. We also developed an experimental approach to biological intercomparison of epithermal beams and

Characteristic 8 keV X rays possess radiobiological properties of higher-LET radiation.

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Shridhar, Ravi; Estabrook, William; Yudelev, Mark; Rakowski, Joseph; Burmeister, Jay; Wilson, George D; Joiner, Michael C

2010-03-01

Electronic brachytherapy systems are being developed that can deliver X rays of varying energy depending on the material of a secondary target. A copper target produces characteristic 8 keV X rays. Our aim was to determine whether 8 keV X rays might deliver greater biological effectiveness than megavoltage photons. Cells of the U251 human glioma cell line were used to compare the biological effects of 8 keV X rays and (60)Co gamma rays in terms of relative biological effectiveness (RBE), oxygen enhancement ratio (OER), and DNA damage. The RBE at 50% and 10% survival was 2.6 and 1.9, respectively. At 50% survival, the OER for cells treated with 8 keV X rays was 1.6 compared with 3.0 for (60)Co gamma rays. The numbers of H2AX foci per Gy after treatment with 8 keV X rays and (60)Co gamma rays were similar; however, the size of the foci generated at 8 keV was significantly larger, possibly indicating more complex DNA damage. The mean area of H2AX foci generated by 8 keV X rays was 0.785 microm(2) (95% CI: 0.756-0.814) compared with 0.491 microm(2) (95% CI: 0.462-0.520) for (60)Co gamma rays (P X rays produce two to three times the biological effectiveness of megavoltage photons, with a radiobiological profile similar to higher-LET radiations.

Proton Therapy for Breast Cancer After Mastectomy: Early Outcomes of a Prospective Clinical Trial

International Nuclear Information System (INIS)

MacDonald, Shannon M.; Patel, Sagar A.; Hickey, Shea; Specht, Michelle; Isakoff, Steven J.; Gadd, Michele; Smith, Barbara L.; Yeap, Beow Y.; Adams, Judith; DeLaney, Thomas F.; Kooy, Hanne; Lu, Hsiao-Ming; Taghian, Alphonse G.

2013-01-01

Purpose: Dosimetric planning studies have described potential benefits for the use of proton radiation therapy (RT) for locally advanced breast cancer. We report acute toxicities and feasibility of proton delivery for 12 women treated with postmastectomy proton radiation with or without reconstruction. Methods and Materials: Twelve patients were enrolled in an institutional review board-approved prospective clinical trial. The patients were assessed for skin toxicity, fatigue, and radiation pneumonitis during treatment and at 4 and 8 weeks after the completion of therapy. All patients consented to have photographs taken for documentation of skin toxicity. Results: Eleven of 12 patients had left-sided breast cancer. One patient was treated for right-sided breast cancer with bilateral implants. Five women had permanent implants at the time of RT, and 7 did not have immediate reconstruction. All patients completed proton RT to a dose of 50.4 Gy (relative biological effectiveness [RBE]) to the chest wall and 45 to 50.4 Gy (RBE) to the regional lymphatics. No photon or electron component was used. The maximum skin toxicity during radiation was grade 2, according to the Common Terminology Criteria for Adverse Events (CTCAE). The maximum CTCAE fatigue was grade 3. There have been no cases of RT pneumonitis to date. Conclusions: Proton RT for postmastectomy RT is feasible and well tolerated. This treatment may be warranted for selected patients with unfavorable cardiac anatomy, immediate reconstruction, or both that otherwise limits optimal RT delivery using standard methods

Dose- and time-dependent gene expression alterations in prostate and colon cancer cells after in vitro exposure to carbon ion and X-irradiation

Science.gov (United States)

Suetens, Annelies; Moreels, Marjan; Quintens, Roel; Soors, Els; Buset, Jasmine; Chiriotti, Sabina; Tabury, Kevin; Gregoire, Vincent; Baatout, Sarah

2015-01-01

Hadrontherapy is an advanced form of radiotherapy that uses beams of charged particles (such as protons and carbon ions). Compared with conventional radiotherapy, the main advantages of carbon ion therapy are the precise absorbed dose localization, along with an increased relative biological effectiveness (RBE). This high ballistic accuracy of particle beams deposits the maximal dose to the tumor, while damage to the surrounding healthy tissue is limited. Currently, hadrontherapy is being used for the treatment of specific types of cancer. Previous in vitro studies have shown that, under certain circumstances, exposure to charged particles may inhibit cell motility and migration. In the present study, we investigated the expression of four motility-related genes in prostate (PC3) and colon (Caco-2) cancer cell lines after exposure to different radiation types. Cells were irradiated with various absorbed doses (0, 0.5 and 2 Gy) of accelerated 13C-ions at the GANIL facility (Caen, France) or with X-rays. Clonogenic assays were performed to determine the RBE. RT-qPCR analysis showed dose- and time-dependent changes in the expression of CCDC88A, FN1, MYH9 and ROCK1 in both cell lines. However, whereas in PC3 cells the response to carbon ion irradiation was enhanced compared with X-irradiation, the effect was the opposite in Caco-2 cells, indicating cell-type–specific responses to the different radiation types. PMID:25190155

Comparison of the dose-response relationships for chromosome aberration frequencies between the T65D and DS86 dosimetries

International Nuclear Information System (INIS)

Preston, D.L.; McConney, M.E.; Awa, A.A.; Ohtaki, Kazuo; Itoh, Masahiro; Honda, Takeo.

1989-05-01

Cytogenetic data, derived from cultured lymphocytes of atomic bomb survivors and controls in the ABCC-RERF Adult Health Study cohort, have been analyzed to determine differences in the dose-response relationships for chromosome aberrations between the T65D and DS86 dose estimates and to assess differences between Hiroshima and Nagasaki. For a linear dose-response model, the average percentage of cells with at least one chromosome aberration increases less rapidly with dose in Nagasaki than in Hiroshima. The magnitude of the intercity difference in the percentage of cells with aberrations per gray is less for DS86 than for T65D, though the difference is statistically significant for both kerma and bone marrow dose with either dosimetry. The percentage of cells with aberrations per gray for DS86 kerma estimates is about 60 % greater than the corresponding T65D slope. Analyses to test nonlinearity in the dose-response function indicate significant departures (p<.001) from linearity, using both dosimetries for both kerma and marrow dose. Therefore, comparative results are presented for a range of RBE relationships under various linear (L) and linearquadratic linear (LQ-L) models. As an illustrative result, if one assumes an LQ-L model similar to models reported in the cytogenetic literature, with a limiting RBE of 20 at zero dose, the DS86 slope (the percentage of cells with aberrations per sievert) is 120 % greater than the corresponding T65D value. (J.P.N.)

Proton Therapy for Breast Cancer After Mastectomy: Early Outcomes of a Prospective Clinical Trial

Energy Technology Data Exchange (ETDEWEB)

MacDonald, Shannon M., E-mail: smacdonald@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Patel, Sagar A.; Hickey, Shea [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Specht, Michelle [Department of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Isakoff, Steven J. [Division of Hematology and Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Gadd, Michele; Smith, Barbara L. [Department of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Yeap, Beow Y. [Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Adams, Judith; DeLaney, Thomas F.; Kooy, Hanne; Lu, Hsiao-Ming; Taghian, Alphonse G. [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States)

2013-07-01

Purpose: Dosimetric planning studies have described potential benefits for the use of proton radiation therapy (RT) for locally advanced breast cancer. We report acute toxicities and feasibility of proton delivery for 12 women treated with postmastectomy proton radiation with or without reconstruction. Methods and Materials: Twelve patients were enrolled in an institutional review board-approved prospective clinical trial. The patients were assessed for skin toxicity, fatigue, and radiation pneumonitis during treatment and at 4 and 8 weeks after the completion of therapy. All patients consented to have photographs taken for documentation of skin toxicity. Results: Eleven of 12 patients had left-sided breast cancer. One patient was treated for right-sided breast cancer with bilateral implants. Five women had permanent implants at the time of RT, and 7 did not have immediate reconstruction. All patients completed proton RT to a dose of 50.4 Gy (relative biological effectiveness [RBE]) to the chest wall and 45 to 50.4 Gy (RBE) to the regional lymphatics. No photon or electron component was used. The maximum skin toxicity during radiation was grade 2, according to the Common Terminology Criteria for Adverse Events (CTCAE). The maximum CTCAE fatigue was grade 3. There have been no cases of RT pneumonitis to date. Conclusions: Proton RT for postmastectomy RT is feasible and well tolerated. This treatment may be warranted for selected patients with unfavorable cardiac anatomy, immediate reconstruction, or both that otherwise limits optimal RT delivery using standard methods.

The relative biological effectiveness of 60Co γ-rays, 55 kVp X-rays, 250 kVp X-rays, and 11 MeV electrons at low doses

International Nuclear Information System (INIS)

Spadinger, I.; Palcic, B.

1992-01-01

The RBE of selected low-LET radiation modalities (55 kVp X- rays, 250 kVp X-rays, 60 Co γ-rays, and 11 MeV electrons) was investigated for survival of two cell lines (V79 and CHO). Detailed measurements were made in the 0 to 3 Gy dose range using an image cytometry device to accurately determine the number of cells assayed at each dose point. Data were also collected in the high dose range (0 to 10 Gy) using conventional counting and plating techniques. RBE values (#+- #1 SE) varied from 1.0±0.07 (V79 cells) and 1.2± 0.05 (CHO cells) at high doses to 1.3±0.07 (V79) and 1.4±0.1 (CHO) at low doses for 55 kVp X-rays, from 1.1±0.05 (V79) and 1.1±0.04 (CHO) at high doses to 1.1±0.06 (V79) and 1.2±0.2 (CHO) at low doses for 250 kVp X-rays, and from 1.1±0.08 (V79) and 1.0±0.04 (CHO) at high doses to 1.0±0.06 (V79) and 0.9±0.1 (CHO) at low doses for 11 MeV electrons. Only the low and high dose RBEs for 55 kVp X-rays relative to 60 Co γ-rays were significantly different. (author)

Dose-response relationship of leukemia incidence among atomic bomb survivors and their controls by absorbed marrow dose and two types of leukemia Hiroshima and Nagasaki, October 1950 - December 1978

International Nuclear Information System (INIS)

Ishimaru, Toranosuke; Otake, Masanori; Ichimaru, Michito; Mikami, Motoko.

1982-07-01

Analysis of the relationship of the incidence of leukemia to gamma and neutron dose among atomic bomb survivors until 1971 has been reported previously by RERF. The present inquiry was prompted by the extension of case finding to 1978 and by the recent availability of new dose estimates for this fixed cohort. It is focused on the relationship of absorbed marrow dose of gamma rays and neutrons to the incidence of two types of leukemia in the fixed cohort of A-bomb survivors and their controls, the Life Span Study extended sample, in the period October 1950-December 1978. Three dose-response models have been fitted to the data on acute leukemia and chronic granulocytic leukemia. The relationship of the incidence of acute leukemia to gamma and neutron dose again suggests that the ''best'' fitting model involves a dependence on the square of the gamma dose and a linear dependence on neutrons. The estimated relative biological effectiveness (RBE) of neutrons in the induction of acute leukemia is approximately 44/√Dn(Dn = neutron dose) under this model. Based on the 95% confidence limits of the estimated RBE, the risk of this disease is estimated as 0.0026 - 0.0072 cases per million person-years per rem 2 of marrow dose. This analysis has failed, however, to produce a significant dose-response function for the incidence of chronic granulocytic leukemia in relation to the two kinds of radiation. (author)

Comparative dosimetry in intracavitary balloon catheter brachytherapy with I-125 and in Cf-252 brachytherapy combined with BNCT for brain tumors

Energy Technology Data Exchange (ETDEWEB)

Brandao, Samia de Freitas, E-mail: samiabrandao@gmail.com [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Departamento de Engenharia Nuclear; Campos, Tarcisio Passos Ribeiro de [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil)

2013-06-15

Objective: comparative analysis of dosimetry in intracavitary balloon catheter brachytherapy with I-125 and in Cf-252 brachytherapy combined with BNCT for treatment of brain tumors. Materials and methods: simulations of intracavitary balloon catheter brachytherapy with I-125 and in Cf-252 brachytherapy combined with BNCT were performed with the MCNP5 code, modeling the treatment of a brain tumor on a voxel computational phantom representing a human head. Absorbed dose rates were converted into biologically weighted dose rates. Results: intracavitary balloon catheter brachytherapy with I-125 produced biologically weighted mean dose rates of 3.2E-11, 1.3E-10, 1.9E-11 and 6.9E-13 RBE.Gy.h{sup -1}.p{sup -1}.s, respectively, on the healthy tissue, on the balloon periphery and on the /{sub 1} and /{sub 2} tumor infiltration zones. On the other hand, Cf-252 brachytherapy combined with BNCT produced a biologically weighted mean dose rate of 5.2E-09, 2.3E-07, 8.7E-09 and 2.4E-09 RBE.Gy.h{sup -1}.p{sup -1}.s, respectively on the healthy tissue, on the target tumor and on the /{sub 1} and /{sub 2} infiltration zones. Conclusion: Cf-252 brachytherapy combined with BNCT delivered a selective irradiation to the target tumor and to infiltration zones, while intracavitary balloon catheter brachytherapy with I-125 delivered negligible doses on the tumor infiltration zones. (author)

Assessment of differences between X and γ rays in order to validate a new generation of irradiators for insect sterilization

International Nuclear Information System (INIS)

Mastrangelo, Thiago; Walder, Julio M.M.; Parker, Andrew G.; Jessup, Andrew; Orozco-Davila, Dina; Islam, Amirul; Dammalage, Thilakasiri; Pereira, Rui

2009-01-01

Recent fears of terrorism provoked an increase in delays and denials of transboundary shipments of radioisotopes. This represents a serious constraint to sterile insect technique (SIT) programs around the world as they rely on the use of ionizing energy from radioisotopes for insect sterilization. In order to validate a novel Xray irradiator, a series of studies on Ceratitis capitata (Wiedemann) and Anastrepha fraterculus (Wiedemann) (Diptera: Tephritidae) were carried out, comparing the relative biological effectiveness (RBE) between X-rays and traditional γ radiation from 60 Co. Male C. capitata pupae and pupae of both sexes of A. fraterculus, both 24 to 48 h before adult emergence, were irradiated with doses ranging from 15 to 120 Gy and 10 to 70 Gy respectively. Estimated mean doses of 91.2 Gy of X and 124.9 Gy of γ radiation induced 99% sterility in C. capitata males. Irradiated A. fraterculus were 99% sterile at about 40-60 Gy for both radiation treatments. Standard quality control parameters were not significantly affected by the two types of radiation. There were no significant differences between X and γ radiation regarding mating indices. The RBE did not differ significantly between the tested X and γ radiation, and X-rays are as biologically effective for SIT purposes as γ rays are. This work confirms the suitability of this new generation of X-ray irradiators for pest control programs in UN Member States. (author)

Comparative analysis of chromosome aberrations in human lymphocytes induced 'in vitro' by various types of ionizing radiation

International Nuclear Information System (INIS)

Todorov, S.

1975-01-01

A quantitative analysis on various types of chromosome aberrations in human peripheral blood lymphocytes after in vitro whole blood irradiation with 180 kV X-rays, gamma rays from cobalt 60, 50 MeV protons and scission neutrons is carried out. The following aberrations are scored: breaks, total number of aberrations, aberrant cells, chromosome fragments, dicentrics and interstitial deletions. The experimental data obtained are statistically processed applying the method of the least squares and employing four mathematical models: Y = cD 2 , Y = cD, Y = a + bD and Y = a + bD + cD 2 . Statistical analysis showed that after treatment with low LET (linear energy transfer) radiations the most suitable for the description of the kinetic of the two break aberrations, total number of aberrations and breaks in relation to dose is the polynomial second degree model, whereas for one break aberrations and aberrant cells - the linear model. The linear model is equally appropriate for one or two breaks aberrations when it is a matter of high LET radiations. Using the linear component of the polynominal second degree equation a comparative characteristic of the RBE (relative biological effectiveness) for the various radiations types is made. The following mean values for RBE are obtained: 0,86 +- 0,44 for gamma radiation from cobalt 60, 0,98 +- 0,06 for 50 MeV protons and 2,38 +- 0,11 for scission neutrons. (A.B.)

Characterization of radiations field in Earth space in term of linear energy transfer (L.E.T.) for the radiation protection and the radiobiology

International Nuclear Information System (INIS)

Lebaron-Jacobs, L.

1994-01-01

The space missions on orbital stations are becoming longer and the radiological risk constitutes a factor limiting the space flights. The tissue-equivalent proportional counters, (CIRCE in 1988 and 1990, then NAUSICAA from 1992), have been conceived to ensure the monitoring and the dosimetry of space travellers. They measure in real time, different parameters of dosimetry and evaluate the microdosimetric spectrum of space radiations on the board of the Mir spatial station. The equivalent of middle day dose measured by CIRCE was situated between 0.6 and 0.8 mSv associated to a quality factor of 1.9; that one measured by NAUSICAA is higher, between 0.9 and 1.0 mSv with a steady quality factor. These systems measure the time and spatial variations of cosmic radiations, in function of solar activity, orbit, and shielding thickness of space vehicles. Values of high doses equivalent (upper than 1 mSv), associated to quality factor of 1.4 have been measured during the South Atlantic Anomaly crossing and during solar eruptions. That is the same for polar regions. The evaluation of Relative Biological Effectiveness (R.B.E.) of the space radiations on Mir station board, in term of carcinogenesis of the Harder gland in the mouse, is here an extrapolation of a relation based on experimental data; the average R.B.E. allows to suppose that radiological risk is low. (N.C.). 69 refs., 74 figs., 19 tabs

Physical and biological dosimetries of Cf-252 radiation

International Nuclear Information System (INIS)

Yamashita, Hisao; Wada, Tadashi; Dokiya, Takushi; Hashimoto, Shozo

1986-01-01

Recently Cf-252 sources containing 300 μg have become available in a size identical to 1 Ci of Cs-137 and with the use of remotely controlled afterloading apparatus, safe therapy with little exposure to the therapist is now possible. Radiation leakage from the Cf-252 apparatus and from the treatment room was measured with REM-meter and it was possible to reduce the leakage from the treatment room to less than 1 mrem/h (gamma rays) and 0.5 mrem/h (neutrons). Measurement of fast neutrons was made with a twin chamber composed of a tissue equivalent ionization chamber and a carbon ionization chamber. The neutron dose in air and the absorbed dose in tissue equivalent water tank were measured, which showed that in air, neutrons were 70% and photons were 30% of dose. In water, greater distances from the source, neutrons attenuate and gamma rays increase in dose. The results of studies on the skin reaction of mice and sperm cleavage delay time of sea urchins indicated that the RBE ranges from 1.5 to 3.0 using the high dose rate system. Neutrons are remarkably affected by a time factor. With the use of high dose rate sources, the dose rate has become higher, but the overall time has been extended through dose fractionation and it was considered advisable to employ an RBE of 3-4 in these studies. (Auth.)

Microdosimetry of light and heavy ions with TEPC - comparison of calculations with experiments

International Nuclear Information System (INIS)

Nikjoo, Hooshang; Lindborg, Lennart; Brahme, Anders; Pinsky, Lawrence

2008-01-01

Full text: For the purposes of radiation protection it is necessary to estimate the exposure and consequent risk to human from environmental, terrestrial and space, industrial and medical radiations. Therefore, accurate measurement of absorbed dose and estimation of quality factor (Q) and relative biological effectiveness (RBE) are of paramount importance. To obtain a better estimation of RBE and Q values microdosimetric techniques have been employed to model and calculate these quantities. A choice instrument for the measurements of dose and monitoring of radiation environment is tissue equivalent proportional counter (TEPC). In this paper we present modelling and calculations of microdosimetric quantities in spherical TEPC, for wall and wall- less, counters for radiations of different qualities and compare the results to measurements. To improve understanding and knowledge underlying mechanism of radiation action and relevant critical microscopic properties, especially at low doses, need quantitative description of the general features of radiation insult. As ionizing radiation is unique amongst biologically damaging agents in their ability to cause clusters of ionizations and excitations in targets sizes of biological importance, Monte Carlo track structure methods have been employed to investigate spatial and temporal patterns of energy depositions and their biological consequences. Data are presented for microdosimetric distributions as a function of LET and target sizes raging from a few nanometers to micrometer active volumes. The data provides an insight into characterization of radiation track at nanometer scale of interest both in radiation protection and therapy. (author)

Cytotoxic and mutagenic effects of high let charged particles on human skin fibroblasts

International Nuclear Information System (INIS)

Tsuboi, Koji.; Park, M.S.; Chen, D.J.; Yang, T.C.

1992-01-01

Cytotoxic and mutagenic effects of high LET charged particles were quantitatively measured using primary cultures of human skin fibroblasts. The span of LETs selected were from 25 keV/μm(330 MeV/u) to 920 keV/μm (600 MeV/u). Mutations were scored at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus using 6-thioguanine (6-TG) for selection. Exposure to these high LET charged particles resulted in exponential survival curves whereas mutant induction was fitted by a linear model. The Relative Biological Effect (RBE) for cell-killing ranged from 3.73 to 1.25, while that for mutant induction ranged from 5.74 to 0.48. Maximum RBE values were obtained at the LET of 150 keV/μm. The inactivation cross-section (σ i ) and the action cross-section for mutant induction (σ m ) ranged from 2.2 to 92.0 μm 2 and 0.09 to 5.56 x 10 -3 μm 2 respectively, the maximum values were obtained by 56 Fe with an LET of 200 keV/μm. The mutagenicity (σ m /σ i ) ranged from 2.05 to 7.99 x 10 -5 with the maximum value at 150 keV/μm. Furthermore, the results of multiplex polymerase chain reaction (PCR) of some of the mutants induced by charged particles indicate that higher LET beams are more likely to cause larger deletions in the hprt locus. (author)

Comparative dosimetry in intracavitary balloon catheter brachytherapy with I-125 and in Cf-252 brachytherapy combined with BNCT for brain tumors

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Samia de Freitas Brandao

2013-07-01

Full Text Available Objective Comparative analysis of dosimetry in intracavitary balloon catheter brachytherapy with I-125 and in Cf-252 brachytherapy combined with BNCT for treatment of brain tumors. Materials and Methods Simulations of intracavitary balloon catheter brachytherapy with I-125 and in Cf-252 brachytherapy combined with BNCT were performed with the MCNP5 code, modeling the treatment of a brain tumor on a voxel computational phantom representing a human head. Absorbed dose rates were converted into biologically weighted dose rates. Results Intracavitary balloon catheter brachytherapy with I-125 produced biologically weighted mean dose rates of 3.2E-11, 1.3E-10, 1.9E-11 and 6.9E-13 RBE.Gy.h-1.p-1.s, respectively, on the healthy tissue, on the balloon periphery and on the I 1 and I 2 tumor infiltration zones. On the other hand, Cf-252 brachytherapy combined with BNCT produced a biologically weighted mean dose rate of 5.2E-09, 2.3E-07, 8.7E-09 and 2.4E-09 RBE.Gy.h-1.p-1.s, respectively on the healthy tissue, on the target tumor and on the I 1 and I 2 infiltration zones. Conclusion Cf-252 brachytherapy combined with BNCT delivered a selective irradiation to the target tumor and to infiltration zones, while intracavitary balloon catheter brachytherapy with I-125 delivered negligible doses on the tumor infiltration zones.

Measurements of Relative Biological Effectiveness and Oxygen Enhancement Ratio of Fast Neutrons of Different Energies

Energy Technology Data Exchange (ETDEWEB)

Barendsen, G. W.; Broerse, J. J. [Radiobiological Institute of the Health Research Council TNO, Rijswijk (ZH) (Netherlands)

1968-03-15

Impairment of the reproductive capacity of cultured cells of human kidney origin (T-l{sub g} cells) has been measured by the Puck cloning technique. From the dose-survival curves obtained in these experiments by irradiation of cells in equilibrium with air and nitrogen, respectively, the relative biological effectiveness (RBE) and the oxygen enhancement ratios (OER) were determined for different beams of fast neutrons. Monoenergetic neutrons of 3 and 15 MeV energy, fission spectrum fast neutrons (mean energy about 1.5 MeV), neutrons produced by bombarding Be with cyclotron-accelerated 16 MeV deuterons (mean energy about 6 MeV) and neutrons produced by bombarding Be with cyclotron- accelerated 20 MeV {sup 3}He ions (mean energy about 10 MeV) have been compared with 250 kVp X-rays as a standard reference. The RBE for 50% cell survival varies from 4.7 for fission-spectrum fast neutrons to 2.7 for 15 MeV monoenergetic neutrons. The OER is not strongly dependent on the neutron energy for the various beams investigated. For the neutrons with the highest and lowest energies used OER values of 1.6 {+-} 0.2 and 1.5 {+-} 0.1 were measured. An interpretation of these data on the basis of the shapes of the LET spectra is proposed and an approximate verification of this hypothesis is provided from measurements in which secondary particle equilibrium was either provided for or deliberately eliminated. (author)

Relative biological effectiveness measurements using murine lethality and survival of intestinal and hematopoietic stem cells after Fermilab neutrons compared to JANUS reactor neutrons and 60Co gamma rays

International Nuclear Information System (INIS)

Hanson, W.R.; Crouse, D.A.; Fry, R.J.M.; Ainsworth, E.J.

1984-01-01

The relative biological effectiveness (RBE) of the 25-MeV (average energy) neutron beam at the Fermi National Accelerator Laboratory was measured using murine bone marrow (LD/sub 50/30/) and gut (LD/sub 50/6/) lethality and killing of hematopoietic colony forming units (CFU-S) or intestinal clonogenic cells (ICC). The LD/sub 50/30/ and LD/sub 50/6/ for mice exposed to the Fermilab neutron beam were 6.6 and 8.7 Gy, respectively, intermediate between those of JANUS neutrons and 60 Co γ rays. The D 0 values for CFU-S and ICC were 47 cGy and 1.05 Gy, respectively, also intermediate between the lowest values found for JANUS neutrons and the highest values found after 60 Co γ rays. The split-dose survival ratios for CFU-S at intervals of 1-6 hr between doses were essentially 1.0 for both neutron sources. The 3-hr split-dose survival ratios for ICC were 1.0 for JANUS neutrons, 1.85 for Fermilab neutrons, and 6.5 for 60 Co γ rays. The RBE estimates for LD/sub 50/30/ were 1.5 and 2.3 for Fermilab and JANUS neutrons, respectively. Based on LD/sub 50/6/, the RBEs were 1.9 (Fermilab) and 3.0 (JANUS). The RBEs for CFU-S D 0 were 1.4 (Fermilab) and 1.9 (JANUS) and for jejunal microcolony D 0 1.4 (Fermilab) and 2.8 (JANUS)

Characterization of radiations field in Earth space in term of linear energy transfer (L.E.T.) for the radiation protection and the radiobiology; Caracterisation du champ de radiation dans l`espace circumterrestre en terme de transfert lineique d`energie (T.L.E.) pour la radioprotection et pour la radiobiologie

Energy Technology Data Exchange (ETDEWEB)

Lebaron-Jacobs, L

1994-07-07

The space missions on orbital stations are becoming longer and the radiological risk constitutes a factor limiting the space flights. The tissue-equivalent proportional counters, (CIRCE in 1988 and 1990, then NAUSICAA from 1992), have been conceived to ensure the monitoring and the dosimetry of space travellers. They measure in real time, different parameters of dosimetry and evaluate the microdosimetric spectrum of space radiations on the board of the Mir spatial station. The equivalent of middle day dose measured by CIRCE was situated between 0.6 and 0.8 mSv associated to a quality factor of 1.9; that one measured by NAUSICAA is higher, between 0.9 and 1.0 mSv with a steady quality factor. These systems measure the time and spatial variations of cosmic radiations, in function of solar activity, orbit, and shielding thickness of space vehicles. Values of high doses equivalent (upper than 1 mSv), associated to quality factor of 1.4 have been measured during the South Atlantic Anomaly crossing and during solar eruptions. That is the same for polar regions. The evaluation of Relative Biological Effectiveness (R.B.E.) of the space radiations on Mir station board, in term of carcinogenesis of the Harder gland in the mouse, is here an extrapolation of a relation based on experimental data; the average R.B.E. allows to suppose that radiological risk is low. (N.C.). 69 refs., 74 figs., 19 tabs.

The comparative investigation of gene mutation induction in Bacillus subtilis and Escherichia coli cells after irradiation by different LET radiation

International Nuclear Information System (INIS)

Borejko, A.V.; Bulah, A.P.

2005-01-01

The data of mutagenetic action of ionizing radiation with different physical characteristics on bacterial cells with various genotypes are presented. It was shown that regularities of inducible mutagenesis in Bacillus subtilis and E. coli are consimilar. The dose-response dependence for both types of cells is described by the linear-quadratic function. The RBE on LET relationship has a local maximum at 20 keV/μm. The crucial role in inducible mutagenesis in E. coli and Bacillus subtilis cells is played by the error-prone SOS-repair

Systems reliability Benchmark exercise part 1-Description and results

International Nuclear Information System (INIS)

Amendola, A.

1986-01-01

The report describes aims, rules and results of the Systems Reliability Benchmark Exercise, which has been performed in order to assess methods and procedures for reliability analysis of complex systems and involved a large number of European organizations active in NPP safety evaluation. The exercise included both qualitative and quantitative methods and was structured in such a way that separation of the effects of uncertainties in modelling and in data on the overall spread was made possible. Part I describes the way in which RBE has been performed, its main results and conclusions

The Comparative Investigation of Gene Mutation Induction in {\\it Bacillus subtilis} and {\\it Escherichia coli} Cells after Irradiation by Different LET Radiation

CERN Document Server

Boreyko, A V

2005-01-01

The data of mutagenic action of ionizing radiation with different physical characteristics on bacterial cells with various genotypes are presented. It was shown that regularities of inducible mutagenesis in {\\it Bacillus subtilis} and {\\it E.coli} are consimilar. The dose-response dependence for both types of cells is described by the linear-quadratic function. The RBE on LET relationship has a local maximum at 20 keV/$\\mu $m. The crucial role in inducible mutagenesis in {\\it E.coli} and {\\it Bacillus subtilis} cells is played by the error-prone $SOS$-repair.