Calculated Dose Equivalents Research Articles

Abstract P6-08-13: Statins and breast cancer recurrence: A population-based case-control study

Abstract Background: Breast cancer is the most common cancer among women and a significant number of women experience recurrence. Statins, drugs for lowering cholesterol, were introduced in 1987, and by 2011-12, 27.9% of U.S. adults over the age of 40 reported using cholesterol-lowering medication. Statins may impact other diseases, beyond cardiovascular disease, including cancer. Statin use and breast cancer recurrence or disease-free survival has previously been explored in 8 cohort studies and 1 case-control study with mixed results. Methods: We designed a nested case-control study with Kaiser Permanente members in NW Oregon and SW Washington to examine the association between statins and breast cancer recurrence. All subjects were women diagnosed with invasive breast cancer from 1980-2010. Subjects were KPNW health plan members at diagnosis, had local or regional stage cancer, were ER and/or PR positive, and were treated with tamoxifen for 180 days or more. Cases had breast cancer recurrence validated by medical record review. Controls were matched on race, SEER stage, age at diagnosis, year of diagnosis and pattern of health plan membership, and were recurrence-free for at least 12 months longer than their matched case (up to 3:1 match). The index date was the recurrence date for the case and the date for an equivalent period after diagnosis for the matched control. We collected data from medical records and from pharmacy, laboratory, tumor registry, and membership health plan databases. We performed bivariate analysis to look at characteristics associated with recurrence. A priori, we identified potential confounding variables based on literature review and clinical knowledge. Using multivariable logistic regression analysis, we assessed statin use in relation to breast cancer recurrence, accounting for factors that may alter the association. Results: We identified 306 cases with breast cancer recurrence and 679 matched controls. Thirty-five cases (11.4%) and 67 controls (9.9%) were prescribed statins at any time between their breast cancer diagnosis and index date. Nearly everyone on statins was prescribed lipophilic statins (99%). We calculated dose equivalents for all statins, using 20 mg of simvastatin as one dose. Among those who took statins, the average number of equivalent doses per day after diagnosis was 1.20 (1.19 for cases; 1.21 for controls) and the average duration of taking statins between diagnosis and recurrence was 2.65 years (2.75 for cases; 2.59 for controls). In our preliminary conditional analysis, we found that post-diagnostic statin use was not associated with a decreased odds of breast cancer recurrence (OR 1.37, 95% CI: 0.79-2.36) after adjusting for age, year of diagnosis, race, BMI, menopause status, tamoxifen use, type of surgery, treatment, smoking history, Charlson score, AJCC summary stage, and Nottingham grade. Conclusions: While other studies have reported that statins may be associated with decreased odds of breast cancer recurrence, our preliminary multivariable analyses that looked at any statin use between diagnosis and index date do not support those results. Citation Format: Vandermeer ML, Francisco MC, Richert-Boe KE, Jenkins CL, Weinmann S. Statins and breast cancer recurrence: A population-based case-control study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-08-13.

Dose Equivalents for Antipsychotic Drugs: The DDD Method.

Dose equivalents of antipsychotics are an important but difficult to define concept, because all methods have weaknesses and strongholds. We calculated dose equivalents based on defined daily doses (DDDs) presented by the World Health Organisation's Collaborative Center for Drug Statistics Methodology. Doses equivalent to 1mg olanzapine, 1mg risperidone, 1mg haloperidol, and 100mg chlorpromazine were presented and compared with the results of 3 other methods to define dose equivalence (the "minimum effective dose method," the "classical mean dose method," and an international consensus statement). We presented dose equivalents for 57 first-generation and second-generation antipsychotic drugs, available as oral, parenteral, or depot formulations. Overall, the identified equivalent doses were comparable with those of the other methods, but there were also outliers. The major strength of this method to define dose response is that DDDs are available for most drugs, including old antipsychotics, that they are based on a variety of sources, and that DDDs are an internationally accepted measure. The major limitations are that the information used to estimate DDDS is likely to differ between the drugs. Moreover, this information is not publicly available, so that it cannot be reviewed. The WHO stresses that DDDs are mainly a standardized measure of drug consumption, and their use as a measure of dose equivalence can therefore be misleading. We, therefore, recommend that if alternative, more "scientific" dose equivalence methods are available for a drug they should be preferred to DDDs. Moreover, our summary can be a useful resource for pharmacovigilance studies.

SU‐E‐T‐594: Out‐Of‐Field Neutron and Gamma Dose Estimated Using TLD‐600/700 Pairs in the Wobbling Proton Therapy System

Purpose:Secondary fast neutrons and gamma rays are mainly produced due to the interaction of the primary proton beam with the beam delivery nozzle. These secondary radiation dose to patients and radiation workers are unwanted. The purpose of this study is to estimate the neutron and gamma dose equivalent out of the treatment volume during the wobbling proton therapy system.Methods:Two types of thermoluminescent (TL) dosimeters, TLD‐600 (6LiF: Mg, Ti) and TLD‐700 (7LiF: Mg, Ti) were used in this study. They were calibrated in the standard neutron and gamma sources at National Standards Laboratory. Annealing procedure is 400°C for 1 hour, 100°C for 2 hours and spontaneously cooling down to the room temperature in a programmable oven. Two‐peak method (a kind of glow curve analysis technique) was used to evaluate the TL response corresponding to the neutron and gamma dose. The TLD pairs were placed outside the treatment field at the neutron‐gamma mixed field with 190‐MeV proton beam produced by the wobbling system through the polyethylene plate phantom. The results of TLD measurement were compared to the Monte Carlo simulation.Results:The initial experiment results of calculated dose equivalents are 0.63, 0.38, 0.21 and 0.13 mSv per Gy outside the field at the distance of 50, 100, 150 and 200 cm.Conclusion:The TLD‐600 and TLD‐700 pairs are convenient to estimate neutron and gamma dosimetry during proton therapy. However, an accurate and suitable glow curve analysis technique is necessary. During the wobbling system proton therapy, our results showed that the neutron and gamma doses outside the treatment field are noticeable.This study was supported by the grants from the Chang Gung Memorial Hospital (CMRPD1C0682).

A Novel Silicon Microdosimeter Using 3D Sensitive Volumes: Modeling the Response in Neutron Fields Typical of Aviation

A 4th generation silicon microdosimeter has been designed by the Centre for Medical Radiation Physics (CMRP) at the University of Wollongong using three dimensional (3D) Sensitive Volumes (SVs). This new microdosimeter design has the advantage of well-defined 3D SVs as well as the elimination of lateral charge diffusion by removal of silicon laterally adjacent to the 3D SVs. The gaps between the sensitive volumes are to be backfilled with PolyMethyl MethAcrylate (PMMA) to produce a surrounding tissue equivalent medium. The advantage of this design avoids the generation of secondary particles from inactive silicon lateral to SVs. The response of the microdosimeter to the neutron field from 252 Cf, Pu-Be sources and an avionic radiation environment were simulated using the Geant4 Monte Carlo toolkit for design optimisation. The simulated energy deposition in the SVs from the neutron fields and microdosimetric spectra is presented. The simulation study shows a significant reduction in silicon nuclear recoil contribution to the energy deposition for the novel microdosimeter design. The reduction of silicon recoil events from outside of the SV's will consequently reduce the uncertainty in the calculated dose equivalent. The simulations have demonstrated that a 3D silicon microdosimeter surrounded by PMMA can produce microdosimetric spectra similar to those of a tissue equivalent microdosimeter.

Track etch based LET spectrometry in beams of neutrons with energies from 0.2 to 200 MeV

There is still need to develop further methods able to characterize an external exposure to neutrons. This contribution presents results obtained with linear energy transfer spectrometer based on the chemically etched track detectors. There were employed two types of polyallyldiglycolcarbonates, Page and Tastrak, to obtain spectra of linear energy transfer. Detectors were exposed to monoenergetic neutron beams with energies of 0.2, 0.5, 1, 3, 7, 15, 20, 100 and 200 MeV. Calculated dose equivalents are compared with delivered reference values.

Proposed dose equivalence for rapid switch between dopamine receptor agonists in Parkinson's disease: A review of the literature

Background: Progressive reduction of the dose of one dopamine receptor agonist and simultaneous, progressive dose escalation of another is a frequently used strategy for controlling motor symptoms of Parkinson's disease (PD) or avoiding specific adverse events. Rapid switch has been proposed as an alternative that might reduce the need for such major limitations as the possible exacerbation of symptoms and the need to monitor patients for several weeks. However, the equivalence of doses of dopamine receptor agonists before and after switching drugs remains empirical because few clinical trials have addressed this issue. Objective: The aim of this review was to use the available data from the literature to calculate conversion factors for rapidly switching between dopamine receptor agonists in patients with PD. Methods: Using the MEDLINE and CochraneLibrary Central databases, we selected clinical trials that allowed paired comparisons of bromocriptine with the most frequently prescribed dopamine receptor agonists in PD (ie, pergolide, piribedil, pramipexole, and ropinirole). From these data, we calculated dose equivalents of optimal daily doses for each pair of dopamine receptor agonists. Results: Six studies comparing 2 dopamine agonists and 4 studies analyzing the switch between dopamine agonists were selected. The proposed conversion factors were 1:6 for bromocriptine to piribedil, 1:6 for pergolide to ropinirole, 10:6 for bromocriptine to ropinirole, 10:1 for bromocriptine to pergolide, and 10:1 to 10:1.5 for bromocriptine to pramipexole. Conclusions: The conversion factors proposed inthis article, based on a literature analysis, could facilitate rapid switches between dopamine receptor agonists in patients with PD, but they must first be confirmed in prospective, double-blind, randomized clinical trials.

Monte Carlo calculation of the radiation field at aircraft altitudes.

Energy spectra of secondary cosmic rays are calculated for aircraft altitudes and a discrete set of solar modulation parameters and rigidity cut-off values covering all possible conditions. The calculations are based on the Monte Carlo code FLUKA and on the most recent information on the interstellar cosmic ray flux including a detailed model of solar modulation. Results are compared to a large variety of experimental data obtained on the ground and aboard aircraft and balloons, such as neutron, proton, and muon spectra and yields of charged particles. Furthermore, particle fluence is converted into ambient dose equivalent and effective dose and the dependence of these quantities on height above sea level, solar modulation, and geographical location is studied. Finally, calculated dose equivalent is compared to results of comprehensive measurements performed aboard aircraft.

The radiation exposure of the patient from stablexenon computed tomography

For stable-xenon computed tomography (CT), an X-ray examination for measurement of cerebral blood circulation in the brain, the radiation exposure of the patient was determined in order to estimate the risk of inducing cancer. Organ doses of brain, eyelenses, thyroid and gonads have been calculated using the measured air kerma free-in-air on the axis of rotation and organ-specific conversion factors calculated with the Monte Carlo method. Dose measurements with TLD-100 rods using a humanoid Alderson phantom were carried out for verification of the calculated organ doses. In the case of brain partially located in the region of primary radiation a mean organ dose of 39 mSv was calculated. The dose measurements showed dose equivalents between 6 and 68 mSv in different regions of the brain and consequently an inhomogeneous dose distribution. From an estimation of the radiation-induced risk using the effective dose of 1.6 mSv it follows that one additional fatal cancer per 12,500 stable-xenon CT examinations has to be expected. The organ doses of eyelenses and thyroid located in the region of scattered radiation are so low that biological effects are hardly to be expected. The calculated dose equivalents of 6.5 mSv and 0.5 mSv, respectively, are in good agreement with measurements. The organ dose of gonads amounted to less than 0.07 mSv.

Radiation issues for piloted Mars mission.

Man is now entering an era of colonizing the moon and exploration of Mars. The crewmembers of a piloted mission to Mars will be exposed to inner belt trapped protons, the outer trapped electrons, and the galactic cosmic radiation. In addition there is always the added risk of acute exposure to a solar particle event. Current radiation risk is estimated using the idea of absorbed dose and ICRP-26, LET-dependent quality factors. In a spacecraft with aluminum walls (2 g cm-2) at solar minimum the calculated dose equivalent is 0.73 Sv for a 406-day mission. Based on the current thinking this leads to an excess cancer mortality in a 35 year male of about 1%. About 75% of the dose equivalent is contributed by HZE particles and target fragments with average quality factors of 10.3 and 20, respectively. The entire concept of absorbed dose, quality factor, and dose equivalent as applied to such missions needs to be reexamined, in light of the fact that less than 50% of the nuclei in the body of the astronaut would have been traversed by a single GCR nuclei in the 406-day mission. Clearly, more biologically relevant information about the effects of heavy ions and target fragments is needed and fluence based risk estimation strategy developed for such long term stays in space.

電子ポケット線量計の性能試験

Several types of electric pocket dosimeters have been developed recently. These dosimeters are distinguished by use of the silicone semiconductor as a radiation (γ-ray, X-ray) detector. Performance tests of a type of dosimeter named the PDM102 were carried out by using a 60CO point source (about 500kBq). The results showed that the minimum detectable dose equivalent for the dosimeter was 1-2μSv. Excluding cases of exposure from the underside or back of the dosimeter and exposure of less than 10μSv, differences between measured and calculated dose equivalents were less than 10%. Consequently the effect of the dose equivalent rate and dose equivalent (>10μSv) on the response of the detectors was determined to be less than 10%, and the directional dependence was also less than 10%. The dosimeter's response for back exposure was about 70-80% of that for front exposure. And for exposure from the underside of the dosimeter, the measured dose equivalents were equal to or less than approximately 50% of the calculated dose equivalents.

Health Physics Concerns in Commercial Aviation

Airline pilots and flight attendants are occupationally exposed to cosmic radiation. There has been uncertainty about how to handle the radiation protection requirements of their unique situation. Calculated dose equivalents associated with typical flight routes and crewmember work patterns have recently been published. The results show that flight attendants and pilots on ordinary subsonic aircraft can receive annual doses approaching 10 mSv y-1. I argue that flight crewmembers should receive specific education regarding the risks to their health from radiation exposure. I also argue that a suitable dosimeter system should be employed to provide crewmembers with information on their total doses. This is of particular importance for pregnant crewmembers who risk exceeding recommended fetal dose limits by working some routes during their pregnancy. In addition to airline crewmembers, business "frequent flyers" may receive significant occupational exposures while traveling. They too need appropriate education in order to assist them in assessing their risks from such exposures. Finally, flying during a large solar proton event would significantly increase the dose that would be received. During such an event, the total dose to the fetus of a pregnant crewmember or passenger might exceed the 0.5 mSv recommended monthly maximum. Warnings and action plans for these special circumstances should be improved.