Study Protocol for Radiation Exposure and Cancer Risk Assessment: The Taiwan Nuclear Power Plants and Epidemiology Cohort Study (TNPECS).

BACKGROUND: This cohort was established to evaluate whether 38-year radiation exposure (since the start of nuclear reactor operations) is related to cancer risk in residents near three nuclear power plants (NPPs). METHODS: This cohort study enrolled all residents who lived within 8 km of any of the three NPPs in Taiwan from 1978 to 2016 (n = 214,502; person-years = 4,660,189). The control population (n = 257,475; person-years = 6,282,390) from three towns comprised all residents having lived more than 15 km from all three NPPs. Radiation exposure will be assessed via computer programs GASPAR-II and LADTAP-II by following methodologies provided in the United States Nuclear Regulatory Commission regulatory guides. We calculated the cumulative individual tissue organ equivalent dose and cumulative effective dose for each resident. This study presents the number of new cancer cases and prevalence in the residence-nearest NPP group and control group in the 38-year research observation period. CONCLUSION: TNPECS provides a valuable platform for research and opens unique possibilities for testing whether radiation exposure since the start of operations of nuclear reactors will affect health across the life course. The release of radioactive nuclear species caused by the operation of NPPs caused residents to have an effective dose between 10-7 and 10-3 mSv/year. The mean cumulative medical radiation exposure dose between the residence-nearest NPP group and the control group was not different (7.69; standard deviation, 18.39 mSv and 7.61; standard deviation, 19.17 mSv; P = 0.114).

MOSFET dose measurements for proton SOBP beam.

PURPOSE: The aim of this work was to develop a computational scheme for the correction of the LET dependence on the MOSFET response in water phantom dose measurements for a spread-out Bragg peak (SOBP) proton beam. METHODS: The LET dependence of MOSFET was attributed to the stopping power ratio of SiO2 to H2O and to the fractional hole yield in the SiO2 layer. Using literature values for the stopping powers of the continuous slowing down approximation and measured fractional hole yields vs. electric field and LET, formulas were derived for the computation of a dose-weighted correction factor of a SOBP beam. RESULTS: Dose-weighted correction factors were computed for a clinical 190-MeV proton SOBP beam in a high-density polyethylene phantom. By applying correction factors to the SOBP beam, which consisted of weighted monoenergetic Bragg peaks, the MOSFET outputs were predicted and agreed well with the measured MOSFET responses. CONCLUSION: By applying LET dependent correction factors to MOSFET data, quality assurance of dose verification based on MOSFET measurements becomes possible for proton therapy.

Assessment of resident doses near nuclear power plants in Taiwan for epidemiology study.

Dose assessments were required for the epidemiological study of residents living near nuclear power plants. In the present work, environmental pathway models have been applied to estimate radiation doses to residents living near the nuclear power plants in Taiwan. Best estimates of doses were made for residents by their age groups in different compass sectors centered at the nuclear power plants. In each sector, radiation doses were assessed using the averaged environmental, consumption and lifestyle data. For epidemiological analyses of cancer risks in different organs or tissues, individual organ absorbed doses were assessed for both the airborne and waterborne effluent releases. Such assessments were performed based on the historic data, including measured effluent releases, detected meteorological parameters, and surveyed data on the production and consumption of local agricultural, fishery and livestock products, etc. Exposure pathways consisted of the external irradiations from air submersion, ground deposition and water immersion plus the internal irradiations from inhalation and ingestion. Age-dependent annual intakes and occupancy time were locally surveyed. Dose conversion coefficients were taken from published data after International Commission on Radiological Protection Publication 60. Annual doses and cumulated doses during residence were assessed and examined for their dependence on age, organ and compass sector.

A Monte Carlo study of bone-tissue interface microdosimeters.

Radiation-induced bone diseases were frequently reported in radiotherapy patients. To study the diseases, microdosimeters were constructed with walls of A150-A150, A150-B100, B100-A150 and B100-B100 interfaces. Monte Carlo simulations of these microdosimeters were performed to determine the lineal energy spectra of an interface site at different depths in water for 230 MeV protons. Comparing these spectra with data of ICRU tissue and bone walls, better agreements were found at shallow depths for protons and delta-rays than deep depths for nuclear interactions.

Radiosensitization of ultrasmall GNP-PEG-cRGDfK in ALTS1C1 exposed to therapeutic protons and kilovoltage and megavoltage photons.

PURPOSE: One of the promising radiosensitizers is the ultrasmall gold nanoparticle (GNP) with a hydrodynamic diameter <3 nm. We studied functionalized ultrasmall GNPs (1.8 nm diameter) coated by polyethylene glycol (PEG) and conjugated with cyclic RGDfK (2.6 nm hydrodynamic diameter) for targeting of alpha(v) beta(3) integrin (αvß3) in the murine ALTS1C1 glioma cell line. MATERIALS AND METHODS: We investigated the uptake, toxicity and radiosensitivity of GNP-PEG-cRGDfKs in ALTS1C1 cells exposed to protons, kilovoltage photons and megavoltage photons. The in vitro uptake and toxicity of GNPs in the hepatocytes and Kupffer cells were assessed for murine AML12 hepatocyte and RAW 264.7 macrophage cell lines. The in vivo biodistribution of GNPs in the ALTS1C1 tumor model was tested using the inductively coupled plasma mass spectrometry. RESULTS: Results indicated GNPs accumulated in the cytoplasm with negligible toxicity for a moderate concentration of GNPs. Observed sensitizer enhancement ratios and dose enhancement factors are 1.21-1.66 and 1.14-1.33, respectively, for all radiations. CONCLUSION: Ultrasmall GNP-PEG-cRGD can be considered as a radiosensitizer. For radiotherapy applications, the delivery method should be developed to increase the GNP uptake in the tumor and decrease the uptakes in undesirable organs.

MCNPX simulation of proton dose distributions in a water phantom.

BACKGROUND: This study presents the Monte Carlo N-Particles Transport Code, Extension (MCNPX) simulation of proton dose distributions in a water phantom. METHODS: In this study, fluence and dose distributions from an incident proton pencil beam were calculated as a function of depth in a water phantom. Moreover, lateral dose distributions were also studied to understand the deviation among different MC simulations and the pencil beam algorithm. MCNPX codes were used to model the transport and interactions of particles in the water phantom using its built-in "repeated structures" feature. Mesh Tally was used in which the track lengths were distributed in a defined cell and then converted into doses and fluences. Two different scenarios were studied including a proton equilibrium case and a proton disequilibrium case. RESULTS: For the proton equilibrium case, proton fluence and dose in depths beyond the Bragg peak were slightly perturbed by the choice of the simulated particle types. The dose from secondary particles was about three orders smaller, but its simulation consumed significant computing time. This suggests that the simulation of secondary particles may only be necessary for radiation safety issues for proton therapy. For the proton disequilibrium case, the impacts of different multiple Coulomb scattering (MCS) models were studied. Depth dose distributions of a 70 MeV proton pencil beam in a water phantom obtained from MCNPX, Geometry and Track, version 4, and the pencil beam algorithm showed significant deviations between each other, because of different MCS models used. CONCLUSIONS: Careful modelling of MCS is necessary when proton disequilibrium exists.

Microdosimetric relative biological effectiveness of therapeutic proton beams.

When compared to photon beams, particle beams have distinct spatial distributions on the energy depositions in both the macroscopic and microscopic volumes. In a macroscopic volume, the absorbed dose distribution shows a rapid increase near the particle range, that is, Bragg peak, as particle penetrates deep inside the tissue. In a microscopic volume, individual particle deposits its energy along the particle track by producing localized ionizations through the formation of clusters. These highly localized clusters can induce complex types of deoxyribonucleic acid (DNA) damage which are more difficult to repair and lead to higher relative biological effectiveness (RBE) as compared to photons. To describe the biological actions, biophysical models on a microscopic level have been developed. In this review, microdosimetric approaches are discussed for the determination of RBE at different depths in a patient under particle therapy. These approaches apply the microdosimetric lineal energy spectra obtained from measurements or calculations. Methods to determine these spectra will be focused on the tissue equivalent proportional counter and the Monte Carlo program. Combining the lineal energy spectrum and the biological model, RBE can be determined. Three biological models are presented. A simplified model applies the dose-mean lineal energy and the measured RBE (linear energy transfer) data. A more detailed model makes use of the full lineal energy spectrum and the biological weighting function spectrum. A comprehensive model calculates the spectrum-averaged yields of DNA damages caused by all primary and secondary particles of a particle beam. Results of these models are presented for proton beams.

Fast Monte Carlo simulation of DNA damage induction by Auger-electron emission.

PURPOSE: A local damage model (LDM) was developed to estimate the biological efficiency of Auger-electron-emitting radionuclides. MATERIALS AND METHODS: The LDM required information on the local dose distribution, local energy spectrum, and clustered DNA damage yields in the cell nucleus. To apply the model, the nucleus was divided into concentric shells where each shell contributed its own local dose, energy spectrum, and damage yield. The local doses and energy spectra were computed using the PENELOPE (PENetration and Energy LOss of Positrons and Electrons) code. The DNA damage yields were estimated using the MCDS (Monte Carlo damage simulation) code. RESULTS: For a typical 4-µm radius mammalian cell nucleus, the absorbed doses to the cell nucleus per unit cumulated activity, equal to 0.0065, 0.00418, 0.0028, 0.0027 and 0.0015 Gy Bq(-1) s(-1) for (125)I, (119)Sb, (123)I, (111)In and (99m)Tc, were within 6% difference with the MIRD (Medical Internal Radiation Dose) published data. The simulated total (simple and complex) single-strand break (SSB) and double-strand break (DSB) yields were in the same order, i.e., (125)I > (119)Sb > (123)I > (111)In > (99m)Tc. The agreement between present results and literature data for the DNA damage yields was generally good. More than 75% of the total SSB and DSB yields were contributed from regions within 2.5 µm of the nucleus center. CONCLUSIONS: The proposed methodology was computationally efficient and could be applied to other irradiation geometries such as cell clusters.

Surveyed data for structural shielding calculations of radiographic x-ray installations in Taiwan.

The use of surveyed data on the x-ray tube workloads and clinical exposure parameters was suggested in NCRP Report No. 147 for the structural shielding design of medical x-ray installations. To guide the shielding design of radiographic x-ray rooms in Taiwan, a large-scale survey was conducted to collect information required for the computations of the transmissions from broad x-ray beams through shielding materials. Surveyed data were collected during one week from 10,750 projections of 6,657 examinations in 13 radiographic rooms from nine hospitals. This survey was the first time that this type of clinical data has been collected in Taiwan on a large scale. The surveyed total workload was divided into separate contributions from x-ray projections directed at the floor, the wall bucky, and all barriers (used for secondary barriers). Based on the surveyed workload distributions, the unshielded air kerma per patient at 1 m from the source was calculated by the PCXMC program using surveyed x-ray tube parameters on the generator waveform, anode material, target angle, and filtration. Subsequently, the transmissions of x-rays through different barrier materials were computed by considering the average workloads and the average workloads plus one standard deviations. The latter computations were for a sensitivity study to find the influence of workload variations in different hospitals on the shielding requirements. All surveyed data and calculated results were compared with corresponding values given in NCRP 147 to analyze the radiographic imaging differences between Taiwan and U.S.

Cellular- and micro-dosimetry of heterogeneously distributed tritium.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: Cellular- and micro-dosimetry models were developed for the assessment of heterogeneously distributed tritium.

Monte Carlo simulations of therapeutic proton beams for relative biological effectiveness of double-strand break.

PURPOSE: The relative biological effectiveness (RBE) values relative to (60)Co for the induction of double-strand breaks (DSB) were calculated for therapeutic proton beams. RBE-weighted absorbed doses were determined at different depths in a water phantom for proton beams. MATERIALS AND METHODS: The depth-dose distributions and the fluence spectra for primary protons and secondary particles were calculated using the FLUKA (FLUktuierende KAskade) MC (Monte Carlo) transport code. These spectra were combined with the MCDS (Monte Carlo damage simulation) code to simulate the spectrum-averaged yields of clustered DNA lesions. RBE for the induction of DSB were then determined at different depths in a water phantom for the unmodulated and modulated proton beams. RESULTS: The maximum RBE for the induction of DSB at 1 Gy absorbed dose was found about 1.5 at 0.5 cm distal to the Bragg peak maximum for an UNMODULATED 160 MeV proton beam. The RBE-weighted absorbed dose extended the biologically effective range of the proton beam by 1.9 mm. The corresponding maximum RBE value was inversely proportional to the proton beam energy, reaching a value of about 1.9 for 70 MeV proton beam. For a modulated 160 MeV proton beam, the RBE weightings were more pronounced near the spread-out Bragg peak (SOBP) distal edge. CONCLUSIONS: It was demonstrated that a fast MCDS code could be used to simulate the DNA damage yield for therapeutic proton beams. Simulated RBE for the induction of DSB were comparable to RBE measured in vitro and in vivo. Depth dependent RBE values in the SOBP region might have to be considered in certain treatment situations.

Model-based radiation dose correction for yttrium-90 microsphere treatment of liver tumors with central necrosis.

PURPOSE: The objectives of this study were to model and calculate the absorbed fraction ϕ of energy emitted from yttrium-90 ((90)Y) microsphere treatment of necrotic liver tumors. METHODS AND MATERIALS: The tumor necrosis model was proposed for the calculation of ϕ over the spherical shell region. Two approaches, the semianalytic method and the probabilistic method, were adopted. In the former method, the range--energy relationship and the sampling of electron paths were applied to calculate the energy deposition within the target region, using the straight-ahead and continuous-slowing-down approximation (CSDA) method. In the latter method, the Monte Carlo PENELOPE code was used to verify results from the first method. RESULTS: The fraction of energy, ϕ, absorbed from (90)Y by 1-cm thickness of tumor shell from microsphere distribution by CSDA with complete beta spectrum was 0.832 ± 0.001 and 0.833 ± 0.001 for smaller (r(T) = 5 cm) and larger (r(T) = 10 cm) tumors (where r is the radii of the tumor [T] and necrosis [N]). The fraction absorbed depended mainly on the thickness of the tumor necrosis configuration, rather than on tumor necrosis size. The maximal absorbed fraction φ that occurred in tumors without central necrosis for each size of tumor was different: 0.950 ± 0.000, and 0.975 ± 0.000 for smaller (r(T) = 5 cm) and larger (r(T) = 10 cm) tumors, respectively (p < 0.0001). CONCLUSIONS: The tumor necrosis model was developed for dose calculation of (90)Y microsphere treatment of hepatic tumors with central necrosis. With this model, important information is provided regarding the absorbed fraction applicable to clinical (90)Y microsphere treatment.

Midline dose verification with diode in vivo dosimetry for external photon therapy of head and neck and pelvis cancers during initial large-field treatments.

During radiotherapy treatments, quality assurance/control is essential, particularly dose delivery to patients. This study was designed to verify midline doses with diode in vivo dosimetry. Dosimetry was studied for 6-MV bilateral fields in head and neck cancer treatments and 10-MV bilateral and anteroposterior/posteroanterior (AP/PA) fields in pelvic cancer treatments. Calibrations with corrections of diodes were performed using plastic water phantoms; 190 and 100 portals were studied for head and neck and pelvis treatments, respectively. Calculations of midline doses were made using the midline transmission, arithmetic mean, and geometric mean algorithms. These midline doses were compared with the treatment planning system target doses for lateral or AP (PA) portals and paired opposed portals. For head and neck treatments, all 3 algorithms were satisfactory, although the geometric mean algorithm was less accurate and more uncertain. For pelvis treatments, the arithmetic mean algorithm seemed unacceptable, whereas the other algorithms were satisfactory. The random error was reduced by using averaged midline doses of paired opposed portals because the asymmetric effect was averaged out. Considering the simplicity of in vivo dosimetry, the arithmetic mean and geometric mean algorithm should be adopted for head/neck and pelvis treatments, respectively.

Measurement-based Monte Carlo dose calculation system for IMRT pretreatment and on-line transit dose verifications.

The aim of this study was to develop a dose simulation system based on portal dosimetry measurements and the BEAM Monte Carlo code for intensity-modulated (IM) radiotherapy dose verification. This measurement-based Monte Carlo (MBMC) system can perform, within one systematic calculation, both pretreatment and on-line transit dose verifications. BEAMnrc and DOSXYZnrc 2006 were used to simulate radiation transport from the treatment head, through the patient, to the plane of the aS500 electronic portal imaging device (EPID). In order to represent the nonuniform fluence distribution of an IM field within the MBMC simulation, an EPID-measured efficiency map was used to redistribute particle weightings of the simulated phase space distribution of an open field at a plane above a patient/phantom. This efficiency map was obtained by dividing the measured energy fluence distribution of an IM field to that of an open field at the EPID plane. The simulated dose distribution at the midplane of a homogeneous polystyrene phantom was compared to the corresponding distribution obtained from the Eclipse treatment planning system (TPS) for pretreatment verification. It also generated a simulated transit dose distribution to serve as the on-line verification reference for comparison to that measured by the EPID. Two head-and-neck (NPC1 and NPC2) and one prostate cancer fields were tested in this study. To validate the accuracy of the MBMC system, film dosimetry was performed and served as the dosimetry reference. Excellent agreement between the film dosimetry and the MBMC simulation was obtained for pretreatment verification. For all three cases tested, gamma evaluation with 3%/3 mm criteria showed a high pass percentage (> 99.7%) within the area in which the dose was greater than 30% of the maximum dose. In contrast to the TPS, the MBMC system was able to preserve multileaf collimator delivery effects such as the tongue-and-groove effect and interleaf leakage. In the NPC1 field, the TPS showed 16.5% overdose due to the tongue-and-groove effect and 14.6% overdose due to improper leaf stepping. Similarly, in the NPC2 field, the TPS showed 14.1% overdose due to the tongue-and-groove effect and 8.9% overdose due to improper leaf stepping. In the prostate cancer field, the TPS showed 6.8% overdose due to improper leaf stepping. No tongue-and-groove effect was observed for this field. For transit dose verification, agreements among the EPID measurement, the film dosimetry, and the MBMC system were also excellent with a minimum gamma pass percentage of 99.6%.

Mathematical estimation and in vivo dose measurement for cone-beam computed tomography on prostate cancer patients.

BACKGROUND AND PURPOSE: Cone-beam computed tomography (CBCT) increases the doses on normal tissues. Our study sought to develop a mathematical model that would provide an estimate of and verify in vivo rectal dose from CBCT in prostate cancer patients. MATERIALS AND METHODS: Thermoluminescent dosimeters (TLDs) and Rando phantoms were used to measure doses to the pelvic region. We used an endorectal balloon to measure rectal doses for 10 prostate cancer patients who underwent radiotherapy and for whom we were able to acquire CBCT images. A solid water phantom and TLDs were used to correlate the rectal doses with body thickness/widths. A mathematical method was established to simulate the dose to which the patient is exposed during CBCT for the determined body parameters. The estimated doses were compared with the measured doses to determine the effectiveness of the model. RESULTS: The average measured rectal dose from CBCT was 2.8+/-0.3 cGy. The mathematical method was able to predict the rectal dose, with the limits of agreement of -0.03+/-0.18 cGy. The average difference between predictions and measurements was -1.1+/-3.6%. CONCLUSION: Our mathematical model was effective in estimating the exposed dose from CBCT.