cGy Min Research Articles

Investigation of the linear accelerator low dose rate mode for pulsed low-dose-rate radiotherapy delivery

Purpose. Pulsed volumetric modulated arc therapy (VMAT) was proposed as an advanced treatment that combines the biological benefits of pulsed low dose rate (PLDR) and the dosimetric benefits of the intensity-modulated beams. In our conventional pulsed VMAT technique, a daily fractional dose of 200 cGy is delivered in 10 arcs with 3 min intervals between the arcs. In this study, we are testing the feasibility of pulsed VMAT that omits the need to split into ten arcs and excludes any beam-off gaps. Methods. The study was conducted using computed tomographic images of 24 patients previously treated at our institution with the conventional PLDR technique. Our newly installed Elekta machine has a low dose rate option on the order of 25 MU min−1. PLDR requires an effective dose rate of 6.7 cGy min−1 with attention being paid to the maximum dose received within any point within the target not to exceed 13 cGy min−1. The quality of treatment plans was judged based on dose-volume histograms, isodose distribution, dose conformality to the target, and target dose homogeneity. The dose delivery accuracy was assessed by measurements using the MatriXX Evolution 2D array system. Results. All cases were normalized to cover 95% of the target volume with 100% of the prescription dose. The average conformity index was 1.03 ± 0.08 while the average homogeneity index was 1.05 ± 0.02. The maximum reported dose rate at any point within the target was 10.44 cGy min−1. The mean dose rate for all pulsed VMAT plans was 6.88 ± 0.1 cGy min−1. All cases passed our gamma analysis with an average passing rate of 99.00% ± 0.48%. Conclusion. The study showed the applicability of planning pulsed VMAT using Eclipse and its successful delivery on our Elekta linac. Pulsed VMAT using the machine’s low dose rate mode is more efficient than our previous pulsed VMAT delivery.

Investigation of the beam quality and dose rate dependence of PAKAG polymer gel dosimeter in optical readout technique

This study aims to evaluate the optical response dependence of the PAKAG polymer gel dosimeter on photon energy and dose rate. The produced gel dosimeters were irradiated using a Varian CL 21EX medical linear accelerator with delivered doses of 0, 2, 4, 6, 8, and 10 Gy. To examine the response dependence on the delivered dose rate, dose rates of 50, 100, 200, and 350 cGy min−1 were investigated. Additionally, two incident beam qualities of 6 and 18 MV were examined to study the response dependence on the incident beam energy. The irradiated polymer gel dosimeters were readout using a UV–vis spectrophotometer in the 300 to 800 nm scan range. The results reveal that a wide variation in dose rate (50–350 cGy.min−1) influences the absorbance-dose response and the sensitivity of PAKAG gel. However, smaller variations did not show a significant effect on the response. Furthermore, the response changed insignificantly with beam quality for investigated energies. It was concluded that the optical reading response of the PAKAG polymer gel dosimeter is satisfactorily independent of external parameters, including dose rate and incident beam quality.

Plasma metabolomic signatures from patients following high-dose total body irradiation.

Despite some advances in the study of radiation injuries, effective methods of prevention and treatment of severe acute radiation syndrome or illness (ARS) are still lacking. Therefore, an in-depth understanding of the biological characteristics associated with high dose radiation is essential to reveal the mechanisms underlying the varied biological processes following high dose radiation and the development of novel potent radioprotective agents. In the present study, plasma metabolic characteristics were investigated using hematopoietic stem cell transplantation patients (n = 36) undergoing total body ionizing irradiation (TBI) utilizing gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). Plasma was collected pre-irradiation, 3 days after completion of fractionated radiation therapy with a total dose of 12 Gy delivered at a dose rate of 8 cGy min-1. These metabolic disorders involve the dysregulation of the gut microflora, a shift in energy supply from aerobic respiration toward ketogenesis, protein synthesis and metabolism in response to TBI. Furthermore, the panel of four metabolic markers with most potential consisting of PC (O-38:5), urate, ornithine, and GCDCS for radiation injury was chosen by combining multiple methods of data processing that included univariate analysis, partial least squares discriminant analysis (PLS-DA), and multivariable stepwise linear regression analysis. While similar patterns of metabolic alterations were observed in patients of different genders, disease types and ages, specific changes were also found in specific patients following high doses of exposure. These findings provide valuable information for selecting metabolic biomarker panels for radiation injury, clues for radiation pathology and therapeutic interventions involved in high-dose radiation exposure.

High optical stability of reusable radiochromic polyvinyl alcohol-iodine gel dosimeter for radiotherapy

In this study, a stable reusable radio-chromic gel dosimeter based on a polyvinyl alcohol-sodium iodide complexes (PVA-NaI) and chemical cross-linking agent glutaraldehyde combined with additives of Glucono-δ-lactone and fructose was prepared and improved by the addition of new additive free radical scavenger dimethyl sulfoxide (DMSO). The radio-chromic gels were exposed to high energy photons (X-rays) to various doses up to 30 Gy, with a constant energy of 6 MV, and a dose rate of 200 cGy min−1 using a medical linear accelerator. UV–Vis spectroscopy technique was used to read out the optical changes of unirradiated and irradiated gel samples in terms of absorbance. The gel samples were transparent, and turn to yellow color after irradiation with a peak absorbance response at 355 nm. The color change is directly related to the absorbed dose. The stability of unirradiated as well as irradiated reusabl gels was remarkably improved by the addition of 500 mM DMSO while maintaining a high dose sensitivity. The developed PVA-NaI radio-chromic gel dosimeter possesses a number of desirable features as a dosimeter, including high sensitivity, excellent dose linearity, dose rate and energy independence, and the PVA-NaI radio-chromic gel dosimeter is reusable, where the color can be decolorized by heating.

Dosimetry of a novel focused monoenergetic beam for radiotherapy

Objective. A novel treatment modality is currently being developed that produces converging monoenergetic x-rays. Conventional application of dosimetric calibration as presented in protocol TG61 is not applicable. Furthermore, the dosimetry of the focal point of the converging beam is on the order of a few millimeters, requiring a high-resolution dosimeter. Here we present a procedure to calibrate radiochromic film for narrow-beam monoenergetic 60 keV photons as well as absolute dosimetry of monoenergetic focused x-rays. A study of the focal spot dose rate after passing through a bone-equivalent material was also done to quantify the effects of heterogeneous materials. Approach. This was accomplished by configuring a polyenergetic beam of equivalent energy using a clinical orthovoltage machine. Calibrated films were then used to perform absolute dosimetry of the converging beam by measuring the beam profile at various depths in water. Main Results. A method for calibrating radiochromic film has been developed and detailed that allows absolute dosimetry of a monoenergetic photon beam. Absolute dosimetry of a focused, mono-energetic beam resulted in a focal spot dose rate of ∼30 cGy min−1 at a depth of 5 cm in water. Significance. This work serves to establish a dosimetry protocol for mono-energetic beam absolute dosimetry as well as the use of such a method for measurement of a novel teletherapy modality.

Small-field output ratio determination using 6 mol% Ge-doped silica fibre dosimeters

This work investigates the suitability of locally fabricated 6 mol% Ge-doped optical fibres as dosimeters for small-field output ratio measurements. Two fabrications of fibre, cylindrical (CF) and flat (FF) fibres, were used to measure doses in small photon fields, from 4 to 15 mm. The findings were compared to those of commercial Ge-doped fibre (COMM), EBT3 film and an IBA CC01 ionization chamber. Irradiations were carried out using a 6 MV SRS photon beam operating at a dose rate of 1000 cGy min−1, delivering a dose of 16 Gy. To minimise the possibility of the fibres failing to be exposed to the intended dose in small fields, the fibres were accommodated in a custom-made Perspex phantom. For the 4 mm cone the CF and FF measured output ratios were found to be smaller than obtained with EBT3 film by 32% and 13% respectively. Conversely, while for the 6 to 15 mm cone fields the FF output ratios were consistently greater than those obtained using EBT3 film, the CF output ratios differed from those of EBT3 film by at most 3.2%, at 6 mm, otherwise essentially agreeing with EBT3 values at the other field sizes. For the 4 to 7.5 mm cones, all output ratios obtained from Ge-doped optical fibre measurements were greater than those of IBA CC01 ionization chamber. The measured FF and CF output ratios for the 7.5 to 15 mm cones agreed with published MC estimates to within 15% and 13%, respectively. Down to 6 mm cone field, present measurements point to the potential of CF as a small-field dosimeter, its use recommended to be complemented by the use of EBT3 film for small-field dosimetry.

Evaluation of ferrous benzoic methylthymol-blue gel as a dosimeter via magnetic resonance imaging.

In previous studies, methylthymol-blue and benzoic acid have been introduced as a diffuser limiter and sensitivity enhancer in the gel dosimeter composition, respectively. This work focused on analyzing a formulation of the Fricke gel dosimeter consisting of methylthymol-blue and benzoic acid through magnetic resonance imaging. The gel dosimeter samples were irradiated using 6, 10, and 15 MV photons with different levels of doses and read using a 1.5T scanner in order to evaluate the dose-response sensitivity and to study the effect of benzoic acid concentration, diffusion coefficient and temperature and to determine the temporal stability of the gel dosimeter. Inspection of radiological properties revealed that this gel dosimeter can be considered as a tissue equivalent medium. Within the dose range 0 to 1000cGy, the R1 sensitivity and R2 sensitivity of the gel dosimeter equaled 0.058±0.003 and 0.092±0.004s-1Gy-1, respectively. The diffusion coefficient was less than 0.85±0.02mm2h-1 for doses higher than 200cGy. In addition, by changing the temperature from 15C to 25, the R1 sensitivity and R2 sensitivity decreased about 5 and 11%, respectively. Further, no significant energy and dose rate dependence were observed over photon energies of 6, 10, and 15 MV and over the range 65 to 525cGymin-1. Based on our observation, the ferrous benzoic acid methylthymol-blue gel dosimeter can be suggested to measure the dose distribution. Further analysis is required to clarify its performance in clinical situations.

Impact of Intrafractional Changes of Abdominal Gas Cavities in MR-guided Adaptive Radiation Therapy: Is Real-time Adaptation Necessary?

With the introduction of the MR-Linac, online adaptation becomes reality in the clinic. Real-time adaptation is introduced to account for the anatomic changes during the process of online adaptation and RT delivery. In the abdomen, these changes include motions due to respiration, peristalsis and unpredictable gas filling of the gastrointestinal (GI) organs. While real-time motion tracking, a form of real-time adaptation, is being developed to address the respiratory and/or peristaltic motions, the intrafractional change of the gas cavities and its impact on dose delivery has not been investigated. In this work, we study the change of gas volumes in a time frame similar to the duration of online adaptation and fraction dose delivery and its dosimetric impacts during MRI-guided adaptive RT (MRgART). Time-sequenced abdominal MRI sets (3D T2 and T1, or motion average MRI from 4DMRI) separated by 15-60 minutes (mimicking the duration of MRgART) from 9 abdominal cancer patients were analyzed. For each set, the pancreatic head, duodenum, bowels, and stomach were delineated. Gas volumes were contoured separately and justified with corresponding CT. An IMRT plan with a prescription of 50.4 Gy for 28 fractions to the target (the pancreatic head) was created and calculated under magnetic field on the first MR. The electron density was forced to 0.25 for gas and 1 otherwise. The plan was recalculated on the second MR. The effects on dose volume histogram (DVH) parameters due to gas volume changes for a single fraction are reported. The GI gas cavity volumes can change substantially in the duration of 15-60 min. Gas cavities of the stomach and duodenum were found to vary, on average, by 38 and 3.5 cc, respectively, for the cases studied. Changes in selected DVH parameters resulting from these (intrafractional) gas cavity changes are tabulated for a single fraction. The IMRT plans generated on the pancreatic head showed a medium correlation between the stomach gas volume and the maximum dose to the target (|r| = 0.3) and a strong correlation to the target V(97%) (|r| = 0.7) and to the duodenum (|r| = 0.7) is reported. There was a low to medium correlation (|r| = 0.2 – 0.6) between the duodenum gas volume change and the observed DVH parameters despite the comparably smaller volume change. Intrafractional gas volumes vary rapidly within GI structures causing anatomical changes near the target. Such changes can result in a negative impact on the dose delivery, even with online adaptation. These results demonstrate the need to consider real-time adaptation as a means to address the effects of bowel gas variation during MRgART.Abstract 3754; Table 1Max Target Dose (cGy)Min Target Dose (cGy)Target V(97%) (%)Max Duodenum Dose (cGy)Average Difference1.8324.85.4Max Difference5.2931414Min Difference0.00.20.00.1 Open table in a new tab

Design of a spherical applicator for intraoperative radiotherapy with a linear accelerator—a Monte Carlo simulation

Currently only flat dose distributions can be generated by electron beams of a linear accelerator for intraoperative radiotherapy (IORT). However, spherical dose distributions are more desirable for certain types of cancers such as breast cancer and brain cancers. In this study, we propose the design of a spherical applicator for delivery of spherical dose distributions. The spherical applicator consists of an upper cylindrical collimator to collimate the electron beam, a middle scattering foil to scatter the beam and a lower hollow sphere with a modulator to shape the beam and a spherical shell used to contain the modulator. Monte Carlo (MC) codes EGSnrc/BEAMnrc and EGS4/DOSXYZ were employed to model the head of the Mobetron, the spherical applicator, and to calculate the dose distributions. Apart from the scattering foil made of tungsten, the region between the scattering foil and the inner surface of the modulator is empty whereas the remainder of the spherical applicator made of soft tissue-equivalent materials such as PMMA. As a measure of how close an object approaches a perfect circle, roundness was introduced to evaluate the dose distributions. In addition, the dose rate after modulation was investigated. A spherical applicator with a 20 mm-diametre cylindrical collimator and a 50 mm-diametre hollow sphere was designed. For electron beams of energies 4, 6, 9 and 12 MeV, the foil thickness was set to 0.3, 0.5, 0.7 and 1.2 mm, and the dose rate was about 30, 40, 50 and 60 cGy min−1, respectively. The roundness of the isodose curves in the coronal plane through the centre of the spherical applicator ranged from 0.01 to 0.12 cm whereas that in the axial plane ranged from 0.05 to 1.38 cm. Experiments are planned to further evaluate the feasibility of this spherical applicator design.Highlights• A spherical applicator with a 20 mm-diametre cylindrical collimator and a 50 mm-diametre hollow sphere was designed for delivery of spherical dose distributions for IORT with a linear accelerator.• For electron beams of energies 4, 6, 9 and 12 MeV, the dose rate was about 30, 40, 50 and 60 cGy min−1, respectively.• As a measure of how close an object approaches a perfect circle, roundness was introduced to evaluate the spherical dose distributions.• Experiments are planned to further evaluate the feasibility of this spherical applicator design.

Value of Low Dose Bevacizumab in the Treatment of Radiation-induced Cerebral Necrosis for Patients with Nasopharyngeal Carcinoma

To evaluate the efficacy of low dose bevacizumab in the treatment of radiation-induced cerebral necrosis for patients with nasopharyngeal carcinoma. Ten patients, who had MRI scan radiographic changes of brain radiation-induced injuries, were included in this analysis. Seven patients were clinical stage III and 3 patients IV according to 7th AJCC stage system. The median irradiation dose of GTV was 7060cGy (range: 7000cGy-7400cGy). All patients received bevacizumab with dose of 100 mg in each cycle over 3 weeks’ schedule for 4 cycles. The efficacy was evaluated by comparing volumes of edema as well as the necrosis area on MRI scan radiography before and after treatment every 3-4 months. The patients’ neurocognitive function was scored using Mini-Mental State Examination (MMSE) before and every 3–4 months after treatment. RECIST were used to test the prognosis of CRN. All patients were male and followed up from 8 to 21 months (median 12 months). The median time of radiation brain injuries from the radiotherapy was 37.4 months (range: 16-63months). Eight patients received conventional radiotherapy, and 2 patients received IMRT. The median dose in T1 gadolinium-enhanced image region was 4444.6cGy (min: 234.9cGy, max: 6885cGy); Median dose in T2 FLAIR region was 2514.3Gy (min: 266.2cGy, max: 4305cGy). Bevacizumab-treated patients demonstrated the volumes of lesions decreases in terms of T2 FLAIR and T1-weighted gadolinium-enhanced image after 4 cycles. On T1-weighted gadolinium-enhanced image, volumes of lesions shrank to PR in 6 patients, and later to 7 during the following time. Other patients remained SD. With regarding to the changes of lesions volumes on T2 FLAIR images, all patients achieved PR after four cycles. The median time of PR was 12 months. The MMSE form indicated the symptoms and signs reached PR in 3 patients, and the others remained stable.Toxicity above level II caused by bevacizumab was not observed. Analysis shows that even low dose of 100 mg of bevacizumab can have good results in terms of reducing the range of radiation-induced necrosis and also the associated brain edema .Optimal dose and duration of treatment should be explored further by randomized trials in the future.

Monte Carlo optimization of a microbeam collimator design for use on the small animal radiation research platform (SARRP)

Microbeam radiation therapy (MRT) is a pre-clinical, spatially-fractionated treatment modality noted for its ability to achieve a large differential response between normal and tumoral tissues. In the present study, TOPAS Monte Carlo (MC) simulations were used to optimize the design of a compact, affordable multi-slit collimator (MSC) suitable for use with the small animal radiation research platform (SARRP). MRT dose distributions in a (1 × 1 × 3)cm3 water phantom were simulated for a tungsten MSC using different focal spot sizes (0.4, 3 mm), beam energies (40, 80, 220 kVp), slit widths (100, 125, 150, 175, 200 µm), collimator thicknesses (1.5, 2.5, 3 cm) and collimator-to-surface distances (CSD of 1 and 3 cm). Key MRT figures of merit, namely the peak-to-valley dose ratio (PVDR), full-width at half-maximum and peak dose rate were determined. Use of the small focal spot maximized the PVDR (~40 at surface) and reduced the system’s sensitivity to changes in CSD, but decreased the collimated beam output to 55.2 cGy min−1. The large focal spot was ill-suited for large CSD irradiations, but increased the beam output by a factor of 2.8, to 153.0 cGy min−1, and decreased the sensitivity to changes in slit width. A modular MSC, using divergent plastic spacer materials in place of excavated slits, was also investigated. Polypropylene and polyethylene terephthalate material spacers were considered and while neither reduced the PVDR compared to air slits, the dose rate was reduced by 37% and 47%, respectively. Lastly, a steel parallel-slit MSC was used in a preliminary test of MRT delivery using the SARRP. Discrepancies between the results of film dosimetry and the corresponding MC simulations highlight the need to fabricate a more well-defined collimator for use in future validation and radiobiological work. The simulated results of this study are being used to inform the design of such a collimator, which will additionally boast a high degree of modularity at reasonable cost.

Use of Proteomic and Hematology Biomarkers for Prediction of Hematopoietic Acute Radiation Syndrome Severity in Baboon Radiation Models.

Use of plasma proteomic and hematological biomarkers represents a promising approach to provide useful diagnostic information for assessment of the severity of hematopoietic acute radiation syndrome. Eighteen baboons were evaluated in a radiation model that underwent total-body and partial-body irradiations at doses of Co gamma rays from 2.5 to 15 Gy at dose rates of 6.25 cGy min and 32 cGy min. Hematopoietic acute radiation syndrome severity levels determined by an analysis of blood count changes measured up to 60 d after irradiation were used to gauge overall hematopoietic acute radiation syndrome severity classifications. A panel of protein biomarkers was measured on plasma samples collected at 0 to 28 d after exposure using electrochemiluminescence-detection technology. The database was split into two distinct groups (i.e., "calibration," n = 11; "validation," n = 7). The calibration database was used in an initial stepwise regression multivariate model-fitting approach followed by down selection of biomarkers for identification of subpanels of hematopoietic acute radiation syndrome-responsive biomarkers for three time windows (i.e., 0-2 d, 2-7 d, 7-28 d). Model 1 (0-2 d) includes log C-reactive protein (p < 0.0001), log interleukin-13 (p < 0.0054), and procalcitonin (p < 0.0316) biomarkers; model 2 (2-7 d) includes log CD27 (p < 0.0001), log FMS-related tyrosine kinase 3 ligand (p < 0.0001), log serum amyloid A (p < 0.0007), and log interleukin-6 (p < 0.0002); and model 3 (7-28 d) includes log CD27 (p < 0.0012), log serum amyloid A (p < 0.0002), log erythropoietin (p < 0.0001), and log CD177 (p < 0.0001). The predicted risk of radiation injury categorization values, representing the hematopoietic acute radiation syndrome severity outcome for the three models, produced least squares multiple regression fit confidences of R = 0.73, 0.82, and 0.75, respectively. The resultant algorithms support the proof of concept that plasma proteomic biomarkers can supplement clinical signs and symptoms to assess hematopoietic acute radiation syndrome risk severity.

Leuco-crystal-violet micelle gel dosimeters: Component effects on dose-rate dependence

Designed experiments were performed to produce empirical models for the dose sensitivity, initial absorbance, and dose-rate dependence respectively for leucocrystal violet (LCV) micelle gel dosimeters containing cetyltrimethylammonium bromide (CTAB) and 2,2,2-trichloroethanol (TCE). Previous gels of this type showed dose-rate dependent behaviour, producing an ∼18% increase in dose sensitivity between dose rates of 100 and 600 cGy min-1. Our models predict that the dose rate dependence can be reduced by increasing the concentration of TCE, CTAB and LCV. Increasing concentrations of LCV and CTAB produces a significant increase in dose sensitivity with a corresponding increase in initial absorbance. An optimization procedure was used to determine a nearly dose-rate independent gel which maintained high sensitivity and low initial absorbance. This gel which contains 33 mM CTAB, 1.25 mM LCV, and 96 mM TCE in 25 mM trichloroacetic acid and 4 wt% gelatin showed an increase in dose sensitivity of only 4% between dose rates of 100 and 600 cGy min-1, and provides an 80% greater dose sensitivity compared to Jordan’s standard gels with similar initial absorbance.

Assessing dose rate distributions in VMAT plans

Dose rate is an essential factor in radiobiology. As modern radiotherapy delivery techniques such as volumetric modulated arc therapy (VMAT) introduce dynamic modulation of the dose rate, it is important to assess the changes in dose rate. Both the rate of monitor units per minute (MU rate) and collimation are varied over the course of a fraction, leading to different dose rates in every voxel of the calculation volume at any point in time during dose delivery.Given the radiotherapy plan and machine specific limitations, a VMAT treatment plan can be split into arc sectors between Digital Imaging and Communications in Medicine control points (CPs) of constant and known MU rate. By calculating dose distributions in each of these arc sectors independently and multiplying them with the MU rate, the dose rate in every single voxel at every time point during the fraction can be calculated. Independently calculated and then summed dose distributions per arc sector were compared to the whole arc dose calculation for validation. Dose measurements and video analysis were performed to validate the calculated datasets. A clinical head and neck, cranial and liver case were analyzed using the tool developed.Measurement validation of synthetic test cases showed linac agreement to precalculated arc sector times within ±0.4 s and doses ±0.1 MU (one standard deviation). Two methods for the visualization of dose rate datasets were developed: the first method plots a two-dimensional (2D) histogram of the number of voxels receiving a given dose rate over the course of the arc treatment delivery. In similarity to treatment planning system display of dose, the second method displays the dose rate as color wash on top of the corresponding computed tomography image, allowing the user to scroll through the variation over time. Examining clinical cases showed dose rates spread over a continuous spectrum, with mean dose rates hardly exceeding 100 cGy min−1 for conventional fractionation.A tool to analyze dose rate distributions in VMAT plans with sub-second accuracy was successfully developed and validated. Dose rates encountered in clinical VMAT test cases show a continuous spectrum with a mean less than or near 100 cGy min−1 for conventional fractionation.

Characterization of the Dose Response Relationship for Lung Injury Following Acute Radiation Exposure in Three Well-established Murine Strains

Approval of radiation countermeasures through the FDA Animal Rule requires pivotal efficacy screening in one or more species that are expected to react with a response similar to humans (21 C.F.R. § 314.610, drugs; § 601.91, biologics). Animal models used in screening studies should reflect the dose response relationship (DRR), clinical presentation, and pathogenesis of lung injury in humans. Over the past 5 y, the authors have characterized systematically the temporal onset, dose-response relationship (DRR), and pathologic outcomes associated with acute, high dose radiation exposure in three diverse mouse strains. In these studies, C57L/J, CBA/J, and C57BL/6J mice received wide field irradiation to the whole thorax with shielding of the head, abdomen, and forelimbs. Doses were delivered at a rate of 69 cGy min using an x-ray source operated at 320 kVp with half-value layer (HVL) of 1 mm Cu. For all strains, radiation dose was associated significantly with 180 d mortality (p < 0.0001). The lethal dose for 50% of animals within the first 180 d (LD50/180) was 11.35 Gy (95% CI 11.1-11.6 Gy) for C57L/J mice, 14.17 Gy (95% CI 13.9-14.5 Gy) for CBA/J mice, and 14.10 Gy (95% CI 12.2-16.4 Gy) for C57BL/6J mice. The LD50/180 in the C57L/J strain was most closely analogous to the DRR for clinical incidence of pneumonitis in non-human primates (10.28 Gy; 95% CI 9.9-10.7 Gy) and humans (10.60 Gy; 95% CI 9.9-12.1 Gy). Furthermore, in the C57L/J strain, there was no gender-specific difference in DRR (p = 0.5578). The reliability of the murine models is demonstrated by the reproducibility of the dose-response and consistency of disease presentation across studies.Health Phys. 106(1):000-000; 2014.

Investigation of pulsed IMRT and VMAT for re-irradiation treatments: dosimetric and delivery feasibilities

Many tumor cells demonstrate hyperradiosensitivity at doses below ∼50 cGy. Together with the increased normal tissue repair under low dose rate, the pulsed low dose rate radiotherapy (PLDR), which separates a daily fractional dose of 200 cGy into 10 pulses with 3 min interval between pulses (∼20 cGy/pulse and effective dose rate 6.7 cGy min−1), potentially reduces late normal tissue toxicity while still providing significant tumor control for re-irradiation treatments. This work investigates the dosimetric and technical feasibilities of intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT)-based PLDR treatments using Varian Linacs. Twenty one cases (12 real re-irradiation cases) including treatment sites of pancreas, prostate, pelvis, lung, head-and-neck, and breast were recruited for this study. The lowest machine operation dose rate (100 MU min−1) was employed in the plan delivery. Ten-field step-and-shoot IMRT and dual-arc VMAT plans were generated using the Eclipse TPS with routine planning strategies. The dual-arc plans were delivered five times to achieve a 200 cGy daily dose (∼20 cGy arc−1). The resulting plan quality was evaluated according to the heterogeneity and conformity indexes (HI and CI) of the planning target volume (PTV). The dosimetric feasibility of retaining the hyperradiosensitivity for PLDR was assessed based on the minimum and maximum dose in the target volume from each pulse. The delivery accuracy of VMAT and IMRT at the 100 MU min−1 machine operation dose rate was verified using a 2D diode array and ion chamber measurements. The delivery reproducibility was further investigated by analyzing the Dynalog files of repeated deliveries. A comparable plan quality was achieved by the IMRT (CI 1.10–1.38; HI 1.04–1.10) and the VMAT (CI 1.08–1.26; HI 1.05–1.10) techniques. The minimum/maximum PTV dose per pulse is 7.9 ± 5.1 cGy/33.7 ± 6.9 cGy for the IMRT and 12.3 ± 4.1 cGy/29.2 ± 4.7 cGy for the VMAT. Six out of the 186 IMRT pulses (fields) were found to exceed 50 cGy maximum PTV dose per pulse while the maximum PTV dose per pulse was within 40 cGy for all the VMAT pulses (arcs). However, for VMAT plans, the dosimetric quality of the entire treatment plan was less superior for the breast cases and large irregular targets. The gamma passing rates for both techniques at the 100 MU min−1 dose rate were at least 94.1% (3%/3 mm) and the point dose measurements agreed with the planned values to within 2.2%. The average root mean square error of the leaf position was 0.93 ± 0.83 mm for IMRT and 0.53 ± 0.48 mm for VMAT based on the Dynalog file analysis. The RMS error of the leaf position was nearly identical for the repeated deliveries of the same plans. In general, both techniques are feasible for PLDR treatments. VMAT was more advantageous for PLDR with more uniform target dose per pulse, especially for centrally located tumors. However, for large, irregular and/or peripheral tumors, IMRT could produce more favorable PLDR plans. By taking the biological benefit of PLDR delivery and the dosimetric benefit of IMRT and VMAT, the proposed methods have a great potential for those previously-irradiated recurrent patients.

Assessment of Total- and Partial-Body Irradiation in a Baboon Model

This biodosimetry study used irradiated baboons to investigate the efficacy of a kinetic multiparameter (clinical, physical, and biological) approach for discriminating partial-body irradiation (PBI) and total-body irradiation (TBI). Animals were unilaterally (front) exposed to 60Co gamma rays (8 to 32 cGy min) using either TBI or vertical left hemi-body irradiation (HBI), as follows: 2.5 Gy TBI (n = 2), 5 Gy TBI (n = 2), 5 Gy HBI (n = 2), and 10 Gy HBI (n = 2). Midline tissue doses were measured at the anterior iliac crest level with an ionization chamber, and body dosimetry was performed using thermoluminescent dosimeters. Blood samples were collected before exposure and from 1 h until 200 d after irradiation. Clinical status, complete blood cell count, biochemical parameters, and cytogenetic analysis were evaluated. The partial least square discriminant analysis chosen for statistical analysis showed that the four groups of irradiated baboons were clearly separated. However, the dicentric chromosome assay may not distinguish HBI from TBI in confounding situations where equivalent whole-body doses are similar and the time of exposure is sufficient for peripheral blood lymphocyte homogenization. Interestingly, as bone marrow shielding in HBI animals prevented aplasia from happening, hematologic parameters such as the platelet count and Flt-3 ligand level helped to distinguish HBI and TBI. Moreover, the ratio of neutrophil to lymphocyte counts, creatine kinase, and citrulline levels may be discriminating biomarkers of dose or injury. Both early and delayed clinical signs and bioindicators appear to be useful for assessment of heterogeneous irradiation.

Investigation of pulsed low dose rate radiotherapy using dynamic arc delivery techniques

There has been no consensus standard of care to treat recurrent cancer patients who have previously been irradiated. Pulsed low dose rate (PLDR) external beam radiotherapy has the potential to reduce normal tissue toxicities while still providing significant tumor control for recurrent cancers. This work investigates the dosimetry feasibility of PLDR treatment using dynamic arc delivery techniques. Five treatment sites were investigated in this study including breast, pancreas, prostate, head and neck, and lung. Dynamic arc plans were generated using the Varian Eclipse system and the RapidArc delivery technique with 6 and 10 MV photon beams. Each RapidArc plan consisted of two full arcs and the plan was delivered five times to achieve a daily dose of 200 cGy. The dosimetry requirement was to deliver approximately 20 cGy/arc with a 3 min interval to achieve an effective dose rate of 6.7 cGy min−1. Monte Carlo simulations were performed to calculate the actual dose delivered to the planning target volume (PTV) per arc taking into account beam attenuation/scattering and intensity modulation. The maximum, minimum and mean doses to the PTV were analyzed together with the dose volume histograms and isodose distributions. The dose delivery for the five plans was validated using solid water phantoms inserted with an ionization chamber and film, and a cylindrical detector array. Two intensity-modulated arcs were used to efficiently deliver the PLDR plans that provided conformal dose distributions for treating complex recurrent cancers. For the five treatment sites, the mean PTV dose ranged from 18.9 to 22.6 cGy/arc. For breast, the minimum and maximum PTV dose was 8.3 and 35.2 cGy/arc, respectively. The PTV dose varied between 12.9 and 27.5 cGy/arc for pancreas, 12.6 and 28.3 cGy/arc for prostate, 12.1 and 30.4 cGy/arc for H&N, and 16.2 and 27.6 cGy/arc for lung. Advanced radiation therapy can provide superior target coverage and normal tissue sparing for PLDR reirradiation of recurrent cancers, which can be delivered using dynamic arc delivery techniques with ten full arcs and an effective dose rate of 6.7 ± 4.0 cGy min−1.

SU-E-T-221: An In-House Developed Resettable MOSFET Dosimeter for Radiotherapy

Purpose: To report the feasibility and clinical validation of an in-house developed MOSFET dosimetry system and describe an integrated nondestructive reset procedure. Methods: Off-the-shelf MOSFETs are connected to a PC using an 18 bit/analogue-input and 16 bit/output data acquisition card. A reading algorithm was developed defining the zero-temperature-coefficient point (ZTC) to determine the threshold voltage. The reset procedure consists of an internal circuit generating a local heating induced by an electrical current. Sensitivity has been investigated as a function of bias voltage (0—9 V) to the gate. Dosimetric properties have been evaluated for 6 MV and 15 MV clinical photon beams and in vivo benchmarking was performed against TLD for conventional treatments and total body irradiation (TBI). Results: Sensitivity of 0.08 mV cGy−1 can be obtained for 200 cGy irradiations at 5 V bias voltage. Ten consecutive measurements at 200 cGy yield a SD of 2.08 cGy (1.05%). Increasing the dose in steps from 5 cGy to 1000 cGy yields a 1.00 Pearson correlation coefficient and agreement within 2.0%. Dose rate dependence (160–800 cGy min−1) was within 2.5%, temperature dependence within 2.0% (25–37° C). Dose response is stable up to 50 Gy (saturation occurs at approximately 90 Gy), which is used as threshold dose before resetting the MOSFET. An average measured-over-calculated dose ratio within 1.05 (SD: 0.04) has been obtained in vivo. TBI midplane-dose assessed by entrance and exit dose measurements agreed within 1.9% with ionization chamber in phantom, and within 1.0% with TLD in vivo. Conclusions: An in-house developed resettable MOSFET-based dosimetry system is proposed. The system has been validated and is currently used for in vivo entrance dose measurement in clinical routine for open field treatment configurations.

Response of Primary Human Fibroblasts Exposed to Solar Particle Event Protons

Solar particle events (SPEs) present a major radiation-related risk for manned exploratory missions in deep space. Within a short period the astronauts may absorb doses that engender acute effects, in addition to the risk of late effects, such as the induction of cancer. Using primary human cells, we studied clonogenic survival and the induction of neoplastic transformation after exposure to a worst case scenario SPE. We simulated such an SPE with monoenergetic protons (50, 100, 1000 MeV) delivered at a dose rate of 1.65 cGy min⁻¹ in a dose range from 0 to 3 Gy. For comparison, we exposed the cells to a high dose rate of 33.3 cGy min⁻¹. X rays (100 kVp, 8 mA, 1.7 mm Al filter) were used as a reference radiation. Overall, we observed a significant sparing effect of the SPE dose rate on cell survival. High-dose-rate protons were also more efficient in induction of transformation in the dose range below 30 cGy. However, as dose accumulated at high dose rate, the transformation levels declined, while at the SPE dose rate, the number of transformants continued to increase up to about 1 Gy. These findings suggest that considering dose-rate effects may be important in evaluating the biological effects of exposure to space radiation. Our analyses of the data based on particle fluence showed that lethality and transforming potential per particle clearly increased with increasing linear energy transfer (LET) and thus with the decreasing energy of protons. Further, we found that the biological response was determined not only by LET but also type of radiation, e.g. particles and photons. This suggests that using γ or X rays may not be ideal for assessing risk associated with SPE exposures.