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Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factors on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression strongly predicted disease progression and death. Future trials should stratify by baseline CA19-9 and incorporate CA19-9 progression as a criterion for progressive disease.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Low dose radiation hypersensitivity and clustered DNA damages in human fibroblasts exposed to low dose and dose rate protons or 137CS y-rays

Effective radioprotection for human space travelers hinges upon understanding the individual properties of charged particles. A significant fraction of particle radiation astronauts will encounter in space exploratory missions will come from high energy protons in galactic cosmic radiation (GCR) and/or possible exposures to lower energy proton flux from solar particle events (SPEs). These potential exposures present major concerns for NASA and others, in planning and executing long term space exploratory missions. We recently reported cell survival and transformation (acquisition of anchorage-independent growth in soft agar) frequencies in apparently normal NFF-28 primary human fibroblasts exposed to 0-30 cGy of 50MeV, 100MeV (SPE-like), or 1000 MeV (GCR-like) monoenergetic protons. These were modeled after 1989 SPE energies at an SPE-like low dose-rate (LDR) of 1.65 cGy/min or high dose rate (HDR) of 33.3 cGy/min delivered at the NASA Space Radiation Laboratory (NSRL) at BNL.

61 RADIATION PROTECTION AND DOSIMETRY↗

Model-based dose calculations for COMS eye plaque brachytherapy using an anatomically realistic eye phantom

Purpose : To investigate the effects of the composition and geometry of ocular media and tissues surrounding the eye on dose distributions for COMS eye plaque brachytherapy with{sup 125}I, {sup 103}Pd, or {sup 131}Cs seeds, and to investigate doses to ocular structures. Methods : An anatomically and compositionally realistic voxelized eye model with a medial tumor is developed based on a literature review. Mass energy absorption and attenuation coefficients for ocular media are calculated. Radiation transport and dose deposition are simulated using the EGSnrc Monte Carlo user-code BrachyDose for a fully loaded COMS eye plaque within a water phantom and our full eye model for the three radionuclides. A TG-43 simulation with the same seed configuration in a water phantom neglecting the plaque and interseed effects is also performed. The impact on dose distributions of varying tumor position, as well as tumor and surrounding tissue media is investigated. Each simulation and radionuclide is compared using isodose contours, dose volume histograms for the lens and tumor, maximum, minimum, and average doses to structures of interest, and doses to voxels of interest within the eye. Results : Mass energy absorption and attenuation coefficients of the ocular media differ from those of water by as much as 12% within the 20–30 keV photon energy range. For all radionuclides studied, average doses to the tumor and lens regions in the full eye model differ from those for the plaque in water by 8%–10% and 13%–14%, respectively; the average doses to the tumor and lens regions differ between the full eye model and the TG-43 simulation by 2%–17% and 29%–34%, respectively. Replacing the surrounding tissues in the eye model with water increases the maximum and average doses to the lens by 2% and 3%, respectively. Substituting the tumor medium in the eye model for water, soft tissue, or an alternate melanoma composition affects tumor dose compared to the default eye model simulation by up to 16%. In the full eye model simulations, the average dose to the lens is larger by 7%–9% than the dose to the center of the lens, and the maximum dose to the optic nerve is 17%–22% higher than the dose to the optic disk for all radionuclides. In general, when normalized to the same prescription dose at the tumor apex, doses delivered to all structures of interest in the full eye model are lowest for{sup 103}Pd and highest for {sup 131}Cs, except for the tumor where the average dose is highest for {sup 103}Pd and lowest for {sup 131}Cs. Conclusions : The eye is not radiologically water-equivalent, as doses from simulations of the plaque in the full eye model differ considerably from doses for the plaque in a water phantom and from simulated TG-43 calculated doses. This demonstrates the importance of model-based dose calculations for eye plaque brachytherapy, for which accurate elemental compositions of ocular media are necessary.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Impact of dose size in single fraction spatially fractionated (grid) radiotherapy for melanoma

Purpose: To evaluate the impact of dose size in single fraction, spatially fractionated (grid) radiotherapy for selectively killing infiltrated melanoma cancer cells of different tumor sizes, using different radiobiological models. Methods: A Monte Carlo technique was employed to calculate the 3D dose distribution of a commercially available megavoltage grid collimator in a 6 MV beam. The linear-quadratic (LQ) and modified linear quadratic (MLQ) models were used separately to evaluate the therapeutic outcome of a series of single fraction regimens that employed grid therapy to treat both acute and late responding melanomas of varying sizes. The dose prescription point was at the center of the tumor volume. Dose sizes ranging from 1 to 30 Gy at 100% dose line were modeled. Tumors were either touching the skin surface or having their centers at a depth of 3 cm. The equivalent uniform dose (EUD) to the melanoma cells and the therapeutic ratio (TR) were defined by comparing grid therapy with the traditional open debulking field. The clinical outcomes from recent reports were used to verify the authors’ model. Results: Dose profiles at different depths and 3D dose distributions in a series of 3D melanomas treated with grid therapy were obtained. The EUDs and TRs for all sizes of 3D tumors involved at different doses were derived through the LQ and MLQ models, and a practical equation was derived. The EUD was only one fifth of the prescribed dose. The TR was dependent on the prescribed dose and on the LQ parameters of both the interspersed cancer and normal tissue cells. The results from the LQ model were consistent with those of the MLQ model. At 20 Gy, the EUD and TR by the LQ model were 2.8% higher and 1% lower than by the MLQ, while at 10 Gy, the EUD and TR as defined by the LQ model were only 1.4% higher and 0.8% lower, respectively. The dose volume histograms of grid therapy for a 10 cm tumor showed different dosimetric characteristics from those of conventional radiotherapy. A significant portion of the tumor volume received a very large dose in grid therapy, which ensures significant tumor cell killing in these regions. Conversely, some areas received a relatively small dose, thereby sparing interspersed normal cells and increasing radiation tolerance. The radiobiology modeling results indicated that grid therapy could be useful for treating acutely responding melanomas infiltrating radiosensitive normal tissues. The theoretical model predictions were supported by the clinical outcomes. Conclusions: Grid therapy functions by selectively killing infiltrating tumor cells and concomitantly sparing interspersed normal cells. The TR depends on the radiosensitivity of the cell population, dose, tumor size, and location. Because the volumes of very high dose regions are small, the LQ model can be used safely to predict the clinical outcomes of grid therapy. When treating melanomas with a dose of 15 Gy or higher, single fraction grid therapy is clearly advantageous for sparing interspersed normal cells. The existence of a threshold fraction dose, which was found in the authors’ theoretical simulations, was confirmed by clinical observations.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Determination of prescription dose for Cs-131 permanent implants using the BED formalism including resensitization correction

Purpose: The current widely used biological equivalent dose (BED) formalism for permanent implants is based on the linear-quadratic model that includes cell repair and repopulation but not resensitization (redistribution and reoxygenation). The authors propose a BED formalism that includes all the four biological effects (4Rs), and the authors propose how it can be used to calculate appropriate prescription doses for permanent implants with Cs-131. Methods: A resensitization correction was added to the BED calculation for permanent implants to account for 4Rs. Using the same BED, the prescription doses with Au-198, I-125, and Pd-103 were converted to the isoeffective Cs-131 prescription doses. The conversion factor F, ratio of the Cs-131 dose to the equivalent dose with the other reference isotope (F{sub r}: with resensitization, F{sub n}: without resensitization), was thus derived and used for actual prescription. Different values of biological parameters such as α, β, and relative biological effectiveness for different types of tumors were used for the calculation. Results: Prescription doses with I-125, Pd-103, and Au-198 ranging from 10 to 160 Gy were converted into prescription doses with Cs-131. The difference in dose conversion factors with (F{sub r}) and without (F{sub n}) resensitization was significant but varied with different isotopes and different types of tumors. The conversion factors also varied with different doses. For I-125, the average values of F{sub r}/F{sub n} were 0.51/0.46, for fast growing tumors, and 0.88/0.77 for slow growing tumors. For Pd-103, the average values of F{sub r}/F{sub n} were 1.25/1.15 for fast growing tumors, and 1.28/1.22 for slow growing tumors. For Au-198, the average values of F{sub r}/F{sub n} were 1.08/1.25 for fast growing tumors, and 1.00/1.06 for slow growing tumors. Using the biological parameters for the HeLa/C4-I cells, the averaged value of F{sub r} was 1.07/1.11 (rounded to 1.1), and the averaged value of F{sub n} was 1.75/1.18. F{sub r} of 1.1 has been applied to gynecological cancer implants with expected acute reactions and outcomes as expected based on extensive experience with permanent implants. The calculation also gave the average Cs-131 dose of 126 Gy converted from the I-125 dose of 144 Gy for prostate implants. Conclusions: Inclusion of an allowance for resensitization led to significant dose corrections for Cs-131 permanent implants, and should be applied to prescription dose calculation. The adjustment of the Cs-131 prescription doses with resensitization correction for gynecological permanent implants was consistent with clinical experience and observations. However, the Cs-131 prescription doses converted from other implant doses can be further adjusted based on new experimental results, clinical observations, and clinical outcomes.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Integral dose investigation of non-coplanar treatment beam geometries in radiotherapy

Purpose: Automated planning and delivery of non-coplanar plans such as 4π radiotherapy involving a large number of fields have been developed to take advantage of the newly available automated couch and gantry on C-arm gantry linacs. However, there is an increasing concern regarding the potential changes in the integral dose that needs to be investigated. Methods: A digital torso phantom and 22 lung and liver stereotactic body radiation therapy (SBRT) patients were included in the study. The digital phantom was constructed as a water equivalent elliptical cylinder with a major axis length of 35.4 cm and minor axis of 23.6 cm. A 4.5 cm diameter target was positioned at varying depths along the major axis. Integral doses from intensity modulated, non-coplanar beams forming a conical pattern were compared against the equally spaced coplanar beam plans. Integral dose dependence on the phantom geometry and the beam number was also quantified. For the patient plans, the non-coplanar and coplanar beams and fluences were optimized using a column generation and pricing approach and compared against clinical VMAT plans using two full (lung) or partial coplanar arcs (liver) entering at the side proximal to the tumor. Both the average dose to the normal tissue volume and the total volumes receiving greater than 2 Gy (V2) and 5 Gy (V5) were evaluated and compared. Results: The ratio of integral dose from the non-coplanar and coplanar plans depended on the tumor depth for the phantom; for tumors shallower than 10 cm, the non-coplanar integral doses were lower than coplanar integral doses for non-coplanar angles less than 60°. Similar patterns were observed in the patient plans. The smallest non-coplanar integral doses were observed for tumor 6–8 cm deep. For the phantom, the integral dose was independent of the number of beams, consistent with the liver SBRT patients but the lung SBRT patients showed slight increase in the integral dose when more beams were used. Larger tumor size and larger patient body size did not change the overall relationship of integral doses between non-coplanar and coplanar cases. However, the thin disk-shaped tumor received at least 40% greater integral doses with the non-coplanar plans. Overall, patient non-coplanar integral doses and V5 were comparable to those of coplanar doses from the same optimization engine and 15%–20% lower than state of the art VMAT plans. However, non-coplanar beams significantly increased V2 in both the phantom and patients. On average, the lung and liver SBRT patient normal tissue volumes receiving dose greater than 2 Gy were increased by 749 and 532 cm{sup 3}, respectively. Conclusions: The authors used a digital phantom simulating a patient torso and 22 SBRT patients to show that the integral doses from the plans employing optimized non-coplanar beams are comparable to those of the coplanar plans using an equal number of discrete beams and are significantly lower than those of VMAT plans. The non-coplanar beams expose a larger normal tissue volume to non-zero doses, whose impact will need to be evaluated individually to determine the risk/benefit ratio of the non-coplanar plans.

61 RADIATION PROTECTION AND DOSIMETRY↗

Comparison of patient specific dose metrics between chest radiography, tomosynthesis, and CT for adult patients of wide ranging body habitus

Purpose: Given the radiation concerns inherent to the x-ray modalities, accurately estimating the radiation doses that patients receive during different imaging modalities is crucial. This study estimated organ doses, effective doses, and risk indices for the three clinical chest x-ray imaging techniques (chest radiography, tomosynthesis, and CT) using 59 anatomically variable voxelized phantoms and Monte Carlo simulation methods. Methods: A total of 59 computational anthropomorphic male and female extended cardiac-torso (XCAT) adult phantoms were used in this study. Organ doses and effective doses were estimated for a clinical radiography system with the capability of conducting chest radiography and tomosynthesis (Definium 8000, VolumeRAD, GE Healthcare) and a clinical CT system (LightSpeed VCT, GE Healthcare). A Monte Carlo dose simulation program (PENELOPE, version 2006, Universitat de Barcelona, Spain) was used to mimic these two clinical systems. The Duke University (Durham, NC) technique charts were used to determine the clinical techniques for the radiographic modalities. An exponential relationship between CTDI{sub vol} and patient diameter was used to determine the absolute dose values for CT. The simulations of the two clinical systems compute organ and tissue doses, which were then used to calculate effective dose and risk index. The calculation of the two dose metrics used the tissue weighting factors from ICRP Publication 103 and BEIR VII report. Results: The average effective dose of the chest posteroanterior examination was found to be 0.04 mSv, which was 1.3% that of the chest CT examination. The average effective dose of the chest tomosynthesis examination was found to be about ten times that of the chest posteroanterior examination and about 12% that of the chest CT examination. With increasing patient average chest diameter, both the effective dose and risk index for CT increased considerably in an exponential fashion, while these two dose metrics only increased slightly for radiographic modalities and for chest tomosynthesis. Effective and organ doses normalized to mAs all illustrated an exponential decrease with increasing patient size. As a surface organ, breast doses had less correlation with body size than that of lungs or liver. Conclusions: Patient body size has a much greater impact on radiation dose of chest CT examinations than chest radiography and tomosynthesis. The size of a patient should be considered when choosing the best thoracic imaging modality.

61 RADIATION PROTECTION AND DOSIMETRY↗

Realistic simulation of reduced-dose CT with noise modeling and sinogram synthesis using DICOM CT images

Purpose: Reducing the patient dose while maintaining the diagnostic image quality during CT exams is the subject of a growing number of studies, in which simulations of reduced-dose CT with patient data have been used as an effective technique when exploring the potential of various dose reduction techniques. Difficulties in accessing raw sinogram data, however, have restricted the use of this technique to a limited number of institutions. Here, we present a novel reduced-dose CT simulation technique which provides realistic low-dose images without the requirement of raw sinogram data. Methods: Two key characteristics of CT systems, the noise equivalent quanta (NEQ) and the algorithmic modulation transfer function (MTF), were measured for various combinations of object attenuation and tube currents by analyzing the noise power spectrum (NPS) of CT images obtained with a set of phantoms. Those measurements were used to develop a comprehensive CT noise model covering the reduced x-ray photon flux, object attenuation, system noise, and bow-tie filter, which was then employed to generate a simulated noise sinogram for the reduced-dose condition with the use of a synthetic sinogram generated from a reference CT image. The simulated noise sinogram was filtered with the algorithmic MTF and back-projected to create a noise CT image, which was then added to the reference CT image, finally providing a simulated reduced-dose CT image. The simulation performance was evaluated in terms of the degree of NPS similarity, the noise magnitude, the bow-tie filter effect, and the streak noise pattern at photon starvation sites with the set of phantom images. Results: The simulation results showed good agreement with actual low-dose CT images in terms of their visual appearance and in a quantitative evaluation test. The magnitude and shape of the NPS curves of the simulated low-dose images agreed well with those of real low-dose images, showing discrepancies of less than +/−3.2% in terms of the noise power at the peak height and +/−1.2% in terms of the spatial frequency at the peak height. The magnitudes of the noise measured for 12 different combinations the phantom size, tube current, and reconstruction kernel for the simulated and real low-dose images were very similar, with differences of 0.1 to 4.7%. Thep value for a statistical testing of the difference in the noise magnitude ranged from 0.99 to 0.11, showing that there was no difference statistically between the noise magnitudes of the real and simulated low-dose images using our method. The strength and pattern of the streak noise in an anthropomorphic phantom was also consistent with expectations. Conclusions: A novel reduced-dose CT simulation technique was developed which uses only CT images while not requiring raw sinogram data. Our method can provide realistic simulation results under reduced-dose conditions both in terms of the noise magnitude and the textual appearance. This technique has the potential to promote clinical research for patient dose reductions.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Toward adaptive radiotherapy for head and neck patients: Uncertainties in dose warping due to the choice of deformable registration algorithm

Purpose: The aims of this work were to evaluate the performance of several deformable image registration (DIR) algorithms implemented in our in-house software (NiftyReg) and the uncertainties inherent to using different algorithms for dose warping. Methods: The authors describe a DIR based adaptive radiotherapy workflow, using CT and cone-beam CT (CBCT) imaging. The transformations that mapped the anatomy between the two time points were obtained using four different DIR approaches available in NiftyReg. These included a standard unidirectional algorithm and more sophisticated bidirectional ones that encourage or ensure inverse consistency. The forward (CT-to-CBCT) deformation vector fields (DVFs) were used to propagate the CT Hounsfield units and structures to the daily geometry for “dose of the day” calculations, while the backward (CBCT-to-CT) DVFs were used to remap the dose of the day onto the planning CT (pCT). Data from five head and neck patients were used to evaluate the performance of each implementation based on geometrical matching, physical properties of the DVFs, and similarity between warped dose distributions. Geometrical matching was verified in terms of dice similarity coefficient (DSC), distance transform, false positives, and false negatives. The physical properties of the DVFs were assessed calculating the harmonic energy, determinant of the Jacobian, and inverse consistency error of the transformations. Dose distributions were displayed on the pCT dose space and compared using dose difference (DD), distance to dose difference, and dose volume histograms. Results: All the DIR algorithms gave similar results in terms of geometrical matching, with an average DSC of 0.85 ± 0.08, but the underlying properties of the DVFs varied in terms of smoothness and inverse consistency. When comparing the doses warped by different algorithms, we found a root mean square DD of 1.9% ± 0.8% of the prescribed dose (pD) and that an average of 9% ± 4% of voxels within the treated volume failed a 2%pD DD-test (DD{sub 2%-pp}). Larger DD{sub 2%-pp} was found within the high dose gradient (21% ± 6%) and regions where the CBCT quality was poorer (28% ± 9%). The differences when estimating the mean and maximum dose delivered to organs-at-risk were up to 2.0%pD and 2.8%pD, respectively. Conclusions: The authors evaluated several DIR algorithms for CT-to-CBCT registrations. In spite of all methods resulting in comparable geometrical matching, the choice of DIR implementation leads to uncertainties in dose warped, particularly in regions of high gradient and/or poor imaging quality.

60 APPLIED LIFE SCIENCES↗

Shared Dosimetry Error in Epidemiological Dose-Response Analyses

Radiation dose reconstruction systems for large-scale epidemiological studies are sophisticated both in providing estimates of dose and in representing dosimetry uncertainty. For example, a computer program was used by the Hanford Thyroid Disease Study to provide 100 realizations of possible dose to study participants. The variation in realizations reflected the range of possible dose for each cohort member consistent with the data on dose determinates in the cohort. Another example is the Mayak Worker Dosimetry System 2013 which estimates both external and internal exposures and provides multiple realizations of "possible" dose history to workers given dose determinants. This paper takes up the problem of dealing with complex dosimetry systems that provide multiple realizations of dose in an epidemiologic analysis. In this paper we derive expected scores and the information matrix for a model used widely in radiation epidemiology, namely the linear excess relative risk (ERR) model that allows for a linear dose response (risk in relation to radiation) and distinguishes between modifiers of background rates and of the excess risk due to exposure. We show that treating the mean dose for each individual (calculated by averaging over the realizations) as if it was true dose (ignoring both shared and unshared dosimetry errors) gives asymptotically unbiased estimates (i.e. the score has expectation zero) and valid tests of the null hypothesis that the ERR slope β is zero. Although the score is unbiased the information matrix (and hence the standard errors of the estimate of β) is biased for β≠0 when ignoring errors in dose estimates, and we show how to adjust the information matrix to remove this bias, using the multiple realizations of dose. Use of these methods for several studies, including the Mayak Worker Cohort and the U.S. Atomic Veterans Study, is discussed.

epidemiological analysis↗

SU-E-T-374: Evaluation and Verification of Dose Calculation Accuracy with Different Dose Grid Sizes for Intracranial Stereotactic Radiosurgery

Purpose: In this study, we aim to evaluate the effect of dose grid size on the accuracy of calculated dose for small lesions in intracranial stereotactic radiosurgery (SRS), and to verify dose calculation accuracy with radiochromic film dosimetry. Methods: 15 intracranial lesions from previous SRS patients were retrospectively selected for this study. The planning target volume (PTV) ranged from 0.17 to 2.3 cm{sup 3}. A commercial treatment planning system was used to generate SRS plans using the volumetric modulated arc therapy (VMAT) technique using two arc fields. Two convolution-superposition-based dose calculation algorithms (Anisotropic Analytical Algorithm and Acuros XB algorithm) were used to calculate volume dose distribution with dose grid size ranging from 1 mm to 3 mm with 0.5 mm step size. First, while the plan monitor units (MU) were kept constant, PTV dose variations were analyzed. Second, with 95% of the PTV covered by the prescription dose, variations of the plan MUs as a function of dose grid size were analyzed. Radiochomic films were used to compare the delivered dose and profile with the calculated dose distribution with different dose grid sizes. Results: The dose to the PTV, in terms of the mean dose, maximum, and minimum dose, showed steady decrease with increasing dose grid size using both algorithms. With 95% of the PTV covered by the prescription dose, the total MU increased with increasing dose grid size in most of the plans. Radiochromic film measurements showed better agreement with dose distributions calculated with 1-mm dose grid size. Conclusion: Dose grid size has significant impact on calculated dose distribution in intracranial SRS treatment planning with small target volumes. Using the default dose grid size could lead to under-estimation of delivered dose. A small dose grid size should be used to ensure calculation accuracy and agreement with QA measurements.

60 APPLIED LIFE SCIENCES↗

Dynamically accumulated dose and 4D accumulated dose for moving tumors

Purpose: The purpose of this work was to investigate the relationship between dynamically accumulated dose (dynamic dose) and 4D accumulated dose (4D dose) for irradiation of moving tumors, and to quantify the dose uncertainty induced by tumor motion. Methods: The authors established that regardless of treatment modality and delivery properties, the dynamic dose will converge to the 4D dose, instead of the 3D static dose, after multiple deliveries. The bounds of dynamic dose, or the maximum estimation error using 4D or static dose, were established for the 4D and static doses, respectively. Numerical simulations were performed (1) to prove the principle that for each phase, after multiple deliveries, the average number of deliveries for any given time converges to the total number of fractions (K) over the number of phases (N); (2) to investigate the dose difference between the 4D and dynamic doses as a function of the number of deliveries for deliveries of a 'pulsed beam'; and (3) to investigate the dose difference between 4D dose and dynamic doses as a function of delivery time for deliveries of a 'continuous beam.' A Poisson model was developed to estimate the mean dose error as a function of number of deliveries or delivered time for both pulsed beam and continuous beam. Results: The numerical simulations confirmed that the number of deliveries for each phase converges to K/N, assuming a random starting phase. Simulations for the pulsed beam and continuous beam also suggested that the dose error is a strong function of the number of deliveries and/or total deliver time and could be a function of the breathing cycle, depending on the mode of delivery. The Poisson model agrees well with the simulation. Conclusions: Dynamically accumulated dose will converge to the 4D accumulated dose after multiple deliveries, regardless of treatment modality. Bounds of the dynamic dose could be determined using quantities derived from 4D doses, and the mean dose difference between the dynamic dose and 4D dose as a function of number of deliveries and/or total deliver time was also established.

60 APPLIED LIFE SCIENCES↗

Estimated dose rates to members of the public from external exposure to patients with {sup 131}I thyroid treatment

Purpose: Estimated dose rates that may result from exposure to patients who had been administered iodine-131 ({sup 131}I) as part of medical therapy were calculated. These effective dose rate estimates were compared with simplified assumptions under United States Nuclear Regulatory Commission Regulatory Guide 8.39, which does not consider body tissue attenuation nor time-dependent redistribution and excretion of the administered {sup 131}I. Methods: Dose rates were estimated for members of the public potentially exposed to external irradiation from patients recently treated with {sup 131}I. Tissue attenuation and iodine biokinetics were considered in the patient in a larger comprehensive effort to improve external dose rate estimates. The external dose rate estimates are based on Monte Carlo simulations using the Phantom with Movable Arms and Legs (PIMAL), previously developed by Oak Ridge National Laboratory and the United States Nuclear Regulatory Commission. PIMAL was employed to model the relative positions of the {sup 131}I patient and members of the public in three exposure scenarios: (1) traveling on a bus in a total of six seated or standing permutations, (2) two nursing home cases where a caregiver is seated at 30 cm from the patient’s bedside and a nursing home resident seated 250 cm away from the patient in an adjacent bed, and (3) two hotel cases where the patient and a guest are in adjacent rooms with beds on opposite sides of the common wall, with the patient and guest both in bed and either seated back-to-back or lying head to head. The biokinetic model predictions of the retention and distribution of {sup 131}I in the patient assumed a single voiding of urinary bladder contents that occurred during the trip at 2, 4, or 8 h after {sup 131}I administration for the public transportation cases, continuous first-order voiding for the nursing home cases, and regular periodic voiding at 4, 8, or 12 h after administration for the hotel room cases. Organ specific activities of {sup 131}I in the thyroid, bladder, and combined remaining tissues were calculated as a function of time after administration. Exposures to members of the public were considered for {sup 131}I patients with normal thyroid uptake (peak thyroid uptake of ∼27% of administered {sup 131}I), differentiated thyroid cancer (DTC, 5% uptake), and hyperthyroidism (80% uptake). Results: The scenario with the patient seated behind the member of the public yielded the highest dose rate estimate of seated public transportation exposure cases. The dose rate to the adjacent room guest was highest for the exposure scenario in which the hotel guest and patient are seated by a factor of ∼4 for the normal and differentiated thyroid cancer uptake cases and by a factor of ∼3 for the hyperthyroid case. Conclusions: It was determined that for all modeled cases, the DTC case yielded the lowest external dose rates, whereas the hyperthyroid case yielded the highest dose rates. In estimating external dose to members of the public from patients with {sup 131}I therapy, consideration must be given to (patient- and case-specific) administered {sup 131}I activities and duration of exposure for a more complete estimate. The method implemented here included a detailed calculation model, which provides a means to determine dose rate estimates for a range of scenarios. The method was demonstrated for variations of three scenarios, showing how dose rates are expected to vary with uptake, voiding pattern, and patient location.

60 APPLIED LIFE SCIENCES↗

Evaluation of various approaches for assessing dose indicators and patient organ doses resulting from radiotherapy cone-beam CT

Purpose: The aim of this study was to evaluate various approaches for assessing patient organ doses resulting from radiotherapy cone-beam CT (CBCT), by the use of thermoluminescent dosimeter (TLD) measurements in anthropomorphic phantoms, a Monte Carlo based dose calculation software, and different dose indicators as presently defined. Methods: Dose evaluations were performed on a CBCT Elekta XVI (Elekta, Crawley, UK) for different protocols and anatomical regions. The first part of the study focuses on using PCXMC software (PCXMC 2.0, STUK, Helsinki, Finland) for calculating organ doses, adapting the input parameters to simulate the exposure geometry, and beam dose distribution in an appropriate way. The calculated doses were compared to readouts of TLDs placed in an anthropomorphic Rando phantom. After this validation, the software was used for analyzing organ dose variability associated with patients’ differences in size and gender. At the same time, various dose indicators were evaluated: kerma area product (KAP), cumulative air-kerma at the isocenter (K{sub air}), cone-beam dose index, and central cumulative dose. The latter was evaluated in a single phantom and in a stack of three adjacent computed tomography dose index phantoms. Based on the different dose indicators, a set of coefficients was calculated to estimate organ doses for a range of patient morphologies, using their equivalent diameters. Results: Maximum organ doses were about 1 mGy for head and neck and 25 mGy for chest and pelvis protocols. The differences between PCXMC and TLDs doses were generally below 10% for organs within the field of view and approximately 15% for organs at the boundaries of the radiation beam. When considering patient size and gender variability, differences in organ doses up to 40% were observed especially in the pelvic region; for the organs in the thorax, the maximum differences ranged between 20% and 30%. Phantom dose indexes provided better correlation with organ doses than K{sub air} and KAP, with average ratios ranging between 0.9 and 1.1 and variations for different organs and protocols below 20%. The triple phantom setup allowed us to take into account scatter dose contributions, but nonetheless, the correlation with the evaluated organ doses was not improved with this method. Conclusions: The simulation of rotational geometry and of asymmetric beam distribution by means of PCXMC 2.0 enabled us to determine patient organ doses depending on weight, height and gender. Alternatively, the measurement of an in phantom dose indicator combined with proper correction coefficients can be a useful tool for a first dose estimation of in-field organs. The data and coefficients provided in this study can be applied to any patient undergoing a scan by an Elekta XVI equipment.

60 APPLIED LIFE SCIENCES↗

Graves' disease radioiodine-therapy: Choosing target absorbed doses for therapy planning

Purpose: The precise determination of organ mass (m{sub th}) and total number of disintegrations within the thyroid gland (A{sup ~}) are essential for thyroid absorbed-dose calculations for radioiodine therapy. Nevertheless, these parameters may vary according to the method employed for their estimation, thus introducing uncertainty in the estimated thyroid absorbed dose and in any dose–response relationship derived using such estimates. In consideration of these points, thyroid absorbed doses for Graves’ disease (GD) treatment planning were calculated using different approaches to estimating the m{sub th} and the A{sup ~}. Methods: Fifty patients were included in the study. Thyroid{sup 131}I uptake measurements were performed at 2, 6, 24, 48, 96, and 220 h postadministration of a tracer activity in order to estimate the effective half-time (T{sub eff}) of {sup 131}I in the thyroid; the thyroid cumulated activity was then estimated using the T{sub eff} thus determined or, alternatively, calculated by numeric integration of the measured time-activity data. Thyroid mass was estimated by ultrasonography (USG) and scintigraphy (SCTG). Absorbed doses were calculated with the OLINDA/EXM software. The relationships between thyroid absorbed dose and therapy response were evaluated at 3 months and 1 year after therapy. Results: The average ratio (±1 standard deviation) betweenm{sub th} estimated by SCTG and USG was 1.74 (±0.64) and that between A{sup ~} obtained by T{sub eff} and the integration of measured activity in the gland was 1.71 (±0.14). These differences affect the calculated absorbed dose. Overall, therapeutic success, corresponding to induction of durable hypothyroidism or euthyroidism, was achieved in 72% of all patients at 3 months and in 90% at 1 year. A therapeutic success rate of at least 95% was found in the group of patients receiving doses of 200 Gy (p = 0.0483) and 330 Gy (p = 0.0131) when m{sub th} was measured by either USG or SCTG and A{sup ~} was determined by the integration of measured {sup 131}I activity in the thyroid gland and based on T{sub eff}, respectively. No statistically significant relationship was found between therapeutic response and patients’ age, administered {sup 131}I activity (MBq), 24-h thyroid {sup 131}I uptake (%) or T{sub eff} (p ≥ 0.064); nonetheless, a good relationship was found between the therapeutic response and m{sub th} (p ≤ 0.035). Conclusions: According to the results of this study, the most effective thyroid absorbed dose to be targeted in GD therapy should not be based on a fixed dose but rather should be individualized based on the patient'sm{sub th} and A{sup ~}. To achieve a therapeutic success (i.e., durable euthyroidism or hypothyroidism) rate of at least 95%, a thyroid absorbed dose of 200 or 330 Gy is required depending on the methodology used for estimating m{sub th} and A{sup ~}.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Dosimetric characterization and output verification for conical brachytherapy surface applicators. Part II. High dose rate {sup 192}Ir sources

Purpose: Historically, treatment of malignant surface lesions has been achieved with linear accelerator based electron beams or superficial x-ray beams. Recent developments in the field of brachytherapy now allow for the treatment of surface lesions with specialized conical applicators placed directly on the lesion. Applicators are available for use with high dose rate (HDR){sup 192}Ir sources, as well as electronic brachytherapy sources. Part I of this paper discussed the applicators used with electronic brachytherapy sources. Part II will discuss those used with HDR {sup 192}Ir sources. Although the use of these applicators has gained in popularity, the dosimetric characteristics have not been independently verified. Additionally, there is no recognized method of output verification for quality assurance procedures with applicators like these. Methods: This work aims to create a cohesive method of output verification that can be used to determine the dose at the treatment surface as part of a quality assurance/commissioning process for surface applicators used with HDR electronic brachytherapy sources (Part I) and{sup 192}Ir sources (Part II). Air-kerma rate measurements for the {sup 192}Ir sources were completed with several models of small-volume ionization chambers to obtain an air-kerma rate at the treatment surface for each applicator. Correction factors were calculated using MCNP5 and EGSnrc Monte Carlo codes in order to determine an applicator-specific absorbed dose to water at the treatment surface from the measured air-kerma rate. Additionally, relative dose measurements of the surface dose distributions and characteristic depth dose curves were completed in-phantom. Results: Theoretical dose distributions and depth dose curves were generated for each applicator and agreed well with the measured values. A method of output verification was created that allows users to determine the applicator-specific dose to water at the treatment surface based on a measured air-kerma rate. Conclusions: The novel output verification methods described in this work will reduce uncertainties in dose delivery for treatments with these kinds of surface applicators, ultimately improving patient care.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

SU-E-T-802: Verification of Implanted Cardiac Pacemaker Doses in Intensity-Modulated Radiation Therapy: Dose Prediction Accuracy and Reduction Effect of a Lead Sheet

Purpose: To verify delivered doses on the implanted cardiac pacemaker, predicted doses with and without dose reduction method were verified using the MOSFET detectors in terms of beam delivery and dose calculation techniques in intensity-modulated radiation therapy (IMRT). Methods: The pacemaker doses for a patient with a tongue cancer were predicted according to the beam delivery methods [step-and-shoot (SS) and sliding window (SW)], intensity levels for dose optimization, and dose calculation algorithms. Dosimetric effects on the pacemaker were calculated three dose engines: pencil-beam convolution (PBC), analytical anisotropic algorithm (AAA), and Acuros-XB. A lead shield of 2 mm thickness was designed for minimizing irradiated doses to the pacemaker. Dose variations affected by the heterogeneous material properties of the pacemaker and effectiveness of the lead shield were predicted by the Acuros-XB. Dose prediction accuracy and the feasibility of the dose reduction strategy were verified based on the measured skin doses right above the pacemaker using mosfet detectors during the radiation treatment. Results: The Acuros-XB showed underestimated skin doses and overestimated doses by the lead-shield effect, even though the lower dose disagreement was observed. It led to improved dose prediction with higher intensity level of dose optimization in IMRT. The dedicated tertiary lead sheet effectively achieved reduction of pacemaker dose up to 60%. Conclusion: The current SS technique could deliver lower scattered doses than recommendation criteria, however, use of the lead sheet contributed to reduce scattered doses.Thin lead plate can be a useful tertiary shielder and it could not acuse malfunction or electrical damage of the implanted pacemaker in IMRT. It is required to estimate more accurate scattered doses of the patient with medical device to design proper dose reduction strategy.

60 APPLIED LIFE SCIENCES↗

Comparison of methods for the measurement of radiation dose distributions in high dose rate (HDR) brachytherapy: Ge-doped optical fiber, EBT3 Gafchromic film, and PRESAGE{sup Registered-Sign} radiochromic plastic

Purpose: Dose distribution measurement in clinical high dose rate (HDR) brachytherapy is challenging, because of the high dose gradients, large dose variations, and small scale, but it is essential to verify accurate treatment planning and treatment equipment performance. The authors compare and evaluate three dosimetry systems for potential use in brachytherapy dose distribution measurement: Ge-doped optical fibers, EBT3 Gafchromic film with multichannel analysis, and the radiochromic material PRESAGE{sup Registered-Sign} with optical-CT readout. Methods: Ge-doped SiO{sub 2} fibers with 6 {mu}m active core and 5.0 mm length were sensitivity-batched and their thermoluminescent properties used via conventional heating and annealing cycles. EBT3 Gafchromic film of 30 {mu}m active thickness was calibrated in three color channels using a nominal 6 MV linear accelerator. A 48-bit transmission scanner and advanced multichannel analysis method were utilized to derive dose measurements. Samples of the solid radiochromic polymer PRESAGE{sup Registered-Sign }, 60 mm diameter and 100 mm height, were analyzed with a parallel beam optical CT scanner. Each dosimetry system was used to measure the dose as a function of radial distance from a Co-60 HDR source, with results compared to Monte Carlo TG-43 model data. Each system was then used to measure the dose distribution along one or more lines through typical clinical dose distributions for cervix brachytherapy, with results compared to treatment planning system (TPS) calculations. Purpose-designed test objects constructed of Solid Water and held within a full-scatter water tank were utilized. Results: All three dosimetry systems reproduced the general shape of the isolated source radial dose function and the TPS dose distribution. However, the dynamic range of EBT3 exceeded those of doped optical fibers and PRESAGE{sup Registered-Sign }, and the latter two suffered from unacceptable noise and artifact. For the experimental conditions used in this study, the useful range from an isolated HDR source was 5-40 mm for fibers, 3-50 mm for EBT3, and 4-21 mm for PRESAGE{sup Registered-Sign }. Fibers demonstrated some over-response at very low dose levels, suffered from volume averaging effects in the dose distribution measurement, and exhibited up to 9% repeatability variation over three repeated measurements. EBT3 demonstrated excellent agreement with Monte Carlo and TPS dose distributions, with up to 3% repeatability over three measurements. PRESAGE{sup Registered-Sign} gave promising results, being the only true 3D dosimeter, but artifacts and noise were apparent. Conclusions: The comparative response of three emerging dosimetry systems for clinical brachytherapy dose distribution measurement has been investigated. Ge-doped optical fibers have excellent spatial resolution for single-direction measurement but are currently too large for complex dose distribution assessment. The use of PRESAGE{sup Registered-Sign} with optical-CT readout gave promising results in the measurement of true 3D dose distributions but further development work is required to reduce noise and improve dynamic range for brachytherapy dose distribution measurements. EBT3 Gafchromic film with multichannel analysis demonstrated accurate and reproducible measurement of dose distributions in HDR brachytherapy. Calibrated dose measurements were possible with agreement within 1.5% of TPS dose calculations. The suitability of EBT3 as a dosimeter for 2D quality control or commissioning work has been demonstrated.

62 RADIOLOGY AND NUCLEAR MEDICINE↗