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Background/Aim: In advanced stage lung cancer, bulky tumors can cause serious symptoms such as malignant airway obstruction (MAO). Prompt response to airway obstruction might be essential to improve quality of life and prolong life expectancy. Palliative external beam radiotherapy (EBRT) is a less invasive and highly safe treatment method that can alleviate symptoms and at the same time treat lung cancer. However, there are few reports on the results of palliative radiotherapy performed for improving airway obstruction and obstructive pneumonia. Therefore, this study retrospectively examined the effectiveness of palliative radiotherapy. Patients and Methods: We reviewed 38 lung cancer patients with MAO who underwent EBRT. Patients were treated with a median dose of 37.5 Gy (range=30-40 Gy) in 10-20 fractions. Whether a patient was a responder or non-responder was assessed by whether the bronchus that was obstructed before EBRT reopened or improvement of obstructive pneumonia was observed on follow-up chest X-ray or computed tomography after EBRT. Results: The median survival time was 135 days (range=31-469 days) for the responders to EBRT and 45 days (range=23-355 days) for non-responders; this difference was statistically significant (p=0.03). One-year overall survival rate was 18.5% and 0% for the responders to EBRT and non-responders, respectively. Conclusion: Palliative EBRT might be an important option for non-curative lung cancer patients with MAO.

PURPOSE The purpose of this study is to evaluate the prediction and classification performances of the gamma passing rate (GPR) for different machine learning models and to select the best model for achieving machine learning-based patient-specific quality assurance (PSQA). METHODS The measurement verification of 356 head-and-neck volumetric modulated arc therapy plans was performed using a diode array phantom (Delta4 Phantom), and GPR values at 2%/2 mm with global normalization and 3%/2 mm with local normalization were calculated. Machine learning models, including ridge regression (RIDGE), random forest (RF), support vector regression (SVR), and stacked generalization (STACKING), were used to predict the GPR. Each machine learning model was trained using 260 plans, and the prediction accuracy was evaluated using the remaining 96 plans. The prediction error between the measured and predicted GPR was evaluated. For the classification evaluation, the lower control limit for the measured GPR and lower control limit for predicted GPR (LCLp ) was defined to identify whether the GPR values represent a "pass" or a "fail." LCLp values with 99% and 99.9% confidence levels were calculated as the upper prediction limits for the GPR estimated from the linear regression between the measured and predicted GPR. RESULTS There was an overestimation trend of the low measured GPR. The maximum prediction errors for RIDGE, RF, SVR, and STACKING were 3.2%, 2.9%, 2.3%, and 2.2% at global 2%/2 mm and 6.3%, 6.6%, 6.1%, and 5.5% at the local 3%/2 mm, respectively. In the global 2%/2 mm, the sensitivity was 100% for all the machine learning models except RIDGE when using 99% LCLp . The specificity was 76.1% for RIDGE, RF, and SVR and 66.3% for STACKING, however, the specificity decreased dramatically when 99.9% LCLp was used. In the local 3%/2 mm, however, only STACKING showed 100% sensitivity when using 99% LCLp . The decrease in the specificity using 99.9% LCLp was smaller than that in the global 2%/2mm, and the specificity for RIDGE, RF, SVR, and STACKING was 61.3%, 61.3%, 72.0%, and 66.8%, respectively. CONCLUSIONS STACKING had better prediction accuracy for low GPR values than other machine learning models. Applying LCLp to a regression model enabled the consistent evaluation of quantitative and qualitative GPR predictions. Adjusting the confidence level of the LCLp helped improve the balance between the sensitivity and specificity. We suggest that STACKING can assist the safe and efficient operation of PSQA. This article is protected by copyright. All rights reserved.

Optimization process in treatment planning for intensity‐modulated radiation therapy varies with the treatment planner. Therefore, a large variation in the quality of dose distribution is usually observed. To reduce variation, an automatic optimizing toolkit was developed for the Monaco treatment planning system (Elekta AB, Stockholm, Sweden) for prostate cancer using volumetric‐modulated arc therapy (VMAT). This toolkit was able to create plans automatically. However, most plans needed two arcs per treatment to ensure the dose coverage for targets. For prostate cancer, providing a plan with a single arc was advisable in clinical practice because intrafraction motion management must be considered to irradiate accurately. The purpose of this work was to develop an automatic treatment planning system with a single arc per treatment for prostate cancer using VMAT. We designed the new algorithm for the automatic treatment planning system to use one arc per treatment for prostate cancer in Monaco. We constructed the system in two main steps: (1) Determine suitable cost function parameters for each case before optimization, and (2) repeat the calculation and optimization until the conditions for dose indices are fulfilled. To evaluate clinical suitability, the plan quality between manual planning and the automatic planning system was compared. Our system created the plans automatically in all patients within a few iterations. Statistical differences between the plans were not observed for the target and organ at risk. It created the plans with no human input other than the initial template setting and system initiation. This system offers improved efficiency in running the treatment planning system and human resources while ensuring high‐quality outputs.

Background International guidelines recommend brachytherapy for patients with dysphagia from esophageal cancer, whereas brachytherapy is infrequently used to palliate dysphagia in some countries. To clarify the availability of palliative treatment for dysphagia from esophageal cancer and explain why brachytherapy is not routinely performed are unknown, this study investigated the use of brachytherapy and external beam radiotherapy for dysphagia from esophageal cancer. Methods Japanese Radiation Oncology Study Group members completed a survey and selected the treatment that they would recommend for hypothetical cases of dysphagia from esophageal cancer. Results Of the 136 invited facilities, 61 completed the survey (44.9%). Four (6.6%) facilities performed brachytherapy of the esophagus, whereas brachytherapy represented the first-line treatment at three (4.9%) facilities. Conversely, external beam radiotherapy alone and chemoradiotherapy were first-line treatments at 61 and 58 (95.1%) facilities, respectively. In facilities that performed brachytherapy, the main reason why brachytherapy of the esophagus was not performed was high invasiveness (30.2%). Definitive-dose chemoradiotherapy with (≥50 Gy) tended to be used in patients with expected long-term survival. Conclusions Few facilities routinely considered brachytherapy for the treatment of dysphagia from esophageal cancer in Japan. Conversely, most facilities routinely considered external beam radiotherapy. In the future, it will be necessary to optimize external beam radiotherapy.

Evidence regarding postoperative radiation therapy (PORT) for metastases to the long bones is lacking. Characterizing the current practice patterns and identifying factors that influence dose-fractionation schedules are essential for future clinical trials. An internet-based survey of the palliative RT subgroup of the Japanese Radiation Oncology Study Group was performed in 2017 to collect data regarding PORT prescription practices and dose-fractionation schedules. Responders were also asked to recommend dose-fractionation schedules for four hypothetical cases that involved a patient with impending pathological fractures and one of four clinical features (poor prognosis, solitary metastasis, radio-resistant primary tumor or expected long-term survival). Responders were asked to indicate their preferred irradiation fields and the reasons for the dose fractionation schedule they chose. Responses were obtained from 89 radiation oncologists (67 institutions and 151 RT plans) who used 22 dose-fractionation schedules, with the most commonly used and recommended schedule being 30 Gy in 10 fractions. Local control was the most common reason for preferring longer-course RT. High-dose fractionated schedules were preferred for oligometastasis, and low-dose regimens were preferred for patients with a poor prognosis; however, single-fraction RT was not preferred. Most respondents recommended targeting the entire orthopedic prosthesis. These results indicated that PORT using 30 Gy in 10 fractions to the entire orthopedic prosthesis is preferred in current Japanese practice and that single-fraction RT was not preferred. Oligometastasis and poor prognosis influenced the selection of high- or low-dose regimens.

This study aimed to research the post-treatment quality of life (QOL) between radiotherapy (RT)- and operation (OP)-treated early cervical cancer survivors, using separate questionnaires for physicians and patients. We administered an observational questionnaire to patients aged 20–70 years old with Stages IB1–IIB cervical cancer who had undergone RT or OP and without recurrence as outpatients for ≥6 months after treatment. We divided 100 registered patients equally into two treatment groups (n = 50 each). The average age was 53 and 44 years in the RT and OP groups, respectively. The RT group included 34 and 66% Stage I and II patients, respectively, whereas the OP group included 66 and 34% Stage I and II patients, respectively. The OP group included 58% of patients with postoperative RT. Combination chemotherapy was performed in 84 and 48% of patients in the RT and OP groups, respectively. On the physicians’ questionnaire, we observed significant differences in bone marrow suppression (RT) and leg edema (OP). On the patients’ questionnaire, significantly more patients had dysuria and leg edema in the OP group than in the RT group, and severe (Score 4–5) leg edema was significantly higher in the post-operative RT group than in the OP only group. The frequency of sexual intercourse decreased after treatment in both groups. On the patients’ questionnaire, there were no significant differences between the two groups regarding sexual activity. These findings are useful to patients and physicians for shared decision-making in treatment choices. The guidance of everyday life and health information including sexual life after treatment is important.

Purpose Improving pain interference in daily activities, rather than mere pain reduction, is a desirable endpoint for palliative radiation therapy. The association between pain response and pain interference has been studied almost exclusively in patients with painful bone metastases (PBMs), whereas nonindex pain has scarcely been explored in palliative radiation therapy. We investigated whether index and nonindex pain endpoints are associated with pain interference changes in patients with both PBMs and painful non-bone-metastasis tumors (PNTs). Methods and Materials Brief pain inventory data collected at baseline and at 2 months post-treatment were used to calculate differences in pain interference scores. Pain response in terms of the index pain was assessed using the international consensus endpoint. Patients were diagnosed with predominance of other pain (POP) if nonindex pain of malignant or unknown origin was present and had a greater pain score than the index pain. Results Of 302 patients, 127 (42%) had PBMs and 175 (58%) had PNTs. The median pain interference score, which is based on the mean of the 7 subscale items, decreased to a greater extent among responders than among nonresponders (PBM group: –3.43 vs –0.57 [P = .005]; PNT group: –2.43 vs –0.29 [P < .001]). Moreover, patients without POP experienced a greater reduction in their median pain interference score than did those with POP (PBM group: –2.71 vs +0.43 [P = .004]; PNT group: –2.00 vs +1.57 [P = .007]). The Jonckheere-Terpstra test showed a significant trend across 4 pain response categories in patients with PBMs and those with PNTs (P < .001 for both). Conclusions The index and nonindex pain endpoints were positively and negatively associated with improvement in pain interference, respectively. There was no apparent difference between patients with PBMs and PNTs in terms of the associations of these endpoints with pain interference.

Objective Since most radiation treatment plans are based on computed tomography (CT) images, which makes it difficult to define the targeted tumor volume located near a metal implant, this study aims to evaluate and compare three treatment plans in order to optimally reduce geometrical uncertainty in external radiation treatment of localized prostate cancer. Methods Experimental subjects were three prostate patients with bilateral hip prosthesis who had undergone radical radiotherapy. The treatment plans were five-field three-dimensional conformal radiation therapy (3D-CRT), fixed 5-field intensity-modulated radiation therapy (IMRT) using similar gantry angles, and single-arc volumetric modulated arc therapy (VMAT). The monitor units (MUs), dose volume histograms (DVHs), the dose indices of planning target volume (PTV), clinical target volume (CTV) and rectum were compared among the three techniques. The geometrical uncertainties were evaluated by shifting the iso-center (2- 10 mm in the anterior, posterior, left, right, superior, and inferior directions). The CTV and rectum dose indexes with and without the iso-center shifts were compared in each plan. Results The Conformity Index of PTV were 1.35 in 3D-CRT, 1.12 in IMRT, and 1.04 in VMAT, respectively. The rectum doses in 3D-CRT are also higher than those in IMRT and VMAT. The iso-center shift little affected the CTV dose when smaller than the margin size. The rectum dose increased especially after a posterior shift. Additionally, this dose increase was larger in the VMAT plan than in the 3D- CRT plan. However, the VMAT achieved a superior rectum DVH to that of 3D- CRT, and this effect clearly exceeded the rectum-dose increase elicited by the iso-center shift. Conclusion For radiotherapy treatment of localized prostate cancer in patients with hip prosthesis, the dose distribution was better in the VMAT and Metal Artifact Reduction (MAR)-CT image methods than the conventional methods. Because the anatomical structure of the male pelvic region is relatively constant among individuals, we consider that VMAT is a valid treatment plan despite analyzing just three cases.

Aim To investigate the variation of tumor volume during moderate hypo-fractionated stereotactic body radiation therapy (SBRT). Patients and Methods Twenty patients, who received SBRT at our institution, were included in the analysis. A prescribed dose was 56 Gy at iso-center in seven fractions. Tumor volumes before and during SBRT were calculated. In order to investigate factors affecting the variation of tumor volume in RT 2 (after first irradiation) and RT 7 (after last irradiation), various parameters were verified by the Mann-Whitney U test. Results With regard to the low maximum standardized uptake values (SUVmax) group, transient increase of tumor volume was found in RT 2, and tumor volume reduction was hardly found in RT 7. With regard to the high SUVmax group, a transient increase was not found, and a definite reduction was found in the treatment course. Conclusion Accurate prediction of tumor volume variation is required for more accurate treatment, such as adaptive radiation therapy.

Purpose: A quality indicator (QI) is a valuable tool to evaluate the quality of health care systems. In palliative radiation oncology, only a few of its related QIs have been developed to date. In this study, we sought to develop and pilot test QIs that assess the quality of care in palliative radiation therapy. Methods and materials: A modified Delphi method was used to establish consensus with an expert panel. The panel consisted of eight radiation oncologists who have expertise in palliative radiation oncology and one expert on Delphi methodology. Online panel meetings and e-mail surveys were conducted to develop QIs on palliative radiation therapy for bone and brain metastases. Feasibility of measurement was assessed though pilot surveys that were conducted by radiation oncologists at five facilities. Results: After three online meetings and two e-mail surveys, we developed four QIs on bone metastases and three QIs on brain metastases. Two email surveys and two pilot surveys confirmed the validity of QIs and the feasibility of measurement, respectively. Conclusions: We developed valid and feasible QIs on palliative radiation therapy for bone and brain metastases. Our work may contribute to reduce the evidence-practice gaps in palliative radiation oncology.

Palliative radiotherapy seems to be rarely performed for incurable gastric cancer. In this first multicenter study, we examined the effectiveness of palliative radiotherapy and investigated whether biologically effective dose (BED) is associated with survival, response, or re-bleeding. Eligibility criteria included blood transfusion or hemoglobin levels

Background/aim To determine whether concurrent chemotherapy with radiotherapy should be performed in elderly patients with esophageal cancer. Patients and methods A total of 185 patients aged 80 years or older who were treated with definitive radiotherapy alone or combined with chemoradiotherapy for esophageal cancer at seven institutions were enrolled. In order to compare survival rates of patients treated with chemoradiotherapy with those of patients treated with radiotherapy alone, propensity score matching was performed to homogenize the two populations. Results For the whole patient cohort, the 3-year overall survival (OS) rate was 52.6% and the median survival was 42.5 months. After propensity score matching, the 3-year OS rate for the chemoradiotherapy group was not significantly better than that for the group treated with radiotherapy alone (53.7% vs. 59.9%, p=0.876). Conclusion Concurrent chemotherapy with radiotherapy for esophageal cancer in patients aged 80 years or older did not have significant OS benefit over radiotherapy alone.

Automated treatment planning may decrease the effort required in planning and promote increased routine clinical use of intensity-modulated radiation therapy (IMRT) for many breast cancer patients. The aim of this study was to evaluate a new commercial automated planning software for tangential breast IMRT by comparing it with clinical plans from whole-breast irradiation. We prospectively enrolled 150 patients with Stage 0-1 breast cancer who underwent breast-conserving surgery at our institution between September 2016 and August 2017. Total doses of 42.56 Gy in 16 fractions (n = 98) or 50 Gy in 25 fractions (n = 44) were used. All treatment plans were retrospectively re-planned using the automated breast planning (ABP) software. All automated plans generated clinically deliverable beam parameters with no patient body collision and no contralateral breast pass through. The mean homogeneity index of the automatically generated clinical target volume, percentage volume of lungs receiving dose more than 20 Gy, mean heart dose, and dose to the highest irradiated 2-cc volumes of the irradiated volume were 0.077 ± 0.019, 4.2% ± 1.2%, 142 ± 69 cGy, and 105.8% ± 1.7% (prescribed dose: 100%), respectively. The mean planning time was 4.8 ± 1.4 min. The ABP software demonstrated high clinical acceptability and treatment planning cost efficiency for tangential breast IMRT. The ABP software may be useful for delivering high-quality treatment to a majority of patients with early-stage breast cancer.

In radiation therapy, a secondary independent dose verification is an important component of a quality control system. Mobius3D calculates three‐dimensional (3D) patient dose using reference beam data and a collapsed cone convolution algorithm and analyzes dose‐volume histogram automatically. There are currently no published data on commissioning and determining tolerance levels of Mobius3D for TomoTherapy. To verify the calculation accuracy and adjust the parameters of this system, we compared the measured dose using an ion chamber and film in a phantom with the dose calculated using Mobius3D for nine helical intensity‐modulated radiation therapy plans, each with three nominal field widths. We also compared 126 treatment plans used in our institution to treat prostate, head‐and‐neck, and esophagus tumors based on dose calculations by treatment planning system for given dose indices and 3D gamma passing rates with those produced by Mobius3D. On the basis of these results, we showed that the action and tolerance levels at the average dose for the planning target volume (PTV) at each treatment site are at μ ± 2σ and μ ± 3σ, respectively. After adjusting parameters, the dose difference ratio on average was −0.2 ± 0.6% using ion chamber and gamma passing rate with the criteria of 3% and 3 mm on average was 98.8 ± 1.4% using film. We also established action and tolerance levels for the PTV at the prostate, head‐and‐neck, esophagus, and for the organ at risk at all treatment sites. Mobius3D calculations thus provide an accurate secondary dose verification system that can be commissioned easily and immediately after installation. Before clinical use, the Mobius3D system needs to be commissioned using the treatment plans for patients treated in each institution to determine the calculational accuracy and establish tolerances for each treatment site and dose index.

Introduction The incidence of prostate cancer in Japan continues to increase, necessitating the continued development of effective therapies and strategies. Recent advances in treatments have improved the prognosis of metastatic disease and highlighted the importance of treating bone metastases to reduce the incidence of skeletal complications and improve patients’ quality of life. With the increasing number of treatment options that have become available, including bone-targeted therapy with the alpha emitter radium-223 dichloride (Ra-223), Japanese clinicians are faced with making difficult decisions on the choice of optimal treatment strategy. In such situations, guidance based on expert opinions can be beneficial. Methods A panel meeting of 27 Japanese experts in the management of prostate cancer was held to share opinions and to establish consensus recommendations on key clinical questions. Panelists were asked to vote on more than 40 questions pertinent to prostate cancer, and the answers helped guide a comprehensive discussion. Results The panel reached a consensus on key topics related to the optimal treatment strategy for Ra-223 therapy, namely, that patients with symptomatic, metastatic castration-resistant prostate cancer (CRPC) would benefit most from the use of this agent and that this treatment therapy should be provided before chemotherapy. Other topics that achieved consensus included: monitoring for osteoporosis and providing treatment if necessary during androgen deprivation therapy; performing magnetic resonance imaging in the presence of discrepancies in bone scintigram and computed tomography scans; monitoring alkaline phosphatase during CRPC treatment; using osteoclast-targeting in patients with CRPC with bone metastases; and using osteoclast-targeted agents combined with Ra-223. Conclusion These consensus recommendations and the updated information which became available subsequent to the panel meeting included here provide useful information for clinicians to aid in designing optimal treatment strategies for their patients. Funding Bayer Yakuhin Ltd. Electronic supplementary material The online version of this article (10.1007/s40487-018-0088-0) contains supplementary material, which is available to authorized users.

Background/Aim: The most severe adverse event of radiotherapy in lung cancer is radiation pneumonitis (RP). Some indices commonly used to prevent RP are evaluated based on the anatomical lung volume. The irradiation dose may be more accurately assessed by using functional lung volume. We evaluated the usefulness of computed tomography (CT) incorporating functional ventilation images acquired by the inhalation of xenon (Xe) gas (Xe-CT functional images). Patients and Methods: Two plans were created for twelve patients: volumetric modulated arc therapy (VMAT) planning using conventional chest CT images (anatomical plans) and VMAT planning using Xe-CT functional images (functional plans), and the dosimetric parameters were compared. Results: Compared to the anatomical plans, the functional plans had significantly reduced V20Gy in the high-functional lungs (p=0.005), but significant differences were not seen in the moderate-functional and low-functional lungs. Conclusion: The incorporation of Xe-CT functional images into VMAT plans enables radiotherapy planning with consideration of lung function.

PURPOSE/OBJECTIVE(S) In the largest prospective study to date, we examined the effectiveness of palliative radiation therapy for bleeding gastric cancer, and the association of the biologically effective dose (BED) with survival, bleeding response, or re-bleeding. MATERIALS/METHODS We recruited patients with incurable gastric cancer for whom palliative radiation therapy was planned. Eligibility criteria included blood transfusion or hemoglobin levels < 8.0 g/dL. The primary endpoint was the intention-to-treat (ITT) response rate at four weeks. Response entailed all of the following criteria: 1) hemoglobin levels ≥ 8.0 g/dL, 2) seven consecutive days from enrollment to blood sampling without blood transfusion, and 3) no salvage treatment (surgery, endoscopic treatment, transcatheter embolization, or reirradiation) for bleeding gastric cancer. Re-bleeding was defined as the need for blood transfusion or salvage treatment. Response was assessed at 2, 4, and 8 weeks after enrollment; re-bleeding was assessed monthly during the 6-month follow-up. Sample size was designed with the probability of obtaining a 90% confidence interval (CI) ≤ ± 15% being set at 0.8, assuming a per-protocol (PP) response rate of 70% at 4 weeks. RESULTS We enrolled 55 patients from 15 institutions. A median total radiation dose of 20 Gy (range, 8-45 Gy) was delivered in a median of five fractions. Of the 55 patients, 38 responded to treatment; of the 38 responders, 19 (50%) died and 12 (32%) experienced re-bleeding. The ITT response rates were 47%, 53% (95% CI, 39%-66%), and 49% at 2, 4, and 8 weeks, respectively. The PP response rates were 55%, 78%, and 90% at 2, 4, and 8 weeks, respectively. Restricted mean response and re-bleeding time up to 8 months were 2.3 months and 0.8 months, respectively. The median overall survival was 3.8 months (median follow-up, 12.1 months). The multivariable Cox model showed that neither response (a time-dependent covariate) (hazard ratio [HR], 1.04; 95% CI, 0.44-2.48) nor BED (alpha/beta = 10) (HR, 0.98; 95% CI, 0.95-1.02) were significant predictors of overall survival. The multivariable Fine-Gray model showed that BED was not a significant predictor of response (subdistribution HR, 1.02; 95% CI, 0.99-1.06). The univariable Cox model on transition hazard from response to re-bleeding showed that BED was not significantly associated with re-bleeding (HR, 0.98; 95% CI, 0.92-1.04). Grade 1, 2, 3, and ≥ 4 radiation-related adverse events were reported in 11, 9, 1, and 0 patients, respectively. CONCLUSION The PP bleeding response rate increased to 90% during the 8-week follow-up period. The frequent occurrence of death from shortly after enrollment lowered the ITT response rate and shortened the duration of response. BED was not significantly associated with survival, bleeding response, or re-bleeding.

Preoperative chemoradiotherapy(CRT)followed by total mesorectal excision(TME)is used for locally advanced rectal cancer, but it can induce postoperative anorectal function. The primary objective of this study is to confirm the efficacy and safety of preoperative CRT and TME without irradiation to the internal and external sphincter muscles.Patients were eligible for this study if they met the following inclusion criteria: histologically proven rectal cancer, clinical T3T4N0-2 disease, and a distance between anal margin of tumor and the rental line is more than 2 cm. Twelve patients who underwent preoperative CRT and TME between 2013 and 2017 were enrolled. The primary endpoint was completion rate of sphincter-preserving surgery.All patients completed preoperative CRT without Grade 3 or higher adverse effect. Sphincter-preserving surgery was performed in all cases. The 5-year disease-free survival rate was 46.7%, and the local recurrence-free survival rate was 75%, and the overall survival rate was 90.9%.It is suggested that preoperative CRT and TME without irradiation to the internal and external sphincter muscles is effective and safe therapy for locally advanced rectal cancer.

Using virtual reality (VR) technology such as head-mounted displays, users can be immersed in a virtual world and perceive it as reality. In radiation therapy departments, pretreatment patients and students rarely observe treatment rooms and treatment devices, making it difficult to understand the overall flow of radiation therapy. In this study, to facilitate the understanding and teaching of radiation therapy, we suggest the implementation of VR technology and develop software compatible with VR to enable a pertinent comprehension of radiation therapy. With versatility and accessibility in mind, the software is developed as an application for Android and iOS devices.Omnidirectional movies in treatment rooms were acquired from both the patient view and a third-person view using an omnidirectional camera. The Android/iOS devices used were AQUOS R (SHARP), iPhone 7 Plus (Apple), and iPad air (Apple). The software was developed using Unity 2018.4.7f (Unity Technologies). The main components of the software were as follows: (i) a home window featuring a user interface with which people can access arbitrarily rooms by tapping on floor maps or a list of treatment rooms, (ii) a snapshot mode providing 2D images of a treatment room as a slide show, and (iii) a movie mode displaying omnidirectional movies from the patient view or a third-person view. The virtual radiation therapy experience was executed by attaching the Android/iOS devices to 3D VR goggles (SAMONIC).The main components of the application operated in good conjunction on the Android/iOS devices, and live viewing in the virtual world ran smoothly with the VR technology. However, there were resolution limitations due to the specs of the camera and the devices. It will therefore be necessary to adjust the resolution and the frame rate according to the performance of the relevant devices. The application is instructive for both patients and students because the virtual radiation therapy experience is immersive when using the VR technology. In addition, the developed software can transfer data in a single package and has the ability to substitute images and omnidirectional movies with those appropriate for diagnostic radiology and nuclear medicine departments. Therefore, the developed application is highly versatile.

There are currently no reliable, established serum biomarkers to predict the prognosis of radiotherapy for advanced cervical cancer. We aimed to identify serum biomarkers for survival after radiotherapy for cervical cancer. In this multicenter prospective cohort study, the usefulness of pre- and posttreatment serum protein levels of potential biomarkers, including squamous cell carcinoma antigen (SCC-Ag), apolipoprotein C-II (ApoC-II), matrix metalloproteinase (MMP)1, and MMP2, were evaluated together with clinical factors in 145 cervical cancer patients in order to determine their suitability to predict survival. Progression-free survival (PFS) was the primary endpoint, and overall survival (OS), pelvic PFS (PPFS), and distant metastasis-free survival (DMFS) were the secondary endpoints. Blood samples were collected before and 1 month after radiotherapy to measure serum biomarker levels. ApoC-II was measured using a monoclonal antibody-based enzyme-linked immunosorbent assay, which was developed for this purpose. Kaplan-Meier method, log-rank test, and univariate and multivariate Cox proportional hazards models were used for statistical analyses. In multivariate analysis, larger tumor size was independently associated with shorter PFS, OS, PPFS, and DMFS, while longer overall treatment time was independently associated with shorter PPFS. Higher pretreatment SCC-Ag (P < 0.001) was associated with shorter DMFS. Higher posttreatment SCC-Ag (P = 0.017) was also associated with shorter DMFS. Pretreatment ApoC-II was associated with PPFS in univariate analysis (P = 0.048), but not in multivariate analysis. Patients with pretreatment ApoC-II levels ≤ 25.8 μg/ml had shorter PPFS than those with pretreatment ApoC-II levels > 25.8 μg/ml (P = 0.023, log-rank test). Pre- and posttreatment serum SCC-Ag and pretreatment serum ApoC-II levels may be important biomarkers to predict survival outcomes of patients with cervical cancer after radiotherapy. Pre- and posttreatment SCC-Ag and pretreatment ApoC-II might be useful in clinical settings for screening patients to improve treatment strategies in cervical cancer.

BackgroundBecause of the lack of evidence on practice patterns of postoperative radiation therapy (PORT)in patients with metastases to the long bones, it is essential to characterize the current practice patterns and identify factors affecting dose-fractionation to aid future clinical trials. MethodsThe palliative radiation therapy subgroup of the Japanese Radiation Oncology Study Group conducted an internet-based survey to determine the prescription practices and various dose-fractionations used for PORT. Additionally, responders were asked to recommend dose-fractionations in four hypothetical cancer cases, wherein each case represented a patient with impending pathological fractures and one of the four features: limited prognosis, solitary metastasis, radio-resistant primary tumor, or long-term survival. Responders were asked to indicate their preferred irradiation fields and the reasons for choosing long-course radiotherapy over short-course radiotherapy (RT). ResultsEighty-nine radiation oncologists from 67 institutions and 151 RT plans were included. Twenty-two different dose-fractionations were used; the most commonly used and recommended dose-fractionation was 30 Gy in 10 fractions. “Local control” was most the common reason for preferring longer course RT. While fractionated higher-dose regimens were preferred in case of oligometastasis, low dose regimens were preferred in case of limited prognosis; single fraction RT was never preferred. Most respondents recommended involvement of “the entire orthopedic prosthesis.” ConclusionFor PORT of metastases to the long bones, 30 Gy in 10 fractions for the entire orthopedic prosthesis is preferred in current practice. Oligometastasis and a limited prognosis influence the selection of high- and low-dose regimens, respectively. Single fraction RT is never preferred.

The objective of this study was to clarify the usefuleness of the K parameters of the independent verification method using V100% (the volume of water receiving 100% of the prescription dose) for institutions implementing the high-dose-rate (HDR) intracavitary brachytherapy for gynecological cancer. The data of 249 plans of 11 institutions in Japan were used, and the constant K value obtained by a parameter fit for single-192Ir, two-192Ir, and three-192Ir systems was calculated. The predicted total dwell time calculated using the constant K value was defined as Tpr, and the total dwell time calculated using a radiation treatment planning system was defined as TRTP. The ratio of Tpr and TRTP for each plan was calculated. The constant K values (95% CI) obtained for each system outlined above were 1233 (1227-1240), 1205 (1199-1211), and 1171 (1167-1175), respectively. Regarding the Tpr/TRTP, the entire data were within 0.9-1.1. For accurate verification, it was clarified that constant K values should be calculated for each system. The Nuclear Regulatory Commission considers a difference of 20% between the prescribed total dose and the administered total dose as a reportable medical event. There is a need for a quick method to verify the accuracy with a minimum of 10% threshold of a plan. The constant K values in this study were obtained from multiple institutions, and the variation in the values among these institutions was small. The data obtained by this study may be used as a parameter of this verification method employed by numerous institutions, particularly those who have recently initiated HDR brachytherapy. In addition, for institutions already using this method, this data might be useful for the validation of the parameters which were used in such institutions.

Background/aim To determine the most reliable predictor for pathologic complete response (pCR) in patients who underwent preoperative chemoradiotherapy and regional hyperthermia (HCRT) for rectal cancer. Patients and methods Thirty-six patients were enrolled. The local control status of the patients was assessed using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), magnetic resonance imaging (MRI), and colonoscopy before and after HCRT. The relationships between various parameters of these clinical examinations and pCR were analyzed. Results Ten (28%) patients achieved pCR. The accuracies of predicting pCR using FDG-PET/CT, MRI, and colonoscopy were 78%, 61%, and 75%, respectively. FDG-PET/CT was the only independent predictive modality for pCR (p=0.021). The maximum standardized uptake value (SUVmax) and SUVmax normalized to liver uptake (SLR) after HCRT showed the highest sensitivity (90%) and the decreasing rate of SUVmax and SLR demonstrated the highest specificity (89%) for pCR. Conclusion SUVmax-based parameters of FDG-PET/CT after HCRT were the most reliable predictors for pCR.

PURPOSE Based on a retrospective analysis, this study aims to develop a simple index for validity of the evaluation point for the dosimetric verification of intensity-modulated radiation therapy (IMRT). METHODS The results for the dosimetric verifications of a total of 69 IMRT plans were analyzed in this study. A Farmer-type ion chamber was used as a dose detector, and a solid water-equivalent phantom was used. Index values were obtained by dividing the difference between the maximum and minimum dosages by the mean dosage of the 69 plans, and the values were classified into five groups with index value 16. A t-test was used to assess the statistical significance of the mean differences of the absolute values of the relative errors among these groups. RESULTS We found that there was no significant difference between the groups with index value

Objective: We evaluated the effects of palliative radiotherapy for cancer recurrence or metastasis on patient QOL and psychophysiology. Materials and Methods: Sixty seven patients who received palliative radiotherapy between 2014 and 2015 were enrolled. Patient diseases were bone metastasis in 51 patients, lymph node metastasis in 7 patients, brain metastasis in 2 patients, local recurrence in 3 patients, and others in 4 patients. Median irradiated dose was 30 Gy in 10 fractions for palliative radiotherapy. We used the questionnaires EORTC-QLQ-C30 and EORTC-QLQ-C15-PAL to evaluate patient QOL and the Hospital Anxiety and Depression Scale to evaluate patient mental healthcare at the start and at the end of radiotherapy. Results: As compared to scores at the start of radiotherapy, at the end of radiotherapy, NRS and face scale significantly decreased. On the other hand, Eastern Cooperative Oncology Group Performance Status did not show any changes during palliative radiotherapy. In functional scales, average scores of RF2 and EF also improved. In symptom scales, average scores of FA, PA, and SL improved. In bone metastasis group, global health status/QOL, PA, and SL significantly improved. There was relationship between anxiety improvement and QOL improvement after palliative radiotherapy. Nausea and vomiting scores of EORTC-QLQ-C15-PAL were associated with the irradiated volume of palliative radiotherapy for pelvic region. Conclusion: Patient QOL of was improved by palliative radiotherapy regardless of PS. The possibility of palliative radiotherapy having a positive influence on patient psychophysiology was also suggested in younger age.

To evaluate the efficacy and safety of carbon-ion radiotherapy for non-squamous cell carcinoma of the head and neck, 35 patients were enrolled in this prospective study. The primary end-point was the 3-year local control rate, and the secondary end-points included the 3-year overall survival rate and adverse events. Acute and late adverse events were evaluated according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up time for all patients was 39 months. Thirty-two and three patients received 64.0 Gy (relative biological effectiveness) and 57.6 Gy (relative biological effectiveness) in 16 fractions, respectively. Adenoid cystic carcinoma was dominant (60%). Four patients had local recurrence and five patients died. The 3-year local control and overall survival rates were 93% and 88%, respectively. Acute grade 2-3 radiation mucositis (65%) and dermatitis (31%) was common, which improved immediately with conservative therapy. Late mucositis of grade 2, grade 3, and grade 4 were observed in 11, one, and no patients, respectively. There were no adverse events of grade 5. Carbon-ion radiotherapy achieved excellent local control and overall survival rates for non-squamous cell carcinoma. However, the late mucosal adverse events were not rare, and meticulous treatment planning is required. Trial registration no. UMIN000007886.

The present study aimed to evaluate a previously reported predictive formula of output-limiting symptoms induced by radiofrequency (RF) to determine the efficacy of this neoadjuvant chemoradiation (NACR) and concurrent RF thermal therapy. The present study included 81 consecutive patients with confirmed diagnoses of rectal adenocarcinoma that was localized in the mid-low rectum (up to 12 cm from the anal verge) who received NACR [intensity-modulated radiotherapy (IMRT), 50 Gy/25 fractions, capecitabine 1,700 mg/m2/day for 5 days/week)] with concurrent thermal therapy (Thermotron-RF8, once a week for 5 weeks with 50 min irradiation). Patients with progressive disease (PD) did not receive RF outputs higher than the predicted value. Some patients who were predicted to receive more output in fact received more than the predicted output. In patients who were predicted to receive moderately higher outputs, 37.5% of the patients experienced pathological complete responses, which was the highest rate, while in those who did not receive more than the predicted output, 66.7% of the patients experienced PD, which was the highest rate in the present study. We speculate that RF thermal therapy may offset the chemoradiation effects in some patients. Adding thermal therapy as a multimodality therapy to NACR potentially affects patients with lower predicted outputs and actual observed outputs slightly higher than the predictive value. Our predictive equation for initial energy output, in which output‑limiting symptoms can be used to predict treatment efficacy, consequently, can be used to decide whether to continue this treatment modality.

Intensity-modulated radiation therapy (IMRT) has become the mainstay of treatment for localized prostate cancer. In IMRT, minimizing differences between the conditions used during planning CT and daily treatment is important to prevent adverse events in normal tissues. In the present study, we evaluated the impact of variation in bladder volume on the doses to various organs. A total of 35 patients underwent definitive radiotherapy at Saitama Medical Center. A Light Speed RT16 (GE Healthcare) was used for planning and to obtain examination CT images. Such images were acquired after 4 - 6 days of planning CT image acquisition. The IMRT plans were optimized using the planning CT data to satisfy the dose constraints set by our in-house protocols for the PTV and the OARs. The dose distributions were then re-calculated using the same IMRT beams, and checked on examination CT images. It was clear that bladder volume affected the doses to certain organs. We focused on the prostate, bladder, rectum, small bowel, and large bowel. Regression coefficients were calculated for variables that correlated strongly with bladder volume (p < 0.05). We found that variation in bladder volume [cm3] predicted deviations in the bladder V70Gy, V50Gy, and V30Gy [%]; the maximum dose to the small bowel [cGy]; and the maximum dose to the large bowel [cGy]. The regression coefficients were -0.065, -0.125, -0.180, -10.22, and -9.831, respectively. We evaluated the impacts of such variation on organ doses. These may be helpful when checking a patient’s bladder volume before daily IMRT for localized prostate cancer.

During radiofrequency (RF) hyperthermia treatment, hot-spot phenomena may occur and prevent treatment continuation if the output is not lowered. We previously reported a significant correlation between the initial energy output at which output-limiting symptoms occurred and patient status. Patients with a complete clinical response had significantly increased temperature, while some patients with partial clinical response and stable disease had increased temperature, depending on the occurrence of output-limiting symptoms. To predict the initial energy output at which output-limiting symptoms occur, we performed multiple regression analysis with the parameters of patients' physical status.Hyperthermia alone or concomitant with chemotherapy and/or radiotherapy was applied in 62 patients with malignant disease for a total of 310 treatments with a Thermotron RF-8 between December 2011 and April 2014.No output-limiting symptoms were shown in 65.5% of 310 treatments. Pain (29.7%), micturition desire (1.9%), skin discomfort (0.6%), subcutaneous induration (1.6%), cold sensation (0.6%), and nausea (0.3%) were reported in the 310 treatments. A good predictive equation for initial energy output at which output-limiting symptoms occur was determined with two parameters, initial time of an output-limiting symptom onset, and thickness of the fat of the abdominal wall. Multiple regression analysis showed an adjusted R(2 )= 0.99 and variance inflation factor 2.We present a good predictive equation for initial energy output at which output-limiting symptoms occur. It is critical to prevent RF hyperthermia-induced output-limiting symptoms and establish new prevention strategies.

Non-secosteroidal VDR ligands without any assymmetric carbon were designed and synthesized based on the structure of the previously reported non-secosteroidal VDR agonist LG190178. The VDR-agonistic activity of all synthesized compounds was evaluated, and 7b emerged as a potent agonist activity with an EC50 value of 9.26 nM. Moreover, a docking simulation analysis was also performed to determine the binding mode of 7b with VDR-LBD.

To determine the most reliable predictor for pathologic complete response (pCR) in patients who underwent preoperative chemoradiotherapy and regional hyperthermia (HCRT) for rectal cancer.Thirty-six patients were enrolled. The local control status of the patients was assessed usingTen (28%) patients achieved pCR. The accuracies of predicting pCR using FDG-PET/CT, MRI, and colonoscopy were 78%, 61%, and 75%, respectively. FDG-PET/CT was the only independent predictive modality for pCR (p=0.021). The maximum standardized uptake value (SUVSUV

The present study aimed to evaluate whether the neoadjuvant chemoradiation response with concurrent thermal therapy for the treatment of rectal cancer can be predicted following the first thermic treatment. Eighty patients with primary rectal adenocarcinoma (≤12 cm from the anal verge) were included in this study. Fifty-four received surgery and pathological response was evaluated. Intensity-modulated radiotherapy was administered conventionally once daily 5 times/week. Neoadjuvant radiotherapy consisted of 50 Gy delivered to the planning target volume in 25 fractions. Concurrent neoadjuvant chemotherapy was delivered in 5-day courses. Capecitabine was administered orally at 1,700 mg/m2/day for 5 days/week. Thermic treatment was performed using the Thermotron-RF 8 and administered once/week for 5 weeks with 50 min irradiation. Patients with a gross tumor volume (GTV) ≤32 cm3 and a radiofrequency (RF) output difference (RO difference) ≥77 Watt/min exhibited pathological complete response (pCR) and CR rates of 50 and 75%, respectively. Those with a GTV ≥80 cm3 and a RO difference ≥77 Watt/min exhibited pCR and CR rates of 42.9 and 42.9%, respectively. The changes in the skin temperature during RF treatment in patients with pCR with a RO difference ≥77 Watt/min increased significantly compared with those of other outcomes, and progressive disease. These data suggest a strategy for predicting which patients will respond best following the first thermic treatment. The results identified that the group of patients with a GTV ≤32 cm3 and a RO difference ≥77 Watt/min (outputable/heatable patients) may respond best.

Purpose To clarify the efficacy of palliative radiotherapy for the relief of symptoms due to skin invasion in patients with breast cancer. Materials and methods We conducted a multi-institutional prospective observational study of patients who received palliative radiotherapy for skin invasion due to a primary lesion or chest wall recurrence. Bleeding/discharge, offensive odor, pain and QOL scores were evaluated before and 1, 3 and 6 months after radiotherapy. Results Twenty-one patients were assessed. Sixteen patients (76%) received 36 Gy in 12 fractions. The mean (±1 SD) score of bleeding/discharge was 1.90 ± 0.89 before radiotherapy, 1.50 ± 0.74 at 1 month, 0.47 ± 0.58 at 3 months, and 0.82 ± 1.04 at 6 months (P = 0.001). The mean score of offensive odor was 1.21 ± 1.38 before radiotherapy, 0.71 ± 0.92 at 1 month, 0.20 ± 0.41 at 3 months, and 0.27 ± 0.62 at 6 months (P = 0.008). The mean score of pain was 2.90 ± 1.22 before radiotherapy, 3.05 ± 1.36 at 1 month, 3.29 ± 1.10 at 3 months, and 3.31 ± 1.54 at 6 months (P = 0.431). The mean total score of QOL-ACD/QOL-ACD-B was 126.2 ± 24.5 before radiotherapy, 130.3 ± 26.3 at 1 month, 136.2 ± 26.6 at 3 months, and 126.6 ± 32.8 at 6 months (P = 0.178). Conclusion Palliative radiotherapy for skin invasion in patients with breast cancer might be effective, especially for the relief of bleeding/discharge and offensive odor.

The molecular interactions and translocation of signal transduction factors in individual cells can be imaged by fluorescence microscopy. Alternatively, downstream promoter activity in single cells can be imaged by bioluminescence microscopy. However, the same stimuli can lead to different gene expression responses in individual cells. For this reason, it is desirable to simultaneously image signal transduction and gene expression events in the same cells. Here, we describe a method that combines fluorescence and bioluminescence microscopy to image protein kinase C (PKC) translocation from the cytosol to the plasma membrane and the expression of nuclear factor kappa-light polypeptide B (NF-κB)-regulated genes. © 2017 by John Wiley & Sons, Inc.

Background and purpose The aim of the study was to evaluate the therapeutic gain of carbon ion (C-ion) radiotherapy using a mouse model. Materials and methods Transplanted fibrosarcoma (NFSa) growing in C3H/He mice and murine small intestine were irradiated with 290MeV/nucleon C-ion beams (C-ions) in 1–12 fractions separated by 4h. The cell killing efficiencies of C-ions were measured using jejunum crypt survival and tumor growth delay (TGD) assays. Results The equieffect dose for crypt survival and TGD increased with increasing number of fractions after X-rays and 20keV/μm C-ions, whereas TGD after 77keV/μm C-ions rather decreased. Crypts showed stronger LET-dependent increase in α terms than the tumor while β terms less depended on LET irrespective of tissues. Therapeutic gain factor, i.e., a ratio of tumor RBE over crypt RBE, of 77keV/μm C-ions was more than unity at any doses while that of 20keV/μm C-ions increased with an increase in dose per fraction. Conclusions These specific data imply that use of large dose per fraction would be suitable for C-ion radiotherapy irrespective of LET from the point of view of therapeutic gain, though small dose per fraction by high-LET radiation decreases total dose for tumor.

Bioluminescence microscopy has revealed that gene expression in individual cells can respond differently to the same stimulus. To understand this phenomenon, it is important to sequentially observe the series of events from cellular signal transduction to gene expression regulated by specific transcription factors derived from signaling cascades in individual cells. However, these processes have been separately analyzed with fluorescence and bioluminescence microscopy. Furthermore, in culture medium, the background fluorescence of luciferin—a substrate of luciferase in promoter assays of gene expression in cultured cells—confounds the simultaneous observation of fluorescence and bioluminescence. Therefore, we optimized conditions for optical filter sets based on spectral properties and the luciferin concentration based on cell permeability for fluorescence observation combined with bioluminescence microscopy. An excitation and emission filter set (492–506 nm and 524–578 nm) was suitable for green fluorescent protein and yellow fluorescent protein imaging of cells, and >100 μM luciferin was acceptable in culture medium based on kinetic constants and the estimated intracellular concentration. Using these parameters, we present an example of sequential fluorescence and bioluminescence microscopic observation of signal transduction (translocation of protein kinase C alpha from the cytoplasm to the plasma membrane) coupled with activation of gene expression by nuclear factor of kappa light polypeptide B in individual cells and show that the gene expression response is not completely concordant with upstream signaling following stimulation with phorbol‐12‐myristate‐13‐acetate. Our technique is a powerful imaging tool for analysis of heterogeneous gene expression together with upstream signaling in live single cells. Microsc. Res. Tech. 78:715–722, 2015. © 2015 Wiley Periodicals, Inc.

The present study investigated the ability of carboplatin and paclitaxel to sensitize human non-small-cell lung cancer (NSCLC) cells to carbon-ion beam irradiation. NSCLC H460 cells treated with carboplatin or paclitaxel were irradiated with X-rays or carbon-ion beams, and radiosensitivity was evaluated by clonogenic survival assay. Cell proliferation was determined by counting the number of viable cells using Trypan blue. Apoptosis and senescence were evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and senescence-associated β-galactosidase (SA-β-gal) staining, respectively. The expression of cleaved caspase-3, Bax, p53 and p21 was analyzed by western blotting. Clonogenic survival assays demonstrated a synergistic radiosensitizing effect of carboplatin and paclitaxel with carbon-ion beams; the sensitizer enhancement ratios (SERs) at the dose giving a 10% survival fraction (D10) were 1.21 and 1.22, respectively. Similarly, carboplatin and paclitaxel showed a radiosensitizing effect with X-rays; the SERs were 1.41 and 1.29, respectively. Cell proliferation assays validated the radiosensitizing effect of carboplatin and paclitaxel with both carbon-ion beam and X-ray irradiation. Carboplatin and paclitaxel treatment combined with carbon-ion beams increased TUNEL-positive cells and the expression of cleaved caspase-3 and Bax, indicating the enhancement of apoptosis. The combined treatment also increased SA-β-gal-positive cells and the expression of p53 and p21, indicating the enhancement of senescence. In summary, carboplatin and paclitaxel radiosensitized H460 cells to carbon-ion beam irradiation by enhancing irradiation-induced apoptosis and senescence.