Thoracic Cancer最新文献

Objectives: Central airway obstruction (CAO) involves the narrowing of the trachea, carina, and main bronchi. This study describes a technique for placing a self-expanding metallic Y-stent using a single guidewire for the palliative management of inoperable malignant stenosis near the carina, evaluating its efficacy and safety.

Materials and methods: We conducted a retrospective analysis of all patients with severe malignant carinal stenosis who were treated with a customized self-expanding metallic Y-stent at our institution between January 2020 and December 2024. In all cases, the left bronchial branch of the stent was positioned using the Seldinger technique with a single guidewire.

Results: The single-guidewire Seldinger technique simplified the procedure, resulting in a significantly shorter stent placement time (38 vs. 51 min; p < 0.0001) and reduced general anesthesia time (53 vs. 71 min; p ≤ 0.0001) compared to a double-guidewire approach. Furthermore, it minimized the number of required X-ray exposures (0-1 vs. 4-5 images; p < 0.0001) and lowered the risk of guidewire dislodgement. No immediate complications were reported.

Conclusion: The placement of a self-expanding Y-stent using a single left-sided guidewire is an efficacious and feasible approach for maintaining airway patency in patients with severe malignant carinal stenosis, offering a simpler and more efficient procedural alternative.

Background: Pleural mesothelioma is a highly aggressive malignancy with a poor prognosis due to the limited efficacy of currently available therapies. Macroautophagy (hereafter "autophagy") is a lysosome-mediated degradation pathway involved in cellular homeostasis that can either support or inhibit cancer progression depending on context. In this study, we investigated the effects of SAR405, an inhibitor of vacuolar protein-sorting 34 (VPS34), which is important for regulating the early stage of autophagy, on pleural mesothelioma.

Methods: Human pleural mesothelioma cell lines H28, H2452, and 211H were cultured with SAR405. The effects of SAR405 on protein expression, cell viability, colony formation, cell invasion, and the cell cycle were investigated, as were its synergistic effects with cisplatin. Autophagy induction was evaluated in mesothelioma cells transfected with the pMRX-IP-GFP-LC3-RFP-LC3ΔG plasmid, which was developed for the quantitative and statistical estimation of autophagy.

Results: SAR405 treatment alone significantly reduced cell viability, colony formation, and cell invasion, and increased G₂/M cell cycle arrest. In addition, SAR405 induced apoptosis in the H2452 cell line. Although cisplatin weakly induced autophagy in mesothelioma cells, its combination with SAR405 did not result in additive or synergistic effects on cell viability.

Conclusions: Based on these results, inhibition of VPS34 by SAR405 effectively suppressed cell viability in all mesothelioma cell lines and induced apoptosis in H2452 cells. The findings of this study indicate the potential for VPS34 inhibition as a new strategy for the treatment of mesothelioma and provide insights into the complex role of autophagy in this malignancy.

Background: Chemoimmunotherapy is the first-line standard for advanced lung adenocarcinoma (LUAD) without driver mutations, but predictive biomarkers are still limited. TP53 is the most frequently mutated gene in LUAD, and its mutation subtypes affect treatment efficacy differently.

Methods: This is a retrospective observational study. We retrospectively analyzed 133 patients with advanced LUAD who received first-line chemoimmunotherapy in our hospital. TP53 mutations were classified using a multidimensional approach. Key subtypes were identified through elastic-net and multivariate Cox regression analyses in clinical cohorts. The underlying mechanisms were further explored by transcriptomic and pathway analyses, including gene set variation analysis (GSVA) and immune cell deconvolution, using TCGA data.

Results: An elastic-net Cox model within the TP53-mutant cohort identified three key features: TP53 variant allele frequency (VAF), CpG site mutation status, and dominant-negative effects (DNE)-loss-of-function (LOF) classification. Subsequent multivariate Cox regression in the full cohort confirmed that TP53 mutations at CpG sites were an independent favorable prognostic factor. Patients harboring CpG site mutations had significantly longer median progression-free survival (PFS) for first-line chemoimmunotherapy than both non-CpG-mutant and wild-type patients. Exploratory transcriptomic analyses revealed that CpG-mutant tumors were associated with an immune-activated tumor microenvironment (TME) characterized by enhanced T-Cell receptor (TCR) signaling, antigen presentation, IFN-γ signaling, and CD8⁺ T-cell infiltration, whereas non-CpG-mutant tumors exhibited a glycolytic metabolic profile and potentially reduced immune activity.

Conclusions: In conclusion, this study demonstrates that TP53 mutations at CpG sites define a distinct subgroup of patients with advanced LUAD who derive significantly greater PFS benefit from first-line chemoimmunotherapy.

Objectives: Radiological surveillance after curative-intent lung cancer resection is essential for early detection of recurrence and second primary tumors. Large-scale health emergencies can compromise oncologic follow-up. This study quantifies the impact of a health crisis on radiological surveillance in a national cohort of resected lung cancer patients.

Methods: A time-segmented observational cohort study was performed using data from the prospective, multicenter GEVATS registry. Surveillance density (CT/month) was evaluated across three predefined periods: pre-pandemic (baseline), state of alarm (maximum healthcare restrictions), and post-alarm (recovery phase). The population at risk was updated for each period. Subgroup analyses during the post-alarm phase assessed prioritization according to neoadjuvant treatment, pathological stage, age, and comorbidity.

Results: Among 2382 eligible patients, surveillance density declined progressively from the pre-pandemic period (0.157 ± 0.079 CT/month) to the state of alarm (0.098 ± 0.071 CT/month). In the post-alarm phase, density dropped sharply to 0.023 ± 0.018 CT/month (equivalent to one CT every 3.6 years), representing a 76.5% reduction compared with the state-of-alarm period (p < 0.001). This under-surveillance was generalized, with no significant differences by pathological stage (p = 0.084), age (p = 0.564), or comorbidity (p = 0.872). Only prior neoadjuvant therapy was associated with a slightly higher density (p = 0.040).

Conclusions: A prolonged health crisis resulted in a profound and persistent reduction in radiological surveillance after lung cancer resection, without evidence of risk-based prioritization. These findings support the need for contingency frameworks within clinical guidelines to preserve continuity of oncologic follow-up during future health emergencies.

Background: Immune checkpoint inhibitors (ICIs) have limited benefit in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). However, they are often tried after tumors develop resistance to EGFR tyrosine kinase inhibitors (TKIs). Because EGFR-TKI treatment alters the tumor microenvironment, biomarkers predictive of ICI response are ideally identified post-EGFR-TKI resistance, but obtaining repeat biopsies at this time can be challenging. The purpose of this study was to explore predictive biomarkers for ICI response using plasma samples collected after EGFR-TKI therapy.

Methods: This retrospective analysis included 28 patients with EGFR-mutant NSCLC treated with an ICI after developing resistance to EGFR-TKI. Plasma samples collected at TKI progression were profiled using an Olink Target 96 immune protein panel to identify differential protein expression. Candidate protein biomarkers were validated by immunohistochemistry in tumor tissue. Durable clinical response (DCB) was defined as patients achieving progression-free survival (PFS) ≥ 6 months during ICI therapy.

Results: Of the 28 patients, 6 (21.4%) achieved durable clinical benefit, with PFS ≥ 6 months. Proteomic analysis identified four plasma proteins that differed significantly between DCB and NCB. Gal-9 and GZMH levels were elevated in NCB, whereas IL-4 and IL-6 were elevated in DCB. Notably, PFS was significantly longer in patients with lower Gal-9 and higher IL-4 levels.

Conclusions: Plasma-based immune markers measured at the time of TKI resistance may help predict which patients with EGFR-mutant NSCLC will respond to subsequent ICI therapy. Such biomarkers could guide immunotherapy decision-making in this clinically challenging population.

Background: Associations between immune-related adverse events (irAEs) and survival outcomes in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs) remain controversial, partly due to inconsistencies in dealing with immortal time bias (ITB). To address this, we adjusted for ITB in this single-center retrospective study.

Methods: We included 129 patients with advanced NSCLC receiving ICIs as first-line therapy and assessed associations between irAE development and progression-free survival (PFS) and overall survival (OS). To mitigate ITB, we performed landmark analyses at 30, 42, and 75 days and used multivariable Cox models with irAEs as a time-dependent covariate.

Results: During a median follow-up of 9.7 months, 58 (45.0%) patients developed irAEs. Unadjusted analyses showed a significant association between irAEs and longer PFS (hazard ratio [HR] 0.55; p < 0.01) and OS (HR 0.42; p < 0.01), but this was no longer evident after adjusting for ITB. Specifically, landmark analyses revealed no significant survival differences, except for PFS at the 42-day landmark. The time-dependent Cox model confirmed no significant association between irAE occurrence and PFS (HR 1.16) or OS (HR 0.93). In contrast, good Eastern Cooperative Oncology Group performance status at baseline was an independent predictor of improved survival.

Conclusion: After appropriate adjustment for ITB, irAE development was not associated with improved survival in NSCLC patients treated with ICIs. Baseline performance status, rather than irAE occurrence, remains a more critical prognostic factor for these patients. The relationship between irAE development and clinical outcome should be evaluated with consideration of ITB.

Background: Immune checkpoint inhibitors (ICIs) frequently cause severe adverse events (AEs) in elderly lung cancer patients due to age-related immune decline. This study combines pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) with real-world data to explore safety profiles in geriatric lung cancer patients.

Methods: AE reports for geriatric lung cancer patients (≥ 65 years) on FDA-approved ICIs from FAERS (Q3 2014-Q3 2024) were analyzed using the Reporting Odds Ratio. Single-center retrospective data was used for clinical contextualization.

Results: A total of 16 062 AE reports were identified, along with 260 AE signals in the FAERS database. The median age of reports was 72 years, with a male predominance (70.8%). Median onset time was 50 days. Reports with fatal outcomes (not causally adjudicated) accounted for 27.6% of cases. The geriatric group had significantly higher odds of reported fatal outcomes compared to the non-elderly group (OR = 1.13, p < 0.001). Further analysis revealed elevated odds of fatal outcomes were associated with reports concerning male patients (OR = 1.46), those originating from Asian geographic regions (OR = 1.36), and anti-PD-1 recipients (OR = 1.22) (all p < 0.001) in geriatric patients. A complementary single-center cohort (n = 225) provided clinical context, identifying immune-mediated pneumonia (21.3%) as the most common AE, predominantly in males (89.6%) and anti - PD-1 users (93.8%).

Conclusion: A higher reported rate of fatal outcomes was observed in geriatric lung cancer patients, especially those reports pertaining to males, Asian regions, and recipients of anti-PD-1 therapy.

Background: Previous studies report variation in the incidence of pulmonary fungal infection rates and associated factors in lung cancer patients. This meta-analysis aimed to provide a comprehensive synthesis of Chinese- and English-language studies to investigate the incidence of pulmonary fungal infections and their associated factors in these patients.

Methods: Studies reporting the incidence of pulmonary fungal infections or their associated factors in lung cancer patients were systematically searched in the WanFang, CNKI, EMBASE, SinoMed, Web of Science, and PubMed databases until April 2025.

Results: In total, 37 studies involving 26 841 lung cancer patients were included. The pooled pulmonary fungal infection rate (95% confidence interval) was 14.00% (12.54%-15.45%) in lung cancer patients. Age ≥ 60 years (odds ratio (OR) = 1.85, p = 0.020), male sex (OR = 1.23, p = 0.019), smoking history (OR = 2.24, p < 0.001), chronic obstructive pulmonary disease (OR = 2.19, p = 0.010), interstitial lung disease (OR = 4.40, p < 0.001), diabetes (OR = 2.31, p < 0.001), anemia (OR = 6.47, p = 0.016), small cell lung cancer (OR = 1.46, p = 0.011), squamous cell carcinoma (OR = 1.38, p = 0.001), tumor stages of III-IV (OR = 2.38, p < 0.001), invasive operation (OR = 3.73, p < 0.001), chemotherapy (OR = 1.64, p = 0.011), chemotherapy cycle > 2 (OR = 2.87, p < 0.001), radiotherapy (OR = 1.67, p = 0.001), chemoradiotherapy (OR = 2.72, p < 0.001), surgery (OR = 1.64, p < 0.001), long-term use of antibiotics (OR = 5.64, p = 0.002), use of glucocorticoid (OR = 4.44, p < 0.001), and hospital stays ≥ 14 days (OR = 3.97, p = 0.006) were linked with higher pulmonary fungal infection risk.

Conclusion: The pulmonary fungal infection rate (95% CI) was 14.00% (12.54%, 15.45%) in lung cancer patients. Furthermore, the associated factors might help screen for and intervene early in pulmonary fungal infections in patients with lung cancer.

Introduction: Accurate clinical staging of early-stage non-small cell lung cancer (NSCLC) is critical to guide treatment recommendations. Clinical and pathological staging concordance for NSCLC is a quality indicator of lung cancer care. We compared clinical and pathological staging of early-stage NSCLC assessed by an established lung cancer multidisciplinary team (MDT), focusing on clinical under-staging.

Method: Retrospective review of all patients with early-stage NSCLC referred by our lung cancer MDT for definitive surgical management between January 2019 and December 2023.

Results: The cohort included 259 patients. The median time from review by respiratory service and referral to cardiothoracic surgery was 82 (IQR 59-132) days. Time from MDT discussion to surgery was 28 (IQR 18-41.5) days. Overall clinical and pathologic staging concordance occurred in 73% of cases, with 18.9% of cases clinically under-staged. Factors associated with clinical under-staging were time between sentinel CT imaging and surgery (p = 0.01) and histopathologic evidence of visceral pleural (p = 0.003), vessel (p = 0.031) and lymphatic (p = 0.014) invasion. At follow-up there was a significantly increased risk of mortality (OR 2.06, p = 0.003) and disease recurrence (OR 2.06, p = 0.037) for clinically under-staged patients. Discrepancies which may have led to different treatment decisions occurred in 18 (7%) patients.

Conclusion: For patients diagnosed with early-stage NSCLC referred for curative surgical management, disagreement between clinical and pathologic staging may be due to treatment delay and malignancy histopathological features. Clinically under-staging increases risk of morbidity and mortality, which could be addressed through improved timeliness of care. Concordance of clinical and pathologic staging should be a routinely assessed benchmark for all lung cancer MDTs.

Background: The increasing detection of pulmonary nodules has made accurate preoperative localization clinically urgent. Although electromagnetic navigation bronchoscopy (ENB)-guided dye marking is effective, evidence is limited, and the optimal dye remains unclear. This study compared methylene blue (MB) and indocyanine green (ICG) to determine the more efficient option for pulmonary nodule localization.

Methods: A total of 101 patients who underwent preoperative ENB localization between 2015 and 2021 were included. Patients were divided into two groups according to the dye used (MB or ICG) for comparative analysis. The primary outcomes were localization success rate and ENB-related complications. Secondary outcomes included the impact of different dyes on operative efficiency, assessed by the time from the beginning of the operation to submission of the specimen for frozen section analysis (target time), concordance between intraoperative freezing and postoperative paraffin results, and 5-year overall survival (OS) and disease-free survival (DFS).

Results: Among 101 patients (ICG: 58 patients, 71 nodules; MB: 43 patients, 47 nodules), all nodules were successfully localized using both dyes, with no serious ENB-related complications. Compared with the MB group, ICG use was associated with a shorter target time. Consistency of intraoperative freezing and postoperative paraffin results was comparable between the two groups (p = 0.96). Five-year DFS and OS were also comparable between the two groups.

Conclusions: ENB-guided dye localization enables accurate and safe minimally invasive resection of pulmonary nodules. Both MB and ICG are effective, while ICG was associated with a shorter operative time and may offer a potential efficiency benefit.