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Background: Carbon ion beams are well accepted as densely ionizing radiation with a high linear energy transfer (LET). However, the current clinical practice does not fully exploit the highest possible dose‐averaged LET (LETd) and, consequently, the biological potential in the target. This aspect becomes worse in larger tumors for which inferior clinical outcomes and corresponding lower LETd was reported. Purpose: The vicinity to critical organs in general and the inferior overall survival reported for larger sacral chordomas treated with carbon ion radiotherapy (CIRT), makes the treatment of such tumors challenging. In this work it was aimed to increase the LETd in large volume tumors while maintaining the relative biological effectiveness (RBE)‐weighted dose, utilizing the LETd optimization functions of a commercial treatment planning system (TPS). Methods: Ten reference sequential boost carbon ion treatment plans, designed to mimic clinical plans for large sacral chordoma tumors, were generated. High dose clinical target volumes (CTV‐HD) larger than 250cm3$250 \,{\rm cm}^{3}$ were considered as large targets. The total RBE‐weighted median dose prescription with the local effect model (LEM) was DRBE,50%=73.6Gy$\textrm {D}_{\rm RBE, 50\%}=73.6 \,{\rm Gy}$ in 16 fractions (nine to low dose and seven to high dose planning target volume). No LETd optimization was performed in the reference plans, while LETd optimized plans used the minimum LETd (Lmin) optimization function in RayStation 2023B. Three different Lmin values were investigated and specified for the seven boost fractions: Lmin=60keV/μm$\textrm {L}_{\rm min}=60 \,{\rm keV}/{\umu }{\rm m}$, Lmin=80keV/μm$\textrm {L}_{\rm min}=80 \,{\rm keV}/{\umu }{\rm m}$ and Lmin=100keV/μm$\textrm {L}_{\rm min}=100 \,{\rm keV}/{\umu }{\rm m}$. To compare the LETd optimized against reference plans, LETd and RBE‐weighted dose based goals similar to and less strict than clinical ones were specified for the target. The goals for the organs at risk (OAR) remained unchanged. Robustness evaluation was studied for eight scenarios (±3.5%$\pm 3.5\%$ range uncertainty and ±3mm$\pm 3 \,{\rm mm}$ setup uncertainty along the main three axes). Results: The optimization method with Lmin=60keV/μm$\textrm {L}_{\rm min}=60 \,{\rm keV}/{\umu }{\rm m}$ resulted in an optimal LETd distribution with an average increase of LETd,98%${\rm {LET}}_{{\rm {d,}}98\%}$ (and LETd,50%${\rm {LET}}_{{\rm {d,}}50\%}$) in the CTV‐HD by 8.9±1.5keV/μm$8.9\pm 1.5 \,{\rm keV}/{\umu }{\rm m}$ (27%$27\%$) (and 6.9±1.3keV/μm$6.9\pm 1.3 \,{\rm keV}/{\umu }{\rm m}$ (17%$17\%$)), without significant difference in the RBE‐weighted dose. By allowing ±5%$\pm 5\%$ over‐ and under‐dosage in the target, the LETd,98%${\rm {LET}}_{{\rm {d,}}98\%}$ (and LETd,50%${\rm {LET}}_{{\rm {d,}}50\%}$) can be increased by 11.3±1.2keV/μm$11.3\pm 1.2 \,{\rm keV}/{\umu }{\rm m}$ (34%$34\%$) (and 11.7±3.4keV/μm$11.7\pm 3.4 \,{\rm keV}/{\umu }{\rm m}$ (29%$29\%$)), using the optimization parameters Lmin=80keV/μm$\textrm {L}_{\rm min}=80 \,{\rm keV}/{\umu }{\rm m}$. The pass rate for the OAR goals in the LETd optimized plans was in the same level as the reference plans. LETd optimization lead to less robust plans compared to reference plans. Conclusions: Compared to conventionally optimized treatment plans, the LETd in the target was increased while maintaining the RBE‐weighted dose using TPS LETd optimization functionalities. Regularly assessing RBE‐weighted dose robustness and acquiring more in‐room images remain crucial and inevitable aspects during treatment. [ABSTRACT FROM AUTHOR]

Background: The combination of magnetic resonance imaging and proton therapy offers the potential to improve cancer treatment. The magnetic field (MF)‐dependent change in the dosage of ionization chambers in magnetic resonance imaging‐integrated proton therapy (MRiPT) is considered by the correction factor kB⃗,M,Q$k_{\vec{B},M,Q}$, which needs to be determined experimentally or computed via Monte Carlo (MC) simulations. Purpose: In this study, kB⃗,M,Q$k_{\vec{B},M,Q}$ was both measured and simulated with high accuracy for a plane‐parallel ionization chamber at different clinical relevant proton energies and MF strengths. Material and methods: The dose‐response of the Advanced Markus chamber (TM34045, PTW, Freiburg, Germany) irradiated with homogeneous 10 ×$\times$ 10 cm 2$^2$ quasi mono‐energetic fields, using 103.3, 128.4, 153.1, 223.1, and 252.7 MeV proton beams was measured in a water phantom placed in the MF of an electromagnet with MF strengths of 0.32, 0.5, and 1 T. The detector was positioned at a depth of 2 g/cm 2$^2$ in water, with chamber electrodes parallel to the MF lines and perpendicular to the proton beam incidence direction. The measurements were compared with TOPAS MC simulations utilizing COMSOL‐calculated 0.32, 0.5, and 1 T MF maps of the electromagnet. kB⃗,M,Q$k_{\vec{B},M,Q}$ was calculated for the measurements for all energies and MF strengths based on the equation: kB⃗,M,Q=MQMQB⃗$k_{\vec{B},M,Q}=\frac{M_\mathrm{Q}}{M_\mathrm{Q}^{\vec{B}}}$, where MQB⃗$M_\mathrm{Q}^{\vec{B}}$ and MQ$M_\mathrm{Q}$ were the temperature and air‐pressure corrected detector readings with and without the MF, respectively. MC‐based correction factors were determined as kB⃗,M,Q=DdetDdetB⃗$k_{\vec{B},M,Q}=\frac{D_\mathrm{det}}{D_\mathrm{det}^{\vec{B}}}$, where DdetB⃗$D_\mathrm{det}^{\vec{B}}$ and Ddet$D_\mathrm{det}$ were the doses deposited in the air cavity of the ionization chamber model with and without the MF, respectively. Furthermore, MF effects on the chamber dosimetry are studied using MC simulations, examining the impact on the absorbed dose‐to‐water (DW$D_{W}$) and the shift in depth of the Bragg peak. Results: The detector showed a reduced dose‐response for all measured energies and MF strengths, resulting in experimentally determined kB⃗,M,Q$k_{\vec{B},M,Q}$ values larger than unity. For all energies and MF strengths examined, kB⃗,M,Q$k_{\vec{B},M,Q}$ ranged between 1.0065 and 1.0205. The dependence on the energy and the MF strength was found to be non‐linear with a maximum at 1 T and 252.7 MeV. The MC simulated kB⃗,M,Q$k_{\vec{B},M,Q}$ values agreed with the experimentally determined correction factors within their standard deviations with a maximum difference of 0.6%. The MC calculated impact on DW$D_{W}$ was smaller 0.2 %. Conclusion: For the first time, measurements and simulations were compared for proton dosimetry within MFs using an Advanced Markus chamber. Good agreement of kB⃗,M,Q$k_{\vec{B},M,Q}$ was found between experimentally determined and MC calculated values. The performed benchmarking of the MC code allows for calculating kB⃗,M,Q$k_{\vec{B},M,Q}$ for various ionization chamber models, MF strengths and proton energies to generate the data needed for a proton dosimetry protocol within MFs and is, therefore, a step towards MRiPT. [ABSTRACT FROM AUTHOR]

Background: Large tumor size has been reported as a predicting factor for inferior clinical outcome in carbon ion radiotherapy (CIRT). Besides the clinical factors accompanied with such tumors, larger tumors receive typically more low linear energy transfer (LET) contributions than small ones which may be the underlying physical cause. Although dose averaged LET is often used as a single parameter descriptor to quantify the beam quality, there is no evidence that this parameter is the optimal clinical predictor for the complex mixed radiation fields in CIRT. Purpose: Purpose of this study was to investigate on a novel dosimetric quantity, namely high‐LET‐dose (D>Lthr$\textrm {D}_{>\textrm {L}_{\textrm {thr}}}$, the physical dose filtered based on an LET threshold) as a single parameter estimator to differentiate between carbon ion treatment plans (cTP) with a small and large tumor volume. Methods: Ten cTPs with a planning target volume, PTV≥500cm3$\mathrm{PTV}\ge {500}\,{{\rm cm}^{3}}$ (large) and nine with a PTV<500cm3$\mathrm{PTV}<{500}\,{{\rm cm}^{3}}$ (small) were selected for this study. To find a reasonable LET threshold (Lthr$\textrm {L}_{\textrm {thr}}$) that results in a significant difference in terms of D>Lthr$\textrm {D}_{>\textrm {L}_{\textrm {thr}}}$, the voxel based normalized high‐LET‐dose (D̂>Lthr$\hat{\textrm {D}}_{>\textrm {L}_{\textrm {thr}}}$) distribution in the clinical target volume (CTV) was studied on a subset (12 out of 19 cTPs) for 18 LET thresholds, using standard distribution descriptors (mean, variance and skewness). The classical dose volume histogram concept was used to evaluate the D>Lthr$\textrm {D}_{>\textrm {L}_{\textrm {thr}}}$ and D̂>Lthr$\hat{\textrm {D}}_{>\textrm {L}_{\textrm {thr}}}$ distributions within the target of all 19 cTPs at the before determined Lthr$\textrm {L}_{\textrm {thr}}$. Statistical significance of the difference between the two groups in terms of mean D>Lthr$\textrm {D}_{>\textrm {L}_{\textrm {thr}}}$ and D̂>Lthr$\hat{\textrm {D}}_{>\textrm {L}_{\textrm {thr}}}$ volume histogram parameters was evaluated by means of (two‐sided) t‐test or Mann‐Whitney‐U‐test. In addition, the minimum target coverage at the above determined Lthr$\textrm {L}_{\textrm {thr}}$ was compared and validated against three other thresholds to verify its potential in differentiation between small and large volume tumors. Results: An Lthr$\textrm {L}_{\textrm {thr}}$ of approximately 30keV/μm${30}\,{\rm keV/}\umu {\rm m}$ was found to be a reasonable threshold to classify the two groups. At this threshold, the D>Lthr$\textrm {D}_{>\textrm {L}_{\textrm {thr}}}$ and D̂>Lthr$\hat{\textrm {D}}_{>\textrm {L}_{\textrm {thr}}}$ were significantly larger (p<0.05$p<0.05$) in small CTVs. For the small tumor group, the near‐minimum and median D>Lthr$\textrm {D}_{>\textrm {L}_{\textrm {thr}}}$ (and D̂>Lthr$\hat{\textrm {D}}_{>\textrm {L}_{\textrm {thr}}}$) in the CTV were in average 9.3±1.5Gy$9.3\pm {1.5}\,{\rm Gy}$ (0.31 ± 0.08) and 13.6±1.6Gy$13.6\pm {1.6}\,{\rm Gy}$ (0.46 ± 0.06), respectively. For the large tumors, these parameters were 6.6±0.2Gy$6.6\pm {0.2}\,{\rm Gy}$ (0.20 ± 0.01) and 8.6±0.4Gy$8.6\pm {0.4}\,{\rm Gy}$ (0.28 ± 0.02). The difference between the two groups in terms of mean near‐minimum and median D>Lthr$\textrm {D}_{>\textrm {L}_{\textrm {thr}}}$ (D̂>Lthr$\hat{\textrm {D}}_{>\textrm {L}_{\textrm {thr}}}$) was 2.7 Gy (11%) and 5.0 Gy (18%), respectively. Conclusions: The feasibility of high‐LET‐dose based evaluation was shown in this study where a lower D>Lthr$\textrm {D}_{>\textrm {L}_{\textrm {thr}}}$ was found in cTPs with a large tumor size. Further investigation is needed to draw clinical conclusions. The proposed methodology in this work can be utilized for future high‐LET‐dose based studies. [ABSTRACT FROM AUTHOR]

Background: Ion beam therapy allows for a substantial sparing of normal tissues and higher biological efficacy. Synthetic single crystal diamond is a very good material to produce high‐spatial‐resolution and highly radiation hard detectors for both dosimetry and microdosimetry in ion beam therapy. Purpose: The aim of this work is the design, fabrication and test of an integrated waterproof detector based on synthetic single crystal diamond able to simultaneously perform dosimetric and microdosimetric characterization of clinical ion beams. Methods: The active elements of the integrated diamond device, that is, dosimeter and microdosimeter, were both realized in a Schottky diode configuration featured by different area, thickness, and shape by means of photolithography technologies for the selective growth of intrinsic and boron‐doped CVD diamond. The cross‐section of the sensitive volume of the dosimetric element is 4 mm2 and 1 μm‐thick, while the microdosimetric one has an active cross‐sectional area of 100 × 100 μm2 and a thickness of about 6.2 μm. The dosimetric and microdosimetric performance of the developed device was assessed at different depths in a water phantom at the MedAustron ion beam therapy facility using a monoenergetic uniformly scanned carbon ion beam of 284.7 MeV/u and proton beam of 148.7 MeV. The particle flux in the region of the microdosimeter was 6·107 cm2/s for both irradiation fields. At each depth, dose and dose distributions in lineal energy were measured simultaneously and the dose mean lineal energy values were then calculated. Monte Carlo simulations were also carried out by using the GATE‐Geant4 code to evaluate the relative dose, dose averaged linear energy transfer (LETd), and microdosimetric spectra at various depths in water for the radiation fields used, by considering the contribution from the secondary particles generated in the ion interaction processes as well. Results: Dosimetric and microdosimetric quantities were measured by the developed prototype with relatively low noise (∼2 keV/μm). A good agreement between the measured and simulated dose profiles was found, with discrepancies in the peak to plateau ratio of about 3% and 4% for proton and carbon ion beams respectively, showing a negligible LET dependence of the dosimetric element of the device. The microdosimetric spectra were validated with Monte Carlo simulations and a good agreement between the spectra shapes and positions was found. Dose mean lineal energy values were found to be in close agreement with those reported in the literature for clinical ion beams, showing a sharp increase along the Bragg curve, being also consistent with the calculated LETd for all depths within the experimental error of 10%. Conclusions: The experimental indicate that the proposed device can allow enhanced dosimetry in particle therapy centers, where the absorbed dose measurement is implemented by the microdosimetric characterization of the radiation field, thus providing complementary results. In addition, the proposed device allows for the reduction of the experimental uncertainties associated with detector positioning and could facilitate the partial overcoming of some drawbacks related to the low sensitivity of diamond microdosimeters to low LET radiation. [ABSTRACT FROM AUTHOR]

Background: Combining carbon ion therapy with on‐bed MR imaging has the potential to bring particle therapy to a new level of precision. However, the introduction of magnetic fields brings challenges for dosimetry and quality assurance. For protons, a small, but significant change in detector response was shown in the presence of magnetic fields previously. For carbon ion beams, so far no such experiments have been performed. Purpose: To investigate the influence of external magnetic fields on the response of air‐filled ionization chambers. Methods: Four commercially available ionization chambers, three thimble type (Farmer, Semiflex, and PinPoint), and a plane parallel (Bragg peak) detector were investigated. Detectors were aligned in water such that their effective point of measurement was located at 2 cm depth. Irradiations were performed using 10×10cm2$10\times 10\nobreakspace \mathrm{cm}^2$ square fields for carbon ions of 186.1, 272.5, and 402.8 MeV/u employing magnetic field strengths of 0, 0.25, 0.5, and 1 T. In addition, the detector response for protons and carbon ions was compared taking into account the secondary electron spectra and employing protons of 252.7 MeV for comparison. Results: For all four detectors, a statistically significant change in detector response, dependent on the magnetic field strength, was found. The effect was more pronounced for higher energies. The highest effects were found at 0.5 T for the PinPoint detector with a change in detector response of 1.1%. The response of different detector types appeared to be related to the cavity diameter. For proton and carbon ion irradiation with similar secondary electron spectra, the change in detector response was larger for carbon ions compared to protons. Conclusion: A small, but significant dependence of the detector response was found for carbon ion irradiation in a magnetic field. The effect was found to be larger for smaller cavity diameters and at medium magnetic field strengths. Changes in detector response were more pronounced for carbon ions compared to protons. [ABSTRACT FROM AUTHOR]

Background: Deep learning‐based auto‐planning is an active research field; however, for some tasks a treatment planning system (TPS) is still required. Purpose: To introduce a deep learning‐based model generating deliverable DICOM RT treatment plans that can be directly irradiated by a linear accelerator (LINAC). The model was based on an encoder‐decoder network and can predict multileaf collimator (MLC) motion sequences for prostate VMAT radiotherapy. Methods: A total of 619 treatment plans from 460 patients treated for prostate cancer with single‐arc VMAT were included in this study. An encoder‐decoder network was trained using 465 clinical treatment plans and validated on 77 plans. The performance was analyzed on a separate test set of 77 treatment plans. Separate L1 losses were computed for the leaf and jaw positions as well as the monitor units, with the leaf loss being weighted by a factor of 100 before being added to the other losses. The generated treatment plans were recalculated in a treatment planning system and the dose‐volume metrics and gamma passing rates were compared to the original dose. Results: All generated treatment plans showed good agreement with the original data, with an average gamma passing rate (3%/3 mm) of 91.9 ± 7.1%. However, the coverage of the PTVs. was slightly lower for the generated plans (D98% = 92.9 ± 2.6%) in comparison to the original plans (D98% = 95.7 ± 2.2%). There was no significant difference in mean dose to the bladder between the predicted and original plan (Dmean of 28.0 ± 13.5 vs. 28.1 ± 13.3% of prescribed dose) or rectum (Dmean of 42.3 ± 7.4 vs. 42.6 ± 7.5%). The maximum dose to bladder was only slightly higher in the predicted plans (D2% of 100.7 ± 5.3 vs. 99.8 ± 4.0%) and for the rectum it was even lower (D2% of 100.5 ± 3.7 vs. 100.1 ± 4.3). Conclusions: The deep learning‐based model could predict MLC motion sequences in prostate VMAT plans, eliminating the need for sequencing inside a TPS, thus revolutionizing autonomous treatment planning workflows. This research completes the loop in deep learning‐based treatment planning processes, enabling more efficient workflows for real‐time or online adaptive radiotherapy. [ABSTRACT FROM AUTHOR]

Background: The increasing number of studies dealing with linear energy transfer (LET)-based evaluation and optimization in the field of carbon ion radiotherapy (CIRT) indicates the rising demand for LET implementation in commercial treatment planning systems (TPS). Benchmarking studies could play a key role in detecting (and thus preventing) computation errors prior implementing such functionalities in a TPS. Purpose: This in silico study was conducted to benchmark the following two LET-related functionalities in a commercial TPS against Monte Carlo simulations: (1) dose averaged LET (LETd) scoring and (2) physical dose filtration based on LET for future LET-based treatment plan evaluation and optimization studies. Methods: The LETd scoring and LET-based dose filtering (in which the deposited dose can be separated into the dose below and above the user specified LET threshold) functionalities for carbon ions in the research version RayStation (RS) 9A-IonPG TPS (RaySearch Laboratories, Sweden) were benchmarked against GATE/Geant4 simulations. Pristine Bragg peaks (BPs) and cuboid targets, positioned at different depths in a homogeneous water phantom and a setup with heterogeneity were used for this study. Results: For all setups (homogeneous and heterogeneous), the mean absolute (and relative) LETd difference was less than 1 keV/μm (3.5%) in the plateau and target and less than 2 keV/μm (8.3%) in the fragmentation tail. The maximum local differences were 4 and 6 keV/μm, respectively. The mean absolute (and relative) physical dose differences for both low- and high-LET doses were less than 1 cGy (1.5%) in the plateau, target and tail with a maximum absolute difference of 2 cGy. Conclusions: No computation error was found in the tested functionalities except for LETd in lateral direction outside the target, showing the limitation of the implemented monochrome model in the tested TPS version. [ABSTRACT FROM AUTHOR]

Background: Radiation therapy is continuously moving towards more precise dose delivery. The combination of online MR imaging and particle therapy, for example, radiation therapy using protons or carbon ions, could enable the next level of precision in radiotherapy. In particle therapy, research towards a combination of MR and particle therapy is well underway, but still far from clinical systems. The combination of high magnetic fields with particle therapy delivery poses several challenges for treatment planning, treatment workflow, dose delivery, and dosimetry. Purpose: To present a workflow for commissioning of a light ion beam line with an integrated dipole magnet to perform MR-guided particle therapy (MRgPT) research, producing not only basic beam data but also magnetic field maps for accurate dose calculation. Accurate dose calculation in magnetic field environments requires high-quality magnetic field maps to compensate for magnetic-field-dependent trajectory changes and dose perturbations. Methods: The research beam line at MedAustron was coupled with a resistive dipole magnet positioned at the isocenter. Beam data were measured for proton and carbon ions with and without an applied magnetic field of 1 T. Laterally integrated depth-dose curves (IDC) as well as beam profiles were measured in water while beam trajectories were measured in air. Based on manufacturer data, an in silico model of the magnet was created, allowing to extract highquality 3D magnetic field data. An existing GATE/Geant4 Monte Carlo (MC) model of the beam line was extended with the generated magnetic field data and benchmarked against experimental data. Results: A 3D magnetic field volume covering fringe fields until 50 mT was found to be sufficient for an accurate beam trajectory modeling. The effect on particle range retraction was found to be 2.3 and 0.3 mm for protons and carbon ions, respectively. Measured lateral beam offsets in water agreed within 0.4 and -0.5 mm with MC simulations for protons and carbon ions, respectively. Experimentally determined in-air beam trajectories agreed within 0.4 mm in the homogeneous magnetic field area. Conclusion: The presented approach based on in silico modeling and measurements allows to commission a beam line for MRgPT while providing benchmarking data for the magnetic field modeling, required for state-of -the art dose calculation methods. [ABSTRACT FROM AUTHOR]

Purpose: Radiochromic films are versatile 2D dosimeters with high‐resolution and near tissue equivalence. To assure high precision and accuracy, a time‐consuming calibration process is required. To improve the time efficiency, a novel calibration method utilizing the ratio of the same dose profile measured at different monitor units (MUs) is introduced and tested in a proton and photon beam. Methods: The calibration procedure employs the dose ratio of film measurements of the same relative profile for different absolute dose values. Hence, the ratio of the dose is constant at any point of the profile, but the ratio of the net optical densities is not constant. The key idea of the method is to optimize the calibration function until the ratio of the calculated doses is constant. The proposed method was tested in the dose range between 0.25–12 and 1–6 Gy in a proton and photon beam, respectively. A radial symmetric profile and a rectangular profile were created, both having a central plateau region of about 3 cm diameter and a dose falloff of about 1.5 cm at larger distances. The dose falloff region was used as input for the optimization method and the central plateau region served as dose reference points. Only the plateau region of the highest dose entered the optimization as an additional objective. The measured data were randomly split into differently sized training and test sets. The optimization was repeated 1000 times with random start value initialization using the same start values for the standard and the gradient method. Finally, a proton plan with four dose levels was created, which were separated spatially, to test the possibility of a full calibration within a single measurement. Results: Parameter estimation was possible with as low as one dose ratio used for optimization in both the photon and the proton case, yet exhibiting a high sensitivity on the dose level. The root mean squared deviation (RMSD) of the dose was less than 1% when the dose ratio was in the order of 20, whereas the median RMSD of all optimizations was 1.7%. Using four dose levels for optimization resulted in a median RMSD of 1% when randomly selecting the dose levels. Having at least one dose ratio of about 20 included in the optimization considerably improved the RMSD of the calibration function. Using six or eight dose levels reduced the sensitivity on the dose level selection and the median RMSD was 0.8%. A full calibration was possible in a single measurement having four dose levels in one plan but spatially separated. Conclusions: The number of measurements required to obtain an EBT3 film calibration function could be reduced using the proposed dose ratio method while maintaining the same accuracy as with the standard method. [ABSTRACT FROM AUTHOR]

Background: Real‐time tumor motion monitoring (TMM) is a crucial process for intra‐fractional respiration management in lung cancer radiotherapy. Since the tumor can be partly or fully located behind the ribs, the TMM is challenging. Purpose: The aim of this work was to develop a bone suppression (BS) algorithm designed for real‐time 2D/3D marker‐less TMM to increase the visibility of the tumor when overlapping with bony structures and consequently to improve the accuracy of TMM. Method: A BS method was implemented in the in‐house developed software for ultrafast intensity‐based 2D/3D tumor registration (Fast Image‐based Registration [FIRE]). The method operates on both, digitally reconstructed radiograph (DRR) and intra‐fractional X‐ray images. The bony structures are derived from computed tomography data by thresholding during ray‐casting, and the resulting bone DRR is subtracted from intra‐fractional X‐ray images to obtain a soft‐tissue‐only image for subsequent tumor registration. The accuracy of TMM utilizing BS was evaluated within a retrospective phantom study with nine different 3D‐printed tumor phantoms placed in the in‐house developed Advanced Radiation DOSimetry (ARDOS) breathing phantom. A 24 mm craniocaudal tumor motion, including rib eclipses, was simulated, and X‐ray images were acquired on the Elekta Versa HD Linac in the lateral and posterior–anterior directions. An error assessment for BS images was evaluated with respect to the ground truth tumor position. Results: A total error (root mean square error) of 0.87 ± 0.23 mm and 1.03 ± 0.26 mm was found for posterior–anterior and lateral imaging; the mean time for BS was 8.03 ± 1.54 ms. Without utilizing BS, TMM failed in all X‐ray images since the registration algorithm focused on the rib position due to the predominant intensity of this tissue within DRR and X‐ray images. Conclusion: The BS algorithm developed and implemented improved the accuracy, robustness, and stability of real‐time TMM in lung cancer in a phantom study, even in the case of rib interlude where normal tumor registration fails. [ABSTRACT FROM AUTHOR]

Purpose: The Local Effect Model version one (LEM I) is applied clinically across Europe to quantify the relative biological effectiveness (RBE) of carbon ion beams. It requires the full particle fluence spectrum differential in energy in each voxel as input parameter. Treatment planning systems (TPSs) use beamline‐specific look‐up tables generated with Monte Carlo (MC) codes. In this study, the changes in RBE weighted dose were quantified using different levels of details in the simulation or different MC codes. Methods: The particle fluence differential in energy was simulated with FLUKA and Geant4 at 500 depths in water in 1‐mm steps for 58 initial carbon ion energies (between 120.0 and 402.8 MeV/u). A dedicated beam model was applied, including the full description of the Nozzle using GATE‐RTionV1.0 (Geant4.10.03p03). In addition, two tables generated with FLUKA were compared. The starting points of the FLUKA simulations were phase space (PhS) files from, firstly, the Geant4 nozzle simulations, and secondly, a clinical beam model where an analytic approach was used to mimic the beamline. Treatment plans (TPs) were generated with RayStation 8B (RaySearch Laboratories AB, Sweden) for cubic targets in water and 10 clinical patient cases using the clinical beam model. Subsequently, the RBE weighted dose was re‐computed using the two other fluence tables (FLUKA PhS or Geant4). Results: The fluence spectra of the primary and secondary particles simulated with Geant4 and FLUKA generally agreed well for the primary particles. Differences were mainly observed for the secondary particles. Interchanging the two energy spectra (FLUKA vs. GEANT4) to calculate the RBE weighted dose distributions resulted in average deviations of less than 1% in the entrance up to the end of the target region, with a maximum local deviation at the distal edge of the target. In the fragment tail, larger discrepancies of up to 5% on average were found for deep‐seated targets. The patient and water phantom cases demonstrated similar results. Conclusion: RBE weighted doses agreed well within all tested setups, confirming the clinical beam model provided by the TPS vendor. Furthermore, the results showed that the open source and generally available MC code Geant4 (in particular using GATE or GATE‐RTion) can also be used to generate basic beam data required for RBE calculation in carbon ion therapy. [ABSTRACT FROM AUTHOR]

Purpose: The accurate knowledge of the effective point of measurement (Peff) is particularly important for measurements in proximity to high dose gradients such as in the distal fall‐off of particle beams. For plane‐parallel ionization chambers (ICs), Peff is well known and located at the center of the inner surface of the entrance window. For cylindrical ICs, Peff is shifted from the chamber's center toward the beam source. According to IAEA TRS‐398, this shift can be calculated as 0.75·rcyl for light ions with rcyl being the radius of the cavity. For proton beams and in absence of a dose gradient, no shift is recommended. We have experimentally determined Peff for the 0.125 cc Semiflex IC in both proton and carbon ion beams. Methods: The first method consisted of simultaneous irradiation of a plane‐parallel IC and the Semiflex in a 4‐cm wide spread‐out Bragg peak. In the second method, a single‐energy beam was used, and both ICs were positioned successively at the same measurement depths. For both approaches, the shift of the distal edge of the depth ionization distributions recorded by the two chambers at different reference points was used to calculate Peff of the Semiflex. Both methods were applied in carbon ion beams, and only the latter was applied in proton beams. Results: Both methods yielded a similar Peff for carbon ions, 0.88·rcyl, and 0.84·rcyl, which results in a difference of only 0.1 mm. The difference to the recommended value of 0.75·rcyl is 0.4 and 0.3 mm, respectively, which is larger than the positioning uncertainty. In the proton beam, a Peff of 0.92·rcyl was obtained. Conclusions: The Peff for the 0.125 cc Semiflex IC is shifted further from the cavity center as recommended by IAEA TRS‐398 for light ions, with the shift for proton beams being even larger than for carbon ion beams. [ABSTRACT FROM AUTHOR]

Purpose: This work presents the validation of an analytical pencil beam dose calculation algorithm in a commercial treatment planning system (TPS) for carbon ions by measurements of dose distributions in heterogeneous phantom geometries. Additionally, a comparison study of carbon ions versus protons is performed considering current best solutions in commercial TPS. Methods: All treatment plans were optimized and calculated using the RayStation TPS (RaySearch, Sweden). The dose distributions calculated with the TPS were compared with measurements using a 24‐pinpoint ionization chamber array (T31015, PTW, Germany). Tissue‐like inhomogeneities (bone, lung, and soft tissue) were embedded in water, while a target volume of 4 x 4 x 4 cm3 was defined at two different depths behind the heterogeneities. In total, 10 different test cases, with and without range shifter as well as different air gaps, were investigated. Dose distributions inside as well as behind the target volume were evaluated. Results: Inside the target volume, the mean dose difference between calculations and measurements, averaged over all test cases, was 1.6% for carbon ions. This compares well to the final agreement of 1.5% obtained in water at the commissioning stage of the TPS for carbon ions and is also within the clinically acceptable interval of 3%. The mean dose difference and maximal dose difference obtained outside the target area were 1.8% and 13.4%, respectively. The agreement of dose distributions for carbon ions in the target volumes was comparable or better to that between Monte Carlo (MC) dose calculations and measurements for protons. Percentage dose differences of more than 10% were present outside the target area behind bone–lung structures, where the carbon ion calculations systematically over predicted the dose. MC dose calculations for protons were superior to carbon ion beams outside the target volumes. Conclusion: The pencil beam dose calculations for carbon ions in RayStation were found to be in good agreement with dosimetric measurements in heterogeneous geometries for points of interest located within the target. Large local discrepancies behind the target may contribute to incorrect dose predictions for organs at risk. [ABSTRACT FROM AUTHOR]

Independent verification of the dose per monitor unit (MU) to deliver the prescribed dose to a patient has been a mainstay of radiation oncology quality assurance (QA). We discuss the role of secondary dose/MU calculation programs as part of a comprehensive QA program. This report provides guidelines on calculation‐based dose/MU verification for intensity modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) provided by various modalities. We provide a review of various algorithms for "independent/second check" of monitor unit calculations for IMRT/VMAT. The report makes recommendations on the clinical implementation of secondary dose/MU calculation programs; on commissioning and acceptance of various commercially available secondary dose/MU calculation programs; on benchmark QA and periodic QA; and on clinically reasonable action levels for agreement of secondary dose/MU calculation programs. [ABSTRACT FROM AUTHOR]

Purpose: To present the technical details of the runner‐up model in the open knowledge‐based planning (OpenKBP) challenge for the dose–volume histogram (DVH) stream. The model was designed to ensure simple and reproducible training, without the necessity of costly advanced generative adversarial network (GAN) techniques. Methods: The model was developed based on the OpenKBP challenge dataset, consisting of 200 and 40 head‐and‐neck patients for training and validation, respectively. The final model is a U‐Net with additional ResNet blocks between up‐ and down convolutions. The results were obtained by training the model with AdamW with the One Cycle scheduler. The loss function is a combination of the L1 loss with a feature loss, which uses a pretrained video classifier as a feature extractor. The performance was evaluated on another 100 patients in the OpenKBP test dataset. The DVH metrics of the test data were evaluated, where D0.1cc, and Dmean were calculated for the organs at risk (OARs) and D1%, D95%, and D99% were computed for the target structures. DVH metric differences between predicted and true dose are reported in percentage. Results: The model achieved 2nd and 4th place in the DVH and dose stream of the OpenKBP challenge, respectively. The dose and DVH score were 2.62 ± 1.10 and 1.52 ± 1.06, respectively. Mean dose differences for the different structures and DVH parameters were within ±1%. Conclusion: This straightforward approach produced excellent results. It incorporated One Cycle Learning, ResNet, and feature‐based losses, which are common computer vision techniques. [ABSTRACT FROM AUTHOR]

Purpose: In the past years, many different neural network‐based conversion techniques for synthesizing computed tomographys (sCTs) from MR images have been published. While the model's performance can be checked during the training against the test set, test datasets can never represent the whole population. Conversion errors can still occur for special cases, for example, for unusual anatomical situations. Therefore, the performance of sCT conversion needs to be verified on a patient specific level, especially in the absence of a planning CT (pCT). In this study, the capability of cone‐beam CTs (CBCTs) for the validation of sCTs generated by a neural network was investigated. Methods: 41 patients with tumors in the head region were selected. 20 of them were used for model training and 10 for validation. Different implementations of CycleGAN (with/without identity and feature loss) were used to generate sCTs. The pixel (MAE, RMSE, PSNR) and geometric error (DICE, Sensitivity, Specificity) values were reported to identify the best model. VMAT plans were created for the remaining 11 patients on the pCTs. These plans were re‐calculated on sCTs and CBCTs. An automatic density overriding method (CBCTRS) and a population‐based dose calculation method (CBCTPop) were employed for CBCT‐based dose calculation. The dose distributions were analysed using 3D global gamma analysis, applying a threshold of 10% with respect to the prescribed dose. Differences in DVH metrics for the PTV and the organs‐at‐risk were compared among the dose distributions based on pCTs, sCTs, and CBCTs. Results: The best model was the CycleGAN without identity and feature matching loss. Including the identity loss led to a metric decrease of 10% for DICE and a metric increase of 20–60 HU for MAE. Using the 2%/2 mm gamma criterion and pCT as reference, the mean gamma pass rates were 99.0 ± 0.4% for sCTs. Mean gamma pass rate values comparing pCT and CBCT were 99.0 ± 0.8% and 99.1 ± 0.8% for the CBCTRS and CBCTPop, respectively. The mean gamma pass rates comparing sCT and CBCT resulted in 98.4 ± 1.6% and 99.2 ± 0.6% for CBCTRS and CBCTPop, respectively. The differences between the gamma‐pass‐rates of the sCT and two CBCT‐based methods were not significant. The majority of deviations of the investigated DVH metrices between sCTs and CBCTs were within 2%. Conclusion: The dosimetric results demonstrate good agreement between sCT, CBCT, and pCT based calculations. A properly applied CBCT conversion method can serve as a tool for quality assurance procedures in an MR only radiotherapy workflow for head patients. Dosimetric deviations of DVH metrics between sCT and CBCTs of larger than 2% should be followed up. A systematic shift of approximately 1% should be taken into account when using the CBCTRS approach in an MR only workflow. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the response of detectors for proton dosimetry in the presence of magnetic fields. Material and Methods: Four ionization chambers (ICs), two thimble‐type and two plane‐parallel‐type, and a diamond detector were investigated. All detectors were irradiated with homogeneous single‐energy‐layer fields, using 252.7 MeV proton beams. A Farmer IC was additionally irradiated in the same geometrical configuration, but with a lower nominal energy of 97.4 MeV. The beams were subjected to magnetic field strengths of 0, 0.25, 0.5, 0.75, and 1 T produced by a research dipole magnet placed at the room's isocenter. Detectors were positioned at 2 cm water equivalent depth, with their stem perpendicular to both the magnetic field lines and the proton beam's central axis, in the direction of the Lorentz force. Normality and two sample statistical Student's t tests were performed to assess the influence of the magnetic field on the detectors' responses. Results: For all detectors, a small but significant magnetic field‐dependent change of their response was found. Observed differences compared to the no magnetic field case ranged from +0.5% to −0.7%. The magnetic field dependence was found to be nonlinear and highest between 0.25 and 0.5 T for 252.7 MeV proton beams. A different variation of the Farmer chamber response with magnetic field strength was observed for irradiations using lower energy (97.4 MeV) protons. The largest magnetic field effects were observed for plane‐parallel ionization chambers. Conclusion: Small magnetic field‐dependent changes in the detector response were identified, which should be corrected for dosimetric applications. [ABSTRACT FROM AUTHOR]

Purpose: To develop a computer‐driven and thus less user‐dependent method, allowing for a simple and straightforward generation of a Monte Carlo (MC) beam model of a scanned proton and carbon ion beam delivery system. Methods: In a first step, experimental measurements were performed for proton and carbon ion energies in the available energy ranges. Data included depth dose profiles measured in water and spot sizes in air at various isocenter distances. Using an automated regularization‐based optimization process (AUTO‐BEAM), GATE/Geant4 beam models of the respective beam lines were generated. These were obtained sequentially by using least square weighting functions with and without regularization, to iteratively tune the beam parameters energy, energy spread, beam sigma, divergence, and emittance until a user‐defined agreement was reached. Based on the parameter tuning for a set of energies, a beam model was semi‐automatically generated. The resulting beam models were validated for all centers comparing to independent measurements of laterally integrated depth dose curves and spot sizes in air. For one representative center, three‐dimensional dose cubes were measured and compared to simulations. The method was applied on one research as well as four different clinical beam lines for proton and carbon ions of three different particle therapy centers using synchrotron or cyclotron accelerator systems: (a) MedAustron ion therapy center, (b) University Proton Therapy Dresden, and (c) Center Antoine Lacassagne Nice. Results: Particle beam ranges in the MC beam models agreed on average within 0.2 mm compared to measurements for all energies and beam lines. Spot sizes in air (full‐width at half maximum) at all positions differed by less than 0.4% from the measurements. Dose calculation with the beam model for the clinical beam line at MedAustron agreed better than 1.7% in absolute dose for a representative clinical case treated with protons. For protons, beam model generation, including geometry creation, data conversion, and validation, was possible within three working days. The number of iterations required for the optimization process to converge, was found to be similar for all beam line geometries and particle types. Conclusion: The presented method was demonstrated to work independently of the beam optics behavior of the different beam lines, particle types, and geometries. Furthermore, it is suitable for non‐expert users and requires only limited user interaction. Beam model validation for different beam lines based on different beam delivery systems, showed good agreement. [ABSTRACT FROM AUTHOR]

Purpose: To design and commission a water phantom suitable for constrained environments and magnetic fields for magnetic resonance (MR)‐guided proton therapy. Methods: A phantom was designed, to enable precise, remote controlled detector positioning in water within the constrained environment of a magnet for MR‐guided proton therapy. The phantom consists of a PMMA enclosure whose outer dimensions of 81×40×12.5cm3 were chosen to optimize space usage inside the 13.5‐cm bore gap of the magnet. The moving mechanism is based on a low‐height H‐shaped non‐ferromagnetic belt drive, driven by stepper motors located outside of the magnetic field. The control system and the associated electronics were designed in house, with similar features as available in commercial water phantoms. Reproducibility as well as accuracy of the phantom positioning were tested using a high‐precision Leica AT 402 laser tracker. Laterally integrated depth dose curves and lateral beam profiles at three depths were acquired repeatedly for a 148.2 MeV proton beam in water. Results: The phantom was successfully operated with and without applied magnetic fields. For complex movements, a positioning uncertainty within 0.16 mm was found with an absolute accuracy typically below 0.3 mm. Laterally integrated depth dose curves agreed within 0.1 mm with data taken using a commercial water phantom. The lateral beam offset determined from beam profile measurements agreed well with data from Monte Carlo simulations. Conclusion: The phantom is optimally suited for detector positioning and dosimetric experiments within constrained environments in high magnetic fields. [ABSTRACT FROM AUTHOR]

Purpose: We developed a target‐based cone beam computed tomography (CBCT) imaging framework for optimizing an unconstrained three dimensional (3D) source‐detector trajectory by incorporating prior image information. Our main aim is to enable a CBCT system to provide topical information about the target using a limited angle noncircular scan orbit with a minimal number of projections. Such a customized trajectory should include enough information to sufficiently reconstruct a particular volume of interest (VOI) under kinematic constraints, which may result from the patient size or additional surgical or radiation therapy‐related equipment. Methods: A patient‐specific model from a prior diagnostic computed tomography (CT) volume is used as a digital phantom for CBCT trajectory simulations. Selection of the best projection views is accomplished through maximizing an objective function fed by the imaging quality provided by different x‐ray positions on the digital phantom data. The final optimized trajectory includes a limited angular range and a minimal number of projections which can be applied to a C‐arm device capable of general source‐detector positioning. The performance of the proposed framework is investigated in experiments involving an in‐house‐built box phantom including spherical targets as well as an Alderson‐Rando head phantom. In order to quantify the image quality of the reconstructed image, we use the average full‐width‐half‐maximum (FWHMavg) for the spherical target and feature similarity index (FSIM), universal quality index (UQI), and contrast‐to‐noise ratio (CNR) for an anatomical target. Results: Our experiments based on both the box and head phantom showed that optimized trajectories could achieve a comparable image quality in the VOI with respect to the standard C‐arm circular CBCT while using approximately one quarter of projections. We achieved a relative deviation <7% for FWHMavg between the reconstructed images from the optimized trajectories and the standard C‐arm CBCT for all spherical targets. Furthermore, for the anatomical target, the relative deviation of FSIM, UQI, and CNR between the reconstructed image related to the proposed trajectory and the standard C‐arm circular CBCT was found to be 5.06%, 6.89%, and 8.64%, respectively. We also compared our proposed trajectories to circular trajectories with equivalent angular sampling as the optimized trajectories. Our results show that optimized trajectories can outperform simple partial circular trajectories in the VOI in term of image quality. Typically, an angular range between 116° and 152° was used for the optimized trajectories. Conclusion: We demonstrated that applying limited angle noncircular trajectories with optimized orientations in 3D space can provide a suitable image quality for particular image targets and has a potential for limited angle and low‐dose CBCT‐based interventions under strong spatial constraints. [ABSTRACT FROM AUTHOR]

Purpose: A relative biological effectiveness (RBE) of 1.1 is commonly used in clinical proton therapy, irrespective of tissue type and depth. This in vitro study was conducted to quantify the RBE of scanned protons as a function of the dose‐averaged linear energy transfer (LETd) and the sensitivity factor (α/ß)X. Additionally, three phenomenological models (McNamara, Rørvik, and Jones) and one mechanistic model (repair‐misrepair‐fixation, RMF) were applied to the experimentally derived data. Methods: Four human cell lines (FaDu, HaCat, Du145, SKMel) with differential (α/ß)X ratios were irradiated in a custom‐designed irradiation setup with doses between 0 and 6 Gy at proximal, central, and distal positions of a 80 mm spread‐out Bragg peak (SOBP) centered at 80 mm (setup A: proton energies 66.5–135.6 MeV) and 155 mm (setup B: proton energies 127.2–185.9 MeV) depth, respectively. LETd values at the respective cell positions were derived from Monte Carlo simulations performed with the treatment planning system (TPS, RayStation). Dosimetric measurements were conducted to verify dose homogeneity and dose delivery accuracy. RBE values were derived for doses that resulted in 90 % (RBE90) and 10 % (RBE10) of cell survival, and survival after a 0.5 Gy dose (RBE0.5Gy), 2 Gy dose (RBE2Gy), and 6 Gy dose (RBE6Gy). Results: LETd values at sample positions were 1.9, 2.1, 2.5, 2.8, 4.1, and 4.5 keV/µm. For the cell lines with high (α/ß)X ratios (FaDu, HaCat), the LETd did not impact on the RBE. For low (α/ß)X cell lines (Du145, SKMel), LQ‐derived survival curves indicated a clear correlation of LETd and RBE. RBE90 values up to 2.9 and RBE10 values between 1.4 and 1.8 were obtained. Model‐derived RBE predictions slightly overestimated the RBE for the high (α/ß)X cell lines, although all models except the Jones model provided RBE values within the experimental uncertainty. For low (α/ß)X cell lines, no agreement was found between experiments and model predictions, that is, all models underestimated the measured RBE. Conclusions: The sensitivity parameter (α/ß)X was observed to be a major influencing factor for the RBE of protons and its sensitivity toward LETd changes. RBE prediction models are applicable for high (α/ß)X cell lines but do not estimate RBE values with sufficient accuracy in low (α/ß)X cell lines. [ABSTRACT FROM AUTHOR]

Particle therapy using protons or heavier ions is currently the most advanced form of radiotherapy and offers new opportunities for improving cancer care and research. Ions deposit the dose with a sharp maximum – the Bragg peak – and normal tissue receives a much lower dose than what is delivered by X‐ray therapy. Particle therapy has also biological advantages due to the high linear energy transfer of the charged particles around the Bragg peak. The introduction of particle therapy has been slow in Europe, but within the last decade, more than 20 clinical facilities have opened and facilitated access to this frontline therapy. In this review article, the basic concepts of particle therapy are reviewed along with a presentation of the current clinical indications, the European clinical research, and the established networks. [ABSTRACT FROM AUTHOR]

Purpose: The dose response of Gafchromic EBT3 films exposed to proton beams depends on the dose, and additionally on the beam quality, which is often quantified with the linear energy transfer (LET) and, hence, also referred to as LET quenching. Fundamentally different methods to determine correction factors for this LET quenching effect have been reported in literature and a new method using the local proton fluence distribution differential in LET is presented. This method was exploited to investigate whether a more practical correction based on the dose‐ or fluence‐averaged LET is feasible in a variety of clinically possible beam arrangements. Methods: The relative effectiveness (RE) was characterized within a high LET spread‐out Bragg peak (SOBP) in water made up by the six lowest available energies (62.4–67.5 MeV, configuration "b1") resulting in one of the highest clinically feasible dose‐averaged LET distributions. Additionally, two beams were measured where a low LET proton beam (252.7 MeV) was superimposed on "b1", which contributed either 50% of the initial particle fluence or 50% of the dose in the SOBP, referred to as configuration "b2" and "b3," respectively. The proton LET spectrum was simulated with GATE/Geant4 at all measurement positions. The net optical density change differential in LET was integrated over the local proton spectrum to calculate the net optical density and therefrom the beam quality correction factor. The LET dependence of the film response was accounted for by an LET dependence of one of the three parameters in the calibration function and was determined from inverse optimization using measurement "b1." This method was then validated on the measurements of "b2" and "b3" and subsequently used to calculate the RE at 900 positions in nine clinically relevant beams. The extrapolated RE set was used to derive a simple linear correction function based on dose‐averaged LET (Ld) and verify the validity in all points of the comprehensive RE set. Results: The uncorrected film dose deviated up to 26% from the reference dose, whereas the corrected film dose agreed within 3% in all three beams in water ("b1", "b2" and "b3"). The LET dependence of the calibration function started to strongly increase around 5 keV/μm and flatten out around 30 keV/μm. All REs calculated from the proton fluence in the nine simulated beams could be approximated with a linear function of dose‐averaged LET (RE = 1.0258−0.0211 μm/keV Ld). However, no functional relationship of RE‐ and fluence‐averaged LET could be found encompassing all beam energies and modulations. Conclusions: The film quenching was found to be nonlinear as a function of proton LET as well as of the dose‐averaged LET. However, the linear relation of RE on dose‐averaged LET was a good approximation in all cases. In contrast to dose‐averaged LET, fluence‐averaged LET could not describe the RE when multiple beams were applied. [ABSTRACT FROM AUTHOR]

Purpose: To present an analytical formalism for the in depth assessment of uncertainties of field output factors in small fields related to detector positioning based on dose profile measurements. Additionally, a procedure for the propagation of these uncertainties was developed. Methods: Based on the assumption that one dimensional and two dimensional second‐order polynomial functions can be fitted to dose profiles of small photon beams, equations for the calculation of the expectation value, the variance, and the standard deviation were developed. The following fitting procedures of the dose profiles were considered: A one‐dimensional case (1D), a quasi two‐dimensional case (2Dq) based on independently measured line profiles and a full 2D case (2Df) which also considers cross‐correlations in a two‐dimensional dose distribution. A rectangular and a Gaussian probability density function (PDF) characterizing the probability of possible positions of the detector relative to the maximum dose were used. Uncertainty components such as the finite resolution of the scanning water phantom, the reproducibility of the determination of the position of the maximum dose, and the reproducibility of the collimator system were investigated. This formalism was tested in a 0.5 x 0.5 cm2 photon field where dose profiles were measured using a radiochromic film, a synthetic diamond detector, and an unshielded diode detector. Additionally, the dose distribution measured with the radiochromic film was convoluted with a convolution kernel mimicking the active volume of the unshielded diode. Results: Analytic expressions for the calculation of uncertainties on field output factors were found for the 1D, the 2Dq, and the 2Df case. The uncertainty of the field output factor related to the relative position of the detector to the maximum dose increased quadratically with increasing limits of possible detector positions. Analysis of the radiochromic film showed that the 2Dq case gave a more conservative assessment of the uncertainty compared to the 2Df case with a difference of < 0.1%. The 2Dq case applied to the film measurements agreed well with the same approach as was applied to the unshielded diode. The investigated uncertainty components propagated to an uncertainty of the field output factors of 0.5% and 0.4% for the synthetic diamond and the unshielded diode, respectively. Additionally, the expectation value was lower than the maximum dose. The difference was 0.4% and 0.3% for the synthetic diamond and the unshielded diode, respectively. Conclusions: The assessment of uncertainties of field output factors related to detector positioning is feasible using the proposed formalism. The 2Dq case is applicable when using online detectors. Accurate positioning in small fields is essential for accurate dosimetry as its related uncertainty increases quadratically. The observed drop of the expectation value needs to be considered in small field dosimetry. [ABSTRACT FROM AUTHOR]

Purpose: Magnetic resonance guidance in proton therapy (MRPT) is expected to improve its current performance. The combination of magnetic fields with clinical proton beam lines poses several challenges for dosimetry, treatment planning and dose delivery. Proton beams are deflected by magnetic fields causing considerable changes in beam trajectories and also a retraction of the Bragg peak positions. A proper prediction and compensation of these effects is essential to ensure accurate dose calculations. This work aims to develop and benchmark a Monte Carlo (MC) beam model for dose calculation of MRPT for static magnetic fields up to 1 T. Methods: Proton beam interactions with magnetic fields were simulated using the GATE/Geant4 toolkit. The transport of charged particle in custom 3D magnetic field maps was implemented for the first time in GATE. Validation experiments were done using a horizontal proton pencil beam scanning system with energies between 62.4 and 252.7 MeV and a large gap dipole magnet (B = 0–1 T), positioned at the isocenter and creating magnetic fields transverse to the beam direction. Dose was measured with Gafchromic EBT3 films within a homogeneous PMMA phantom without and with bone and tissue equivalent material slab inserts. Linear energy transfer (LET) quenching of EBT3 films was corrected using a linear model on dose‐averaged LET method to ensure a realistic dosimetric comparison between simulations and experiments. Planar dose distributions were measured with the films in two different configurations: parallel and transverse to the beam direction using single energy fields and spread‐out Bragg peaks. The MC model was benchmarked against lateral deflections and spot sizes in air of single beams measured with a Lynx PT detector, as well as dose distributions using EBT3 films. Experimental and calculated dose distributions were compared to test the accuracy of the model. Results: Measured proton beam deflections in air at distances of 465, 665, and 1155 mm behind the isocenter after passing the magnetic field region agreed with MC‐predicted values within 4 mm. Differences between calculated and measured beam full width at half maximum (FWHM) were lower than 2 mm. For the homogeneous phantom, measured and simulated in‐depth dose profiles showed range and average dose differences below 0.2 mm and 1.2%, respectively. Simulated central beam positions and widths differed <1 mm to the measurements with films. For both heterogenous phantoms, differences within 1 mm between measured and simulated central beam positions and widths were obtained, confirming a good agreement of the MC model. Conclusions: A GATE/Geant4 beam model for protons interacting with magnetic fields up to 1 T was developed and benchmarked to experimental data. For the first time, the GATE/Geant4 model was successfully validated not only for single energy beams, but for SOBP, in homogeneous and heterogeneous phantoms. EBT3 film dosimetry demonstrated to be a powerful dosimetric tool, once the film response function is LET corrected, for measurements in‐line and transverse to the beam direction in magnetic fields. The proposed MC beam model is foreseen to support treatment planning and quality assurance (QA) activities toward MRPT. [ABSTRACT FROM AUTHOR]

Purpose: Radiochromic film dosimetry is extensively used for quality assurance in photon and proton beam therapy. So far, GafchromicTM EBT3 film appears as a strong candidate to be used in future magnetic resonance (MR) based therapy systems. The response of Gafchromic EBT3 films in the presence of magnetic fields has already been addressed for different MR‐linacs systems. However, a detailed evaluation of the influence of external magnetic fields on the film response and calibration curves for proton therapy has not yet been reported. This study aims to determine the dose responses of EBT3 films for clinical proton beams exposed to magnetic field strengths up to 1 T in order to investigate the feasibility of EBT3 film as an accurate dosimetric tool for a future MR particle therapy system (MRPT). Methods: The dosimetric characteristics of EBT3 films were studied for a proton beam passing through magnetic field strengths of B = 0, 0.5, and 1 T. Absorbed dose calibration and measurements were performed using clinical proton beams in the nominal energy range of 62.4–252.6 MeV. Irradiations were done using an in‐house developed PMMA slab phantom placed in the center of a dipole research magnet. Monte Carlo (MC) simulations using the GATE/Geant4 toolkit were performed to predict the effect of magnetic fields on the energy deposited by proton beams in the phantom. Planned and measured doses from 3D box cube irradiations were compared to assess the accuracy of the dosimetric method using EBT3 films with/without the external magnetic field. Results: Neither for the mean pixel value nor for the net optical density, any significant deviations were observed due to the presence of an external magnetic field (B ≤ 1T) for doses up to 10 Gy. Dose‐response curves for the red channel were fitted by a three‐parameter function for the field‐free case and for B = 1T, showing for both cases an R‐square coefficient of unity and almost identical fitting parameters. Independently of the magnetic field, EBT3 films showed an under‐response as high as 8% in the Bragg peak region, similarly to previously reported effects for particle therapy. No noticeable influence of the magnetic field strength was observed on the quenching effect of the EBT3 films. Conclusions: For the first time detailed absorbed dose calibrations of EBT3 films for proton beams in magnetic field regions were performed. Results showed that EBT3 films represent an attractive solution for the dosimetry of a future MRPT system. As film response functions for protons are not affected by the magnetic field strenght, they can be used for further investigations to evaluate the dosimetric effects induced due to particle beams bending in magnetic fields regions. [ABSTRACT FROM AUTHOR]

Purpose: The dose core of a proton pencil beam (PB) is enveloped by a low dose area reaching several centimeters off the central axis and containing a considerable amount of the dose. Adequate modeling of the different components of the PB profile is, therefore, required for accurate dose calculation. In this study, we experimentally validated one electromagnetic and two nuclear scattering models in GATE/Geant4 for dose calculation of proton beams in the therapeutic energy window (62–252 MeV) with and without range shifter (RaShi). Methods: The multiple Coulomb scattering (MCS) model was validated by lateral dose core profiles measured for five energies at up to four depths from beam plateau to Bragg peak region. Nuclear halo profiles of single PBs were evaluated for three (62.4, 148.2, and 252.7 MeV) and two (97.4 and 124.7 MeV) energies, without and with RaShi, respectively. The influence of the dose core and nuclear halo on field sizes varying from 2–20 cm was evaluated by means of output factors (OFs), namely frame factors (FFs) and field size factors (FSFs), to quantify the relative increase of dose when increasing the field size. Results: The relative increase in the dose core width in the simulations deviated negligibly from measurements for depths until 80% of the beam range, but was overestimated by up to 0.2 mm in σ toward the end of range for all energies. The dose halo region of the lateral dose profile agreed well with measurements in the open beam configuration, but was notably overestimated in the deepest measurement plane of the highest energy or when the beam passed through the RaShi. The root‐mean‐square deviations (RMSDs) between the simulated and the measured FSFs were less than 1% at all depths, but were higher in the second half of the beam range as compared to the first half or when traversing the RaShi. The deviations in one of the two tested hadron physics lists originated mostly in elastic scattering. The RMSDs could be reduced by approximately a factor of two by exchanging the default elastic scattering cross sections for protons. Conclusions: GATE/Geant4 agreed satisfyingly with most measured quantities. MCS was systematically overestimated toward the end of the beam range. Contributions from nuclear scattering were overestimated when the beam traversed the RaShi or at the depths close to the end of the beam range without RaShi. Both, field size effects and calculation uncertainties, increased when the beam traversed the RaShi. Measured field size effects were almost negligible for beams up to medium energy and were highest for the highest energy beam without RaShi, but vice versa when traversing the RaShi. [ABSTRACT FROM AUTHOR]

Purpose: The feasibility of magnetic resonance image (MRI)‐based proton therapy is based, among several other factors, on the implementation of appropriate extensions on current dose calculation methods. This work aims to develop a pencil beam algorithm (PBA) for dose calculation of proton beams within magnetic field regions of up to 3 T. Methods: Monte Carlo (MC) simulations using the GATE 7.1/GEANT4.9.4p02 toolkit were performed to generate calibration and benchmarking data for the PBA. Dose distributions from proton beams in the clinical required energy range 60–250 MeV impinging on a 400 × 400 × 400 mm3 water phantom and transverse magnetic fields ranging from 0 to 3 T were considered. Energy depositions in homogeneous and heterogeneous phantoms filled with water, adipose, bone, and air were evaluated for proton energies of 80, 150, and 240 MeV, combining a trajectory calculation method and look‐up tables (LUT). A novel parametrization model, using independent tailed Gauss fitting functions, was employed to describe the nonsymmetric shape of lateral beam profiles. Integrated depth‐dose curves (IDD), lateral dose profiles, and two‐dimensional dose distributions calculated with the PBA were compared with results from MC simulations to assess the performance of the algorithm. A gamma index criterion of 2%/2 mm was used for analysis. Results: A close to perfect agreement was observed for PB‐based dose calculations in water in magnetic fields of 0.5, 1.5, and 3 T. IDD functions showed differences between the PBA and MC of less than 0.1% before the Bragg peak, and deviations of 2–8% in the distal energy falloff region. Gamma index pass rates higher than 99% and mean values lower than 0.1 were encountered for all analyzed configurations. For homogeneous phantoms, only the full bone configuration offered deviations in the Bragg peak position of up to 1.7% and overestimations of the lateral beam spot width for high‐energy protons and magnetic field intensities. An excellent agreement between PBA and MC dose calculation was also achieved using slab‐like and lateral heterogeneous phantoms, with gamma index passing rates above 98% and mean values between 0.1 and 0.2. As expected, agreement reduced for high‐energy protons and high‐intensity magnetic fields, although results remained good enough to be considered for future implementation in clinical practice. Conclusions: The proposed pencil beam algorithm for protons can accurately account for dose distortion effects induced by external magnetic fields. The application of an analytical model for dose estimation and corrections reduces the calculation times considerably, making the presented PBA a suitable candidate for integration in a treatment planning system. [ABSTRACT FROM AUTHOR]

Purpose To investigate and model effects of magnetic fields on proton and carbon ion beams for dose calculation. Methods In a first step, Monte Carlo simulations using Gate 7.1/Geant4.10.0.p03 were performed for proton and carbon ion beams in magnetic fields ranging from 0 to 3 T. Initial particle energies ranged from 60 to 250 MeV (protons) and 120 to 400 MeV/u (carbon ions), respectively. The resulting dose distributions were analyzed focusing on beam deflection, dose deformation, as well as the impact of material heterogeneities. In a second step, a numerical algorithm was developed to calculate the lateral beam position. Using the Runge-Kutta method, an iterative solution of the relativistic Lorentz equation, corrected for the changing particle energy during penetration, was performed. For comparison, a γ-index analysis was utilized, using a criteria of 2%/2 mm of the local maximum. Results A tilt in the dose distribution within the Bragg peak area was observed, leading to non-negligible dose distribution changes. The magnitude was found to depend on the magnetic field strength as well as on the initial beam energy. Comparison of the 3 T dose distribution with non-B field (nominal) dose distributions, resulted in a γ mean (mean value of the γ distribution) of 0.6, with 14.4% of the values above 1 and γ1% (1% of all points have an equal or higher γ value) of 1.8. The presented numerical algorithm calculated the lateral beam offset with maximum errors of less than 2% with calculation times of less than 5 μs. The impact of tissue interfaces on the proton dose distributions was found to be less than 2% for a dose voxel size of 1 × 1 × 1 mm3. Conclusion Non-negligible dose deformations at the Bragg peak area were identified for high initial energies and strong magnetic fields. A fast numerical algorithm based on the solution of the energy-corrected relativistic Lorentz equation was able to describe the beam path, taking into account the particle energy, magnetic field, and material. [ABSTRACT FROM AUTHOR]

Purpose: For commercially available linear accelerators (Linacs), the electron energies of flattening filter free (FFF) and flattened (FF) beams are either identical or the electron energy of the FFF beam is increased to match the percentage depth dose curve (PDD) of the FF beam (in reference geometry). This study focuses on the primary dose components of FFF beams for both kinds of settings, studied on the same Linac. Methods: The measurements were conducted on a VersaHD Linac (Elekta, Crawley, UK) for both FF and FFF beams with nominal energies of 6 and 10 MV. In the clinical setting of the VersaHD, the energy of FFFM (Matched) beams is set to match the PDDs of the FF beams. In contrast the incident electron beam of the FFFU beam was set to the same energy as for the FF beam. Half value layers (HVLs) and a dual parameter beam quality specifier (DPBQS) were determined. Results: For the 6 MV FFFM beam, HVL and DPBQS values were very similar compared to those of the 6 MV FF beam, while for the 10 MV FFFM and FF beams, only %dd(10)x and HVL values were comparable (differences below 1.5%). This shows that matching the PDD at one depth does not guarantee other beam quality dependent parameters to be matched. For FFFU beams, all investigated beam quality specifiers were significantly different compared to those for FF beams of the same nominal accelerator potential. The DPBQS of the 6 MV FF and FFFM beams was equal within the measurement uncertainty and was comparable to published data of a machine with similar TPR20,10 and %dd(10)x. In contrast to that, the DPBQS's two parameters of the 10 MV FFFM beam were substantially higher compared to those for the 10 MV FF beam. Conclusions: PDD-matched FF and FFF beams of both nominal accelerator potentials were observed to have similar HVL values, indicating similarity of their primary dose components. Using the DPBQS revealed that the mean attenuation coefficient was found to be the same within the uncertainty of 0.8% for 6 MV FF and 6 MV FFFM beams, while for 10 MV beams, they differed by 6.4%. This shows that the DPBQS can provide a differentiation of photon beam characteristics that would remain hidden by the use of a single beam quality specifier, such as %dd(10)x or HVL. [ABSTRACT FROM AUTHOR]

Purpose: A fully heterogeneous population averaged mechanistic tumor control probability (TCP) model is appropriate for the analysis of external beam radiotherapy (EBRT). This has been accomplished for EBRT photon treatment of intermediate-risk prostate cancer. Extending the TCP model for low and high-risk patients would be beneficial in terms of overall decision making. Furthermore, different radiation treatment modalities such as protons and carbon-ions are becoming increasingly available. Consequently, there is a need for a complete TCP model. Methods: A TCP model was fitted and validated to a primary endpoint of 5-year biological no evidence of disease clinical outcome data obtained from a review of the literature for low, intermediate, and high-risk prostate cancer patients (5218 patients fitted, 1088 patients validated), treated by photons, protons, or carbon-ions. The review followed the preferred reporting item for systematic reviews and meta-analyses statement. Treatment regimens include standard fractionation and hypofractionation treatments. Residual analysis and goodness of fit statistics were applied. Results: The TCP model achieves a good level of fit overall, linear regression results in a p-value of <0.000 01 with an adjusted-weighted-R² value of 0.77 and a weighted root mean squared error (wRMSE) of 1.2%, to the fitted clinical outcome data. Validation of the model utilizing three independent datasets obtained from the literature resulted in an adjusted-weighted-R² value of 0.78 and a wRMSE of less than 1.8%, to the validation clinical outcome data. The weighted mean absolute residual across the entire dataset is found to be 5.4%. Conclusions: This TCP model fitted and validated to clinical outcome data, appears to be an appropriate model for the inclusion of all clinical prostate cancer risk categories, and allows evaluation of current EBRT modalities with regard to tumor control prediction. [ABSTRACT FROM AUTHOR]

In Zhu et al.,1 the COI disclosure statement missed disclosing two authors who are from commercial companies, thus the COI disclosure statement are corrected. Report of AAPM Task Group 219 on independent calculation-based dose/MU verification for IMRT. Erratum: "Report of AAPM Task Group 219 on independent calculation-based dose/MU verification for IMRT". [Extracted from the article]

Purpose: Helium ions (4He) may supplement current particle beam therapy strategies as they possess advantages in physical dose distribution over protons. To assess potential clinical advantages, a dose calculation module accounting for relative biological effectiveness (RBE) was developed and integrated into the treatment planning system Hyperion. Methods: Current knowledge on RBE of 4He together with linear energy transfer considerations motivated an empirical depth-dependent "zonal" RBE model. In the plateau region, a RBE of 1.0 was assumed, followed by an increasing RBE up to 2.8 at the Bragg-peak region, which was then kept constant over the fragmentation tail. To account for a variable proton RBE, the same model concept was also applied to protons with a maximum RBE of 1.6. Both RBE models were added to a previously developed pencil beam algorithm for physical dose calculation and included into the treatment planning system Hyperion. The implementation was validated against Monte Carlo simulations within a water phantom using -index evaluation. The potential benefits of 4He based treatment plans were explored in a preliminary treatment planning comparison (against protons) for four treatment sites, i.e., a prostate, a base-of-skull, a pediatric, and a head-and-neck tumor case. Separate treatment plans taking into account physical dose calculation only or using biological modeling were created for protons and 4He. Results: Comparison of Monte Carlo and Hyperion calculated doses resulted in a γmean of 0.3, with 3.4% of the values above 1 and γ1% of 1.5 and better. Treatment plan evaluation showed comparable planning target volume coverage for both particles, with slightly increased coverage for 4He. Organ at risk (OAR) doses were generally reduced using 4He, some by more than to 30%. Improvements of 4He over protons were more pronounced for treatment plans taking biological effects into account. All OAR doses were within tolerances specified in the QUANTEC report. Conclusions: The biological 4He model proposed above is a first approach matching biological data published so far. The advantage of 4He seems to lie in the reduction of dose to surrounding tissue and to OARs. Nevertheless, additional biological experiments and treatment planning studies with larger patient numbers and more tumor indications are necessary to study the possible benefits of helium ion beam therapy in detail. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the present study is to provide a comprehensive set of detector specific correction factors for beam output measurements for small beams, for a wide range of real time and passive detectors. The detector specific correction factors determined in this study may be potentially useful as a reference data set for small beam dosimetry measurements. Methods: Dose response of passive and real time detectors was investigated for small field sizes shaped with a micromultileaf collimator ranging from 0.6 × 0.6 cm² to 4.2 × 4.2 cm² and the measurements were extended to larger fields of up to 10 × 10 cm². Measurements were performed at 5 cm depth, in a 6 MV photon beam. Detectors used included alanine, thermoluminescent dosimeters (TLDs), stereotactic diode, electron diode, photon diode, radiophotoluminescent dosimeters (RPLDs), radioluminescence detector based on carbon-doped aluminium oxide (Al2O3:C), organic plastic scintillators, diamond detectors, liquid filled ion chamber, and a range of small volume air filled ionization chambers (volumes ranging from 0.002 cm³ to 0.3 cm³). All detector measurements were corrected for volume averaging effect and compared with dose ratios determined from alanine to derive a detector correction factors that account for beam perturbation related to nonwater equivalence of the detector materials. Results: For the detectors used in this study, volume averaging corrections ranged from unity for the smallest detectors such as the diodes, 1.148 for the 0.14 cm³ air filled ionization chamber and were as high as 1.924 for the 0.3 cm³ ionization chamber. After applying volume averaging corrections, the detector readings were consistent among themselves and with alanine measurements for several small detectors but they differed for larger detectors, in particular for some small ionization chambers with volumes larger than 0.1 cm³. Conclusions: The results demonstrate how important it is for the appropriate corrections to be applied to give consistent and accurate measurements for a range of detectors in small beam geometry. The results further demonstrate that depending on the choice of detectors, there is a potential for large errors when effects such as volume averaging, perturbation and differences in material properties of detectors are not taken into account. As the commissioning of small fields for clinical treatment has to rely on accurate dose measurements, the authors recommend the use of detectors that require relatively little correction, such as unshielded diodes, diamond detectors or microchambers, and solid state detectors such as alanine, TLD, Al2O3:C, or scintillators. [ABSTRACT FROM AUTHOR]

Purpose: To develop a flexible pencil beam algorithm for helium ion beam therapy. Dose distributions were calculated using the newly developed pencil beam algorithm and validated using Monte Carlo (MC) methods. Methods: The algorithm was based on the established theory of fluence weighted elemental pencil beam (PB) kernels. Using a new real-time splitting approach, a minimization routine selects the optimal shape for each sub-beam. Dose depositions along the beam path were determined using a look-up table (LUT). Data for LUT generation were derived from MC simulations in water using GATE 6.1. For materials other than water, dose depositions were calculated by the algorithm using water-equivalent depth scaling. Lateral beam spreading caused by multiple scattering has been accounted for by implementing a non-local scattering formula developed by Gottschalk. A new nuclear correction was modelled using a Voigt function and implemented by a LUT approach. Validation simulations have been performed using a phantom filled with homogeneous materials or heterogeneous slabs of up to 3 cm. The beams were incident perpendicular to the phantoms surface with initial particle energies ranging from 50 to 250 MeV/A with a total number of 107 ions per beam. For comparison a special evaluation software was developed calculating the gamma indices for dose distributions. Results: In homogeneous phantoms, maximum range deviations between PB and MC of less than 1.1% and differences in the width of the distal energy falloff of the Bragg-Peak from 80% to 20% of less than 0.1 mm were found. Heterogeneous phantoms using layered slabs satisfied a γ-index criterion of 2%/2mm of the local value except for some single voxels. For more complex phantoms using laterally arranged bone-air slabs, the γ-index criterion was exceeded in some areas giving a maximum γ-index of 1.75 and 4.9% of the voxels showed γ-index values larger than one. The calculation precision of the presented algorithm was considered to be sufficient for clinical practice. Although only data for helium beams was presented, the performance of the pencil beam algorithm for proton beams was comparable. Conclusions: The pencil beam algorithm developed for helium ions presents a suitable tool for dose calculations. Its calculation speed was evaluated to be similar to other published pencil beam algorithms. The flexible design allows easy customization of measured depth-dose distributions and use of varying beam profiles, thus making it a promising candidate for integration into future treatment planning systems. Current work in progress deals with RBE effects of helium ions to complete the model. [ABSTRACT FROM AUTHOR]

Purpose: Positron emission tomography (PET) is considered to be the state of the art technique to monitor particle therapy in vivo. To evaluate the beam delivery the measured PET image is compared to a predicted β+-distribution. Nowadays the range assessment is performed by a group of experts via visual inspection. This procedure is rather time consuming and requires well trained personnel. In this study an approach is presented to support human decisions in an automated and objective way. Methods: The automated comparison presented uses statistical measures, namely, Pearson's correlation coefficient (PCC), to detect ion beam range deviations. The study is based on 12 in-beam PET patient data sets recorded at GSI and 70 artificial beam range modifications per data set. The range modifications were 0, 4, 6, and 10 mm water equivalent path length (WEPL) in positive and negative beam directions. The reference image to calculate the PCC was both an unmodified simulation of the activity distribution (Test 1) and a measured in-beam PET image (Test 2). Based on the PCCs sensitivity and specificity were calculated. Additionally the difference between modified and unmodified data sets was investigated using the Wilcoxon rank sum test. Results: In Test 1 a sensitivity and specificity over 90% was reached for detecting modifications of ±10 and ±6 mm WEPL. Regarding Test 2 a sensitivity and specificity above 80% was obtained for modifications of ±10 and -6 mm WEPL. The limitation of the method was around 4 mm WEPL. Conclusions: The results demonstrate that the automated comparison using PCC provides similar results in terms of sensitivity and specificity compared to visual inspections of in-beam PET data. Hence the method presented in this study is a promising and effective approach to improve the efficiency in the clinical workflow in terms of particle therapy monitoring by means of PET. [ABSTRACT FROM AUTHOR]

Purpose: Flattening filters (FFs) have been considered as an integral part of the treatment head of a medical accelerator for more than 50 years. The reasons for the longstanding use are, however, historical ones. Advanced treatment techniques, such as stereotactic radiotherapy or intensity modulated radiotherapy have stimulated the interest in operating linear accelerators in a flattening filter free (FFF) mode. The current manuscript reviews treatment head physics of FFF beams, describes their characteristics and the resulting potential advantages in their medical use, and closes with an outlook. Methods: A number of dosimetric benefits have been determined for FFF beams, which range from increased dose rate and dose per pulse to favorable output ratio in-air variation with field size, reduced energy variation across the beam, and reduced leakage and out-of-field dose, respectively. Finally, the softer photon spectrum of unflattened beams has implications on imaging strategies and radiation protection. Results: The dosimetric characteristics of FFF beams have an effect on treatment delivery, patient comfort, dose calculation accuracy, beam matching, absorbed dose determination, treatment planning, machine specific quality assurance, imaging, and radiation protection. When considering conventional C-arm linacs in a FFF mode, more studies are needed to specify and quantify the clinical advantages, especially with respect to treatment plan quality and quality assurance. Conclusions: New treatment units are already on the market that operate without a FF or can be operated in a dedicated clinical FFF mode. Due to the convincing arguments of removing the FF, it is expected that more vendors will offer dedicated treatment units for advanced photon beam therapy in the near future. Several aspects related to standardization, dosimetry, treatment planning, and optimization need to be addressed in more detail in order to facilitate the clinical implementation of unflattened beams. [ABSTRACT FROM AUTHOR]

Purpose: Recently, there has been an increasing interest in operating conventional linear accelerators without a flattening filter. The aim of this study was to determine beam quality variations as a function of off-axis ray angle for unflattened beams. In addition, a comparison was made with the off-axis energy variation in flattened beams. Methods: Two Elekta Precise linear accelerators were modified in order to enable radiation delivery with and without the flattening filter in the beam line. At the Medical University Vienna (Vienna, Austria), half value layer (HVL) measurements were performed for 6 and 10 MV with an in-house developed device that can be easily mounted on the gantry. At St. Luke’s Hospital (Dublin, Ireland), measurements were performed at 6 MV in narrow beam geometry with the gantry tilted around 270° with pinhole collimators, an attenuator, and the chamber positioned on the table. All attenuation measurements were performed with ionization chambers and a buildup cap (2 mm brass) or a PMMA mini phantom (diameter 3 cm, measurement depth 2.5 cm). Results: For flattened 6 and 10 MV photon beams from the Elekta linac the relative HVL(θ) varies by about 11% for an off-axis ray angle θ=10°. These results agree within ±2% with a previously proposed generic off-axis energy correction. For unflattened beams, the variation was less than 5% in the whole range of off-axis ray angles up to 10°. The difference in relative HVL data was less than 1% for unflattened beams at 6 and 10 MV. Conclusions: Off-axis energy variation is rather small in unflattened beams and less than half the one for flattened beams. Thus, ignoring the effect of off-axis energy variation for dose calculations in unflattened beams can be clinically justified. [ABSTRACT FROM AUTHOR]

In this article, the authors evaluate a merit function for 2D/3D registration called stochastic rank correlation (SRC). SRC is characterized by the fact that differences in image intensity do not influence the registration result; it therefore combines the numerical advantages of cross correlation (CC)-type merit functions with the flexibility of mutual-information-type merit functions. The basic idea is that registration is achieved on a random subset of the image, which allows for an efficient computation of Spearman’s rank correlation coefficient. This measure is, by nature, invariant to monotonic intensity transforms in the images under comparison, which renders it an ideal solution for intramodal images acquired at different energy levels as encountered in intrafractional kV imaging in image-guided radiotherapy. Initial evaluation was undertaken using a 2D/3D registration reference image dataset of a cadaver spine. Even with no radiometric calibration, SRC shows a significant improvement in robustness and stability compared to CC. Pattern intensity, another merit function that was evaluated for comparison, gave rather poor results due to its limited convergence range. The time required for SRC with 5% image content compares well to the other merit functions; increasing the image content does not significantly influence the algorithm accuracy. The authors conclude that SRC is a promising measure for 2D/3D registration in IGRT and image-guided therapy in general. [ABSTRACT FROM AUTHOR]

The verification of dose distributions with high dose gradients as appearing in brachytherapy or stereotactic radiotherapy for example, calls for dosimetric methods with sufficiently high spatial resolution. Polymer gels in combination with a MR or optical scanner as a readout device have the potential of performing the verification of a three-dimensional dose distribution within a single measurement. The purpose of this work is to investigate the spatial resolution achievable in MR-based polymer gel dosimetry. The authors show that dosimetry on a very small spatial scale (voxel size: 94×94×1000 μm3) can be performed with normoxic polymer gels using parameter selective T2 imaging. In order to prove the spatial resolution obtained we are relying on the dose-modulation transfer function (DMTF) concept based on very fine dose modulations at half periods of 200 μm. Very fine periodic dose modulations of a 60Co photon field were achieved by means of an absorption grid made of tungsten-carbide, specifically designed for quality control. The dose modulation in the polymer gel is compared with that of film dosimetry in one plane via the DMTF concept for general access to the spatial resolution of a dose imaging system. Additionally Monte Carlo simulations were performed and used for the calculation of the DMTF of both, the polymer gel and film dosimetry. The results obtained by film dosimetry agree well with those of Monte Carlo simulations, whereas polymer gel dosimetry overestimates the amplitude value of the fine dose modulations. The authors discuss possible reasons. The in-plane resolution achieved in this work competes with the spatial resolution of standard clinical film-scanner systems. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the possibility of detecting patient mispositioning in carbon-ion therapy with particle therapy positron emission tomography (PET) in an automated image registration based manner. Methods: Tumors in the head and neck (H&N), pelvic, lung, and brain region were investigated. Biologically optimized carbon ion treatment plans were created with TRiP98. From these treatment plans, the reference β+-activity distributions were calculated using a Monte Carlo simulation. Setup errors were simulated by shifting or rotating the computed tomography (CT). The expected β+ activity was calculated for each plan with shifts. Finally, the reference particle therapy PET images were compared to the 'shifted' β+-activity distribution simulations using the Pearson's correlation coefficient (PCC). To account for different PET monitoring options the inbeam PET was compared to three different inroom scenarios. Additionally, the dosimetric effects of the CT misalignments were investigated. Results: The automated PCC detection of patient mispositioning was possible in the investigated indications for cranio-caudal shifts of 4 mm and more, except for prostate tumors. In the rather homogeneous pelvic region, the generated β+-activity distribution of the reference and compared PET image were too much alike. Thus, setup errors in this region could not be detected. Regarding lung lesions the detection strongly depended on the exact tumor location: in the center of the lung tumor misalignments could be detected down to 2 mm shifts while resolving shifts of tumors close to the thoracic wall was more challenging. Rotational shifts in the H&N and lung region of +6° and more could be detected using inroom PET and partly using inbeam PET. Comparing inroom PET to inbeam PET no obvious trend was found. However, among the inroom scenarios a longer measurement time was found to be advantageous. Conclusions: This study scopes the use of various particle therapy PET verification techniques in four indications. The automated detection of patients' setup errors was investigated in a broad accumulation of data sets. The evaluation of introduced setup errors is performed automatically, which is of utmost importance to introduce highly required particle therapy monitoring devices into the clinical routine. [ABSTRACT FROM AUTHOR]

Purpose: Recent developments in radiation therapy such as intensity modulated radiotherapy (IMRT) or dose painting promise to provide better dose distribution on the tumor. For effective application of these methods the exact positioning of the patient and the localization of the irradiated organ and surrounding structures is crucial. Especially with respect to the treatment of the prostate, ultrasound (US) allows for differentiation between soft tissue and was therefore applied by various repositioning systems, such as BAT or Clarity. The authors built a new system which uses 3D US at both sites, the CT room and the intervention room and applied a 3D/3D US/US registration for automatic repositioning. Methods: In a first step the authors applied image preprocessing methods to prepare the US images for an optimal registration process. For the 3D/3D registration procedure five different metrics were evaluated. To find the image metric which fits best for a particular patient three 3D US images were taken at the CT site and registered to each other. From these results an US registration error was calculated. The most successful image metric was then applied for the US/US registration process. The success of the whole repositioning method was assessed by taking the results of an ExacTrac system as golden standard. Results: The US/US registration error was found to be 2.99 ± 1.54 mm with respect to the mutual information metric by Mattes (eleven patients) which revealed to be the most suitable of the assessed metrics. For complete repositioning chain the error amounted to 4.15 ± 1.20 mm (ten patients). Conclusions: The authors developed a system for patient repositioning which works automatically without the necessity of user interaction with an accuracy which seems to be suitable for clinical application. [ABSTRACT FROM AUTHOR]