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.

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.

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.

Assessment of the deep learning-based gamma passing rate prediction system for 1.5 T magnetic resonance-guided linear accelerator.

Measurement-based verification is impossible for the patient-specific quality assurance (QA) of online adaptive magnetic resonance imaging-guided radiotherapy (oMRgRT) because the patient remains on the couch throughout the session. We assessed a deep learning (DL) system for oMRgRT to predict the gamma passing rate (GPR). This study collected 125 verification plans [reference plan (RP), 100; adapted plan (AP), 25] from patients with prostate cancer treated using Elekta Unity. Based on our previous study, we employed a convolutional neural network that predicted the GPRs of nine pairs of gamma criteria from 1%/1 mm to 3%/3 mm. First, we trained and tested the DL model using RPs (n = 75 and n = 25 for training and testing, respectively) for its optimization. Second, we tested the GPR prediction accuracy using APs to determine whether the DL model could be applied to APs. The mean absolute error (MAE) and correlation coefficient (r) of the RPs were 1.22 ± 0.27% and 0.29 ± 0.10 in 3%/2 mm, 1.35 ± 0.16% and 0.37 ± 0.15 in 2%/2 mm, and 3.62 ± 0.55% and 0.32 ± 0.14 in 1%/1 mm, respectively. The MAE and r of the APs were 1.13 ± 0.33% and 0.35 ± 0.22 in 3%/2 mm, 1.68 ± 0.47% and 0.30 ± 0.11 in 2%/2 mm, and 5.08 ± 0.29% and 0.15 ± 0.10 in 1%/1 mm, respectively. The time cost was within 3 s for the prediction. The results suggest the DL-based model has the potential for rapid GPR prediction in Elekta Unity.

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.

Nicaraven attenuates the acquired radioresistance of established tumors in mouse models via PARP inhibition.

Nicaraven has been reported to inhibit the activity of poly (ADP-ribose) polymerase (PARP). In this study, we investigated the probable ability of nicaraven to attenuate cancer radioresistance during fractionated radiotherapy. Tumor models were established in C57BL/6 mice and BALB/c nude mice by subcutaneous injection of Lewis mouse lung carcinoma cancer cells and A549 human lung cancer cells, respectively. When the tumors had grown to approximately 100 mm3, we initiated fractionated radiotherapy. Nicaraven or saline was administered immediately after each irradiation exposure. Compared to saline treatment, nicaraven administration significantly induced gamma-H2AX foci formation and cell apoptosis in tumors at 1 or 3 days after an additional challenge exposure to 10 Gy and inhibited tumor growth during the short-term follow-up period, suggesting increased radiosensitivity of cancer cells. Moreover, the expression of PARP in tumor tissue was decreased by nicaraven administration. Our data suggest that nicaraven likely attenuates the acquired radioresistance of cancers through PARP inhibition.

A Retrospective Study of Clinical Outcomes for Patients with Esophageal Cancer Who Were Treated with Radiotherapy Alone.

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.

Survival prediction nomogram for patients with vertebral bone metastases treated with palliative radiotherapy.

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.