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To assess the planned dose, in vivo dosimetry, acute skin toxicity, pain, and distress using Thermoplastic Elastomer (TPE) bolus for postmastectomy radiotherapy (PMRT).Thirty-two PMRT patients with TPE bolus (17 patients for 25 fractions, 15 patients for the first 20 fractions) were selected for the study. The acute skin toxicity, pain, and psychological distress were assessed from the first treatment week to the fourth week after the end of treatment. At the first treatment, the MOSFET was used in vivo dosimetry measurement.In vivo dosimetry with the bolus, the dose deviation ranged from -6.22% to -1.56% for 5 points. The presence of grade 1 and 2 skin toxicity reached its peak (70.0% and 13.3%) in the sixth week. Two patients (6.6%) with 25 fractions bolus experienced moist desquamation in the fifth and seventh week, with pain score 2 and 3, and interruptions of 3 and 5 days, respectively. The incidence of pain score 1, 2, and 3 peaked in the fifth (33.3%), fourth (33.3%), and seventh (10.0%) week. No patients experienced grade 3 skin toxicity and severe pain. One patient had significant anxiety, and two patients had significant depression.The TPE bolus can accurately fit skin and improve the surface dose to more than 90%. Twenty fractions with TPE bolus had similar skin toxicity and pain to those without bolus and did not increase patients' distress and clinical workload, compared with the literature's data, which is an alternative to the 3D printing bolus for PMRT.

Using intra-fractional cone-beam CT (CBCT) to evaluate the amplitude changes and baseline shifts of respiratory motion in liver stereotactic body radiation therapy (SBRT).The amplitude changes and baseline shifts of respiratory motion for 24 liver patients were evaluated by the four-dimensional (4D) CT, inter- and intra-fractional CBCT. The difference of the average liver position errors among all treatment fractions and the 4D CT representthe baseline shifts. According to the baseline shifts, the ITV to PTV margin was recalculated and the plan was re-designed to compare the dosimetric variation.The systematic and random errors of the baseline shifts for intra-fractional CBCT in the left-right (LR), superior-inferior (SI), and anterior-posterior (AP) directions were 0.99/1.60 mm, 2.03/2.46 mm, and 1.02/2.07 mm, respectively. The new ITV to PTV margins should be 4.0 mm, 7.0 mm, and 4.0 mm, respectively. The amplitude change of motion between the 4D CT and the intra-fractional CBCT was 1.03 ± 4.35 mm, with 31% of fractions exceeding 5 mm. To achieve the same dose coverage of the new PTV, the DSignificant amplitude changes and baseline shifts of motion occurred during dose delivery compared with those in 4D CT. Using the ITV to PTV margin of 4.0 mm (LR), 7.0 mm (SI), and 4.0 mm (AP) can ensure the target dose coverage and keep the dose constrain of normal tissues at an acceptable level.

The aim of the study was to evaluate the clinical feasibility of a 3D-print silica bolus for nasal NK/T-cell lymphoma radiation therapy. Intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) plans were designed using an anthropomorphic head phantom with a 3D-print silica bolus and other kinds of bolus used clinically, and the surface dose was measured by a metal oxide semiconductor field-effect transistor (MOSFET) dosimeter. Four nasal NK/T patients with or without 3D-print silica bolus were treated and the nose surface dose was measured using a MOSFET dosimeter during the first treatment. Plans for the anthropomorphic head phantom with 3D-print bolus have more uniform dose and higher conformity of the planning target volume (PTV) compared to other boluses; the homogeneity index (HI) and conformity index (CI) of the VMAT plan were 0.0589 and 0.7022, respectively, and the HI and CI of the IMRT plan were 0.0550 and 0.7324, respectively. The MOSFET measurement results showed that the surface dose of the phantom with 3D-print bolus was >180 cGy, and that of patients with 3D-print bolus was higher than patients without bolus. The air gap volume between the 3D-print bolus and the surface of patients was

To design a new breast vacuum bag to reduce global and local setup errors in post-mastectomy radiation therapy (PMRT). A total of 24 PMRT patients were immobilized with an old vacuum bag and 26 PMRT patients were immobilized with a new vacuum bag. The registration results were analysed using four regions of interest (ROI): the global ROI [including the whole region of the planning target volume (PTV), GROI], the supraclavicular area (SROI), the ipsilateral chest wall region (CROI) and the ipsilateral arm region (AROI). The global and local setup errors of the two groups were compared. The global setup errors of the new vacuum group were significantly smaller than those in the old vacuum group with the exception of yaw axes (P

PURPOSE Applying statistical process control (SPC) to intensity-modulated radiotherapy (IMRT)/volumetric modulated arc therapy (VMAT) patient-specific quality assurance (PSQA) program was recommended by the American Association of Physics in Medicine Task Group 218 report, but a comprehensive analysis of PSQA processes with non-normal distributions is lacking. This study investigates SPC and process capability analysis (PCA) methods for non-normal IMRT/VMAT PSQA processes. METHODS 1119 VMAT PSQAs were performed on three beam-matched linear accelerators (linacs), using gamma analysis. The Anderson-Darling statistic was used to test normality. The control charts for each PSQA process were obtained using three non-normal-based methods and compared with the conventional Shewhart method. The ability of each PSQA process to produce an output within the specification limit was measured using the Cpk index; in this study, the Cpk index was calculated using two transformation methods and compared with that calculated using the conventional method. The performances of the three linacs were assessed using SPC and PCA methods. RESULTS All three PSQA processes were non-normal (P

The purpose of the study was to quantify local setup errors and evaluate the planning target volume (PTV) margins for sub-regions in cone-beam computed tomography (CBCT)-guided post-mastectomy radiation therapy (PMRT). The local setup errors of 20 patients undergoing CBCT-guided PMRT were analysed retrospectively. Image registration between CBCT and planning CT was performed using four sub-regions of interest (ROIs): the supraclavicular area (SROI), ipsilateral chest wall region (CROI), ipsilateral chest wall plus supraclavicular region (SROI + CROI) and vertebral region (TROI). Bland–Altman analysis, correlation, local setup errors and PTV margins among these ROIs were evaluated. There was no significant consistency or correlation for registration results between the TROI and the CROI or SROI regions on any translational axis. When using the SROI + CROI as the ROI, the systematic error (Σ) and random error (σ) of the local setup errors for the CROI region were 1.81, 1.19 and 1.76 mm and 1.84, 2.64 and 3.00 mm along the medial–lateral (ML), superior–inferior (SI) and anterior–posterior (AP) directions, respectively. The PTV margins for the CROI region were 5.80, 4.82 and 6.50 mm. The Σ and σ of the local setup errors for the SROI region were 1.29, 1.15 and 0.77 mm and 1.96, 2.65 and 2.2 mm, respectively, and the PTV margins were 4.59, 4.73 and 3.47 mm. Large setup errors and local setup errors occur in PMRT. The vertebral body should not be a position surrogate for the supraclavicular region or chest wall. To compensate for the local setup errors, different PTV margins are required, even with CBCT guidance.

Background Prostate alignment is subject to interobserver variability in cone-beam CT (CBCT)-based soft-tissue matching. This study aims to analyze the impact of possible interobserver variability in CBCT-based soft-tissue matching for prostate cancer radiotherapy. Methods Retrospective data, consisting of 156 CBCT images from twelve prostate cancer patients with elective nodal irradiation were analyzed in this study. To simulate possible interobserver variability, couch shifts of 2 mm relative to the resulting patient position of prostate alignment were assumed as potential patient positions (27 possibilities). For each CBCT, the doses of the potential patient positions were re-calculated using deformable image registration-based synthetic CT. The impact of the simulated interobserver variability was evaluated using tumor control probabilities (TCPs) and normal tissue complication probabilities (NTCPs). Results No significant differences in TCPs were found between prostate alignment and potential patient positions (0.944 ± 0.003 vs 0.945 ± 0.003, P = 0.117). The average NTCPs of the rectum ranged from 5.16 to 7.29 (%) among the potential patient positions and were highly influenced by the couch shift in the anterior–posterior direction. In contrast, the average NTCPs of the bladder ranged from 0.75 to 1.12 (%) among the potential patient positions and were relatively negligible. Conclusions The NTCPs of the rectum, rather than the TCPs of the target, were highly influenced by the interobserver variability in CBCT-based soft-tissue matching. This study provides a theoretical explanation for daily CBCT-based image guidance and the prostate-rectum interface matching procedure. Trial registration: Not applicable.

The purpose of the study was to evaluate the accuracy of monochromatic energy (MonoE) computed tomography (CT) images reconstructed by spectral CT in predicting the stopping power ratio $( SP{R}_w)$ of materials in the presence of metal. The CIRS062 phantom was scanned three times using spectral CT. In the first scan, a solid water insert was placed at the center of the phantom $(C{T}_{no\ metal})$. In the second scan, the solid water insert was replaced with a titanium alloy femoral head $(C{T}_{metal})$. The metal artifact reduction (MAR) algorithm was used in the last scan $(C{T}_{metal+ MAR})$. The MonoE-CT images of 40 keV and 80 keV were reconstructed. Finally, the single-energy CT method (SECT) and the dual-energy CT method (DECT) were used to calculate the $SP{R}_w$. The mean absolute error (MAE) of the $SP{R}_w$ of the inner layer inserts calculated by the SECT method were 3.19%, 13.88% and 2.71%, corresponding to $C{T}_{no\ metal}$, $C{T}_{metal}$ and $C{T}_{metal+ MAR}$, respectively. For the outer layer inserts, the MAE of $SP{R}_w$ were 3.43%, 5.42% and 2.99%, respectively. Using the DECT method, the MAE of the $SP{R}_w$ of the inner layer inserts was 1.30%, 3.69% and 1.46% and the MAE of the outer layer inserts– was 1.34%, 1.36% and 1.05%. The studies shows that, compared with the SECT method, the accuracy of the DECT method in predicting the $SP{R}_w$ of a material is more robust to the presence of metal. Using the MAR algorithm when performing CT scans can further improve the accuracy of predicting the SPR of materials in the presence of metal.

Background: Prostate alignment is subject to interobserver variability in cone-beam CT (CBCT)-based soft-tissue matching. This study aims to analyze the impact of interobserver variability in CBCT-based soft-tissue matching for prostate cancer radiotherapy.Methods: Retrospective data, consisting of 156 CBCT images from twelve patients with intermediate- or high-risk prostate cancer were analyzed in this study. To simulate interobserver variability, couch shifts of 2 mm relative to the resulting patient position of prostate alignment were assumed as potential patient positions (27 possibilities). For each CBCT, the doses of the potential patient positions were recalculated using deformable image registration-based synthetic CT. The impact of the simulated interobserver variability was evaluated using tumor control probabilities (TCPs) and normal tissue complication probabilities (NTCPs).Results: No significant differences in TCPs were found between prostate alignment and potential patient positions (0.944 ± 0.003 vs 0.945 ± 0.003, P = 0.117). The average NTCPs of the rectum ranged from 5.16 (%) to 7.29 (%) among the potential patient positions and were highly influenced by the couch shift in anterior-posterior direction. In contrast, the average NTCPs of the bladder ranged from 0.75 (%) to 1.12 (%) among the potential patient positions and were relatively negligible.Conclusions: The NTCPs of the rectum, rather than the TCPs of the target, were highly influenced by the interobserver variability in CBCT-based soft-tissue matching. This study provides a theoretical explanation for daily CBCT-based image guidance and the prostate-rectum interface matching procedure.Trial registration: Not applicable.

PURPOSE Establishing the tolerance limits of patient-specific quality assurance (PSQA) processes based on the gamma passing rate (GPR) by using normal statistical process control (SPC) methods involves certain problems. The aim of this study was threefold: (a) to show that the heuristic SPC method can replace the quantile method for establishing tolerance limits in PSQA processes and is more robust, (b) to introduce an iterative procedure of "Identify-Eliminate-Recalculate" for establishing the tolerance limits in PSQA processes with unknown states based on retrospective GPRs, and (c) to recommend a workflow to define tolerance limits based on actual clinical retrospective GPRs. MATERIALS AND METHODS A total of 1671 volumetric-modulated arc therapy (VMAT) pretreatment plans were measured on four linear accelerators (linacs) and analyzed by treatment sites using the GPRs under the 2%/2 mm, 3%/2 mm, and 3%/3 mm criteria. Normality testing was performed using the Anderson-Darling (AD) statistic and the optimal distributions of GPRs were determined using the Fitter Python package. The iterative "Identify-Eliminate-Recalculate" procedure was used to identify the PSQA outliers. The tolerance limits of the initial PSQAs, remaining PSQAs after elimination, and in-control PSQAs after correction were calculated using the conventional Shewhart method, two transformation methods, three heuristic methods, and two quantile methods. The tolerance limits of PSQA processes with different states for the respective methods, linacs, and treatment sites were comprehensively compared and analyzed. RESULTS It was found that 75% of the initial PSQA processes and 63% of the in-control processes were non-normal (AD test, p

Virtual monochromatic images (VMI) that reconstructed on dual-energy computed tomography (DECT) have further application prospects in radiotherapy, and there is still a lack of clinical dose verification. In this study, GE Revolution CT scanner was used to perform conventional imaging and gemstone spectral imaging on the simulated head and body phantom. The CT images were imported to radiotherapy treatment planning system (TPS), and the same treatment plans were transplanted to compare the CT value and the dose distribution. The results show that the VMI can be imported into TPS for CT value-relative electron density conversion and dose calculation. Compared to conventional images, the VMI varies from 70 to 140 keV, has little difference in dose distribution of 6 MV photon treatment plan.

BACKGROUND The aim of this study is to assess the effect of home enteral nutrition (HEN) on the myelosuppression of patients with nasopharyngeal cancer (NPC) during the course of concurrent chemoradiotherapy (CCRT). METHODS A total of 18 outpatients with NPC administered oral nutritional supplementation intervention at home during the course of CCRT were designated as the HEN group, whereas 36 patients with NPC who had previously completed CCRT were retrospectively included as the control group. Patient Generated Subjective Global Assessment, body mass index (BMI), and blood test were evaluated prior to CCRT. During the course of CCRT, blood test was assessed every 2 weeks. RESULTS In male patients, hemoglobin (HB) and red blood cell were decreased (P

In order to adapt to different target shapes and protect the surrounding normal tissues, the design of two-dimensional electron beam radiotherapy planning requires additional lead blocks. But the Pinnacle treatment planning system can not directly shape the lead block conformity to the size of the beam field given by the doctor. Every time, physicists need to manually drag the lead block to form the required beam field. When meeting a two-dimensional electron beam treatment planning with the same field parameters as before, physicists need to rearrange the field for dose calculation, which greatly reduces the design efficiency of the two-dimensional electron beam treatment planning. In this study, we independently developed a two-dimensional electron beam radiotherapy planning system based on Qt Creator. The system can quickly design a two-dimensional electron beam radiotherapy plan, which reduces the repeated work of physicists.

Purpose Electronic portal imaging detector (EPID)-based patient positioning verification is an important component of safe radiotherapy treatment delivery. In computer simulation studies, learning-based approaches have proven to be superior to conventional gamma analysis in the detection of positioning errors. To approximate a clinical scenario, the detectability of positioning errors via EPID measurements was assessed using radiomics analysis for patients with thyroid-associated ophthalmopathy. Methods Treatment plans of 40 patients with thyroid-associated ophthalmopathy were delivered to a solid anthropomorphic head phantom. To simulate positioning errors, combinations of 0-, 2-, and 4-mm translation errors in the left–right (LR), superior-inferior (SI), and anterior-posterior (AP) directions were introduced to the phantom. The positioning errors-induced dose differences between measured portal dose images were used to predict the magnitude and direction of positioning errors. The detectability of positioning errors was assessed via radiomics analysis of the dose differences. Three classification models—support vector machine (SVM), k-nearest neighbors (KNN), and XGBoost—were used for the detection of positioning errors (positioning errors larger or smaller than 3 mm in an arbitrary direction) and direction classification (positioning errors larger or smaller than 3 mm in a specific direction). The receiver operating characteristic curve and the area under the ROC curve (AUC) were used to evaluate the performance of classification models. Results For the detection of positioning errors, the AUC values of SVM, KNN, and XGBoost models were all above 0.90. For LR, SI, and AP direction classification, the highest AUC values were 0.76, 0.91, and 0.80, respectively. Conclusions Combined radiomics and machine learning approaches are capable of detecting the magnitude and direction of positioning errors from EPID measurements. This study is a further step toward machine learning-based positioning error detection during treatment delivery with EPID measurements.

Background Partial breast radiotherapy (PBI) has emerged as an option after breast-conserving surgery for early-stage breast cancer patients. Methods A total of 55 patients with early-stage breast cancer between 2009 and 2013 were enrolled in this single-institutional phase II prospective clinical trial. All patients received adjuvant PBI-IMRT after lumpectomy, with the prescription of 48 Gy in 12 fractions at 4 Gy per fraction, 5 days a week. The primary endpoint was ipsilateral breast tumor recurrence (IBTR), the other endpoints were a regional nodal failure (RNF), distant metastasis (DM) rate, disease-free survival (DFS), and overall survival (OS). These endpoints were used to evaluate clinical outcomes. The cosmetic effects and the late toxicity were assessed according to Harvard standard scale and CTCAE 3.0, respectively. Results In our cohorts, the median age was 45.60 years old (range 31 to 65 years) and 29.09% of these patients were post-menopause (n = 16). Most patients were T1 stage (65.45%) or N0 stage (70.91%). 80% of patients were ER-positive, 67.27% PR positive, and 61.82% HER2 negative. At the median follow-up of 9.25 years, RNF was 0% and IBTR occurred in only one patient (1.82%) to the chest wall. Except for one patient (1.82%) had DM to lung and pleura and died from disease progression, the remaining patients were alive at the end of the ten-year follow-up. The ten-year DFS and OS were 94.55% and 98.18%. One patient (1.82%) was diagnosed with endometrial cancer after PBI. Except for 9 patients who declined the cosmetic assessment, the rest of the 46 patients (83.64%) were all rated as good and well-satisfied with the appearance of the irradiated breast. No breast retraction and fibrosis were observed in any of the patients. Additionally, only 4 patients experienced grade 1 late toxicity (7.28%). None had grade 3 or higher late toxicity. Conclusion This is the first study to report the ten-year results of PBI after breast-conserving surgery in Chinese patients. Our study suggested that PBI had durable local control and maintained good cosmetic outcomes with minimal late toxicity at long term follow up for the early-stage breast cancer patients.

BackgroundTo develop a low-dose cone beam CT (LD-CBCT) reconstruction method named simultaneous algebraic reconstruction technique and dual-dictionary learning (SART-DDL) joint algorithm for image guided radiation therapy (IGRT) and evaluate its imaging quality and clinical application ability.MethodsIn this retrospective study, 62 CBCT image sets from February 2018 to July 2018 at west china hospital were randomly collected from 42 head and neck patients (mean [standard deviation] age, 49.7 [11.4] years, 12 females and 30 males). All image sets were retrospectively reconstructed by SART-DDL (resultant D-CBCT image sets) with 18% less clinical raw projections. Reconstruction quality was evaluated by quantitative parameters compared with SART and Total Variation minimization (SART-TV) joint reconstruction algorithm with pairedttest. Five-grade subjective grading evaluations were done by two oncologists in a blind manner compared with clinically used Feldkamp-Davis-Kress algorithm CBCT images (resultant F-CBCT image sets) and the grading results were compared by paired Wilcoxon rank test. Registration results between D-CBCT and F-CBCT were compared. D-CBCT image geometry fidelity was tested.ResultsThe mean peak signal to noise ratio of D-CBCT was 1.7 dB higher than SART-TV reconstructions (P P > .05). In clinical registration, the maximum translational and rotational difference was 1.8 mm and 1.7 degree respectively. The horizontal, vertical and sagittal geometry fidelity of D-CBCT were acceptable.ConclusionsThe image quality, geometry fidelity and clinical application ability of D-CBCT are comparable to that of the F-CBCT for head-and-neck patients with 18% less projections by SART-DDL.

Purpose: To evaluate the amplitude changes and baseline drift of respiratory motion in liver stereotactic body radiation therapy based on intra-fraction cone beam CT (CBCT).Materials and methods: Twenty-four liver SBRT patients underwent a four-dimensional computed tomography (4D CT) scan, inter-fraction cone-beam computed tomography (CBCT), and intra-fraction CBCT to evaluate the amplitude changes and baseline drift of respiratory motion. The amplitude changes were defined as the variations between the amplitude measured in the 4D CT and those measured with fluoroscopy in inter- and intra-fraction CBCT. The baseline drifts were defined as the difference between the liver position errors and the setup errors in inter- and intra-fraction CBCT. Manual registration of the liver contour was performed to obtain liver position errors, and bone registration was performed to obtain setup errors. Meanwhile, the correlation among the liver position errors, the relative diaphragm position, and the amplitude changes was evaluated. Results: The systematic and random errors of the baseline drifts for intra-fraction CBCT in the medial-lateral (ML), superior-inferior (SI), and anterior-posterior (AP) views were 0.99 and 1.6 mm, 2.03 and 2.46 mm, and 1.02 and 2.07 mm, respectively. The corresponding PTV margin was 3.61 mm, 6.8 mm, and 4.00 mm, respectively. The amplitude variation ranged from -169.33% to 65.47% in inter-fraction CBCT and from -171.04% to 60.00% in intra-fraction CBCT. Inter-fraction liver position errors were significantly related to the setup errors. The relative diaphragm position was not statistically related to the baseline drifts in the inter-fraction nor in the intra-fraction. Conclusions: Using intra-fraction CBCT, significant amplitude variations and baseline drifts of respiratory motion were found compared with those in 4D CT. The relative diaphragm position in a single breathing cycle cannot reflect the liver position during dose delivery. At least a 6.8 mm PTV margin in the SI direction is recommended to compensate for the baseline drift.

Additional file 1. Mathematical description of dual-dictionary learning theory (DDL).

This study describes a new plan complexity metric for volumetric-modulated arc therapy (VMAT) and evaluates the relationship of this metric with the VMAT dosimetric accuracy. The new modulation complexity score for VMAT (NMCSv) that is based on the aperture shape and multi-leaf collimator (MLC) leaf travel is described. Its performance is evaluated through correlation and receiver operating characteristic (ROC) analyses with patient-specific gamma passing rates using 2 3-dimensional diode arrays. For comparison, the following metrics are evaluated using the same correlation analyses: average field width, average leaf travel, modulation complexity score, and leaf travel modulation complexity score. Spearman's rank correlation analysis is performed to examine any relationships between the complexity metrics and the patient-specific gamma passing rates. ROC curves are used to assess the performance of the plan metrics using a gamma passing rate of 3%/3 mm criterion with a 95% tolerance level. In both the diode arrays, the gamma passing rates (3%/3 mm and 2%/2 mm) for patient-specific dosimetric verification of VMAT plans are moderately or weakly correlated to all the complexity metrics. NMCSv demonstrates the highest correlation with the passing rates (r = 0.652, p0.001 for Delta4 and r = 0.499, p0.001 for ArcCheck) and the highest area under the curve value (0.809, p0.01 for Delta4 and 0.734, p0.01 for ArcCheck). While using the Delta4 system, NMCSv exhibits an excellent classification performance with area under the curves of 0.926 (sensitivity: 0.913; specificity: 0.860; p0.01) and 0.918 (sensitivity: 0.943; specificity: 0.720; p0.01) for rectal and cervical cancer plans, respectively. NMCSv as a novel potential clinical plan complexity metric is moderately correlated with the gamma passing rate. It demonstrates the best performance with respect to distinguishing the dosimetric accuracy of VMAT plans among the evaluated metrics. The classification performance of complexity metrics can be affected by various dosimetry verification devices and treatment sites.

Purpose: To analyze the influence of the bladder and rectum filling and the body contour changes on the prostate target dose. Methods: A total of 190 cone-beam CT (CBCT) image data sets from 16 patients with prostate cancer were used in this study. Dose reconstruction was performed on the virtual CT generated by the deformable planning CT. Then, the effects of the bladder filling, rectal filling, and the patient’s body contour changes of the PCTV1 (the prostate area, B1) and PCTV2 (the seminal vesicle area, B2) on the target dose were analyzed. Correlation analysis was performed for the ratio of bladder and rectal volume variation and the variation of the bladder and rectal dose. Results: The mean Dice coefficients of B1, B2, bladder, and rectum were 0.979, 0.975, 0.888 and 0.827, respectively, and the mean Hausdorff distances were 0.633, 1.505, 2.075, and 1.533, respectively. With the maximum volume variations of 142.04 ml for the bladder and 40.50 ml for the rectum, the changes of V100, V95, D2, and D98 were 1.739 ± 1.762 (%), 0.066 ± 0.169 (%), 0.562 ± 0.442 (%), and 0.496 ± 0.479 (%) in PCTV1 and 1.686 ± 1.051 (%), 0.240 ± 0.215 (%), 1.123 ± 0.925 (%), and 0.924 ± 0.662 (%) in PCTV2, respectively. With a 10% increase in the volume of the bladder and rectum, the V75, V70, and V65 of rectum increased at 0.73 (%), 0.71 (%), and 1.18 (%), and the V75, V70, and V65 of bladder changed at −0.21 (%), −0.32 (%), and −0.39 (%), respectively. Conclusion: Significant correlations were observed between the volume variation and the dose variation of the bladder and rectum. However, when a bladder and rectal filling protocol was adopted, the target dose coverage can be effectively ensured based on CBCT guidance to correct the prostate target position.

Purpose To study the inter- and intrafraction tumor reproducibility with active breath control (ABC) utilizing cone-beam computed tomography (CBCT), and compare validity of registration with two different regions of interest (ROI). Methods and materials Thirty-one lung tumors in 19 patients received conventional or stereotactic body radiotherapy with ABC. During each treatment, patients had three CBCT scanned before and after online position correction and after treatment. These CBCT images were aligned to the planning CT using the gray scale registration of tumor and bony registration of the thorax, and tumor position uncertainties were then determined. Results The interfraction systematic and random translation errors in the left–right (LR), superior–inferior (SI) and anterior–posterior (AP) directions were 3.6, 4.8, and 2.9 mm; 2.5, 4.5, and 3.5 mm, respectively, with gray scale alignment; 1.9, 4.3, 2.0 mm and 2.5, 4.4, 2.9 mm, respectively, with bony alignment. The interfraction systematic and random rotation errors with gray scale and bony alignment groups ranged from 1.4° to 3.0° and 0.8° to 2.3°, respectively. The intrafraction systematic and random errors with gray scale registration in LR, SI, AP directions were 0.9, 2.0, 1.8 mm and 1.5, 1.7, 2.9 mm, respectively, for translation; 1.5°, 0.9°, 1.0° and 1.2°, 2.2°, 1.8°, respectively, for rotation. The translational errors in SI direction with bony alignment were significantly larger than that of gray scale ( p Conclusions With CBCT guided online correction the interfraction positioning errors can be markedly reduced. The intrafraction errors were not diminished by the use of ABC. Rotation errors were not very remarkable both inter- and intrafraction. Gray scale alignment of tumor may provide a better registration in SI direction.

Objective: To analyse which local set-up errors can be covered by a 5-mm margin for cone beam computed tomography (CBCT)-guided radiotherapy in nasopharyngeal carcinoma (NPC). Methods: 11 regions of interest (ROIs) were registered for 24 NPC patients, with a total of 323 CBCT scans. According to the registration results, clinical target volume–planning target volume (CTV–PTV)/organs at risk-planning risk volume (OAR-PRV) margin analysis; Pearson correlation analysis; Bland–Altman plots; and a receiver operating characteristic (ROC) analysis were used to investigate which local set-up errors of substructure can be represented by the PTVROI. Results: The clinical target volume-PTV/OAR-planning risk volume margins were less than 5 mm for C1ROI-C4ROI, mandible (MROI), and sphenoid sinus (SROI) with respect to PTVROI. C1ROI-C4ROI, MROI, and SROI exhibited significant correlations and consistencies in the mediolateral, superior–inferior, and anteroposterior (AP) directions and significant receiver operating characteristic analysis results in the anteroposterior direction. Conclusion: Only the upper local set-up error of C1ROI-C4ROI, MROI, and SROI can be covered by a 5-mm margin for CBCT-guided NPC radiotherapy with a large ROI. Using these ROIs as an integral reference ROI is better than individual bony landmark. Advances in knowledge: This report is helpful to CBCT registration for NPC radiotherapy in clinical practice.

Background and purpose Online adaptive correction in image-guided intensity-modulated radiotherapy appeared to be a promising approach for precision radiation treatment in head and neck tumors. This protocol was designed to evaluate the clinical feasibility and effect of online cone beam computed tomography (CBCT) guidance in IMRT of nasopharyngeal cancer (NPC). Methods and materials The Elekta Synergy system, which integrates an X-ray volumetric imager (XVI), was used to deliver radiation treatment for 22 cases of NPC. The acquired CBCT was registered to the planning CT for online and offline analysis. The systematic and random setup errors, as well as planning target volume (PTV) margin, were calculated at different correction threshold levels. The impact of online setup correction on dosimetry was evaluated by simulation of pre-correction errors. Results The correction-of-setup-errors frequencies for 1, 2 and 3mm thresholds were 41.3–53.9%, 12.7–21.2% and 6.3–10.3%, respectively. Online correction was effective at the 2mm threshold level for all three axes. The pre-correction systematic errors for the whole group ranged 1.1–1.3mm, and the random errors were also 1.1–1.3mm. After online correction, the systematic and random errors ranged 0.4–0.5mm and 0.7–0.8mm, respectively, in the three directions. The PTV margins for the pre-correction, pretreatment and post-treatment positions were 3.5–4.2mm, 1.6–1.8mm and 2.5–3.2mm, respectively, in three directions. Analysis of hypothetical dosimetric change due to a translational isocenter shift of 3mm showed that if no correction was applied, the mean maximum dose to both the brain stem and spinal cord would be increased by 10Gy, the mean dose to the left and right parotids would be increased by 7.8 and 8.5Gy, respectively, and the dose to target volumes would be decreased: 4Gy for 95% GTV and 5.6Gy for 95% CTV 60. Conclusions CBCT-based online correction increased the accuracy of IMRT for NPC and reduced irradiated margins, by decreasing both the systematic and random errors. Online CBCT correction reduces the radiation dose to normal tissue and creates room for further dose escalation of tumors.

Background Non-small cell lung cancer (NSCLC) harboring kinase-domain mutations in epidermal growth factor receptors (EGFR) has been observed to be sensitive to ionizing radiation (IR). We explore Rad51-dependent homologous recombination (HR) DNA repair in regulating radiosensitivity in two NSCLC cell lines with different EGFR mutation status. Methods NSCLC cell lines, wild-type EGFR A549 and mutant EGFR H820 with an in-frame deletion in exon 19 of EGFR (ΔE746–E750), were cultured. Radiosensitivity was estimated by colony forming assay. Rad51 expression was evaluated by quantitative real time-polymerase chain reaction and Western-blot. Lentiviral small hairpin ribonucleic acid-Rad51 and ΔE746–E750 deletion mutant EGFR were constructed and transfected into cells. Flowcytometry assay was used to analyze DNA double strand breaks, cell cycle alterations, and apoptosis. Results A549 had a higher survival factor (SF)2 (0.66 vs. 0.44) and lower α/β value (4.07 vs. 9.01). Compared with the A549 cell, the H820 cell exhibited defective arrest in the S-phase, a higher rate of G2/M accumulation, early apoptosis, and residual γ-H2AX. Downregulated Rad51 expression decreased SF2 (0.42 vs. 0.31) and increased the α/β ratio (7.51 vs. 10.5), G2/M accumulation, early apoptosis, and γ-H2AX in two cell lines. H820 had a low IR-induced Rad51 expression and nuclear translocation. Exogenous expression of the ΔE746–E750 deletion mutant EGFR caused the A549 cell to become more radiosensitive. Conclusions An EGFR mutated NSCLC cell line is sensitive to IR, which is correlated with reduced IR-induced Rad51 expression and nuclear translocation. The signaling pathway of EGFR maintaining Rad51 protein levels maybe a novel lung cancer therapeutic target to overcome radioresistance.

Interfractional variations of the bladder, rectum and vagina may affect the accuracy of postoperative intensity-modulated radiotherapy in patients with cervical cancer. This study aimed to assess the interfractional variations with daily kV cone-beam computed tomography (CBCT). All the patients were instructed to control the filling status of the bladder and rectum. CBCT images were obtained daily after set-up and the bladder, rectum and vagina were contoured on each CBCT scan. All the contours were transferred to the planning CT following image fusion. Interfractional variations in pelvic organs were assessed with CBCT based on two reference lines, which were identified as A (the midsaggital line across the superior border of pubic symphysis) and B (a parallel line 1.5 cm above line A). The mean volume (range) of the bladder and rectum was 156.5 (1.7-626.5) and 48.2 (11.3-139.7) ml, respectively. The uniform planning target volume (PTV) margin of 10 mm failed to encompass the vagina in 17.3 and 18.1% of the fractions on lines A and B, respectively. The motion of the vagina (standard deviation) was 0.3 (0.3) and 0.1 (0.5) cm on lines A and B, respectively. The anteroposterior dimension and position of the vagina were significantly affected by the filling status of the bladder (P

To investigate the impact of respiratory movement to determine the target volume on cone beam CT (CBCT) for lung tumor, we used CIRS dynamic thorax phantom (Model-CIRS008) to simulate the sinusoidal motion of lung tumor. With a constant amplitude, the ratio of the time of near-end-expiratory and near-end-inspiratory (E/I) changed when it was scanned with CBCT. We analyzed the contrast changes of target by extracting the CT value of each pixel on the center line of the target movement direction. The targets were contoured with region growing method and compared with the motion volume generated by the tumor trajectory method. The result showed that the contrast of near-end-expiratory increased and the contrast of near-end-inspiratory decreased with increasing E/I. The contoured volume generated by region growing method decreased with increasing E/I. When E/I = 4, the amplitude A = 1 cm, diameter of 1 cm and 3 cm target volumes were reduced by 48.2% and 22.7%. The study showed that CBCT was not suitable to be used to accurately determine the range of lung tumor movement. The internal target volume (ITV) may be underestimated in CBCT images.

Background To analyze the feasibility of active breath control (ABC), the lung tumor reproducibility and the rationale for single-breath-hold cone beam CT (CBCT)-guided hypofraction radiotherapy. Methods Single-breath-hold CBCT images were acquired using ABC in a cohort of 83 lung cancer patients (95 tumors) treated with hypofraction radiotherapy. For all alignments between the reference CT and CBCT images (including the pre-correction, post-correction and post-treatment CBCT images), the tumor reproducibility was evaluated via online manual alignment of the tumors, and the vertebral bone uncertainties were evaluated via offline manual alignment of the vertebral bones. The difference between the tumor reproducibility and the vertebral bone uncertainty represents the change in the tumor position relative to the vertebral bone. The relative tumor positions along the coronal, sagittal and transverse axes were measured based on the reference CT image. The correlations between the vertebral bone uncertainty, the relative tumor position, the total treatment time and the tumor reproducibility were evaluated using the Pearson correlations. Results Pre-correction, the systematic/random errors of tumor reproducibility were 4.5/2.6 (medial-lateral, ML), 5.1/4.8 (cranial-caudal, CC) and 4.0/3.6 mm (anterior-posterior, AP). These errors were significantly decreased to within 3 mm, both post-correction and post-treatment. The corresponding PTV margins were 4.7 (ML), 7.4 (CC) and 5.4 (AP) mm. The changes in the tumor position relative to the vertebral bone displayed systematic/random errors of 2.2/2.0 (ML), 4.1/4.4 (CC) and 3.1/3.3 (AP) mm. The uncertainty of the vertebral bone significantly correlated to the reproducibility of the tumor position (P 0.05). Conclusions Using ABC for single-breath-hold CBCT guidance is an effective method to reduce the PTV margin of hypofraction radiotherapy for lung cancer. Using ABC, the tumor position was significantly altered relative to the vertebral position. The reproducibility of the tumor position was affected by the vertebral bone but not by the relative tumor position or the total treatment time.

Some patients who have neck tumor but cannot tolerate the thermoplastic immobilization may be supported by simple cushions, and are marked on the neck skin during CT simulation. We therefore set 5 mm as the spinal cord-planning risk volume margin in the intensity-modulated radiotherapy plans in our Centre. Cone beam CT (CBCT) scans were acquired for three times, and matched with the simulation CT images in each radiotherapy. The mean and the standard deviation of the individual, the root mean-square and the standard deviation of the individual were calculated. The matched results of the third CBCT were used to calculate the spinal cord- planning risk volume margin. The results showed that the interfraction error was significantly reduced and the intrafraction error was stable by CBCT guiding. CBCT and 5 mm spinal cord-planning organ is feasible and safe without threatening volume margin to high dose radiotherapy for the patients with neck tumor and not able to tolerate thermoplastic immobilization.

Background and purpose To evaluate the feasibility and validity of cone beam computed tomography (CBCT) and active breath control (ABC) by long breath-holding in hypofraction radiotherapy of liver tumor. Methods and materials Twenty-four patients received hypofraction radiotherapy of liver tumor with long breath-holding at end-inhale; four prescriptions were used: 6Gy×7 ( n =8), 10Gy×4 ( n =7), 5Gy×9 ( n =6), 4Gy×10 ( n =3). For each fraction, all patients received pre-correction CBCT scans with ABC, some patients received post-correction and post-treatment CBCT. The interfraction and intrafraction liver positioning errors on medial–lateral (ML), cranial–caudal (CC) and anterior–posterior (AP) directions were obtained. The theoretic margin from clinical target volume (CTV) to planning target volume (PTV) was calculated based on post-treatment error. The dosimetric parameters of PTV and normal tissue were compared between ABC and free breathing (FB). Results The interfraction error in liver positioning showed system errors (Σ) of 3.18mm (ML), 6.80mm (CC) and 3.05mm (AP); random error ( σ ) of 3.03mm (ML), 6.78mm (CC) and 3.62mm (AP). These errors were significantly reduced with CBCT guided online correction. The intrafraction systematic error was 0.72mm (ML), 2.21mm (CC), 1.49mm (AP), and random error was 2.30mm (ML), 3.58mm (CC), 2.49mm (AP). Dosimetric parameters such as PTV, the liver's volume included by 23, 30Gy isodose curve (V23, V30), mean dose to normal liver (MDTNL) and mean dose to cord were significantly larger for FB ( P Conclusion Liver radiotherapy with long time breath-holding at end-inhale is an effective method to reduce liver motion, PTV and dose to normal tissue. Interfraction and intrafraction liver positioning errors were substantial. CBCT guided online correction of positioning error is recommended for liver radiotherapy with end-inhale ABC.

Image guided radiotherapy (IGRT) is a new precise radiotherapy applied in clinic. The aim of this study is to evaluate the impact of using active breath control (ABC) and stereotactic body frame on reducing the positioning error and increasing treatment precision during radiotherapy for pulmonary cancer.Seven patients with pulmonary recurrences or metastasis after prior treatment were enrolled. A total number of 13 tumor targets received irradiation, with a fraction dose of 7Gy treated every other day to a total of 7 fractions. X-ray beam volume CT was done at every fraction for correction of positioning error at 3 dimensions.The errors between pre-treatment positioning and treatment planning at left-right, anterior-posterior and cephalic-caudal directions were 0.30cm±0.14cm, 0.22cm±0.15cm and 0.28cm ±0.21cm, respectively. The positioning error was reduced after correction by volume CT and after treatment but the errors between pre-correction, post-correction and post-treatment had no statistical significance at all 3 directions. Eight targets had complete response, 4 targets had partial response, and 1 had no change.Image guided hypofractionation radiotherapy with ABC and stereotactic body frame has the advantage of increasing radiation dose and reducing overall treatment time and radiation toxicity.

Purpose To evaluate the positioning accuracy of four different immobilizations by use of cone-beam computed tomography guidance for radiotherapy of non–small-cell lung cancer (NSCLC). Methods and Materials Sixty-seven patients with NSCLC received conventional or stereotactic body radiotherapy. Of these, 30 were immobilized with a thermoplastic frame (TF), 16 with a thermoplastic frame and active breathing control (TF-ABC), 7 with a stereotactic body frame (SBF), and 14 with a stereotactic body frame and active breathing control (SBF-ABC). Cone-beam computed tomography scans at initial setup and after correction were registered to planning computed tomography. The positional errors in the left-to-right, superior-inferior, and anterior-posterior directions were analyzed. The planning target volume margins were calculated. Results The precorrection systematic and random errors ranged from 1.9 to 4.2 mm for TF, 1.9 to 4.3 mm for SBF, 1.2 to 5.8 mm for TF-ABC, and 2.3 to 3.9 mm for SBF-ABC. The postcorrection systematic and random errors ranged from 0.3 to 1.9 mm for the four immobilizations. The planning target volume margins (conventional vs. stereotactic body radiotherapy) were 15.6 vs. 13.9 mm (TF), 14.9 vs. 14.8 mm (TF-ABC), 14.4 vs. 13.4 mm (SBF), and 9.9 vs. 9.4 mm (SBF-ABC) before correction and 7.3 vs. 6.9 mm (TF), 4.0 vs. 3.8 mm (TF-ABC), 7.5 vs. 7.1 mm (SBF), and 4.5 vs. 4.2 mm (SBF-ABC) after correction. Conclusions The positioning accuracies of SBF and TF were similar. Active breathing control increased positioning error but reduced internal margin. Cone-beam computed tomography online correction improved the positioning accuracy of NSCLC patients.

Purpose To study the intrafraction tumour position error utilizing cone beam CT (CBCT) in patients receiving radiotherapy. Methods and materials Fifty-four patients were treated with Elekta Synergy S system, including 19 head and neck, 25 thoracic and 10 abdominal-pelvic tumours. All patients received CBCT after initial setup and some of them received CBCT after correction and after treatment. CBCT were registered to planning CT and errors of isocenter position on the left-to-right (LR), superior–inferior (SI) and anterior–posterior (AP) directions were analyzed. Results After treatment the systematic ( Σ ) and random uncertainty ( σ ) increased, the increments of tumour Σ were 0.1–0.3, 0.2–0.5 and 0.2–0.6mm, respectively, while the increments of σ were 0.1–0.3, 0.2–0.4 and 0.1–0.4mm, respectively, for the head and neck, thoracic and abdominal-pelvic tumours. Based on 380 paired pre- and post-treatment CBCT, the intrafraction errors (mean±SD) in the LR, SI and AP directions were −0.1±0.9, −0.3±1.0 and −0.2±0.7mm, respectively, for head and neck tumours, −0.1±1.2, −0.1±1.9 and 0.1±1.3mm, respectively, for thoracic tumours, −0.1±1.1, 0.2±1.4 and −0.1±1.5mm, respectively, for abdominal-pelvic tumours. Isotropic planning margins of 3.4, 6.1 and 5.4mm were generated with linear addition of internal margin (IM) to CTV for the head and neck, thoracic and abdominal-pelvic tumours, respectively, while margins were only 2.4, 4.4 and 3.9mm, respectively, if IM was added in quadrature. Conclusions Utilizing CBCT measurements before and after treatment to detect intrafraction tumour position errors was clinically feasible. The detected intrafraction errors could be applied to improve the accuracy of radiation delivery.

Purpose: Atlas‐based auto‐segmentation and model‐based auto‐segmentation were combined to improve accuracy of auto‐segmentation for thorax and abdomen cancer patient,herein referred to as AM 0.95 vs. 0.96 (p=0.42); 0.93 vs. 0.91 (p

Background To study the set-up errors, PTV margin and toxicity of cone beam CT (CBCT) guided hypofractionated radiotherapy with active breathing control (ABC) for patients with non-small cell lung cancer (NSCLC) or metastatic tumors in lung. Methods 32 tumors in 20 patients were treated. Based on the location of tumor, dose per fraction given to tumor was divided into three groups: 12 Gy, 8 Gy and 6 Gy. ABC is applied for every patient. During each treatment, patients receive CBCT scan for online set-up correction. The pre- and post-correction setup errors between fractions, the interfractional and intrafractional, set-up errors, PTV margin as well as toxicity are analyzed. Results The pre-correction systematic and random errors in the left-right (LR), superior-inferior (SI), anterior-posterior (AP) directions were 3.7 mm and 5.3 mm, 3.1 mm and 2.1 mm, 3.7 mm and 2.8 mm, respectively, while the post-correction residual errors were 0.6 mm and 0.8 mm, 0.8 mm and 0.8 mm, 1.2 mm and 1.3 mm, respectively. There was an obvious intrafractional shift of tumor position. The pre-correction PTV margin was 9.5 mm in LR, 14.1 mm in SI and 8.2 mm in AP direction. After CBCT guided online correction, the PTV margin was markedly reduced in all three directions. The post-correction margins ranged 1.5 to 2.1 mm. The treatment was well tolerated by patients, of whom there were 4 (20%) grade1-2 acute pneumonitis, 3 (15%) grade1 acute esophagitis, 2 (10%) grade1 late pneumonitis and 1 (5%) grade 1 late esophagitis. Conclusion The positioning errors for lung SBRT using ABC were significant. Online correction with CBCT image guidance should be applied to reduce setup errors and PTV margin, which may reduce radiotherapy toxicity of tissues when ABC was used.

Background Whole brain radiotherapy (WBRT) plus sequential focal radiation boost is a commonly used therapeutic strategy for patients with brain metastases. However, recent reports on WBRT plus simultaneous in-field boost (SIB) also showed promising outcomes. The objective of present study is to retrospectively evaluate the efficacy and toxicities of WBRT plus SIB with image guided intensity-modulated radiotherapy (IG-IMRT) for inoperable brain metastases of NSCLC. Methods Twenty-nine NSCLC patients with 87 inoperable brain metastases were included in this retrospective study. All patients received WBRT at a dose of 40 Gy/20 f, and SIB boost with IG-IMRT at a dose of 20 Gy/5 f concurrent with WBRT in the fourth week. Prior to each fraction of IG-IMRT boost, on-line positioning verification and correction were used to ensure that the set-up errors were within 2 mm by cone beam computed tomography in all patients. Results The one-year intracranial control rate, local brain failure rate, and distant brain failure rate were 62.9%, 13.8%, and 19.2%, respectively. The two-year intracranial control rate, local brain failure rate, and distant brain failure rate were 42.5%, 30.9%, and 36.4%, respectively. Both median intracranial progression-free survival and median survival were 10 months. Six-month, one-year, and two-year survival rates were 65.5%, 41.4%, and 13.8%, corresponding to 62.1%, 41.4%, and 10.3% of intracranial progression-free survival rates. Patients with Score Index for Radiosurgery in Brain Metastases (SIR) >5, number of intracranial lesions