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During pregnancy, the use of radiation therapy for cancer treatment is often considered impossible due to the assumed associated fetal risks. However, suboptimal treatment of pregnant cancer patients and unjustifiable delay in radiation therapy until after delivery can be harmful for both patient and child. In non‐pregnant patients, proton‐radiation therapy is increasingly administered because of its favorable dosimetric properties compared with photon‐radiation therapy. Although data on the use of pencil beam scanning proton‐radiation therapy during pregnancy are scarce, different case reports and dosimetric studies have indicated a more than 10‐fold reduction in fetal radiation exposure compared with photon‐radiation therapy. Nonetheless, the implementation of proton‐radiation therapy during pregnancy requires complex fetal dosimetry for the neutron‐dominated out‐of‐field radiation dose and faces a lack of clinical guidelines. Further exploration and standardization of proton‐radiation therapy during pregnancy will be necessary to improve radiotherapeutic management of pregnant women with cancer and further reduce risks for their offspring. [ABSTRACT FROM AUTHOR]

Purpose: The integration of auto‐segmentation and automated treatment planning methods on a fast‐rotating O‐ring linac may improve the time efficiency of online adaptive radiotherapy workflows. This study investigates whether automated treatment planning of prostate SBRT with focal boosting on the O‐ring linac could generate plans that are of similar quality as those obtained through manual planning on clinical C‐arm linacs. Methods: For 20 men with prostate cancer, reference treatment plans were generated on a TrueBeam STx C‐arm linac with HD120 MLC and a TrueBeam C‐arm linac with Millennium 120 MLC using 6 MV flattened dual arc VMAT. Manual planning on the Halcyon fast‐rotating O‐ring linac was performed using 6 MV FFF dual arc VMAT (HA2‐DL10) and triple arc VMAT (HA3‐DL10) to investigate the performance of the dual‐layer MLC system. Automated planning was performed for triple arc VMAT on the Halcyon linac (ET3‐DL10) using the automated planning algorithms of Ethos Treatment Planning. The prescribed dose was 35 Gy to the prostate and 30 Gy to the seminal vesicles in five fractions. The iso‐toxic focal boost to the intraprostatic tumor nodule(s) was aimed to receive up to 50 Gy. Plan deliverability was verified using portal image dosimetry measurements. Results: Compared to the C‐arm linacs, ET3‐DL10 shows increased seminal vesicles PTV coverage (D99%) and reduced high‐dose spillage to the bladder (V37Gy) and urethra (D0.035cc) but this came at the cost of increased high‐dose spillage to the rectum (V38Gy) and a higher intermediate dose spillage (D2cm). No statistically significant differences were found when benchmarking HA2‐DL10 and HA3‐DL10 with the C‐arm linacs. All plans passed the patient‐specific QA tolerance limit. Conclusions: Automated planning of prostate SBRT with focal boosting on the fast‐rotating O‐ring linac is feasible and achieves similar plan quality as those obtained on clinical C‐arm linacs using manual planning. [ABSTRACT FROM AUTHOR]

Purpose: Intrafractional motion during radiotherapy delivery can deteriorate the delivered dose. Dynamic rotational motion of up to 38 degrees has been reported during prostate cancer radiotherapy, but methods to determine the dosimetric consequences of such rotations are lacking. Here, we create and experimentally validate a dose reconstruction method that accounts for dynamic rotations and translations in a commercial treatment planning system (TPS). Interplay effects are quantified by comparing dose reconstructions with dynamic and constant rotations. Methods: The dose reconstruction accumulates the dose in points of interest while the points are moved in six degrees of freedom (6DoF) in a precalculated time‐resolved four‐dimensional (4D) dose matrix to emulate dynamic motion in a patient. The required 4D dose matrix was generated by splitting the original treatment plan into multiple sub‐beams, each representing 0.4 s dose delivery, and recalculating the dose of the split plan in the TPS (Eclipse). The dose accumulation was performed via TPS scripting by querying the dose of each sub‐beam in dynamically moving points, allowing dose reconstruction with any dynamic motion. The dose reconstruction was validated with film dosimetry for two prostate dual arc VMAT plans with intra‐prostatic lesion boosts. The plans were delivered to a pelvis phantom with internal dynamic rotational motion of a film stack (21 films with 2.5 mm separation). Each plan was delivered without motion and with three prostate motion traces. Motion‐including dose reconstruction was performed for each motion experiment using the actual dynamic rotation as well as a constant rotation equal to the mean rotation during the experiment. For each experiment, the 3%/2 mm γ failure rate of the TPS dose reconstruction was calculated with the film measurement being the reference. For each motion experiment, the motion‐induced 3%/2 mm γ failure rate was calculated using the static delivery as the reference and compared between film measurements and TPS dose reconstruction. DVH metrics for RT structures fully contained in the film volume were also compared between film and TPS. Results: The mean γ failure rate of the TPS dose reconstructions when compared to film doses was 0.8% (two static experiments) and 1.7% (six dynamic experiments). The mean (range) of the motion‐induced γ failure rate in film measurements was 35.4% (21.3–59.2%). The TPS dose reconstruction agreed with these experimental γ failure rates with root‐mean‐square errors of 2.1% (dynamic rotation dose reconstruction) and 17.1% (dose reconstruction assuming constant rotation). By DVH metrics, the mean (range) difference between dose reconstructions with dynamic and constant rotation was 4.3% (−0.3–10.6%) (urethra D2%), −0.6% (−5.6%–2.5%) (urethra D99%), 1.1% (−7.1–7.7%) (GTV D2%), −1.4% (−17.4–7.1%) (GTV D95%), −1.2% (−17.1–5.7%) (GTV D99%), and −0.1% (−3.2–7.6%) (GTV mean dose). Dose reconstructions with dynamic motion revealed large interplay effects (cold and hot spots). Conclusions: A method to perform dose reconstructions for dynamic 6DoF motion in a TPS was developed and experimentally validated. It revealed large differences in dose distribution between dynamic and constant rotations not identifiable through dose reconstructions with constant rotation. [ABSTRACT FROM AUTHOR]

Purpose: One of the main sources of uncertainty in proton therapy is the conversion of the Hounsfield Units of the planning CT to (relative) proton stopping powers. Proton radiography provides range error maps but these can be affected by other sources of errors as well as the CT conversion (e.g., residual misalignment). To better understand and quantify range uncertainty, it is desirable to measure the individual contributions and particularly those associated to the CT conversion. Methods: A workflow is proposed to carry out an assessment of the CT conversion solely on the basis of proton radiographs of real tissues measured with a multilayer ionization chamber (MLIC). The workflow consists of a series of four stages: (a) CT and proton radiography acquisitions, (b) CT and proton radiography registration in postprocessing, (c) sample‐specific validation of the semi‐empirical model both used in the registration and to estimate the water equivalent path length (WEPL), and (d) WEPL error estimation. The workflow was applied to a pig head as part of the validation of the CT calibration of the proton therapy center PARTICLE at UZ Leuven, Belgium. Results: The CT conversion‐related uncertainty computed based on the well‐established safety margin rule of 1.2 mm + 2.4% were overestimated by 71% on the pig head. However, the range uncertainty was very much underestimated where cavities were encountered by the protons. Excluding areas with cavities, the overestimation of the uncertainty was 500%. A correlation was found between these localized errors and HUs between −1000 and −950, suggesting that the underestimation was not a consequence of an inaccurate conversion but was probably rather due to the resolution of the CT leading to material mixing at interfaces. To reduce these errors, the CT calibration curve was adapted by increasing the HU interval corresponding to the air up to −950. Conclusion: The application of the workflow as part of the validation of the CT conversion to RSPs showed an overall overestimation of the expected uncertainty. Moreover, the largest WEPL errors were found to be related to the presence of cavities which nevertheless are associated with low WEPL values. This suggests that the use of this workflow on patients or in a generalized study on different types of animal tissues could shed sufficient light on how the contributions to the CT conversion‐related uncertainty add up to potentially reduce up to several millimeters the uncertainty estimations taken into account in treatment planning. All the algorithms required to perform the workflow were implemented in the computational tool named openPR which is part of openREGGUI, an open‐source image processing platform for adaptive proton therapy. [ABSTRACT FROM AUTHOR]

End‐to‐end testing of a new breast radiotherapy technique preferably requires realistic phantom geometries, which is challenging to achieve using currently commercially available solutions. We have developed a series of three‐dimensional (3D)‐printed breast phantoms, with ionization chamber and radiochromic film inserts, which can be attached to a commercial anthropomorphic thorax phantom. A contoured left breast from a patient's planning CT was mapped onto a CT of the CIRS E2E thorax phantom (CIRS Inc.) and cropped to fit the surface. Four versions of the breast were 3D printed, containing a cavity for an ionization chamber and slits for radiochromic film insertion in the three cardinal planes, respectively. The phantoms were fully compatible with surface scanning technology used for setup. The phantoms were validated using a whole‐breast volumetric modulated arc therapy protocol with a simultaneous integrated boost to the tumor bed (VMAT‐SIB). Six patient plans and one original plan on the breast phantom were verified with planar portal imaging, point dose, and film measurements in the MultiCube phantom and planar γ‐analysis using ArcCHECK diode array. Six patient plans were recalculated on the breast phantom (hybrid plans) and delivered with point dose and film measurements with 3% (local)/2 mm γ‐analysis. One complete end‐to‐end test on the breast phantom was performed. All plan quality verifications had point dose differences below 2.4% from the calculated dose and γ‐agreement scores (γAS) > 87.3% for film measurements in the MultiCube, portal dosimetry, and ArcCHECK. Point dose differences in the 3D‐printed phantoms were below 2.6% (median −1.4%, range −2.6%; 0.3%). Median γAS was 96.4% (range 80.1%–99.7%) for all film inserts. The proposed 3D‐printed attachable breast dosimetry phantoms have been shown to be a valuable tool for end‐to‐end testing of a new radiotherapy protocol. The workflow described in this report can aid users to create their own phantom‐specific breast 3D‐printed phantoms. [ABSTRACT FROM AUTHOR]

This work evaluated the use of a class solution specific calibration for an extra-large BaFBr-based optically stimulated luminescence film (OSL; 43 × 35 cm2; Zeff = 4.55). The clinical need for such large dosimeters follows from the increased use of extended-field radiation therapy (EFRT). E.g. for prostate cancer EFRT is currently used in the first prospective trial investigating the benefit of adding elective irradiation of the para-aortic lymph nodes in pN1 prostate cancer. The full extent of these EFRT dose distributions is not covered by the well-established standard sized radiochromic film or 2D detector arrays. Here we investigate an OSL calibration methodology, that tackles BaFBr-based OSL's inherent energy dependence by a class solution specific calibration. 10 EFRT treatment plans used in the PART trial were investigated. One plan was used to build a class solution specific bilinear calibration model, that distinguishes between in-field and penumbra dose contributions. The effect of this calibration was evaluated with respect to a standard linear calibration, using standard IMRT patterns, the nine remaining patient plans, and to smaller prostate treatment plans. A single OSL-dosimeter could be reused for all measurements. The dosimeter captured the full extent of the dose distributions (maximum EFRT field size = 33.5 cm). The bilinear correction reduced the residual dose differences from above 10% to an average of 0.7% (max 3.6%) in comparison with a Monte Carlo simulation. Consequently global gamma agreement scores (3%-3 mm) of 95.5% ± 2.7% were reached. A more strict local evaluation resulted in an average gamma-agreement score of 93.3% ± 3.2%. The BaFBr-based OSL film, with reduced Zeff requires a class-solution specific correction. The current work shows that such a correction can be as simple as a bilinear residual dose correction driven by the measured signal. As far as we know this is the first 2D dosimeter combining reusability, a sub-mm resolution, and a size covering the typical EFRT treatment plans. [ABSTRACT FROM AUTHOR]

Purpose: To validate a normal tissue complication probability (NTCP) model for late unfavourable aesthetic outcome (AO) after breast-conserving therapy. Materials/Methods: The BCCT.core software evaluated the AO using standardized photographs of patients treated at the University Hospitals Leuven between April 2015 and April 2016. Dose maps in 2 Gy equivalents were calculated assuming α/β = 3.6 Gy. The discriminating ability of the model was described by the AUC of the receiver operating characteristic curve. A 95% confidence interval (CI) of AUC was calculated using 10,000 bootstrap replications. Calibration was evaluated with the calibration plot and Nagelkerke R2. Patients with unfavourable AO at baseline were excluded. Patient, tumour and treatment characteristics were compared between the development and the validation cohort. The prognostic value of the characteristics in the validation cohort was further evaluated in univariable and multivariable analysis. Results: Out of 175 included patients, 166 were evaluated two years after RT and 44 (26.51%) had unfavourable AO. AUC was 0.66 (95% CI 0.56; 0.76). Calibration was moderate with small overestimations at higher risk. When applying all of the univariable significant clinicopathological and dosimetrical variables from the validation cohort in a multivariable model, the presence of a seroma and V45 were selected as significant risk factors for unfavourable AO (Odds Ratio 4.40 (95% CI 1.96; 9.86) and 1.14 (95% CI 1.03; 1.27), p-value <.001 and.01, respectively). Conclusions: The NTCP model for unfavourable AO shows a moderate discrimination and calibration in the present prospective validation cohort with a small overestimation in the high risk patients. [ABSTRACT FROM AUTHOR]

Purpose: A fast‐rotating O‐ring dedicated intensity modulated radiotherapy (IMRT)/volumetric modulated arc therapy (VMAT) delivery system, the Halcyon, is delivered by default with a fully preconfigured photon beam model in the treatment planning system (TPS). This work reports on the validation and achieved IMRT/VMAT delivery quality on the system. Methods: Acceptance testing followed the vendor's installation product acceptance and was supplemented with mechanical QA. The dosimetric calibration was performed according to the IAEA TRS‐398 code‐of‐practice, delivering 600 cGy/min at 10 cm depth, a 90 cm source‐surface distance, and a 10 × 10 cm² field size. The output factors, multileaf collimator (MLC) transmission and dosimetric leaf gap (DLG) were validated by comparing measurements with the modeled values in the TPS. Validation of IMRT/VMAT was conducted following AAPM reports (MPPG 5.a, TG‐119). Next, dose measurements were performed for end‐to‐end (E2E) checks in heterogeneous anthropomorphic phantoms using radiochromic film in multiple planes and using ionization chambers (IC) point measurements. E2E checks were performed for VMAT (cranial, rectum, spine, and head and neck) and IMRT (lung). Additionally, IROC Houston mailed dosimetry audits were performed for the beam calibration and E2E measurements using a thorax phantom (IMRT) and a head and neck phantom (VMAT). Lastly, extensive patient‐specific QA was performed for the first patients of each new indication, 26 in total (nrectum = 2, nspine = 5, nlung = 5, nesophagus = 2, nhead and neck = 7, ncranial = 5), treated on the fast‐rotating O‐ring linac. The patient‐specific QA followed the AAPM TG‐218 guidelines and comprised of portal dosimetry, ArcCHECK diode array, radiochromic film dosimetry in a MultiCube phantom, and IC point measurements. Results: The measured output factors showed an agreement <1% for fields ≥3 × 3 cm². Field sizes ≤2 × 2 cm² had a difference of <2%. The measured single‐layer MLC transmission was 0.42 ± 0.01% and the measured DLG was 0.27 ± 0.22 mm. The AAPM MPPG 5.a measurements were fully compliant with the guideline criteria. Dose differences larger than 2% were found for the PDD at large depths (>25 cm). TG‐119's confidence limits were achieved for the VMAT point dose measurements and for both the IMRT and VMAT radiochromic film measurements. The TG‐119 confidence limits were not achieved for IMRT point dose measurements in both the target (5.9%) and the avoidance structure (6.4%). All E2E tests had point differences below 2.3% and gamma agreement scores above 90.6%. The IROC beam calibration audit showed agreement of <1%. The IROC lung IMRT audit and head and neck VMAT audit had results compliant with the IROC Houston's credentialing criteria. All IMRT and VMAT plans selected for patient‐specific QA were within the action limits suggested by TG‐218. Conclusions: The fast‐rotating O‐ring linac and its preconfigured TPS are compliant with the international commissioning criteria of AAPM MPPG 5.a and AAPM TG‐119. E2E measurements on heterogeneous anthropomorphic phantoms were within clinically acceptable tolerances. IROC Houston's audits satisfied the credentialing criteria. This work comprises the first extensive dataset reporting on the preconfigured fast‐rotating O‐ring linac. [ABSTRACT FROM AUTHOR]

Abstract: Electron beam collimators for non‐standard field sizes and shapes are typically fabricated using Styrofoam molds to cast the aperture cut‐out. These molds are often produced using a dedicated foam cutter, which may be expensive and only serves a single purpose. An increasing number of radiotherapy departments, however, has a 3D printer on‐site, to create a wide range of custom‐made treatment auxiliaries, such as bolus and dosimetry phantoms. The 3D printer can also be used to produce patient‐specific aperture cut‐outs, as elaborated in this note. Open‐source programming language was used to automatically generate the mold's shape in a generic digital file format readable by 3D printer software. The geometric mold model has the patient's identification number integrated and is to be mounted on a uniquely fitting, reusable positioning device, which can be 3D printed as well. This assembly likewise fits uniquely onto the applicator tray, ensuring correct and error‐free alignment of the mold during casting of the aperture. For dosimetric verification, two aperture cut‐outs were cast, one using a conventionally cut Styrofoam mold and one using a 3D printed mold. Using these cut‐outs, the clinical plan was delivered onto a phantom, for which the transversal dose distributions were measured at 2 cm depth using radiochromic film and compared using gamma‐index analysis. An agreement score of 99.9% between the measured 2D dose distributions was found in the (10%–80%) dose region, using 1% (local) dose‐difference and 1.0 mm distance‐to‐agreement acceptance criteria. The workflow using 3D printing has been clinically implemented and is in routine use at the author's institute for all patient‐specific electron beam aperture cut‐outs. It allows for a standardized, cost‐effective, and operator‐friendly workflow without the need for dedicated equipment. In addition, it offers possibilities to increase safety and quality of the process including patient identification and methods for accurate mold alignment. [ABSTRACT FROM AUTHOR]

Purpose/Objectives: To develop a normal tissue complication probability (NTCP) model for late unfavourable aesthetic outcome (AO) after breast-conserving therapy. Material and Methods: The BCCT.core software evaluated the AO using standardized photographs of patients treated between 2009 and 2014. Dose maps in 2Gy equivalents were calculated assuming α/ β = 3.6 Gy. Uni- and multivariable logistic regression analysis was performed to study the predictive value of clinicopathological and dosimetric variables for unfavourable AO. The Lyman Kutcher Burman (LKB) model was fit to the data with dose modifying factors (dmf). Model performance was assessed with the area under the curve (AUC) of the receiver operating characteristic curve and bootstrap sampling. Results: Forty-four of the 121 analysed patients (36%) developed unfavourable AO. In the optimal multivariable logistic regression model, a larger breast volume receiving_55 Gy (V55), a seroma and an axillary lymph node dissection (ALND) were independently associated with an unfavourable AO, AUC = 0.75 (95%CI 0.64;0.85). Beta-estimates were -2.68 for β;0, 0.057 for V55, 1.55 for seroma and 1.20 for ALND. The optimal LKB model parameters were EUD3.6(50) = 63.3 Gy, n = 1.00, m = 0.23, dmf(seroma) = 0.83 and dmf(ALND) = 0.84, AUC = 0.74 (95%CI 0.61;0.83). Conclusions: An NTCP model for late unfavourable AO after breast-conserving therapy was developed including seroma, axillary lymphadenectomy and V55. [ABSTRACT FROM AUTHOR]

Purpose: Liquid fiducial markers have shown to be a promising alternative to solid gold markers in terms of imaging artifact reduction, patient comfort, and compatibility with different imaging modalities. This study aims to investigate the performance of the novel BioXmark® liquid marker for state‐of‐the‐art multimodal imaging used in prostate cancer (PCa) radiotherapy, encompassing kV CT/CBCT, multiparametric MRI, and kV x‐ray imaging. In addition, automatic detection of the liquid markers in x‐ray imaging for prostate motion monitoring during treatment was investigated. Methods: A total of eight BioXmark® liquid markers with varying volumes (range 5–300 μL) were casted on a square grid into a gelatin phantom insert. A cylindrical gold marker (QLRAD, length = 7 mm, Ø = 1 mm) was inserted for reference. Liquid marker visibility and streaking artifacts in CT/CBCT imaging were evaluated by placing the gelatin phantom into a CIRS anthropomorphic phantom. Relevant MRI characteristics such as the T2 and T1 relaxation times, the ADC value, and the relative proton density ( ρ H) were quantified by placing the gelatin phantom insert next to a T1MES mapping phantom and a water‐filled syringe for reference. Ex vivo multiparametric MRI images were acquired by placing the gelatin phantom next to a resected prostate specimen. Anterior–posterior x‐ray projection images were obtained by placing the gelatin phantom insert on top of an anthropomorphic pelvic phantom with internal pelvic bony structures and were acquired for five positions relative to the bony anatomy and 24 clinically relevant x‐ray exposure settings. To quantify individual automatic marker detection, single markers were artificially isolated in the x‐ray images using postprocessing. Results: Markers of all sizes were clearly visible on CT and CBCT images with only the largest marker volumes (100–300 μL) displaying artifacts similar in size to the gold fiducial marker. Artifact size increased with increasing liquid marker volume. Liquid markers displayed good contrast in ex vivo T1‐weighted and ρ H‐weighted images. The markers were not visible in the ex vivo T2‐weighted image. The liquid markers induced a chemical shift artifact in the obtained ADC‐map. Automated detection in x‐ray imaging was feasible with high detection success (four of five positions) for marker volumes in the range of 25–200 μL. None of the liquid markers were detected successfully when superimposed on a bony edge, independent of their size. Conclusions: This study is the first to show the compatibility of BioXmark® liquid markers with multimodal image‐guided radiotherapy for PCa. Compared to a solid gold marker, they had favorable results in both visibility and induced imaging artifacts. Liquid marker visibility in MRI imaging of the prostate does not solely depend on the low ρ H value (not visible on T2‐weighted image) but is also influenced by its relaxation times. Automated marker detection in x‐ray images was feasible but better adapted marker detection algorithms are necessary for marker localization in the presence of bony edges. Hence, the liquid marker provides a minimally invasive (fine needles) and highly applicable alternative to current solid gold markers for multimodal image‐guided prostate radiotherapy treatments. [ABSTRACT FROM AUTHOR]

Purpose The aim of this work was to model the dose dependence of the darkening of GafChromic™ EBT3 films by combining the optical properties of the polydiacetylene polymer phases, and a modified version of the single-hit model, which will take the stick-like shape of the monomer microcrystals into account. Second, a comparison is made between the quantification of the film darkening by flatbed scanning and by UV-vis absorption spectroscopy. Method GafChromicTM EBT3 films were irradiated with a 6 MV photon beam at dose levels between 0 and 50 Gy. The radiation-induced darkening of the films is quantified by a flatbed scanner, and by UV-vis absorption spectroscopy in the wavelength range of 220-750 nm. From the UV-vis absorption spectra, the contribution of each polymer phase to the absorbance was deduced. Next, the dose dependence of the polymer content is described by a modified single-hit model where the size distribution of polymerizable centers is approximated by way of the size distribution of the monomer microcrystals in the film. Results The absorption properties of the film can be accurately quantified by UV-vis spectroscopy for dose levels between 0 and 10 Gy. Over 10 Gy, the absorption spectrum saturates due to the limited sensitivity of the spectrometer. The modified single-hit model was successful in describing the increasing polymer concentration with radiation dose, using a log-normal distribution for the length of the stick-like monomer microcrystals. The dose dependence of the polymer content, deduced from the UV-vis absorption spectrum, differs from that of the flatbed scanning method and is more sensitive to changes in dose. Conclusion The dose dependence of the polymer concentration can be modeled by taking into account the distribution of active centers using the microstructure of the active layer for dose levels between 0 and 10 Gy. The dissimilar dose dependence of the polymer concentration and the absorbance must be accounted for when modeling darkening from the kinetics of the photopolymerization reaction. [ABSTRACT FROM AUTHOR]

Purpose: 3D printing technology is investigated for the purpose of patient immobilization during proton therapy. It potentially enables a merge of patient immobilization, bolus range shifting, and other functions into one single patient-specific structure. In this first step, a set of 3D printed materials is characterized in detail, in terms of structural and radiological properties, elemental composition, directional dependence, and structural changes induced by radiation damage. These data will serve as inputs for the design of 3D printed immobilization structure prototypes. Methods: Using four different 3D printing techniques, in total eight materials were subjected to testing. Samples with a nominal dimension of 20×20×80 mm³ were 3D printed. The geometrical printing accuracy of each test sample was measured with a dial gage. To assess the mechanical response of the samples, standardized compression tests were performed to determine the Young's modulus. To investigate the effect of radiation on the mechanical response, the mechanical tests were performed both prior and after the administration of clinically relevant dose levels (70 Gy), multiplied with a safety factor of 1.4. Dual energy computed tomography (DECT) methods were used to calculate the relative electron density to water e, the effective atomic number Zeff, and the proton stopping power ratio (SPR) to water SPR. In order to validate the DECT based calculation of radiological properties, beam measurements were performed on the 3D printed samples as well. Photon irradiations were performed to measure the photon linear attenuation coefficients, while proton irradiations were performed to measure the proton range shift of the samples. The directional dependence of these properties was investigated by performing the irradiations for different orientations of the samples. Results: The printed test objects showed reduced geometric printing accuracy for 2 materials (deviation > 0.25 mm). Compression tests yielded Young's moduli ranging from 0.6 to 2940 MPa. No deterioration in the mechanical response was observed after exposure of the samples to 100 Gy in a therapeutic MV photon beam. The DECT-based characterization yielded Zeff ranging from 5.91 to 10.43. The SPR and e both ranged from 0.6 to 1.22. The measured photon attenuation coefficients at clinical energies scaled linearly with e. Good agreement was seen between the DECT estimated SPR and the measured range shift, except for the higher Zeff. As opposed to the photon attenuation, the proton range shifting appeared to be printing orientation dependent for certain materials. Conclusions: In this study, the first step toward 3D printed, multifunctional immobilization was performed, by going through a candidate clinical workflow for the first time: from the material printing to DECT characterization with a verification through beam measurements. Besides a proof of concept for beam modification, the mechanical response of printed materials was also investigated to assess their capabilities for positioning functionality. For the studied set of printing techniques and materials, a wide variety of mechanical and radiological properties can be selected from for the intended purpose. Moreover the elaborated hybrid DECT methods aid in performing in-house quality assurance of 3D printed components, as these methods enable the estimation of the radiological properties relevant for use in radiation therapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article discusses challenges related to the implementation of volumetric modulated arc therapy for rectal cancer. Topics discussed include use of radiochemotherapy followed by total mesorectal excision surgery for the treatment of rectal cancer, methods including patients undergoing planning computed tomography, analysis of dosimetric parameters, and future strategy to reduce treatment-related toxicity.

Movement of tumours, mostly by respiration, has been a major problem for treating lung cancer, liver tumours and other locations in the abdomen and thorax. Organ motion is indeed one component of geometrical uncertainties that includes delineation and target definition uncertainties, microscopic disease and setup errors. At present, minimising motion seems to be the easiest to implement in clinical practice. If combined with adaptive approaches to correct for gradual anatomical variations, it may be a practical strategy. Other approaches such as repainting and tracking could increase the accuracy of proton therapy delivery, but advanced 4D solutions are needed. Moreover, there is a need to perform clinical studies to investigate which approach is the best in a given clinical situation. The good news is that existing and emerging technology and treatment planning systems as will without doubt lead in the forthcoming future to practical solutions to tackle intra-fraction motion in proton therapy. These developments may also improve motion management in photon therapy as well. [ABSTRACT FROM AUTHOR]

Purpose: This work presents a method for fast volumetric modulated arc therapy (VMAT) adaptation in response to interfraction anatomical variations. Additionally, plan parameters extracted from the adapted plans are used to verify the quality of these plans. The methods were tested as a prostate class solution and compared to replanning and to their current clinical practice. Methods: The proposed VMAT adaptation is an extension of their previous intensity modulated radiotherapy (IMRT) adaptation. It follows a direct (forward) planning approach: the multileaf collimator (MLC) apertures are corrected in the beam’s eye view (BEV) and the monitor units (MUs) are corrected using point dose calculations. All MLC and MU corrections are driven by the positions of four fiducial points only, without need for a full contour set. Quality assurance (QA) of the adapted plans is performed using plan parameters that can be calculated online and that have a relation to the delivered dose or the plan quality. Five potential parameters are studied for this purpose: the number of MU, the equivalent field size (EqFS), the modulation complexity score (MCS), and the components of the MCS: the aperture area variability (AAV) and the leaf sequence variability (LSV). The full adaptation and its separate steps were evaluated in simulation experiments involving a prostate phantom subjected to various interfraction transformations. The efficacy of the current VMAT adaptation was scored by target mean dose (CTVmean), conformity (CI95%), tumor control probability (TCP), and normal tissue complication probability (NTCP). The impact of the adaptation on the plan parameters (QA) was assessed by comparison with prediction intervals (PI) derived from a statistical model of the typical variation of these parameters in a population of VMAT prostate plans (n = 63). These prediction intervals are the adaptation equivalent of the tolerance tables for couch shifts in the current clinical practice. Results: The proposed adaptation of a two-arc VMAT plan resulted in the intended CTVmean (Δ ≤ 3%) and TCP (ΔTCP ≤ 0.001). Moreover, the method assures the intended CI95% (Δ ≤ 11%) resulting in lowered rectal NTCP for all cases. Compared to replanning, their adaptation is faster (13 s vs 10 min) and more intuitive. Compared to the current clinical practice, it has a better protection of the healthy tissue. Compared to IMRT, VMAT is more robust to anatomical variations, but it is also less sensitive to the different correction steps. The observed variations of the plan parameters in their database included a linear dependence on the date of treatment planning and on the target radius. The MCS is not retained as QA metric due to a contrasting behavior of its components (LSV and AAV). If three out of four plan parameters (MU, EqFS, AAV, and LSV) need to lie inside a 50% prediction interval (3/4--50%PI), all adapted plans will be accepted. In contrast, all replanned plans do not meet this loose criterion, mainly because they have no connection to the initially optimized and verified plan. Conclusions: A direct (forward) VMAT adaptation performs equally well as (inverse) replanning but is faster and can be extended to real-time adaptation. The prediction intervals for the machine parameters are equivalent to the tolerance tables for couch shifts in the current clinical practice. A 3/4--50%PI QA criterion accepts all the adapted plans but rejects all the replanned plans. [ABSTRACT FROM AUTHOR]

Purpose: Because frame rates on current clinical available electronic portal imaging devices (EPID's) are limited to 7.5 Hz, a new commercially available PerkinElmer EPID (XRD 1642 AP19) with a maximum frame rate of 30 Hz and a new scintillator (Kyokko PI200) with improved sensitivity (light output) for megavolt (MV) irradiation was evaluated. In this work, the influence of MV pulse artifacts and pulsing artifact suppression techniques on fiducial marker and marker-less detection of a lung lesion was investigated, because target localization is an important component of uncertainty in geometrical verification of real-time tumor tracking. Methods: Visicoil™markers with a diameter of 0.05 and 0.075 cm were used forMVmarker tracking with a frame rate of, respectively, 7.5, 15, and 30 Hz. A 30 Hz readout of the detector was obtained by a 2×2 pixel binning, reducing spatial resolution. Static marker detection was conducted in function of increasing phantom thickness. Additionally, marker-less tracking was conducted and compared with the ground-truth fiducial marker motion. Performance of MV target detection was investigated by comparing the least-square sine wave fit of the detected marker positions with the predefined sine wave motion. For fiducial marker detection, a Laplacian-of-Gaussian enhancement was applied after which normalized cross correlation was used to find the most probable marker position. Marker-less detection was performed by using the scale and orientation adaptive mean shift tracking algorithm. For each MV fluoroscopy, a free running (FR-nF) (ignoring MV pulsing during readout) acquisition mode was compared with two acquisition modes intending to reduce MV pulsing artifacts, i.e., combined wavelet-FFT filtering (FR-wF) and electronic readout synchronized with respect to MV pulses. Results: A 0.05 cm Visicoil marker resulted in an unacceptable root-mean square error (RMSE) > 0.2 cm with a maximum frame rate of 30 Hz during FR-nF readout. With a 30 Hz synchronized readout (S-nF) and during 15 Hz readout (independent of readout mode), RMSE was submillimeter for a static 0.05 cm Visicoil. A dynamic 0.05 cm Visicoil was not detectable on the XRD 1642 AP19, despite a fast synchronized readout. For a 0.075 cm Visicoil, deviations of sine wave motion were submillimeter (RMSE < 0.08 cm), independent of the acquisition mode (FR, S). For marker-less tumor detection, FR-nF images resulted in RMSE > 0.3 cm, while for MV fluoroscopy in S-mode RMSE < 0.1 cm for 15 Hz and RMSE < 0.16 cm for 30 Hz. Largest consistency in target localization was experienced during 15 Hz S-nF readout. Conclusions: In general, marker contrast decreased in function of higher frame rates, which was detrimental for marker detection success. In this work, Visicoils with a thickness of 0.075 cm were showing best results for a 15 Hz frame rate, while non-MV compatible 0.05 cm Visicoil markers were not visible on the new EPID with improved sensitivity compared to EPID models based on a Kodak Lanex Fast scintillator. No noticeable influence of pulsing artifacts on the detection of a 0.075 cm Visicoil was observed, while a synchronized readout provided most reliable detection of a marker-less soft-tissue structure. [ABSTRACT FROM AUTHOR]

Purpose: This paper describes the design and experimental evaluation of the Methods and Advanced Equipment for Simulation and Treatment in Radiation Oncology (MAESTRO) thorax phantom, a new anthropomorphic moving ribcage combined with a 3D tumor positioning system to move target inserts within static lungs. Methods: The new rib cage design is described and its motion is evaluated using Vicon Nexus, a commercial 3D motion tracking system. CT studies at inhale and exhale position are used to study the effect of rib motion and tissue equivalence. Results: The 3D target positioning system and the rib cage have millimetre accuracy. Each axis of motion can reproduce given trajectories from files or individually programmed sinusoidal motion in terms of amplitude, period, and phase shift. The maximum rib motion ranges from 7 to 20 mm SI and from 0.3 to 3.7 mm AP with LR motion less than 1 mm. The repeatability between cycles is within 0.16 mm root mean square error. The agreement between CT electron and mass density for skin, ribcage, spine hard and inner bone as well as cartilage is within 3%. Conclusions: The MAESTRO phantom is a useful research tool that produces programmable 3D rib motions which can be synchronized with 3D internal target motion. The easily accessible static lungs enable the use of a wide range of inserts or can be filled with lung tissue equivalent and deformed using the target motion system. [ABSTRACT FROM AUTHOR]