The research background for risk assessment of ethylene oxide: aspects of dose

Data for relationships between in vivo doses inferred from levels of hemoglobin (Hb) or DNA adducts and administered (by inhalation or injection) doses of ethylene oxide (EO) in mice, rats and humans are reviewed. At low absorbed doses or dose rates these relationships appear to be linear, whereas at higher dose rates deviations from linearity due to saturation kinetics of detoxification and of DNA repair as well as certain toxic effects have to be allowed for. If these factors are taken into consideration, a rather consistent picture is obtained for animal studies, with a variation by less than a factor 2 between estimates of adduct level increments or in vivo dose increments per unit of administered dose. Although the value for in vivo dose per unit of exposure dose (ppm-hour) in humans is uncertain because of unreliable data for the time-weighted average exposure level, the most likely value for this relationship, supported by data for ethene, agrees with data for the rodents. In the animal species testis doses are approximately one-half of the blood doses inferred from Hb adducts.     

Tissue composition effect on dose distribution in neutron brachytherapy/neutron capture therapy

Aim

The aim of this study is to assess the effect of the compositions of various soft tissues and tissue-equivalent materials on dose distribution in neutron brachytherapy/neutron capture therapy.

Background

Neutron brachytherapy and neutron capture therapy are two common radiotherapy modalities.

Materials and methods

Dose distributions were calculated around a low dose rate ²⁵²Cf source located in a spherical phantom with radius of 20.0 cm using the MCNPX code for seven soft tissues and three tissue-equivalent materials. Relative total dose rate, relative neutron dose rate, total dose rate, and neutron dose rate were calculated for each material. These values were determined at various radial distances ranging from 0.3 to 15.0 cm from the source.

Results

Among the soft tissues and tissue-equivalent materials studied, adipose tissue and plexiglass demonstrated the greatest differences for total dose rate compared to 9-component soft tissue. The difference in dose rate with respect to 9-component soft tissue varied with compositions of the materials and the radial distance from the source. Furthermore, the total dose rate in water was different from that in 9-component soft tissue.

Conclusion

Taking the same composition for various soft tissues and tissue-equivalent media can lead to error in treatment planning in neutron brachytherapy/neutron capture therapy. Since the International Commission on Radiation Units and Measurements (ICRU) recommends that the total dosimetric uncertainty in dose delivery in radiotherapy should be within ±5%, the compositions of various soft tissues and tissue-equivalent materials should be considered in dose calculation and treatment planning in neutron brachytherapy/neutron capture therapy.     

Effects of shielding on pelvic and abdominal IORT dose distributions

PurposeTo study the impact of shielding elements in the proximity of Intra-Operative Radiation Therapy (IORT) irradiation fields, and to generate graphical and quantitative information to assist radiation oncologists in the design of optimal shielding during pelvic and abdominal IORT.MethodAn IORT system was modeled with BEAMnrc and EGS++ Monte Carlo codes. The model was validated in reference conditions by gamma index analysis against an experimental data set of different beam energies, applicator diameters, and bevel angles. The reliability of the IORT model was further tested considering shielding layers inserted in the radiation beam. Further simulations were performed introducing a bone-like layer embedded in the water phantom. The dose distributions were calculated as 3D dose maps.ResultsThe analysis of the resulting 2D dose maps parallel to the clinical axis shows that the bevel angle of the applicator and its position relative to the shielding have a major influence on the dose distribution. When insufficient shielding is used, a hotspot nearby the shield appears near the surface. At greater depths, lateral scatter limits the dose reduction attainable with shielding, although the presence of bone-like structures in the phantom reduces the impact of this effect.ConclusionsDose distributions in shielded IORT procedures are affected by distinct contributions when considering the regions near the shielding and deeper in tissue: insufficient shielding may lead to residual dose and hotspots, and the scattering effects may enlarge the beam in depth. These effects must be carefully considered when planning an IORT treatment with shielding.     

Bladder dose–surface maps and urinary toxicity: Robustness with respect to motion in assessing local dose effects

The purpose of this study was to quantify the impact of inter-fraction modifications of bladder during RT of prostate cancer on bladder dose surface maps (DSM).Eighteen patients treated with daily image-guided Tomotherapy and moderate hypofractionation (70–72.8 Gy at 2.5–2.6 Gy/fr in 28 fractions and full bladder) were considered. Bladder contours were delineated on co-registered daily Megavoltage CT (MVCT) by a single observer and copied on the planning CT to generate dose–volume/surface histograms (DVH/DSH) and bladder DSMs. Discrepancies between planned and daily absorbed doses were analyzed through the average of individual systematic errors, the population systematic errors and the population random errors for the DVH/DSHs and DSMs.In total, 477 DVH/DSH and 472 DSM were available. DSH and DVH showed small population systematic errors of absolute surfaces (<3.4 cm²) and volumes (<8.4 cm³) at the highest doses.The dose to the posterior bladder base assessed on DSMs showed a mean systematic error below 1 Gy, with population systematic and random errors within 4 and 3 Gy, respectively. The region surrounding this area shows higher mean systematic errors (1–3 Gy), population systematic (8–11 Gy) and random (5–7 Gy) errors.In conclusion, DVH/DSH and DSMs are quite stable with respect to inter-fraction variations in the high-dose region, within about 2 cm from bladder base. Larger systematic variations occur in the anterior portion and cranially 2.5–3.5 cm from the base.Results suggest that dose predictors related to the high dose area (including the trigone dose) are likely to be sufficiently reliable with respect to the expected variations due to variable bladder filling.     

Analysis of mutagenic DNA repair in a thermoconditional mutant of Saccharomyces cerevisiae. III. Dose-response pattern of mutation induction in UV-irradiated rev2ts cells

Summary Recent studies regarding the influence of cycloheximide on the temperature-dependent increase in survival and mutation frequencies of a thermoconditional rev2 mutant lead to the suggestion that the REV2-coded mutagenic repair function is UV-inducible. In the present study we show that stationary-phase rev2 ^ts cells are characterized by a biphasic linear-quadratic dose-dependence of mutation induction (mutation kinetics) of ochre alleles at 23° C (permissive temperature) but linear kinetics at the restrictive temperature of 36° C. Mathematical analysis using a model based on Poisson statistics and a further mathematical procedure, the calculation of apparent survival, support the assumption that the quadratic component of the reverse mutation kinetics investigated can be attributed to a UV-inducible component of mutagenic DNA repair controlled by the REV2 gene.     

When your MR linac is down: Can an automated pipeline bail you out of trouble?

PurposeThe unique treatment delivery technique provided by magnetic resonance guided radiotherapy (MRgRT) can represent a significant drawback when system fail occurs. This retrospective study proposes and evaluates a pipeline to completely automate the workflow necessary to shift a MRgRT treatment to a traditional radiotherapy linac.Material and methodsPatients undergoing treatment during the last MRgRT system failure were retrospectively included in this study. The core of the proposed pipeline was based on a tool able to mimic the original MR linac dose distribution. The so obtained dose distribution (AUTO) has been compared with the distribution obtained in the conventional radiotherapy linac (MAN). Plan comparison has been performed in terms of time required to obtain the final dose distribution, DVH parameters, dosimetric indices and visual analogue scales scoring by radiation oncologists.ResultsAUTO plans generation has been obtained within 10 min for all the considered cases. All AUTO plans were found to be within clinical tolerance, showing a mean target coverage variation of 1.7% with a maximum value of 4.3% and a minimum of 0.6% when compared with MAN plans. The highest OARs mean variation has been found for rectum V60 (6.7%). Dosimetric indices showed no relevant differences, with smaller gradient measure in favour of AUTO plans. Visual analogue scales scoring has confirmed comparable plan quality for AUTO plans.ConclusionThe proposed workflow allows a fast and accurate generation of automatic treatment plans. AUTO plans can be considered equivalent to MAN ones, with limited clinical impact in the worst-case scenario.     

Dose–injury relationships for cryoprotective agent injury to human chondrocytes

Vitrification of articular cartilage (AC) could enhance tissue availability but requires high concentrations of cyroprotective agents (CPAs). This study investigated relative injuries caused by commonly used CPAs. We hypothesized that the in situ chondrocyte dose–injury relationships of five commonly used CPAs are nonlinear and that relative injuries could be determined by comparing cell death after exposure at increasing concentrations. Human AC samples were used from four patients undergoing total knee arthroplasty surgery. Seventy μm slices were exposed in a stepwise protocol to increasing concentrations of 5 CPAs (max = 8 M); dimethyl sulfoxide (Me₂SO), glycerol (Gly), propylene glycol (PG), ethylene glycol (EG), and formamide (FM). Chondrocyte viability was determined by membrane integrity stains. Statistical analysis included t-tests and nonlinear least squares estimation methods. The dose–injury to chondrocytes relationships for all CPAs were found to be nonlinear (sigmoidal best fit). For the particular loading protocol in this study, the data identified the following CPA concentrations at which chondrocyte recoveries statistically deviated significantly from the control recovery; 1 M for Gly, 4 M for FM and PG, 6 M for Me₂SO, and 7 M for EG. Comparison of individual means demonstrated that Gly exposure resulted in the lowest recovery, followed by PG, and then Me₂SO, FM and EG in no specific order. The information from this study provides an order of damage to human chondrocytes in situ of commonly used CPAs for vitrification of AC and identifies threshold CPA concentrations for a stepwise loading protocol at which chondrocyte recovery is significantly decreased. In general, Gly and PG were the most damaging while DMSO and EG were among the least damaging.