Intra- and inter-fractional variations of tumors with fiducial markers measured using respiratory-correlated computed tomography images for respiratory gated lung stereotactic body radiation therapy.

PURPOSE: This study evaluated the intra- and inter-fractional variation of tumors with fiducial markers (FMs), relative to the tumor-FM distance, to establish how close an FM should be inserted for respiratory-gated stereotactic body radiation therapy (RG-SBRT). METHODS: Forty-five lung tumors treated with RG-SBRT were enrolled. End-expiratory computed tomography (CT) (CTplan) and four-dimensional-CT (4D-CT) scans were obtained for planning. End-expiratory CT (CTfr) scanning was performed before each fraction. The FMs were divided into two groups based on the median tumor-FM distance in the CTplan (Dp). For the intra-fractional variation, the correlations between the corresponding tumor and FM intra-fractional motions, defined as the centroid coordinates of those in each 0-90% phase, with the 50% phase of 4D-CT as the origin, were calculated in the left-right, anterior-posterior, and superior-inferior directions. Furthermore, the maximum difference in the tumor-FM distance in each phase of 4D-CT scan, based on those in the 50% phase of 4D-CT scan (Dmax), was obtained. Inter-fractional variation was defined as the maximum distance between the tumors in CTplan and CTfr, when the CT scans were fused based on each FM or vertebra. RESULTS: The median Dp was 26.1 mm. While FM intra-fractional motions were significantly and strongly correlated with the tumor intra-fractional motions in only anterior-posterior and superior-inferior directions for the Dp > 26 mm group, they were significantly and strongly correlated in all directions for the Dp ≤ 26 mm group. In all directions, Dmax values of the Dp ≤ 26 mm group were lower than those of the Dp > 26 mm group. The inter-fractional variations based on the Dp ≤ 26 mm were smaller than those on the Dp > 26 mm and on the vertebra in all directions. CONCLUSIONS: Regarding intra- and inter-fractional variation, FMs for Dp ≤ 26 mm can increase the accuracy for RG-SBRT.

Investigation of the combination of intratumoral and peritumoral radiomic signatures for predicting epidermal growth factor receptor mutation in lung adenocarcinoma.

PURPOSE: We investigated optimal peritumoral size and constructed predictive models for epidermal growth factor receptor (EGFR) mutation. METHODS: A total of 164 patients with lung adenocarcinoma were retrospectively analyzed. Radiomic signatures for the intratumoral region and combinations of intratumoral and peritumoral regions (3, 5, and 7 mm) from computed tomography images were extracted using analysis of variance and least absolute shrinkage. The optimal peritumoral region was determined by radiomics score (rad-score). Intratumoral radiomic signatures with clinical features (IRS) were used to construct predictive models for EGFR mutation. Combinations of intratumoral and 3, 5, or 7 mm-peritumoral signatures with clinical features (IPRS3, IPRS5, and IPRS7, respectively) were also used to construct predictive models. Support vector machine (SVM), logistic regression (LR), and LightGBM models with five-fold cross-validation were constructed, and the receiver operating characteristics were evaluated. Area under the curve (AUC) of the training and test cohorts values were calculated. Brier scores (BS) and decision curve analysis (DCA) were used to evaluate the predictive models. RESULTS: The AUC values of the SVM, LR, and LightGBM models derived from IRS were 0.783 (95% confidence interval: 0.602-0.956), 0.789 (0.654-0.927), and 0.735 (0.613-0.958) for training, and 0.791 (0.641-0.920), 0.781 (0.538-0.930), and 0.734 (0.538-0.930) for test cohort, respectively. Rad-score confirmed that the 3 mm-peritumoral size was optimal (IPRS3), and AUCs values of SVM, LR, and lightGBM models derived from IPRS3 were 0.831 (0.666-0.984), 0.804 (0.622-0.908), and 0.769 (0.628-0.921) for training and 0.765 (0.644-0.921), 0.783 (0.583-0.921), and 0.796 (0.583-0.949) for test cohort, respectively. The BS and DCA of the LR and LightGBM models derived from IPRS3 were better than those from IRS. CONCLUSION: Accordingly, the combination of intratumoral and 3 mm-peritumoral radiomic signatures may be helpful for predicting EGFR mutations.

A novel dynamic robotic moving phantom system for patient-specific quality assurance in real-time tumor-tracking radiotherapy.

In this study, we assess a developed novel dynamic moving phantom system that can reproduce patient three-dimensional (3D) tumor motion and patient anatomy, and perform patient-specific quality assurance (QA) of respiratory-gated radiotherapy using SyncTraX. Three patients with lung cancer were enrolled in a study. 3D printing technology was adopted to obtain individualized lung phantoms using CT images. A water-equivalent phantom (WEP) with the 3D-printed plate lung phantom was set at the tip of the robotic arm. The log file that recorded the 3D positions of the lung tumor was used as the input to the dynamic robotic moving phantom. The WEP was driven to track 3D respiratory motion. Respiratory-gated radiotherapy was performed for driving the WEP. The tracking accuracy was calculated as the differences between the actual and measured positions. For the absolute dose and dose distribution, the differences between the planned and measured doses were calculated. The differences between the planned and measured absolute doses were <1.0% at the isocenter and <4.0% for the lung region. The gamma pass ratios of γ3 mm/3% and γ2 mm/2% under the conditions of gating and no-gating were 99.9 ± 0.1% and 90.1 ± 8.5%, and 97.5 ± 0.9% and 68.6 ± 17.8%, respectively, for all the patients. Furthermore, for all the patients, the mean ± SD of the root mean square values of the positional error were 0.11 ± 0.04 mm, 0.33 ± 0.04 mm, and 0.20 ± 0.04 mm in the LR, AP, and SI directions, respectively. Finally, we showed that patient-specific QA of respiratory-gated radiotherapy using SyncTraX can be performed under realistic conditions using the moving phantom.

Assessment of biological dosimetric margin for stereotactic body radiation therapy.

PURPOSE: To develop a novel biological dosimetric margin (BDM) and to create a biological conversion factor (BCF) that compensates for the difference between physical dosimetric margin (PDM) and BDM, which provides a novel scheme of a direct estimation of the BDM from the physical dose (PD) distribution. METHODS: The offset to isocenter was applied in 1-mm steps along left-right (LR), anterior-posterior (AP), and cranio-caudal (CC) directions for 10 treatment plans of lung stereotactic body radiation therapy (SBRT) with a prescribed dose of 48 Gy. These plans were recalculated to biological equivalent dose (BED) by the linear-quadratic model for the dose per fraction (DPF) of d = 3-20 Gy/fr and α / ß = 3 - 10 . BDM and PDM were defined so that the region that satisfied that the dose covering 95% (or 98%) of the clinical target volume was greater than or equal to the 90% of the prescribed PD and BED, respectively. An empirical formula of the BCF was created as a function of the DPF. RESULTS: There was no significant difference between LR and AP directions for neither the PDM nor BDM. On the other hand, BDM and PDM in the CC direction were significantly larger than in the other directions. BCFs of D95% and D98% were derived for the transverse (LR and AP) and longitudinal (CC) directions. CONCLUSIONS: A novel scheme to directly estimate the BDM using the BCF was developed. This technique is expected to enable the BED-based SBRT treatment planning using PD-based treatment planning systems.

Estimation of effective imaging dose and excess absolute risk of secondary cancer incidence for four-dimensional cone-beam computed tomography acquisition.

This study was conducted to estimate the organ equivalent dose and effective imaging dose for four-dimensional cone-beam computed tomography (4D-CBCT) using a Monte Carlo simulation, and to evaluate the excess absolute risk (EAR) of secondary cancer incidence. The EGSnrc/BEAMnrc were used to simulate the on-board imager (OBI) from the TrueBeam linear accelerator. Specifically, the OBI was modeled based on the percent depth dose and the off-center ratio was measured using a three-dimensional (3D) water phantom. For clinical cases, 15 lung and liver cancer patients were simulated using the EGSnrc/DOSXYZnrc. The mean absorbed doses to the lung, stomach, bone marrow, esophagus, liver, thyroid, bone surface, skin, adrenal glands, gallbladder, heart, intestine, kidney, pancreas and spleen, were quantified using a treatment planning system, and the equivalent doses to each organ were calculated. Subsequently, the effective dose was calculated as the weighted sum of the equivalent dose, and the EAR of the secondary cancer incidence was determined for each organ with the use of the biologic effects of ionizing radiation (BEIR) VII model. The effective doses were 3.9 ± 0.5, 15.7 ± 2.0, and 7.3 ± 0.9 mSv, for the lung, and 4.2 ± 0.6, 16.7 ± 2.4, and 7.8 ± 1.1 mSv, for the liver in the respective cases of the 3D-CBCT (thorax, pelvis) and 4D-CBCT modes. The lung EARs for males and females were 7.3 and 10.7 cases per million person-years, whereas the liver EARs were 9.9 and 4.5 cases per million person-years. The EAR increased with increasing time since radiation exposure. In clinical studies, we should use 4D-CBCT based on consideration of the effective dose and EAR of secondary cancer incidence.

Evaluation of the effects of motion mitigation strategies on respiration-induced motion in each pancreatic region using cine-magnetic resonance imaging.

PURPOSE: This study aimed to quantify the respiration-induced motion in each pancreatic region during motion mitigation strategies and to characterize the correlations between this motion and that of the surrogate signals in cine-magnetic resonance imaging (MRI). We also aimed to evaluate the effects of these motion mitigation strategies in each pancreatic region. METHODS: Sagittal and coronal two-dimensional cine-MR images were obtained in 11 healthy volunteers, eight of whom also underwent imaging with abdominal compression (AC). For each pancreatic region, the magnitude of pancreatic motion with and without motion mitigation and the positional error between the actual and predicted pancreas motion based on surrogate signals were evaluated. RESULTS: The magnitude of pancreatic motion with and without AC in the left-right (LR) and superior-inferior (SI) directions varied depending on the pancreatic region. In respiratory gating (RG) assessments based on a surrogate signal, although the correlation was reasonable, the positional error was large in the pancreatic tail region. Furthermore, motion mitigation in the anterior-posterior and SI directions with RG was more effective than was that with AC in the head region. CONCLUSIONS: This study revealed pancreatic region-dependent variations in respiration-induced motion and their effects on motion mitigation outcomes during AC or RG. The magnitude of pancreatic motion with or without AC and the magnitude of the positional error with RG varied depending on the pancreatic region. Therefore, during radiation therapy for pancreatic cancer, it is important to consider that the effects of motion mitigation during AC or RG may differ depending on the pancreatic region.

Photon and electron backscatter dose and energy spectrum analysis around Lipiodol using flattened and unflattened beams.

PURPOSE: The aim of the current study was to evaluate the backscatter dose and energy spectrum from the Lipiodol with flattening filter (FF) and flattening filter-free (FFF) beams. Moreover, the backscatter range, that was defined as the backscatter distance (BD) are revealed. METHODS: 6 MVX FF and FFF beams were delivered by TrueBeam. Two dose calculation methods with Monte Carlo calculation were used with a virtual phantom in which the Lipiodol (3 × 3 × 3 cm3 ) was located at a depth of 5.0 cm in a water-equivalent phantom (20 × 20 × 20 cm3 ). The first dose calculation was an analysis of the dose and energy spectrum with the complete scattering of photons and electrons, and the other was a specified dose analysis only with scattering from a specified region. The specified dose analysis was divided into a scattering of primary photons and a scattering of electrons. RESULTS: The lower-energy photons contributed to the backscatter, while the high-energy photons contributed the difference of the backscatter dose between the FF and FFF beams. Although the difference in the dose from the scattered electrons between the FF and FFF beams was within 1%, the difference of the dose from the scattered photons between the FF and FFF beams was 5.4% at a depth of 4.98 cm. CONCLUSIONS: The backscatter range from the Lipiodol was within 3 mm and depended on the Compton scatter from the primary photons. The backscatter dose from the Lipiodol can be useful in clinical applications in cases where the backscatter region is located within a tumor.

Biological dose-enhancement analysis with Monte Carlo simulation for Lipiodol for photon beams.

BACKGROUND: Previously, the physical dose-enhancement factor (DphysEF) enhancement was introduced. However, the dose enhancement considering the biological effectiveness was not shown. PURPOSE: The aim of the current study was to evaluate the biological dose-enhancement factor (DbioEF) by the dose rate and to compare the DphysEF and the DbioEF in Lipiodol for liver Stereotactic Body Radiation Therapy (SBRT). MATERIALS AND METHODS: Flattening-filter-free (FFF) 6-MV (6MVX) and 10MVX beams were delivered by TrueBeam. A virtual inhomogeneity phantom and a liver SBRT patient-treatment plan were used. The DphysEF and lineal energy distribution ( y ) distribution was calculated from Monte Carlo simulations. Using a microdosimetric-kinetic (MK) model that is estimated based on the linear-quadratic formula for Lipiodol using human liver hepatocellular cells (HepG2), the biological dose and biological dose enhancement factor (DbioEF) were calculated. The dose rate in the simulation was changed from 0.1 to 24 Gy/min. RESULTS: The DbioEF (DR:2Gy/min) and DphysEF with 10MVX FFF beam were 23.2% and 19.1% at maximum and 12.8% and 11.1% on average in the Lipiodol. In the comparison of the DbioEF between 0.1-24 Gy/min, the DbioEF was 21.2% and 11.1% with 0.1 Gy/min for 6MVX and 10 MVX, respectively. The DbioEF was larger than DEF for the 6MVX and 10MVX FFF beams. In clinical cases with the 10MVX FFF beam, the DbioEF and DphysEF in the Lipiodol region can increase the in-tumor dose by approximately 11% and 10%, respectively, without increasing the dose to normal tissue. CONCLUSIONS: The lower-energy and higher-dose-rate beams were contributed to the biological dose. The Lipiodol caused the enhancement of the physical dose and biological effectiveness. ADVANCES IN KNOWLEDGE: The biological dose enhancement (DbioEF) should be considered in the high-density material such as the Lipiodol.

Evaluation of raw-data-based and calculated electron density for contrast media with a dual-energy CT technique.

OBJECTIVES: The aim of the current study is to evaluate the accuracy and the precision of raw-data-based relative electron density (REDraw) and the calibration-based RED (REDcal) at a range of low-RED to high-RED for tissue-equivalent phantom materials by comparing them with reference RED (REDref) and to present the difference of REDraw and REDcal for the contrast medium using dual-energy CT (DECT). METHODS: The REDraw images were reconstructed by raw-data-based decomposition using DECT. For evaluation of the accuracy of the REDraw, REDref was calculated for the tissue-equivalent phantom materials based on their specified density and elemental composition. The REDcal images were calculated using three models: Lung-Bone model, Lung-Ti model and Lung-Ti (SEMAR) model which used single-energy metal artifact reduction (SEMAR). The difference between REDraw and REDcal was calculated. RESULTS: In the titanium rod core, the deviations of REDraw and REDcal (Lung-Bone model, Lung-Ti model and Lung-Ti model with SEMAR) from REDref were 0.45%, 50.8%, 15.4% and 15.0%, respectively. The largest differences between REDraw and REDcal (Lung-Bone model, Lung-Ti model and Lung-Ti model with SEMAR) in the contrast medium phantom were 8.2%, -23.7%, and 28.7%, respectively. However, the differences between REDraw and REDcal values were within 10% at 20 mg/ml. The standard deviation of the REDraw was significantly smaller than the REDcal with three models in the titanium and the materials that had low CT numbers. CONCLUSION: The REDcal values could be affected by beam hardening artifacts and the REDcal was less accurate than REDraw for high-Z materials as titanium. ADVANCES IN KNOWLEDGE: The raw-data-based reconstruction method could reduce the beam hardening artifact compared with image-based reconstruction and increase the accuracy for the RED estimation in high-Z materials, such as titanium and iodinated contrast medium.

Evaluation of a combined respiratory-gating system comprising the TrueBeam linear accelerator and a new real-time tumor-tracking radiotherapy system: a preliminary study.

A combined system comprising the TrueBeam linear accelerator and a new real-time, tumor-tracking radiotherapy system, SyncTraX, was installed in our institution. The goals of this study were to assess the capability of SyncTraX in measuring the position of a fiducial marker using color fluoroscopic images, and to evaluate the dosimetric and geometric accuracy of respiratory-gated radiotherapy using this combined system for the simple geometry. For the fundamental evaluation of respiratory-gated radiotherapy using SyncTraX, the following were performed:1) determination of dosimetric and positional characteristics of sinusoidal patterns using a motor-driven base for several gating windows; 2) measurement of time delay using an oscilloscope; 3) positional verification of sinusoidal patterns and the pattern in the case of a lung cancer patient; 4) measurement of the half-value layer (HVL in mm AL), effective kVp, and air kerma, using a solid-state detector for each fluoroscopic condition, to determine the patient dose. The dose profile in a moving phantom with gated radiotherapy having a gating window ≤ 4 mm was in good agreement with that under static conditions for each photon beam. The total time delay between TrueBeam and SyncTraX was < 227 ms for each photon beam. The mean of the positional tracking error was < 0.4 mm for sinusoidal patterns and for the pattern in the case of a lung cancer patient. The air-kerma rates from one fluoroscopy direction were 1.93 ± 0.01, 2.86 ± 0.01, 3.92 ± 0.04, 5.28 ± 0.03, and 6.60 ± 0.05 mGy/min for 70, 80, 90, 100, and 110 kV X-ray beams at 80 mA, respectively. The combined system comprising TrueBeam and SyncTraX could track the motion of the fiducial marker and control radiation delivery with reasonable accuracy; therefore, this system provides significant dosimetric improvement. However, patient exposure dose from fluoroscopy was not clinically negligible.

Dosimetric impact of dental metallic crown on intensity-modulated radiotherapy and volumetric-modulated arc therapy for head and neck cancer.

Metal dental restoration materials cause dose enhancement upstream and dose disturbance downstream of the high-density inhomogeneous regions in which these materials are used. In this study, we evaluated the impact of a dental metallic crown (DMC) on intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) for head and neck cancer. Additionally, the possibility of sparing the oral mucosa from dose enhancement using an individual intraoral mouthpiece was evaluated. An experimental oral phantom was designed to verify the dosimetric impact of a DMC. We evaluated the effect on single beam, parallel opposing beam, arc beam, IMRT, and VMAT treatment plans. To evaluate the utility of a 3-mm-thick intraoral mouthpiece, the doses across the mouthpiece were measured. For single beam irradiation, the measured doses at the entrance and exit planes of the DMC were 51% higher and 21% lower than the calculated dose by the treatment planning system, respectively. The maximum dose enhancements were 22% and 46% for parallel opposing beams and the 90° arc rotation beam, respectively. For IMRT and VMAT, the measured doses adjacent to the DMC were 12.2% ± 6.3% (mean ± 1.96SD) and 12.7% ± 2.5% higher than the calculated doses, respectively. With regard to the performance of the intraoral mouthpiece for the IMRT and VMAT cases, the disagreement between measured and calculated doses at the outermost surface of the mouthpieces were -2.0%, and 2.0%, respectively. Dose enhancements caused by DMC-mediated radiation scattering occurred during IMRT and VMAT. Because it is difficult to accurately estimate the dose perturbations, careful consideration is necessary when planning head and neck cancer treatments in patients with DMCs. To spare the oral mucosa from dose enhancement, the use of an individual intraoral mouthpiece should be considered.

Dosimetric impact of gold markers implanted closely to lung tumors: a Monte Carlo simulation.

We are developing an innovative dynamic tumor tracking irradiation technique using gold markers implanted around a tumor as a surrogate signal, a real-time marker detection system, and a gimbaled X-ray head in the Vero4DRT. The gold markers implanted in a normal organ will produce uncertainty in the dose calculation during treatment planning because the photon mass attenuation coefficient of a gold marker is much larger than that of normal tissue. The purpose of this study was to simulate the dose variation near the gold markers in a lung irradiated by a photon beam using the Monte Carlo method. First, the single-beam and the opposing-beam geometries were simulated using both water and lung phantoms. Subsequently, the relative dose profiles were calculated using a stereotactic body radiotherapy (SBRT) treatment plan for a lung cancer patient having gold markers along the anterior-posterior (AP) and right-left (RL) directions. For the single beam, the dose at the gold marker-phantom interface laterally along the perpendicular to the beam axis increased by a factor of 1.35 in the water phantom and 1.58 in the lung phantom, respectively. Furthermore, the entrance dose at the interface along the beam axis increased by a factor of 1.63 in the water phantom and 1.91 in the lung phantom, while the exit dose increased by a factor of 1.00 in the water phantom and 1.12 in the lung phantom, respectively. On the other hand, both dose escalations and dose de-escalations were canceled by each beam for opposing portal beams with the same beam weight. For SBRT patient data, the dose at the gold marker edge located in the tumor increased by a factor of 1.30 in both AP and RL directions. In clinical cases, dose escalations were observed at the small area where the distance between a gold marker and the lung tumor was ≤ 5 mm, and it would be clinically negligible in multibeam treatments, although further investigation may be required.

Biomechanical imaging biomarker during chemoradiotherapy predicts treatment response in head and neck squamous cell carcinoma.

Objective. For response-adapted adaptive radiotherapy (R-ART), promising biomarkers are needed to predict post-radiotherapy (post-RT) responses using routine clinical information obtained during RT. In this study, a patient-specific biomechanical model (BM) of the head and neck squamous cell carcinoma (HNSCC) was proposed using the pre-RT maximum standardized uptake value (SUVmax) of18F-fluorodeoxyglucose (FDG) and tumor structural changes during RT as evaluated using computed tomography (CT). In addition, we evaluated the predictive performance of BM-driven imaging biomarkers for the treatment response of patients with HNSCC who underwent concurrent chemoradiotherapy (CCRT).Approach. Patients with histologically confirmed HNSCC treated with definitive CCRT were enrolled in this study. All patients underwent CT two times as follows: before the start of RT (pre-RT) and 3 weeks after the start of RT (mid-RT). Among these patients, 67 patients who underwent positron emission tomography/CT during the pre-RT period were included in the final analysis. The locoregional control (LC), progression-free survival (PFS), and overall survival (OS) prediction performances of whole tumor stress change (TS) between pre- and mid-RT computed using BM were assessed using univariate, multivariate, and Kaplan-Meier survival curve analyses, respectively. Furthermore, performance was compared with the pre and post-RT SUVmax, tumor volume reduction rate (TVRR) during RT, and other clinical prognostic factors.Main results. For both univariate, multivariate, and survival curve analyses, the significant prognostic factors were as follows (p< 0.05): TS and TVRR for LC; TS and pre-RT FDG-SUVmaxfor PFS; and TS only for OS. In addition, for 2 year LC, PFS, and OS prediction, TS showed a comparable predictive performance to post-RT FDG-SUVmax.Significance. BM-driven TS is an effective prognostic factor for tumor treatment response after CCRT. The proposed method can be a feasible functional imaging biomarker that can be acquired during RT using only routine clinical data and may provide useful information for decision-making during R-ART.

Assessing tumor volumetric reduction with consideration for setup errors based on mathematical tumor model and microdosimetric kinetic model in single-isocenter VMAT for brain metastases.

The volumetric reduction rate (VRR) was evaluated with consideration for six degrees-of-freedom (6DoF) patient setup errors based on a mathematical tumor model in single-isocenter volumetric modulated arc therapy (SI-VMAT) for brain metastases. Simulated gross tumor volumes (GTV) of 1.0 cm and dose distribution were created (27 Gy/3 fractions). The distance between the GTV center and isocenter (d) was set at 0-10 cm. The GTV was translated within 0-1.0 mm (Trans) and rotated within 0-1.0° (Rot) in the three axis directions using affine transformation. The tumor growth volume was calculated using a multicomponent mathematical model (MCTM), and lethal effects of irradiation and repair from damage during irradiation were calculated by a microdosimetric kinetic model (MKM) for non-small cell lung cancer (NSCLC) A549 and NCI-H460 (H460) cells. The VRRs were calculated 5 days after the end of irradiation using the physical dose to the GTV for varying d and 6DoF setup errors. The tolerance value of VRR, the GTV volume reduction rate, was set at 5%, based on the pre-irradiation GTV volume. With the exception of the only one A549 condition where (Trans, Rot) = (1.0 mm, 1.0°) was repeated for 3 fractions, all conditions met all the tolerance VRR values for A549 and H460 cells with varying d from 0 to 10 cm. Evaluation based on the mathematical tumor model suggested that if the 6DoF setup errors at each irradiation could be kept within 1.0 mm and 1.0°, there would be little effect on tumor volume regardless of the distance from the isocenter in SI-VMAT.

Deep inspiration breath hold real-time tumor-tracking radiation therapy (DBRT) as a novel stereotactic body radiation therapy approach for lung tumors.

Radiotherapy with deep inspiration breath hold (DIBH) reduces doses to the lungs and organs at risk. The stability of breath holding and reproducibility of tumor location are higher during expiration than during inspiration; therefore, we developed an irradiation method combining DIBH and real-time tumor-tracking radiotherapy (RTRT) (DBRT). Nine patients were enrolled in this study. Fiducial markers were placed near tumors using bronchoscopy. Treatment planning computed tomography (CT) was performed thrice during DIBH, assisted by spirometer-based device. Each CT scan was fused using fiducial markers. Gross tumor volume (GTV) was contoured for each dataset and summed to create GTVsum; adding a 5-mm margin around GTVsum generated the planning target volume. The prescribed dose was mainly 42 Gy in four fractions. The treatment plan was created using DIBH CT (DBRT-plan), with a similar treatment plan created for expiratory CT for cases for which DBRT could not be performed (conv-plan). Vx defined as the volume of the lung received x Gy, and the mean lung dose, V20, V10, and V5 were evaluated. DBRT was completed in all patients. Mean dose, V20, and V10 were significantly lower in the DBRT-plan than in the conv-plan (all p = 0.003). Mean rates of decrease for mean dose, V20, and V10 were 14.0%, 27.6%, and 19.1%, respectively. No significant difference was observed in V5. We developed DBRT, a stereotactic body radiation therapy performed with the DIBH technique; it combines a spirometer-based breath-hold support system with an RTRT system. All patients who underwent DBRT completed the procedure without any technical or mechanical complications. This is a promising methodology that may significantly reduce lung doses.

Effects of interportal error on dose distribution in patients undergoing breath-holding intensity-modulated radiotherapy for pancreatic cancer: evaluation of a new treatment planning method.

In patients with pancreatic cancer, intensity-modulated radiotherapy (IMRT) under breath holding facilitates concentration of the radiation dose in the tumor, while sparing the neighboring organs at risk and minimizing interplay effects between movement of the multileaf collimator and motion of the internal structures. Although the breath-holding technique provides high interportal reproducibility of target position, dosimetric errors caused by interportal breath-holding positional error have not been reported. Here, we investigated the effects of interportal breath-holding positional errors on IMRT dose distribution by incorporating interportal positional error into the original treatment plan, using random numbers in ten patients treated for pancreatic cancer. We also developed a treatment planning technique that shortens breath-holding time without increasing dosimetric quality assurance workload. The key feature of our proposed method is performance of dose calculation using the same optimized fluence map as the original plan, after dose per fraction in the original plan was cut in half and the number of fractions was doubled. Results confirmed that interportal error had a negligible effect on dose distribution over multiple fractions. Variations in the homogeneity index and the dose delivered to 98%, 2%, and 50% of the volume for the planning target volume, and the dose delivered to 1 cc of the volume for the duodenum and stomach were ±1%, on average, in comparison with the original plan. The new treatment planning method decreased breath-holding time by 33%, and differences in dose-volume metrics between the original and the new treatment plans were within ± 1%. An additional advantage of our proposed method is that interportal errors can be better averaged out; thus, dose distribution in the proposed method may be closer to the planned dose distribution than with the original plans.

Pseudo dual-energy CT-derived iodine mapping using single-energy CT data based on a convolution neural network.

Objective: The objectives of this study are: (1) to develop a convolutional neural network model that yields pseudo high-energy CT (CTpseudo_high) from simple image processed low-energy CT (CTlow) images, and (2) to create a pseudo iodine map (IMpseudo) and pseudo virtual non-contrast (VNCpseudo) images for thoracic and abdominal regions. Methods: Eighty patients who underwent dual-energy CT (DECT) examinations were enrolled. The data obtained from 55, 5, and 20 patients were used for training, validation, and testing, respectively. The ResUnet model was used for image generation model and was trained using CTlow and high-energy CT (CThigh) images. The proposed model performance was evaluated by calculating the CT values, image noise, mean absolute errors (MAEs), and histogram intersections (HIs). Results: The mean difference in the CT values between CTpseudo_high and CThigh images were less than 6 Hounsfield unit (HU) for all evaluating patients. The image noise of CTpseudo_high was significantly lower than that of CThigh. The mean MAEs was less than 15 HU, and HIs were almost 1.000 for all the patients. The evaluation metrics of IM and VNC exhibited the same tendency as that of the comparison between CTpseudo_high and CThigh images. Conclusions: Our results indicated that the proposed model enables to obtain the DECT images and material-specific images from only single-energy CT images. Advances in knowledges: We constructed the CNN-based model which can generate pseudo DECT image and DECT-derived material-specific image using only simple image-processed CTlow images for the thoracic and abdominal regions.

Mathematical model combined with microdosimetric kinetic model for tumor volume calculation in stereotactic body radiation therapy.

We proposed a new mathematical model that combines an ordinary differential equation (ODE) and microdosimetric kinetic model (MKM) to predict the tumor-cell lethal effect of Stereotactic body radiation therapy (SBRT) applied to non-small cell lung cancer (NSCLC). The tumor growth volume was calculated by the ODE in the multi-component mathematical model (MCM) for the cell lines NSCLC A549 and NCI-H460 (H460). The prescription doses 48 Gy/4 fr and 54 Gy/3 fr were used in the SBRT, and the effect of the SBRT on tumor cells was evaluated by the MKM. We also evaluated the effects of (1) linear quadratic model (LQM) and the MKM, (2) varying the ratio of active and quiescent tumors for the total tumor volume, and (3) the length of the dose-delivery time per fractionated dose (tinter) on the initial tumor volume. We used the ratio of the tumor volume at 1 day after the end of irradiation to the tumor volume before irradiation to define the radiation effectiveness value (REV). The combination of MKM and MCM significantly reduced REV at 48 Gy/4 fr compared to the combination of LQM and MCM. The ratio of active tumors and the prolonging of tinter affected the decrease in the REV for A549 and H460 cells. We evaluated the tumor volume considering a large fractionated dose and the dose-delivery time by combining the MKM with a mathematical model of tumor growth using an ODE in lung SBRT for NSCLC A549 and H460 cells.