Microwave ablation for non-small cell lung cancer with synchronous solitary extracranial metastasis.
- 作者列表："Ni Y","Ye X","Yang X","Huang G","Li W","Wang J","Han X","Wei Z","Meng M","Zou Z
AIMS:Local therapy including surgery or radiotherapy has been reported for the treatment of non-small cell lung cancer (NSCLC) with synchronous solitary metastasis, while studies with other local ablative treatment are rare. Here, we summarized our single-center experience of microwave ablation (MWA) for both primary and metastatic lesions in NSCLC patients with synchronous solitary extracranial metastases. PATIENTS AND METHODS:We retrospectively screened our institute database from January 2014 to Jun 2019. NSCLC patients with synchronous extracranial solitary metastasis with primary and metastatic lesions that were treated with MWA were identified and analyzed. RESULTS:Of the 1472 stage IV NSCLC patients found, 38 were diagnosed with synchronous extracranial solitary metastasis and 29 of them received MWA for primary and metastatic lesions. The most common distant metastases were contralateral lung metastases (14 cases), followed by bone (6), liver (4), adrenal gland (3) and pleura metastases (1). Median OS and PFS was 21.5 and 12.5 months, respectively. Patients with N0 had significantly longer PFS (median 18.5 vs. 8.0 months) and OS (median 42.7 vs. 19.0 months). In addition, systemic therapy was showed to be a prognostic factor for better PFS (12.9 vs. 7.5 months). Clinical pathological factors including age, histology, T stage, PS score, and metastasis locations are not significantly associated with survival. CONCLUSIONS:MWA may serve as an alternative treatment for NSCLCs with synchronous solitary extracranial metastases.
目的: 已经报道了包括手术或放疗在内的局部治疗用于治疗伴有同步孤立性转移的非小细胞肺癌 (NSCLC)，而其他局部消融治疗的研究很少。在此，我们总结了单中心微波消融 (MWA) 治疗同期孤立性颅外转移NSCLC患者原发灶和转移灶的经验。 患者和方法: 我们回顾性筛选了 2014 年 1 月至 2019 年 6 月我们研究所的数据库。对接受MWA治疗的伴有原发和转移病灶的同步颅外孤立性转移的NSCLC患者进行鉴定和分析。 结果: 在发现的 1472 例IV期NSCLC患者中，38 例诊断为同步颅外孤立性转移，其中 29 例因原发灶和转移灶接受MWA。最常见的远处转移是对侧肺转移 (14 例)，其次是骨 (6 例) 、肝 (4 例) 、肾上腺 (3 例) 和胸膜转移 (1 例)。中位OS和PFS分别为 21.5 和 12.5 个月。N0 患者具有显著较长的PFS (中位 18.5 个月vs. 8.0 个月) 和OS (中位 42.7 个月vs. 19.0 个月)。此外，系统治疗被证明是更好的PFS的预后因素 (12.9 个月对 7.5 个月)。包括年龄、组织学、T分期、PS评分和转移位置在内的临床病理因素与生存没有显著相关性。 结论: MWA可作为同期孤立性颅外转移的nsclc的替代治疗方法。
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.