Translational lung cancer research最新文献

{"title":"International cost-effectiveness analysis of nivolumab plus ipilimumab-based for metastatic non-small cell lung cancer with PD-L1 lower than 1.","authors":"Wolong Zhou, Shuishi Li, Yanwu Zhou","doi":"10.21037/tlcr-2025-222","DOIUrl":"10.21037/tlcr-2025-222","url":null,"abstract":"<p><strong>Background: </strong>Dual immunotherapy has demonstrated efficacy in treating non-small cell lung cancer (NSCLC) with tumor programmed cell death ligand 1 (PD-L1) lower than 1%. However, its widespread clinical implementation has been hindered by high costs, necessitating cost-effectiveness evaluations in the context of national healthcare payers. This study aims to evaluate the cost and clinical effect of nivolumab plus ipilimumab versus chemotherapy for NSCLC with PD-L1 lower than 1% from the perspective of payers in the USA and China.</p><p><strong>Methods: </strong>The CheckMate 227 and CheckMate 9LA trials were leveraged to devise a three-state Markov model using pooled data to simulate the disease trajectory in NSCLC with PD-L1 lower than 1%. The model assessed the lifetime total costs, incremental cost-effectiveness ratios (ICERs), and incremental net health benefit (INHB) of nivolumab plus ipilimumab versus chemotherapy in the contexts of American and Chinese payers. The respective willingness-to-pay (WTP) thresholds were set at $100,000 and $36,255 per quality-adjusted life-year (QALY). Sensitivity and subgroup analyses were performed to assess the robustness of the model.</p><p><strong>Results: </strong>Nivolumab plus ipilimumab provided an incremental gain of 1.11 and 0.96 QALYs over chemotherapy in the USA and China, respectively. However, this regimen was related to significantly higher total costs ($262,974 versus $146,772 in the USA and $43,217 versus $15,269 in China), yielding ICERs of $104,126/QALY and $29,143/QALY in the USA and in China, respectively. Among various influencing factors, patient body weight emerged as the most significant determinant. Subgroup analyses suggested that patients with brain metastases and squamous carcinoma were associated with greater benefits from the dual-immunotherapy approach.</p><p><strong>Conclusions: </strong>First-line nivolumab plus ipilimumab was deemed cost-effective for metastatic NSCLC with PD-L1 lower than 1% in China but did not meet cost-effectiveness in the USA.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2560-2570"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Literature review of advances and challenges in <i>KRAS</i> <i>G12C</i> mutant non-small cell lung cancer.","authors":"Jiang-Xia Yuan, Yue Hao, Xian-Zi Dai, Jiao-Jiao Hong, Cheng-Yu Chen, Zheng-Xing Huo, Jia Zhu, Qian Wang","doi":"10.21037/tlcr-2025-164","DOIUrl":"10.21037/tlcr-2025-164","url":null,"abstract":"<p><strong>Background and objective: </strong>Kirsten rat sarcoma viral oncogene homolog (<i>KRAS</i>) mutations are one of the most common oncogenic driver mutations in non-small cell lung cancer (NSCLC), with the KRAS G12C mutation being the most common prevalent subvariant. The review aims to explore optimal diagnostic and therapeutic strategies for <i>KRAS G12C</i> mutant NSCLC, and to provide guidance for the development of precise treatment approaches for affected.</p><p><strong>Methods: </strong>A comprehensive search was conducted in PubMed, Embase, Web of Science, MEDLINE, the Cochrane Library, and major international conferences proceedings for all English-language publications available up to December 31, 2024. Relevant studies were systematically reviewed, analyzed, and synthesized to inform this review.</p><p><strong>Key content and findings: </strong>In this review, we explore the <i>KRAS G12C</i> mutation and its associated signaling pathways, detection techniques, recent advancements in drug development and mechanisms of therapeutic resistance. The <i>KRAS G12C</i> mutation was once considered \"undruggable\" until the breakthrough approval of two targeted inhibitors: AMG510 (sotorasib) and MRTX849 (adagrasib). In China, IBI351 and D-1553 have also been approved for the treatment of adult patients with advanced NSCLC harboring the <i>KRAS G12C</i> mutation. Although currently approved only as second-line therapies for metastatic disease, these inhibitors-along with ongoing development of additional <i>KRAS</i>-targeted agents-are significantly advancing our understanding of <i>KRAS</i>-driven tumor biology. Notably, recent findings indicate that combining dual immune checkpoint inhibitors (ICIs; durvalumab and tremelimumab) with chemotherapy (CT) in patients with advanced NSCLC, including those with KRAS mutations, can result in durable survival benefits. This approach is emerging as a promising first-line treatment strategy.</p><p><strong>Conclusions: </strong>The landscape of <i>KRAS</i>-mutant NSCLC has undergone substantial progress, marked by the successive approval of multiple <i>KRAS G12C</i> inhibitors and the development of novel targeted therapies. Moreover, the POSEIDON trial has highlighted the potential of dual ICI therapy combined with CT to achieve sustained clinical benefits. Despite these advances, the heterogeneity of tumor responses underscores the need for further investigation into intrinsic resistance mechanisms and the strategic optimization of combination therapies to enhance treatment outcomes.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2799-2820"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pleural mesothelioma patients and ex-exposed asbestos workers are immunologically poor responders to oncogenic Merkel cell polyomavirus.","authors":"Chiara Mazziotta, Carmen Lanzillotti, Christian Felice Cervellera, Giada Badiale, Roberta Libener, Antonio Maconi, Elisabetta Casalone, Alessandra Allione, Giuseppe Matullo, Manlio Mencoboni, Ilaria Bononi, Fernanda Martini, John Charles Rotondo, Mauro Tognon","doi":"10.21037/tlcr-2025-198","DOIUrl":"10.21037/tlcr-2025-198","url":null,"abstract":"<p><strong>Background: </strong>Pleural mesothelioma (PM) is an aggressive tumor of the serous cavities primarily caused by the inhalation of asbestos, a carcinogenic and immunomodulatory mineral. Other factors, such as oncogenic viruses, might be involved in PM onset. Merkel cell polyomavirus (MCPyV) is a ubiquitous oncogenic DNA virus whose increased activity has been documented in conditions of immunosuppression. In this study, we aimed to investigate the immunological response to MCPyV in PM patients and workers ex-exposed to asbestos (WEA).</p><p><strong>Methods: </strong>MCPyV serology was investigated herein in sera from 108 PM patients, 102 WEA, and 110 healthy subjects (HS). Total serum immunoglobulin G (IgG) levels were evaluated. The presence of MCPyV DNA and viral protein (VP)1 and large T (LT) messenger RNAs (mRNAs) was evaluated by droplet-digital polymerase chain reaction (ddPCR)/quantitative polymerase chain reaction (qPCR) in 50 tumor specimens from PM patients unrelated to PM serum donors.</p><p><strong>Results: </strong>Reduced serum anti-MCPyV IgG rates and optical densities (ODs) were detected in PM (26.9% and 0.08-0.09) and WEA (27.5% and 0.08-0.09) compared to HS (60.9% and 0.16-0.33) (P<0.001), while the mean total IgG concentrations were similar among groups (4.3-5.7 mg/mL) (P>0.05). Biphasic PM histotype exhibited the lowest MCPyV IgG levels. WEAs with the highest asbestos exposure had the lowest rate and ODs of serum anti-MCPyV IgGs (5.6% and 0.074-0.083) in contrast to WEA (44.4% and 0.083-0.096) with lower exposure. Spearman analyses revealed an inverse correlation between ODs and both cumulative asbestos exposure and years of asbestos exposure (P<0.05), while a direct correlation was detected between years since last exposure and ODs (P=0.02). MCPyV DNA was detected in 32% of PM specimens with a mean viral DNA load of 0.39±0.2 copy/cell. VP1 mRNA was detected in all MCPyV DNA-positive PMs, while 69% of these specimens tested LT mRNA-positive.</p><p><strong>Conclusions: </strong>Our study provides the first evidence that PM and WEA may experience a specific impairment of their immune response to MCPyV. This might possibly depend on the immunomodulatory effect of asbestos, a well-known immunosuppressive mineral.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2611-2625"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic models for large cell neuroendocrine lung carcinoma: a machine learning and regression approach.","authors":"Xian Gong, Maojie Pan, Yuxing Lin, Xiaoxuan Ye, Jiekun Qian, Guoliang Liao, Jianting Du, Bin Zheng, Chun Chen, Zhang Yang","doi":"10.21037/tlcr-2025-130","DOIUrl":"10.21037/tlcr-2025-130","url":null,"abstract":"<p><strong>Background: </strong>Large cell neuroendocrine lung carcinoma (LCNEC) is a rare and aggressive subtype of lung cancer with high rates of lymph node metastasis (60-80%) and distant metastasis (40%) at diagnosis. This study aimed to develop and evaluate 5-year survival prognostic models for patients with LCNEC, comparing the traditional Cox proportional hazards regression model with machine learning approaches, including Gradient Boosting, XGboost, Random Survival Forests, Extra Survival Trees, and Neural Networks.</p><p><strong>Methods: </strong>This retrospective cohort study utilized data from the Surveillance, Epidemiology, and End Results (SEER) database (2000-2021), including 6,062 patients with pathologically confirmed LCNEC. The primary outcome was the 5-year survival probability. The study employed regression and machine learning approaches, with data that was stratified into training and testing sets based on the year of diagnosis, and four stratification variables were analyzed. Internal-external cross-validation assessed the model performance, while decision curve analysis (DCA) evaluated clinical utility.</p><p><strong>Results: </strong>The Gradient Boosting model showed better discrimination than all others, achieving the best pooled metrics. Harrell's C-index of 0.799, Brier score of 0.047, Calibration slope of 1.126 and Calibration-in-the-large of 0.155. Our SHAP value analysis identified chemotherapy as one of the most influential predictors of survival outcomes in LCNEC patients, highlighting its potential clinical importance in guiding treatment strategies for this population. DCA confirmed its superior clinical utility.</p><p><strong>Conclusions: </strong>Gradient Boosting exhibited excellent predictive accuracy and clinical utility, demonstrating its potential for prognostic evaluation for LCNEC patients.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2470-2482"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fructose-diphosphate aldolase C as a novel diagnostic biomarker for early-stage non-small cell lung cancer: a low-abundance proteomics study.","authors":"Changsen Bai, Qianhui Hao, Yunxiang Chen, Jiayi Wang, Jiawei Xiao, Da Hyun Kang, Li Ren","doi":"10.21037/tlcr-2025-530","DOIUrl":"10.21037/tlcr-2025-530","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer remains one of the leading causes of cancer-related deaths worldwide. Early detection is crucial for improving prognosis and survival rates. This study aimed to identify the low-abundance plasma proteins as potential diagnostic biomarkers for early-stage non-small cell lung cancer (NSCLC) and to distinguish malignant from benign lung nodules.</p><p><strong>Methods: </strong>Using a sodium-type Y zeolite-polymer polyanionic complex (NaY-PPC)-based low-abundance proteomics, we analyzed 181 plasma samples from healthy controls (HC; n=65), patients with benign lung nodules (BNs; n=21), and patients with early-stage NSCLC (n=95). Principal component analysis (PCA) and heatmap visualization were employed for differential analysis. The diagnostic performance of candidate biomarkers was evaluated using receiver operating characteristic (ROC) curves, and enzyme-linked immunosorbent assay (ELISA) was used for validation. Functional studies, including fructose-bisphosphate aldolase C (ALDOC) knockdown, were conducted to assess the role of ALDOC in NSCLC progression.</p><p><strong>Results: </strong>We identified 23 significantly differentially expressed proteins, with ALDOC showing the most promising diagnostic potential. ALDOC could effectively distinguish NSCLC patients from HCs [area under the curve (AUC) =0.994] and from those with BNs (AUC =0.720). Combining ALDOC with the traditional biomarkers carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and cytokeratin fragment 21-1 (CYFRA21-1) improved the differentiation between NSCLC and BN (AUC =0.824). ELISA validation confirmed the findings from the proteomics analysis. Additionally, ALDOC was upregulated in NSCLC tissues, and its high expression correlated with poor overall survival. Knockdown of ALDOC significantly reduced NSCLC cell growth and motility, suggesting its tumor-promoting role.</p><p><strong>Conclusions: </strong>ALDOC is a promising diagnostic biomarker for early-stage NSCLC, with potential clinical utility in distinguishing malignant lung nodules from BNs. This study highlights the value of low-abundance proteomics in identifying novel biomarkers for lung cancer detection and risk assessment.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"2239-2256"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An explainable AI approach to surgical and radiotherapy interventions for optimized treatment decision-making in early-stage non-small cell lung cancer.","authors":"Qunzhe Ding, Chendong Wang, Zhe Zhang, Junjie Liao, Lufan Tang, Jiade Jay Lu, Zhibo Tan","doi":"10.21037/tlcr-2025-152","DOIUrl":"10.21037/tlcr-2025-152","url":null,"abstract":"<p><strong>Background: </strong>For individual patients with early-stage non-small cell lung cancer (NSCLC), robust evidence to guide treatment selection between surgery and stereotactic body radiotherapy (SBRT) remains limited. This study aimed to develop machine learning-driven predictive models using the Surveillance, Epidemiology, and End Results (SEER) database to evaluate the efficacy of these treatments, thereby providing a data-driven foundation for personalized treatment decisions.</p><p><strong>Methods: </strong>Stage I or IIA NSCLC patients diagnosed between 2012 and 2018 were identified from the SEER database. Six machine learning models, spanning from classical to advanced approaches, were employed to predict 1-, 3-, and 5-year survival, with their performance assessed using seven metrics. The SHAP (SHapley Additive exPlanations) interpretability method was employed to explain the optimal predictive model, focusing on analyzing the differences between surgical and radiotherapy treatments under various factors, providing valuable insights to optimizing treatment strategies. Patients diagnosed between 2019 and 2021 were selected as an external validation cohort to assess the generalizability and robustness of the previously developed models.</p><p><strong>Results: </strong>A total of 26,566 patients were included in the training and internal testing cohort of the study. LightGBM (light gradient boosting machine) outperformed other models across most metrics for survival predictions. The SHAP interpretability analysis revealed that tumor location, tumor size, pathology, and treatment type were significant factors for 3- and 5-year predictions. Furthermore, at 3- and 5-year intervals, the efficacy of radiotherapy was comparable to surgery for left upper lobe tumors, while radiotherapy appeared slightly inferior to surgery for right lower lobe tumors. Meanwhile, for tumors <1.5 cm or 3.5-5 cm, lobectomy exhibited the best efficacy, while for tumors measuring 1.5-3.5 cm, the efficacy of lobectomy seemed to be slightly inferior to radiotherapy and sublobar resection. For adenocarcinoma and squamous cell carcinoma, radiotherapy and lobectomy could be regarded as the preferred treatment methods, respectively. Besides, for patients <45 or >75 years old, sublobar resection showed the best efficacy at the 5-year interval. The external validation cohort of 11,927 patients further confirmed the effectiveness of the models in predicting 1-, 3-, and 5-year survival outcomes, reinforcing their reliability and applicability in clinical decision-making.</p><p><strong>Conclusions: </strong>This study provides valuable insights into treatment decision-making for stages I and IIA NSCLC. The LightGBM model is a reliable tool for survival prediction for early-stage NSCLC. By utilizing this model, it can be concluded that tumor location, tumor size, pathological type and age are vital factors significantly influencing the choice of treatment methods.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"2011-2030"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing the intraoperative identification of high-grade patterns in invasive lung adenocarcinoma via radiomics.","authors":"Yuanxin Sun, Hao Dong, Weiqiu Jin, Haoxiang Xuan, Zheng Yuan, Lukas Käsmann, Leilei Shen, Tingting Wang, Xiaodan Ye, Mengsu Zeng","doi":"10.21037/tlcr-2025-504","DOIUrl":"10.21037/tlcr-2025-504","url":null,"abstract":"<p><strong>Background: </strong>High-grade patterns (HGPs) are important for surgical decision-making in patients with invasive lung adenocarcinoma (IAC), but the sensitivity of intraoperative frozen section (FS) is not high. Radiomics has the potential to improve the sensitivity of intraoperative detection. The purpose of the present study was to evaluate the value of combining radiomics with FS analysis for predicting HGPs in patients with clinical T1 (cT1) IAC.</p><p><strong>Methods: </strong>Data from a total of 490 patients who were surgically diagnosed with IAC from January 2019 to April 2019 were retrospectively analyzed; the patients were randomly divided into a training set (n=392) and a test set (n=98). The presence of HGPs (micropapillary, solid, and complex glandular patterns) was evaluated according to the final pathology (FP). Radiomics features were extracted from thin-slice computed tomography (CT) images, and feature selection was performed via the mutual information method and least absolute shrinkage and selection operator regression algorithm. The radiomics (R), FS, and radiomics-frozen section (R-FS) models were established to predict the presence of HGPs in FP. The area under the receiver operating characteristic (ROC) curve, the precision-recall curve, the calibration curve, and decision curve analysis were used to evaluate model performances. The permutation importance algorithm (PIA) and local interpretable model-agnostic explanations (LIME) were used to provide interpretations for the R model. Additionally, the predictive performance was compared among tumors with different CT densities.</p><p><strong>Results: </strong>The R and R-FS models outperformed the FS model, with the R-FS model achieving the best area under the curve value of 0.907 (95% confidence interval: 0.830-0.956) in the test set. PIA and LIME determined the interpretability of outputs from both the overall model and individual sample perspectives. Among the three models, the R model performed best in pure ground-glass nodules and pure-solid tumors.</p><p><strong>Conclusions: </strong>Radiomics could function as a complementary check to FS to provide a more sensible and accurate intraoperative identification of HGPs as compared to the use of FS alone, thus better informing clinical decision-making.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"2145-2158"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paving the way for ctDNA-guided trials in lung cancer: insights from the LIBELULE study.","authors":"Jose Carlos Benitez, Antonio Rueda-Domínguez","doi":"10.21037/tlcr-2025-427","DOIUrl":"10.21037/tlcr-2025-427","url":null,"abstract":"","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"2347-2352"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surgical treatment of small-cell lung cancer: long-term prognosis and patterns of adjuvant therapy.","authors":"Ruichen Cui, Xiaohu Hao, Jiahan Cheng, Jacobo Rogado, Qiang Pu, Yunke Zhu","doi":"10.21037/tlcr-2025-490","DOIUrl":"10.21037/tlcr-2025-490","url":null,"abstract":"<p><strong>Background: </strong>Small-cell lung cancer (SCLC) is a highly aggressive malignancy predominantly treated with chemotherapy or chemoradiotherapy. The role of surgical intervention in SCLC, however, remains inadequately defined. This study aimed to retrospectively analyze the clinical data of patients with SCLC who underwent surgical treatment to assess the impact of surgery combined with perioperative adjuvant therapy on long-term prognosis, with the goal of informing future treatment strategies.</p><p><strong>Methods: </strong>This study included patients with SCLC who underwent surgical treatment at West China Hospital, Sichuan University, between 2005 and 2021. Prognostic factors influencing overall survival (OS) and disease-free survival (DFS) were analyzed using univariate and multivariate Cox regression models, in conjunction with the Kaplan-Meier method.</p><p><strong>Results: </strong>A cohort of 121 patients with SCLC who underwent surgical treatment was included. Multivariate Cox regression analysis indicated that postoperative adjuvant chemotherapy [hazard ratio (HR) =0.45; 95% confidence interval (CI): 0.24-0.85] was significantly associated with improved OS, whereas a smoking index exceeding 400 (HR =1.0011; 95% CI: 1.0004-1.0018) was identified as an independent adverse prognostic factor. Pathological stratification showed that prophylactic cranial irradiation (PCI) was significantly associated with improved OS in stage II/III patients (P<0.05) but had not in stage I patients (P>0.05). Regarding DFS, preoperative neoadjuvant chemotherapy was associated with significantly prolonged DFS (HR =0.44; 95% CI: 0.21-0.94), while lymph node metastasis was identified as a negative predictor (HR =1.97; 95% CI: 1.16-3.36).</p><p><strong>Conclusions: </strong>Surgical intervention combined with perioperative adjuvant therapy provides significant survival benefits for patients with SCLC. Notably, preoperative neoadjuvant chemotherapy and postoperative adjuvant chemotherapy were associated with prolonged DFS and OS. For early-stage patients, the application of PCI should be approached cautiously. Further prospective studies are warranted to better balance its potential risks and benefits.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"2227-2238"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A retrospective real-world single-arm study evaluating the efficacy and safety of neoadjuvant chemotherapy in patients with selected limited-stage small-cell lung cancer.","authors":"Wengang Zhang, Yujie Li, Jing Nie, Wencheng Zhao, Zhiyi Guo, Shunjia Li, Qianqian Zhang, Bing Bo, Xuyang Chen, Li Ye, Zhimin Chen, Hao Wang, Kandi Xu, Lishu Zhao, Xinyue Liu, Yujin Liu, Yuhang Li, Lihua Huang, Yayi He","doi":"10.21037/tlcr-2025-209","DOIUrl":"10.21037/tlcr-2025-209","url":null,"abstract":"<p><strong>Background: </strong>With the advancement of surgical techniques and the introduction of neoadjuvant therapies, the risk of recurrence or distant metastases has been significantly decreased for non-small-cell lung cancer (non-SCLC) after surgery. In recent years, the application of these advanced techniques and therapies in SCLC has also shown promise. This study aims to explore the efficacy and safety of neoadjuvant chemotherapy combined with surgery in selected limited-stage SCLC (LS-SCLC).</p><p><strong>Methods: </strong>In this retrospective, single-arm clinical trial, we conducted a thorough review of electronic medical records from the Shanghai Pulmonary Hospital between December 2015 and December 2022. Patients with a pathological diagnosis of SCLC who underwent neoadjuvant chemotherapy followed by radical surgery were enrolled. Baseline demographic and clinical characteristics, specifics of neoadjuvant therapy and surgery, survival outcomes, and safety profiles of included patients were systematically collected and analyzed.</p><p><strong>Results: </strong>A total of 47 patients [7 (14.89%) females and 40 (85.11%) males; median age 61.00 years, interquartile range (IQR), 55.50-67.50 years] were enrolled. The disease control rate was 100%, with an objective response rate of 70.21% and a downstaging rate of 65.9%. The percentage of patients with a complete pathological response (CPR) and major pathological response (MPR) was 10.64% (5/47) and 12.77% (6/47, excluding CPR), respectively. In subgroups stratified by baseline demographic and clinical characteristics, the MPR rate showed no significant differences, yet a trend toward higher MPR was observed among smoking patients. At the data cutoff (October 2, 2024), the median follow-up period was 35.367 months [IQR, 26.367 months-not reached (NR)]. The median event-free survival (EFS) was 16.27 months [95% confidence interval (CI): 12.20-30.53] and the median overall survival (OS) was NR, with 2-, 3-, and 4-year survival rates of 79.96% (95% CI: 68.36-93.52%), 71.39% (95% CI: 57.12-89.22%), and 64.90% (95% CI: 48.52-86.82%), respectively. The stratified analysis revealed that patients achieving an MPR and those undergoing postoperative adjuvant radiotherapy exhibited longer EFS and OS. Treatment-related adverse events of grade 3-4 were observed in 21.28% of patients, with the most frequent occurrences being a decrease in neutrophil count (12.77%), followed by a decrease in platelet count (8.51%), and a decrease in white blood cell count (4.26%).</p><p><strong>Conclusions: </strong>Neoadjuvant chemotherapy combined with surgery could be a potential treatment strategy for LS-SCLC, with a high proportion of patients achieving an MPR, and manageable safety profile, that did not compromise surgical resection. Further prospective clinical trials are warranted to delineate the benefits of neoadjuvant chemotherapy and optimize LS-SCLC treatment.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 6","pages":"2031-2046"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}