清水 秀年

PURPOSE: A novel classification system has been proposed to stratify patients undergoing palliative radiation therapy based on their pain response and time to progression. This study used prospective observational data to quantify quality of life (QoL) changes associated with pain response and the classification system. METHODS AND MATERIALS: Between August 2021 and September 2022, 366 painful lesions with a numerical rating scale of 2 or more from the 261 eligible patients underwent palliative radiation therapy. Patients were followed-up prospectively at 2, 4, 12, 24, 36, and 52 weeks postradiation therapy, with EORTC QLQ-C15-PAL and QLQ-BM22 questionnaires obtained simultaneously with pain response assessments. The primary endpoint was defined as the global health status/QoL improvements at 12 weeks based on minimally clinically important differences and compared by the pain response (responders vs. nonresponders) and by class 1 (no opioids, no reirradiation, n = 89), 2 (neither class 1 nor 3, n = 211), and 3 (opioids and reirradiation, n = 66). RESULTS: With a median follow-up time of 21 weeks for pain response and 13 weeks for QoL assessment, 1773 pairs of QLQ-C15-PAL and QLQ-BM22 questionnaires were collected. The QoL assessment at baseline was covered with 97% (355/366) of lesions and 67% (183/273) at 12 weeks: this compliance was lower in nonresponders than in responders (57% vs. 72%, P = .004) and highest in class 1, followed by classes 2 and 3 (70% vs. 44% vs. 39%, P = .001). The improvement rate was significantly different by class, with class 3 having the lowest in all subscales except nausea and psychosocial aspects: the improvement rate of global health status/QoL was 33% in class 1, 31% in class 2, and 20% in class 3, P = .001). CONCLUSIONS: The QoL changes associated with pain response and the classification system were identified, suggesting that the classification system may help identify populations more or less likely to improve QoL, in addition to separating pain response rates.

PURPOSE: Total body irradiation before bone marrow transplantation for hematological malignancies using Radixact, a high-precision radiotherapy machine, can potentially reduce side effects and the risk of secondary malignancies. However, stable control of couch speed is critical, and direct assessment methods outlined in quality assurance guidelines are lacking. This study aims to develop a real-time couch speed verification system for the Radixact. METHODS: The developed system used a linear encoder to measure couch speed directly. Accuracy was verified via a linear stage, comparing measurements with a laser distance sensor. After placing a phantom simulating the human body on the Radixact couch, the couch speed was verified using predefined speed plans. RESULTS: Operating the linear stage at 0.1, 0.5, and 1.0 mm/s revealed that the maximum position error of the developed verification system compared to the laser distance sensor was nearly equivalent to the distance resolution of the system (0.05 mm/pulse), with negligible average speed error. When the Radixact couch operated at 0.1, 0.5, and 1.0 mm/s, the values obtained by the verification system agreed with the theoretical values within the sampling period (0.01 s) and distance resolution (0.05 mm). CONCLUSION: The verification system developed provides real-time monitoring of the speed of the Radixact table, ensuring treatment effectiveness and patient safety. It would guarantee the couch speed's soundness and contribute to the "visualization" of safety.

BACKGROUND AND PURPOSE: Hypothyroidism is a recognized late adverse event following radiotherapy for head and neck cancer (HNC). In the JCOG1008 trial, we treated patients with high-risk HNC with postoperative chemoradiotherapy. We aimed to elucidate factors associated with hypothyroidism by analyzing the JCOG1008 data. MATERIALS AND METHODS: In 2012-2018, 261 patients from 28 institutions were enrolled in JCOG1008. Thyroid function tests were conducted to assess hypothyroidism, including free thyroxine (FT4) and thyroid-stimulating hormone assays. Hypothyroidism was defined as Grade 2 or higher in CTCAE v4.0. Various clinical and dosimetric parameters were analyzed. In radiotherapy, there were no dose constraints for the thyroid. Multivariable analysis was conducted on these variables to identify predictive factors for hypothyroidism. RESULTS: The analysis included 162 patients (57 with 3D-CRT and 105 with IMRT), with a median follow-up of 4.7 years (0.3-9.3 years). Among these, 27 (16.7 %) developed hypothyroidism within 2 years after radiotherapy. In a multivariable analysis, the weekly cisplatin [OR=7.700 (CI: 1.632-36.343, p = 0.010)] and baseline FT4 [OR=0.009 (CI: <0.001-0.313, p = 0.010)] were significantly associated with hypothyroidism in the IMRT group. Regarding dosimetric characteristics, V60Gy [OR=1.069 (CI: 0.999-1.143, p = 0.054)] was potentially associated with the development of hypothyroidism. CONCLUSION: The study revealed that the incidence of hypothyroidism within 2 years after postoperative chemoradiotherapy for high-risk HNC was 16.7 % based on analytical results from prospective clinical trials.

Background/Objectives: Despite advancements in treatment for patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC), overall survival (OS) remains poor. The specific effects of varying heart and lung doses on OS in LA-NSCLC patients have not been thoroughly investigated, especially their combined impact on survival. This study aimed to examine the impact on OS of both individual and combined heart and lung doses in patients with LA-NSCLC treated with radiotherapy over a three-year follow-up period. Methods: A total of 120 patients who received definitive radiotherapy for LA-NSCLC (stage III, 92.5%) from January 2015 to January 2020 were retrospectively reviewed. The endpoint in this study was OS. Each patient was followed for a fixed period of three years. Results: Univariate Cox regression analysis showed that OS was significantly related to mean heart dose (MHD, hazard ratio [HR], 3.4 [1.8-6.3]; p < 0.001), pericardium V40 (HR, 3.2 [1.7-6.0]; p < 0.001), and total lung V20 (HR, 2.6 [1.4-5.0]; p = 0.003), and these were independent predictors for worse OS in multivariate analysis. Kaplan-Meier curve analysis with log-rank tests revealed that survival was significantly worse in patients with higher MHD (p < 0.001), pericardium V40 (p < 0.001), and total lung V20 (p = 0.002). Combining MHD and total lung V20, and pericardium V40 and total lung V20 provided enhanced risk stratification for OS (p < 0.001 for both combinations). Conclusions: The combination of heart and lung doses provided enhanced and more detailed risk stratification in prediction of OS for a fixed period of three years in LA-NSCLC patients treated with radiotherapy.

PURPOSE: This study aimed to analyze the domestic and international landscape of imaging diagnostics and treatments, focusing on Japan, to provide current insights for policymaking, clinical practice enhancement, and international collaboration. METHODS: Data from 1996 to 2021 were collected from Japan's Ministry of Health, Labor and Welfare database for medical device counts of CT, MRI, PET, mammography, and radiotherapy. The National Database of Health Insurance Claims and Specific Health Checkups of Japan was utilized for examination numbers. An international comparison was made with data from 41 countries using the Organization for Economic Cooperation and Development (OECD) database. RESULTS: The data included a total of 108,596 CT devices, 47,233 MRI devices, 2998 PET devices, 20,641 MMG devices, and 8023 RT devices during the survey period. Upon international comparison, Japan ranked first in CT and MRI devices per million people and second in examination numbers per 1000 people. The number of PET devices per million people exceeded OECD averages; however, the number of examinations per 1000 people was below the OECD average in 2020 (Japan: 4.0, OECD: 4.9). Although Japan exceeded OECD averages in mammography device counts (Japan: 33.8, OECD: 24.5 in 2020), radiotherapy device counts were similar to OECD averages (Japan: 8.3, OECD: 7.9 in 2020). CONCLUSION: We have analyzed the utilization of equipment in the context of diagnostic imaging and radiotherapy in Japan. Since the initial survey year, all devices have shown an upward trend. However, it is essential not only to increase the number of devices and examinations but also to address the chronic shortage of radiologists and allied health professionals. Based on the insights gained from this study, understanding the actual status of diagnostic imaging and radiation therapy equipment is critical for grasping the domestic situation and may contribute to improving the quality of healthcare in Japan.

PURPOSE: This study aimed to identify factors affecting pain response to develop a patient classification system for palliative radiation therapy (RT). METHODS AND MATERIALS: Our prospective observational study (UMIN000044984) provided data on patients who received palliative RT for painful tumors. The eligibility criteria were having a numerical rating scale (NRS) score of 2 or more before treatment and receiving palliative RT between August 2021 and September 2022. Post-RT follow-up was scheduled prospectively at 2, 4, 12, 24, 36, and 52 weeks. Pain response was assessed using the International Consensus Pain Response Endpoints criteria, with the primary outcome being the response rate within 12 weeks. Multivariable logistic regression was performed to identify factors affecting pain response and develop the classification system. Each class evaluated the differences in response rate, time to response, and progression. RESULTS: Of the 488 registered lesions, 366 from 261 patients met the criteria. Most patients had bone metastases (75%), of whom 72% were using opioids and 22% underwent reirradiation. Conventional RT (eg, 8-Gy single fraction, 20 Gy in 5 fractions) was administered to 93% of patients. Over a median of 6.8 months of follow-up, the average NRS decreased from 6.1 to 3.4 at 12 weeks for 273 evaluable lesions, with a 60% response rate. Opioid use and reirradiation negatively affected the response rate in multivariate analysis (P < .01). Lesions were categorized into class 1 (no opioid use and no reirradiation; 89 lesions), class 2 (neither class 1 nor 3; 211 lesions), and class 3 (opioid use and reirradiation; 66 lesions), with respective response rates of 75%, 61%, and 36% (P < .001). Time to response was similar across the classes (P = .91), but the progression rates at 24 weeks differed (11%, 27%, and 63%, respectively; P < .001). CONCLUSIONS: Opioid use and reirradiation are factors leading to significant variations in pain response rates and time to progression.

PURPOSE: This study aimed to identify factors associated with local recurrence after spinal stereotactic body radiation therapy (SBRT), focusing on patient movement during treatment and tumor characteristics. METHODS: A total of 48 patients who underwent spinal SBRT alone without surgery from August 2017 to October 2022 were evaluated. Logistic regression analysis was conducted to identify factors associated with local recurrence, including patient movement and tumor characteristics such as soft tissue involvement and tumor volume. Patient movement during treatment was measured using cone beam computed tomography before and after irradiation. RESULTS: Among the included cases, 68.7% and 42.6% had soft tissue involvement and movement exceeding 1 mm, respectively. The median follow-up duration for local recurrence was 11.6 (range: 0.7-44.9) months, whereas the median duration to local recurrence was 6.3 months. Within 12 months, 29.3% of the patients experienced local recurrence, among whom 43.9% moved ≥ 1 mm during treatment, whereas 15.8% did not move. Univariable analysis found that both soft tissue involvement (OR = 10.3, 1.21-87.9; p = 0.033) and patient movement ≥ 1 mm (OR = 5.75, 1.45-22.8; p = 0.013) were associated with local recurrence. Multivariable analysis identified patient movement as an independent prognostic factor for local recurrence (OR = 5.15, 1.06-25.0; p = 0.042). CONCLUSION: Our results suggest that patient movement during spinal SBRT was associated with local recurrence, emphasizing the need for better immobilization techniques and shorter delivery times to improve tumor control.

This study aimed to explore the distribution of external radiation therapy (RT) facilities, the status of related device installations and the adoption of high-precision RT using Survey of Medical Institutions from the Ministry of Health, Labour and Welfare in Japan. Analysis, categorized by the hospital size and prefecture, provides specific insights into the trends in treatment facility healthcare capabilities. Data on the number of RT facilities, high-precision RT facilities, RT devices and treatment planning systems (TPS) categorized by the number of beds and prefecture from 1996 to 2020 were analyzed. In addition, the study examined the correlation between the high-precision implementation rate and the number of TPSs or radiation oncologists and other medical staff. High-precision RT exceeded 95% in large facilities (800+ beds) but remained <50% in medium-sized facilities (300-499 beds). In a prefecture-by-prefecture analysis, calculation of the maximum-minimum ratio of RT facilities per million population and per 30 km2 revealed a disparity of 3.7 and 73.1 times in the population ratio and the density ratio, respectively. Although a correlation was found between the number of TPSs per RT device or the number of medical physicists per million population and the rate of high-precision RT implementation, no correlation was found among other professions. Detailed analysis based on the hospital size and prefecture provided more specific information on the medical functions of RT facilities in Japan. These findings can potentially contribute to the future development of RT, including the standardization of treatment techniques and optimal resource allocation.

AIM: We aimed to investigate the impact of concurrent antibody-drug conjugates (ADC) and radiotherapy on symptomatic radiation necrosis (SRN) in breast cancer patients with brain metastases (BM). METHODS: This multicenter retrospective study uses four institutional data. Eligibility criteria were histologically proven breast cancer, diagnosed BM with gadolinium-enhanced MRI, a Karnofsky performance status of 60 or higher, and radiotherapy for all BM lesions between 2017 and 2022. Patients with leptomeningeal dissemination were excluded. Concurrent ADC was defined as using ADC within four weeks before or after radiotherapy. The cumulative incidence of SRN until December 2023 with death as a competing event was compared between the groups with and without concurrent ADC. Multivariable analysis was performed using the Fine-Gray model. RESULTS: Among the 168 patients enrolled, 48 (29%) received ADC, and 19 (11%) had concurrent ADC. Of all, 36% were HER2-positive, 62% had symptomatic BM, and 33% had previous BM radiation histories. In a median follow-up of 31 months, 18 SRNs (11%) were registered (11 in grade 2 and 7 in grade 3). The groups with and without concurrent ADC had 5 SRNs in 19 patients and 13 SRNs in 149, and the two-year cumulative incidence of SRN was 27% vs. 7% (P = 0.014). Concurrent ADC was associated with a higher risk of SRN on multivariable analysis (subdistribution hazard ratio, 3.0 [95% confidence interval: 1.1-8.3], P = 0.030). CONCLUSIONS: This study suggests that concurrent ADC and radiotherapy are associated with a higher risk of SRN in HER2-positive breast cancer patients.

Purpose: This study aimed to develop a deep learning model for the prediction of V₂₀ (the volume of the lung parenchyma that received ≥20 Gy) during intensity-modulated radiation therapy using chest X-ray images. Methods: The study utilized 91 chest X-ray images of patients with lung cancer acquired routinely during the admission workup. The prescription dose for the planning target volume was 60 Gy in 30 fractions. A convolutional neural network-based regression model was developed to predict V₂₀. To evaluate model performance, the coefficient of determination (R²), root mean square error (RMSE), and mean absolute error (MAE) were calculated with conducting a four-fold cross-validation method. The patient characteristics of the eligible data were treatment period (2018–2022) and V₂₀ (19.3%; 4.9%–30.7%). Results: The predictive results of the developed model for V₂₀ were 0.16, 5.4%, and 4.5% for the R², RMSE, and MAE, respectively. The median error was −1.8% (range, −13.0% to 9.2%). The Pearson correlation coefficient between the calculated and predicted V₂₀ values was 0.40. As a binary classifier with V₂₀ &lt;20%, the model showed a sensitivity of 75.0%, specificity of 82.6%, diagnostic accuracy of 80.6%, and area under the receiver operator characteristic curve of 0.79. Conclusions: The proposed deep learning chest X-ray model can predict V₂₀ and play an important role in the early determination of patient treatment strategies.

BACKGROUND: Inadequate computed tomography (CT) number calibration curves affect dose calculation accuracy. Although CT number calibration curves registered in treatment planning systems (TPSs) should be consistent with human tissues, it is unclear whether adequate CT number calibration is performed because CT number calibration curves have not been assessed for various types of CT number calibration phantoms and TPSs. PURPOSE: The purpose of this study was to investigate CT number calibration curves for mass density (ρ) and relative electron density (ρe ). METHODS: A CT number calibration audit phantom was sent to 24 Japanese photon therapy institutes from the evaluating institute and scanned using their individual clinical CT scan protocols. The CT images of the audit phantom and institute-specific CT number calibration curves were submitted to the evaluating institute for analyzing the calibration curves registered in the TPSs at the participating institutes. The institute-specific CT number calibration curves were created using commercial phantom (Gammex, Gammex Inc., Middleton, WI, USA) or CIRS phantom (Computerized Imaging Reference Systems, Inc., Norfolk, VA, USA)). At the evaluating institute, theoretical CT number calibration curves were created using a stoichiometric CT number calibration method based on the CT image, and the institute-specific CT number calibration curves were compared with the theoretical calibration curve. Differences in ρ and ρe over the multiple points on the curve (Δρm and Δρe,m , respectively) were calculated for each CT number, categorized for each phantom vendor and TPS, and evaluated for three tissue types: lung, soft tissues, and bones. In particular, the CT-ρ calibration curves for Tomotherapy TPSs (ACCURAY, Sunnyvale, CA, USA) were categorized separately from the Gammex CT-ρ calibration curves because the available tissue-equivalent materials (TEMs) were limited by the manufacturer recommendations. In addition, the differences in ρ and ρe for the specific TEMs (ΔρTEM and Δρe,TEM , respectively) were calculated by subtracting the ρ or ρe of the TEMs from the theoretical CT-ρ or CT-ρe calibration curve. RESULTS: The mean ± standard deviation (SD) of Δρm and Δρe,m for the Gammex phantom were -1.1 ± 1.2 g/cm3 and -0.2 ± 1.1, -0.3 ± 0.9 g/cm3 and 0.8 ± 1.3, and -0.9 ± 1.3 g/cm3 and 1.0 ± 1.5 for lung, soft tissues, and bones, respectively. The mean ± SD of Δρm and Δρe,m for the CIRS phantom were 0.3 ± 0.8 g/cm3 and 0.9 ± 0.9, 0.6 ± 0.6 g/cm3 and 1.4 ± 0.8, and 0.2 ± 0.5 g/cm3 and 1.6 ± 0.5 for lung, soft tissues, and bones, respectively. The mean ± SD of Δρm for Tomotherapy TPSs was 2.1 ± 1.4 g/cm3 for soft tissues, which is larger than those for other TPSs. The mean ± SD of Δρe,TEM for the Gammex brain phantom (BRN-SR2) was -1.8 ± 0.4, implying that the tissue equivalency of the BRN-SR2 plug was slightly inferior to that of other plugs. CONCLUSIONS: Latent deviations between human tissues and TEMs were found by comparing the CT number calibration curves of the various institutes.

PURPOSE:  We aimed to evaluate the efficacy and safety of re-irradiation stereotactic body radiation therapy (SBRT) in patients with metastatic epidural spinal cord compression (MESCC) following high-dose conventional radiotherapy. MATERIALS AND METHODS:  Twenty-one patients met the following eligibility criteria: with an irradiation history of 50 Gy2 equivalent dose in 2-Gy fractions (EQD2) or more, diagnosed MESCC in the cervical or thoracic spines, and treated with re-irradiation SBRT of 24 Gy in 2 fractions between April 2018 and March 2023. Prior treatment was radiotherapy alone, not including surgery. The primary endpoint was a 1-year local failure rate. Overall survival (OS) and treatment-related adverse events were assessed as the secondary endpoints. Since our cohort includes one treatment-related death (TRD) of esophageal perforation, the cumulative esophageal dose was evaluated to find the dose constraints related to severe toxicities. RESULTS:  The median age was 68, and 14 males were included. The primary tumor sites (esophagus/lung/head and neck/others) were 6/6/7/2, and the median initial radiotherapy dose was 60 Gy2 EQD2 (range: 50-105 Gy2, 60-70/ > 70 Gy2 were 11/4). Ten patients underwent surgery followed by SBRT and 11 SBRT alone. At the median follow-up time of 10.4 months, 17 patients died of systemic disease progression including one TRD. No radiation-induced myelopathy or nerve root injuries occurred. Local failure occurred in six patients, with a 1-year local failure rate of 29.3% and a 1-year OS of 55.0%. Other toxicities included five cases of vertebral compression fractures (23.8%) and one radiation pneumonitis. The cumulative esophageal dose was recommended as follows: Dmax < 203, D0.035 cc < 187, and D1cc < 167 (Gy3 in biological effective dose). CONCLUSION:  Re-irradiation spine SBRT may be effective for selected patients with cervical or thoracic MESCC, even with high-dose irradiation histories. The cumulative dose assessment across the original and re-irradiated esophagus was recommended to decrease the risk of severe esophageal toxicities.

Abstract Purpose This retrospective study aimed to assess the efficacy and safety of palliative radiotherapy for painful non-bone lesions in patients with advanced cancer. Materials and methods We enrolled patients with painful non-bone lesions who underwent conventional palliative radiotherapy between September 2018 and September 2022. The treatment targets included primary tumor lesions, lymph node metastases, non-bone hematogenous metastases, and other lesions. The primary endpoint was the overall pain response rate in evaluable patients, determined based on the International Consensus Pain Response Endpoint criteria. The secondary endpoints included overall survival, pain recurrence, and adverse events. Results Of the 420 screened patients, 142 received palliative radiotherapy for painful non-bone lesions, and 112 were evaluable. A pain response was achieved in 67 patients (60%) of the 112 evaluable patients within a median of 1.2 months. Among these patients, 25 exhibited complete response, 42 partial response, 18 indeterminate response, and 27 pain progression. The median survival time was 5.5 months, recorded at a median follow-up of 6.0 months, during which 67 patients died. Multivariate analysis identified poor performance status scores of 2–4, opioid use, and re-irradiation as independent factors associated with a reduced likelihood of achieving a pain response. Pain recurrence occurred in 18 patients over a median of 4.1 months. Seventeen patients had grade 1–2 adverse events, while none experienced grade 3 or higher toxicity. Conclusion Palliative radiotherapy can potentially be a safe and well-tolerated modality for managing painful non-bone lesions, with a low rate of adverse events.

Previous studies have primarily focused on quality of imaging in radiotherapy planning computed tomography (RTCT), with few investigations on imaging doses. To our knowledge, this is the first study aimed to investigate the imaging dose in RTCT to determine baseline data for establishing national diagnostic reference levels (DRLs) in Japanese institutions. A survey questionnaire was sent to domestic RT institutions between 10 October and 16 December 2021. The questionnaire items were volume computed tomography dose index (CTDIvol), dose-length product (DLP), and acquisition parameters, including use of auto exposure image control (AEC) or image-improving reconstruction option (IIRO) for brain stereotactic irradiation (brain STI), head and neck (HN) intensity-modulated radiotherapy (IMRT), lung stereotactic body radiotherapy (lung SBRT), breast-conserving radiotherapy (breast RT), and prostate IMRT protocols. Details on the use of motion-management techniques for lung SBRT were collected. Consequently, we collected 328 responses. The 75th percentiles of CTDIvol were 92, 33, 86, 23, and 32 mGy and those of DLP were 2805, 1301, 2416, 930, and 1158 mGy·cm for brain STI, HN IMRT, lung SBRT, breast RT, and prostate IMRT, respectively. CTDIvol and DLP values in institutions that used AEC or IIRO were lower than those without use for almost all sites. The 75th percentiles of DLP in each treatment technique for lung SBRT were 2541, 2034, 2336, and 2730 mGy·cm for free breathing, breath holding, gating technique, and real-time tumor tracking technique, respectively. Our data will help in establishing DRLs for RTCT protocols, thus reducing imaging doses in Japan.

Abstract Purpose This study evaluated the trends in the platform for stereotactic radiotherapy to the brain (SRT), utilizing the open data of the National Database published by the Ministry of Health, Labour, and Welfare. Materials and methods This study analyzed data from FY2014 to FY2021. The practices included in the study were gamma knife surgery (GKS) and SRT with a linear accelerator (LINAC). The total number of outpatient and inpatient cases in each SRT system was evaluated annually. Results From April 2014 to March 2022, the study included 212,016 cases (102,691 GKS and 109,325 LINAC) of the registered 1,996,540 radiotherapy cases. In the first year, 13,117 (54.1%) cases were GKS, and 11,128 (45.9%) were LINAC; after that, GKS decreased, and LINAC increased, reaching the same rate in FY2017. Compared to the first year, the final year showed 11,702 GKS (− 1415 or − 10.8%) and 17,169 LINAC (+ 6041 or + 54.3%), with an increase of 4626 total SRT cases to 28,871 (+ 19.1%). The percentage of outpatient treatment also increased from 4.6 to 11.8% for GKS and from 44.7 to 57.9% for LINAC. Conclusion The study found a gradual decrease in the selection of GKS, an increasing trend in the selection of LINAC, and an increase in the overall number of stereotactic irradiations. In particular, the proportion of outpatient treatment increased, indicating that more than half of LINAC was selected for outpatient treatment.

This study aims to evaluate the dosimetric accuracy of a deep learning (DL)-based deliverable volumetric arc radiation therapy (VMAT) plan generated using DL-based automated planning assistant system (AIVOT, prototype version) for patients with prostate cancer. The VMAT data (cliDose) of 68 patients with prostate cancer treated with VMAT treatment (70-74 Gy/28-37 fr) at our hospital were used (n = 55 for training and n = 13 for testing). First, a HD-U-net-based 3D dose prediction model implemented in AIVOT was customized using the VMAT data. Thus, a predictive VMAT plan (preDose) comprising AIVOT that predicted the 3D doses was generated. Second, deliverable VMAT plans (deliDose) were created using AIVOT, the radiation treatment planning system Eclipse (version 15.6) and its vender-supplied objective functions. Finally, we compared these two estimated DL-based VMAT treatment plans-i.e. preDose and deliDose-with cliDose. The average absolute dose difference of all DVH parameters for the target tissue between cliDose and deliDose across all patients was 1.32 ± 1.35% (range: 0.04-6.21%), while that for all the organs at risks was 2.08 ± 2.79% (range: 0.00-15.4%). The deliDose was superior to the cliDose in all DVH parameters for bladder and rectum. The blinded plan scoring of deliDose and cliDose was 4.54 ± 0.50 and 5.0 ± 0.0, respectively (All plans scored ≥4 points, P = 0.03.) This study demonstrated that DL-based deliverable plan for prostate cancer achieved the clinically acceptable level. Thus, the AIVOT software exhibited a potential for automated planning with no intervention for patients with prostate cancer.

We investigated the risk of secondary cancers in rectum and bladder for prostate cancer radiotherapy using a feasibility assessment tool. We calculated the risk of secondary cancer by generating a dose-volume histogram based on an ideal dose falloff function (f-value). This study found a smaller f-value was associated with a lower secondary cancer risk in the rectum but a higher risk in the bladder. The study suggests setting the f-value at 0-0.1 as the optimization goal for the rectum and 0.4 for the bladder is reasonable and feasible for reducing the risk of secondary cancer and other adverse events.

Abstract Objective We aimed to evaluate recent trends in characteristics and treatments among patients with brain metastases in clinical practice. Methods All newly diagnosed patients with brain metastases during 2016–2021 at a single cancer center were enrolled. We collected the detailed features of each patient and estimated the number of candidates considered to meet the following criteria used in common clinical trials: Karnofsky performance status ≥ 70 and mutated non-small cell lung cancer, breast cancer or melanoma. The brain metastases treatments were classified as follows: (i) stereotactic radiosurgery, (ii) stereotactic radiosurgery and systemic therapy, (iii) whole-brain radiotherapy, (iv) whole-brain radiotherapy and systemic therapy, (v) surgery, (vi) immune checkpoint inhibitor or targeted therapy, (vii) cytotoxic agents and (ix) palliative care. Overall survival and intracranial progression-free survival were estimated from brain metastases diagnosis to death or intracranial progression. Results A total of 800 brain metastases patients were analyzed; 597 (74.6%) underwent radiotherapy, and 422 (52.7%) underwent systemic therapy. In addition, 250 (31.3%) patients were considered candidates for common clinical trials. Compared to 2016, the later years tended to shift from whole-brain radiotherapy to stereotactic radiosurgery (whole-brain radiotherapy: 35.7–29.1% and stereotactic radiosurgery: 33.4–42.8%) and from cytotoxic agents to immune checkpoint inhibitor/targeted therapy (cytotoxic agents: 10.1–5.0 and immune checkpoint inhibitor/targeted therapy: 7.8–10.9%). There was also an increase in the proportion of systemic therapy combined with radiation therapy (from 26.4 to 36.5%). The median overall survival and progression-free survival were 12.7 and 5.3 months, respectively. Conclusions This study revealed the diversity of brain metastases patient characteristics, recent changes in treatment selection and the percentage of candidates in clinical trials.

Abstract Background This study aimed to investigate preoperative spirometry and BMI as early predictors of the mean heart and lung dose (MHD, MLD) in deep inspiration breath-hold (DIBH) radiotherapy. Methods Left-sided breast cancer patients underwent breast-conserving surgery followed by DIBH radiotherapy enrolled. Patients who were not available for preoperative spirometry were excluded. One hundred eligible patients were performed free-breathing (FB-) CT and DIBH-CT for plan comparison. We completed the correlative and multivariate analysis to develop the linear regression models for dose prediction. The residuals were calculated to explore the unpreferable subgroups and compare the prediction accuracy. Results Among the parameters, vital capacity (VC) and BMI showed the strongest negative correlation with MHD (r = − 0.33) and MLD (r = − 0.34), respectively. They were also significant in multivariate analysis (P &lt; 0.001). Elderly and less VC were independent predictors of increasing absolute residuals (AR). The VC model showed no significant difference in AR compared to the model using the CT parameter of lung volume in FB (LV-FB): median AR of the LV-FB model vs. the VC model was 0.12 vs. 0.11 Gy (P = 0.79). On the other hand, the median AR of the MLD model was 0.38 Gy, showing no specific subgroups of larger AR. Conclusion Preoperative spirometry and BMI are significant predictors of MHD and MLD, respectively. Although elderly and low-VC patients may have larger predictive variations, spirometry might be a substitute for LV-FB as a predictor of MHD.

AIM: This study aimed to evaluate the clinical benefits of systemic therapy (ST) combined with stereotactic radiosurgery (SRS) for brain metastases (BM). METHODS: The patient data were extracted from the institutional disease database from 2016 to 2021. Surgical and whole-brain radiotherapy cases and poor Karnofsky performance status (KPS < 70) were excluded. The eligible patients were divided into monotherapy (SRS alone or ST alone) and combined therapy (SRS and ST, combined within a month). Univariate and multivariate Cox proportional hazards analyses were used to examine factors associated with increased risk of death and intracranial progression. The propensity score for selecting treatment was calculated based on existing prognostic covariates. Two groups were matched 1:1 and compared for intracranial progression-free survival (PFS) and overall survival (OS). RESULTS: We identified 1605 patients and analyzed 928 (monotherapy: n = 494, combined therapy: n = 434). In a multivariable model, the combined therapy was independently associated with improved PFS and OS relative to the monotherapy. At the median follow-up of 383 days in the matched dataset, the combined therapy group showed significantly longer PFS (median, 7.4 vs. 5.0 months, P < 0.001) and OS (median, 23.1 vs. 17.2 months, P = 0.036) than the monotherapy group. The overall intracranial progression and mortality risk was reduced in the combined therapy group, with an estimated HR of 0.70 and 0.78. CONCLUSIONS: Combined therapy exhibited longer PFS and OS than monotherapy in BM patients. The results support the recent trend toward combining systemic and local therapies, encouraging future clinical trials.

In this study, a prototype device was developed to quickly remove the mask used to immobilize the head and neck by remotely releasing the quick fasteners. As a first step in investigating the usefulness of this prototype, we performed repeated removal tests and examined the accuracy of dose calculation. The results showed that the quick-release fasteners of a Type-S system (CIVCO Medical Solutions, Iowa, USA) could be removed remotely and accurately (success rate: 100%). Additionally, the dose errors in treatment planning were negligible (< 1.0%), and the gamma pass rate was equivalent (99.9%). Therefore, this prototype device with a remote system would help manage patient safety in emergencies, such as a disaster or a sudden change in the patient's condition. However, age-related deterioration with long-term clinical use or its ability to link with beam-off still requires further exploration.

Abstract Deep inspiration breath-hold (DIBH) is widely used to reduce the cardiac dose in left-sided breast cancer radiotherapy. This study aimed to develop a deep learning chest X-ray model for cardiac dose prediction to select patients with a potentially high risk of cardiac irradiation and need for DIBH radiotherapy. We used 103 pairs of anteroposterior and lateral chest X-ray data of left-sided breast cancer patients (training cohort: n = 59, validation cohort: n = 19, test cohort: n = 25). All patients underwent breast-conserving surgery followed by DIBH radiotherapy: the treatment plan consisted of three-dimensional, two opposing tangential radiation fields. The prescription dose of the planning target volume was 42.56 Gy in 16 fractions. A convolutional neural network-based regression model was developed to predict the mean heart dose (∆MHD) reduction between free-breathing (MHD_FB) and DIBH. The model performance is evaluated as a binary classifier by setting the cutoff value of ∆MHD &gt; 1 Gy. The patient characteristics were as follows: the median (IQR) age was 52 (47–61) years, MHD_FB was 1.75 (1.14–2.47) Gy, and ∆MHD was 1.00 (0.52–1.64) Gy. The classification performance of the developed model showed a sensitivity of 85.7%, specificity of 90.9%, a positive predictive value of 92.3%, a negative predictive value of 83.3%, and a diagnostic accuracy of 88.0%. The AUC value of the ROC curve was 0.864. The proposed model could predict ∆MHD in breast radiotherapy, suggesting the potential of a classifier in which patients are more desirable for DIBH.

BACKGROUND: JCOG1015A1 is an ancillary research study to determine the organ-specific dose constraints in head and neck carcinoma treated with intensity-modulated radiation therapy (IMRT) using data from JCOG1015. METHODS: Individual patient data and dose-volume histograms of organs at risk (OAR) were collected from 74 patients with nasopharyngeal carcinoma treated with IMRT who enrolled in JCOG1015. The incidence of late toxicities was evaluated using the cumulative incidence method or prevalence proportion. ROC analysis was used to estimate the optimal DVH cut-off value that predicted toxicities. RESULTS: The 5-year cumulative incidences of Grade (G) 1 myelitis, ≥ G1 central nervous system (CNS) necrosis, G2 optic nerve disorder, ≥ G2 dysphagia, ≥ G2 laryngeal edema, ≥ G2 hearing impaired, ≥ G2 middle ear inflammation, and ≥ G1 hypothyroidism were 10%, 5%, 2%, 11%, 5%, 26%, 34%, and 34%, respectively. Significant associations between DVH parameters and incidences of toxicities were observed in the brainstem for myelitis (D1cc ≥ 55.8 Gy), in the brain for CNS necrosis (D1cc ≥ 72.1 Gy), in the eyeball for optic nerve disorder (Dmax ≥ 36.6 Gy), and in the ipsilateral inner ear for hearing impaired (Dmean ≥ 44 Gy). The optic nerve, pharyngeal constrictor muscle (PCM), and thyroid showed tendencies between DVH parameters and toxicity incidence. The prevalence proportion of G2 xerostomia at 2 years was 17 versus 6% (contralateral parotid gland Dmean ≥ 25.8 Gy vs less). CONCLUSIONS: The dose constraint criteria were appropriate for most OAR in this study, although more strict dose constraints might be necessary for the inner ear, PCM, and brainstem.

PURPOSE: To quantify dose delivery errors for high-dose-rate image-guided brachytherapy (HDR-IGBT) using an independent end-to-end dose delivery quality assurance test at multiple institutions. The novelty of our study is that this is the first multi-institutional end-to-end dose delivery study in the world. MATERIALS AND METHODS: The postal audit used a polymer gel dosimeter in a cylindrical acrylic container for the afterloading system. Image acquisition using computed tomography, treatment planning, and irradiation were performed at each institution. Dose distribution comparison between the plan and gel measurement was performed. The percentage of pixels satisfying the absolute-dose gamma criterion was reviewed. RESULTS: Thirty-five institutions participated in this study. The dose uncertainty was 3.6% ± 2.3% (mean ± 1.96σ). The geometric uncertainty with a coverage factor of k = 2 was 3.5 mm. The tolerance level was set to the gamma passing rate of 95% with the agreement criterion of 5% (global)/3 mm, which was determined from the uncertainty estimation. The percentage of pixels satisfying the gamma criterion was 90.4% ± 32.2% (mean ± 1.96σ). Sixty-six percent (23/35) of the institutions passed the verification. Of the institutions that failed the verification, 75% (9/12) had incorrect inputs of the offset between the catheter tip and indexer length in treatment planning and 17% (2/12) had incorrect catheter reconstruction in treatment planning. CONCLUSIONS: The methodology should be useful for comprehensively checking the accuracy of HDR-IGBT dose delivery and credentialing clinical studies. The results of our study highlight the high risk of large source positional errors while delivering dose for HDR-IGBT in clinical practices.

Gold nanoparticles (AuNPs) can be used with megavolt (MV) X-rays to exert radiosensitization effects, as demonstrated in cell survival assays and mouse experiments. However, the detailed mechanisms are not clear; besides physical dose enhancement, several chemical and biological processes have been proposed. Reducing the AuNP concentration while achieving sufficient enhancement is necessary for the clinical application of AuNPs. Here, we used positively charged (+) AuNPs to determine the radiosensitization effects of AuNPs combined with MV X-rays on DNA damage in vitro. We examined the effect of low concentrations of AuNPs on DNA damage and reactive oxygen species (ROS) generation. DNA damage was promoted by 1.4 nm +AuNP with dose enhancement factors of 1.4 ± 0.2 for single-strand breaks and 1.2 ± 0.1 for double-strand breaks. +AuNPs combined with MV X-rays induced radiosensitization at the DNA level, indicating that the effects were physical and/or chemical. Although -AuNPs induced similar ROS levels, they did not cause considerable DNA damage. Thus, dose enhancement by low concentrations of +AuNPs may have occurred with the increase in the local +AuNP concentration around DNA or via DNA binding. +AuNPs showed stronger radiosensitization effects than -AuNPs. Combining +AuNPs with MV X-rays in radiation therapy may improve clinical outcomes.

The present study aimed to reduce the parotid gland dose in the hippocampus avoidance with whole-brain radiotherapy (HA-WBRT) using the helical tomotherapy (HT). Ten patients who had previously undergone WBRT were randomly selected and enrolled in this study. During the treatment planning, two different techniques to the jaw were applied for each patient, namely, 1.0 cm fixed jaw and 2.5 cm dynamic jaw. To efficiently reduce the dose in the bilateral parotid glands, directional block (DB) mode was set. The DB is a function of a treatment planning system for the dose reduction in organs at risk. The standard HA-WBRT plan which did not reduce the parotid gland dose was also designed to compare the plan quality. Compared with the standard HA-WBRT plan, the parotid gland dose could be reduced by approximately 70% without extending the delivery time by adding the parotid gland on the DB mode to the dose constraint. In addition, the differences in dosimetric parameters observed between the plans employing the 1.0 cm fixed jaw and 2.5 cm dynamic jaw were almost negligible. Moreover, delivery time in the 2.5 cm dynamic jaw could be greatly reduced by 60% compared with that in the 1.0 cm fixed jaw.

Abstract To confirm the fully automated rigid image registration (A-RIR) accuracy in postoperative spine stereotactic body radiation therapy (SBRT), we conducted a multicenter non-inferiority study compared to the human rigid image registration (H-RIR). Twenty-eight metastatic cancer patients who underwent postoperative spine SBRT are enrolled—image registration (IR) of planning computed tomography (CT) and CT-myelogram for delineating the spinal cord. The adopted A-RIR workflow is a contour-focused algorithm performing a rigid registration by maximizing normalized mutual information (NMI) restricted to the data contained within the automatically extracted contour. Three radiation oncologists (ROs) from multicenters were prompted to review two blinded registrations and choose one for clinical use. Indistinguishable cases were allowed to vote equivalent, counted A-RIR side. A-RIR is considered non-inferior to H-RIR if the lower limit of the 95% confidence interval (CI) of A-RIR preferable/equivalent is greater than 0.45. We also evaluated the NMI improvement from the baseline and the translational/rotational errors between A-RIR and H-RIR. The A-RIR preferable/equivalent was selected in 21 patients (0.75, 95% CI: 0.55–0.89), demonstrating non-inferiority to H-RIR. The A-RIR’s NMI improvement was greater than H-RIR in 24 patients: the mean value ± SD was 0.225 ± 0.115 in A-RIR and 0.196 ± 0.114 in H-RIR (P &amp;lt; 0.001). The absolute translational error was 0.38 ± 0.31 mm. The rotational error was −0.03 ± 0.20, 0.05 ± 0.19, −0.04 ± 0.20 degrees in axial, coronal, and sagittal planes (range: −0.66–0.52). In conclusion, A-RIR shows non-inferior to H-RIR in CT and CT-myelogram registration for postoperative spine SBRT planning.

OBJECTIVE: To clarify the peripheral dose changes, especially in the eye lens and thyroid gland regions, using an acrylic-lead shield in cone-beam computed tomography (CBCT). METHODS: The acrylic-lead shield consists of system walls and a system mat. The radiophotoluminescence glass dosemeter was set on the eye lens and thyroid gland regions on the RANDO phantom. The system mat was laid under the RANDO phantom ranging from the top of the head to the shoulders, and then, the system walls shielded the phantom's head. Additionally, the phantom was covered anteriorly with a band that had the same shielding ability as the system mat to cover the thyroid gland region. Protocols for CBCT imaging of the thoracic or pelvic region in clinical practice were used. The measurement was performed with and without the acrylic-lead shield. RESULTS: The dose to the eye lens region was reduced by 45% using the system wall. Conversely, the dose to the thyroid gland was unchanged. The use of the system mat reduced the dose to the thyroid gland region by 47%, and the dose to the eye lens was reduced by 22%. The dose to the eye lens region decreased to the background level using the system walls and mat. CONCLUSION: The newly proposed device using an acrylic-lead shield reduced the peripheral dose in CBCT imaging. ADVANCES IN KNOWLEDGE: Attention is focused on managing peripheral dose in image-guided radiation therapy. The peripheral dose reduction using the acrylic-lead shield is a new proposal in radiotherapy that has never been studied.

This study aimed to develop a poly-ε-caprolactone (PCL) material that has a low melting point while maintaining the deformation ability. The new PCL (abbreviated as 4b45/2b20) was fabricated by mixing two types of PCL with different molecular weights, numbers of branches, and physical properties. To investigate the melting point, crystallization temperature, elastic modulus, and elongation at break for 4b45/2b20 and three commercially available masks, differential scanning calorimetry and tensile tests were performed. The melting point of 4b45/2b20 was 46.0 °C, and that of the commercially available masks was approximately 56.0 °C (55.7 °C-56.5 °C). The elastic modulus at 60 °C of 4b45/2b20 was significantly lower than the commercially available masks (1.1 ± 0.3 MPa and 46.3 ± 5.4 MPa, p = 0.0357). In addition, the elongation at break of 4b45/2b20 were significantly larger than the commercially available masks (275.2 ± 25.0% and 216.0 ± 15.2%, p = 0.0347). The crystallization temperature of 4b45/2b20 (22.1 °C) was clinically acceptable and no significant difference was found in the elastic modulus at 23 °C (253.7 ± 24.3 MPa and 282.0 ± 44.3 MPa, p = 0.4). As a shape memory-based thermoset material, 4b45/2b20 has a low melting point and large deformation ability. In addition, the crystallization temperature and strength are within the clinically acceptable standards. Because masks made using the new PCL material are formed with less pressure on the face than commercially available masks, it is a promising material for making a radiotherapy mask that can reduce the burden on patients.

Deep-inspiration breath-hold radiotherapy (DIBH-RT) to reduce the cardiac dose irradiation is widely used but some patients experience little or no reduction. We constructed and compared two prediction models to evaluate the usefulness of our new synthetic DIBH-CT (sCT) model. Ninety-four left-sided breast cancer patients (training cohort: n = 64, test cohort: n = 30) underwent both free-breathing and DIBH planning. The U-Net-based sCT generation model was developed to create the sCT treatment plan. A linear prediction model was constructed for comparison by selecting anatomical predictors of past literature. The primary prediction outcome is the mean heart dose (MHD) reduction, and the coefficient of determination (R2), root mean square error (RMSE) and mean absolute error (MAE) were calculated. Moreover, we evaluated the heart and lungs contours' similarity and Hounsfield unit (HU) difference between both images. The median MHD reduction was 1.14 Gy in DIBH plans and 1.09 Gy in sCT plans (P = 0.96). The sCT model achieved better performance than the linear model (R2: 0.972 vs 0.450, RMSE: 0.120 vs 0.551, MAE: 0.087 vs 0.412). The organ contours were similar between DIBH-CT and sCT: the median Dice (DSC) and Jaccard similarity coefficients (JSC) were 0.912 and 0.838 for the heart and 0.910 and 0.834 for the lungs. The HU difference in the soft-tissue region was smaller than in the air or bone. In conclusion, our new model can generate the affected CT by breath-holding, resulting in high performance and well-visualized prediction, which may have many potential uses in radiation oncology.

A radiophotoluminescent glass dosimeter (RGD) is used for a postal audit of a photon beam because of its various excellent characteristics. However, it has not been used for scanning proton beams because its response characteristics have not been verified. In this study, the response of RGD to scanning protons was investigated to develop a dosimetry protocol using the linear energy transfer (LET)-based correction factor. The responses of RGD to four maximum-range-energy-pattern proton beams were verified by comparing it with ionization chamber (IC) dosimetry. The LET at each measurement depth was calculated via Monte Carlo (MC) simulation. The LET correction factor ( k LET RGD ) was the ratio between the uncorrected RGD dose ( D raw RGD ) and the IC dose at each measurement depth. k LET RGD can be represented as a function of LET using the following equation: k LET RGD LET = - 0.035 LET + 1.090 . D raw RGD showed a linear under-response with increasing LET, and the maximum dose difference between the IC dose and D raw RGD was 15.2% at an LET of 6.07 keV/μm. The LET-based correction dose ( D LET RGD ) conformed within 3.6% of the IC dose. The mean dose difference (±SD) of D raw RGD and D LET RGD was -2.5 ± 6.9% and 0.0 ± 1.6%, respectively. To achieve accurate dose verification for scanning proton beams using RGD, we derived a linear regression equation based on LET. The results show that with appropriate LET correction, RGD can be used for dose verification of scanning proton beams.

PURPOSE: We experimentally determined the radiophotoluminescent glass dosimeter (RPLD) dose responses for TomoTherapy, CyberKnife, and flattening-filter-free (FFF) linear accelerator (linac) outputs for dosimetry audits in Japan. METHODS: A custom-made solid phantom with a narrow central-axis spacing of three RPLD elements was used for output measurement to minimise the dose-gradient effect of the non-flattening filter beams. For RPLD dose estimation, we used the ISO 22127 formalism. Additional unit-specific correction factors were introduced and determined via the measured data. For TomoTherapy (7 units) and CyberKnife (4 units), the doses were measured under machine-specific reference fields. For FFF linac (5 units), in addition to the reference condition, we obtained the field-size effects for the range from 5×5 cm to 25×25 cm. RESULTS: The correction factors were estimated as 1.008 and 0.999 for TomoTherapy and CyberKnife, respectively. For FFF linac, they ranged from 1.011 to 0.988 for 6 MV and from 1.011 to 0.997 for 10 MV as a function of the side length of the square field from 5 to 25 cm. The estimated uncertainties of the absorbed dose to water measured by RPLD for the units were 1.32%, 1.35%, and 1.30% for TomoTherapy, CyberKnife, and FFF linac, respectively. A summary of the dosimetry audits of these treatment units using the obtained correction factors is also presented. The average percentage differences between the measured and hospital-stated doses were <1% under all conditions. CONCLUSION: RPLD can be successfully used as a dosimetry audit tool for modern treatment units.

Atlas-based auto-segmentation (ABS) procedure used in radiotherapy can be classified into two groups, one using one atlas per patient (sSM) and the other using multiple atlases (sMM). This study evaluated auto-contouring accuracy and contouring time in patients with prostate cancer using the two procedures. The Dice similarity coefficient of sMM was significantly better than that of sSM (prostate [median, 0.81 (range, 0.66-0.91) vs. 0.64 (0.27-0.71), p < 0.01], seminal vesicles [0.49 (0.31-0.80) vs. 0.18 (0.01-0.60), p < 0.05], and rectum [0.81 (0.37-0.91) vs. 0.57 (0.31-0.77), p < 0.01]). The median contouring times were 2.6 (sMM) and 1.3 min (sSM).

To establish a predictive model for pain response following radiotherapy using a combination of radiomic and clinical features of spinal metastasis. This retrospective study enrolled patients with painful spine metastases who received palliative radiation therapy from 2018 to 2019. Pain response was defined using the International Consensus Criteria. The clinical and radiomic features were extracted from medical records and pre-treatment CT images. Feature selection was performed and a random forests ensemble learning method was used to build a predictive model. Area under the curve (AUC) was used as a predictive performance metric. 69 patients were enrolled with 48 patients showing a response. Random forest models built on the radiomic, clinical, and 'combined' features achieved an AUC of 0.824, 0.702, 0.848, respectively. The sensitivity and specificity of the combined features model were 85.4% and 76.2%, at the best diagnostic decision point. We built a pain response model in patients with spinal metastases using a combination of clinical and radiomic features. To the best of our knowledge, we are the first to examine pain response using pre-treatment CT radiomic features. Our model showed the potential to predict patients who respond to radiation therapy.

PURPOSE: In radiotherapy, the dose to organs-at-risk must be kept as low as possible to preserve their function. We aimed to determine the acceptable f-value upper bound of the Feasibility DVH in the PlanIQ software to achieve dose reduction to the normal lung in patients with stage III non-small cell lung cancer. METHODS: By using the Feasibility DVH, the f-values corresponding to the pulmonary dosimetric parameters of each treatment plan for 11 patients were calculated. The acceptable f-value upper bound was defined as the value that added one standard deviation of the f-value to the mean. Additionally, the treatment plan for additional fourteen patients was designed to evaluate the effectiveness of the acceptable f-value upper bound for the normal lung dose reduction. The value beyond the acceptable f-value upper bound was judged as inadequate dose reduction. RESULTS: The acceptable f-value upper bound was different for dosimetric parameters (range, 0.22-0.26). These values were < 0.5, which is typically used as the acceptable f-value upper bound. Evaluation by the treatment plan of fourteen patients detected that the f-value of the normal lung of five patients exceeded the acceptable f-value upper bound, and the replanning was able to reduce the dose of the normal lung. CONCLUSIONS: We could efficiently reduce the normal-lung dose using the acceptable f-value upper bound calculated in this study and provide an effective acceptable f-value upper bound of the normal lung dose in the lung cancer radiotherapy.

The parotid gland is recognized as a major-risk organ in whole-brain irradiation; however, the beam delivery from the left and right sides cannot reduce the parotid gland dose. The four-field box technique using a head-tilting device has been reported to reduce the parotid gland dose by excluding it from the radiation field. This study aimed to determine the appropriate head tilt angle to reduce the parotid gland dose in the four-field box technique. The bilateral, anterior, and posterior beams were set for each of ten patients. The orbitomeatal plane angle (OMPA) was introduced as an indicator that expresses the head tilt angle. Next, principal component analysis (PCA) was performed to understand the interrelationship between variables (dosimetric parameters of the lens and parotid gland and OMPA). In PCA, the angle between the OMPA vector and maximum lens dose or mean parotid gland dose vector was approximately opposite or close, indicating a negative or positive correlation [r = -0.627 (p < 0.05) or 0.475 (p < 0.05), respectively]. The OMPA that reduced the maximum lens dose to <10 Gy with a 95% confidence interval was approximately 14°. If the lens dose was not considered, the parotid gland dose could be reduced by decreasing the OMPA.

A radiophotoluminescent glass dosimeter (RGD) is widely used in postal audit system for photon beams in Japan. However, proton dosimetry in RGDs is scarcely used owing to a lack of clarity in their response to beam quality. In this study, we investigated RGD response to beam quality for establishing a suitable linear energy transfer (LET)-corrected dosimetry protocol in a therapeutic proton beam. The RGD response was compared with ionization chamber measurement for a 100-225 MeV passive proton beam. LET of the measurement points was calculated by the Monte Carlo method. An LET-correction factor, defined as a ratio between the non-corrected RGD dose and ionization chamber dose, of 1.226×(LET)-0.171 was derived for the RGD response. The magnitude of the LET-dependence of RGD increased with LET; for an LET of 8.2 keV/μm, the RGD under-response was up to 16%. The coefficient of determination, mean difference ± SD of non-corrected RGD dose, residual range-corrected RGD dose, and LET-corrected RGD dose to the ionization chamber are 0.923, 3.7 ± 4.2%, -2.4 ± 7.5%, and 0.04 ± 2.1%, respectively. The LET-corrected RGD dose was within 5% of the corresponding ionization chamber dose at all energies until 200 MeV, where it was 5.3% lower than the ionization chamber dose. A corrected LET-dependence of RGD using a correction factor based on a power function of LET and precise dosimetric verification close to the maximum LET were realized here. We further confirmed establishment of an accurate postal audit under various irradiation conditions.

PURPOSE: Gold nanoparticles (AuNPs) are candidate radiosensitizers for medium-energy photon treatment, such as γ-ray radiation in high-dose-rate (HDR) brachytherapy. However, high AuNP concentrations are required for sufficient dose enhancement for clinical applications. Here, we investigated the effect of positively (+) charged AuNP radiosensitization of plasmid DNA damage induced by 192Ir γ-rays, and compared it with that of negatively (-) charged AuNPs. METHODS: We observed DNA breaks and reactive oxygen species (ROS) generation in the presence of AuNPs at low concentrations. pBR322 plasmid DNA exposed to 64 ng/mL AuNPs was irradiated with 192Ir γ-rays via HDR brachytherapy. DNA breaks were detected by observing the changes in the form of the plasmid and quantified by agarose gel electrophoresis. The ROS generated by the AuNPs were measured with the fluorescent probe sensitive to ROS. The effects of positively (+) and negatively (-) charged AuNPs were compared to study the effect of surface charge on dose enhancement. RESULTS: +AuNPs at lower concentrations promoted a comparable level of radiosensitization by producing both single-stranded breaks (SSBs) and double-stranded breaks (DSBs) than those used in cell assays and Monte Carlo simulation experiments. The dose enhancement factor (DEF) for +AuNPs was 1.3 ± 0.2 for SSBs and 1.5 ± 0.4 for DSBs. The ability of +AuNPs to augment plasmid DNA damage is due to enhanced ROS generation. While -AuNPs generated similar ROS levels, they did not cause significant DNA damage. Thus, dose enhancement using low concentrations of +AuNPs presumably occurred via DNA binding or increasing local +AuNP concentration around the DNA. CONCLUSION: +AuNPs at low concentrations displayed stronger radiosensitization compared to -AuNPs. Combining +AuNPs with 192Ir γ-rays in HDR brachytherapy is a candidate method for improving clinical outcomes. Future development of cancer cell-specific +AuNPs would allow their wider application for HDR brachytherapy.

PURPOSE: The in-room laser which is used for patient positioning in radiotherapy is generally projected on the radiation isocenter determined by the Winston-Lutz test and so on. In this study, a couch-mounted verification device was developed that could evaluate all in-room lasers' alignment including the horizontality and verticality at one time. The device has the function to perform the light/radiation field coincidence test and the Winston-Lutz test at the same time. The aim of this report was to introduce the verification procedure for two tests, using the newly developed software and device, and to present the tuning flow of the in-room laser. Moreover, the analysis accuracy of the developed software was evaluated in comparison with commercial software. METHODS: First, the light/radiation field was evaluated by using tungsten markers on the central surface of the device. Next, after aligning the long-carved lines on the front and sides of the device with the in-room lasers, the Winston-Lutz test was carried out by using the tungsten sphere in the center of the device. The acquired images were collectively analyzed using the developed software equipped with the reporting function. Additionally, the result of this Winston-Lutz test was compared with the result from commercial software. RESULTS: A series of the light/radiation field coincidence test and the Winston-Lutz test were analyzed using the developed device and software. The results could be easily confirmed using the reporting function of the software. Regarding the result of the Winston-Lutz test, most of the analysis differences between the developed software and commercially available software were within the pixel size (0.22 mm). DISCUSSIONS: Since the accuracy of the radiation field affects the result of the Winston-Lutz test, the presented procedure of performing the light/radiation coincidence field test in advance facilitates the interpretation of the error of the Winston-Lutz test. Based on the results of the Winston-Lutz test, we were able to demonstrate the tuning flow of all in-room lasers including the horizontality and verticality by using the developed device. CONCLUSIONS: We have developed a couch-mounted verification device and software that can evaluate the light/radiation coincidence field test and the alignment including the horizontality and verticality of the in-room laser used for patient positioning in radiotherapy, and reported its usefulness. The analysis accuracy of the developed software was comparable to that of commercially available software. The use of this device and the developed software would contribute to not only the efficiency of adjusting all in-room lasers' alignment including the horizontality and verticality but also reflect accurately the result of the Winston-Lutz test.

PURPOSE: We developed a thermoset shape memory bolus (shape memory bolus) made from poly-ε-caprolactone (PCL) polymer. This study aimed to investigate whether the shape memory bolus can be applied to radiotherapy as a bolus that conformally adheres to the body surface, can be created in a short time, and can be reused. METHODS: The shape memory bolus was developed by cross-linking tetrabranch PCL with reactive acrylate end groups. Dice similarity coefficient (DSC) was used to evaluate shape memory characterization before deformation and after restoration. In addition, the degree of adhesion to the body surface and crystallization time were calculated. Moreover, dosimetric characterization was evaluated using the water equivalent phantom and an Alderson RANDO phantom. RESULTS: The DSC value between before deformation and after restoration was close to 1. The degree of adhesion of the shape memory bolus (1.9%) was improved compared with the conventional bolus (45.6%) and was equivalent to three-dimensional (3D) printer boluses (1.3%-3.5%). The crystallization time was approximately 1.5 min, which was clinically acceptable. The dose calculation accuracy, dose distribution, and dose index were the equivalent compared with 3D boluses. CONCLUSION: The shape memory bolus has excellent adhesion to the body surface, can be created in a short time, and can be reused. In addition, the shape memory bolus needs can be made from low-cost materials and no quality control systems are required for individual clinical departments, and it is useful as a bolus for radiotherapy.

The Japan Clinical Oncology Group-Radiation Therapy Study Group (JCOG-RTSG) has initiated several multicenter clinical trials for high-precision radiotherapy, which are presently ongoing. When conducting multi-center clinical trials, a large difference in physical quantities, such as the absolute doses to the target and the organ at risk, as well as the irradiation localization accuracy, affects the treatment outcome. Therefore, the differences in the various physical quantities used in different institutions must be within an acceptable range for conducting multicenter clinical trials, and this must be verified with medical physics consideration. In 2011, Japan's first Medical Physics Working Group (MPWG) in the JCOG-RTSG was established to perform this medical-physics-related verification for multicenter clinical trials. We have developed an auditing method to verify the accuracy of the absolute dose and the irradiation localization. Subsequently, we credentialed the participating institutions in the JCOG multicenter clinical trials that were using stereotactic body radiotherapy (SBRT) for lungs, intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) for several disease sites, and proton beam therapy (PT) for the liver. From the verification results, accuracies of the absolute dose and the irradiation localization among the participating institutions of the multicenter clinical trial were assured, and the JCOG clinical trials could be initiated.

BACKGROUND AND PURPOSE: Post-operative spine stereotactic body radiation therapy (SBRT) represents a significant challenge as there are many restrictions on beam geometry to avoid metal hardware as it surrounds the target volume. In this study, an international multi-institutional end-to-end test using an in-house spine phantom was developed and executed. The aim was to evaluate the impact of titanium spine hardware on planned and delivered dose for post-operative spine SBRT. MATERIALS AND METHODS: Five centers performed simulation, planning and irradiation of the spine phantom, with/without titanium metal hardware (MB/B), following our pre-specified protocol. The doses were calculated using the centers' treatment planning system (TPS) and measured with radiophotoluminescent glass dosimeters (RPLDs) embedded within each phantom. RESULTS: The dose differences between the RPLD measured and calculated doses in the target region were within ± 5% for both phantoms studied. Differences greater than 5% were observed for the spinal cord and the out-of-the target regions due to steeper dose gradient regions that are created in these plans. Dose measurements within ± 3% were observed between RPLDs that were embedded in MB and B inserts. For the spinal cord and the out-of-target regions surrounded by metal hardware, the dose measured using RPLDs was within 3% different near the titanium screws compared to the dose measured near only the metal rods. CONCLUSION: We have successfully performed the first multi-institutional end-to-end dose analysis using an in-house phantom built specifically for post-operative spine SBRT. The differences observed between the measured and planned doses in the presence of metal hardware were clinically insignificant.

BACKGROUND: A phase II study of adaptive two-step intensity-modulated radiotherapy (IMRT) with chemotherapy for nasopharyngeal cancer (NPC) (JCOG1015) was conducted to evaluate the efficacy and safety. METHODS: Patients aged 20-75 years with stages II-IVB NPC were enrolled. As adaptive two-step IMRT, computed tomography planning was performed twice before IMRT for the initial plan of 46 Gy/23 fractions and during treatment for the boost plan of 24 Gy/12 fractions with a total dose of 70 Gy. Chemotherapy (cisplatin 80 mg/m2/3-weeks × 3 courses) was administered concurrently with IMRT, followed by adjuvant chemotherapy (cisplatin at 70 mg/m2 with 5-FU 700 at mg/m2 for 5 days/4 weeks × 3 courses). RESULTS: Between 2011 and 2014, 75 patients were enrolled from 12 institutions. The 3-year overall survival (OS) for the 75 patients was 88%, and the upper and lower limits of the 95% CI of 78%-94% were higher than the expected 3-year OS of 75% for the target population adjusted by the actual proportion of stage II:III:IV = 21%:44%:35%. The 3-year progression-free survival (PFS) and loco-regional PFS were 71% [59-80%] and 77% [66-85%], respectively. Although no grade 4-5 late toxicities were observed, 15 patients (20%) developed grade 3 late toxicities. Grade 2 xerostomia was noted in 26%, 12%, and 9% at 1, 2, and 3 years after starting IMRT, respectively. CONCLUSIONS: Adaptive two-step IMRT for NPC demonstrated an excellent 3-year OS with acceptable toxicities. This method may be one treatment option for locally advanced NPC.

INTRODUCTION: The epidural disease progression is the most common pattern of failure after spine stereotactic body radiotherapy. The aim of this study was to clarify the effect of the dose calculation grid size (CGS) during volumetric modulated arc therapy planning on the dose to the epidural space target. MATERIALS AND METHODS: In the planning, the volume obtained by subtracting the planning organ at risk volume (PRV) of the spinal cord and/or cauda equina from the planning target volume (PTV) was defined as the PTVeval. First, we compared the epidural space dose that overlapped with the PTVeval at dose CGSs of 1 mm and 2 mm. Next, we compared the dose that can be given, according to the isotropic distance from the PRV of the spinal cord and/ or cauda equina at dose CGSs of 1 mm and 2 mm. RESULTS: The dose to the epidural space overlapping with the PTVeval was significantly larger at the dose CGS of 1 mm (60 to 80 cGy, 3% of the prescription dose) than at the dose CGS of 2 mm (p < 0.01). In addition, compared with the dose CGS of 2 mm, the dose CGS of 1 mm provided a larger dose to 95% of the volume in the regions where the PTVeval overlapped at isotropic distances of 0 to < 1, 1 to 2, 2 to 3, 3 to 4, and 4 to 5 mm from the PRV of the spinal cord and/or cauda equina. CONCLUSIONS: During spine stereotactic body radiotherapy by volumetric modulated arc therapy, the dose CGS of 1 mm improved the dose calculation accuracy and increased the dose to the epidural space target compared with the dose CGS of 2 mm.

This study aimed to obtain details regarding treatment planning techniques for lung stereotactic body radiation therapy (SBRT) employed at each institution in Japan by using a questionnaire survey. An Internet questionnaire survey on SBRT procedures performed in 2016 was conducted by the QA/QC committee of the Japan Society of Medical Physics from April to June 2017. The questionnaire assessed two aspects: the environment for SBRT at each institution and the treatment planning techniques with and without respiratory motion management techniques (RMMT). Of the 309 evaluated responses, 218 institutions had performed SBRT. A total of 186 institutions performed SBRT without RMMT and 139 institutions performed SBRT with RMMT. When respiratory motion was ≥10 mm, 69 institutions applied RMMT. The leading RMMT were breath holding (77 institutions), respiratory gating (49 institutions) and real-time tumor tracking (11 institutions). The most frequently used irradiation technique was 3D conformal radiotherapy, which was used in 145 institutions without RMMT and 119 institutions with RMMT. Computed tomography (CT) images acquired under free breathing were mostly used for dose calculation for patients treated without RMMT. The usage ratio of IMRT/VMAT to SBRT is low in Japan, compared to elsewhere in the world (<20% vs ≥70%). Among the available dose calculation algorithms, superposition convolution was the most frequently used regardless of RMMT; however, 2% of institutions have not yet made heterogeneity corrections. In the prescription setting, about half of the institutions applied point prescriptions. The survey results revealed the most frequently used conditions, which may facilitate standardization of treatment techniques in lung SBRT.