ObjectiveTo explore the risk factors for lymph node metastasis in patients with T2 stage non-small cell lung cancer.MethodsThe clinical data of 271 patients with non-small cell lung cancer who underwent surgical treatment in our hospital from 2014 to 2017 were collected, including 179 males and 92 females, with an average age of 62.73±0.58 years. The patients were divided into N0, N1, and N2 groups according to the lymph node metastasis status. The clinical data of the patients in different groups were compared.ResultsThe body mass index (BMI, P=0.043), preoperative lymph node enlargement (P<0.001), and tumor diameter (P<0.001) were significantly different among groups. The BMI (OR=1.131, 95%CI 1.001-1.277, P=0.048) and preoperative lymph node enlargement (OR=3.498, 95%CI 1.666-7.342, P=0.001) were independent risk factors for N2 lymph node metastasis, and tumor diameter was an independent risk factor for both N1 (OR=1.538, 95%CI 1.067-2.218, P=0.021) and N2 (OR=1.814, 95%CI 1.196-2.752, P=0.005) lymph node metastasis.ConclusionPatients with high BMI or enlarged lymph nodes before surgery have a high risk for N2 lymph node metastasis, and those with large tumor diameter have a high risk for both N1 and N2 lymph node metastasis.
Objective To compare the perioperative results between uniportal and three-portal thoracoscopic lobectomy for non-small cell lung cancer (NSCLC). Methods Electronic databases including PubMed, Web of Science, EMbase, CNKI, Wanfang were systematically searched from the establishment of each database until April 2022. Literature screening, data extraction and bias risk assessment were independently conducted by two researchers. All combined results were performed by RevMan 5.3 and Stata 16.0. The quality of the literature and the risk of bias were evaluated using the Cochrane Bias Risk Assessment Tool. Results Eighteen eligible randomized controlled trials (1 597 patients) were identified eventually, including 800 patients undergoing uniportal thoracoscopic lobectomy and 797 patients undergoing three-portal thoracoscopic lobectomy. Meta-analysis results showed that compared to the three-portal approach, uniportal lobectomy took longer operation time (WMD=7.63, 95%CI 2.36 to 12.91, P=0.005) with less intraoperative blood loss (WMD=–28.81, 95%CI –42.54 to –15.08, P<0.001). Furthermore, patients undergoing uniportal lobectomy achieved lower visual analogue score within 24 hours after the operation (WMD=–1.60, 95%CI –2.26 to –0.94, P<0.001), less volume of drainage after the operation (WMD=–25.30, 95%CI –46.22 to –4.37, P=0.020), as well as shorter drainage duration (WMD=–0.36, 95%CI –0.72 to –0.01, P=0.040). Besides, patients undergoing uniportal lobectomy were also observed with shorter length of hospital stay (WMD=–2.28, 95%CI –2.68 to –1.88, P<0.001) and lower incidence of postoperative complications (RR=0.49, 95%CI 0.38 to 0.63, P<0.001). However, the number of lymph nodes harvested during the operation (WMD=–0.01, 95%CI –0.24 to 0.21, P=0.930) was similar between the two groups. Conclusion Both uniportal and three-portal thoracoscopic lobectomy for NSCLC are safe and feasible. The uniportal approach is superior in reducing short-term postoperative pain, postoperative complications and shortening the length of hospital stay.
Objective To investigate the prognostic value of ERBB2 Exon20ins (Exon20ins) in advanced non-small cell lung cancer (NSCLC) patients receiving first-line chemotherapy combined with immunotherapy. Methods A retrospective analysis was conducted on clinical data from ERBB2-mutant stage IV NSCLC patients who received first-line chemotherapy combined with immunotherapy at West China Hospital of Sichuan University between 2020 and 2024. ERBB2 wild-type patients were matched using propensity score matching. Clinical pathological characteristics, distant metastatic sites, and treatment outcomes were compared among patients with different mutation statuses. The primary endpoint was progression-free survival (PFS), and Kaplan-Meier method was used to plot survival curves. Cox regression analysis was performed to adjust for confounding factors. Results This study included 41 ERBB2-mutant stage IV NSCLC patients, of whom 22 had Exon20ins mutations, and 19 had other ERBB2 mutations. Forty-one ERBB2 wild-type patients were matched for comparison. The mean age of all patients was 60.0±9.3 years, with 61 males (74.4%). A total of 67 patients (81.7%) received chemotherapy combined with immunotherapy, and 15 patients (18.3%) received chemotherapy combined with immunotherapy and anti-angiogenesis therapy. The Exon20ins group showed a higher incidence of lymph node metastasis compared with the ERBB2 other mutation group and the wild-type group (36.4% vs. 15.8% vs. 9.8%, P=0.045). The median PFS in the Exon20ins group was significantly shorter than in the other mutation group (5.8 months vs. 10.3 months, P=0.025) and the wild-type group (5.8 months vs. 8.3 months, P=0.023). Univariate Cox regression analysis indicated that the ERBB2 Exon20ins mutation was an adverse prognostic factor (Exon20ins vs. other ERBB2 mutations, HR=2.9, 95%CI 1.18 - 7.1, P=0.014; Exon20ins vs. wild-type, HR=2.6, 95%CI 1.25 - 5.6, P=0.014). The combination with anti-angiogenesis therapy did not significantly affect the prognosis of PFS (HR=0.66, 95%CI 0.28 - 1.6, P=0.363). Multivariate Cox regression analysis revealed that the ERBB2 Exon20ins mutation was an independent adverse prognostic factor for PFS (Exon20ins vs. other ERBB2 mutations, HR=3.3, 95%CI 1.27 - 8.3, P=0.015; Exon20ins vs. wild-type, HR=2.7, 95%CI 1.2 - 5.88, P=0.014). For the 67 patients receiving chemotherapy combined with immunotherapy, Cox regression analysis showed that the ERBB2 Exon20ins mutation was still associated with poor prognosis in advanced NSCLC (Exon20ins vs. other ERBB2 mutations, HR=3.2, 95%CI 1.12 - 9.1, P=0.030; Exon20ins vs. wild-type, HR=2.5, 95%CI 1 - 5.88, P=0.040). Conclusions Advanced NSCLC patients with ERBB2 Exon20ins mutation have a worse prognosis compared with those with other ERBB2 mutation subtypes or ERBB2 wild-type when treated with first-line chemotherapy combined with immunotherapy. This suggests that ERBB2 Exon20ins mutation, as a particularly refractory mutation, requires the exploration of new combination strategies based on molecular subtyping to improve survival outcomes.
Medical studies have found that tumor mutation burden (TMB) is positively correlated with the efficacy of immunotherapy for non-small cell lung cancer (NSCLC), and TMB value can be used to predict the efficacy of targeted therapy and chemotherapy. However, the calculation of TMB value mainly depends on the whole exon sequencing (WES) technology, which usually costs too much time and expenses. To deal with above problem, this paper studies the correlation between TMB and slice images by taking advantage of digital pathological slices commonly used in clinic and then predicts the patient TMB level accordingly. This paper proposes a deep learning model (RCA-MSAG) based on residual coordinate attention (RCA) structure and combined with multi-scale attention guidance (MSAG) module. The model takes ResNet-50 as the basic model and integrates coordinate attention (CA) into bottleneck module to capture the direction-aware and position-sensitive information, which makes the model able to locate and identify the interesting positions more accurately. And then, MSAG module is embedded into the network, which makes the model able to extract the deep features of lung cancer pathological sections and the interactive information between channels. The cancer genome map (TCGA) open dataset is adopted in the experiment, which consists of 200 pathological sections of lung adenocarcinoma, including 80 data samples with high TMB value, 77 data samples with medium TMB value and 43 data samples with low TMB value. Experimental results demonstrate that the accuracy, precision, recall and F1 score of the proposed model are 96.2%, 96.4%, 96.2% and 96.3%, respectively, which are superior to the existing mainstream deep learning models. The model proposed in this paper can promote clinical auxiliary diagnosis and has certain theoretical guiding significance for TMB prediction.
Objective To investigate the expression and clinical significance of S100A4 protein in tumorstroma of nonsmall cell lung cancer（NSCLC） to study its correlation with invasion, metastasis and prognosis. Methods Immunohistochemical staining（SP method）for S100A4 protein expression was performed in tissue sections from 130 patients with NSCLC operated and to analyze association of S100A4 protein with clinicopathological parameters in lung cancer and prognosis. Results The total positive expression rates of S100A4 protein in stroma of NSCLC was 72.3%. The positive expression rates of S100A4 protein in stroma of squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma and large cell lung cancer were 84.3%，59.6%，70.0% and 75% respectively.The expression of S100A4 protein was significantly associated with lymph node metastasis (χ2=18.91, P=0.000), distant metastasis(χ2=5.51, P=0.019) and TNM stage (χ2=21.54, P=0.000). The 3 years survival rates of patients whose tumourstroma stained positive for S100A4 was lower than that of patients whose tumourstroma stained negative (36.2% vs. 63.9%, P=0.003). Cox’ risk ratio model analysis indicated that age ≤50 years (OR=1.866), lymph node metastasis(OR=1.826), distant metastasis(OR=6.224), lower histology differentiation and undifferentiation (OR=1.793), TNM stage Ⅲ-Ⅳ (OR=2.573) and positive expression of S100A4 protein in stroma of NSCLC(OR=1.776) were significantly independent prognostic factors which affected survival. Conclusion Expression of S100A4 protein in stroma of NSCLC is significantly associated with invasion, metastasis, TNM stage and prognosis. S100A4 protein might become a marker for prediction of tumor progression of disease and clinical therapy.
Surgical resection is the only radical method for the treatment of early-stage non-small cell lung cancer. Intraoperative frozen section (FS) has the advantages of high accuracy, wide applicability, few complications and real-time diagnosis of pulmonary nodules. It is one of the main means to guide surgical strategies for pulmonary nodules. Therefore, we searched PubMed, Web of Science, CNKI, Wanfang and other databases for nearly 30 years of relevant literature and research data, held 3 conferences, and formulated this consensus by using the Delphi method. A total of 6 consensus contents were proposed: (1) Rapid intraoperative FS diagnosis of benign and malignant diseases; (2) Diagnosis of lung cancer types including adenocarcinoma, squamous cell carcinoma, others, etc; (3) Diagnosis of lung adenocarcinoma infiltration degree; (4) Histological subtype diagnosis of invasive adenocarcinoma; (5) The treatment strategy of lung adenocarcinoma with inconsistent diagnosis on degree of invasion between intraoperative FS and postoperative paraffin diagnosis; (6) Intraoperative FS diagnosis of tumor spread through air space, visceral pleural invasion and lymphovascular invasion. Finally, we gave 11 recommendations in the above 6 consensus contents to provide a reference for diagnosis of pulmonary nodules and guiding surgical decision-making for peripheral non-small cell lung cancer using FS, and to further improve the level of individualized and precise diagnosis and treatment of early-stage lung cancer.
Recent research data showed the concept that "surgery is still the main treatment for early non-small cell lung cancer (NSCLC)" now has new connotation: (1) Pure ground glass nodule (GGO) like lung adenocarcinoma should be regarded as a new clinical issue compared to solid tumors to avoid over-treatment. (2) The deep meaning of multidisciplinary pathological classification of lung adenocarcinoma should be fully understood to avoid over-diagnosis. (3) The T staging of lung adenocarcinoma mixed with GGO components should be correctly understood to avoid over-staging. (4) We should carefully understand the new data of relationship between lung resection extent and prognosis to avoid excessive resection. (5) Attention should be paid to the research progress of minimal residual disease (MRD) to avoid possible insufficient treatment.
ObjectiveTo evaluate the clinical efficacy and safety of artieral infusion chemotherapy combined with 125I seed implantation in treatment of non-small cell lung cancer (NSCLC). MethodsBetween February 2012 to June 2014, 34 patients with unresectable NSCLC received 125I seed implantation, in which 16 patients also received artieral infusion chemotherapy. All the patients were followed up and two months after 125I seed implantation the thoracic CT scanning was carried out in all patients. The response to treatment was evaluated in accordance with Response Evaluation Criteria in Solid Tumors and the accumulated survival rate was analyzed by means of Kaplan-Meier. ResultsThe operation successful rate was 100% and no severe complications were observed. Two months later the thoracic CT scanning showed that patients who only received 125I seed implantation with a total effective rate of 72.2% and those received artieral infusion chemotherapy combined with 125I seed implantation with an effective rate of 87.5%, with no significant difference between two groups in the effective rate (χ2=1.122, P>0.05). Median survival time of two groups was 361 days and 470 days (χ2=2.985, P < 0.05), respectively. Survival rate of 1 year was 43.5% and 83.5%(χ2=4.101, P < 0.05), respectively. ConclusionArtieral infusion chemotherapy combined with 125I seed implantation is safe, reliable and effective in treatment of unresectable NSCLC, which can prolong the patient's survival time.
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.
Tyrosine kinase inhibitors (TKIs) are the standard of care for non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutation. The efficacy of TKIs and prognosis of EGFR-mutated patients with compound EGFR mutation, oncogene mutation, suppresser gene mutation or other diver gene mutation are worse than those of patients with a single EGFR mutation. This article makes a review of related clinical researches aiming to provide references for clinical scenarios. To sum up, molecular alterations and clinical features should be correlated as accurately and dynamically as possible in the diagnostic and therapeutic process, and combined therapeutic strategies should be chosen flexibly and reasonably to improve patients’ survival and prognosis.