Technical Note: Improving the workflow in a carbon ion therapy center with custom software for enhanced patient care.

Carbon-ion radiation therapy (CIRT) is an up-and-coming modality for cancer treatment. Implementation of CIRT requires collaboration among specialists like radiation oncologists, medical physicists, and other healthcare professionals. Effective communication among team members is necessary for the success of CIRT. However, the current workflows involving data management, treatment planning, scheduling, and quality assurance (QA) can be susceptible to errors, leading to delays and decreased efficiency. With the aim of addressing these challenges, a team of medical physicists developed an in-house workflow management software using FileMaker Pro. This tool has streamlined the workflow and improved the efficiency and quality of patient care.

Development and characterization of a dedicated dose monitor for ultrahigh-dose-rate scanned carbon-ion beams.

The current monochromatic beam mode (i.e., uHDR irradiation mode) of the scanned carbon-ion beam lacks a dedicated dose monitor, making the beam control challenging. We developed and characterized a dedicated dose monitor for uHDR-scanned carbon-ion beams. Furthermore, a simple measurable dose rate (dose rate per spot (DRspot)) was suggested by using the developed dose monitor and experimentally validating quantities relevant to the uHDR scanned carbon-ion beam. A large plane-parallel ionization chamber (IC) with a smaller electrode spacing was used to reduce uHDR recombination effects, and a dedicated operational amplifier was manufactured for the uHDR-scanned carbon-ion beam. The dose linearity of the IC was within ± 1% in the range of 1.8-12.3 Gy. The spatial inhomogeneity of the dose response of the IC was ± 0.38% inside the ± 40-mm detector area, and a systematic deviation of approximately 2% was measured at the edge of the detector. uHDR irradiation with beam scanning was tested and verified for different doses at the corresponding dose rates (in terms of both the average dose rate and DRspot). We confirmed that the dose monitor can highlight the characteristics (i.e., dose, dose rate, and dose profile) of uHDR-scanned carbon-ion beams at several dose levels in the monochromatic beam mode.

Beam delivery characteristics of the Hitachi carbon ion scanning system at Osaka Heavy Ion Medical Accelerator in Kansai (HIMAK).

BACKGROUND: Using the pencil beam raster scanning method employed at most carbon beam treatment facilities, spots can be moved without interrupting the beam, allowing for the delivery of a dose between spots (move dose). This technique is also known as Dose-Driven-Continuous-Scanning (DDCS). To minimize its impact on HIMAK patient dosimetry, there's an upper limit to the move dose. Spots within a layer are grouped into sets, or "break points," allowing continuous irradiation. The beam is turned off when transitioning between sets or at the end of a treatment layer or spill. The control system beam-off is accomplished by turning off the RF Knockout (RFKO) extraction and after a brief delay the High Speed Steering Magnet (HSST) redirects the beam transport away from isocenter to a beam dump. PURPOSE: The influence of the move dose and beam on/off control on the dose distribution and irradiation time was evaluated by measurements never before reported and modelled for Hitachi Carbon DDCS. METHOD: We conducted fixed-point and scanning irradiation experiments at three different energies, both with and without breakpoints. For fixed-point irradiation, we utilized a 2D array detector and an oscilloscope to measure beam intensity over time. The oscilloscope data enabled us to confirm beam-off and beam-on timing due to breakpoints, as well as the relative timing of the RFKO signal, HSST signal, and dose monitor (DM) signals. From these measurements, we analyzed and modelled the temporal characteristics of the beam intensity. We also developed a model for the spot shape and amplitude at isocenter occurring after the beam-off signal which we called flap dose and its dependence on beam intensity. In the case of scanning irradiation, we measured move doses using the 2D array detector and compared these measurements with our model. RESULT: We observed that the most dominant time variation of the beam intensity was at 1 kHz and its harmonic frequencies. Our findings revealed that the derived beam intensity cannot reach the preset beam intensity when each spot belongs to different breakpoints. The beam-off time due to breakpoints was approximately 100 ms, while the beam rise time and fall time (tdecay ) were remarkably fast, about 10 ms and 0.2 ms, respectively. Moreover, we measured the time lag (tdelay ) of approximately 0.2 ms between the RFKO and HSST signals. Since tdelay ≈ tdecay at HIMAK then the HSST is activated after the residual beam intensity, resulting in essentially zero flap dose at isocenter from the HSST. Our measurements of the move dose demonstrated excellent agreement with the modelled move dose. CONCLUSION: We conducted the first move dose measurement for a Hitachi Carbon synchrotron, and our findings, considering beam on/off control details, indicate that Hitachi's carbon synchrotron provides a stable beam at HIMAK. Our work suggests that measuring both move dose and flap dose should be part of the commissioning process and possibly using our model in the Treatment Planning System (TPS) for new facilities with treatment delivery control systems with higher beam intensities and faster beam-off control.

Validation of robust radiobiological optimization algorithms based on the mixed beam model for intensity-modulated carbon-ion therapy.

Currently, treatment planning systems (TPSs) that can compute the intensities of intensity-modulated carbon-ion therapy (IMCT) using scanned carbon-ion beams are limited. In the present study, the computational efficacy of the newly designed IMCT algorithms was analyzed for the first time based on the mixed beam model with respect to the physical and biological doses; moreover, the validity and effectiveness of the robust radiobiological optimization were verified. A dose calculation engine was independently generated to validate a clinical dose determined in the TPS. A biological assay was performed using the HSGc-C5 cell line to validate the calculated surviving fraction (SF). Both spot control (SC) and voxel-wise worst-case scenario (WC) algorithms were employed for robust radiobiological optimization followed by their application in a Radiation Therapy Oncology Group benchmark phantom under homogeneous and heterogeneous conditions and a clinical case for range and position errors. Importantly, for the first time, both SC and WC algorithms were implemented in the integrated TPS platform that can compute the intensities of IMCT using scanned carbon-ion beams for robust radiobiological optimization. For assessing the robustness, the difference between the maximum and minimum values of a dose-volume histogram index in the examined error scenarios was considered as a robustness index. The relative biological effectiveness (RBE) determined by the independent dose calculation engine exhibited a -0.6% difference compared with the RBE defined by the TPS at the isocenter, whereas the measured and the calculated SF were similar. Regardless of the objects, compared with the conventional IMCT, the robust radiobiological optimization enhanced the sensitivity of the examined error scenarios by up to 19% for the robustness index. The computational efficacy of the novel IMCT algorithms was verified according to the mixed beam model with respect to the physical and biological doses. The robust radiobiological optimizations lowered the impact of range and position uncertainties considerably in the examined scenarios. The robustness of the WC algorithm was more enhanced compared with that of the SC algorithm. Nevertheless, the SC algorithm can be used as an alternative to the WC IMCT algorithm with respect to the computational cost.

Treatment planning of carbon ion radiotherapy for prostate cancer based on cellular experiments with PC3 human prostate cancer cells.

[Purpose] Treatment plans for carbon ion radiotherapy (CIRT) in Japan are designed to uniformly deliver the prescribed clinical dose based on the radiosensitivity of human salivary gland (HSG) cells to the planning target volume (PTV). However, sensitivity to carbon beams varies between cell lines, that is, it should be checked that the clinical dose distribution based on the cell radiosensitivity of the treatment site is uniform within the PTV. [Methods] We modeled the linear energy transfer (LET) dependence of the linear-quadratic (LQ) coefficients specific to prostate cancer, which accounts for the majority of CIRT. This was achieved by irradiating prostate cancer cells (PC3) with X-rays from a 4 MV-Linac and carbon beams with different LETs of 11.1-214.3 keV/µm. By using the radiosensitivity of PC3 cells derived from cellular experiments, we reconstructed prostate-cancer-specific clinical dose distributions on patient computed tomography (CT). [Results] The LQ coefficient, α, of PC3 cells was larger than that of HSG cells at low (<50 keV/µm) LET and smaller at high (>50 keV/µm) LET, which was validated by cellular experiments performed on rectangular SOBPs. The reconstructed dose distribution on patient CT was sloped when 1 fraction incident from the one side of the patient was considered, but remained uniform from the sum of 12 fractions of the left-right opposing beams (as is used in clinical practice). [Conclusion] Our study reveals the inhomogeneity of clinical doses in single-field plans calculated using the PC3 radiosensitivity data. However, this inhomogeneity is compensated by using the combination of left-right opposing beams.

Ultra-high Dose-rate Carbon-ion Scanning Beam With a Compact Medical Synchrotron Contributing to Further Development of FLASH Irradiation.

BACKGROUND/AIM: The focus of this report is establishing an irradiation arrangement to realize an ultra-high dose-rate (uHDR; FLASH) of scanned carbon-ion irradiation possible with a compact commonly available medical synchrotron. MATERIALS AND METHODS: Following adjustments to the operation it became possible to extract ≥1.0×109 carbon ions at 208.3 MeV/u (86 mm in range) per 100 ms. The design takes the utmost care to prevent damage to monitors, particularly in the nozzle, achieved by the uHDR beam not passing through this part of the apparatus. Doses were adjusted by extraction times, using a function generator. After one scan by the carbon-ion beam it became possible to create a field within the extraction time. The Advanced Markus chamber (AMC) and Gafchromic film are then able to measure the absolute dose and field size at a plateau depth, with the operating voltage of the chamber at 400 V at the uHDR for the AMC. RESULTS: The beam scanning utilizing this uHDR irradiation could be confirmed at a dose of 6.5±0.08 Gy (±3% homogeneous) at this volume over at least 16×16 mm2 corresponding to a dose-rate of 92.3 Gy/s (±1.3%). The dose was ca. 0.7, 1.5, 2.9, and 5.4 Gy depending on dose-rate and field size, with the rate of killed cells increasing with the irradiation dose. CONCLUSION: The compact medical synchrotron achieved FLASH dose-rates of >40 Gy/s at different dose levels and in useful field sizes for research with the apparatus and arrangement developed here.

Clinical dose assessment for scanned carbon-ion radiotherapy using linear energy transfer measurements and Monte Carlo simulations.

Objective. Dosimetric commissioning of treatment planning systems (TPS) focuses on validating the agreement of the physical dose with experimental data. For carbon-ion radiotherapy, the commissioning of the relative biological effectiveness (RBE) is necessary to predict the clinical outcome based on the radiation quality of the mixed radiation field. In this study, we proposed a approach for RBE commissioning using Monte Carlo (MC) simulations, which was further strengthen by RBE validation based on linear energy transfer (LET) measurements.Approach. First, we tuned the MC simulation based on the results of dosimetric experiments including the beam ranges, beam sizes, and MU calibrations. Furthermore, we compared simulated results to measured depth- and radial-LET distributions of the 430 MeV u-1carbon-ion spot beam with a 1.5 mm2, 36µm thick silicon detector. The measured dose-averaged LET (LETd) and RBE were compared with the simulated results. The RBE was calculated based on the mixed beam model with linear-quadratic parameters depending on the LET. Finally, TPS-calculated clinical dose profiles were validated through the tuned MC-based calculations.Main results. A 10 keVµm-1and 0.15 agreement for LETdand RBE, respectively, were found between simulation and measurement results obtained for a 2σlateral size of 430 MeV u-1carbon-ion spot beam in water. These results suggested that the tuned MC simulation can be used with acceptable precision for the RBE and LET calculations of carbon-ion spot beam within the clinical energy range. For physical and clinical doses, the TPS- and MC-based calculations showed good agreements within 1.0% at the centre of the spread-out Bragg peaks.Significance. The tuned MC simulation can accurately reproduce the actual carbon-ion beams, and it can be used to validate the physical and clinical dose distributions calculated by TPS. Moreover, the MC simulation can be used for dosimetric commissioning, including clinical doses, without LET measurements.

Commissioning a newly developed treatment planning system, VQA Plan, for fast-raster scanning of carbon-ion beams.

In this study, we report our experience in commissioning a commercial treatment planning system (TPS) for fast-raster scanning of carbon-ion beams. This TPS uses an analytical dose calculation algorithm, a pencil-beam model with a triple Gaussian form for the lateral-dose distribution, and a beam splitting algorithm to consider lateral heterogeneity in a medium. We adopted the mixed beam model as the relative biological effectiveness (RBE) model for calculating the RBE values of the scanned carbon-ion beam. To validate the modeled physical dose, we compared the calculations with measurements of various relevant quantities as functions of the field size, range and width of the spread-out Bragg peak (SOBP), and depth-dose and lateral-dose profiles for a 6-mm SOBP in water. To model the biological dose, we compared the RBE calculated with the newly developed TPS to the RBE calculated with a previously validated TPS that is in clinical use and uses the same RBE model concept. We also performed patient-specific measurements to validate the dose model in clinical situations. The physical beam model reproduces the measured absolute dose at the center of the SOBP as a function of field size, range, and SOBP width and reproduces the dose profiles for a 6-mm SOBP in water. However, the profiles calculated for a heterogeneous phantom have some limitations in predicting the carbon-ion-beam dose, although the biological doses agreed well with the values calculated by the validated TPS. Using this dose model for fast-raster scanning, we successfully treated more than 900 patients from October 2018 to October 2020, with an acceptable agreement between the TPS-calculated and measured dose distributions. We conclude that the newly developed TPS can be used clinically with the understanding that it has limited accuracies for heterogeneous media.

A Consistent Protocol Reveals a Large Heterogeneity in the Biological Effectiveness of Proton and Carbon-Ion Beams for Various Sarcoma and Normal-Tissue-Derived Cell Lines.

This study investigated variations in the relative biological effectiveness (RBE) values among various sarcoma and normal-tissue-derived cell lines (normal cell line) in proton beam and carbon-ion irradiations. We used a consistent protocol that specified the timing of irradiation after plating cells and detailed the colony formation assay. We examined the cell type dependence of RBE for proton beam and carbon-ion irradiations using four human sarcoma cell lines (MG63 osteosarcoma, HT1080 fibrosarcoma, SW872 liposarcoma, and SW1353 chondrosarcoma) and three normal cell lines (HDF human dermal fibroblast, hTERT-HME1 mammary gland, and NuLi-1 bronchus epithelium). The cells were irradiated with gamma rays, proton beams at the center of the spread-out Bragg peak, or carbon-ion beams at 54.4 keV/µm linear energy transfer. In all sarcoma and normal cell lines, the average RBE values in proton beam and carbon-ion irradiations were 1.08 ± 0.11 and 2.08 ± 0.36, which were consistent with the values of 1.1 and 2.13 used in current treatment planning systems, respectively. Up to 34% difference in the RBE of the proton beam was observed between MG63 and HT1080. Similarly, a 32% difference in the RBE of the carbon-ion beam was observed between SW872 and the other sarcoma cell lines. In proton beam irradiation, normal cell lines had less variation in RBE values (within 10%), whereas in carbon-ion irradiation, RBE values differed by up to 48% between hTERT-HME1 and NuLi-1. Our results suggest that specific dose evaluations for tumor and normal tissues are necessary for treatment planning in both proton and carbon-ion therapies.

Commissioning of carbon-ion radiotherapy for moving targets at the Osaka Heavy-Ion Therapy Center.

PURPOSE: Herein, we report the methods and results of the Hitachi carbon-ion therapy facility commissioning to determine the optimum values of the magnitude of movement and repaint number in respiratory-gated irradiation. METHODS: A virtual-cylinder target was created using the treatment-planning system (VQA Plan), and measurements were performed to study the effects of respiratory movements using a two-dimensional ionization-chamber array detector and a phantom with movable wedge and stage. For simulations, we selected a 10 × 10 × 10 cm3 cubic irradiation pattern with a uniform physical dose and two actual cases of liver-cancer treatments, whose prescribed doses were 60 Gy(RBE)/4 fraction (Case 1) and 60 Gy(RBE)/12 fraction (Case 2). We employed two types of repainting methods, one produced by the algorithm of VQA Plan (VQA algorithm) and the other by ideal repainting. The latter completely repeats all spots with set number of repaintings. We performed flatness calculations and gamma analysis to evaluate the effects of each condition. RESULTS: From the measurements, the gamma passing rates for which the criteria were 3%/3 mm exceeded 95% for displacements in the head-to-tail direction if the repaint number was greater than 3 and the magnitude of the residual motions was less than 5.0 mm. In simulations with the cubic irradiation pattern, the gamma passing rates (with criteria of 2%/2 mm) exceeded 95% when the magnitude of the residual motions was 3.0 mm and the repaint number was greater than 3. When the repaint number was set to 4 in the VQA with the actual liver cases, the flatness results for Case 2 was minimal. For ideal repainting, the flatness results for all ports fell within ∼3.0% even when the magnitude of the residual motions was 5.0 mm if the repaint number was 6. However, the flatness was less than 3.0% for almost all ports if the magnitude of the residual motions was less than 3.0 mm with a repaint number of 4 in case of both types of repaint methods. CONCLUSIONS: At our facility, carbon-ion radiotherapy can be provided safely to a moving target with residual motions of 3.0 mm magnitude and with a repaint number of 4.

Carbon ion radiotherapy using fiducial markers for prostate cancer in Osaka HIMAK: Treatment planning.

PURPOSE: Carbon ion radiotherapy for prostate cancer was performed using two fine needle Gold Anchor (GA) markers for patient position verification in Osaka Heavy Ion Medical Accelerator in Kansai (Osaka HIMAK). The present study examined treatment plans for prostate cases using beam-specific planning target volume (bsPTV) based on the effect of the markers on dose distribution and analysis of target movements. MATERIALS AND METHODS: Gafchromic EBT3 film was used to measure dose perturbations caused by markers. First, the relationships between the irradiated film density and absolute dose with different linear energy transfer distributions within a spread-out Bragg peak (SOBP) were confirmed. Then, to derive the effect of markers, two types of markers, including GA, were placed at the proximal, center, and distal depths within the same SOBP, and dose distributions behind the markers were measured using the films. The amount of internal motion of prostate was derived from irradiation results and analyzed to determine the margins of the bsPTV. RESULTS: The linearity of the film densities against absolute doses was constant within the SOBP and the amount of dose perturbations caused by the markers was quantitatively estimated from the film densities. The dose perturbation close behind the markers was smallest (<10% among depths within the SOBP regardless of types of markers) and increased with depth. The effect of two types of GAs on dose distributions was small and could be ignored in the treatment planning. Based on the analysis results of internal motions of prostate, required margins of the bsPTV were found to be 8, 7, and 7 mm in left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions, respectively. CONCLUSION: We evaluated the dose reductions caused by markers and determined the margins of the bsPTV, which was applied to the treatment using fiducial markers, using the analysis results of prostate movements.

Physical and biological beam modeling for carbon beam scanning at Osaka Heavy Ion Therapy Center.

We have developed physical and biological beam modeling for carbon scanning therapy at the Osaka Heavy Ion Therapy Center (Osaka HIMAK). Carbon beam scanning irradiation is based on continuous carbon beam scanning, which adopts hybrid energy changes using both accelerator energy changes and binary range shifters in the nozzles. The physical dose calculation is based on a triple Gaussian pencil-beam algorithm, and we thus developed a beam modeling method using dose measurements and Monte Carlo simulation for the triple Gaussian. We exploited a biological model based on a conventional linear-quadratic (LQ) model and the photon equivalent dose, without considering the dose dependency of the relative biological effectiveness (RBE), to fully comply with the carbon passive dose distribution using a ridge filter. We extended a passive ridge-filter design method, in which carbon and helium LQ parameters are applied to carbon and fragment isotopes, respectively, to carbon scanning treatment. We then obtained radiation quality data, such as the linear energy transfer (LET) and LQ parameters, by Monte Carlo simulation. The physical dose was verified to agree with measurements to within ±2% for various patterns of volume irradiation. Furthermore, the RBE in the middle of a spread-out Bragg peak (SOBP) reproduced that from passive dose distribution results to within ±1.5%. The developed carbon beam modeling and dose calculation program was successfully applied in clinical use at Osaka HIMAK.

Metal artifact reduction using iterative CBCT reconstruction algorithm for head and neck radiation therapy: A phantom and clinical study.

PURPOSE: To investigate whether a novel iterative cone-beam computed tomography (CBCT) reconstruction algorithm reduces metal artifacts in head and neck patient images. METHOD: An anthropomorphic phantom and 35 patients with dental metal prostheses or implants were analyzed. All CBCT images were acquired using a TrueBeam linear accelerator and reconstructed with a Feldkamp-Davis-Kress algorithm-based CBCT (FDK-CBCT) and an iterative CBCT algorithm. The mean Hounsfield unit (HU) and standard deviation values were measured on the tongue near the metal materials and the unaffected region as reference values. The artifact index (AI) was calculated. For objective image analysis, the HU value and AI were compared between FDK-CBCT and iterative CBCT images in phantom and clinical studies. Subjective image analyses of metal artifact scores and soft tissue visualizations were conducted using a five-point scale by two reviewers in the clinical study. RESULTS: The HU value and AI showed significant artifact reduction for the iterative CBCT than for the FDK-CBCT images (phantom study: 389.8 vs.-10.3 for HU value, 322.9 vs. 96.2 for AI, FDK-CBCT vs. iterative CBCT, respectively; clinical study: 210.3 vs. 69.0 for HU value, 149.6 vs. 70.7 for AI). The subjective scores in the clinical patient study were improved in the iterative CBCT images (metal artifact score: 1.1 vs. 2.9, FDK-CBCT vs. iterative CBCT, respectively; soft tissue visualization: 1.8 vs. 3.6). CONCLUSIONS: The iterative CBCT reconstruction algorithm substantially reduced metal artifacts caused by dental metal prostheses and improved soft tissue visualization compared to FDK-CBCT in phantom and clinical studies.

The Promising Treatment Schedule of Concurrent Chemoradiotherapy for Stage III Non-small Cell Lung Cancer: Alternative for Conventional Fractionation Using Mathematical Analysis.

BACKGROUND/AIM: To evaluate treatment schedules involving concurrent chemoradiotherapy in stage III non-small cell lung cancer (NSCLC) using the tumor control probability (TCP) and normal tissue complication probability (NTCP) parameters. PATIENTS AND METHODS: The standard schedules were compared with two types of schedules, the dose escalation and the short-term schedules. Standard schedules were 60-74 Gy in 30-37 fractions. The dose escalation schedules with hypofractionation and hyperfractionation were 69 Gy in 30 fractions and 69.6 Gy in 58 fractions, respectively, twice per day (b.i.d). The short-term schedules were concomitant boost, 64 Gy in 40 fractions b.i.d. and the accelerated radiotherapy schedule, 57.6 Gy in 36 fractions, three fractions per day (t.i.d). RESULTS: The average TCP for the short-term schedules was more than 16% in two tumor models; however, the TCP for standard and dose escalation schedules was less than 5%. In each organ, the increase in NTCP for the short-term schedule compared with standard schedules was less than 15%. CONCLUSION: The short-term schedules had an advantage over standard schedules for NSCLC.

Deep learning-based virtual noncontrast CT for volumetric modulated arc therapy planning: Comparison with a dual-energy CT-based approach.

PURPOSE: The aim of this study was to develop a deep learning (DL) method for generating virtual noncontrast (VNC) computed tomography (CT) images from contrast-enhanced (CE) CT images (VNCDL ) and to evaluate its performance in dose calculations for head and neck radiotherapy in comparison with VNC images derived from a dual-energy CT (DECT) scanner (VNCDECT ). METHODS: This retrospective study included data for 61 patients who underwent head and neck radiotherapy. All planning CT images were obtained with a single-source DECT scanner (80 and 140 kVp) with rapid kVp switching. The DL-based method used a pair of virtual monochromatic images (VMIs) at 70 keV with and without contrast materials. VMIs without contrast materials were used as reference true noncontrast (TNC) images. Deformable image registration was used between the TNC and CE images. We used the data of 45 patients, chosen randomly, for training (7922 paired images), and data from the other 16 patients as test data. We generated the VNCDL images with a densely connected convolutional network. As the VNCDECT images, we used VMIs with the iodine signal suppressed, reconstructed from the CE images of the 16 test patients. The CT numbers of the tumor, common carotid artery, internal jugular vein, muscle, fat, bone marrow, cortical bone, and mandible of each VNC image were compared with those of the TNC image. The dose of the reference TNC plan was recalculated using the CE, VNCDL , and VNCDECT images. Difference maps of the dose distributions and dose-volume histograms were evaluated. RESULTS: The mean prediction time for the VNCDL images was 3.4 s per patient, and the mean number of slices was 204. The absolute differences in CT numbers of the VNCDL images were significantly smaller than those of the VNCDECT images for the bone marrow (8.0 ± 6.5 vs 175.1 ± 40.9 HU; P < 0.001) and mandible (20.3 ± 19.3 vs 106.2 ± 80.5 HU; P = 0.002). The DL-based model provided the dose distribution most similar to that of the TNC plan. With the VNCDECT plans, dose errors >1.0% were observed in bone regions. The dose-volume histogram analysis showed that the VNCDL plans yielded the smallest errors for the primary target, although dose differences were <1.0% for all the approaches. For the maximum dose to the mandible, the mean ± SD errors for the CE, VNCDL , and VNCDECT plans were -0.13% ± 0.23% (range: -0.46% to 0.31%; P = 0.037), -0.01% ± 0.22% (range: -0.40% to 0.36%; P = 1.0), and 0.53% ± 0.47% (range: -0.21% to 1.41%; P < 0.001), respectively. CONCLUSIONS: In this study, we developed a method based on DL that can rapidly generate VNC images from CE images without a DECT scanner. Compared with the DECT approach, the DL-based method improved the prediction accuracy of CT numbers in bone regions. Consequently, there was greater agreement between the VNCDL and TNC plan dose distributions than with the CE and VNCDECT plans, achieved by suppressing the contrast material signals while retaining the CT numbers of bone structures.

Feasibility of synthetic computed tomography generated with an adversarial network for multi-sequence magnetic resonance-based brain radiotherapy.

The aim of this work is to generate synthetic computed tomography (sCT) images from multi-sequence magnetic resonance (MR) images using an adversarial network and to assess the feasibility of sCT-based treatment planning for brain radiotherapy. Datasets for 15 patients with glioblastoma were selected and 580 pairs of CT and MR images were used. T1-weighted, T2-weighted and fluid-attenuated inversion recovery MR sequences were combined to create a three-channel image as input data. A conditional generative adversarial network (cGAN) was trained using image patches. The image quality was evaluated using voxel-wise mean absolute errors (MAEs) of the CT number. For the dosimetric evaluation, 3D conformal radiotherapy (3D-CRT) and volumetric modulated arc therapy (VMAT) plans were generated using the original CT set and recalculated using the sCT images. The isocenter dose and dose-volume parameters were compared for 3D-CRT and VMAT plans, respectively. The equivalent path length was also compared. The mean MAEs for the whole body, soft tissue and bone region were 108.1 ± 24.0, 38.9 ± 10.7 and 366.2 ± 62.0 hounsfield unit, respectively. The dosimetric evaluation revealed no significant difference in the isocenter dose for 3D-CRT plans. The differences in the dose received by 2% of the volume (D2%), D50% and D98% relative to the prescribed dose were <1.0%. The overall equivalent path length was shorter than that for real CT by 0.6 ± 1.9 mm. A treatment planning study using generated sCT detected only small, clinically negligible differences. These findings demonstrated the feasibility of generating sCT images for MR-only radiotherapy from multi-sequence MR images using cGAN.

Estimation of electron density, effective atomic number and stopping power ratio using dual-layer computed tomography for radiotherapy treatment planning.

PURPOSE: Assess the accuracy for quantitative measurements of electron density relative to water (ρe/ρe,w), effective atomic number (Zeff) and stopping power ratio relative to water (SPRw) using a dual-layer computed tomography (DLCT) system. METHODS AND MATERIALS: A tissue characterization phantom was scanned using DLCT with varying scanning parameters (i.e., tube voltage, rotation time, CTDIvol, and scanning mode) and different reference materials. Then, electron density ρe/ρe,w and atomic number Zeff images were reconstructed, and their values were determined for each reference materials. Based on these two values, SPRw was calculated. Finally, the percent error (PE) against the theoretical values was calculated for reference materials. RESULTS: Significant linear relationships (p < 0.001) were observed between the measured and theoretical ρe/ρe,w (r = 1.000), Zeff (r = 0.989) and SPRw (r = 1.000) values. The PE for each reference material varied from -2.0 to 1.2% (mean, <0.1%) for electron density ρe/ρe,w, from -6.4 to 8.0% (mean, -2.0%) for atomic number Zeff, and from -2.0 to 1.9% (mean, 0.3%) for stopping power ratio SPRw. The mean PE of ρe/ρe,w (<0.1%), Zeff (<-2.5%) and SPRw (<0.4%) was verified across the variation of scanning parameters (p > 0.85). CONCLUSIONS: DLCT provides a reasonable accuracy in the measurements of ρe/ρe,w, Zeff and SPRw, and could enhance radiotherapy treatment planning and the subsequent outcomes.

The effect of beam shape on physical parameters of head and neck simultaneous-integrated boost intensity-modulated radiation therapy.

AIM: To evaluate the influence of the beam shape created by X-rays with "flat beams" and without "flattening-filter-free [FFF] beams" a flattening filter, and the isocenter locations for FFF beams on the treatment of a large irradiated volume for tumours. BACKGROUND: The increase of dose rate and the decrease of out-of-field dose can be expected for FFF beams and lead to effective and safety radiotherapy. On the other hand, the bell-shaped dose profile is thought to be a factor of negating these advantages. MATERIALS AND METHODS: Treatment plans for 15 patients with head and neck cancer were created using XiO (Elekta, Stockholm AB, Sweden) in fixed-gantry step-and-shoot delivery under the same dose constraints. Seven fields of FFF beams with 7 MV and flat beams with 6 MV were used with the technique of intensity-modulated radiation therapy (IMRT). We compared the dose homogeneity and conformity of targets and dose constraints for organs as the plan quality and evaluated physical parameters: monitor unit (MU) values, number of segments and their locations from the isocenter in beam's-eye-view. RESULTS: No significant differences were found in the plan quality. The isocenter locations do not affect the physical parameters for FFF beams. It has been confirmed that the number of segments and MU values were 40% higher with FFF beams than with flat beams (p < 0.05). CONCLUSION: This study demonstrates flat dose distribution is more suitable for IMRT with large and complex targets.

Treatment planning based on water density image generated using dual-energy computed tomography for pancreatic cancer with contrast-enhancing agent: Phantom and clinical study.

PURPOSE: A contrast-enhancing agent is imperative for the accurate target delineation of pancreatic tumors. This study demonstrates the potential use of treatment planning for patients with pancreatic tumors based on the water density image (WDI) generated by dual-energy computed tomography (DECT). METHODS: Tissue characterization and multi-energy phantom scanning were performed through DECT and the physical characteristics of the WDI and a virtual monochromatic image (VMI) were assessed. The measured and the corresponding theoretical electron density relative to water (RED) and mass density (MD) were compared. Treatment plans based on the WDI (TPWDI ) and VMI (TPVMI ) were compared for 22 pancreatic cancer patients who underwent contrast-enhanced DECT scan. RESULTS: The total absolute difference in the HU value between the conventional 120 kVp images and the VMI was the smallest at the energy level of 77 keV (3.3 HU), and the VMI at 77 keV was used for subsequent analysis. The difference between the measured and theoretical values of RED and MD for iodine using the VMI (>15%) was larger than that using WDI (<4%). In clinical cases, the maximum difference in the dosimetric parameters between TPWDI and TPWDI for the planning target volume was 3.0% when the doses were calculated using AXB, and for the duodenum, it was 1.7%. CONCLUSIONS: The WDI estimated the RED and MD accurately and could form the basis for a new treatment planning approach for pancreatic cancer using contrast-enhancing agent.

Radiobiological effects of flattening filter-free photon beams on A549 non-small-cell lung cancer cells.

Flattening filter-free (FFF) photon beams minimize the intrafraction motion of tumors, and this feature is useful in pulmonary malignancies, such as non-small-cell lung cancer (NSCLC). However, the radiobiological effects of such beams on NSCLC cells, which are often treated with stereotactic body radiotherapy (SBRT), have not been investigated sufficiently. Although cell motility may be promoted by photon beams with a low dose, the relationship between cell motility and the dose rate of photon beams has not been evaluated. The purpose of this study was to evaluate the radiobiological effects of FFF photon beams on cell survival and motility in NSCLC. A human lung cancer cell line (A549) was irradiated with conventional flattening filter (FF) and FFF photon beams at dose rates of 300 (FF), 500 and 2000 MU/min (FFF). While cell survival was estimated using the colony formation assay, cell motility was evaluated using the Boyden chamber and Matrigel invasion assays. FFF photon beams with a high dose rate neither affected the survival of A549 cells nor caused any significant difference in their motility. On the other hand, high-dose irradiation reduced cell survival and motility regardless of the dose rate. Photon beams with a high dose rate used for radiation therapy are suitable for SBRT from the standpoint of both cell survival and motility, in addition to their physical characteristics.