- 作者列表："Kim ST","An HJ","Kim JI","Yoo JR","Kim HJ","Park JM
OBJECTIVE:This study aimed to compare the plan quality of non-coplanar partial arc (NPA) volumetric modulated arc therapy (VMAT) to that of coplanar partial arc (CPA) VMAT for stereotactic ablative radiotherapy (SABR) for lung cancer. METHODS:A total of 20 patients treated for lung cancer with the SABR VMAT technique and whose lung tumors were close to the heart were retrospectively selected for this study. For the CPA VMAT, three coplanar half arcs were used while two coplanar half arcs and one noncoplanar arc rotating 315°-45° with couch rotations of 315° ± 5° were used for the NPA VMAT. For each patient, identical CT image sets and identical structures were used for both the CPA and NPA VMAT plans. Dose-volumetric parameters of each plan were analyzed. RESULTS:For the planning target volume and both lungs, no statistically significant differences between the CPA and NPA VMAT plans were observed in general. For the heart, average values of D0.1cc of the CPA and NPA VMAT plans were 29.42 ± 13.37 and 21.71 ± 9.20 Gy, respectively (p < 0.001). For whole body, the mean dose and the gradient index of the CPA VMAT plans were 1.2 ± 0.5 Gy and 4.356 ± 0.608 while those of the NPA VMAT plans were 1.1 ± 0.5 Gy and 4.111 ± 0.480, respectively (both with p < 0.001). CONCLUSION:The NPA VMAT proposed in this study showed more favorable plan quality than the CPA VMAT plans for lung SABR with tumors located close to the heart. ADVANCES IN KNOWLEDGE:For lung SABR, NPA VMAT can reduce doses to the heart as well as whole-body irradiation.
目的: 本研究旨在比较非共面部分弧 (NPA) 容积调制弧治疗 (VMAT) 与共面部分弧 (CPA) 的计划质量VMAT用于肺癌的立体定向消融放疗 (SABR)。 方法: 回顾性选择 20 例采用SABR VMAT技术治疗的肺癌患者，其肺部肿瘤靠近心脏。对于注册会计师VMAT来说，使用三个共面半弧，而两个共面半弧和一个旋转 315 °-45 ° 的非共面弧，其中沙发旋转为 315 ° ± 5 °，用于NPA VMAT。对于每个患者，将相同的CT图像集和相同的结构用于CPA和NPA VMAT计划。分析每个计划的剂量-体积参数。 结果: 对于计划目标体积和双肺，总体上没有观察到CPA和NPA VMAT计划之间的统计学显著差异。对于心脏，CPA和NPA VMAT计划的D0.1cc平均值分别为 29.42 ± 13.37 和 21.71 ± 9.20 Gy (p <0.001)。对于整个身体，CPA VMAT计划的平均剂量和梯度指数分别为 1.2 ± 0.5 Gy和 4.356 ± 0.608，NPA VMAT计划的平均剂量和梯度指数分别为 1.1 ± 0.5 Gy和 4.111 ± 0.480，分别 (均与p <0.001)。 结论: 本研究中提出的NPA VMAT比CPA VMAT计划更有利于肿瘤靠近心脏的肺SABR的计划质量。 知识进展: 对于肺SABR，NPA VMAT可以减少对心脏的剂量以及全身照射。
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.