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At least 1,027 records · Page 57

WE-F-BRB-00: New Developments in Knowledge-Based Treatment Planning and Automation

Advancements in informatics in radiotherapy are opening up opportunities to improve our ability to assess treatment plans. Models on individualizing patient dose constraints from prior patient data and shape relationships have been extensively researched and are now making their way into commercial products. New developments in knowledge based treatment planning involve understanding the impact of the radiation dosimetry on the patient. Akin to radiobiology models that have driven intensity modulated radiotherapy optimization, toxicity and outcome predictions based on treatment plans and prior patient experiences may be the next step in knowledge based planning. In order to realize these predictions, it is necessary to understand how the clinical information can be captured, structured and organized with ontologies and databases designed for recall. Large databases containing radiation dosimetry and outcomes present the opportunity to evaluate treatment plans against predictions of toxicity and disease response. Such evaluations can be based on dose volume histogram or even the full 3-dimensional dose distribution and its relation to the critical anatomy. This session will provide an understanding of ontologies and standard terminologies used to capture clinical knowledge into structured databases; How data can be organized and accessed to utilize the knowledge in planning; and examples of research and clinical efforts to incorporate that clinical knowledge into planning for improved care for our patients. Learning Objectives: Understand the role of standard terminologies, ontologies and data organization in oncology Understand methods to capture clinical toxicity and outcomes in a clinical setting Understand opportunities to learn from clinical data and its application to treatment planning Todd McNutt receives funding from Philips, Elekta and Toshiba for some of the work presented.

60 APPLIED LIFE SCIENCES↗

WE-F-BRB-01: The Power of Ontologies and Standardized Terminologies for Capturing Clinical Knowledge

Advancements in informatics in radiotherapy are opening up opportunities to improve our ability to assess treatment plans. Models on individualizing patient dose constraints from prior patient data and shape relationships have been extensively researched and are now making their way into commercial products. New developments in knowledge based treatment planning involve understanding the impact of the radiation dosimetry on the patient. Akin to radiobiology models that have driven intensity modulated radiotherapy optimization, toxicity and outcome predictions based on treatment plans and prior patient experiences may be the next step in knowledge based planning. In order to realize these predictions, it is necessary to understand how the clinical information can be captured, structured and organized with ontologies and databases designed for recall. Large databases containing radiation dosimetry and outcomes present the opportunity to evaluate treatment plans against predictions of toxicity and disease response. Such evaluations can be based on dose volume histogram or even the full 3-dimensional dose distribution and its relation to the critical anatomy. This session will provide an understanding of ontologies and standard terminologies used to capture clinical knowledge into structured databases; How data can be organized and accessed to utilize the knowledge in planning; and examples of research and clinical efforts to incorporate that clinical knowledge into planning for improved care for our patients. Learning Objectives: Understand the role of standard terminologies, ontologies and data organization in oncology Understand methods to capture clinical toxicity and outcomes in a clinical setting Understand opportunities to learn from clinical data and its application to treatment planning Todd McNutt receives funding from Philips, Elekta and Toshiba for some of the work presented.

60 APPLIED LIFE SCIENCES↗

WE-F-BRB-02: Setting the Stage for Incorporation of Toxicity Measures in Treatment Plan Assessments

Advancements in informatics in radiotherapy are opening up opportunities to improve our ability to assess treatment plans. Models on individualizing patient dose constraints from prior patient data and shape relationships have been extensively researched and are now making their way into commercial products. New developments in knowledge based treatment planning involve understanding the impact of the radiation dosimetry on the patient. Akin to radiobiology models that have driven intensity modulated radiotherapy optimization, toxicity and outcome predictions based on treatment plans and prior patient experiences may be the next step in knowledge based planning. In order to realize these predictions, it is necessary to understand how the clinical information can be captured, structured and organized with ontologies and databases designed for recall. Large databases containing radiation dosimetry and outcomes present the opportunity to evaluate treatment plans against predictions of toxicity and disease response. Such evaluations can be based on dose volume histogram or even the full 3-dimensional dose distribution and its relation to the critical anatomy. This session will provide an understanding of ontologies and standard terminologies used to capture clinical knowledge into structured databases; How data can be organized and accessed to utilize the knowledge in planning; and examples of research and clinical efforts to incorporate that clinical knowledge into planning for improved care for our patients. Learning Objectives: Understand the role of standard terminologies, ontologies and data organization in oncology Understand methods to capture clinical toxicity and outcomes in a clinical setting Understand opportunities to learn from clinical data and its application to treatment planning Todd McNutt receives funding from Philips, Elekta and Toshiba for some of the work presented.

60 APPLIED LIFE SCIENCES↗

WE-F-BRB-03: Inclusion of Data-Driven Risk Predictions in Radiation Treatment Planning in the Context of a Local Level Learning Health System

Advancements in informatics in radiotherapy are opening up opportunities to improve our ability to assess treatment plans. Models on individualizing patient dose constraints from prior patient data and shape relationships have been extensively researched and are now making their way into commercial products. New developments in knowledge based treatment planning involve understanding the impact of the radiation dosimetry on the patient. Akin to radiobiology models that have driven intensity modulated radiotherapy optimization, toxicity and outcome predictions based on treatment plans and prior patient experiences may be the next step in knowledge based planning. In order to realize these predictions, it is necessary to understand how the clinical information can be captured, structured and organized with ontologies and databases designed for recall. Large databases containing radiation dosimetry and outcomes present the opportunity to evaluate treatment plans against predictions of toxicity and disease response. Such evaluations can be based on dose volume histogram or even the full 3-dimensional dose distribution and its relation to the critical anatomy. This session will provide an understanding of ontologies and standard terminologies used to capture clinical knowledge into structured databases; How data can be organized and accessed to utilize the knowledge in planning; and examples of research and clinical efforts to incorporate that clinical knowledge into planning for improved care for our patients. Learning Objectives: Understand the role of standard terminologies, ontologies and data organization in oncology Understand methods to capture clinical toxicity and outcomes in a clinical setting Understand opportunities to learn from clinical data and its application to treatment planning Todd McNutt receives funding from Philips, Elekta and Toshiba for some of the work presented.

60 APPLIED LIFE SCIENCES↗

Influence of source batch S{sub K} dispersion on dosimetry for prostate cancer treatment with permanent implants

Purpose: In clinical practice, specific air kerma strength (S{sub K}) value is used in treatment planning system (TPS) permanent brachytherapy implant calculations with {sup 125}I and {sup 103}Pd sources; in fact, commercial TPS provide only one S{sub K} input value for all implanted sources and the certified shipment average is typically used. However, the value for S{sub K} is dispersed: this dispersion is not only due to the manufacturing process and variation between different source batches but also due to the classification of sources into different classes according to their S{sub K} values. The purpose of this work is to examine the impact of S{sub K} dispersion on typical implant parameters that are used to evaluate the dose volume histogram (DVH) for both planning target volume (PTV) and organs at risk (OARs). Methods: The authors have developed a new algorithm to compute dose distributions with different S{sub K} values for each source. Three different prostate volumes (20, 30, and 40 cm{sup 3}) were considered and two typical commercial sources of different radionuclides were used. Using a conventional TPS, clinically accepted calculations were made for {sup 125}I sources; for the palladium, typical implants were simulated. To assess the many different possible S{sub K} values for each source belonging to a class, the authors assigned an S{sub K} value to each source in a randomized process 1000 times for each source and volume. All the dose distributions generated for each set of simulations were assessed through the DVH distributions comparing with dose distributions obtained using a uniform S{sub K} value for all the implanted sources. The authors analyzed several dose coverage (V{sub 100} and D{sub 90}) and overdosage parameters for prostate and PTV and also the limiting and overdosage parameters for OARs, urethra and rectum. Results: The parameters analyzed followed a Gaussian distribution for the entire set of computed dosimetries. PTV and prostate V{sub 100} and D{sub 90} variations ranged between 0.2% and 1.78% for both sources. Variations for the overdosage parameters V{sub 150} and V{sub 200} compared to dose coverage parameters were observed and, in general, variations were larger for parameters related to {sup 125}I sources than {sup 103}Pd sources. For OAR dosimetry, variations with respect to the reference D{sub 0.1cm{sup 3}} were observed for rectum values, ranging from 2% to 3%, compared with urethra values, which ranged from 1% to 2%. Conclusions: Dose coverage for prostate and PTV was practically unaffected by S{sub K} dispersion, as was the maximum dose deposited in the urethra due to the implant technique geometry. However, the authors observed larger variations for the PTV V{sub 150}, rectum V{sub 100}, and rectum D{sub 0.1cm{sup 3}} values. The variations in rectum parameters were caused by the specific location of sources with S{sub K} value that differed from the average in the vicinity. Finally, on comparing the two sources, variations were larger for {sup 125}I than for {sup 103}Pd. This is because for {sup 103}Pd, a greater number of sources were used to obtain a valid dose distribution than for {sup 125}I, resulting in a lower variation for each S{sub K} value for each source (because the variations become averaged out statistically speaking)

60 APPLIED LIFE SCIENCES↗

Technical Note: MRI only prostate radiotherapy planning using the statistical decomposition algorithm

Purpose: In order to enable a magnetic resonance imaging (MRI) only workflow in radiotherapy treatment planning, methods are required for generating Hounsfield unit (HU) maps (i.e., synthetic computed tomography, sCT) for dose calculations, directly from MRI. The Statistical Decomposition Algorithm (SDA) is a method for automatically generating sCT images from a single MR image volume, based on automatic tissue classification in combination with a model trained using a multimodal template material. This study compares dose calculations between sCT generated by the SDA and conventional CT in the male pelvic region. Methods: The study comprised ten prostate cancer patients, for whom a 3D T2 weighted MRI and a conventional planning CT were acquired. For each patient, sCT images were generated from the acquired MRI using the SDA. In order to decouple the effect of variations in patient geometry between imaging modalities from the effect of uncertainties in the SDA, the conventional CT was nonrigidly registered to the MRI to assure that their geometries were well aligned. For each patient, a volumetric modulated arc therapy plan was created for the registered CT (rCT) and recalculated for both the sCT and the conventional CT. The results were evaluated using several methods, including mean average error (MAE), a set of dose-volume histogram parameters, and a restrictive gamma criterion (2% local dose/1 mm). Results: The MAE within the body contour was 36.5 ± 4.1 (1 s.d.) HU between sCT and rCT. Average mean absorbed dose difference to target was 0.0% ± 0.2% (1 s.d.) between sCT and rCT, whereas it was −0.3% ± 0.3% (1 s.d.) between CT and rCT. The average gamma pass rate was 99.9% for sCT vs rCT, whereas it was 90.3% for CT vs rCT. Conclusions: The SDA enables a highly accurate MRI only workflow in prostate radiotherapy planning. The dosimetric uncertainties originating from the SDA appear negligible and are notably lower than the uncertainties introduced by variations in patient geometry between imaging sessions.

60 APPLIED LIFE SCIENCES↗

Radiotherapy for stage I seminoma of the testis: Organ equivalent dose to partially in-field structures and second cancer risk estimates on the basis of a mechanistic, bell-shaped, and plateau model

Purpose: The aim of the current study was to (a) calculate the organ equivalent dose (OED) and (b) estimate the associated second cancer risk to partially in-field critical structures from adjuvant radiotherapy for stage I seminoma of the testis on the basis of three different nonlinear risk models. Methods: Three-dimensional plans were created for twelve patients who underwent a treatment planning computed tomography of the abdomen. The plans for irradiation of seminoma consisted of para-aortic anteroposterior and posteroanterior fields giving 20 Gy to the target site with 6 MV photons. The OED of stomach, colon, liver, pancreas, and kidneys, that were partially included in the treatment volume, was calculated using differential dose–volume histograms. The mechanistic, bell-shaped, and plateau models were employed for these calculations provided that organ-specific parameters were available for the subsequent assessment of the excess absolute risk (EAR) for second cancer development. The estimated organ-specific lifetime risks were compared with the respective nominal intrinsic probabilities for cancer induction. Results: The mean OED, which was calculated from the patients’ treatment plans, varied from 0.54 to 6.61 Gy by the partially in-field organ of interest and the model used for dosimetric calculations. The difference between the OED of liver derived from the mechanistic model with those from the bell-shaped and plateau models was less than 1.8%. An even smaller deviation of 1.0% was observed for colon. For the rest organs of interest, the differences between the OED values obtained by the examined models varied from 8.6% to 50.0%. The EAR for stomach, colon, liver, pancreas, and kidney cancer induction at an age of 70 yr because of treatment of a typical 39-yr-old individual was up to 4.24, 11.39, 0.91, 3.04, and 0.14 per 10 000 persons-yr, respectively. Patient’s irradiation was found to elevate the lifetime intrinsic risks by 8.3%–63.0% depending upon the organ of interest and the model employed for risk analysis. Conclusions: Radiotherapy for stage I seminoma of the testis may result in an excess risk for the appearance of secondary malignancies in partially in-field organs. The organ- and model-dependent second cancer risk assessments of this study may be of value for patient counseling and follow-up.

60 APPLIED LIFE SCIENCES↗

Quantifying the performance of in vivo portal dosimetry in detecting four types of treatment parameter variations

Purpose: To quantify the ability of electronic portal imaging device (EPID) dosimetry used during treatment (in vivo) in detecting variations that can occur in the course of patient treatment. Methods: Images of transmitted radiation from in vivo EPID measurements were converted to a 2D planar dose at isocenter and compared to the treatment planning dose using a prototype software system. Using the treatment planning system (TPS), four different types of variability were modeled: overall dose scaling, shifting the positions of the multileaf collimator (MLC) leaves, shifting of the patient position, and changes in the patient body contour. The gamma pass rate was calculated for the modified and unmodified plans and used to construct a receiver operator characteristic (ROC) curve to assess the detectability of the different parameter variations. The detectability is given by the area under the ROC curve (AUC). The TPS was also used to calculate the impact of the variations on the target dose–volume histogram. Results: Nine intensity modulation radiation therapy plans were measured for four different anatomical sites consisting of 70 separate fields. Results show that in vivo EPID dosimetry was most sensitive to variations in the machine output, AUC = 0.70 − 0.94, changes in patient body habitus, AUC = 0.67 − 0.88, and systematic shifts in the MLC bank positions, AUC = 0.59 − 0.82. These deviations are expected to have a relatively small clinical impact [planning target volume (PTV) D{sub 99} change <7%]. Larger variations have even higher detectability. Displacements in the patient’s position and random variations in MLC leaf positions were not readily detectable, AUC < 0.64. The D{sub 99} of the PTV changed by up to 57% for the patient position shifts considered here. Conclusions: In vivo EPID dosimetry is able to detect relatively small variations in overall dose, systematic shifts of the MLC’s, and changes in the patient habitus. Shifts in the patient’s position which can introduce large changes in the target dose coverage were not readily detected.

60 APPLIED LIFE SCIENCES↗

Improved accuracy of quantitative parameter estimates in dynamic contrast-enhanced CT study with low temporal resolution

Purpose: A previously proposed method to reduce radiation dose to patient in dynamic contrast-enhanced (DCE) CT is enhanced by principal component analysis (PCA) filtering which improves the signal-to-noise ratio (SNR) of time-concentration curves in the DCE-CT study. The efficacy of the combined method to maintain the accuracy of kinetic parameter estimates at low temporal resolution is investigated with pixel-by-pixel kinetic analysis of DCE-CT data. Methods: The method is based on DCE-CT scanning performed with low temporal resolution to reduce the radiation dose to the patient. The arterial input function (AIF) with high temporal resolution can be generated with a coarsely sampled AIF through a previously published method of AIF estimation. To increase the SNR of time-concentration curves (tissue curves), first, a region-of-interest is segmented into squares composed of 3 × 3 pixels in size. Subsequently, the PCA filtering combined with a fraction of residual information criterion is applied to all the segmented squares for further improvement of their SNRs. The proposed method was applied to each DCE-CT data set of a cohort of 14 patients at varying levels of down-sampling. The kinetic analyses using the modified Tofts’ model and singular value decomposition method, then, were carried out for each of the down-sampling schemes between the intervals from 2 to 15 s. The results were compared with analyses done with the measured data in high temporal resolution (i.e., original scanning frequency) as the reference. Results: The patients’ AIFs were estimated to high accuracy based on the 11 orthonormal bases of arterial impulse responses established in the previous paper. In addition, noise in the images was effectively reduced by using five principal components of the tissue curves for filtering. Kinetic analyses using the proposed method showed superior results compared to those with down-sampling alone; they were able to maintain the accuracy in the quantitative histogram parameters of volume transfer constant [standard deviation (SD), 98th percentile, and range], rate constant (SD), blood volume fraction (mean, SD, 98th percentile, and range), and blood flow (mean, SD, median, 98th percentile, and range) for sampling intervals between 10 and 15 s. Conclusions: The proposed method of PCA filtering combined with the AIF estimation technique allows low frequency scanning for DCE-CT study to reduce patient radiation dose. The results indicate that the method is useful in pixel-by-pixel kinetic analysis of DCE-CT data for patients with cervical cancer.

61 RADIATION PROTECTION AND DOSIMETRY↗

Computer-aided diagnosis for classifying benign versus malignant thyroid nodules based on ultrasound images: A comparison with radiologist-based assessments

Purpose: To develop a semiautomated computer-aided diagnosis (CAD) system for thyroid cancer using two-dimensional ultrasound images that can be used to yield a second opinion in the clinic to differentiate malignant and benign lesions. Methods: A total of 118 ultrasound images that included axial and longitudinal images from patients with biopsy-confirmed malignant (n = 30) and benign (n = 29) nodules were collected. Thyroid CAD software was developed to extract quantitative features from these images based on thyroid nodule segmentation in which adaptive diffusion flow for active contours was used. Various features, including histogram, intensity differences, elliptical fit, gray-level co-occurrence matrixes, and gray-level run-length matrixes, were evaluated for each region imaged. Based on these imaging features, a support vector machine (SVM) classifier was used to differentiate benign and malignant nodules. Leave-one-out cross-validation with sequential forward feature selection was performed to evaluate the overall accuracy of this method. Additionally, analyses with contingency tables and receiver operating characteristic (ROC) curves were performed to compare the performance of CAD with visual inspection by expert radiologists based on established gold standards. Results: Most univariate features for this proposed CAD system attained accuracies that ranged from 78.0% to 83.1%. When optimal SVM parameters that were established using a grid search method with features that radiologists use for visual inspection were employed, the authors could attain rates of accuracy that ranged from 72.9% to 84.7%. Using leave-one-out cross-validation results in a multivariate analysis of various features, the highest accuracy achieved using the proposed CAD system was 98.3%, whereas visual inspection by radiologists reached 94.9% accuracy. To obtain the highest accuracies, “axial ratio” and “max probability” in axial images were most frequently included in the optimal feature sets for the authors’ proposed CAD system, while “shape” and “calcification” in longitudinal images were most frequently included in the optimal feature sets for visual inspection by radiologists. The computed areas under curves in the ROC analysis were 0.986 and 0.979 for the proposed CAD system and visual inspection by radiologists, respectively; no significant difference was detected between these groups. Conclusions: The use of thyroid CAD to differentiate malignant from benign lesions shows accuracy similar to that obtained via visual inspection by radiologists. Thyroid CAD might be considered a viable way to generate a second opinion for radiologists in clinical practice.

61 RADIATION PROTECTION AND DOSIMETRY↗

Evaluation of a commercial MRI Linac based Monte Carlo dose calculation algorithm with GEANT 4

Purpose: This paper provides a comparison between a fast, commercial, in-patient Monte Carlo dose calculation algorithm (GPUMCD) and GEANT4. It also evaluates the dosimetric impact of the application of an external 1.5 T magnetic field. Methods: A stand-alone version of the Elekta™ GPUMCD algorithm, to be used within the Monaco treatment planning system to model dose for the Elekta™ magnetic resonance imaging (MRI) Linac, was compared against GEANT4 (v10.1). This was done in the presence or absence of a 1.5 T static magnetic field directed orthogonally to the radiation beam axis. Phantoms with material compositions of water, ICRU lung, ICRU compact-bone, and titanium were used for this purpose. Beams with 2 MeV monoenergetic photons as well as a 7 MV histogrammed spectrum representing the MRI Linac spectrum were emitted from a point source using a nominal source-to-surface distance of 142.5 cm. Field sizes ranged from 1.5 × 1.5 to 10 × 10 cm{sup 2}. Dose scoring was performed using a 3D grid comprising 1 mm{sup 3} voxels. The production thresholds were equivalent for both codes. Results were analyzed based upon a voxel by voxel dose difference between the two codes and also using a volumetric gamma analysis. Results: Comparisons were drawn from central axis depth doses, cross beam profiles, and isodose contours. Both in the presence and absence of a 1.5 T static magnetic field the relative differences in doses scored along the beam central axis were less than 1% for the homogeneous water phantom and all results matched within a maximum of ±2% for heterogeneous phantoms. Volumetric gamma analysis indicated that more than 99% of the examined volume passed gamma criteria of 2%—2 mm (dose difference and distance to agreement, respectively). These criteria were chosen because the minimum primary statistical uncertainty in dose scoring voxels was 0.5%. The presence of the magnetic field affects the dose at the interface depending upon the density of the material on either sides of the interface. This effect varies with the field size. For example, at the water-lung interface a 33.94% increase in dose was observed (relative to the D{sub max}), by both GPUMCD and GEANT4 for the field size of 2 × 2 cm{sup 2} (compared to no B-field case), which increased to 47.83% for the field size of 5 × 5 cm{sup 2} in the presence of the magnetic field. Similarly, at the lung-water interface, the dose decreased by 19.21% (relative to D{sub max}) for a field size of 2 × 2 cm{sup 2} and by 30.01% for 5 × 5 cm{sup 2} field size. For more complex combinations of materials the dose deposition also becomes more complex. Conclusions: The GPUMCD algorithm showed good agreement against GEANT4 both in the presence and absence of a 1.5 T external magnetic field. The application of 1.5 T magnetic field significantly alters the dose at the interfaces by either increasing or decreasing the dose depending upon the density of the material on either side of the interfaces.

61 RADIATION PROTECTION AND DOSIMETRY↗

Technical Note: Development and performance of a software tool for quality assurance of online replanning with a conventional Linac or MR-Linac

Purpose: To develop an integrated quality assurance (QA) software tool for online replanning capable of efficiently and automatically checking radiation treatment (RT) planning parameters and gross plan quality, verifying treatment plan data transfer from treatment planning system (TPS) to record and verify (R&V) system, performing a secondary monitor unit (MU) calculation with or without a presence of a magnetic field from MR-Linac, and validating the delivery record consistency with the plan. Methods: The software tool, named ArtQA, was developed to obtain and compare plan and treatment parameters from both the TPS and the R&V system database. The TPS data are accessed via direct file reading and the R&V data are retrieved via open database connectivity and structured query language. Plan quality is evaluated with both the logical consistency of planning parameters and the achieved dose–volume histograms. Beams in between the TPS and R&V system are matched based on geometry configurations. To consider the effect of a 1.5 T transverse magnetic field from MR-Linac in the secondary MU calculation, a method based on modified Clarkson integration algorithm was developed and tested for a series of clinical situations. Results: ArtQA has been used in their clinic and can quickly detect inconsistencies and deviations in the entire RT planning process. With the use of the ArtQA tool, the efficiency for plan check including plan quality, data transfer, and delivery check can be improved by at least 60%. The newly developed independent MU calculation tool for MR-Linac reduces the difference between the plan and calculated MUs by 10%. Conclusions: The software tool ArtQA can be used to perform a comprehensive QA check from planning to delivery with conventional Linac or MR-Linac and is an essential tool for online replanning where the QA check needs to be performed rapidly.

60 APPLIED LIFE SCIENCES↗

Radiation dose and cancer risk to out-of-field and partially in-field organs from radiotherapy for symptomatic vertebral hemangiomas

Purpose: Vertebral hemangiomas (VHs) are the most common benign tumors of the spine that may cause bone resorption. Megavoltage irradiation is usually the treatment of choice for the management of symptomatic VHs. The current study was conducted to estimate the risk for carcinogenesis from radiotherapy of this benign disease on the basis of the calculated radiation doses to healthy organs. Methods: The Monte Carlo N-particle transport code was employed to simulate the irradiation with 6 MV x-rays of a VH presented in the cervical, upper thoracic, lower thoracic, and lumbar spine. The average radiation dose (D{sub av}) received by each critical organ located outside the primarily irradiated area was calculated. Three-dimensional treatment plans were also generated for the VHs occurring at the four different sites of the spinal cord based on patients’ computed tomography data. The organ equivalent dose (OED) to each radiosensitive structure, which was partly encompassed by the applied treatment fields, was calculated with the aid of differential dose–volume histograms. The D{sub av} and the OED values were combined with a linear-no-threshold model and a nonlinear mechanistic model, respectively, to estimate the organ-, age-, and gender-specific lifetime attributable risks (LARs) for cancer development. The estimated risks were compared with the respective nominal lifetime intrinsic risks (LIRs) for the unexposed population. Results: For a standard target dose of 34 Gy, the OED varied from 0.39–5.15 Gy by the organ of interest and the irradiation site. The D{sub av} range for the out-of-field organs was 4.9 × 10{sup −4} to 0.56 Gy. The LAR for the appearance of malignancies in the partially in-field organs after radiotherapy of male and female patients was (0.08%–1.8%) and (0.09%–1.9%), respectively. These risk values were 1.5–15.5 times lower when compared to the respective LIRs. The lifetime probability for out-of-field cancer induction in irradiated males and females was (2.5 × 10{sup −4} to 7.7 × 10{sup −2})% and (1.4 × 10{sup −4} to 2.6 × 10{sup −1})%, respectively. The above risks were one to four orders of magnitude lower than the LIRs. Conclusions: The probability for the development of out-of-field malignancies due to radiotherapy for VHs is trivial with respect to the nominal risk for unexposed population. The respective cancer risks to partially in-field organs are smaller than the nominal probabilities but they should not be considered as inconsiderable. These risks may be taken into account during the follow-up of patients treated for a symptomatic VH.

60 APPLIED LIFE SCIENCES↗

Potential benefits of dosimetric VMAT tracking verified with 3D film measurements

Purpose: To evaluate three different plan adaptation strategies using 3D film-stack dose measurements of both focal boost and hypofractionated prostate VMAT treatments. The adaptation strategies (a couch shift, geometric tracking, and dosimetric tracking) were applied for three realistic intrafraction prostate motions. Methods: A focal boost (35 × 2.2 and 35 × 2.7 Gy) and a hypofractionated (5 × 7.25 Gy) prostate VMAT plan were created for a heterogeneous phantom that allows for internal prostate motion. For these plans geometric tracking and dosimetric tracking were evaluated by ionization chamber (IC) point dose measurements (zero-D) and measurements using a stack of EBT3 films (3D). The geometric tracking applied translations, rotations, and scaling of the MLC aperture in response to realistic prostate motions. The dosimetric tracking additionally corrected the monitor units to resolve variations due to difference in depth, tissue heterogeneity, and MLC-aperture. The tracking was based on the positions of four fiducial points only. The film measurements were compared to the gold standard (i.e., IC measurements) and the planned dose distribution. Additionally, the 3D measurements were converted to dose volume histograms, tumor control probability, and normal tissue complication probability parameters (DVH/TCP/NTCP) as a direct estimate of clinical relevance of the proposed tracking. Results: Compared to the planned dose distribution, measurements without prostate motion and tracking showed already a reduced homogeneity of the dose distribution. Adding prostate motion further blurs the DVHs for all treatment approaches. The clinical practice (no tracking) delivered the dose distribution inside the PTV but off target (CTV), resulting in boost dose errors up to 10%. The geometric and dosimetric tracking corrected the dose distribution’s position. Moreover, the dosimetric tracking could achieve the planned boost DVH, but not the DVH of the more homogeneously irradiated prostate. A drawback of both the geometric and dosimetric tracking was a reduced MLC blocking caused by the rotational component of the MLC aperture corrections. Because of the used CTV to PTV margins and the high doses in the considered fractionation schemes, the TCP differed less than 0.02 from the planned value for all targets and all correction methods. The rectal NTCP constraints, however, could not be realized using any of these methods. Conclusions: The geometric and dosimetric tracking use only a limited input, but they deposit the dose distribution with higher geometric accuracy than the clinical practice. The latter case has boost dose errors up to 10%. The increased accuracy has a modest impact [Δ(NT)CP < 0.02] because of the applied margins and the high dose levels used. To allow further margin reduction tracking methods are vital. The proposed methodology could further be improved by implementing a rotational correction using collimator rotations.

60 APPLIED LIFE SCIENCES↗

Technical Note: Statistical dependences between channels in radiochromic film readings. Implications in multichannel dosimetry

Purpose: This note studies the statistical relationships between color channels in radiochromic film readings with flatbed scanners. The same relationships are studied for noise. Finally, their implications for multichannel film dosimetry are discussed. Methods: Radiochromic films exposed to wedged fields of 6 MV energy were read in a flatbed scanner. The joint histograms of pairs of color channels were used to obtain the joint and conditional probability density functions between channels. Then, the conditional expectations and variances of one channel given another channel were obtained. Noise was extracted from film readings by means of a multiresolution analysis. Two different dose ranges were analyzed, the first one ranging from 112 to 473 cGy and the second one from 52 to 1290 cGy. Results: For the smallest dose range, the conditional expectations of one channel given another channel can be approximated by linear functions, while the conditional variances are fairly constant. The slopes of the linear relationships between channels can be used to simplify the expression that estimates the dose by means of the multichannel method. The slopes of the linear relationships between each channel and the red one can also be interpreted as weights in the final contribution to dose estimation. However, for the largest dose range, the conditional expectations of one channel given another channel are no longer linear functions. Finally, noises in different channels were found to correlate weakly. Conclusions: Signals present in different channels of radiochromic film readings show a strong statistical dependence. By contrast, noise correlates weakly between channels. For the smallest dose range analyzed, the linear behavior between the conditional expectation of one channel given another channel can be used to simplify calculations in multichannel film dosimetry.

60 APPLIED LIFE SCIENCES↗

Nanoscale measurements of proton tracks using fluorescent nuclear track detectors

Purpose: The authors describe a method in which fluorescence nuclear track detectors (FNTDs), novel track detectors with nanoscale spatial resolution, are used to determine the linear energy transfer (LET) of individual proton tracks from proton therapy beams by allowing visualization and 3D reconstruction of such tracks. Methods: FNTDs were exposed to proton therapy beams with nominal energies ranging from 100 to 250 MeV. Proton track images were then recorded by confocal microscopy of the FNTDs. Proton tracks in the FNTD images were fit by using a Gaussian function to extract fluorescence amplitudes. Histograms of fluorescence amplitudes were then compared with LET spectra. Results: The authors successfully used FNTDs to register individual proton tracks from high-energy proton therapy beams, allowing reconstruction of 3D images of proton tracks along with delta rays. The track amplitudes from FNTDs could be used to parameterize LET spectra, allowing the LET of individual proton tracks from therapeutic proton beams to be determined. Conclusions: FNTDs can be used to directly visualize proton tracks and their delta rays at the nanoscale level. Because the track intensities in the FNTDs correlate with LET, they could be used further to measure LET of individual proton tracks. This method may be useful for measuring nanoscale radiation quantities and for measuring the LET of individual proton tracks in radiation biology experiments.

60 APPLIED LIFE SCIENCES↗

Impact of SPECT corrections on 3D-dosimetry for liver transarterial radioembolization using the patient relative calibration methodology

Purpose: Many centers aim to plan liver transarterial radioembolization (TARE) with dosimetry, even without CT-based attenuation correction (AC), or with unoptimized scatter correction (SC) methods. This work investigates the impact of presence vs absence of such corrections, and limited spatial resolution, on 3D dosimetry for TARE. Methods: Three voxelized phantoms were derived from CT images of real patients with different body sizes. Simulations of {sup 99m}Tc-SPECT projections were performed with the SIMIND code, assuming three activity distributions in the liver: uniform, inside a “liver’s segment,” or distributing multiple uptaking nodules (“nonuniform liver”), with a tumoral liver/healthy parenchyma ratio of 5:1. Projection data were reconstructed by a commercial workstation, with OSEM protocol not specifically optimized for dosimetry (spatial resolution of 12.6 mm), with/without SC (optimized, or with parameters predefined by the manufacturer; dual energy window), and with/without AC. Activity in voxels was calculated by a relative calibration, assuming identical microspheres and {sup 99m}Tc-SPECT counts spatial distribution. 3D dose distributions were calculated by convolution with {sup 90}Y voxel S-values, assuming permanent trapping of microspheres. Cumulative dose-volume histograms in lesions and healthy parenchyma from different reconstructions were compared with those obtained from the reference biodistribution (the “gold standard,” GS), assessing differences for D95%, D70%, and D50% (i.e., minimum value of the absorbed dose to a percentage of the irradiated volume). γ tool analysis with tolerance of 3%/13 mm was used to evaluate the agreement between GS and simulated cases. The influence of deep-breathing was studied, blurring the reference biodistributions with a 3D anisotropic gaussian kernel, and performing the simulations once again. Results: Differences of the dosimetric indicators were noticeable in some cases, always negative for lesions and distributed around zero for parenchyma. Application of AC and SC reduced systematically the differences for lesions by 5%–14% for a liver segment, and by 7%–12% for a nonuniform liver. For parenchyma, the data trend was less clear, but the overall range of variability passed from −10%/40% for a liver segment, and −10%/20% for a nonuniform liver, to −13%/6% in both cases. Applying AC, SC with preset parameters gave similar results to optimized SC, as confirmed by γ tool analysis. Moreover, γ analysis confirmed that solely AC and SC are not sufficient to obtain accurate 3D dose distribution. With breathing, the accuracy worsened severely for all dosimetric indicators, above all for lesions: with AC and optimized SC, −38%/−13% in liver’s segment, −61%/−40% in the nonuniform liver. For parenchyma, D50% resulted always less sensitive to breathing and sub-optimal correction methods (difference overall range: −7%/13%). Conclusions: Reconstruction protocol optimization, AC, SC, PVE and respiratory motion corrections should be implemented to obtain the best possible dosimetric accuracy. On the other side, thanks to the relative calibration, D50% inaccuracy for the healthy parenchyma from absence of AC was less than expected, while the optimization of SC was scarcely influent. The relative calibration therefore allows to perform TARE planning, basing on D50% for the healthy parenchyma, even without AC or with suboptimal corrections, rather than rely on nondosimetric methods.

60 APPLIED LIFE SCIENCES↗

Four-dimensional dose reconstruction through in vivo phase matching of cine images of electronic portal imaging device

Purpose: A method is proposed to reconstruct a four-dimensional (4D) dose distribution using phase matching of measured cine images to precalculated images of electronic portal imaging device (EPID). Methods: (1) A phantom, designed to simulate a tumor in lung (a polystyrene block with a 3 cm diameter embedded in cork), was placed on a sinusoidally moving platform with an amplitude of 1 cm and a period of 4 s. Ten-phase 4D computed tomography (CT) images of the phantom were acquired. A planning target volume (PTV) was created by adding a margin of 1 cm around the internal target volume of the tumor. (2) Three beams were designed, which included a static beam, a theoretical dynamic beam, and a planning-optimized dynamic beam (PODB). While the theoretical beam was made by manually programming a simplistic sliding leaf motion, the planning-optimized beam was obtained from treatment planning. From the three beams, three-dimensional (3D) doses on the phantom were calculated; 4D dose was calculated by means of the ten phase images (integrated over phases afterward); serving as “reference” images, phase-specific EPID dose images under the lung phantom were also calculated for each of the ten phases. (3) Cine EPID images were acquired while the beams were irradiated to the moving phantom. (4) Each cine image was phase-matched to a phase-specific CT image at which common irradiation occurred by intercomparing the cine image with the reference images. (5) Each cine image was used to reconstruct dose in the phase-matched CT image, and the reconstructed doses were summed over all phases. (6) The summation was compared with forwardly calculated 4D and 3D dose distributions. Accounting for realistic situations, intratreatment breathing irregularity was simulated by assuming an amplitude of 0.5 cm for the phantom during a portion of breathing trace in which the phase matching could not be performed. Intertreatment breathing irregularity between the time of treatment and the time of planning CT was considered by utilizing the same reduced amplitude when the phantom was irradiated. To examine the phase matching in a humanoid environment, the matching was also performed in a digital phantom (4D XCAT phantom). Results: For the static, the theoretical, and the planning-optimized dynamic beams, the 4D reconstructed doses showed agreement with the forwardly calculated 4D doses within the gamma pass rates of 92.7%, 100%, and 98.1%, respectively, at the isocenter plane given by 3%/3 mm criteria. Excellent agreement in dose volume histogram of PTV and lung-PTV was also found between the two 4D doses, while substantial differences were found between the 3D and the 4D doses. The significant breathing irregularities modeled in this study were found not to be noticeably affecting the reconstructed dose. The phase matching was performed equally well in a digital phantom. Conclusions: The method of retrospective phase determination of a moving object under irradiation provided successful 4D dose reconstruction. This method will provide accurate quality assurance and facilitate adaptive therapy when distinguishable objects such as well-defined tumors, diaphragm, and organs with markers (pancreas and liver) are covered by treatment beam apertures.

60 APPLIED LIFE SCIENCES↗