College of American Pathologists Tumor Regression Grading System for Long-Term Outcome in Patients with Locally Advanced Rectal Cancer

BackgroundThe National Comprehensive Cancer Network''s Rectal Cancer Guideline Panel recommends American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) system to evaluate pathologic response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC). Yet, the clinical significance of the AJCC/CAP TRG system has not been fully defined.Materials and MethodsThis was a multicenter, retrospectively recruited, and prospectively maintained cohort study. Patients with LARC from one institution formed the discovery set, and cases from external independent institutions formed a validation set to verify the findings from discovery set. Overall survival (OS), disease‐free survival (DFS), local recurrence‐free survival (LRFS), and distant metastasis‐free survival (DMFS) were assessed by Kaplan‐Meier analysis, log‐rank test, and Cox regression model.ResultsThe discovery set (940 cases) found, and the validation set (2,156 cases) further confirmed, that inferior AJCC/CAP TRG categories were closely /ccorrelated with unfavorable survival (OS, DFS, LRFS, and DMFS) and higher risk of disease progression (death, accumulative relapse, local recurrence, and distant metastasis) (all p < .05). Significantly, pairwise comparison revealed that any two of four TRG categories had the distinguished survival and risk of disease progression. After propensity score matching, AJCC/CAP TRG0 category (pathological complete response) patients treated with or without adjuvant chemotherapy displayed similar survival of OS, DFS, LRFS, and DMFS (all p > .05). For AJCC/CAP TRG1–3 cases, adjuvant chemotherapy treatment significantly improved 3‐year OS (90.2% vs. 84.6%, p < .001). Multivariate analysis demonstrated the AJCC/CAP TRG system was an independent prognostic surrogate.ConclusionAJCC/CAP TRG system, an accurate prognostic surrogate, appears ideal for further strategizing adjuvant chemotherapy for LARC.Implications for PracticeThe National Comprehensive Cancer Network recommends the American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) four‐category system to evaluate the pathologic response to neoadjuvant treatment for patients with locally advanced rectal cancer; however, the clinical significance of the AJCC/CAP TRG system has not yet been clearly addressed. This study found, for the first time, that any two of four AJCC/CAP TRG categories had the distinguished long‐term survival outcome. Importantly, adjuvant chemotherapy may improve the 3‐year overall survival for AJCC/CAP TRG1–3 category patients but not for AJCC/CAP TRG0 category patients. Thus, AJCC/CAP TRG system, an accurate surrogate of long‐term survival outcome, is useful in guiding adjuvant chemotherapy management for rectal cancer.     

Semi-supervised medical image segmentation via a tripled-uncertainty guided mean teacher model with contrastive learning

Due to the difficulty in accessing a large amount of labeled data, semi-supervised learning is becoming an attractive solution in medical image segmentation. To make use of unlabeled data, current popular semi-supervised methods (e.g., temporal ensembling, mean teacher) mainly impose data-level and model-level consistency on unlabeled data. In this paper, we argue that in addition to these strategies, we could further utilize auxiliary tasks and consider task-level consistency to better excavate effective representations from unlabeled data for segmentation. Specifically, we introduce two auxiliary tasks, i.e., a foreground and background reconstruction task for capturing semantic information and a signed distance field (SDF) prediction task for imposing shape constraint, and explore the mutual promotion effect between the two auxiliary and the segmentation tasks based on mean teacher architecture. Moreover, to handle the potential bias of the teacher model caused by annotation scarcity, we develop a tripled-uncertainty guided framework to encourage the three tasks in the student model to learn more reliable knowledge from the teacher. When calculating uncertainty, we propose an uncertainty weighted integration (UWI) strategy for yielding the segmentation predictions of the teacher. In addition, following the advance of unsupervised learning in leveraging the unlabeled data, we also incorporate a contrastive learning based constraint to help the encoders extract more distinct representations to promote the medical image segmentation performance. Extensive experiments on the public 2017 ACDC dataset and the PROMISE12 dataset have demonstrated the effectiveness of our method.     

Impact of Duration of Diagnostic Workup on Prognosis for Early Lung Cancer

IntroductionGrowth assessment for pulmonary nodules is an important diagnostic tool; however, the impact on prognosis due to time delay for follow-up diagnostic scans needs to be considered.MethodsUsing the data between 2003 and 2019 from the International Early Lung Cancer Action Program, a prospective cohort study, we determined the size-specific, 10-year Kaplan-Meier lung cancer (LC) survival rates as surrogates for cure rates. We estimated the change in LC diameter after delays of 90, 180, and 365 days using three representative LC volume doubling times (VDTs) of 60 (fast), 120 (moderate), and 240 (slow). We then estimated the decrease in the LC cure rate resulting from time between computed tomography scans to assess for growth during the diagnostic workup.ResultsUsing a regression model of the 10-year LC survival rates on LC diameter, the estimated LC cure rate of a 4.0 mm LC with fast (60-d) VDT is 96.0% (95% confidence interval [CI]: 95.2%–96.7%) initially, but it would decrease to 94.3% (95% CI: 93.2%–95.0%), 92.0% (95% CI: 90.5%–93.4%), and 83.6%(95% CI: 80.6%–86.6%) after delays of 90, 180, and 365 days, respectively. A 20.0-mm LC with the same VDTs has a lower LC cure rate of 79.9% (95% CI: 76.2%–83.5%) initially and decreases more rapidly to 71.5% (95% CI: 66.4%–76.7%), 59.8% (95% CI: 52.4%–67.1%), and 17.9% (95% CI: 3.0%–32.8%) after the same delays of 90, 180, and 365 days, respectively.ConclusionsTime between scans required to measure growth of lung nodules affects prognosis with the effect being greater for fast growing and larger cancers. Quantifying the extent of change in prognosis is required to understand efficiencies of different management protocols.     

Current status on tissue factor activation of factor VIIa

Free factor VIIa displays a zymogen-like behavior with low intrinsic activity. Formation of a complex between factor VIIa and tissue factor is necessary to enhance the procoagulant activity of factor VIIa, not only by providing membrane localization, substrate exosites and positioning the active site at an appropriate distance above the surface but also by allosteric enhancement of the enzymatic activity, and this event signals initiation of blood coagulation. The interaction is of high affinity and all the domains are engaged at the interface. The crosstalk between the protease domain of factor VIIa, in particular residue Met-306, and the N-terminal domain of tissue factor provides the starting point for the allosteric activation of factor VIIa. The pathway(s) of conformational transitions in factor VIIa ensuing tissue factor binding has not been entirely mapped. The present paper is a brief compilation of our current knowledge of the allosteric mechanism by which tissue factor induces and stabilizes the active conformation of factor VIIa.     

MR加速器呼吸导航引导肝癌SBRT的初步临床应用研究

目的 初步探讨MR加速器呼吸导航引导肝癌立体定向体部放疗（SBRT）的流程、可行性及应用优势。方法 回顾分析2021年9—12月10例使用MR加速器接受呼吸导航引导,行SBRT的肝癌患者临床数据。所有患者均行CT模拟定位和Unity MR定位,采集平扫、增强和4D CT,及T₁ 3D、T₂ 3D MR影像。选择4D CT呼气末端图像设计参考计划,治疗前采集呼吸导航（呼气末端）T₂ Navigator MR图像,并结合实时监控2D MR影像调整或修改靶区位置和形状,选择合适的在线自适应计划流程。目测定位CT、T₂ 3D MR和T₂ 3D Navigator MR图像显示肿瘤的清晰度;统计靶区体积变化;比较自适应计划和参考计划的剂量学差异;评估患者疗效和不良反应。结果 在自由呼吸状态下,T₂ 3D Navigator MR图像质量明显优于常规T₂ 3D MR图像,可更清楚显示肿瘤及其边界。10例患者采用位置适应（ATP）和形状适应（ATS）自适应计划分别为37分次和22分次,3例患者肿瘤消退明显。自适应计划的靶区平均适形指数（CI）与参考计划无差异,但靶区外剂量跌落稍慢（P<0.05）,尤其是ATS计划较明显。ATP自适应计划的正常肝平均受量与参考计划基本一致,但平均机器跳数明显增加,且差异有统计学意义（P<0.05）。ATS自适应计划的平均机器跳数、平均子野数和正常肝D_mean和V_{10 Gy}比参考计划有所降低,V_{5 Gy}轻微增加,但均无显著差异。7例患者进行放疗后1个月和3个月疗效评价,野内病灶控制较好,放疗不良反应轻微,未见≥3级不良反应。结论 MR加速器的呼吸导航提高了自由呼吸状态下肿瘤和MR影像的目测清晰度,在肝脏肿瘤的精准自适应放疗特别是立体定向自适应放疗中展现了优势。