Synchronous multiple primary lung cancer (sMPLC) exhibits distinct histopathological characteristics among pulmonary nodules. However, a comprehensive understanding of the somatic mutation landscape and transcriptome heterogeneity is lacking. Therefore, our study aims to meticulously investigate genomic distinctions among multiple pulmonary nodules within individual patients. We performed targeted DNA sequencing on tumor specimens and conducted bulk RNA transcriptome analysis on 53 multiple nodules originating from 26 lung cancer patients. The multiple nodules from the same patient was determined as major nodule and minor nodule. Additionally, the tumor tissues underwent histopathological evaluation through H E staining, complemented by a comprehensive series of immunohistochemistry (IHC) analyses to detect protein expression. The detected protein markers encompassed PD-L1, Ki67, and others. For the 53 nodule samples from 26 MPLCs patients, EGFR was the mostly mutated genes, and the TP53 mutation frequency was notably different between major and minor nodules. Furthermore, pathway enrichment analysis based on the differentially expressed genes (DEGs) between major and minor nodules revealed the significantly active cell cycle and p53 pathways in the major nodules. Additionally, both major and minor nodules demonstrated mostly similar immune microenvironment and PD-L1 protein expression, and a significantly higher expression of Ki67. A noteworthy suppression was observed in the immune microenvironment in nodules, revealed by the expression of macrophage, neutrophils, and NK cells. Furthermore, minor nodules exhibited a modestly elevated expression of macrophages compared to major nodules. Additionally, among the significantly up-regulated cell cycle-related genes in the major nodules when compared with minor nodules, CCNE1 mRNA expression demonstrated significant correlation with poor prognosis in the lung cancer. Furthermore, the MYC inhibitor demonstrated more sensitivity for the major nodules than minor nodules. This study validated molecular distinctions between samples from major and minor nodules in patients with sMPLC at both genomic and transcriptomic levels. The major nodules exhibited heightened activity in tumor cell proliferation pathways and demonstrated malignancy-related biological characteristics, which correlated with pathological assessment results.

BACKGROUND:Circulating tumor DNA (ctDNA) has emerged as a potential novel biomarker to predict molecular residual disease (MRD) in lung cancer after definitive treatment. Herein, we investigated the value of ctDNA in prognosing risk of relapse and monitoring the effect of adjuvant therapy in surgical non-small cell lung cancer (NSCLC). METHODS:We enrolled 58 NSCLC patients in a real-world setting, and 58 tumor tissues and 325 plasma samples were analyzed. Tumor tissues and plasma samples were subjected to targeted next-generation sequencing (NGS) of 1021 cancer-related and ultra-deep targeted NGS covering 338 genes, respectively. RESULTS:ctDNA was detected in 31.0% of cases at the first postoperative time, which was associated with advanced tumor stage, T stage and KEAP1 or GRIN2A mutations in tissues. ctDNA positivity at landmark and longitudinal indicated the shorter disease-free survival. For patients with ctDNA positivity at the first postoperative time, regardless of adjuvant therapy, all patients who were persistently ctDNA positive during postoperative surveillance had disease recurrence. Among the patients who were ctDNA negative, only two patients (15.4%, 2/13) receiving adjuvant therapy relapsed, while one patient (50.0%, 1/2) without adjuvant therapy relapsed. For the first postoperative ctDNA negative patients, the recurrence rate of patients with adjuvant therapy was and higher than without adjuvant therapy (22.6% [7/31] vs. 11.1% [1/9]). The patients who became ctDNA positive may also benefit from intervention therapy. CONCLUSION:Postoperative ctDNA is a prognostic marker, and ctDNA-detection may facilitate personalized adjuvant therapy, and applying adjuvant therapy to the patients with detectable ctDNA could bring clinical benefits for them.

目的 探讨老年肺癌患者行单孔胸腔镜下肺叶或肺段切除术后并发症发生的危险因素。方法 纳入2020年1月至2021年12月首都医科大学宣武医院胸外科行单孔胸腔镜肺叶或肺段切除手术的≥60岁的387例老年肺癌患者作为研究对象，平均年龄67.5±5.1（60~87）岁，其中男性171例（44.2%），女性216例（55.8%）。对老年肺癌患者的术后并发症进行分析，评估老年肺癌患者行单孔胸腔镜肺段或肺叶切除术后并发症发生的危险因素。结果 387例患者中共有66例(17.1%)术后出现并发症，其中1例(0.3%)患者死亡。单因素及多因素分析显示：男性（P=0.020）、第1秒用力呼气容积（forced expiratory volume in the first second，FEV1）<1.5 L(P=0.017)、一氧化碳弥散量占预计值百分比（diffusion capacity of the lungs for carbon monoxide as a percentage of the predicted value，DLCO%pred）<80%(P=0.016)、伴有肺部合并症病史(P<0.001)、脑卒中病史(P<0.001) 、手术时长≥3 h（P=0.018）为术后出现并发症的独立预测因素。而伴有肺部合并症病史(P<0.001)及手术时长≥3 h(P=0.002)是术后出现肺部并发症的独立危险因素（P<0.05）。结论 老年肺癌患者可能因肺部合并症、低肺功能、手术时间等出现术后并发症，因此术前应充分评估老年肺癌患者的生理情况。通过加强围术期管理降低术后并发症的发生率，降低术后并发症对老年肺癌患者行单孔胸腔镜手术治疗效果的影响。

Circulating tumor DNA (ctDNA) has potential as a promising biomarker for molecular residual disease (MRD) detection in lung cancer. As the next-generation sequencing standardized panel for ctDNA detection emerges, its clinical utility needs to be validated. We prospectively recruited 184 resectable lung cancer patients from four medical centers. Serial postoperative ctDNAs were analyzed by a standardized panel. A total of 427 postoperative plasma samples from 177 eligible patients were enrolled. ctDNA positivity after surgery was an independent predictor for disease recurrence and preceded radiological recurrence by a median of 6.6 months (range, 0.7-27.0 months). ctDNA-positive or -negative patients with tumors of any stage had similar disease-free survival (DFS). Patients who received targeted therapy had significantly improved DFS than those not receiving adjuvant therapy or receiving chemotherapy, regardless of baseline/preadjuvant ctDNA status. According to whether the ctDNA variants were detected in its matched tissue, they were classified into tissue derived and non-tissue derived. Patients with detectable postoperative ctDNA with tissue-derived mutations had comparable DFS with those with non-tissue-derived mutations. Collectively, we demonstrated that postoperative ctDNA has the potential to stratify prognosis and optimize tumor stage in resectable lung cancer. ctDNA variants not identified in tissue samples should be considered in MRD test.

目的 探讨电子计算机断层扫描(computed tomography,CT)引导下经皮肺穿刺活检磨玻璃结节(ground-glass nodule,GGN)的诊断价值.方法 回顾性分析2014年1月至2019年1月期间217例接受CT引导下经皮肺穿刺活检的GGN患者的临床病理资料,对穿刺为恶性的病例判断为阳性,对于穿刺为良性的患者结合随访结果做出临床诊断,将穿刺病理与临床最终诊断作对比.根据临床特点进行分组,统计分析每组穿刺活检的准确率、灵敏度、阴性预测值及并发症发生率.结果 217例患者总体准确率93.5％(203/217),灵敏度92.2％(165/179),阴性预测值为73.1％(38/52).并发症总体发生率35.5％,以咯血和气胸为主.结论 CT引导下对GGN穿刺活检具有较高的准确性和灵敏度,但需要警惕假阴性的结果,妥善处理并发症.

BACKGROUND:Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) capable of overcoming non-small cell lung cancer (NSCLC) with EGFR T790M mutation. Although the addition of bevacizumab to 1st generation EGFR-TKIs confers a significant improvement in progression-free survival (PFS) in treatment-naive EGFR mutant NSCLC patients, osimertinib plus bevacizumab combination failed to show prolongation in the phase 2 study WJOG8715L. Data of such combination in Chinese patients are still lacking. This study aimed to explore the efficacy of the addition of bevacizumab to osimertinib as second-line therapy in real-world data, and to evaluate the role of anti-angiogenesis plus osimertinib combination therapeutic strategies in pretreated Chinese NSCLC patients with acquired EGFR T790M mutation.METHODS:A total of 42 advanced NSCLC patients with acquired EGFR T790M mutation after prior EGFR-TKIs treatment were collected between January 2020 to August 2021, with 16 cases treated with osimertinib plus bevacizumab and 26 cases treated with osimertinib. The treatment effect of patients were analyzed.RESULTS:The objective response rate (ORR) in combination group and osimertinib group were 43.8% and 50.0% respectively (P=0.694). No statistically significant difference in median PFS (14.0 mon vs 13.0 mon, P=0.797) and overall survival (OS) (29.0 mon vs 26.0 mon, P=0.544) between the combination group and osimertinib group were observed. Prior history of bevacizumab was identified as an independent predictor of PFS (P=0.045) and OS (P=0.023).CONCLUSIONS:Our study demonstrated that adding bevacizumab to osimertinib could not show advantages in PFS and OS in pretreated NSCLC patients harboring EGFR T790M-mutation.

Background Lung adenocarcinoma which invades ovaries is very rare. However, with the increase of long-survival female lung cancer, more patients will suffer ovarian metastasis. On grounds of the paucity of reported cases, the clinicopathological features and treatment strategies remain unknown. Case presentation This patient was stage IV lung adenocarcinoma at first diagnosis. Following multiple-line systemic treatments, she experienced extensive pelvic metastasis. After debulking surgery and reevaluation about the drive genes, she was administered by targeted therapy. Up to now, the patient has shown no evidence of progression for 8 years after the initial diagnosis of primary lung cancer and 46 months after her ovarian metastasis. Conclusion The comprehensive treatment modality for the bilateral ovarian metastasis is effective in clinical course.

Objective:To investigate the value of the folate receptor (FR)-positive circulating tumor cell (CTC) detection in the diagnosis of benign and malignant subcentimeter pulmonary nodules(the maximum diameter ≤10 mm).Methods:Thirty-seven patients with subcentimeter pulmonary nodules (the chest CT showed the maximum diameter was ≤10 mm) in the Xuanwu Hospital of Capital Medical University from July to December 2018 were collected. Among them, 22 cases were diagnosed with early stage lung adenocarcinoma by postoperative pathological diagnosis and another 15 cases were benign lung lesion. Venous blood samples from these patients were collected before surgery and then utilized to detect FR + CTC level (defined unit as FU/3 ml) by novel ligand-targeted polymerase chain reaction (LT-PCR), and the enzyme-linked immunosorbent assay was used to detect the levels of tumor markers, including carcinoembryonic antigen (CEA), neuron-specific enolase(NSE), cytokeratin 19 fragment CYFRA21-1, carbohydrate antigen 125 (CA125), CA199, pro-gastrin releasing peptide (pro-GRP), etc. The t-test was used to compare the measurement values between the groups. The CTC value 8.70 FU/3 ml described in the detection kit instruction was used as the threshold. The binary logistic regression was used to analyze the risk factors of malignant pulmonary nodules. The kappa consistency test was used to identify the consistency of the diagnosis results obtained by the FR + CTC level and the pathological results of surgically resected specimens. The receiver operating characteristic curve (ROC) was drawn to evaluate the efficiency of each index for the diagnosis of benign and malignant subcentimeter pulmonary nodules. Results:The level of FR + CTC in patients with early stage lung cancer was higher than that in patients with benign lung lesion, and the difference was statistically significant [(11.0±3.0) FU/3 ml vs. (7.0±3.7) FU/3 ml, t=-3.327, P = 0.001]. The level of FR + CTC was not related to the age, gender and smoking history of patients (all P>0.05). Logistic regression analysis indicated that high-level FR + CTC was one of the risk factors for malignant pulmonary nodules ( OR = 37.333, 95% CI 3.994-349.010, P = 0.002). The kappa consistency test indicated that the level of FR + CTC used for the diagnosis of lung subcentimeter nodules presented a certain accuracy ( κ = 0.627, P < 0.01). ROC illustrated that the FR + CTC was better than CEA, NSE and CYFRA21-1 when it was used as an indicator for the diagnosis of malignant pulmonary nodules. The area under the curve(AUC) of FR + CTC was 0.830 (95% CI 0.639-0.968), and the diagnostic sensitivity and specificity were 72.7% (95% CI 49.6%-88.4%) and 93.3% (95% CI 66.0%-99.7%), respectively. When FR + CTC, CEA, NSE and CYFRA21-1 were combined for lung cancer diagnosis, the AUC, sensitivity and specificity were 0.776 (95% CI 0.614-0.938), 86.4% and 73.3%, respectively. Conclusion:The detection of FR + CTC has a high value in the diagnosis of benign and malignant subcentimeter pulmonary nodules.

Objective To assess the long-term results and relevant influencing factors of extended thymectomy and medicine-alone treatment of non-thymomatous myasthenia gravis (MG) patients. Methods We retrospectively analyzed the clinical data of 174 patients with non-thymomatous MG diagnosed and treated in our department from December 2009 to April 2017, including 81 males and 93 females, aged 13-88 (47.1±17.8) years. According to the different treatment methods, the patients were divided into two groups: an operation group (91 patients receiving extended thymectomy) and a medicine-alone group (83 patients receiving medical therapy alone). The efficacy was evaluated according to the Myasthenia Gravis Foundation of America (MGFA). Survival curves of the patients were plotted using the Kaplan-Meier method to evaluate the remission rate and survival rate. Cox regression analysis was used to assess the influencing factors of the outcomes. Results The patients were followed up for 3 to 94 (39.1±26.9) months. As a result, 29 patients (31.9％) achieved complete remission in the surgery group and 13 patients (15.7％) were completely relieved in the medicine-alone group (P=0.014). Further analysis showed that treatment pattern (P=0.018) and MG type (P=0.021) were the main factors related to the efficacy. Conclusion For patients with non-thymomatous MG, extended thymectomy is superior to the medicine-alone in terms of complete remission rate and the postoperative immunosuppression ratio.

Lung cancer (LC) is the most common cancer and the leading cause of cancer-related death worldwide. The 5-year survival rate for LC remains low at 18% and is 5% for patients with metastatic disease, while the 5-year overall survival rate of patients with stage I NSCLC can reach 77.9%, hence early diagnosis and treatment of LC is the key to improve the prognosis. As a non-invasive detection technique, Raman spectroscopy can realize the non-destructive detection of the differences in molecular level structure between cancerous tissues and normal tissues, which can be used for the early diagnosis of lung cancer. The aim of this review is to summarize the progress of Raman spectroscopycombined with different tissue or body fluid samplesin the diagnosis of early LC.
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