Development of RLK-Unet: a clinically favorable deep learning algorithm for brain metastasis detection and treatment response assessment.

Purpose/objectives: Previous deep learning (DL) algorithms for brain metastasis (BM) detection and segmentation have not been commonly used in clinics because they produce false-positive findings, require multiple sequences, and do not reflect physiological properties such as necrosis. The aim of this study was to develop a more clinically favorable DL algorithm (RLK-Unet) using a single sequence reflecting necrosis and apply it to automated treatment response assessment. Methods and materials: A total of 128 patients with 1339 BMs, who underwent BM magnetic resonance imaging using the contrast-enhanced 3D T1 weighted (T1WI) turbo spin-echo black blood sequence, were included in the development of the DL algorithm. Fifty-eight patients with 629 BMs were assessed for treatment response. The detection sensitivity, precision, Dice similarity coefficient (DSC), and agreement of treatment response assessments between neuroradiologists and RLK-Unet were assessed. Results: RLK-Unet demonstrated a sensitivity of 86.9% and a precision of 79.6% for BMs and had a DSC of 0.663. Segmentation performance was better in the subgroup with larger BMs (DSC, 0.843). The agreement in the response assessment for BMs between the radiologists and RLK-Unet was excellent (intraclass correlation, 0.84). Conclusion: RLK-Unet yielded accurate detection and segmentation of BM and could assist clinicians in treatment response assessment.

Optimal planning target margin for prostate radiotherapy based on interfractional and intrafractional variability assessment during 1.5T MRI-guided radiotherapy.

Introduction: We analyzed daily pre-treatment- (PRE) and real-time motion monitoring- (MM) MRI scans of patients receiving definitive prostate radiotherapy (RT) with 1.5 T MRI guidance to assess interfractional and intrafractional variability of the prostate and suggest optimal planning target volume (PTV) margin. Materials and methods: Rigid registration between PRE-MRI and planning CT images based on the pelvic bone and prostate anatomy were performed. Interfractional setup margin (SM) and interobserver variability (IO) were assessed by comparing the centroid values of prostate contours delineated on PRE-MRIs. MM-MRIs were used for internal margin (IM) assessment, and PTV margin was calculated using the van Herk formula. Results: We delineated 400 prostate contours on PRE-MRI images. SM was 0.57 ± 0.42, 2.45 ± 1.98, and 2.28 ± 2.08 mm in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions, respectively, after bone localization and 0.76 ± 0.57, 1.89 ± 1.60, and 2.02 ± 1.79 mm in the LR, AP, and SI directions, respectively, after prostate localization. IO was 1.06 ± 0.58, 2.32 ± 1.08, and 3.30 ± 1.85 mm in the LR, AP, and SI directions, respectively, after bone localization and 1.11 ± 0.55, 2.13 ± 1.07, and 3.53 ± 1.65 mm in the LR, AP, and SI directions, respectively, after prostate localization. Average IM was 2.12 ± 0.86, 2.24 ± 1.07, and 2.84 ± 0.88 mm in the LR, AP, and SI directions, respectively. Calculated PTV margin was 2.21, 5.16, and 5.40 mm in the LR, AP, and SI directions, respectively. Conclusions: Movements in the SI direction were the largest source of variability in definitive prostate RT, and interobserver variability was a non-negligible source of margin. The optimal PTV margin should also consider the internal margin.

Preclinical assessment and randomized Phase I study of CT-P63, a broadly neutralizing antibody targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in significant morbidity and mortality worldwide. Despite a successful vaccination programme, the emergence of mutated variants that can escape current levels of immunity mean infections continue. Herein, we report the development of CT-P63, a broad-spectrum neutralizing monoclonal antibody. In vitro studies demonstrated potent neutralizing activity against the most prevalent variants, including Delta and the BA.1 and BA.2 sub-lineages of Omicron. In a transgenic mouse model, prophylactic CT-P63 significantly reduced wild-type viral titres in the respiratory tract and CT-P63 treatment proved efficacious against infection with Beta, Delta, and Omicron variants of SARS-CoV-2 with no detectable infectious virus in the lungs of treated animals. A randomized, double-blind, parallel-group, placebo-controlled, Phase I, single ascending dose study in healthy volunteers (NCT05017168) confirmed the safety, tolerability, and pharmacokinetics of CT-P63. Twenty-four participants were randomized and received the planned dose of CT-P63 or placebo. The safety and tolerability of CT-P63 were evaluated as primary objectives. Eight participants (33.3%) experienced a treatment-emergent adverse event (TEAE), including one grade ≥3 (blood creatine phosphokinase increased). There were no deaths, treatment-emergent serious adverse events, TEAEs of special interest, or TEAEs leading to study drug discontinuation in the CT-P63 groups. Serum CT-P63 concentrations rapidly peaked before declining in a biphasic manner and systemic exposure was dose proportional. Overall, CT-P63 was clinically safe and showed broad-spectrum neutralizing activity against SARS-CoV-2 variants in vitro and in vivo.

Compact bunker shielding assessment for 1.5 T MR-Linac.

This study evaluated the effect of the 1.5 T magnetic field of the magnetic resonance-guided linear accelerator (MR-Linac) on the radiation leakage doses penetrating the bunker radiation shielding wall. The evaluated 1.5 T MR-Linac Unity system has a bunker of the minimum recommended size. Unlike a conventional Linac, both primary beam transmission and secondary beam leakage were considered independently in the design and defined at the machine boundary away from the isocenter. Moreover, additional shielding was designed considering the numerous ducts between the treatment room and other rooms. The Linac shielding was evaluated by measuring the leakage doses at several locations. The intrinsic vibration and magnetic field were inspected at the proposed isocenter of the system. For verification, leakage doses were measured before and after applying the magnetic field. The intrinsic vibration and magnetic field readings were below the permitted limit. The leakage dose (0.05-12.2 µSv/week) also complied with internationally stipulated limits. The special shielding achieved a five-fold reduction in leakage dose. Applying the magnetic field increased the leakage dose by 0.12 to 4.56 µSv/week in several measurement points, although these values fall within experimental uncertainty. Thus, the effect of the magnetic field on the leakage dose could not be ascertained.

Age and sex-related differences in risk factors for elderly suicide: Differentiating between suicide ideation and attempts.

OBJECTIVE: The purpose of this study was to analyze the age and sex-related differences in socio-demographic factors that influence suicide ideation and attempts in the elderly. METHODS: The total number of subjects was 93 151, of whom 8441 belonged to the high suicide-risk group (2064 male; 6377 female). Following this identification, we investigated their socio-demographic information, health status, and depressive symptoms, which might have influenced their suicide ideation and attempts. RESULTS: Residence in an urban area was identified as a risk factor for both male and female elderly in their 60s and 70s and female elderly in their 80s. Marital status showed a different influence on suicide ideation depending on age and sex. A negative perception of one's own health status was a significant risk factor that increased the likelihood of suicide ideation in all ages, except the female elderly in their 60s. No factor was identified that significantly influenced suicide attempts in the male elderly. However, in the female elderly, residence in an urban area and a negative perception of one's own health status were identified as significant risk factors. CONCLUSIONS: This study revealed that factors known to influence suicide ideation in the elderly from previous studies, such as residence area, separation from a spouse, education level, religion, and drinking, show changed influence as the elderly reach their 70s and 80s. However, a negative perception of one's own health status was a risk factor that encompassed most ages and sexes.