Abstract： Objective To evaluate the safety, feasibility, and clinical outcome of complete video-assisted thoracoscopic surgery （VATS） lobectomy for patients with early-stage non-small cell lung cancer （NSCLC）. Methods We retrospectively analyzed the clinical data of 160 consecutive patients（the VATS group, 83 males and 77 females with average age at 60.8 years）with early-stage NSCLC who underwent complete VATS lobectomy between January 2005 andDecember 2008 in Zhongshan Hospital of Fudan University，and compared them with 357 patients（the thoracotomy group, 222 males and 135 females with average age at 59.5 years）who underwent open thoracotomy in the same period. Results The conversion rate of the VATS group was 5.0%（8/160）. The operation time of the VATS group was significantly shorter than that of the thoracotomy group（113.0 min vs.125.0 min, P=0.039）. Length of postoperative hospital stay was not statistically different between the two groups（10.3±4.3 d vs.9.1±4.6 d，P=0.425）. The postoperative morbidity of the VATS lobectomy group and the thoracotomy group was 9.4%（15/160）and 10.1% （36/357） respectively，and the postoperative mortality of the two groups was 0.6%（1/160）and 2.0%（7/357）respectively. There was no statistical difference in the mean group of lymph node dissection （2.4±1.5 groups vs.2.4±1.7 groups，P=0.743） and the mean number of lymph node dissection （9.8±6.3 vs.10.1±6.4，P=0.626） between the two groups. The overall 5-year survival rate of the VATS group was significantly higher than that of the thoracotomy group （81.5% vs.67.8%, P=0.001）. Subgroup analysis showed that the 5-year survival rate of pⅠa stage, pⅠb stage, and pⅢa stage was 86.0%, 84.5%, and 58.8% respectively in the VATS group, and 92.9%, 76.4%, and 25.3% respectively in the thoracotomy group. Conclusion Complete VATS lobectomy is technically safe and feasible for patients with early-stage NSCLC. The lymph node dissection extension of complete VATS lobectomy is similar to that of open thoracotomy, and long-term outcome of complete VATS lobectomy is superior to that of open thoracotomy. Randomized controlled trials of large sample size are further needed to demonstrate superiority.
ObjectiveTo analyze the correlation between the molecular biological information of SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC) and its clinical prognosis, and to explore the spatial features and molecular mechanisms of interactions between cells in the tumor microenvironment (TME) of SMARCA4-dNSCLC. MethodsUsing data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), this study conducted functional enrichment analysis on differentially expressed genes (DEGs) in SMARCA4-dNSCLC and depicted its genomic variation landscape. Through weighted gene co-expression network analysis (WGCNA) and a combination of 10 different machine learning algorithms, patients in the training group were divided into a low-risk group and a high-risk group based on a median risk score (RiskScore). A corresponding prognostic prediction model was established, and on this basis, a nomogram was constructed to predict the 1, 3, and 5-year survival rates of patients. K-M survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves were drawn to evaluate the predictive ability of the model. External datasets from GEO further validated the prognostic value of the prediction model. In addition, we also evaluated the immunological characteristics of the TME of the prognostic model. Finally, using single-cell RNA sequencing (scRNA-seq) and spatial transcriptome (ST), we explored the spatial features of interactions between cells in the TME of SMARCA4-dNSCLC, intercellular communication, and molecular mechanisms. ResultsA total of 56 patients were included in the training group, including 38 males and 18 females, with a median age of 62 (56-70) years. There were 28 patients in both the low-risk and high-risk groups. A total of 474 patients were included in the training group, including 265 males and 209 females, with a median age of 65 (58-70) years. A risk score model composed of 8 prognostic feature genes (ELANE, FSIP2, GFI1B, GPR37, KRT81, RHOV, RP1, SPIC) was established. Compared with patients in the low-risk group, those in the high-risk group showed a more unfavorable prognostic outcome. Immunological feature analysis revealed differences in the infiltration of various immune cells between the low-risk and high-risk groups. ScRNA-seq and ST analyses found that interactions between cells were mainly through macrophage migration inhibitory factor (MIF) signaling pathways (MIF-CD74+CXCR4 and MIF-CD74+CD44) via ligand-receptor pairs, while also describing the niche interactions of the MIF signaling pathway in tissue regions. ConclusionThe 8-gene prognostic model constructed in this study has certain predictive accuracy in predicting the survival of SMARCA4-dNSCLC. Combining the ScRNA-seq and ST analyses, cell-to-cell crosstalk and spatial niche interaction may occur between cells in the TME via the MIF signaling pathway (MIF-CD74+CXCR4 and MIF-CD74+CD44).
【摘要】 目的 探讨后程适形放射治疗（3 dimensional comformal radiation therapy，3D-CRT）同步化学疗法治疗Ⅲ期非小细胞肺癌（non-small-cell lung cancer，NSCLC）的近期疗效。 方法 搜集2005年1月-2008年6月NSCLC患者共115例，其中53例行单纯后程3D-CRT（单放组），62例行后程3D-CRT联合同步化学疗法（联合组），所有患者均经病理证实为Ⅲ期NSCLC。两组放射治疗方案均采用常规分割治疗加后程3D-CRT，DT 62～72 Gy。联合组化学疗法采用TP（紫杉醇 + 顺铂）方案。 结果 单放组和联合组近期疗效（完全缓解+部分缓解）分别为75.47%、91.94%，差异有统计学意义（Plt;0.05）。单放组和联合组的治疗不良反应主要有白细胞、血小板减少，放射性食管炎，放射性气管炎，恶心、呕吐等胃肠道反应。骨髓抑制和消化道反应，联合组稍高于单放组。经对症治疗后，所有患者均可耐受。 结论 后程3D-CRT联合TP方案化学疗法较单纯后程适形放射治疗明显提高Ⅲ期NSCLC近期疗效。患者耐受性尚可。【Abstract】 Objective To observe the recent therapeutic effect of late course 3 dimensional conformal therapy concomitant with chemotherapy on locally advanced stage Ⅲ non-small-cell lung cancer (NSCLC). Methods From January 2005 to June 2008, 115 patients with stage Ⅲ NSCLC were confirmed by pathology, in whom 53 only underwent late course conformal therapy (radiotherapy group), and another 62 underwent late course conformal therapy concomitant with chemotherapy (combined group). The radiotherapy schema of the two groups was routine division plus late course conformal therapy (with DT 62-72 Gy). The chemotherapy schema in the combined group was performed with TP (paclitaxel and DDP). Results The recent curative effect (complete remission plus partial remission) in radiotherapy group and combined group was 75.47% and 91.94%, respectively (Plt;0.05). The frequent adverse reactions in the two groups included leucocytopenia, thrombocytopenia, radioactive esophagitis, radioactive tracheitis, nauseated, and emesia. The rate of bone marrow depression and alimentary canal reaction in combined group was higher than that in the radiotherapy group. In the two groups, all patients could tolerance the treatments. Conclusion Late course 3 dimensional conformal therapy concomitant with TP schema chemotherapy for NSCLC could raise the recent curative effect. The patients could tolerance the treatments.
Objective For potential patients with better prognosis of non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations, a simpler and more effective model with easy-to-obtain histopathological parameters was established. MethodsThe computed tomography (CT) images of 158 patients with EGFR-mutant NSCLC who were first diagnosed in West China Hospital of Sichuan University were retrospectively analyzed, and the target areas of the lesions were described. Patients were randomly assigned to either a model training group or a test group.The radiomics features were extracted from the CT images, and the least absolute shrinkage and selection operator (LASSO) regression method was used to screen out the valuable radiomics features. The logistic regression method was used to establish a radiomic model, and the nomogram was used to evaluate the discrimination ability. Finally, the calibration curve, receiver characteristic curve (ROC), Kaplan-Meier curve and decision curve analysis (DCA) were employed to assess model efficacy. ResultsA nomogram combining three important clinical factors : gender, lesion location, treatment, and imaging risk score was established to predict the 3-year, 5-year, and 8-year survival rates of NSCLC patients with EGFR mutation. The calibration curve demonstrated highly consistent between model-predicted survival probabilities and observed overall survival (OS). The area under the curve (AUC) -ROC of the predicted 3-year, 5-year and 8-year OS was 0.70, 0.79 and 0.68, respectively. The Kaplan-Meier curve revealed significant OS disparities when comparing high- and low-risk patient subgroups. The DCA curve showed that the predicted 3-year and 5-year OS increased more clinical benefits than the treatment of all patients or no treatment.ConclusionThe nomogram for predicting the survival prognosis of NSCLC patients with EGFR mutation was constructed and verified, which can effectively predict the survival time range of NSCLC patients, and provide a reference for more individualized treatment decisions for such patients in clinical practice.
Cuproptosis, recently defined as a unique form of cell death distinct from programmed cell death, is triggered by copper overload within mitochondria. Genes associated with cuproptosis have been found to correlate with tumorigenesis and tumor progression, making the targeting of cuproptosis pathways a promising direction for anti-tumor therapies. Copper ion carriers can transport copper ions into cells, inducing cuproptosis and laying the foundation for its application in cancer treatment. This article elaborates on the homeostasis of copper and the mechanisms related to cuproptosis, further clarifying the relationship between cuproptosis and lung cancer treatment targets. This review aims to summarize current progress in research related to cuproptosis and lung cancer, providing new theories and bases for the clinical treatment of lung cancer.
Objective To evaluate the role of topotecan in the treatment of small cell lung cancer (SCLC). Methods Up to 2006, we searched The Cochrane Library, MEDLINE, EMbase, Cancerlit, CBM, CNKI and VIP. Handsearch and additional search were also conducted. The quality of included studies was evaluated and meta-analyses were performed for the results of homogeneous studies by RevMan 4.2.8 software. Results Fourteen studies involving 2 099 participants with SCLC were included. All included studies were adequate in reporting randomization, while inadequate in allocation concealment and blinding. Meta-analyses showed that the response rate of TP (topotecan + cisplatin) regimen had no significant difference compared with EP regimen (etoposide + cisplatin) with OR 0.83 and 95%CI 0.63 to 1.09, but myelo-suppression such as leucopenia and thrombopenia was more severe with TP regimen; the response rate of monotherapy with topotecan was similar with that of CE (carboplatin + etoposide) regimen with OR 0.59 and 95%CI 0.22 to 1.60; the response rate of TEP (topotecan + etoposide + cisplatin) regimen was comparable with that of EP regimen with OR 1.37 and 95%CI 0.82 to –2.28, but myelosuppression and anemia were more severe with TEP regimen; the response rate with OR 0.97 and 95％CI 0.60 to –1.57, median time to progression with WMD –2.32 and 95％CI –5.72 to 1.09 and median survival time with WMD –1.65 and 95％CI –7.13 to 3.83 of IV topotecan were similar to those of oral topotecan, while neutropenia was more severe with IV topotecan. Forty-five treatment-related deaths were reported in all included studies. Conclusions Topotecan is an effective agent for SCLC when used as monotherapy or in combined treatment, but myelosuppression such as leucopenia and thrombopenia was relatively severe. Although it has been recommended as a second-line agent for recurrence of sensitive SCLC, more clinical trials are needed to define its role in first-line treatment. Due to a high risk of selection bias and detection bias in included studies, the evidence is insufficient to determine the effect of topotecan. Further large-scale trials are required to define the role of topotecan in the treatment of SCLC.
Objective To explore the safety and feasibility of preferential manual bronchoplasty in single-port video-assisted thoracoscopic surgery (VATS) upper lobectomy. MethodsThe clinical data of 457 patients with non-small cell lung cancer who underwent single-port VATS lobectomy in the Department of Thoracic Surgery of Peking University First Hospital from March 2020 to March 2022 were retrospectively analyzed. The patients were divided into a preferential manual bronchoplasty group and a traditional single-port VATS lobectomy group with a 1 : 1 propensity score matching for further research. Results A total of 204 patients were matched, and there were 102 patients in each group. There were 50 males and 52 females aged 62.2±10.1 years in the preferential bronchoplasty group, and 49 males and 53 females aged 61.2±10.7 years in the traditional single-port VATS group. The preferential bronchoplasty group had shorter surgical time (154.4±37.0 min vs. 221.2±68.9 min, P<0.01), less bleeding (66.5±116.9 mL vs. 288.6±754.5 mL, P=0.02), more lymph node dissection (19.8±7.5 vs. 15.2±4.7, P<0.01), and a lower conversion rate to multi-port or open surgery (2.3% vs. 13.8%, P=0.04) in left upper lobe resection. In the right upper lobe resection surgery, there was no statistical difference in postoperative results between two groups. There was no perioperative death or occurrence of bronchopleural fistula in both groups. ConclusionCompared with traditional single-port VATS upper lobectomy, preferential bronchoplasty has similar safety and feasibility. In addition, priority bronchoplasty in left upper lobectomy has the advantages of shorter surgical time, less bleeding, more lymph node dissection, and lower conversion rate to multi-port or open surgery.
ObjectiveTo investigate the expression of autophagy-related genes and proteins in the lung tissues of patients with non-small cell lung cancer (NSCLC).MethodsPulmonary tissues were obtained from the surgically resected lung tissues of patients with NSCLC who were clinical diagnosed. The lung cancer tissues were derived from the pathologically diagnosed NSCLC and the normal tissues were from lung tissues 5 cm away from the lung lesions (29 cases in the lung cancer group and 32 cases in the normal group). The expression of autophagy-related proteins ATG5, LC3B, and p62 in lung tissues were measured by Western blot, and mRNA expression of ATG5 and p62 in the lung tissues were measured by real-time PCR.ResultsWestern blot analysis showed that the expression of ATG5 and p62 in lung cancer group were significantly higher than those in normal group (P<0.05). However, the expression of LC3B in lung cancer group was significantly lower than that in normal group (P<0.05). Real-time PCR analysis found that the mRNA expression of ATG5 and p62 in lung cancer group were significantly higher than those in normal group (P<0.05). The expression of ATG5, LC3B and p62 had no relationship with gender, age, smoking history, tumor location, tumor size, clinicopathological classification, differentiation or TNM stage. The expression of ATG5 had statistical significance in lymph node metastasis (P<0.05), but there was no difference for LC3B or p62 in lymph node metastasis (P>0.05).ConclusionsAutophagy plays a role in the tumorigenesis of lung cancer. If it’s possible to regulate and control autophagy-related genes and proteins effectively, it may supply new insights or targets into treatment for lung cancer patients.