Development of deep learning-based novel auto-segmentation for the prostatic urethra on planning CT images for prostate cancer radiotherapy.

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.

Craniospinal irradiation for leptomeningeal metastasis of solid tumors: survival analysis and prognostic factors.

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.

Clinical significance of cerebral microbleeds in patients with germinoma who underwent long-term follow-up.

PURPOSE: This study identified the factors affecting cerebral microbleed (CMBs) development. Moreover, their effects on intelligence and memory and association with stroke in patients with germinoma who had long-term follow-up were evaluated. METHODS: This study included 64 patients with germinoma who were histologically and clinically diagnosed with and treated for germinoma. These patients were evaluated cross-sectionally, with a focus on CMBs on susceptibility-weighted magnetic resonance imaging (SWI), brain atrophy assessed through volumetric analysis, and intelligence and memory. RESULTS: The follow-up period was from 32 to 412 (median: 175.5) months. In total, 43 (67%) patients had 509 CMBs and 21 did not have CMBs. Moderate correlations were observed between the number of CMBs and time from initial treatments and recurrence was found to be a risk factor for CMB development. Increased temporal CMBs had a marginal effect on the processing speed and visual memory, whereas brain atrophy had a statistically significant effect on verbal, visual, and general memory and a marginal effect on processing speed. Before SWI acquisition and during the follow-up periods, eight strokes occurred in four patients. All of these patients had ≥ 15 CMBs on SWI before stroke onset. Meanwhile, 33 patients with < 14 CMBs or 21 patients without CMBs did not experience stroke. CONCLUSION: Patients with a longer time from treatment initiation had a higher number of CMBs, and recurrence was a significant risk factor for CMB development. Furthermore, brain atrophy had a stronger effect on memory than CMBs. Increased CMBs predict the stroke onset.

Impact of dose distribution by a 3D planning system for brachytherapy with 198Au grains for head and neck cancer.

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.

Lymphopenia after palliative radiotherapy for vertebral metastases.

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.

Beginning of clinical treatment using the 1.5 Tesla MR-Linac system in Japan: a narrative review.

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.

Glasgow prognostic score for assessing the efficacy of whole-brain radiation therapy in cases of recursive partitioning analysis class 2 and class 3 multiple brain metastases: a retrospective study.

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.

Current status of remote radiotherapy treatment planning in Japan: findings from a national survey†.

The purpose of this study was to investigate the status of remote-radiotherapy treatment planning (RRTP) in Japan through a nationwide questionnaire survey. The survey was conducted between 29 June and 4 August 2022, at 834 facilities in Japan that were equipped with linear accelerators. The survey utilized a Google form that comprised 96 questions on facility information, information about the respondent, utilization of RRTP between facilities, usage for telework and the inclination to implement RRTPs in the respondent's facility. The survey analyzed the utilization of the RRTP system in four distinct implementation types: (i) utilization as a supportive facility, (ii) utilization as a treatment facility, (iii) utilization as a teleworker outside of the facility and (iv) utilization as a teleworker within the facility. The survey response rate was 58.4% (487 facilities responded). Among the facilities that responded, 10% (51 facilities) were implementing RRTP. 13 served as supportive facilities, 23 as treatment facilities, 17 as teleworkers outside of the facility and 5 as teleworkers within the facility. In terms of system usage between supportive and treatment facilities, 70-80% of the participants utilized the system for emergencies or as overtime work for external workers. A substantial number of facilities (38.8%) reported that they were unfamiliar with RRTP implementation. The survey showed that RRTP utilization in Japan is still limited, with a significant number of facilities unfamiliar with the technology. The study highlights the need for greater understanding and education about RRTP and financial funds of economical compensation.

VMAT with DIBH in hypofractionated radiotherapy for left-sided breast cancer after breast-conserving surgery: results of a non-inferiority clinical study.

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.

Intractable Ventricular Tachycardia Prior to an Overt Cardiac Tumor Mass of Metastatic Cardiac Rhabdomyosarcoma (Spindle-cell Type).

We herein report a 37-year-old man who experienced recurrence of metastatic cardiac rhabdomyosarcoma along with intractable ventricular tachycardia (VT) 7 years after resection of rhabdomyosarcoma in his right elbow. At 36 years old, he developed VT unresponsive to radiofrequency catheter ablation (RFCA). Initially, the cardiac tumor was not detected, but it gradually grew in size at the RFCA site. A surgical biopsy confirmed the diagnosis of metastatic cardiac rhabdomyosarcoma. Despite radiation therapy, cardiac tumor progression and VT instability could not be prevented. Ultimately, the patient died 27 months after the initial documentation of VT.

The Impact of Pathological Grade Group 3 on Relapse-free Survival After Salvage Radiotherapy for Postoperative Prostate Cancer.

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.

Pre-treatment Evaluation of Patients Eligible for Whole Brain Radiation Therapy: The Risk of Hippocampal Metastases in a Retrospective Study of 248 Cases at a Single Institution.

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.

Acute hematologic toxicity of radiation therapy - a comprehensive analysis and predictive nomogram.

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.

Evaluation of deep learning-based deliverable VMAT plan generated by prototype software for automated planning for prostate cancer 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.

Development of a prediction model for head and neck volume reduction by clinical factors, dose-volume histogram parameters and radiomics in head and neck cancer†.

In external radiotherapy of head and neck (HN) cancers, the reduction of irradiation accuracy due to HN volume reduction often causes a problem. Adaptive radiotherapy (ART) can effectively solve this problem; however, its application to all cases is impractical because of cost and time. Therefore, finding priority cases is essential. This study aimed to predict patients with HN cancers are more likely to need ART based on a quantitative measure of large HN volume reduction and evaluate model accuracy. The study included 172 cases of patients with HN cancer who received external irradiation. The HN volume was calculated using cone-beam computed tomography (CT) for irradiation-guided radiotherapy for all treatment fractions and classified into two groups: cases with a large reduction in the HN volume and cases without a large reduction. Radiomic features were extracted from the primary gross tumor volume (GTV) and nodal GTV of the planning CT. To develop the prediction model, four feature selection methods and two machine-learning algorithms were tested. Predictive performance was evaluated by the area under the curve (AUC), accuracy, sensitivity and specificity. Predictive performance was the highest for the random forest, with an AUC of 0.662. Furthermore, its accuracy, sensitivity and specificity were 0.692, 0.700 and 0.813, respectively. Selected features included radiomic features of the primary GTV, human papillomavirus in oropharyngeal cancer and the implementation of chemotherapy; thus, these features might be related to HN volume change. Our model suggested the potential to predict ART requirements based on HN volume reduction .

Clinical impact of multimodal treatment including chemoradiotherapy, conversion surgery and postoperative chemotherapy for borderline resectable and unresectable locally advanced pancreatic cancer without disease progression after gemcitabine plus nab-paclitaxel.

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.

Recent Postoperative Radiotherapy for Left-sided Breast Cancer Does Not Increase Mortality of Heart Disease in Asians or Pacific Islanders: SEER Database Analysis.

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.

Clinical impact of radiation-induced myocardial damage detected by cardiac magnetic resonance imaging and dose-volume histogram parameters of the left ventricle as prognostic factors of cardiac events after chemoradiotherapy for esophageal cancer.

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.

Retrospective analysis of local recurrence pattern by computed tomography image-guided intracavitary and interstitial brachytherapy for locally advanced cervical cancer in a single Japanese institution.

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.

Definitive radiotherapy consisting of external beam radiotherapy without central shielding and 3D image-guided brachytherapy for patients with cervical cancer: feasibility for Japanese patients and dose-response analyses for local control in the low-dose range.

OBJECTIVE: To assess the feasibility of external beam radiotherapy without central shielding in definitive radiotherapy for Japanese patients with cervical cancer. METHODS: We retrospectively analysed the data of cervical cancer patients treated with definitive radiotherapy consisting of external beam radiotherapy without central shielding and three-dimensional-image-guided brachytherapy. RESULTS: The study included 167 patients (T1 + 2 = 108, T3 + 4 = 59) from eight Japanese institutions. For three-dimensional-image-guided brachytherapy, intra-cavitary and interstitial brachytherapy was utilized in 33 patients (20%). The median follow-up was 26.6 months (interquartile range, 20-43.2). The maximum rectal D2 (75 Gy)/bladder D2 (90 Gy) constraints were deviated by 6%/10% and 10%/5% for T1 + 2 and T3 + 4, respectively. The 2-year incidence of ≥grade 3 proctitis/cystitis was 4%/1% for T1 + 2 and 10%/2% for T3 + 4. The 2-year local progression-free survival was 89% for T1 + 2 and 82% for T3 + 4. For T1 + 2, the 2-year local progression-free survival for the high-risk clinical target volume D90 ≥ 68 Gy (indicated by receiver operating characteristic analysis; area under the curve = 0.711) was 92% versus 67% for <68 Gy (log-rank; P = 0.019). Cox multivariate analysis indicated that the high-risk clinical target volume D90 was one of independent predictors of local failure (P = 0.0006). For T3 + 4, the 2-year local progression-free survival was 87% for the high-risk clinical target volume <82 cm3 (area under the curve = 0.67) and 43% for ≥82 cm3 (P = 0.0004). Only the high-risk clinical target volume was an independent predictor of local failure (P = 0.0024). CONCLUSIONS: Definitive radiotherapy consisting of external beam radiotherapy without central shielding and three-dimensional-image-guided brachytherapy was feasible for Japanese patients with cervical cancer. Dose de-escalation from the current global standards is suggested for patients with T1 + 2 disease.