- 作者列表："Dobelbower MC","Popple RA","Minnich DJ","Nader DA","Zimmerman F","Paris GE","Herth FJF","Gompelmann D","Roeder FF","Parikh PJ","McDonald AM
PURPOSE:The Calypso Beacon transponder has been modified by the addition of a nitinol anchor feature to allow for positional stability when implanted bronchoscopically into the lung. The purpose of this study was to confirm the feasibility and safety of anchored transponder placement and feasibility of lung target localization and tracking. METHODS AND MATERIALS:This study enrolled patients with histologically confirmed cancer in the lung (primary or metastatic) who were scheduled to receive external beam radiation therapy. Three anchored transponders were implanted via flexible bronchoscopy into small (approximately 2- to 2.5-mm diameter) airways. Patient alignment at each radiation fraction was performed with the Calypso system, and anchored transponder position was tracked during radiation delivery. The primary endpoint was defined as the ability to localize at least 85% of the patients during the first week of treatment. Four follow-up visits were specified including a posttreatment assessment and every 3 months up to 1 year. RESULTS:A total of 69 patients underwent anchored transponder placement, and all 207 implanted anchored transponders were visible on the treatment-planning simulation computed tomography scan. Sixty-seven patients underwent radiation therapy, and localization was successful in 66 cases (98.5%). With 1 failure in 67 cases, the P value for rejecting the null hypothesis was <.001 and the primary objective of the study met. Five adverse events in 5 patients were potentially attributed to the study device or implantation procedure, consisting of pneumonia (2 cases), pleural abscess (1 case), and pneumothorax (2 cases). Two serious events (cardiac arrest and acute hypotension) were attributed to anesthesia during the implantation procedure. CONCLUSIONS:This study strongly supports that anchored transponders are safe, positionally stable, and useful for lung tumor localization and monitoring.
目的: 通过增加镍钛诺锚定功能对Calypso信标应答器进行了修改，以允许在支气管植入肺部时的位置稳定性。本研究的目的是证实锚定应答器放置的可行性和安全性以及肺目标定位和跟踪的可行性。 方法和材料: 本研究纳入了计划接受外照射放射治疗的组织学证实的肺癌 (原发性或转移性) 患者。通过柔性支气管镜将三个锚定的应答器植入小 (直径约 2 至 2.5mm) 气道中。使用Calypso系统在每个辐射分数下进行患者对准，并在辐射递送期间跟踪锚定应答器位置。主要终点定义为在治疗的第一周内定位至少 85% 的患者的能力。指定了 4 次随访，包括治疗后评估和每 3 个月至 1 年。 结果: 共有 69 例患者接受了锚定应答器放置，所有 207 个植入的锚定应答器在治疗计划模拟计算机断层扫描中可见。67 例患者行放射治疗，定位成功 66 例 (98.5%)。67 例中有 1 例失败，拒绝零假设的p值 <.001，并且符合研究的主要目标。5 例患者中的 5 例不良事件可能归因于研究装置或植入程序，包括肺炎 (2 例) 、胸膜脓肿 (1 例) 和气胸 (2 例)。两个严重事件 (心脏骤停和急性低血压) 归因于植入过程中的麻醉。 结论: 本研究强烈支持锚定应答器是安全的，定位稳定的，并且可用于肺肿瘤定位和监测。
METHODS::Pulmonary artery sling is a rare congenital anomaly of the origin and course of the left pulmonary artery. Patients with this condition typically present with respiratory failure in young infancy, and asymptomatic cases are uncommon. We describe the case of an adult patient with a lung adenocarcinoma of the right upper lobe, extending into the hilum and superior mediastinum, and with a previously unknown pulmonary artery sling anomaly. The local invasiveness of the tumor and the peculiar vascular anatomy contributed to a unique surgical scenario, wherein multiple reconstructive procedures were required.
METHODS::Patients with idiopathic pulmonary fibrosis (IPF) have higher risk of developing lung cancer, for example, squamous cell carcinoma (SCC), and show poor prognosis, while the molecular basis has not been fully investigated. Here we conducted DNA methylome analysis of lung SCC using 20 SCC samples with/without IPF, and noncancerous lung tissue samples from smokers/nonsmokers, using Infinium HumanMethylation 450K array. SCC was clustered into low- and high-methylation epigenotypes by hierarchical clustering analysis. Genes hypermethylated in SCC significantly included genes targeted by polycomb repressive complex in embryonic stem cells, and genes associated with Gene Ontology terms, for example, "transcription" and "cell adhesion," while genes hypermethylated specifically in high-methylation subgroup significantly included genes associated with "negative regulation of growth." Low-methylation subgroup significantly correlated with IPF (78%, vs. 17% in high-methylation subgroup, p = 0.04), and the correlation was validated by additional Infinium analysis of SCC samples (n = 44 in total), and data from The Cancer Genome Atlas (n = 390). The correlation between low-methylation subgroup and IPF was further validated by quantitative methylation analysis of marker genes commonly hypermethylated in SCC (HOXA2, HOXA9 and PCDHGB6), and markers specifically hypermethylated in high-methylation subgroup (DLEC1, CFTR, MT1M, CRIP3 and ALDH7A1) in 77 SCC cases using pyrosequencing (p = 0.003). Furthermore, low-methylation epigenotype significantly correlated with poorer prognosis among all SCC patients, or among patients without IPF. Multivariate analysis showed that low-methylation epigenotype is an independent predictor of poor prognosis. These may suggest that lung SCC could be stratified into molecular subtypes with distinct prognosis, and low-methylation lung SCC that significantly correlates with IPF shows unfavorable outcome.
METHODS::The role of Fyn-related kinase (FRK) in malignant tumors remains controversial. Our study investigated the function of FRK in lung cancer. Immunohistochemistry staining and generating a knockout of FRK by CRISPR/Cas9 in H1299 (FRK-KO-H1299) cells were strategies used to explore the role of FRK. Immunohistochemistry staining indicated that FRK expression was elevated in 223 lung cancer tissues compared to 26 distant normal lung tissues. FRK contributed to poor survival status in lung cancer patients and acted as a predictor for poor prognosis of lung cancer. Knockout of FRK by CRISPR/Cas9 markedly inhibited proliferation, invasion, colony formation and epithelial-mesenchymal transition (EMT) process in the lung cancer cell line H1299. Further exploration indicated that FRK-KO damaged the stemness phenotype of H1299 by inhibiting CD44 and CD133 expression. Seahorse detection and a U-13 C flux assay revealed that FRK-KO induced metabolism reprogramming by inhibiting the Warburg effect and changing the energy type in H1299 cells. Epidermal growth factor stimulation recovered the expression of FRK and biological functions, metabolic reprogramming and stemness phenotype of H1299 cells. FRK plays an oncogenic role in lung cancer cells via a novel regulation mechanism of enhancing the stemness of H1299 cells by inducing metabolism reprogramming, which finally promotes EMT and metastasis. Our study also indicates that FRK could be used as a potential therapeutic target for drug development.