BACKGROUND/AIM: The aim of this multi-center retrospective study was to investigate the results of stereotactic body radiotherapy (SBRT) for pulmonary oligometastases from esophageal cancer. PATIENTS AND METHODS: Oligometastases from the esophagus were identified from a dataset of a Japanese survey. The Kaplan-Meier method and Cox regression were applied to perform analyses. RESULTS: A total of 114 patients with 132 pulmonary oligometastases were collected. The 3-year local control rate, freedom from further metastasis (FFFM) rate and overall survival (OS) rate were 70.2%, 25.3% and 37.5%, respectively. Performance status (PS) (PS 1 vs. PS 0, p<0.01), disease-free interval (p=0.03) and history of local therapy for metastasis (p=0.01) had significant relationships with FFFM and only PS was an independent prognostic factor for OS (PS 1 vs. PS 0, p=0.02; PS 2-3 vs. PS 0, p=0.04). CONCLUSION: SBRT for pulmonary oligometastases from esophageal cancer provided good local control and survival.

PURPOSE: Radiographic severity of radiation-induced lung injury (RILI) has not been well-studied. The goal of this study was to assess the CT appearance pattern and severity of RILI without consideration of the clinical presentation. MATERIAL AND METHODS: A total of 49 patients, 41 with primary lung cancer and 8 with metastatic lung cancer, were treated by 4-fraction stereotactic body radiotherapy (SBRT). RILI after SBRT was separately assessed by two observers. The early and late CT appearance patterns and CT-based severity grading were explored. RESULTS: The median follow-up period was 39.0 months. In the early CT findings of observers 1 and 2, there was diffuse consolidation in 15 and 8, diffuse ground glass opacity (GGO) in 0 and 0, patchy consolidation and GGO in 17 and 20, patchy GGO in 3 and 3, and no changes in 10 and 14, respectively (kappa = 0.61). In late CT findings of observer 1 and 2, there were modified conventional pattern in 28 and 24, mass-like pattern in 8 and 11, scar-like pattern in 12 and 12, and no changes in 1 and 2, respectively (kappa = 0.63). In the results of the CT-based grading by observers 1 and 2, there were grade 0 in 1 and 2, grade 1 in 10 and 14, grade 2 in 31 and 29, grade 3 in 7 and 4, and none of grade 4 or more, respectively (kappa = 0.66). According to multivariate analyses (MVA), the significant predicting factors of grade 2 or more CT-based RILI were age (p = 0.01), oxygen dependence (p = 0.03) and interstitial shadow (p = 0.03). CONCLUSIONS: The agreement of the CT appearance and CT-based grading between two observers was good. These indicators may be able to provide us with more objective information and a better understanding of RILI.

This study aimed to evaluate the clinical validity of a dose-mimicking automated planning for volumetric-modulated arc therapy (VMAT) in patients with stage III non-small cell lung cancer (NSCLC), through direct comparison with a commercial dose volume histogram (DVH)-predicted system. We retrospectively analyzed volumetric-modulated arc therapy plans from 75 patients with stage III NSCLC treated at our institution (60 for training, 15 for testing). The dose-mimicking method was implemented using RatoGuide, and the DVH-predicted method was implemented using RapidPlan. The RatoGuide 3D dose-prediction model was trained on the 60 training cases. For each test case, a predicted dose distribution was generated and converted to a deliverable plan (RGDose) in Eclipse using vendor-provided objective functions. A RapidPlan model trained and generated deliverable plans (RPDose) for the same dataset. The clinical plan dose distribution (CliDose) was the reference. We compared dose distributions and DVH parameters among RGDose, RPDose and CliDose. Mean absolute errors (MAEs) relative to CliDose were 0.83 ± 0.66% (targets) and 2.06 ± 3.14% (organs at risk [OARs]) for RGDose, and 0.88 ± 0.66% (targets) and 2.49 ± 3.63% (OARs) for RPDose. There were no significant differences in OAR DVH parameters between RGDose and CliDose. In contrast, compared to CliDose, RPDose showed a significant reduction in the Esophagus D1cc and a significant increase in the Lungs V5Gy. The dose-mimicking method more faithfully reproduced the original clinical plans than the conventional DVH-predicted system, suggesting that dose-mimicking method can capture complex inter-OAR trade-offs and consistently reflect planner intent.

During the coronavirus disease 2019 (COVID-19) pandemic, a short-term decline in radiotherapy use was reported. In this study, we investigated long-term changes in the use of radiotherapy and hypofractionated radiotherapy before and after the COVID-19 pandemic period in Japan and assessed whether the pandemic influenced the adoption of hypofractionation. We obtained data for analysis from the National Database Open Data for fiscal years (FYs) 2014 to 2023. For the 5 years from FY2019 to FY2023, with detailed monthly data available, we used interrupted time series (ITS) analysis to examine changes in the level and slope of claims at the boundaries of the baseline, pandemic and post-pandemic periods. During the 10-year study period, the number of radiotherapy claims increased by an average of 1.6% per year. In FY2020, the peak of the COVID-19 pandemic, the number of radiotherapy claims decreased by 2.0% compared to the previous year. The number of claims for extra fees for hypofractionated radiotherapy for breast and prostate cancer showed a steady increase, except for a temporary decline around the April 2022 policy change in payment requirements for prostate cancer. In the ITS analysis, there were no significant changes in the level and slope of claims for radiotherapy and extra fees for hypofractionated radiotherapy at the onset of the pandemic. In conclusion, the impact of the COVID-19 pandemic on the utilization of radiotherapy in Japan was minimal, and the use of hypofractionated radiotherapy showed a steady increase throughout this period.

Cone-beam computed tomography-based online adaptive radiotherapy (CBCT-based online ART) is currently used in clinical practice; however, deep learning-based segmentation of CBCT images remains challenging. Previous studies generated CBCT datasets for segmentation by adding contours outside clinical practice or synthesizing tissue contrast-enhanced diagnostic images paired with CBCT images. This study aimed to improve CBCT segmentation by matching the treatment planning CT (tpCT) image quality to CBCT images without altering the tpCT image or its contours. A deep-learning-based CBCT segmentation model was trained for the male pelvis using only the tpCT dataset. To bridge the quality gap between tpCT and routine CBCT images, an artificial pseudo-CBCT dataset was generated using Gaussian noise and Fourier domain adaptation (FDA) for 80 tpCT datasets (the hybrid FDA method). A five-fold cross-validation approach was used for model training. For comparison, atlas-based segmentation was performed with a registered tpCT dataset. The Dice similarity coefficient (DSC) assessed contour quality between the model-predicted and reference manual contours. The average DSC values for the clinical target volume, bladder, and rectum using the hybrid FDA method were 0.71 ± 0.08, 0.84 ± 0.08, and 0.78 ± 0.06, respectively. Conversely, the values for the model using plain tpCT were 0.40 ± 0.12, 0.17 ± 0.21, and 0.18 ± 0.14, and for the atlas-based model were 0.66 ± 0.13, 0.59 ± 0.16, and 0.66 ± 0.11, respectively. The segmentation model using the hybrid FDA method demonstrated significantly higher accuracy than models trained on plain tpCT datasets and those using atlas-based segmentation.

The National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) is a database that stores anonymized information on medical receipts and health checkups in Japan. The NDB Open Data is a publicly accessible summary table of the NDB database. To reveal annual trends and regional disparities in radiotherapy utilization in Japan, we analyzed the NDB Open Data tables for a 9-year period from 2014 to 2022. We extracted medical cost codes for radiotherapy management fees and specific types of radiotherapy, such as stereotactic irradiation (STI) and intensity-modulated radiotherapy (IMRT), to analyze nationwide changes over time. To investigate regional disparities, we counted the three subitems representing 3-dimensional conformal radiotherapy (3D-CRT), IMRT, and STI for each prefecture per year. The utilization of advanced radiotherapy techniques, such as IMRT (199% increase), increased, while the use of simpler forms of irradiation, such as 1 or 2-opposite fields irradiation (40% decrease), decreased in the period from 2014 to 2022. Regarding regional disparities, the coefficients of variation in 47 prefectures for 3D-CRT remained relatively stable at 0.17 in 2014 and 0.18 in 2022, while the coefficients of variation for IMRT and STI decreased from 0.64 and 0.39 in 2014 to 0.31 and 0.36 in 2022, respectively. The popularization of IMRT was correlated with the number of certified radiation oncologists in the prefecture. In conclusion, although the utilization of high-precision radiotherapy in Japan has been increasing and regional differences have been diminishing, there are still persistent disparities.

Lung function assessment is essential for determining the optimal treatment strategy for radiation therapy in patients with lung tumors. This study aimed to develop radiomics and dosiomics approaches to estimate pulmonary function test (PFT) results in post-stereotactic body radiation therapy (SBRT). Sixty-four patients with lung tumors who underwent SBRT were included. Models were created to estimate the PFT results at 0-6 months (Cohort 1) and 6-24 months (Cohort 2) after SBRT. Radiomics and dosiomics features were extracted from the computed tomography (CT) images and dose distributions, respectively. To estimate the PFT results, Models A (dose-volume histogram [DVH] + radiomics features) and B (DVH + radiomics + dosiomics features) were created. In the PFT results, the forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were estimated using each model, and the ratio of FEV1 to FVC (FEV1/FVC) was calculated. The Pearson's correlation coefficient (Pearson r) and area under the curve (AUC) for FEV1/FVC (< 70%) were calculated. The models were evaluated by comparing them with the conventional calculation formulae (Conventional). The Pearson r (FEV1/FVC) values were 0.30, 0.64, and 0.69 for Conventional and Models A and B (Cohort 2), respectively, and the AUC (FEV1/FVC < 70%) values were 0.63, 0.80, and 0.78, respectively. This study demonstrates the possibility of estimating lung function after SBRT using radiomics and dosiomics features based on planning CT images and dose distributions.

We conducted a study to examine the treatment outcomes and prognostic factors for patients who underwent craniospinal irradiation (CSI) for leptomeningeal metastasis of solid tumors. This retrospective study included patients who received CSI for leptomeningeal metastasis at a single institute between 2010 and 2021. Data from clinical records and the radiation information system were obtained and analyzed. A total of 25 patients were included in the study. Eighteen patients (72%) completed the scheduled CSI. The median overall survival (OS) period was 4.8 months (95% confidence interval (CI): 3.2-10.0 months). Symptom relief was achieved in four out of 23 symptomatic patients (17%). Non-hematological adverse events occurred in 12 patients (48%), with 1 patient (4%) developing Grade 3 bacterial meningitis and the other patients having Grade 1-2 events. Twenty patients (80%) had hematological adverse events of Grade 3 or higher. Grade 4 hematologic toxicities occurred in 3 patients (12%) due to neutropenia and in 11 patients (44%) due to lymphopenia. In multivariate Cox regression analysis, the systemic immune-inflammation index (SII) was identified as the only significant parameter for predicting OS. The median OS periods for patients with SII < 607 and SII ≥ 607 were 6.1 and 2.1 months, respectively (P = 0.003). In conclusion, this study showed the treatment outcomes of CSI for leptomeningeal metastasis of solid tumors. It was shown that a high baseline SII was associated with shorter OS after CSI. The findings will contribute to the evaluation of prognosis after CSI.

Urinary toxicities are one of the serious complications of radiotherapy for prostate cancer, and dose-volume histogram of prostatic urethra has been associated with such toxicities in previous reports. Previous research has focused on estimating the prostatic urethra, which is difficult to delineate in CT images; however, these studies, which are limited in number, mainly focused on cases undergoing brachytherapy uses low-dose-rate sources and do not involve external beam radiation therapy (EBRT). In this study, we aimed to develop a deep learning-based method of determining the position of the prostatic urethra in patients eligible for EBRT. We used contour data from 430 patients with localized prostate cancer. In all cases, a urethral catheter was placed when planning CT to identify the prostatic urethra. We used 2D and 3D U-Net segmentation models. The input images included the bladder and prostate, while the output images focused on the prostatic urethra. The 2D model determined the prostate's position based on results from both coronal and sagittal directions. Evaluation metrics included the average distance between centerlines. The average centerline distances for the 2D and 3D models were 2.07 ± 0.87 mm and 2.05 ± 0.92 mm, respectively. Increasing the number of cases while maintaining equivalent accuracy as we did in this study suggests the potential for high generalization performance and the feasibility of using deep learning technology for estimating the position of the prostatic urethra.

Lymphopenia is a well-known side effect of radiotherapy and has been shown to have a negative impact on patient outcomes. However, the extent of lymphopenia caused by palliative radiotherapy and its effect on patient prognosis has not been clarified. The aim of this study was to determine the incidence and severity of lymphopenia after palliative radiotherapy for vertebral metastases and to determine their effects on patients' survival outcomes. We conducted a retrospective analysis for patients who underwent palliative radiotherapy for vertebral metastases and could be followed up for 12 weeks. Lymphocyte counts were documented at baseline and throughout the 12-week period following the start of radiotherapy and their medians and interquartile ranges (IQRs) were recorded. Exploratory analyses were performed to identify predictive factors for lymphopenia and its impact on overall survival (OS). A total of 282 cases that met the inclusion criteria were analyzed. The median baseline lymphocyte count was 1.26 × 103/μl (IQR: 0.89-1.72 × 103/μl). Peak lymphopenia occurred at a median of 26 days (IQR: 15-45 days) with a median nadir of 0.52 × 103/μl (IQR: 0.31-0.81 × 103/μl). Long-term analysis of patients surviving for 1 year showed that lymphopenia persisted at 1 year after radiotherapy. The main irradiation site, radiation field length and pretreatment lymphocyte count were significantly related to grade 3 or higher lymphopenia. Lymphopenia was identified as a significant predictor of OS by multivariate Cox regression analysis. This study demonstrated the incidence of lymphopenia after palliative radiotherapy for vertebral metastases and its effect on patients' OS.

BACKGROUND: There has been no study in which the correlation between clinical results and dosimetry based on a 3D treatment planning system in patients with 198Au grains for head and neck cancer was evaluated. METHODS: Thirty-two patients who were treated with 198Au grains for head and neck cancer were reviewed. Twenty-five patients were treated with brachytherapy alone and seven patients were treated with a combination of brachytherapy and neoadjuvant external beam radiation therapy. RESULTS: With a median observation period of 60 months, the 5-year local control rate was 82.9%. V85Gy of CTV in patients with local recurrence tended to be lower than that in patients without local recurrence (p = 0.07). The maximum dose of the keratinized gingiva in patients in whom bone exposure occurred was significantly higher than that in patients in whom bone exposure did not occur (p = 0.001). CONCLUSIONS: Dose distribution with 198Au grains can predict local control and late adverse events.

BACKGROUND AND OBJECTIVE: In the field of radiation therapy, image-guided radiotherapy (IGRT) technology has been gradually improving and highly accurate radiation treatment has been possible. Research on IGRT using 1.5 Tesla magnetic resonance imaging (MRI) began in 1999, and a radiation therapy device called 1.5 Tesla magnetic resonance linear accelerator (MR-Linac), which combines a linear accelerator with 1.5 Tesla MRI, was developed in Europe. The aim of this review is to present an overview of 1.5 Tesla MR-Linac with a review of the literature and our experience. METHODS: Reports related to 1.5 Tesla MR-Linac were searched for in PubMed and are discussed in relation to our experience. KEY CONTENT AND FINDINGS: The 1.5 Tesla MR-Linac enables IGRT using 1.5 Tesla MRI, further enhancing the precision of radiation therapy. Position verification by cone-beam computed tomography (CBCT) is performed in many institutions, but soft tissue contrast is often unclear in CBCT images of the abdomen and mediastinal organs. Since the 1.5 Tesla MR-Linac allows position verification using MRI, position verification can be performed using clear MRI even in regions where CBCT is unclear. With the 1.5 Tesla MR-Linac, it is possible to perform online adaptive radiotherapy (ART) using 1.5 Tesla MRI. Online ART is a method in which images are acquired while the patient is on the treatment table. The method is based on the current condition of the organs in the body on that day and an optimal treatment field is recreated. Additionally, it allows monitoring of tumor motion using cine images obtained by 1.5 Tesla MRI during the delivery of X-ray radiation. A previous report showed that patients with prostate cancer who received radiotherapy by MR-Linac had fewer side effects than those in patients who received conventional CBCT radiation therapy. CONCLUSIONS: The 1.5 Tesla MR-Linac obtained CE-mark certification in Europe in August 2018 and it has been used for clinical treatment. In Japan, clinical treatment using this device started in 2021. By using 1.5 Tesla MR-Linac, patients can be provided with higher precision radiotherapy. In this review, we provide an overview of 1.5 Tesla MR-Linac.

BACKGROUND AND PURPOSE: This study aimed to investigate the intrafractional movement of the spinal cord and spinal canal during MR-guided online adaptive radiotherapy (MRgART) for kidney cancer. MATERIALS AND METHODS: All patients who received stereotactic MRgART for kidney cancer between February 2022 and February 2024 were included in this study. Patients received 30-42 Gy in 3-fraction MRgART for kidney cancer using the Elekta Unity, which is equipped with a linear accelerator and a 1.5 Tesla MRI. MRI scans were performed at three points during each fraction: for online planning, position verification, and posttreatment assessment. The spinal cord was contoured from the upper edge of Th12 to the medullary cone, and the spinal canal was contoured from Th12 to L3, using the first MRI. These contours were adjusted to the second and third MR images via deformable image registration, and movements were measured. Margins were determined via the formula "1.3×Σ+0.5×σ" and 95% prediction intervals. RESULTS: A total of 22 patients (66 fractions) were analyzed. The median interval between the first and third MRI scans were 38 minutes. The mean ± standard deviation of the spinal cord movements after this interval were -0.01 ± 0.06 for the x-axis (right-left), 0.01 ± 0.14 for the y-axis (caudal-cranial), 0.07 ± 0.05 for the z-axis (posterior-anterior), and 0.15 ± 0.08 for the 3D distance, respectively. The correlation coefficients of the 3D distance between the spinal cord and the spinal canal was high (0.92). The calculated planning organ at risk volume margin for all directions was 0.11 cm for spinal cord. The 95% prediction intervals for the x-axis, y-axis, and z-axis were -0.11-0.09 cm, -0.23-0.25 cm and -0.14-0.03 cm, respectively. CONCLUSIONS: Margins are necessary in MRgART to compensate for intrafractional movement and ensure safe treatment delivery.

The purpose of this study was to show the safety of volumetric modulated arc therapy (VMAT) with deep inspiration breath-hold (DIBH) in hypofractionated radiotherapy for left-sided breast cancer after breast-conserving surgery in a clinical setting. Twenty-five Japanese women, aged 20-59 years, who were enrolled in this prospective non-inferiority study received VMAT under the condition of DIBH with 42.4 Gy/16 fractions for whole-breast irradiation (WBI) ± boost irradiation for the tumor bed to show the non-inferiority of VMAT with DIBH to conventional fractionated WBI with free breathing. The primary endpoint was the rate of occurrence of radiation dermatitis of Grade 3 or higher or pneumonitis of Grade 2 or higher within 6 months after the start of radiotherapy. This study was registered with UMIN00004321. All of the enrolled patients completed the planned radiotherapy without interruption. The evaluation of adverse events showed that three patients (12.0%) had Grade 2 radiation dermatitis. There was no other Grade 2 adverse event and there was no patient with an adverse event of Grade 3 or higher. Those results confirmed our hypothesis that the experimental treatment method is non-inferior compared with our historical results. There was no patient with locoregional recurrence or metastases. In conclusion, VMAT under the condition of DIBH in hypofractionated radiotherapy for left-sided breast cancer after breast-conserving surgery can be performed safely in a clinical setting.

Whole brain radiation therapy (WBRT) is effective for multiple brain metastases (BMs) but may impair neurocognitive function (NCF). The incidence of hippocampal metastasis (HM) is low, and the factors associated with the occurrence of HM remain unclear. This study aimed to assess the occurrence of limbic system metastasis (LSM), including HM, and to analyze the risk of HM. We retrospectively analyzed 248 patients who underwent three-dimensional conformal radiation therapy for BMs between May 2008 and October 2015. Gadolinium-enhanced brain MRI or CT scans were used for diagnosis. Statistical analysis involved assessing clinical factors, including age, gender, primary tumor, number of BMs, and maximum metastasis diameter, in relation to the presence of HMs using logistic regression and receiver operating characteristic (ROC) curve analysis. The median age at treatment was 62 years (range: 11-83 years). Primary lesion sites included the lung (n = 150; 60.5%), breast (n = 45; 18.1%), gastrointestinal tract (n = 18; 7.3%), and bone and soft tissue (n = 2; 0.8%). Histological cancer types included adenocarcinoma (n = 113; 45.6%), squamous cell carcinoma (n = 26; 10.5%), small cell carcinoma (n = 28; 11.3%), invasive ductal carcinoma (n = 35; 14.1%), sarcoma (n = 3; 1.2%), and others (n = 43; 17.3%). MRI or CT scans of the 248 patients were analyzed, indicating a total count of 2,163 brain metastases (median: five metastases per patient). HMs were identified in 18 (7.3%) patients. The most common location for LSMs was the cingulum/cingulate gyrus in 26 (10.5%) patients. In univariate and multivariate analyses, patients with 15 or fewer BMs had a significantly lower incidence of HMs (odds ratio (OR), 0.018 (95% confidence interval (CI), 0.030-0.24)) (p < 0.0001). A maximal tumor size of less than 2 cm significantly increased the incidence of HMs (OR, 13.8 (95%CI, 1.80-105.3)) (p = 0.0003). The presence of cingulum/cingulate gyrus metastases also demonstrated a significant increase in the incidence of HMs (OR, 9.42 (95%CI, 3.30-26.84)) (p < 0.0001). The present study has uncovered a novel association between a high number of metastases in the cingulate gyrus and the development of HMs. Patients with BMs eligible for WBRT with metastases in the cingulate gyrus may be at risk of developing HM.

BACKGROUND/AIM: This retrospective study aimed to investigate the outcomes of relapse-free survival (RFS) after salvage radiation therapy (SRT) to the prostate bed for postoperative biochemical recurrence of prostate cancer. PATIENTS AND METHODS: A total of 87 patients were analyzed. There were 27, 32, and 24 patients with pathological grade groups of 1-2, 3, and 4-5, respectively. SRT doses of 64, 66 or 70 Gy were administered to 24, 3 and 60 patients, respectively. The Kaplan-Meier method was used to estimate time-to-event outcomes. The multiple imputations method was used to impute missing values, and Cox proportional-hazards models were applied for multivariate analyses. RESULTS: The median follow-up period for patients overall was 58.6 months. The 5-year RFS rates of the whole cohort was 59.4% and those for pathological grade groups 1-2, 3 and 4-5 were 88.9%, 37.7% and 39.5%, respectively. In multivariate analyses, higher pathological grade group [4-5 vs. 3 vs. 1-2: hazard radio (HR)=8.65, p<0.01], negative surgical resection margin (positive vs. negative: HR=0.41, p=0.02) and higher pre-salvage treatment serum prostate-specific antigen (cutoff value 0.31 ng/ml: HR=3.50, p<0.01) were significantly associated with poorer RFS. The cumulative incidences of grade 2 or more late rectal bleeding and late hematuria were 4.9% and 8.7%, respectively, at 5 years and 4.9% and 15.7%, respectively, at 8 years. These toxicities occurred only in the 70 Gy-treated arm. CONCLUSION: Our study revealed that pathological grade group 3 prostate cancer patients experienced moderately unfavorable RFS after SRT. Higher radiation doses might increase late toxicities without improving RFS.

PURPOSE: Whole-brain radiotherapy (WBRT) may not be beneficial for patients with brain metastases (BMs). The Glasgow Prognostic Score (GPS) is a suggested prognostic factor for malignancies. However, GPS has never been assessed in patients with BMs who have undergone WBRT. The purpose of this study was to determine whether GPS can be used to identify subgroups of patients with BMs who have a poor prognosis, such as recursive partitioning analysis (RPA) Class 2 and Class 3, and who will not receive clinical prognostic benefits from WBRT. MATERIALS AND METHODS: A total of 180 Japanese patients with BMs were treated with WBRT between May 2008 and October 2015. We examined GPS, age, Karnofsky Performance Status (KPS), RPA, graded prognostic assessment (GPA), number of lesions, tumor size, history of brain surgery, presence of clinical symptoms, and radiation doses. RESULTS: The overall median survival time (MST) was 6.1 months. seventeen patients (9.4%) were alive more than 2 years after WBRT. In univariate analysis, KPS ≤ 70 (p = 0.0066), GPA class 0-2 (p = 0.0008), > 3 BMs (p = 0.012), > 4 BMs (p = 0.02), patients who received ≥ 3 Gy per fraction (p = 0.0068), GPS ≥ 1 (p = 0.0003), and GPS ≥ 2 (p = 0.0009) were found to significantly decrease the MST. Patients who had brain surgery before WBRT (p = 0.036) had a longer survival. On multivariate analysis, GPS ≥ 1 (p = 0.008) was found to significantly decrease MST. CONCLUSION: Our results suggest that GPS ≥ 1 indicates a poor prognosis in patients undergoing WBRT for intermediate and poor prognosis BMs.

To investigate radiation-induced cytopenia and establish predictive nomograms for hematological toxicity, we reviewed 3786 patients aged 18 or older who received radiation monotherapy between 2010 and 2021 for non-hematologic malignancies. We collected data on patient background, treatment content and hematologic toxicities for 12 weeks after the start of radiotherapy. The patients were randomly divided into training and test groups in 7:3 ratio. In the training group, we conducted ordered logistic regression analysis to identify predictive factors for neutropenia, lymphocytopenia, anemia and thrombocytopenia. Nomograms to predict Grade 2-4 cytopenia were generated and validated in the test group. Grade 3 or higher hematologic toxicities were observed in 9.7, 44.6, 8.3 and 3.1% of patients with neutropenia, lymphocytopenia, anemia and thrombocytopenia, respectively. We identified six factors for neutropenia grade, nine for lymphocytopenia grade and six for anemia grade with statistical significance. In the analysis of thrombocytopenia, the statistical model did not converge because of a small number of events. Nomograms were generated using factors with high predictive power. In evaluating the nomograms, we found high area under the receiver operating characteristic curve values (neutropenia; 0.75-0.85, lymphopenia; 0.89-0.91 and anemia; 0.85-0.86) in predicting Grade 2-4 cytopenia in the test group. We established predictive nomograms for neutropenia, leukocytopenia and anemia and demonstrated high reproducibility when validated in an independent cohort of patients.

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.

BACKGROUND/AIM: The purpose of this study was to evaluate the impact of recent radiotherapy on mortality from heart disease in Asians or Pacific islanders with breast cancer using the Surveillance, Epidemiology, and End Results (SEER) database. PATIENTS AND METHODS: Asians or Pacific islanders with stage 0 or I (AJCC 6th) breast cancer between 2000 and 2015 were analyzed. The impact of radiotherapy for mortality from heart disease after treatment was evaluated by comparing patients who received radiotherapy for left-sided breast cancer, patients who received radiotherapy for right-sided breast cancer and patients who did not receive radiotherapy. RESULTS: In 25,684 Asians or Pacific islanders, the incidence of cardiac death was higher in patients who did not receive radiotherapy than in patients who received radiotherapy. Among patients who received external beam irradiation, the incidence of cardiac death was 2.00% for patients with left-sided breast cancer and 1.69% for patients with right-sided breast cancer, with no significant difference (chi-square test, p=0.427). In the period from 2000 to 2008, there was no significant difference between the cumulative heart-related death rates in patients who received radiotherapy and in patients who did not receive radiotherapy (Tarone-Ware test, p=0.406); however, in 2009-2015, the cumulative heart-related death rate in patients who did not receive radiotherapy was significantly higher than that in patients who received radiotherapy (log-rank test, p<0.001). CONCLUSION: Heart-related death after treatment for breast cancer is relatively rare in Asians or Pacific islanders. Since at least 2000, the cardiac impact of postoperative radiotherapy has not been significant.

BACKGROUND: The purpose of this study was to investigate treatment outcomes of chemoradiotherapy (CRT) using S-1 with or without conversion surgery after gemcitabine plus nab-paclitaxel (GnP) for borderline resectable (BR) and unresectable locally advanced (UR-LA) pancreatic cancer. METHODS: From 2016 to 2020, patients without disease progression after GnP for BR or UR-LA pancreatic cancer underwent CRT with S-1. If distant metastasis was not detected after CRT, conversion surgery and oral administration of S-1 as postoperative adjuvant chemotherapy for at least 6 months was performed. RESULTS: Forty patients were included in the present study. The median number of cycles of GnP was 6. Surgery was performed after CRT in 25 patients. The median progression-free survival (PFS) and overall survival (OS) periods from the start of radiotherapy were 24.6 and 27.4 months, respectively. The OS periods from the start of radiotherapy in patients who underwent conversion surgery and those who did not undergo conversion surgery were 41.3 and 16.8 months, respectively. The PFS periods from the start of radiotherapy in patients who underwent surgery and those who did not undergo surgery were 28.3 and 8.6 months, respectively. Patients who were able to receive S-1 after conversion surgery for more than 6 months had better OS than those who were not (p = 0.039), although there was no significant difference of PFS (p = 0.365). CONCLUSIONS: In BR/UR-LA pancreatic cancer without disease progression after GnP, multimodal treatment including CRT, conversion surgery and the scheduled postoperative chemotherapy may be effective.

This prospective study aimed to evaluate whether radiation (RT)-induced myocardial damage by cardiac magnetic resonance (CMR) imaging could be a predictor of cardiac events after chemoradiotherapy (CRT) for esophageal cancer and determine the dose-volume histogram (DVH) parameters of the left ventricle (LV) in predicting cardiac events. CMR imaging was performed before and 6 months after CRT in patients receiving definitive CRT. RT-induced myocardial damage was defined as abnormal CMR findings indicating myocardial fibrosis corresponding to an isodose line of ≥30 Gy. The cutoff values of the LV DVH parameters were calculated using the receiver operating characteristic curve based on the presence of RT-induced myocardial damage. The prognostic factors related to cardiac events of Grade 3 or higher were examined. Twenty-three patients were enrolled in the study. RT-induced myocardial damage by late gadolinium enhancement and/or an increase of 100 ms or higher in native T1 post-CRT was detected in 10 of the 23 patients. LV V45 was the best predictive factor for RT-induced myocardial damage with a cutoff value of 2.1% and an area under the curve of 0.75. The median follow-up period was 82.1 months. The 5- and 7-year cumulative incidences of cardiac events of Grade 3 or higher were 14.7 and 22.4%, respectively. RT-induced myocardial damage and LV V45 were significant risk factors (P = 0.015 and P = 0.013, respectively). RT-induced myocardial damage is a significant predictor of cardiac events. LV V45 is associated with RT-induced myocardial damage and subsequent cardiac events.

Radiotherapy for breast cancer has attracted attention in Western countries because radiation to the heart can cause cardiac events. The purposes of this study were to evaluate the relationship between radiotherapy after breast-conserving surgery and the frequency of cardiac events in Japanese patients and to investigate the risk factors of cardiac events after postoperative radiotherapy in those patients. Female patients who received postoperative radiotherapy following breast-conserving surgery between 2007 and 2012 at our hospital were evaluated. In this study, we estimated the cumulative incidence of cardiac events including angina pectoris, myocardial infarction, ischemic heart disease, heart failure and cardiomyopathy after radiotherapy. Of 311 eligible patients, 7.1% of the patients had a smoking history, 20.3% of the patients were obese and 22.2% of the patients had hypertension. The median follow-up period was 118 months (interquartile range, 102-132 months). Twelve patients (3.9%) experienced cardiac events after treatment. The mean time to cardiac events was 126 months. The 10-year cumulative incidences of cardiac events after treatment were 4.2% and 4.3% for patients with left-sided and right-sided breast cancer, respectively, without a significant difference. Multivariate analysis showed that only hypertension was a risk factor for cardiac events (hazard ratio = 16.67, P = 0.0003). In conclusion, postoperative radiotherapy for breast cancer did not increase the incidence of cardiac events. Since at least 2007, postoperative radiotherapy for breast cancer has been safely performed without effects on the heart.

This study assessed the efficacy of chemoradiotherapy for squamous cell carcinoma of the anal canal (SCCAC). Patients with T1-4N0-3M0 SCCAC received chemoradiotherapy with 5-fluorouracil (5-FU, 800 mg/m2/day, 96-h infusion) and mitomycin-C (MMC, 10 mg/m2 bolus). Patients treated with 3-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) were administered 36.0 Gy in 20 fractions or 49.5 Gy in 33 fractions for elective nodal irradiation and 59.4 Gy in 33 fractions for primary tumor and metastatic nodal irradiation. The sample size was considered sufficient to estimate 95% confidence intervals (CIs) for the true 2-year disease-free survival (DFS) within a width of +15% when the expected true 2-year DFS was 70%. The primary endpoint was 2-year DFS. The secondary endpoints were 2-year overall survival (OS), locoregional control (LC), colostomy-free survival (CFS) and adverse events. Thirty-one patients were enrolled between January 2014 and July 2019. The median follow-up was 33.3 months (range, 16.2-65.8 months). Among the 31 patients, 13%, 32%, 16% and 39% had stage I, II, IIIA and IIIB disease, respectively. Thirty patients were treated with IMRT. Complete response (CR) was achieved in 27 patients. The 2-year DFS, OS, LC and CFS rates were 77.4% (95% CI, 58.4-88.5%), 93.5% (95% CI, 76.6-98.3%), 83.9% (95% CI, 65.5-92.9%) and 80.6% (95% CI, 61.9-90.8%), respectively. One patient experienced grade 3 late adverse events; however, no grade ≥ 4 late adverse events occurred. Good DFS with a low rate of late adverse events was observed. Chemoradiotherapy with 5-FU and MMC was effective for SCCAC.

BACKGROUND: In the treatment of vertebral bone metastases, estimating patient prognosis is important to select the optimal treatment strategy. The purpose of this study was to identify prognostic factors for vertebral bone metastases treated with palliative radiotherapy and to establish a nomogram for predicting patient survival. MATERIALS AND METHODS: We analyzed patients who underwent palliative radiotherapy for vertebral bone metastasis between January 2010 and December 2020 at a single institution. Exclusion criteria were as follows: (1) primary bone malignancy, (2) stereotactic body radiotherapy, (3) concurrent radiotherapy to sites other than the vertebral bone, (4) radiotherapy to other sites within 12 weeks before or after the current radiotherapy, and (5) lack of more than half of blood test data before radiotherapy. RESULTS: A total of 487 patients met the inclusion criteria. Clinical and hematologic data were collected from the patient record system. Patients were divided into training and test groups in a 7:3 ratio. Multivariate Cox regression analysis in the training cohort revealed six significant factors, including a history of chemotherapy, primary site (breast cancer, prostate cancer, or hematologic malignancy), use of analgesics, neutrophil-lymphocyte ratio, serum albumin, and lactate dehydrogenase. A prognostic nomogram was developed and validated in the test cohort. The area under the curve (AUC) values in predicting survival at 6, 24, and 60 months were 0.83, 0.88, and 0.88 in the training cohort and 0.85, 0.81, and 0.79 in the test cohort, respectively. CONCLUSIONS: This nomogram may help to select the treatment strategy for vertebral bone metastases.

INTRODUCTION: Patients with esophageal cancer who are in a poor general condition receive radiotherapy alone, but outcomes are often unsatisfactory. The aim of this study was to clarify recent outcomes of radiotherapy alone for esophageal cancer. METHODS: Patients who underwent 50 Gy or more of radiotherapy without chemotherapy were retrospectively reviewed. Endpoints were overall survival (OS), disease-specific survival (DSS), local control (LC), and progression-free survival (PFS). Survival curves were drawn using the Kaplan-Meier method, and predictors were analyzed using the Cox proportional hazards model. RESULTS: Sixty-nine patients were included. The median follow-up period was 17.9 months. The 5-year OS, DSS, LC, and PFS rates were 33.2%, 49.8%, 46.2%, and 16.8%, respectively. In the multivariate Cox proportional hazard model, clinical stage was a significant predictor for OS (hazard ratio [HR]: 4.42, 95% confidence interval [CI]: 1.80-11.17, p = 0.001), DSS (HR: 2.08, 95% CI: 1.43-3.12, p = 0.0001), LC (HR: 1.86, 95% CI: 1.28-2.74, p = 0.001), and PFS (HR: 1.65, 95% CI: 1.25-2.18, p = 0.0004). Radiation dose was a significant predictor for LC (HR: 0.87, 95% CI: 0.78-0.97, p = 0.018) and tumor location was a significant predictor for PFS (HR: 1.55, 95% CI: 1.10-2.19, p = 0.018). In subgroup analysis, the 5-year OS, DSS, LC, and PFS rates for stage I were 60.0%, 80.0%, 71.9%, and 46.1%, respectively. CONCLUSIONS: Stage, radiation dose, and tumor location are significant predictors for outcomes. Patients with stage I esophageal cancer can be cured by radiotherapy alone.

PURPOSE: The purpose of this study was to investigate the treatment results with focus on local control (LC) by computed tomography (CT)-guided intracavity brachytherapy and interstitial brachytherapy (ICBT/ISBT) for locally advanced cervical cancer (LACC). METHODS AND MATERIALS: Patients with LACC undergoing ICBT/ISBT at least once in our institution between January 2017 and June 2019 were analyzed retrospectively. The primary endpoint was local control (LC), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and late toxicities. Differences between patient subgroups for prognostic factors in LC, PFS, and OS were analyzed using the log-rank test. The recurrence patterns of LC were also investigated. RESULTS: Forty-four patients were included in the present study. The median high-risk clinical target volume (HR-CTV) at the initial brachytherapy was 48.2 cc. The median total dose of HR-CTV D90 (EQD2) was 70.7 Gy. The median followup period was 39.4 months. The 3-year LC, PFS and OS rates in all patients were 88.2%, 56.6%, and 65.4% (95% CI 50.3-78.0%), respectively. Corpus invasion and large HR-CTV (70 cc or more) were significant prognostic factors in LC, PFS, and OS. Marginal recurrences at the fundus of the uterus were detected in 3 of 5 patients in whom local recurrence was observed. Late toxicities of Grade 3 or higher were detected in 3 patients (6.8%). CONCLUSIONS: Favorable LC was achieved by performing CT-guided ICBT/ISBT for LACC. The brachytherapy strategy for patients with corpus invasion or large HR-CTV may need to be reconsidered.

OBJECTIVES: In the treatment of castration-resistant prostate cancer (CRPC) with bone metastases, radium-223 dichloride (Ra-223) is the only bone-targeted drug that shows survival benefits. Completing six courses of Ra-223 treatment is thought to be associated with better patient survival, but this treatment has a relatively high rate of acute adverse events. METHODS: This retrospective study included 85 patients from 12 institutions in Japan to investigate the clinical significance of the completion of Ra-223 treatment and acute adverse events in CRPC patients. RESULTS: Six courses of Ra-223 treatment were completed in 65.9% of the patients. Grade 3 or higher acute adverse events were observed in 27.1% of patients. The prostate specific antigen and alkaline phosphatase declined at 26.9% and 87.9%, respectively. The overall survival rates at 12 and 24 months were 80.7% and 63.2%, respectively. Both completion of six courses of Ra-223 treatment and absence of grade 3 or higher acute adverse events were associated with longer overall survival. In univariate analysis, factors related to the history of treatment (five or more hormone therapy agents and cytotoxic chemotherapy) and hematological parameters (Prostate specific antigen (PSA) doubling time, alkaline phosphatase, hemoglobin, albumin, and serum calcium) were associated with completing six courses of Ra-223 treatment without experiencing grade 3 or higher acute adverse events. Multivariate analysis showed that a history of chemotherapy, PSA doubling time, hemoglobin, and serum calcium showed statistical significance. We built a predictive score by these four factors. Patients with lower scores showed higher rates of treatment success (p<0.001) and longer overall survival (p<0.001) with statistical significance. CONCLUSIONS: Accomplishing six courses of Ra-223 treatment without grade 3 or higher acute adverse events was a prognostic factor in patients with mCRPC treated with Ra-223. We built a predictive score of treatment success and need future external validation.

Purpose: Intensity-modulated radiotherapy (IMRT) is currently used more commonly than 3-dimensional conformal radiation for definitive thoracic radiation. We examined the efficacy profiles of concurrent chemoradiotherapy (CCRT) with IMRT after durvalumab became clinically available. Methods: We reviewed the clinical records of patients with stage III non-small cell lung cancer (NSCLC) treated with CCRT and IMRT at seven centers in Japan and investigated relapse and survival from May 2018 to December 2019. The primary endpoint of this report was progression-free survival (PFS). Results: Among 107 patients enrolled in the study, 87 were sequentially administered durvalumab. From CCRT commencement, patients were followed up for a median period of 29.7 months. The median PFS at the end of the CCRT was 20.7 months. Among the 87 patients, 58 experienced disease relapses, of whom 36 (62.1 %) had distant metastases. Multivariate Cox regression analysis revealed that a favorable response to CCRT, a radiation dose ≥ 62 Gy, and stage IIIA NSCLC were associated with prolonged PFS (all P = 0.04). Multivariate logistic regression by landmark analysis revealed that mortality risk factors were durvalumab treatment duration ≤ 11.7 months, a lower maximum grade of immune-related adverse events, FEV1 < 2805 mL, and radiation dose < 62 Gy (P = 0.01, 0.01, 0.03, and 0.04, respectively). Conclusions: In patients with NSCLC receiving CCRT using IMRT, long PFS was associated with a better response to CCRT, stage IIIA NSCLC, and an increased radiation dose. The duration of durvalumab consolidation also played an essential role in the survival of patients receiving CCRT with IMRT. (250 words).

BACKGROUND: Hematomas that slowly increase in size for more than 1 month after the initial hemorrhage are referred to as chronic expanding hematomas. Chronic expanding hematoma can also occur after radiosurgery; however, there have been no reports about chronic expanding hematoma in the trunk after stereotactic body radiotherapy. We report a case of chronic expanding hematoma of the left erector spinae muscle after stereotactic body radiotherapy for renal cell carcinoma. CASE PRESENTATION: A 74-year-old Japanese male complained of back pain 7 years after stereotactic body radiotherapy for renal cell carcinoma of the left kidney. There was no history of surgery or trauma to his back. After stereotactic body radiotherapy, there was no acute or late complication of more than grade 2. The renal cell carcinoma did not show shrinkage or progression, and he was diagnosed with stable disease on computed tomography. The patient remains in a stable disease condition 7 years after treatment without surgery or chemotherapy; however, he came to the hospital with gradually worsening back pain for several months. Computed tomography revealed the left erector spinae muscle to be swollen compared with the contralateral side at the third lumbar level. Ultrasonography showed a tumor of 30 mm in size without blood flow in the left paraspinal muscle. Positron emission tomography-computed tomography revealed uptake in the left paraspinal muscle. Pathological examination showed radiation-induced chronic expanding hematoma. CONCLUSIONS: We present the first case report of chronic expanding hematoma of the left erector spinae muscle after stereotactic body radiotherapy for renal cell carcinoma. Usually, stereotactic body radiotherapy for renal cell carcinoma would be considered unlikely to cause chronic expanding hematoma, but the introduction of dialysis and antiplatelet drugs may have increased the risk.

This study evaluated accuracy of deformable image registration (DIR) with twelve parameter settings for thoracic images. We used peak-inhale and peak-exhale images for ten patients provided by DIR-lab. We used a prototype version of iCView software (ITEM Corporation) with DIR to perform intensity, structure, and hybrid-based DIR with the twelve parameter settings. DIR accuracy was evaluated by a target registration error (TRE) using 300 bronchial bifurcations and the Dice similarity coefficient (DSC) of the lungs. For twelve parameter settings, TRE ranged from 2.83 mm to 5.27 mm, whereas DSC ranged from 0.96 to 0.98. These results demonstrated that DIR accuracy differed among parameter settings and show that appropriate parameter settings are required for clinical practice.

The purpose of this study was to compare acute gastrointestinal (GI) toxicities in patients who underwent 3-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) in chemoradiotherapy (CRT) with S-1 including prophylactic regions for pancreatic cancer. We also investigated the predictive factor of acute GI toxicities in dose volume histogram (DVH) parameters. Patients who received CRT with S-1 for pancreatic cancer between January 2014 and March 2021 were included. Radiotherapy (RT) with a total dose of 50-54 Gy was delivered. We examined the differences in the frequencies of acute GI toxicity of grade 2 or higher and DVH parameters of the stomach (ST) and duodenum (DU) between the 3DCRT group and the IMRT group. The RT-related predictive factors of acute GI toxicities were investigated by univariate and multivariate analyses. There were 25 patients in the 3DCRT group and 31 patients in the IMRT group. The frequencies of acute GI toxicity of G2 or higher were 36% in the 3DCRT group and 9.7% in the IMRT group (p = 0.035). ST V50 was the most predictive factor (p = 0.001), and the incidences of acute GI toxicity of G2 or higher in ST V50 ≥ 4.1 cc and < 4.1cc were 43.7% and 7.7%, respectively. ST V40 was also a significant predictive factor of acute GI toxicity (p = 0.002). IMRT could reduce acute GI toxicities in CRT with S-1 including prophylactic regions for pancreatic cancer. Acute GI toxicities may be affected by moderate to high doses to the ST.

Purpose: A phase II study carried out to assess the efficacy of a risk-adapted strategy of stereotactic radiosurgery (SRS) for lung cancer. The primary endpoint was 3-year local recurrence, and the secondary endpoints were overall survival (OS), disease-free survival (DFS), rate of start of systemic therapy or best supportive care (SST-BSC), and toxicity. Materials and Methods: Eligible patients fulfilled the following criteria: performance status of 2 or less, forced expiratory volume in 1 s of 700 mL or more, and tumor not located in central or attached to the chest wall. Twenty-eight Gy was prescribed for primary lung cancers with diameters of 3 cm or less and 30 Gy was prescribed for primary lung cancers with diameters of 3.1–5.0 cm or solitary metastatic lung cancer diameters of 5 cm or less. Results: Twenty-one patients were analyzed. The patients included 7 patients with adenocarcinoma, 2 patients with squamous cell carcinoma, 1 patient with metastasis, and 11 patients with clinical diagnosis. The median tumor diameter was 1.9 cm. SRS was prescribed at 28 Gy for 18 tumors and 30 Gy for 3 tumors. During the median follow-up period of 38.9 months for survivors, 1 patient had local recurrence, 7 patients had regional or distant metastasis, and 5 patients died. The 3-year local recurrence, SST-BSC, DFS, and OS rates were 5.3% (95% confidence interval [CI]: 0.3–22.2%), 20.1% (95% CI: 6.0–40.2%), 59.2% (95% CI: 34.4–77.3%), and 78.2% (95% CI: 51.4–91.3%), respectively. The 95% CI upper value of local recurrence was lower than the null local recurrence probability. There was no severe toxicity, and grade 2 radiation pneumonitis occurred in 1 patient. Conclusions: Patients who received SRS for lung cancer had a low rate of 3-year local recurrence and tolerable toxicity.

PURPOSE: We aimed to assess radiomics approaches for estimating three pulmonary function test (PFT) results (forced expiratory volume in one second [FEV1], forced vital capacity [FVC], and the ratio of FEV1 to FVC [FEV1/FVC]) using data extracted from chest computed tomography (CT) images. METHODS: This retrospective study included 85 lung cancer patients (mean age, 75 years ±8; 69 men) who underwent stereotactic body radiotherapy between 2012 and 2020. Their pretreatment chest breath-hold CT and PFT data before radiotherapy were obtained. A total of 107 radiomics features (Shape: 14, Intensity: 18, Texture: 75) were extracted using two methods: extraction of the lung tissue (<-250 HU) (APPROACH 1), and extraction of small blood vessels and lung tissue (APPROACH 2). The PFT results were estimated using the least absolute shrinkage and selection operator regression. Pearson's correlation coefficients (r) were determined for all PFT results, and the area under the curve (AUC) was calculated for FEV1/FVC (<70 %). Finally, we compared our approaches with the conventional formula (Conventional). RESULTS: For the estimated FEV1/FVC, the Pearson's r were 0.21 (P =.06), 0.69 (P <.01), and 0.73 (P <.01) for Conventional, APPROACH 1, and APPROACH 2, respectively; the AUCs for FEV1/FVC (<70 %) were 0.67 (95 % confidence interval [CI]: 0.55, 0.79), 0.82 (CI: 0.72, 0.91; P =.047) and 0.86 (CI: 0.78, 0.94; P =.01), respectively. CONCLUSIONS: The radiomics approach performed better than the conventional equation and may be useful for assessing lung function based on CT images.

PURPOSE: To evaluate the benefit of concurrent chemotherapy with radiotherapy (RT) for esophageal cancer in Asian patients aged ≥ 80 years using the Surveillance, Epidemiology, and End Results (SEER) database. MATERIALS AND METHODS: Among more than 7000 patients with squamous cell carcinoma or adenocarcinoma who were treated by RT without surgery for esophageal cancer in the SEER database, 2047 patients aged ≥ 80 years were analyzed. Patients who received chemoradiotherapy (CRT group) and patients who received RT alone (RT alone group) were matched with a propensity score. RESULTS: The median observation period for survivors was 57 months. The 3-year and 5-year overall survival rates in all patients were 15.2% and 8.5%, respectively. The 3-year and 5-year cause-specific survival rates in all patients were 20.8% and 14.5%, respectively. After propensity score matching, the overall survival rate in the CRT group was significantly higher than that in the RT alone group (5-year overall survival rates: 11.9% and 3.2%, respectively, p < 0.001). In 108 Asian or Pacific Islander patients, there was no significant difference (5-year overall survival rates: 13.5% and 0%, respectively, p = 0.291), although the overall survival rate in the CRT group was significantly higher than that in the RT alone group in any other race. CONCLUSIONS: It is controversial whether CRT is beneficial for Asian or Pacific Islander patients aged 80 years or older with esophageal cancer based on Analysis of data in SEER database.

Radiation therapy (RT) is one of the definitive treatments for early-stage nasal vestibular carcinoma and has similar local control rates to resection surgery. There are various methods, including external beam RT and brachytherapy. This report describes a case who showed local control for more than 5 years after brachytherapy alone using Au-198 grains for nasal vestibular carcinoma. A 68-year-old Japanese man complained of swelling and pain in his left nasal cavity. He was diagnosed with squamous cell carcinoma (SCC) (cT1N0M0, stage I). An elevated mass of 8 mm in long diameter was found inside the left nasal cavity. Since the patient selected brachytherapy, nine Au-198 grains 185 mBq were permanently injected percutaneously under local anesthesia, and 85 Gy was prescribed. Grade three dermatitis was observed as an acute adverse event. After 2 years, mild telangiectasia of the left nasal skin and epilation of nasal hair in the left nasal cavity was regarded as late adverse events. The patient continues to keep a complete response for 5 years. For small nasal vestibular SCC, brachytherapy with Au-198 grains might be a good option.

The purpose of this study is to introduce differential dose-volume histogram (dDVH) features into machine learning for radiation pneumonitis (RP) prediction and to demonstrate the predictive performance of the developed model based on integrated cumulative dose-volume histogram (cDVH) and dDVH features. Materials and methods: cDVH and dDVH features were calculated for 153 patients treated for non-small-cell lung cancer with 60-66 Gy and dose bins ranging from 2 to 8 Gy in 2 Gy increments. RP prediction models were developed with the least absolute shrinkage and selection operator (LASSO) through fivefold cross-validation. Results: Among the 152 patients in the patient cohort, 41 presented ≥grade 2 RP. The interdependencies between cDVH features evaluated by Spearman's correlation were significantly resolved by the inclusion of dDVH features. The average area under curve for the RP prediction model using cDVH and dDVH model was 0.73, which was higher than the average area under curve using cDVH model for 0.62 with statistically significance (p &lt; 0.01). An analysis using the entire set of regression coefficients determined by LASSO demonstrated that dDVH features represented four of the top five frequently selected features in the model fitting, regardless of dose bin. Conclusions: We successfully developed an RP prediction model that integrated cDVH and dDVH features. The best RP prediction model was achieved using dDVH (dose bin = 4 Gy) features in the machine learning process.

PURPOSE: The purpose of the present study was to evaluate patterns of recurrence after salvage chemoradiotherapy (SCRT) for postoperative loco-regional recurrent esophageal cancer. METHODS: We reviewed records for 114 patients with postoperative loco-regional recurrent esophageal cancer treated by platinum-based chemoradiotherapy between 2000 and 2020, and we evaluated the patterns of failure in patients who had recurrence again or who had been observed for 2 years or more after SCRT at the last observation date. RESULTS: One hundred and three patients were enrolled in this study. The median observation period for survivors was 60 months. Fifty-three patients died of esophageal cancer and nine patients died of other diseases. The 5-year overall survival rate, cause-specific survival rate and disease-control rate were 43.7%, 45.3% and 37.0%, respectively. Sixty-five patients had failure after SCRT. In those patients, 26 patients had only distant organ or non-regional lymph node metastases, 26 patients had only loco-regional failure, and 13 patients had both. Of those 65 patients, 64 patients showed failure within 42 months after SCRT. Of 39 patients with loco-regional failure, failure in the irradiated field was observed in 28 patients. Of those 28 patients, 27 patients showed failure within 24 months and the other patient showed failure at 26.5 months. CONCLUSIONS: The patterns of failure after SCRT for patients with postoperative loco-regional recurrent esophageal cancer were shown. The patterns of failure suggest that follow-up for at least 4 years after SCRT should be performed for those patients.

BACKGROUND: Palliative radiotherapy for gastric cancer bleeding has been reported to be a safe and effective treatment, but predictive factors for achievement of hemostasis and overall survival have not been established. METHODS: In this retrospective study, 120 courses of palliative radiotherapy for gastric cancer bleeding in 117 patients in 4 institutes in Japan were reviewed with approval of the ethical committee in each institute. The rate of achieving hemostasis was evaluated by 50% or more reduction of red blood cell transfusion before and after the start of radiotherapy, elevation of blood hemoglobin concentration in a period of 4 weeks from the start of radiotherapy or improvement of subjective or objective clinical symptoms in a period of 4 weeks from the start of radiotherapy. Predictive factors for overall survival and achieving hemostasis were investigated with the Cox hazards model. RESULTS: The median overall survival period was 3.7 months. Multivariate analysis showed that absence of metastatic disease, higher biological effective dose, higher serum albumin level, lower blood urea nitrogen level and lower neutrophil-to-lymphocyte ratio (NLR) were associated with longer overall survival. Elevation of hemoglobin concentration in a period of 4 weeks from the start of radiotherapy (mean concentration: 8.2 g/dL vs. 8.9 g/dL, p = 0.006) and decrease in the amount of red cell transfusion from a 4-week period before to a 4-week period after the start of radiotherapy (mean amount: 716 mL vs. 230 mL, p < 0.0001) were observed. The overall rate of achievement of hemostasis was 59.6%. In multivariate analysis, higher biological effective dose was associated with achievement of hemostasis. Grade 2 or higher acute adverse effects related to radiotherapy were observed in 17.5% of cases in 120 treatment courses. Six cases (5.0%) had grade 3 or 4 adverse effects including gastric penetration in 1 patient and anorexia requiring total parental nutrition in 3 patients. No grade 5 adverse effects were observed. CONCLUSIONS: Palliative radiotherapy for gastric cancer bleeding seems to be an effective and safe treatment strategy. Higher treatment dose was associated with longer overall survival and a hemostatic effect. Some hematological parameters may predict overall survival, and they would be helpful for deciding the treatment strategy.

BACKGROUND: In clinical practice, the effect of durvalumab and radiation pneumonitis (RP) on survival after intensity-modulated radiotherapy (IMRT) is not fully understood. The purpose of this retrospective study was to investigate factors related to distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) after IMRT for locally advanced non-small cell lung cancer (LA-NSCLC). METHODS: All patients who were treated with conventional fractionated IMRT for LA-NSCLC between April 2016 and March 2021 were eligible. Time-to-event data were assessed by using the Kaplan-Meier estimator, and the Cox proportional hazards model was used for prognostic factor analyses. Factors that emerged after the start of IMRT, such as durvalumab administration or the development of RP, were analysed as time-dependent covariates. RESULTS: A total of 68 consecutive patients treated with conventional fractionated IMRT for LA-NSCLC were analysed. Sixty-six patients completed radiotherapy, 50 patients received concurrent chemotherapy, and 36 patients received adjuvant durvalumab. During the median follow-up period of 14.3 months, 23 patients died, and tumour progression occurred in 37 patients, including 28 patients with distant metastases. The 1-year DMFS rate, PFS rate and OS rate were 59.9%, 48.7% and 84.2%, respectively. Grade 2 RP occurred in 16 patients, grade 3 in 6 patients and grade 5 in 1 patient. The 1-year cumulative incidences of grade 2 or higher RP and grade 3 or higher RP were 33.8% and 10.3%, respectively. The results of multivariate analyses showed that durvalumab had a significantly lower hazard ratio (HR) for DMFS, PFS and OS (HR 0.31, p < 0.01; HR 0.33, p < 0.01 and HR 0.32, p = 0.02), respectively. Grade 2 or higher RP showed significance for DMFS and a nonsignificant trend for OS (HR 2.28, p = 0.04 and HR 2.12, p = 0.13), respectively, whereas a higher percentage of lung volume receiving 20 Gy or higher was significant for PFS (HR 2.25, p = 0.01). CONCLUSIONS: In clinical practice, durvalumab administration following IMRT with concomitant chemotherapy showed a significant survival benefit. Reducing the risk of grade 2 or higher RP would also be beneficial.

BACKGROUND: The abscopal effect is a phenomenon in which a tumor located far from irradiated lesions regresses. We have experienced a case in which both intracranial and extracranial lesions showed an abscopal effect after radiotherapy for spinal metastases of unknown primary. We report the differential abscopal effect in extracranial and intracranial lesions. CASE PRESENTATION: A 57-year-old Japanese man was diagnosed with multiple lung nodules, bone metastases, and brain metastases. The results of pathological examination at the previous hospital he visited suggested adenocarcinoma of the lung. However, there was a possibility that the biopsy specimen was inadequate. Radiation therapy was performed on the ninth thoracic vertebra for a total dose of 39 Gy in 13 fractions because the lesion in the ninth thoracic vertebra was destructively extending. After thorough examination, the primary lesion could not be identified, and we made diagnosis of cancer of unknown primary. The patient did not want to receive systemic chemotherapy; however, all of the lesions except for the brain metastases had spontaneously shrunk 2 months after radiation therapy. Although the brain metastases had partially shrunk, whole-brain radiotherapy for a total dose of 36 Gy in 12 fractions was performed. Fifteen months after initial radiation therapy, the brain metastasis recurred, and Gamma Knife radiosurgery was additionally performed. The brain metastases disappeared after the radiosurgery. During a period of 30 months after radiation therapy for the ninth vertebra, the lesions of the trunk all maintained their shrinkage without systemic chemotherapy. Right cervical lymph node metastasis and brain metastases occurred 30 months after the initial radiation therapy. A biopsy of the right cervical lymph node led to the diagnosis of clear cell carcinoma. Although we considered additional radiation therapy or chemotherapy, the patient died 3 months after the progression of recurrence lesions. DISCUSSION AND CONCLUSIONS: We report a rare case in which radiotherapy alone for an extracranial metastatic lesion of a vertebra resulted in an abscopal effect on both extracranial and intracranial lesions. Notably, the abscopal effect in the intracranial lesions was weaker than that in the extracranial lesions.

Patients with breast cancer who refuse standard treatment often suffer from malignant wounds due to the growth of local tumors. However, treatment strategies for patients with unresectable locally advanced breast cancer who refuse standard treatment remain unclear. Usually, such cases are treated with palliative irradiation and do not achieve local control by irradiation alone. This is the first case report discussing the role of high-dose local irradiation and the treatment course for a patient with a massive breast tumor (mucinous adenocarcinoma) who refused standard treatment. A 44-year-old female was diagnosed with mucinous carcinoma of the breast in the right breast (cT1N0M0, cStage I). She refused standard treatment for six years. She visited the emergency department because of acute bleeding from the right breast with malignant wounds. Macroscopically, the tumor in the right breast measured over 20 cm in diameter. The tumor was exudative, exhibited ulceration and slight bleeding, and emitted an odor. Imaging findings showed multiple lymph nodes and bone metastases, and the final diagnosis was stage IV breast cancer (cT4bN1M1). Although the surgeon recommended chemotherapy for breast cancer, the patient refused chemotherapy or other therapy due to concerns regarding treatment-related complications. Considering the symptoms of advanced breast cancer with malignant wounds, she finally agreed to receive radiation therapy (RT). We performed RT at 70 Gy in 35 fractions over seven weeks. The tumor-associated symptoms disappeared after RT. Three months after RT, the tumor had almost disappeared. We administered luteinizing hormone-releasing hormone agonists after RT. Two years after RT, she died due to multiple liver metastases and ascites; however, there was no disease progression in the right breast. High-dose RT for locally advanced mucinous carcinoma of the breast with malignant wounds is considered an effective therapeutic option.

Advanced squamous cell carcinoma (SCC) of the mandibular gingiva in elderly patients is difficult to cure. The treatment policy for elderly patients with advanced SCC of the mandibular gingiva has not been clear. We report a case of right mandibular gingival carcinoma that was successfully treated by palliative chemoradiotherapy. An 83-year-old female complained of pain and an ulcer in her right mandibular gingiva. Oral examination revealed a lesion of about 20 mm in size in the right mandibular gingiva. A diagnosis of SCC in the right mandibular gingiva was made by histology. Imaging findings revealed some right neck lymph node metastases. Based on these findings, a clinical diagnosis before treatment was SCC in the right mandibular gingiva (cT4aN2bM0, stage IV) by the 7th edition of the Union of International Cancer Control. She refused to receive definitive surgery or chemoradiotherapy due to concerns about the invasiveness of these definitive therapies and requested palliative chemoradiotherapy. We delivered S-1 (a combination of tegafur, gimeracil, and oteracil) and radiation therapy (RT) to the primary tumor alone with 30 Gy in 10 fractions using 4-megavoltage equipment via a multiple leaf collimator by three-dimensional RT. Although we could not complete the delivery of S-1 because of an acute side effect, the palliative chemoradiotherapy resulted in a complete response, and the lymph node metastases also disappeared. The patient remains in complete remission for 5 years without surgery or chemotherapy. Palliative chemoradiotherapy for elderly patients with mandibular gingival carcinoma is considered to be one of the therapeutic options.

<title>Abstract</title> In this article, we highlight the fundamental importance of the simultaneous use of dose-volume histogram (DVH) and dose-function histogram (DFH) features based on functional images calculated from 4-dimensional computed tomography (4D-CT) and deformable image registration (DIR) in developing a multivariate radiation pneumonitis (RP) prediction model. The patient characteristics, DVH features and DFH features were calculated from functional images by Hounsfield unit (HU) and Jacobian metrics, for an RP grade ≥ 2 multivariate prediction models were computed from 85 non-small cell lung cancer patients. The prediction model is developed using machine learning via a kernel-based support vector machine (SVM) machine. In the patient cohort, 21 of the 85 patients (24.7%) presented with RP grade ≥ 2. The median area under curve (AUC) was 0.58 for the generated 50 prediction models with patient clinical features and DVH features. When HU metric and Jacobian metric DFH features were added, the AUC improved to 0.73 and 0.68, respectively. We conclude that predictive RP models that incorporate DFH features were successfully developed via kernel-based SVM. These results demonstrate that effectiveness of the simultaneous use of DVH features and DFH features calculated from 4D-CT and DIR on functional image-guided radiotherapy.

Several types of SARS-CoV-2 vaccine have been developed. However, the relationship between SARS-CoV-2 vaccine and radiation therapy (RT) is unclear. Recently, there have been some reports of radiation recall phenomenon (RRP) caused by a SARS-CoV-2 vaccine. We report a case of RRP after administration of the mRNA-1273 SARS-CoV-2 vaccine. A 51-year-old female was diagnosed with breast cancer (cT4N1M0, cStage IIIB) and underwent breast total mastectomy with axillary lymph node dissection after neoadjuvant chemotherapy. After mastectomy, the patient received RT with 50 Gy in 25 fractions. An acute side effect of grade 2 dermatitis according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. occurred after RT. The patient had not started any new systemic medication after RT; however, the patient received the mRNA-1273 SARS-CoV-2 vaccine (Moderna) 1 month after the end of the initial RT. Seven days after vaccination, the patient had a skin reaction with burning sensation and redness. This skin reaction was induced in an area corresponding to the irradiation field of the chest wall. There was no skin reaction in areas other than that described. The reaction was cured within 1 week with topical hydrocortisone. This report is an interesting case report with a RPP after administration of the mRNA-1273 SARS-CoV-2 vaccine.

BACKGROUND AND PURPOSE: The purpose of this prospective study was to investigate changes in longitudinal parameters after stereotactic radiotherapy for lung cancer and to identify possible pretreatment factors related to radiation-induced lung toxicity and the decline in pulmonary function after radiotherapy. MATERIALS AND METHODS: Protocol-specified examinations, including 4-D CT, laboratory tests, pulmonary function tests (PFTs) and body composition measurements, were performed before SRT and at 1 month, 4 months and 12 months after stereotactic radiotherapy. Longitudinal differences were tested by using repeated-measures analysis of variance. Correlations were examined by using the Pearson product-moment correlation coefficient (r). RESULTS: Sixteen patients were analyzed in this study. During a median follow-up period of 26.6 months, grade 1 and 2 lung toxicity occurred in 11 patients and 1 patient, respectively. The mean Hounsfield units (HU) and standard deviation (SD) of the whole lung, as well as sialylated carbohydrate antigen KL-6 (KL-6) and surfactant protein-D (SP-D), peaked at 4 months after radiotherapy (p = 0.11, p<0.01, p = 0.04 and p<0.01, respectively). At 4 months, lung V20 Gy (%) and V40 Gy (%) were correlated with changes in SP-D, whereas changes in the mean HU of the lung were related to body mass index and lean body mass index (r = 0.54, p = 0.02; r = 0.57, p = 0.01; r = 0.69, p<0.01; and r = 0.69, p<0.01, respectively). The parameters of PFTs gradually declined over time. When regarding the change in PFTs from pretreatment to 12 months, lung V5 Gy (cc) showed significant correlations with diffusion capacity for carbon monoxide (DLCO), DLCO/alveolar volume and the relative change in DLCO (r = -0.72, p<0.01; r = -0.73, p<0.01; and r = -0.63, p = 0.01, respectively). CONCLUSIONS: The results indicated that some parameters peaked at 4 months, but PFTs were the lowest at 12 months. Significant correlations between lung V5 Gy (cc) and changes in DLCO and DLCO/alveolar volume were observed.

PURPOSE: Re-irradiation is a treatment option for recurrent esophageal cancer patients with a history of radiotherapy, but there is a risk of severe late adverse effects. This study focused on the efficacy and safety of re-irradiation using hyperfractionated radiotherapy. MATERIALS AND METHODS: Twenty-six patients who underwent re-irradiation by the hyperfraction technique using twice-daily irradiation of 1.2 Gy per fraction for recurrent esophageal cancer were retrospectively included in this study. The overall survival period after the start of secondary radiotherapy and the occurrence of late adverse effects were investigated. RESULTS: Of 26 patients, 21 (81%) received re-irradiation with definitive intention and 21 (81%) underwent concurrent chemotherapy. The median re-irradiation dose was 60 Gy in 50 fractions in 25 treatment days, and the median accumulated irradiation dose in equivalent dose in 2 Gy per fraction was 85.4 Gy with an α/β value of 3. The median interval between two courses of radiotherapy was 21.0 months. The median overall survival period was 15.8 months and the 1-year and 3-year overall survival rates were 64.3% and 28.3%, respectively. Higher dose of re-irradiation and concurrent chemotherapy significantly improved survival (p < 0.001 and p = 0.019, respectively). Severe late adverse effects with the Common Terminology Criteria for Adverse Events grade 3 or higher were observed in 5 (19.2%) patients, and 2 (7.7%) of them developed a grade 5 late adverse effect. CONCLUSION: High-dose re-irradiation using a hyperfractionated schedule with concurrent chemotherapy might be related to good prognosis, while the rate of late severe adverse effects is not high compared with the rates in past reports.

BACKGROUND: Desmoid-type fibromatosis is a rare disease that can result in hydronephrosis. Hydronephrosis associated with desmoid-type fibromatosis often requires surgery or ureteral stent insertion. Although radiation therapy is recommended for inoperable cases of desmoid-type fibromatosis, there has been no report of treatment for hydronephrosis associated with desmoid-type fibromatosis by radiation therapy alone. We herein report a case of successful treatment for inoperable recurrence of desmoid-type fibromatosis with unilateral hydronephrosis by radiation therapy alone. CASE PRESENTATION: A 43-year-old Japanese female underwent resection of desmoid-type fibromatosis in the right inguinal region and combined resection of the right external iliac vein 5 years before. Other treatment was not performed because of her pregnancy. Four years after surgery, desmoid-type fibromatosis recurred in the right pelvic wall. Cyclooxygenase-2 selective inhibitor treatment was given for 1 year, but her desmoid-type fibromatosis enlarged to more than 10 cm, and she had swelling of her right leg and hydronephrosis of her right kidney. The patient received 50.4 Gy in 28 fractions of prophylactic irradiation using 10 MV X-ray and 9 Gy in five fractions of a sequential boost for the recurrent desmoid-type fibromatosis. Although there was temporary tumor progression at 1 month after radiation therapy, slow regression of the tumor was seen. At 5 years after radiation therapy, there was no disease progression or severe complications. CONCLUSION: We experienced successful treatment for an inoperable case of desmoid-type fibromatosis with hydronephrosis. Moderate-dose radiation therapy alone is an effective and feasible approach for the management of hydronephrosis associated with desmoid-type fibromatosis.

OBJECTIVE: Aging of populations has been rapidly increasing worldwide. The aim of this study was to identify prognostic factors of overall survival (OS) and progression-free survival (PFS) in patients aged 80 years or older who had esophageal cancer and received radiotherapy. METHODS: Patients aged 80 years or older who received radiotherapy between 2004 and 2015 were retrospectively reviewed. Pretreatment age, gender, performance status, Charlson comorbidity index score, tumor location, histology, clinical stage, results of blood tests and treatment methods were obtained to determine prognostic factors of OS and PFS. Survival curves were drawn using the Kaplan-Meier method and prognostic factors were analyzed using Cox's hazards model. RESULTS: Ninety-two patients were included. Thirty-five patients were treated with chemo-radiotherapy. The median follow-up period was 19.0 months. The 3-year OS and PFS rates were 44.7% and 28.4%, respectively. In multivariate analysis, clinical stage (hazard ratio [HR] 2.28, 95% confidence interval [CI] 1.40-3.73, p = 0.001) and the geriatric nutritional risk index (GNRI, HR 0.95, 95% CI 0.92-0.97, p < 0.001) were significant prognostic factors of OS. Clinical stage (HR 2.06, 95% CI 1.34-3.18, p = 0.001), tumor location (HR 2.04, 95% CI 1.39-3.01, p < 0.001) and GNRI (HR 0.96, 95% CI 0.94-0.99, p = 0.003) were significant prognostic factors of PFS. CONCLUSION: Clinical stage and GNRI were significant prognostic factors of OS and PFS. Tumor location was a significant prognostic factor of PFS. These prognostic factors might be useful for decision-making for elderly patients with esophageal cancer.

BACKGROUND: It is still controversial whether intensity-modulated radiotherapy has an obvious advantage over conventional radiotherapy. The purposes of this study were to evaluate prognostic factors in pre-treatment characteristics for nasopharyngeal carcinoma and to compare treatment outcomes in patients who received intensity-modulated radiotherapy and patients who received two-dimensional radiotherapy or three-dimensional radiotherapy. METHODS: We reviewed patients with nasopharyngeal carcinoma who received chemoradiotherapy in our hospital during the period from 2000 to 2017, and we excluded patients who had a history of surgery for nasopharyngeal carcinoma and those who had distant metastases before treatment. A total of 72 patients who were treated by radiotherapy with concurrent chemotherapy were enrolled. All of the patients were irradiated with a total dose of 58-70 Gy. Overall survival, locoregional control and progression-free survival rates were compared in the groups treated by intensity-modulated radiotherapy and two-dimensional/three-dimensional radiotherapy. Propensity score matching was performed to homogenize the two groups. RESULTS: The median follow-up period was 62.5 months. After propensity score matching, in patients treated with intensity-modulated radiotherapy, the 5-year rate of overall survival, locoregional control and progression-free survival were 73.5, 95.2 and 72.7%, respectively. In patients treated with two-dimensional/three-dimensional radiotherapy, the 5-year rate of overall survival, locoregional control and progression-free survival were 69.1, 67.7 and 51.8%, respectively. There was a significant difference between the groups only in locoregional control. Late toxicities of grade 2 or higher were occurred in 38.5 and 24.2% of the patients treated by two-dimensional/three-dimensional radiotherapy and intensity-modulated radiotherapy, respectively. CONCLUSIONS: Our results suggested that intensity-modulated radiotherapy is more effective than two-dimensional/three-dimensional radiotherapy in patients with nasopharyngeal carcinoma, especially in locoregional control.

BACKGROUND AND PURPOSE: Intensity-modulated radiation therapy (IMRT) is increasingly applied in concurrent chemoradiotherapy (CCRT) for locally-advanced non-small cell lung cancer (NSCLC), with improvement of target coverage and better sparing of normal tissue. IMRT tends to have a larger low-dose irradiation volume than 3D conformal radiotherapy, but the incidence of and risk factors for pneumonitis remain unclear, especially following the approval of durvalumab. MATERIALS AND METHODS: We retrospectively reviewed the records of NSCLC patients treated by CCRT using IMRT at seven Japanese institutions. Primary outcomes were incidence of symptomatic pneumonitis and progression-free survival (PFS). Multivariate logistic regression analysis was used to identify risk factors for ≥grade 2 pneumonitis. RESULTS: Median follow-up from the start of CCRT was 14.3 months (n = 107 patients; median age 70 years, 29% female). Median lung V5 and V20 was 49.2% and 19.5%, respectively. Durvalumab was administered to 87 patients (81%). Pneumonitis developed in 95 (89%) patients of which 53% had grade 1, 28% grade 2, 6.5% grade 3, and 0.9% grade 4. Durvalumab had been discontinued in 16 patients (18.4%) due to pneumonitis. By multivariate analysis, age ≥70 years, male sex, and V5 ≥58.9% were identified as significantly associated with ≥grade 2 pneumonitis (p = 0.0065, 0.036 and 0.0013 respectively). The median PFS from the start of CCRT was not reached (95% CI, 14.2 months to not reached) in patients receiving durvalumab. CONCLUSION: CCRT using IMRT followed by durvalumab was generally effective and tolerable; V5 <60% would be recommended to avoid symptomatic pneumonitis.

PURPOSE: To evaluate the differences in patterns of recurrence and treatment results by histology after definitive radiotherapy for stage III non-small cell lung cancer (NSCLC) in Japan. MATERIALS AND METHODS: Patients with stage III NSCLC who underwent definitive radiotherapy between 2000 and 2016 in our institution were included. A total of 217 patients were enrolled. Propensity score matching was used to exclude the following confounding factors: (1) age (≥70 years or <70 years), (2) gender, (3) T factor, (4) N factor, (5) Eastern Cooperative Oncology Group performance status score and (6) smoking status (Brinkman index ≥400 or <400). RESULTS: The median observation period for survivors was 55.1 months. After propensity score matching, the Sqcc and adenocarcinoma groups each included 62 paired patients. There was no significant difference in OS or PFS between the adenocarcinoma and Sqcc groups. However, rates of recurrence in the GTV-primary site (p = 0.009) and GTV-lymph node site (p = 0.037) were significantly higher in patients with Sqcc than in patients with adenocarcinoma. New metastatic recurrence was more frequent in patients with adenocarcinoma than in patients with Sqcc (p = 0.025). CONCLUSION: There were significant differences in patterns of recurrence after definitive (chemo)radiotherapy between patients with Sqcc and patients with adenocarcinoma.

BACKGROUND: Radiomics is a new technology to noninvasively predict survival prognosis with quantitative features extracted from medical images. Most radiomics-based prognostic studies of non-small-cell lung cancer (NSCLC) patients have used mixed datasets of different subgroups. Therefore, we investigated the radiomics-based survival prediction of NSCLC patients by focusing on subgroups with identical characteristics. METHODS: A total of 304 NSCLC (Stages I-IV) patients treated with radiotherapy in our hospital were used. We extracted 107 radiomic features (i.e., 14 shape features, 18 first-order statistical features, and 75 texture features) from the gross tumor volume drawn on the free breathing planning computed tomography image. Three feature selection methods [i.e., test-retest and multiple segmentation (FS1), Pearson's correlation analysis (FS2), and a method that combined FS1 and FS2 (FS3)] were used to clarify how they affect survival prediction performance. Subgroup analysis for each histological subtype and each T stage applied the best selection method for the analysis of All data. We used a least absolute shrinkage and selection operator Cox regression model for all analyses and evaluated prognostic performance using the concordance-index (C-index) and the Kaplan-Meier method. For subgroup analysis, fivefold cross-validation was applied to ensure model reliability. RESULTS: In the analysis of All data, the C-index for the test dataset is 0.62 (FS1), 0.63 (FS2), and 0.62 (FS3). The subgroup analysis indicated that the prediction model based on specific histological subtypes and T stages had a higher C-index for the test dataset than that based on All data (All data, 0.64 vs. SCCall, 060; ADCall, 0.69; T1, 0.68; T2, 0.65; T3, 0.66; T4, 0.70). In addition, the prediction models unified for each T stage in histological subtype showed a different trend in the C-index for the test dataset between ADC-related and SCC-related models (ADCT1-ADCT4, 0.72-0.83; SCCT1-SCCT4, 0.58-0.71). CONCLUSIONS: Our results showed that feature selection methods moderately affected the survival prediction performance. In addition, prediction models based on specific subgroups may improve the prediction performance. These results may prove useful for determining the optimal radiomics-based predication model.

<title>Abstract</title> The purpose of this retrospective study was to investigate survival outcomes and irradiated tumor control (local control [LC]) and locoregional control (LRC) after stereotactic body radiotherapy (SBRT) for T1 or recurrent T1 (rT1) kidney cancer. Twenty-nine nonconsecutive patients with 30 tumors were included. SBRT doses of 70 Gy, 60 Gy or 50 Gy in 10 fractions were prescribed with a linear accelerator using daily image guidance. The Kaplan–Meier method was used to estimate time-to-event outcomes, and the log-rank test was used to compare survival curves between groups divided by each possible factor. The median follow-up periods for all patients and survivors were 57 months and 69.6 months, respectively. The five-year LC rate, LRC rate, progression-free survival (PFS) rate, disease-specific survival (DSS) rate and overall survival (OS) rate were 94%, 88%, 50%, 96% and 68%, respectively. No significant factor was related to OS and PFS. Three of 24 non-hemodialysis (HD) patients had new-onset-HD because of the progression of underlying kidney disease. Grade 3 or higher toxicities from SBRT did not occur. In conclusion, SBRT for kidney cancer provided a high rate of LC, LRC and DSS with minimal toxicities, but patient selection and indication for SBRT should be done carefully considering the relatively low OS rate.

Background: Xerostomia is one of the most common adverse events of radiotherapy in head and neck cancer patients. There have been many reports on functional changes of the parotid gland after radiation therapy, but there have been few reports on the volume of the parotid gland and its relationship with oral quality of life (QOL) and even fewer reports on longitudinal change of the parotid gland volume. The purpose of this study was to evaluate the long-term change of the parotid gland volume after intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma and the relationship between parotid irradiation dose and xerostomia symptoms. Methods: We retrospectively analyzed 26 patients with nasopharyngeal cancer treated by IMRT. Longitudinal changes of parotid gland volumes after IMRT were evaluated on CT images. The parotid gland volumes in each period were converted to the ratio to parotid gland volumes before radiotherapy (relative parotid volume). Dunnett's test was used to evaluate the longitudinal changes in relative parotid volumes at 0-6, 7-18, 19-30, 31-42, 43-54 and 55-66 months after IMRT. We assessed xerostomia 3 years or more after IMRT by measuring the degree of oral moisture using a moisture-checking device (Mucus, Life Co., Ltd.) and oral QOL evaluation by GOHAI (General Oral Health Assessment Index). Results: The relative parotid volumes during radiotherapy and at 0-6, 7-18, 19-30, 31-42, 43-54 and 55-66 months after IMRT were 75.2 ± 14.3%, 67.2 ± 11.4%, 68.5 ± 15.9%, 72.4 ± 14.8%, 73.0 ± 13.8%, 76.2 ± 17.5%, and 77.1% ± 17.3%, respectively. The parotid volume had recovered significantly at 43-54 and 55-66 months after IMRT, especially in parotids receiving less than 40 Gy as the mean dose. The mean irradiated dose for bilateral parotids showed negative correlations with oral QOL score and oral moisture after a long period. Conclusions: The parotid volume recovered gradually but had not reached a plateau even 3 years after radiotherapy, especially in parotids receiving less than 40 Gy as the mean dose.

We compared predictive performance between dose volume histogram (DVH) parameter addition and deformable image registration (DIR) addition for gastrointestinal (GI) toxicity in cervical cancer patients. A total of 59 patients receiving brachytherapy and external beam radiotherapy were analyzed retrospectively. The accumulative dose was calculated by three methods: conventional DVH parameter addition, full DIR addition and partial DIR addition. ${D}_{2{cm}^3}$, ${D}_{1{cm}^3}$ and ${D}_{0.1{cm}^3}$ (minimum doses to the most exposed 2 cm3, 1cm3 and 0.1 cm3 of tissue, respectively) of the rectum and sigmoid were calculated by each method. V50, V60 and V70 Gy (volume irradiated over 50, 60 and 70 Gy, respectively) were calculated in full DIR addition. The DVH parameters were compared between toxicity (≥grade1) and non-toxicity groups. The area under the curve (AUC) of the receiver operating characteristic (ROC) curves were compared to evaluate the predictive performance of each method. The differences between toxicity and non-toxicity groups in ${D}_{2{cm}^3}$ were 0.2, 5.7 and 3.1 Gy for the DVH parameter addition, full DIR addition and partial DIR addition, respectively. The AUCs of ${D}_{2{cm}^3}$ were 0.51, 0.67 and 0.57 for DVH parameter addition, full DIR addition and partial DIR addition, respectively. In full DIR addition, the difference in dose between toxicity and non-toxicity was the largest and AUC was the highest. AUCs of V50, V60 and V70 Gy were 0.51, 0.63 and 0.62, respectively, and V60 and V70 were high values close to the value of ${D}_{2{cm}^3}$ of the full DIR addition. Our results suggested that the full DIR addition may have the potential to predict toxicity more accurately than the conventional DVH parameter addition, and that it could be more effective to accumulate to all pelvic irradiation by DIR.

We quantified intra-fractional dose variation and organ movement during CT-based 3D-image guided brachytherapy (3D-IGBT) in cervical cancer patients. Fifteen patients who underwent CT-based 3D-IGBT were studied. For all patients, pre-delivery CT for treatment planning after applicator insertion and post-delivery CT after dose delivery without changing the applicator position were acquired. Pre- and post-delivery CT were rigidly fused by matching the inserted applicator and planned dose on pre-delivery CT (pre-delivery dose) was mapped on post-delivery CT (post-delivery dose). D2, D1, and D0.1 cm3 of the rectum and bladder were compared between pre- and post-delivery doses with contours on each CT image. Organ movement and deformation was evaluated using deformation vector fields calculated by deformable image registration between pre- and post-delivery CT. We also evaluated dose variation and DVF between with and without a catheter to control filling. Differences in all DVH parameters were <±3% in physical dose and ± 5% in EQD2. However, a > 15% dose difference was found in 13.8% of the fractions in rectum D2 cm3 and in 11.1% of those in bladder D2 cm3. The mean value of DVF for bladder was larger than that of rectum, especially for the superior-inferior (S-I) direction. Insertion catheters in bladder reduced mean dose and DVF variation compared with that of without catheters. In fraction groups with large dose increasing, DVF in the S-I direction was significantly larger than that of other fraction groups. Our results indicated that preparation is needed to reduce changes in the S-I direction affect dose variation.

PURPOSE: Radiomics is a new technique that enables noninvasive prognostic prediction by extracting features from medical images. Homology is a concept used in many branches of algebra and topology that can quantify the contact degree. In the present study, we developed homology-based radiomic features to predict the prognosis of non-small-cell lung cancer (NSCLC) patients and then evaluated the accuracy of this prediction method. METHODS: Four data sets were used: two to provide training and test data and two for the selection of robust radiomic features. All the data sets were downloaded from The Cancer Imaging Archive (TCIA). In two-dimensional cases, the Betti numbers consist of two values: b0 (zero-dimensional Betti number), which is the number of isolated components, and b1 (one-dimensional Betti number), which is the number of one-dimensional or "circular" holes. For homology-based evaluation, CT images must be converted to binarized images in which each pixel has two possible values: 0 or 1. All CT slices of the gross tumor volume were used for calculating the homology histogram. First, by changing the threshold of the CT value (range: -150 to 300 HU) for all its slices, we developed homology-based histograms for b0 , b1 , and b1 /b0 using binarized images All histograms were then summed, and the summed histogram was normalized by the number of slices. 144 homology-based radiomic features were defined from the histogram. To compare the standard radiomic features, 107 radiomic features were calculated using the standard radiomics technique. To clarify the prognostic power, the relationship between the values of the homology-based radiomic features and overall survival was evaluated using LASSO Cox regression model and the Kaplan-Meier method. The retained features with non-zero coefficients calculated by the LASSO Cox regression model were used for fitting the regression model. Moreover, these features were then integrated into a radiomics signature. An individualized rad score was calculated from a linear combination of the selected features, which were weighted by their respective coefficients. RESULTS: When the patients in the training and test data sets were stratified into high-risk and low-risk groups according to the rad scores, the overall survival of the groups was significantly different. The C-index values for the homology-based features (rad score), standard features (rad score), and tumor size were 0.625, 0.603, and 0.607, respectively, for the training data sets and 0.689, 0.668, and 0.667 for the test data sets. This result showed that homology-based radiomic features had slightly higher prediction power than the standard radiomic features. CONCLUSIONS: Prediction performance using homology-based radiomic features had a comparable or slightly higher prediction power than standard radiomic features. These findings suggest that homology-based radiomic features may have great potential for improving the prognostic prediction accuracy of CT-based radiomics. In this result, it is noteworthy that there are some limitations.

AIM: This study was performed to confirm the superior overall survival (OS) after pulmonary oligo-recurrence compared to pulmonary sync-oligometastases in a large nationwide study. PATIENTS AND METHODS: Patients that met the following criteria were included: 1 to 5 lung-only metastases at the beginning of stereotactic body radiation therapy (SBRT) was performed between January 2004 and June 2015, and the biological effective dose (BED) of SBRT was 75 Gy or more. The parameters included in the analyses were age, gender, ECOG PS, primary lesion, pathology, oligoetastatic state, SBRT date, chemotherapy before SBRT, chemotherapy concurrent SBRT, chemotherapy after SBRT, maximum tumor diameter, number of metastases, field coplanarity, dose prescription, BED10, OTT of SBRT. RESULTS: In total, 1,378 patients with 1,547 tumors were enrolled. Oligo-recurrence occurred in 1,016 patients, sync-oligometastases in 118, and unclassified oligometastases in 121. The three-year OS was 64.0% for oligo-recurrence and 47.5% for sync-oligometastasis (p<0.001). In the multivariate analysis, the hazard ratio (HR) for sync-oligometastases versus oligo-recurrence was 1.601 (p=0.014). Adverse events of Grade 5 were occurred in 3 patients. CONCLUSION: This is the first nationwide to indicate that the OS of patients with pulmonary oligo-recurrence is better than that of patients with sync-oligometastases.

BACKGROUND: In Japan, positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) has been covered by the national health insurance for esophageal cancer since 2006. FDG-PET is commonly performed in advanced esophageal cancer. The aim of this study was to determine the effect of FDG-PET on survival in patients with locally advanced inoperable esophageal cancer. METHODS: We retrospectively reviewed all patients with cT4 and without M1 esophageal cancer on CT in our institution between 2000 and 2014, and data for 78 patients who meet the eligibility criteria described below were used for analysis in this study. The eligibility criteria included (1) cT4 esophageal cancer without distant metastases or M1 lymph node metastasis (UICC 2002), (2) histologically proven squamous cell carcinoma, (3) 20-79 years of age, (4) having undergone at least 1 cycle of concomitant chemotherapy, (5) having been irradiated with 50 Gy or more, and (6) no other active malignant tumor during treatment. RESULTS: Two patients were excluded because abdominal lymph node metastases or neck lymph node metastases were detected by FDG-PET. In 78 eligible patients, FDG-PET was not performed before treatment in 41 of the 78 patients and was performed in the other patients. The median observation period was 68 months. The 3-year and 5-year overall survival rates in 78 patients were 36.9% and 30.8%, respectively. There was no significant difference in overall survival or progression-free survival between patients in whom FDG-PET was performed and those in whom FDG-PET was not performed (12.0 months vs. 11.0 months, p = 0.920 and 6.0 months vs. 6.0 months, p = 0.844, respectively). CONCLUSIONS: Compared with only CT, additional information from FDG-PET is not associated with improving survival in patients with locally advanced esophageal cancer. Our results suggest that FDG-PET might not have much meaning for survival in locally advanced esophageal cancer.

頭頸部メルケル細胞癌(MCC)に対して、緩和照射を除く放射線治療施行症例10例をデータベースから抽出した。新鮮例9例、局所再発に対する術後照射1例であった。全患者の観察期間中央値は49.8ヵ月、最終観察時点にて生存6例、死亡4例で、原病死は1例であった。再発転移は4例に認め、領域リンパ節のみの再発2例、遠隔転移1例、局所の遺残および領域リンパ節の同時再発1例であった。生存期間中央値は84.1ヵ月で、3年全生存率は67.5%であった。無再発生存期間中央値は18.6ヵ月で、3年無再発生存率は46.6%であった。領域リンパ節への照射の有無によって無再発生存率を比較すると、有意では無いものの、領域リンパ節照射群では良好な結果であった。領域リンパ節照射群のイベントは遠隔転移の1例のみであった。晩期有害事象としては、放射線角膜症Grade 2を照射後3年で1例に認めた。その他、口腔内乾燥Grade 2が1例、Grade 1が1例、Grade不明の患側眼瞼下垂を1例に認めた。