Purpose The purpose of this study was to evaluate the effect of a lead block for alveolar bone protection in image-guided high-dose-rate interstitial brachytherapy for tongue cancer. Material and methods We treated 6 patients and delivered 5,400 cGy in 9 fractions using a lead block. Effects of lead block (median thickness, 4 mm) on dose attenuation by distance were visually examined using TG-43 formalism-based dose distribution curves to determine whether or not the area with the highest dose is located in the alveolar bone, where there is a high-risk of infection. Dose re-calculations were performed using TG-186 formalism with advanced collapsed cone engine (ACE) for inhomogeneity correction set to cortical bone density for the whole mandible and alveolar bone, water density for clinical target volume (CTV), air density for outside body and lead density, and silastic density for lead block and its’ silicon replica, respectively. Results The highest dose was detected outside the alveolar bone in five of the six cases. For dose-volume histogram analysis, median minimum doses delivered per fraction to the 0.1 cm3 of alveolar bone (D0.1cm3TG-43, ACE-silicon, and ACE-lead) were 344.3 (range, 262.9-427.4) cGy, 336.6 (253.3-425.0) cGy, and 169.7 (114.9-233.3) cGy, respectively. D0.1cm3ACE-lead was significantly lower than other parameters. No significant difference was observed between CTV-related parameters. Conclusions The results suggested that using a lead block for alveolar bone protection with a thickness of about 4 mm, can shift the highest dose area to non-alveolar regions. In addition, it reduced D0.1cm3 of alveolar bone to about half, without affecting tumor dose.

Purpose The Task Group 218 (TG-218) report was published by the American Association of Physicists in Medicine in 2018, recommending the appropriate use of gamma index analysis for patient-specific quality assurance (PSQA). The paper demonstrates that PSQA for radiotherapy in Japan appropriately applies the gamma index analysis considering TG-218. Materials/methods This survey estimated the acceptance state of radiotherapeutic institutes or facilities in Japan for the guideline using a web-based questionnaire. To investigate an appropriate PSQA of the facility-specific conditions, we researched an optimal tolerance or action level for various clinical situations, including different treatment machines, clinical policies, measurement devices, staff or their skills, and patient conditions. The responded data were analyzed using principal component analysis (PCA) and multidimensional scaling (MDS). The PCA focused on factor loading values of the first contribution over 0.5, whereas the MDS focused on mapped distances among data. Results Responses were obtained from 148 facilities that use intensity-modulated radiation therapy (IMRT), which accounted for 42.8% of the probable IMRT use in Japan. This survey revealed the appropriate application of the following universal criteria for gamma index analysis from the guideline recommendation despite the facility-specific variations (treatment machines/the number of IMRT cases/facility attributes/responded [representative] expertise or staff): (a) 95% pass rate, (b) 3% dose difference and 2-mm distance-to-agreement, and (c) 10% threshold dose. Conditions (a)-(c) were the principal components of the data by the PCA method and were mapped in a similar distance range, which was easily clustered from other gamma index analytic factors by the MDS method. Conditions (a)-(c) were the universally essential factors for the PSQA in Japan. Conclusion We found that the majority of facilities using IMRT in each region of Japan complied with the guideline and conducted PSQA with deliberation under the individual facility-specific conditions.

Background/Aim: To evaluate the surrogate-guided registration accuracy of two computed tomography (CT) image sets, expiratory phase four-dimensional (Ex4D) CT and breath-holding CT (BHCT), in respiratory-gated radiotherapy for liver cancer. Materials and Methods: The surrogate-guided registration errors were defined as the differences between the diaphragm- and fiducial-guided registrations or the differences between upper and lower fiducial registrations in three directions: left–right (LR), anterior–posterior (AP), and cranio–caudal (CC). Results: The mean±SDs of the absolute errors for diaphragm-guided registration were 1.9±1.3, 2.7±1.8, and 2.6±1.7 mm with Ex4D and 1.8±1.8, 2.6±1.9, and 1.8±1.7 mm with BHCT in the LR, AP and CC directions, respectively (CC direction, p<0.01). In the fiducial-guided registration, there were no significant differences in any direction. In registration with Ex4D, there were positive correlations between registration errors and the respiratory irregularity during 4D scanning (correlation coefficient; diaphragm: 0.65, fiducial: 0.54). Conclusion: BHCT has the advantage of accurate surrogate-guided registration compared with Ex4D.

Abstract The purpose of this study was to evaluate the effect of dose rate to the rectum on late rectal complications in patients treated with computed tomography (CT)-based image-guided brachytherapy (IGBT) for cervical cancer. The subjects were 142 patients with cervical cancer who underwent Ir-192 high-dose-rate (HDR)-IGBT between March 2012 and January 2018. The dose rate to the rectum was calculated using in-house software. The minimum, mean and maximum effective dose rate (EDR) was calculated for voxels of the rectal volume covered by cumulative doses >D0.1cc, >D2cc, and > D5cc. The average EDR of three to four brachytherapy sessions was calculated (EDR for patients; EDRp). The total dose of the rectum was calculated as the biologically equivalent dose in 2-Gy fractions (EQD2). The associations between EDRp for D0.1cc, D2cc, and D5cc and the respective rectal EQD2 values with late rectal complications were then analyzed. The median follow-up period was 40 months. Patients with rectal complications of ≥Grade 1 received a significantly higher mean EDRp for D0.1cc–5cc and had a greater EQD2 for D0.1cc–5cc. Multivariate analysis was performed using the mean EDRp for D2cc, EQD2 for D2cc, heavy smoking and BMI. Of these four variables, mean EDRp for D2cc (HR = 3.38, p = 0.004) and EQD2 for D2cc (HR = 2.59, p = 0.045) emerged as independent predictors for late rectal complications. In conclusion, mean EDRp and EQD2 were associated with late rectal complications in patients treated with HDR CT-based IGBT for cervical cancer.

Abstract The purpose of this study was to compare single-arc (SA) and double-arc (DA) treatment plans, which are planning techniques often used in prostate cancer volumetric modulated arc therapy (VMAT), in the presence of intrafractional deformation (ID) to determine which technique is superior in terms of target dose coverage and sparing of the organs at risk (OARs). SA and DA plans were created for 27 patients with localized prostate cancer. ID was introduced to the clinical target volume (CTV), rectum and bladder to obtain blurred dose distributions using an in-house software. ID was based on the motion probability function of each structure voxel and the intrafractional motion of the respective organs. From the resultant blurred dose distributions of SA and DA plans, various parameters, including the tumor control probability, normal tissue complication probability, homogeneity index, conformity index, modulation complexity score for VMAT, dose–volume indices and monitor units (MUs), were evaluated to compare the two techniques. Statistical analysis showed that most CTV and rectum parameters were significantly larger for SA plans than for DA plans (P < 0.05). Furthermore, SA plans had fewer MUs and were less complex (P < 0.05). The significant differences observed had no clinical significance, indicating that both plans are comparable in terms of target and OAR dosimetry when ID is considered. The use of SA plans is recommended for prostate cancer VMAT because they can be delivered in shorter treatment times than DA plans, and therefore benefit the patients.

Abstract Treatment time with the CyberKnife frameless radiosurgery system is prolonged due to the motion of the robotic arm. We have developed a novel scanning irradiation method to reduce treatment time. We generated treatment plans mimicking eight-field intensity-modulated radiotherapy (IMRT) plans generated for the Novalis radiosurgery system. 2D dose planes were generated with multiple static beam spots collimated by a fixed circular cone. The weights of the uniformly distributed beam spots in each dose plane were optimized using the attraction–repulsion model. The beam spots were converted to the scanning speed to generate the raster scanning plan. To shorten treatment time, we also developed a hybrid scanning method which combines static beams with larger cone sizes and the raster scanning method. Differences between the Novalis and the scanning plan’s dose planes were evaluated with the criterion of a 5% dose difference. The mean passing rates of three cases were > 85% for cone sizes ≤ 12.5 mm. Although the total monitor units (MU) increased for smaller cone sizes in an inverse-square manner, the hybrid scanning method greatly reduced the total MU, while maintaining dose distributions comparable to those with the Novalis plan. The estimated treatment time of the hybrid scanning with a 12.5 mm cone size was on average 22% shorter than that of the sequential plans. This technique will be useful in allowing the CyberKnife with conventional circular cones to achieve excellent dose distribution with a shortened treatment time.

Background: The present study aimed to estimate geometric changes in applicators and prostate over 3 days in patients with high-dose-rate brachytherapy (HDR-BT) and to assess the need for daily replanning. Patients and Methods: This study retrospectively investigated 18 patients who underwent HDR-BT as monotherapy from February 2016 to October 2018. Results: Without replanning, the planning target volume coverage significantly worsened on day 2 (p<0.001) and day 3 (p=0.003). The minimum dose distributed to the highest irradiated rectal volume of 5 cc became significantly higher on day 2 (p=0.02), and the maximum dose distributed to the urethra became significantly higher on day 2 (p=0.01). Conclusion: Conformal, high-dose delivery of HDR-BT is impaired without replanning not only on the second day but also on the third day. Daily replanning is required for achieving accuracy of HDR-BT.

Objective: Although various single genetic factors have been shown to affect radiosensitivity, high-throughput DNA sequencing analyses have revealed complex genomic landscapes in many cancer types. The aim of this study is to elucidate the association between accumulated alterations in driver and passenger genes and radiation therapy response. Methods: We used 59 human solid cancer cell lines derived from 11 organ sites. Radiation-induced cell death was measured using a standard colony-forming assay delivered as a single dose ranging from 0 to 12 Gy. Comprehensive genomic data for the cell lines were acquired from the Catalogue Of Somatic Mutations In Cancer v. 80. Random forest classifiers were constructed to predict radioresistant phenotypes using genomic features. The Cancer Genome Atlas data sets were used to evaluate the clinical impact of the genomic feature following radiotherapy. Results: The 59 cancer cell lines harbored either nucleotide variations or copy number variations in a median of 157 genes per cell. Radiosensitivity of the cancer cells was correlated with neither the number of driver gene mutations nor the number of passenger gene mutations. However, the proportion of driver gene alterations to total gene alterations in gene sets selected from the Kyoto Encyclopedia Genes and Genomes predicted radioresistant cells with sensitivity of 85% and specificity of 73%. High probability of radioresistance predicted by the model was associated with worse overall survival following definitive radiotherapy in patients of The Cancer Genome Atlas data sets. Conclusion: Cellular radiosensitivity was associated with the proportion of driver to total gene alterations in the selected oncogenic pathways, which may be a biomarker candidate for response to radiation therapy. Advances in knowledge: These findings suggest that accumulated alterations in not only driver genes but also passenger genes affect radiosensitivity.

Background: The aim of this study was to clarify factors predicting the performance of knowledge-based planning (KBP) models in volume modulated arc therapy for prostate cancer in terms of sparing the organ at risk (OAR). Materials and methods: In three institutions, each KBP model was trained by more than 20 library plans (LP) per model. To validate the characterization of each KBP model, 45 validation plans (VP) were calculated by the KBP system. The ratios of overlap between the OAR volume and the planning target volume (PTV) to the whole organ volume (V-overlap/V-whole) were analyzed for each LP and VP. Regression lines between dose-volume parameters (V-90, V-75, and V-50) and V-overlap/V-whole were evaluated. The mean OAR dose, V-90, V-75, and V-50 of LP did not necessarily match those of VP. Results: In both the rectum and bladder, the dose-volume parameters for VP were strongly correlated with V-overlap/V-whole at institutes A, B, and C (R > 0.74, 0.85, and 0.56, respectively). Except in the rectum at institute B, the slopes of the regression lines for LP corresponded to those for VP. For dose-volume parameters for the rectum, the ratios of slopes of the regression lines in VP to those in LP ranged 0.51-1.26. In the bladder, most ratios were less than 1.0 (mean: 0.77). Conclusion: For each OAR, each model made distinct dosimetric characterizations in terms of V-overlap/V-whole. The relationship between dose-volume parameters and V-overlap/V-whole of OARs in LP predicts the KBP models' performance sparing OARs. (C) 2020 Greater Poland Cancer Centre. Published by Elsevier B.V. All rights reserved.

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.

Background: This study aimed to evaluate knowledge-based volume modulated arc therapy (VMAT) plans for oesophageal cancers using a model trained with plans optimised with a different treatment planning system (TPS) and to compare lung dose sparing in two TPSs, Eclipse and RayStation. Materials and methods: A total of 64 patients with stage I-III oesophageal cancers were treated using hybrid VMAT (H-VMAT) plans optimised using RayStation. Among them, 40 plans were used for training the model for knowledge-based planning (KBP) in RapidPlan. The remaining 24 plans were recalculated using RapidPlan to validate the KBP model. H-VMAT plans calculated using RapidPlan were compared with H-VMAT plans optimised using RayStation with respect to planning target volume doses, lung doses, and modulation complexity. Results: In the lung, there were significant differences between the volume ratios receiving doses in excess of 5, 10, and 20 Gy (V-5, V-10, and V-20). The V-5 for the lung with H-VMAT plans optimised using RapidPlan was significantly higher than that of H-VMAT plans optimised using RayStation (p < .01), with a mean difference of 10%. Compared to H-VMAT plans optimised using RayStation, the V-10 and V-20 for the lung were significantly lower with H-VMAT plans optimised using RapidPlan (p = .04 and p = .02), with differences exceeding 1.0%. In terms of modulation complexity, the change in beam output at each control point was more constant with H-VMAT plans optimised using RapidPlan than with H-VMAT plans optimised using RayStation. The range of the change with H-VMAT plans optimised using RapidPlan was one third that of H-VMAT plans optimised using RayStation. Conclusion: Two optimisers in Eclipse and RayStation had different dosimetric performance in lung sparing and modulation complexity. RapidPlan could not improve low lung doses, however, it provided an appreciate intermediated doses compared to plans optimised with RayStation.

Abstract Purpose To investigate the detectability of fiducial markers’ positions for real‐time target tracking system equipping with a standard linac. The hypothesis is that the detectability depends on the type of fiducial marker and the gantry angle of acquired triggered images. Methods Three types of ball fiducials and four slim fiducials with lengths of 3 and 5 mm were prepared for this study. Triggered images with three similar fiducials were acquired at every 10° during the conformal arc irradiation to detect the target position. Although only one type of arrangement was prepared for the ball fiducials, a three‐type arrangement was prepared for the slim fiducials, such as parallel, orthogonal, and oblique with 45° to the gantry‐couch direction. To measure the detectability of the real‐time target tracking system for each fiducial and arrangement, detected marker positions were compared with expected marker positions at every angle of acquired triggered images. Results For the ball‐type fiducial, the maximum difference between the detected marker positions and expected marker positions was 0.3 mm in all directions. For the slim fiducial arranged parallel and oblique with 45°, the maximum difference was 0.4 mm in all directions. When each slim fiducial was arranged orthogonal to the gantry‐couch direction, the maximum difference was 1.5 mm for the length of 3 mm, and 3.2 mm for the length of 5 mm. Conclusions The detectability of fiducial markers’ positions for the real‐time target tracking system equipping with a standard linac depends on the form and insertion angles of the fiducials.

Purpose: This study aims to investigate the feasibility of using convolutional neural networks to predict an accurate and high resolution dose distribution from an approximated and low resolution input dose. Methods: Sixty-six patients were treated for prostate cancer with VMAT. We created the treatment plans using the Acuros XB algorithm with 2 mm grid size, followed by the dose calculated using the anisotropic analytical algorithm with 5 mm grid with the same plan parameters. U-net model was used to predict 2 mm grid dose from 5 mm grid dose. We investigated the two models differing for the training data used as input, one used just the low resolution dose (D model) and the other combined the low resolution dose with CT data (DC model). Dice similarity coefficient (DSC) was calculated to ascertain how well the shape of the dose-volume is matched. We conducted gamma analysis for the following: DVH from the two models and the reference DVH for all prostate structures. Results: The DSC values in the DC model were significantly higher than those in the D model (p < 0.01). For the CTV, PTV, and bladder, the gamma passing rates in the DC model were significantly higher than those in the D model (p < 0.002-0.02). The mean doses in the CTV and PTV for the DC model were significantly better matched to those in the reference dose (p < 0.0001). Conclusions: The proposed U-net model with dose and CT image used as input predicted more accurate dose.

Outcomes for patients with Stage IB1-IVA cervical cancer treated with computed tomography (CT)-based image-guided brachytherapy (IGBT) were examined in this study. A total of 84 patients were analyzed between March 2012 and June 2015. Whole-pelvic radiotherapy with a central shield was performed for each patient, and the total pelvic sidewall dose was 50 Gy. IGBT was delivered in 2-4 fractions. The initial prescription dose (6.8 Gy) was delivered at Point A, and the dose distribution was modified manually by graphical optimization. The total dose was calculated as the biologically equivalent dose in 2 Gy fractions (EQD2). Concurrent chemotherapy was administered to 64 patients (76%). The median follow-up period was 36 months (range 2-62 months). The 3-year overall survival, local control, and progression-free survival rates were 94%, 89% and 81%, respectively. The mean EQD2 for HR-CTV D90 was 73.4 Gy, and the EQD2 for HR-CTV D90 was not significantly associated with the local control rate. In multivariate analysis, adenocarcinoma (P = 0.03) and tumor size ≥45 mm (P = 0.06) were risk factors for local control. The patients were divided into four groups based on histology (squamous cell carcinoma vs adenocarcinoma) and tumor size (<45 vs ≥45 mm). Those with large adenocarcinomas had significantly worse outcomes. In conclusion, CT-based IGBT achieved favorable local control, but different treatment strategies may be necessary for large adenocarcinomas.

Over the last several decades, there have been great advances in radiotherapy with the development of new technologies and modalities, and radiotherapy trends have changed rapidly. To comprehend the current state of radiotherapy in Japan, the QA/QC 2016-2017 Committee of the Japan Society of Medical Physics set up an intensity-modulated radiotherapy/image-guided radiotherapy (IMRT/IGRT) working group and performed a Web-based survey to show the current status of radiotherapy in Japan. The Web-based questionnaire, developed using Google Forms, contained 42 items: 7 on stereotactic radiotherapy implementation, 4 on IMRT, 24 on IGRT, and 7 on respiratory motion management. The survey was conducted from 17 January to 9 March of 2018; in total, 335 institutions provided data. The results show that volumetric modulated arc therapy was used at a level comparable to that of static gantry IMRT. For IGRT, machine-integrated computed tomography (CT), including kilovoltage or megavoltage cone-beam CT and megavoltage CT, was used at many institutions in conjunction with target-based image registration. For respiratory motion management, breath holding was the most commonly used technique. Our hope is that multi-institutional surveys such as this one will be conducted periodically to elucidate the current status of radiotherapy and emerging developments in this field. If our questionnaire was distributed worldwide, in the same format, then global trends in radiotherapy could be better understood.

ABSTRACT 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.

This study aims to produce non-contrast computed tomography (CT) images using a deep convolutional neural network (CNN) for imaging. Twenty-nine patients were selected. CT images were acquired without and with a contrast enhancement medium. The transverse images were divided into 64 × 64 pixels. This resulted in 14 723 patches in total for both non-contrast and contrast-enhanced CT image pairs. The proposed CNN model comprises five two-dimensional (2D) convolution layers with one shortcut path. For comparison, the U-net model, which comprises five 2D convolution layers interleaved with pooling and unpooling layers, was used. Training was performed in 24 patients and, for testing of trained models, another 5 patients were used. For quantitative evaluation, 50 regions of interest (ROIs) were selected on the reference contrast-enhanced image of the test data, and the mean pixel value of the ROIs was calculated. The mean pixel values of the ROIs at the same location on the reference non-contrast image and the predicted non-contrast image were calculated and those values were compared. Regarding the quantitative analysis, the difference in mean pixel value between the reference contrast-enhanced image and the predicted non-contrast image was significant (P < 0.0001) for both models. Significant differences in pixels (P < 0.0001) were found using the U-net model; in contrast, there was no significant difference using the proposed CNN model when comparing the reference non-contrast images and the predicted non-contrast images. Using the proposed CNN model, the contrast-enhanced region was satisfactorily reduced.

AIM:To evaluate the toxicity and efficacy of re-irradiation with salvage stereotactic radiotherapy (SRT) for recurrent glioma using CyberKnife.PATIENTS AND METHODS:This study retrospectively investigated 35 patients with 48 recurrent grade 2-4 gliomas who received SRT between 1998 and 2011. Six patients (17.1%) had grade 2 gliomas, nine (25.7%) had grade 3 gliomas, and 20 (57.1%) had glioblastomas; all initially underwent surgery and conventional radiotherapy. The median initial and subsequent radiotherapy doses were 60 and 26 Gy, respectively.RESULTS:After a median follow-up period of 9.0 months, the only toxicity of grade 2 or more was radiation-induced brain necrosis in four patients (11.4%). The median overall and progression-free survival periods following re-irradiation were 9.0 and 3.0 months, respectively. Univariate analysis revealed that performance status at salvage re-irradiation was a significant predictor of progression-free survival.CONCLUSION:Salvage re-irradiation using CyberKnife is feasible, with an acceptable toxicity profile, for patients with recurrent glioma.