Translational lung cancer research最新文献

Background: Visceral pleural invasion (VPI) is associated with a poor outcome in early-stage non-small cell lung cancer (NSCLC). Preoperative prediction of VPI could have an impact on surgical planning. The aim of this study was to establish a nomogram model based on computed tomography (CT) features to predict VPI in early-stage NSCLC.

Methods: This study is a retrospective review of patients enrolled with surgically pathologically confirmed NSCLC between December 2019 and June 2022. Patients were divided into training and testing cohorts at a ratio of 7:3. Clinicopathologic and radiologic characteristics such as types of tumor pleura relationships (types I-V) were recorded. Multivariable logistic regression analysis was used to identify independent risk factors for VPI, and the optimized variables were used to build a nomogram model. Model performance was evaluated with receiver operating characteristic (ROC) curves and calibration curves. The clinical utility of the nomogram was determined using decision curve analysis (DCA).

Results: Of the 766 patients [56.9% female patients; median age, 59 years; interquartile range (IQR): 53, 66] with early-stage NSCLC, VPI was confirmed in 250 patients (32.6%). There were 536 individuals in the training cohort (172 with VPI and 364 without VPI), and 230 individuals in the testing cohort (78 with VPI and 152 without VPI). The preoperative CT features related to VPI were tumor pleura relationship of type I and type III, solid, maximum diameter of tumor, lobulation, and lymphadenopathy. There was good discriminative power in the nomogram that included these six features. The training and testing cohorts' areas under the ROC curve (AUCs) were 0.815 and 0.825, respectively, with well-fitting calibration curves. DCA demonstrated that the nomogram was clinically useful.

Conclusions: The nomogram established with the identified CT features has the potential to assist with the prediction of VPI preoperatively in early-stage NSCLC and facilitate the selection of a rational treatment strategy.

Background: The combination therapy of the B-Raf proto-oncogene (BRAF) inhibitor dabrafenib and the mitogen-activated protein kinase kinase (MEK) inhibitor Trametinib has shown favorable outcomes in patients initially identified with BRAF^V600E mutations. However, there are currently no large-scale study data focusing on the use of a triple therapy regimen of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) plus dabrafenib and trametinib in patients with newly concomitant BRAF mutations after acquiring resistance to EGFR-TKIs. Our study aimed to explore the efficacy and safety of the triple therapy regimen through a multi-center real-world experience.

Methods: We reviewed the medical records of 1,861 patients who were treated with EGFR-TKI targeted drugs at three major medical centers in Shanghai between June 2015 and August 2024. Among 1,288 patients who developed disease progression, we identified 14 patients who were treated with a triple therapy regimen of EGFR-TKI plus dabrafenib and trametinib due to newly acquired BRAF^V600E mutation after EGFR-TKI resistance. The assessments comprised progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). We also performed further subgroup analysis to aid in identifying potential factors that influence treatment outcomes and enhance clinical decision-making.

Results: At the time of the data cutoff (August 1, 2024), the estimated median PFS was 6.7 months [95% confidence interval (CI): 2.5-not evaluated (NE)]. The median OS was not reached in 14 patients. ORR was 35.7% (95% CI: 14.0-64.4%) and DCR was 78.6% (95% CI: 52.4-92.4%). Three patients (21.4%) reported progressive disease (PD) and that was the best response. The median PFS was 8.35 months (95% CI: 2.0-NE) in 8 patients receiving third-generation TKI followed by first-/second-generation EGFR-TKIs and 6.9 months (95% CI: 2.5-NE) in 6 patients receiving third-generation TKI as first-line treatment directly. There was no significant difference in PFS between the two groups of patients receiving third-generation TKIs in different treatment sequences above [hazard ratio (HR): 1.107; 95% CI: 0.318-3.854; P=0.85]. Subgroup analysis indicated that a complex genetic mutation background may be a potential factor contributing to poorer PFS. No unexpected adverse effects were reported. Apart from pyrexia, gastrointestinal-related adverse reactions and skin-related adverse reactions warrant close attention.

Conclusions: The triple therapy regimen of EGFR-TKI plus dabrafenib and trametinib was found to have substantial and durable clinical benefit, with a manageable safety profile, in patients with newly concomitant BRAF^V600E mutations after osimertinib failure.

Background: Ground-glass opacity (GGO) on computed tomography (CT) has been suggested as a potential prognostic factor in lung adenocarcinoma (LUAD), but its significance in patients with pathological stage IA3 LUAD, particularly in relation to micropapillary (MIP) status, remains unclear. This study addresses the clinical need to stratify patients based on GGO and MIP status to optimize prognosis prediction and follow-up strategies.

Methods: A multicenter retrospective study was conducted on 411 patients with pathological stage IA3 LUAD, enrolled between July 2012 and July 2020. Patients were divided into two groups based on the presence of GGO. The association of GGO with recurrence-free survival (RFS) and cancer-specific survival (CSS) of patients with different MIP status was assessed, stratified by MIP status (MIP ≥5% was classified as positive, and MIP <5% as negative). A life-table analysis was used to calculate dynamic recurrence curves of subgroups formed by GGO and MIP and to establish a personalized follow-up strategy.

Results: The analysis indicated that GGO was associated with prolonged RFS (P<0.001) and CSS (P=0.006) in MIP-negative patients but not for MIP-positive patients. Time-dependent Cox multivariate analysis further showed that GGO was a favorable prognostic factor for RFS (P=0.03) and CSS (P=0.04) even at 2 years postoperatively. Based on GGO components and MIP status, patients were categorized into the four following subgroups: MIP(+)-GGO(+), MIP(+)-GGO(-), MIP(-)-GGO(+), and MIP(-)-GGO(-); the recommended number of follow-up visits for these four subgroups within 5 years were 3, 9, 3, and 11, respectively.

Conclusions: The GGO component demonstrated a beneficial prognostic effect primarily in MIP-negative patients with pathological stage IA3 LUAD, sustained for up to 2 years. The variation in recurrence risk across subgroups underscores the importance of personalized follow-up strategies based on GGO and MIP status to optimize patient monitoring and care.

Background and objective: As the most common cancer to progress to brain metastases (BMs), lung cancer presents with intracranial involvement in approximately 20% of patients at the time of diagnosis and lung cancer BMs constitute approximately half of all BMs. The current clinical strategy for managing lung cancer BMs involves a combination of systemic anticancer therapies with local radiation or surgical interventions. The efficacy of systemic treatments is often constrained by the blood-brain barrier (BBB) and the poor inhibition effect of the drug itself. Despite these treatments, the median survival for patients with lung cancer BMs frequently does not exceed 2 years, underscoring the urgent need for novel and effective therapeutic approaches. Antibody-drug conjugate (ADC) consists of three components: monoclonal antibodies, payload, and linkers. Novel ADCs have demonstrated therapeutic advantages in a variety of tumors, including BMs. This review aims to summarize the latest advancements of ADCs in lung cancer BM.

Methods: For this review, we searched the literature published in the field of ADCs for lung cancer BMs over the past 10 years.

Key content and findings: New-generation ADCs, represented by trastuzumab deruxtecan (T-DXd) and others, have demonstrated prominent intracranial antitumor activities and have shown significant therapeutic advantages on lung or breast cancer BMs in both preclinical and clinical studies. Several factors may contribute to the efficacies of ADCs in the intracranial cancers including specific payload, a higher and uniform drug:antibody ratio (DAR) as well as potent bystander effect. Whether intracranial tumors express these target antigens should also be taken into consideration.

Conclusions: ADCs have demonstrated promising antitumor activities in non-small cell lung cancer (NSCLC) patients with BMs and could offer a new systemic treatment option for this subset population of patients. More research exploring the efficacy, safety and mechanism of ADCs in BMs are needed. Combining ADCs with conventional treatments for BMs, such as radiotherapy and immunotherapy, may be a new direction for future treatment.

Background: Despite the decrease of morbidity rate of non-small cell lung cancer (NSCLC) in recent years, it is still a cancer with poor prognosis. Lung cancers (LCs) are usually diagnosed at a late stage of the disease due to non-specific clinical symptoms. Proper regulation of carnitine levels is important in the context of development and increased risk of cancer cells proliferation. The expression profiles and clinical value of SLC family members in LC remain largely unexplored. The aim of the study was the assessment of SLC22A16, SLC22A5 and SLC6A14 mRNA expression level among patients suffering from NSCLC. The obtained results were compared with the clinical and the pathological features of NSCLC patients.

Methods: Through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and bioinformatics studies, the evaluation of carnitine transporting genes (SLC22A16, SLC22A5 and SLC6A14) mRNA levels was performed in order to elucidate their connection to clinical features of patients and influence on overall survival (OS).

Results: The analysis showed a significant difference for the SLC22A5 gene of NSCLC patients and for SLC6A14 and SLC22A5 genes in LUSC patients in terms of sex (P=0.002, P=0.02 and P=0.001, respectively) and in terms of tobacco smoking (P=0.04). Analysis also revealed a significant negative correlation for SLC22A5 and SLC22A16 genes expression level in the lung adenocarcinoma (LUAD) subtype with standardized uptake value (SUV) (r=-0.40, P=0.02 and r=-0.43, P=0.04). The significant downregulation of gene expression compared to normal adjacent tissue was observed for SLC22A5 in lung squamous cell carcinoma (LUSC) and for SLC6A14 in both LUAD and LUSC subtypes. The effect of the SLC22A5, SLC22A16 and SLC6A14 gene expression at the time of diagnosis on the OS time of LC patients revealed that lower expression correlated with a shorter 5 years OS (all P values <0.01). The effects were distinct after division for LUAD and LUSC subtypes.

Conclusions: The expression levels of genes encoding carnitine transporters are diverse, hinting at a potentially altered carnitine metabolism in LC patients. Notably, this variance is not uniform and exhibits specificity across LC subtypes, with marked distinctions between LUAD and LUSC. The correlation between gene expression levels and OS of patients underlines the prognostic significance of SLC genes within these cancer subtypes.

Background: The current standard for the surgical management of lung cancer involves anatomic lung resection combined with systemic lymph node dissection/sampling. The purpose of this study was to investigate the patterns of pathological lymph nodes in invasive non-small cell lung cancer (NSCLC), explore the occurrence in lymph node metastasis (LNM), and provide recommendations for optimal lymph node resection/sampling in lung cancer operation.

Methods: There were 1,678 patients with NSCLC who underwent lobectomy between 2018 and 2021 at the Taizhou Hospital of Zhejiang Province were reviewed retrospectively. The location and incidence of LNM and postoperative pathological findings were studied. We analysed the metastasis rates of lymph node dissection stations using Pearson's χ² and Fisher's exact tests.

Results: There were 1,308 patients assessed as eligible and included in the study. The median number of lymph nodes cleared in the cohort was 11.2±5.1. In patients with lung adenocarcinoma, the rate of LNM was significantly higher in central than in peripheral lung cancer, especially in 2R/2L, L7, L9, L10, L11, and L12. Lung cancer patients with tumors ≤1 cm had no N2 lymph node metastases but few (2/191, 1.1%) N1 lymph node metastases. The likelihood of N2 metastasis increased (T1a, 0%, 0/191; T1b 3.5%, 22/625; T1c, 5.6%, 14/249; T2 and above, 18.9%, 46/243) with increasing tumor diameter. Thirty-four patients with stage N2 lung adenocarcinoma and 1-3 cm tumors displayed lobe-specific lymph node metastases in the mediastinum. In patients diagnosed with squamous cell carcinoma, no significant differences were observed in mediastinal LNM across various parameters (central versus peripheral location, tumor site, and tumor size).

Conclusions: Our study proposes recommendations for lymph node resection according to the pathological type of lung cancer, tumor location, lung lobes affected and tumor size, which may provide a certain reference value for the clinical work.

Background and objective: Liquid biopsy has emerged as a transformative approach in the diagnosis, monitoring, and treatment of lung cancer. This review aims to provide an updated overview of the latest advancements in liquid biopsy for lung cancer, highlighting the key developments and their clinical implications.

Methods: A comprehensive literature search was conducted using databases, such as PubMed, Embase, and Web of Science, covering the period from January 2018 to July 2024. The search terms included "liquid biopsy", "lung cancer", "circulating tumor DNA", "circulating tumor cells", and "exosomes". Studies were selected based on their relevance, novelty, and impact on the field.

Key content and findings: The review discusses recent innovations in liquid biopsy technologies, including improvements in the sensitivity and specificity of these technologies, and the role of various biomarkers, including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes, circulating tumor RNA (ctRNA), extracellular vesicles (EVs), tumor metabolites, tumor-educated platelets (TEPs), and plasma protein biomarkers, in early detection, prognosis, and personalized therapy. It also examines challenges and future directions for integrating liquid biopsy into routine clinical practice.

Conclusions: Liquid biopsy represents a promising non-invasive diagnostic tool for lung cancer and has significant potential to enhance patient outcomes. It is anticipated that continued research and technological advancements will further refine its clinical utility, potentially transforming the landscape of lung cancer management.

Background: For locally advanced central lung cancer, lung autotransplantation allows for complete tumor resection while maximizing the preservation of lung parenchyma. Neoadjuvant chemotherapy combined with immunotherapy has shown benefits for patients with advanced lung cancer, providing longer progression-free survival compared to chemotherapy alone. This study aims to evaluate the feasibility and safety of neoadjuvant immuno-chemotherapy followed by lung autotransplantation in the treatment of locally advanced central non-small cell lung cancer (NSCLC).

Methods: We retrospectively analyzed ten patients with central NSCLC who underwent lung autotransplantation after neoadjuvant immuno-chemotherapy from June 2019 to December 2023. Of the grafts, there was 1 right upper lobe, 3 right lower lobe, 1 left lower lobe, 5 basal segments (3 right and 2 left). Nine cases were performed ex situ except one in situ without graft perfusion. All patients were followed up regularly.

Results: Ten cases received neoadjuvant immuno-chemotherapy [programmed cell death protein 1 (PD-1) inhibitor combined with platinum plus paclitaxel], the average number of cycles was 2.3±0.5 cycles, and the average interval between neoadjuvant therapy and surgery was 35.0±13.3 days. Following treatment, there was 1 complete response (CR), 6 partial responses (PRs), and 3 stable diseases (SDs). All cases achieved R0 resection, with 6 cases attaining complete pathological remission (CPR) and 2 cases exhibiting major pathological remission (MPR). No operative death occurred within 30 days. Six cases developed perioperative complications, with five cases being mild to moderate in severity, all of which recovered after standardized treatment. Only one instance of severe pulmonary artery embolism was observed, which improved with systemic anticoagulation therapy. The median follow-up time was 9.5 (range, 1.1-54.2) months. One patient had 4R lymph node recurrence (improved after radiotherapy and immunotherapy), and seven patients survived without recurrence.

Conclusions: Lung autotransplantation for advanced central NSCLC after neoadjuvant immuno-chemotherapy is feasible and safe, with maximal preservation of lung function and a high rate of R0 resection. This also demonstrates the advantages of organ preservation strategies. The procedure can be technically challenging, but lethal complications are uncommon. Overall, outcomes are satisfactory, and patients achieved reasonable survival during the follow-up period.

Background: The gut microbiome is associated with the occurrence and severity of immune-related adverse events (irAEs) in cancer patients undergoing immunotherapy. However, the relationship between the lower respiratory tract (LRT) microbiome and checkpoint inhibitor pneumonitis (CIP) in lung cancer patients who underwent immunotherapy is unclear. The aim of the present study was to investigate the associations between the LRT microbiome and CIP in lung cancer patients receiving immunotherapy.

Methods: This retrospective study included lung cancer patients who received immunotherapy and had metagenomic next-generation sequencing (mNGS) results of LRT specimens [bronchoalveolar lavage fluid (BALF)]. Based on their final diagnosis, the patients were allocated to either the CIP group or the non-CIP group. We conducted an exploratory analysis of the LRT microbiome in the CIP and non-CIP patients, delineating the microbial composition, and comparing the differences between the two groups.

Results: In total, 52 lung patients were included in the study, of whom 33 were allocated to the CIP group and 19 to the non-CIP group. The alpha- and beta-diversity analyses revealed no significant differences between the two groups. In the CIP group, the dominant phyla were Firmicutes (41.7%), Acinetobacter (18.2%), and Proteobacteria (16.3%). In the non-CIP group, the dominant phyla were Firmicutes (38.2%), Acinetobacter (18.4%), and Proteobacteria (17.8%). Notably, the relative abundance of the Proteobacteria phylum (P<0.001) and Firmicutes phylum (P=0.01) was significantly higher in the CIP group than the non-CIP group.

Conclusions: The elevated relative abundance of the Proteobacteria and Firmicutes phyla in the LRT samples is associated with CIP in lung cancer patients.