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.
ObjectiveTo explore the adjuvant treatment options for elderly patients or those with low cardiopulmonary function who cannot tolerate lobectomy for peripheral solid pathological stage ⅠA (pⅠA) non-small cell lung cancer (NSCLC). MethodsA retrospective analysis was conducted on the clinical data of patients with peripheral solid pⅠA stage NSCLC treated with lobectomy and compromised sublobar resection (CSR) in our center from 2018 to 2019. The incidence of postoperative complications and independent predictors of postoperative recurrence were analyzed. Patients in the CSR group were divided into a targeted therapy group, a chemotherapy group, and an observation group based on postoperative treatment measures. The 3-year recurrence-free survival (RFS) rate and 5-year overall survival (OS) rate of the three subgroups before and after propensity score matching (PSM) were compared. ResultsA total of 586 patients were included, including 288 males (49.15%) and 298 females (50.85%), with a median age of 64.00 years. There were 335 patients of lobectomy and 251 patients of compromised sublobar resection. There was no statistically significant difference in the incidence of postoperative complications between the lobectomy group and CSR group [RR=0.987, 95%CI (0.898, 1.085), P=0.789). Multivariate analysis showed that gender, tumor location, and size were independent risk factors for recurrence after CSR. After PSM, 17 patients were enrolled in each of the three subgroups of CSR. Kaplan-Meier survival curve analysis showed that there was no statistically significant difference in the 3-year RFS rate (P=0.115) and 5-year OS rate (P=0.101) between the targeted therapy group and the chemotherapy group after PSM, but both were significantly better than those in the observation group (P=0.041, P=0.009). Compared with lobectomy, there was no statistically significant difference in the 3-year RFS rate (P=0.069) and 5-year OS rate (P=0.540) in the targeted therapy group, while the chemotherapy group and observation group were significantly inferior to the lobectomy group (P<0.05). ConclusionCSR for treating elderly patients or those with low cardiopulmonary function with peripheral solid pⅠA stage NSCLC does not increase the incidence of postoperative complications. Gender, tumor location, and size are independent risk factors for postoperative recurrence. In terms of 3-year RFS rate and 5-year OS rate, adjuvant targeted therapy after CSR is not only superior to chemotherapy or observation but is also not inferior to lobectomy.
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).
ObjectiveTo investigate the clinical effect of thoracoscopic lobectomy versus segmentectomy in the treatment of T1bN0M0 non-small cell lung cancer (NSCLC). MethodsClinical data of 181 patients with T1bN0M0 NSCLC admitted to our hospital from 2012 to 2015 were retrospectively analyzed. They were divided into a lobectomy group and a segmentectomy group according to surgical methods. There were 117 patients in the lobectomy group (46 males and 71 females aged 61.32±8.94 years) and 64 patients in the segmentectomy group (20 males and 44 females aged 58.55±12.57 years). Perioperative indicators and prognosis were compared between the two groups. ResultsThe segmentectomy group had longer operation time, less intraoperative blood loss, shorter postoperative hospital stay and more preservation of lung function compared with the lobectomy group (P<0.05). The lobectomy group had higher consolidation tumor ratio, bigger tumor diameter, and more lymph node sampling compared with the segmentectomy group (P<0.05). There was no statistical difference in 5-year overall survival or recurrence-free survival between the two groups (P<0.05). ConclusionFor patients with T1bN0M0 NSCLC, thoracoscopic segmentectomy and lobectomy have similar prognosis, but segmentectomy has advantages with less injury and faster recovery over lobectomy.
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 determine the most appropriate T-stage and surgical resection range of non-small cell lung cancer(NSCLC) with adjacent lobe invasion (ALI). Methods Fifty one NSCLC patients who were confirmed as direct ALI were divided into an ALI-T2 and an ALI-T3 group according to the eighth edition of TNM classification. Cases were matched by propensity score matching method at a ratio of 2∶1. The overall survival (OS), progression free survival (PFS), postoperative hospitalization, and postoperative complications among the groups were compared. Results Patients' characteristics were comparable among the groups. Three-year or 5-year survival rate in the ALI-T2 group, the single-lobe invasion T2 (SLI-T2) group, and the T3 (SLI-T3) group was 73.90% and 61.60%, 89.60% and 89.60%, 68.90% and 61.20%, respectively. The OS of SLI-T2 group was significantly higher than that of the ALI-T2 ( P=0.042) group and with similar survival in the SLI-T3 group( P=0.955). In the survival analysis of the ALI-T3 group, the 3-year or 5-year OS of the SLI-T3 group was 70.80% and 65.70%, respectively, while in the poorest prognosis ALI-T3 group was only 31.60% and 21.00% ( P=0.009), respectively. However, no statistical difference was detected between the ALI-T3 and SLI-T4 groups ( P=0.343). The PFS of the patients in the ALI-T3 group was closer to the SLI-T4 group level while lower than that of the SLI-T3 group, but the trend had not been confirmed by statistical analysis ( P 1=0.071, P 2=0.648). The OS and PFS did not differ between the patients undergoing a lobectomy plus wedge resection (LWR) and those undergoing a bilobectomy or pneumonectomy. Compared with a bilobectomy or pneumonectomy, LWR had distinct advantages in the postoperative hospital stay (6.90±3.11days vs. 9.23± 4.43 days, P=0.030), the postoperative duration of drainage (4.41±2.98 days vs. 6.50±4.11 days, P=0.041) and complication rates (4.00% vs. 31.58%, P=0.032). Conclusions We believe that T1-2 stage tumor invading adjacent lobe should be classified as T3 and ALI-T3 tumor should be revised as T4. Beside that, LWR could be considered as a reasonable surgical option for patients with lesser invasive depth (less than 2 cm) in the adjacent lobes.
This study reports a case of a 56-year-old female patient with BRAF-mutated non-small cell lung cancer (NSCLC) who successfully underwent curative surgery after neoadjuvant targeted therapy with the BRAF inhibitor dabrafenib combined with the MEK inhibitor trametinib. The chest drainage tube was removed 2 days postoperatively, and the patient was discharged smoothly. Postoperative pathology indicated invasive adenocarcinoma, moderately to highly differentiated, with 80% being lepidic type, and the maximum tumor diameter was 4 cm. No vascular invasion, nerve invasion, air cavity dissemination, pleural invasion, or lymph node metastasis were observed. The postoperative staging was ypT2aN0M0. The patient continued with adjuvant treatment with dabrafenib combined with trametinib postoperatively, and no signs of recurrence were found in the follow-up examination six months after surgery.
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.
With the publication of several phase Ⅱ and Ⅲ clinical studies, the multidisciplinary diagnostic and therapeutic strategies for early resectable non-small cell lung cancer (rNSCLC) are rapidly evolving. These studies have elucidated the significant effects of neoadjuvant and adjuvant therapies on improving the prognosis of rNSCLC patients, while also highlighting the urgent need to revise and refine corresponding treatment protocols and clinical pathways. In response, the International Association for the Study of Lung Cancer has assembled a diverse, multidisciplinary international expert panel to evaluate current clinical trials related to rNSCLC and to provide diagnostic, staging, and treatment recommendations for rNSCLC patients in accordance with the 8th edition of the AJCC-UICC staging system. The consensus recommendations titled "Neoadjuvant and adjuvant treatments for early stage resectable non-small cell lung cancer: Consensus recommendations from the International Associationfor the Study of Lung Cancer" outline 20 recommendations, 19 of which received over 85% agreement from the experts. The recommendations indicate that early rNSCLC patients should undergo evaluation by a multidisciplinary team and complete necessary imaging studies. For stage Ⅱ patients, consideration should be given to either adjuvant therapy following surgery or direct neoadjuvant/perioperative treatment, while stage Ⅲ patients are recommended to receive neoadjuvant chemoimmunotherapy followed by surgery. Postoperatively, adjuvant immunotherapy should be considered based on the expression levels of programmed cell death ligand 1, along with testing for other oncogenic driver mutations. For patients with epidermal growth factor receptor or anaplastic lymphoma kinase mutations sensitive to tyrosine kinase inhibitors, corresponding adjuvant targeted therapy is recommended. These recommendations aim to provide personalized and precise treatment strategies for early rNSCLC patients to enhance the efficacy of neoadjuvant and adjuvant therapies. This article provides an in-depth interpretation of these consensus recommendations.
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.