Translational lung cancer research最新文献

Background: Brain metastases (BMs) are common in non-small cell lung cancer (NSCLC) and are associated with poor prognosis. Immune checkpoint inhibitors (ICIs) have improved survival outcomes in NSCLC, but their impact on intracranial progression (IP) and survival, particularly in patients with or without baseline BMs, remains unclear. The objective of this study is to determine whether baseline BM status in patients with NSCLC BMs treated with ICIs impacts IP and survival outcomes.

Methods: A systematic review and meta-analysis were conducted on observational studies published from 2015-2025 across PubMed, Embase, and Cochrane. Studies included NSCLC patients treated with ICIs, stratified by baseline BM status. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios (ORs) for IP, were extracted and pooled using random-effects models. Heterogeneity and risk of bias were assessed.

Results: Of 2,679 screened studies, 12 met the inclusion criteria. Among real-world studies (RWs) (n=12), HRs for OS and PFS were extracted from 10 studies. Pooled analysis showed a modest but significant increase in the hazard of death and PFS for BM+ vs. BM- patients [OS: HR =1.15, 95% confidence interval (CI): 1.04-1.28; PFS: HR =1.19, 95% CI: 1.07-1.32]. Additionally, 11/12 studies found no significant survival differences, and 11/12 reported comparable efficacy of ICIs across groups. In 6 studies reporting raw data, BM- patients had lower odds of IP compared to patients with baseline BMs (pooled OR =0.10, 95% CI: 0.05-0.20).

Conclusions: ICIs appear effective regardless of BM status; however, pooled RWs suggest modestly better survival outcomes in patients without baseline BMs. Additionally, these patients may be at a lower risk for IP. Prospective studies are needed to validate these findings and guide future BM prevention strategies.

Background: Stage III (N2-3) non-small cell lung cancer (NSCLC) represents a highly heterogeneous group, with limited evidence to guide multidisciplinary management in real-world settings. This study aimed to evaluate treatment patterns and associated pathological and survival outcomes in this population.

Methods: This study analyzed patients with stage III (N2-3) NSCLC treated at our center between 2009 and 2024. All patients had pathologically confirmed mediastinal lymph node involvement and received neoadjuvant therapy. Treatment patterns, pathological responses, and survival outcomes were systematically assessed. Survival was estimated using the Kaplan-Meier method, and prognostic factors were identified with Cox regression analyses.

Results: A total of 243 eligible patients were included. Treatment allocation was stratified by oncogenic driver status, with 75 receiving neoadjuvant immunotherapy-chemotherapy (IO-chemo), 46 targeted therapy, and 122 chemotherapy. Following neoadjuvant treatments, 175 patients (72.0%) underwent surgical resection, 46 (18.9%) received radiotherapy, and 22 (9.1%) continued systemic therapy. The IO-chemo group had the most surgical patients (77.3%) and demonstrated superior pathological responses among resected cases, with pathological complete response (pCR) and major pathological response (MPR) rates of 34.5% and 48.3%, respectively. Median event-free survival (EFS) and overall survival (OS) for the entire cohort were 28.7 months and 67.2 months. Patients treated with chemotherapy had worse survival compared with those treated with IO-chemo and targeted therapy, while survival outcomes were similar between the latter two groups. Multivariate analysis identified neoadjuvant IO-chemo as an independent favorable factor for both EFS and OS. At last, maintenance therapy following surgery or radiotherapy was associated with improved survival.

Conclusions: In this real-world cohort of stage III (N2-3) NSCLC, novel neoadjuvant therapies, including IO-chemo and targeted therapy, achieved superior pathological responses and improved survival compared with chemotherapy. Importantly, even patients with N3 disease derived meaningful benefit from surgery when combined with effective neoadjuvant treatment.

Leptomeningeal metastases (LMs) cause neurological symptoms, including nausea, headache, radicular pain, gait disturbance, and cranial nerve palsies. Lung and breast cancer as well as melanoma are the most common primary tumors in patients with leptomeningeal metastasis. The incidence of LMs is increasing, and this may be due to the improved survival of patients following the development of novel therapies, which may be less effective within the central nervous system. Barrier mechanisms in central nervous system such as blood-brain barrier constitute the critical interfaces between the periphery and brain that actively restrict the entry of solutes and cells into the brain parenchyma and leptomeninges. However, cancer cells could metastasize into the meninges via the brain or choroid plexus, by crossing pial blood vessels, or through vascular channels which connect the bone marrow and meninges. Conventional treatments for LMs, such as chemotherapy, photon-based radiation therapy, and intrathecal chemotherapy, have limited efficacy. However, advances in the understanding of the pathophysiology of LMs and novel treatment modalities are shifting this paradigm. Recent advances in molecularly targeted therapies, antibody-drug conjugates therapies, immunotherapies, intrathecal therapies, proton craniospinal irradiation, and expected therapies such as dendritic and NK cell-engaging therapies may improve the outcomes of patients with LMs. This mini review briefly outlines the pathophysiology and current treatment options for LMs.

Background: Immune checkpoint inhibitors (ICIs) targeting the programmed death ligand 1 (PD-L1)/programmed death-1 pathway are a mainstay for the treatment of patients with advanced/metastatic non-small cell lung cancer (NSCLC). Although some benefit has been observed in patients with low or no PD-L1 expression, ICIs are particularly recommended for those with PD-L1 expressing tumors. The limited availability of companion diagnostic (CDx) assays poses challenges for clinicians. Despite high analytical concordance among PD-L1 assays, the ability of alternative (non-comparison) assays to predict the clinical benefit of ICIs in the respective study populations has not been confirmed. This systematic literature review assessed whether alternative PD-L1 assays can predict the clinical benefit of ICI monotherapy for advanced/metastatic NSCLC with PD-L1 expression.

Methods: Studies were sourced from PubMed and Google Scholar up to December 20, 2023. Included studies analyzed PD-L1 expression of patients with NSCLC treated with ICI monotherapy, reporting clinical outcomes [objective response rates (ORRs), progression-free survival (PFS), or overall survival (OS)].

Results: From 2,239 titles, four relevant trials (N=1,364) were included: two randomized controlled trials of atezolizumab, and two retrospective studies of nivolumab. These trials indicated that the PD-L1 22C3 pharmDx and Ventana PD-L1 SP263 assays may predict the benefit of atezolizumab in patients with NSCLC.

Conclusions: These results may expand the therapeutic options for patients with PD-L1-expressing advanced/metastatic NSCLC using alternative PD-L1 assays. This review was limited by different patient populations, small numbers, possible inter-pathological discordance, and study heterogeneity. Evidence for nivolumab, pembrolizumab, or durvalumab remains inconclusive.

Background: Epidermal growth factor receptor (EGFR) mutations are the most common oncogenic subtype in non-small cell lung cancer (NSCLC) among Asians. EGFR tyrosine kinase inhibitors (TKIs) have become the mainstay of therapy, significantly improving survival outcomes. However, prognostic factors influencing survival in real-world settings among patients treated with EGFR-TKIs remain underexplored. This study aims to identify prognostic factors in EGFR-TKI-treated patients using data from a nationwide registry.

Methods: Patient data were sourced from the "Meina Xinsheng" registry, with survival metrics provided by the China Center for Disease Control. We analyzed the impact of sex, age, disease stage, histology, gene mutation type, and Karnofsky Performance Status (KPS) score on duration of treatment (DoT), overall survival (OS), and the incidence of long-term survival (>5 years), using both univariate and multivariate analyses. A reference cohort of EGFR wild-type patients receiving EGFR-TKI therapy was also included.

Results: Among 231,699 patients registered for EGFR-TKI treatment across 3,445 hospitals nationally, 221,788 cases of advanced NSCLC were analyzed. Within the subset of 83,791 patients eligible for survival analysis spanning 2012 to 2018, the median OS was 3.2 years [95% confidence interval (CI): 3.18-3.3], and the median lung cancer-specific survival (LCSS) was 4.1 years (95% CI: 4.02-4.1). At least 7.7% of patients achieved a survival milestone of more than 5 years. Factors associated with improved OS and higher long-term survival rates included female sex, stage IIIb disease, adenocarcinoma histology, EGFR exon 19 deletion, superior KPS scores, prolonged DoT, receiving EGFR-TKI as first-line treatment, and achieving a complete response (CR). Younger patients (<40 years) exhibited better OS, albeit with a shorter DoT. Notably, patients maintaining disease control for 22 months had significantly higher long-term survival (12.8%) compared with those who did not (2.7%).

Conclusions: In this large real-world cohort of advanced NSCLC patients treated with EGFR-TKI, female sex, stage IIIb (vs. stage IV) disease, adenocarcinoma histology, EGFR exon 19 deletion, and the use of EGFR-TKI as first-line therapy were independently associated with longer DoT and/or OS. These factors may help identify patients more likely to derive durable benefit from EGFR-TKIs and support risk stratification and treatment optimization in EGFR-mutant NSCLC.

Background: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality, with mutations in key oncogenes such as epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) affecting treatment response. While genetic testing remains the gold standard for mutation detection, it is invasive, expensive, and limited by sampling bias. Radiomics and deep learning (DL) models based on computed tomography (CT) imaging have emerged as non-invasive alternatives to predict genetic mutations. This study aimed to develop and externally validate a multimodal CT-based DL model integrating clinical variables, for non-invasive prediction of EGFR and KRAS mutations in NSCLC, and to benchmark its performance against other DL models across multiple datasets.

Methods: The study used datasets from The Cancer Imaging Archive (TCIA), including NSCLC Radiogenomics, The Cancer Genome Atlas (TCGA) Program-Lung Squamous Cell Carcinoma (TCGA-LUSC) and Lung Adenocarcinoma (TCGA-LUAD). CT scans were preprocessed, and a DL model was trained to predict mutation status based on DL features and clinical variables such as age, sex, and smoking status. Model performance was assessed using area under the curve (AUC), accuracy, sensitivity, specificity, and F1 score, and compared to other machine learning (ML) and DL models.

Results: For KRAS mutations, it achieved AUCs of 0.977 [95% confidence interval (CI): 0.943-0.995] in internal validation set and 0.941 (95% CI: 0.846-0.991) in external validation set 1. For EGFR mutations, the model achieved AUCs of 0.976 (95% CI: 0.937-0.993) in internal validation set, 0.960 (95% CI: 0.892-0.990) and 0.943 (95% CI: 0.896-0.989) in external validation sets 1 and 2, respectively. Multimodal models integrating clinical variables further improved accuracy. Compared to other models, Local-Global Mutation Network (LG-MutaNet) consistently outperformed traditional ML and DL algorithms.

Conclusions: The LG-MutaNet, combining CT imaging and clinical variables, offers a non-invasive and precise approach for predicting EGFR and KRAS mutations in NSCLC patients, supporting personalized treatment decisions and advancing precision medicine.